Objective: Lutetium-177 prostate-specific membrane antigen-617 is a novel alternative therapeutic option in metastatic castration-resistant prostate cancer, especially useful for patients who do not respond to standard therapy methods. The aim of this study was to define the efficacy and safety profile of lutetium-177 prostate specific membrane antigen-617 treatment in a group of patients with metastatic castration-resistant prostate cancer. Materials and Methods: Study group included 34 men with metastatic castration-resistant prostate cancer (median, 69.6 ± 7.7 years) who were treated with lutetium-177 prostate-specific membrane antigen-617 therapy (22/34; 4 courses, 12/34; 2 courses). Patients were evaluated by physical examination, Eastern coop erative oncology group performance status, gallium-68 prostate-specific membrane antigen positron emis sion tomography/computed tomography, brief pain inventory-short form questionnaire, biochemical tests, and complete blood counts. Treatment response and adverse effects were examined by brief pain inventory scores, SUVmax values, biochemical tests, and complete blood counts. Independent variables were analyzed statistically (significance; P < .05). Results: The Eastern cooperative oncology group performance was grade 0 in 5/34 (14.7%), grade 1 in 25/34 (73.5%), and grade 2 in 4/34 (11.8%) patients. Distribution of patient numbers according to brief pain inven tory scores (score: <1, scores: 1-4, and scores: 5-10) was 2, 10 and 22 at the beginning, 6, 16 and 12 after the second course, and 10, 10 and 2 after the fourth course of treatment, respectively. Serum prostate-specific antigen decreased in 15 of 22 patients (68%) (P < .05). Before and after the treatment, we found a substan tial decrease in SUVmax values (22.3 vs. 11.8, P < .001) and brief pain inventory scores (score ≥ 5; 22/34 pts vs. 0/22 pts). The counts of white blood cells (P < .05), hemoglobin (P < .05), and thrombocytes (P=.001) were all significantly lower at the conclusion of the therapy. The most important adverse events were severe leukopenia (1/34 pts; 2.29 × 103 /µL) and thrombocytopenia (3/34 pts; 32 000, 36 000, 32 000 × 106 /L). Conclusion: We found that lutetium-177 prostate-specific membrane antigen-617 therapy is a promising treatment method for metastatic castration-resistant prostate cancer patients who are unresponsive to conventional therapy, according to our biochemical, positron emission tomography/computed tomography, and pain score outcomes.

Objectives: Our previous study indicated that USP1 inhibitor ML323 downregulated USP1 in colorectal cancer (CRC) cells, but the specific mechanism was still unknown. Methods: CRC cells were lysed for immunoblotting to detect protein expressions. Quantitative real-time PCR was per- formed to examine mRNA levels. Cycloheximide chase assays were carried out to evaluate the half-life of USP1. Co- immunoprecipitation was used to analyze the polyubiquitination of USP1. Results: USP1 protein stability was enhanced by the proteasome inhibitor MG132 in CRC cells. The wild-type USP1 was upregulated by MG132, but not its catalytic mutant. Additionally, the polyubiquitination of USP1 was enhanced by MG132 as well, which indicated USP1 was degraded through the ubiquitin-proteasome pathway. Meanwhile, we confirmed ML323 downregulated USP1 expression in CRC cells, and cycloheximide chase assay also revealed ML323 reduced USP1 protein stability. Further results showed ML323-induced USP1 downregulation and destabilization were abolished by MG132. Moreover, USP1 protein destabilization was not reversed by the caspase inhibitor Z-VAD, which further suggested ML323-induced USP1 downregulation was not dependent on the effects of cell death in CRC cells. Conclusion: Our results showed USP1 was auto-ubiquitinated, and ML323 destabilized USP1 through the ubiquitin- proteasome pathway in CRC cells, providing a theoretical basis for anti-CRC drugs’ development targeting USP1.

Objectives: Accumulating evidence has implicated DNA methylation in the development of non-syndromic cleft pal- ate only (NSCPO); however, little is known about the underlying epigenetic mechanism. This study was to elucidate the role of SATB2 5'untranslated region (UTR) promoter methylation in formation of NSCPO. Methods: DNA methylation profiling was performed on discarded human palatal tissue after repair of NSCPO (case) or maxillofacial and palate trauma (control), using an Illumina 850K-EPIC BeadChip methylation array. The SATB2 5'UTR promoter methylation level was confirmed by pyrosequencing. Results: Five CpG sites (cg14273610, cg22334352, cg25103650, cg22845542 and cg06199336) in the SATB2 5'UTR pro- moter was hypermethylated in cases compared with controls (P<0.05). Pyrosequencing revealed a mean methylation rate of 31.81% vs. 16.45% (p=0.0019) at the cg14273610 CpG site, 22.12% vs. 9.28% (p=0.0102) at the cg22334352 CpG site, 24.41% vs. 8.74% (p=0.0003) at the cg25103650 CpG site, 51.66% vs. 23.97%(p=0.0165) at the cg22845542 CpG site and 31.05% vs. 16.43% (p=0.0091) at the cg06199336 CpG site for cases and controls, respectively. The pyrosequencing results were consistent with those from the Illumina 850K-EPIC methylation BeadChip array. Conclusion: Our results suggested that the SATB2 may be responsible for NSCPO formation and could be a potential biomarker for NSCPO.

Objectives: The aim of this study is to investigate the prognostic impact of CXCL12 and CD44v5 on patients with ad- vanced cervical cancer. Methods: Paraffin specimens from 130 advanced cervix cancer before radiotherapy were examined using immunohis- tochemistry to test the expressions of CXCL12 and CD44v5. The correlations between the expressions of CXCL12 and CD44v5 and the five-year survival rate were analyzed. The expression changes of CXCL12 and CD44v5 in residual cancer tissues after a total radiotherapy dose of 50 Gy were tested by Real-Time PCR. Results: In the 130 patients, a significant correlation was found between CXCL12 and CD44v5 (P=0.028). The coexpres- sion occurred in 34 patients with lower five-year survival rate of 22.9%.There was no correlation between the expression of CXCL12 and CD44v5 and age, tumor stage, size, pelvic lymph node involvement and therapeutic schedule. Log-rank and multi-factor survivals analysis showed that tumor stage, lymph node involvement, CXCL12 expression, CD44v5 expression, CXCL12 and CD44v5 co-expression were independent prognostic factors. The expressions of CXCL12 and CD44 were significant elevated in residual tumor tissues, when compared to pre-radiotherapy, (p<0.05). Conclusion: A significant positive correlation occurred between the expression of CXCL12 and CD44v5. The coexpres- sion might be informative regarding poor prognosis in patients with radical radiotherapy.

Objectives: A standardized nomenclature to report Antinuclear antibody(ANA) is given by the International consensus on ANA pattern (ICAP). The cytoplasmic, mitotic and rare nuclear patterns are infrequently reported.The study was done to understand the clinical significance and frequency of these unconventional patterns in our population. Methods: Retrospective one year blinded study of ANA patterns in serum samples. Results: Of the 4730 samples, 4568 were included after deleting 162 repeat samples. ANA positivity was seen in 673 cases (14.7%). Cytoplasmic patterns were found in 184 cases (27.3%) and mitotic pattern in 16 (2.4%) cases. Exclusive cytoplasmic patterns were seen in 100 cases (14.3%) and exclusive mitotic pattern in 14 cases (2.08%). Rare nuclear pat- terns were seen in 30 cases (4.5%).The most common exclusive cytoplasmic pattern was filamentous(n=39), whereas the common cytoplasmic pattern associated with nuclear pattern (mixed pattern) was cytoplasmic homogeneous (AC- 19). The rare nuclear patterns included Topo-I (n=9), nuclear envelope (n=5), multiple (n=6) and few (n=8) nuclear dots. While some of the common cytoplasmic patterns like filamentous and homogeneous were more frequent in AIDs the uncommon patterns showed varied clinical associations. Conclusion: The study demonstrates the clinical significance of reporting exclusive and mixed non nuclear ANA pat- terns on IIF as many of these have known autoimmune associations.

Objectives: Linked color imaging (LCI) helps to differentiate minor mucosal changes, which can be objectively judged by red–green–blue pixel brightness. However, whether this color analytic model based on pixel brightness can be ap- plied to diagnose Helicobacter pylori infection remains unknown. Methods: Consecutive adult patients with indications and underwent esophagogastroduodenoscopy for the 1st time were enrolled in the training (n=166) and validation (n=79) set. Demographic and clinical characteristics were recorded. Target region in gastric antrum was pictured before biopsy for rapid urea test, and pixel brightness was calculated by MATLAB software. Results: In training set, 25 patients had H. pylori infection. Pixel brightness for R and B in patients with H. pylori infection was greatly higher than those in patients without H. pylori infection (R: 210.203±27.233 vs. 196.401±29.018, p=0.043; B: 127.621±26.112 vs. 125.334±27.812, p=0.025). At the cut off of R = 210 and B = 127, the specificity and sensitivity were 0.696 and 0.701. In validation set, 10 patients had H. pylori infection and the findings were consistent with those in training set. Conclusion: Color analytic model based on pixel brightness under LCI was useful in diagnosing H. pylori infection in gastric antrum.

Objectives: It remains unclear whether hypofractionated (Hypo) thoracic radiotherapy (TRT) is superior to hyperfrac- tionated or conventionally fractionated (Con) TRT in limited-stage small-cell lung cancer. Methods: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched for eligible studies until April 30, 2023. The outcomes of interest were overall survival (OS), and grade ≥3 esophagitis and pneumonitis, reported as hazard ratios (HRs) or odds ratios (ORs) with their 95% confidence intervals (CIs). Results: A total of 23 studies with 7987 patients were identified. Hypo-TRT showed similar OS compared to Hyper-TRT (HR = 1.22, 95% CI: 0.80-1.86 in randomized controlled trials [RCTs] and HR = 1.12, 95% CI: 0.99-1.28 in retrospective studies) and better OS compared to Con-TRT (HR =0.83, 95% CI: 0.70-0.97). Hyper-TRT achieved longer OS compared to Con-TRT in retrospective studies (HR = 0.91, 95% CI: 0.84-0.99), but not in RCTs (HR = 0.90, 95% CI: 0.80-1.01). There were no significant differences in incidence of grade ≥3 esophagitis or pneumonitis between the three schedules. Conclusion: Hyper-TRT (45 Gy) or Con-TRT (60-70 Gy) remains a standard schedule. Hypo-TRT (40-45 Gy) is likely to be an alternative regimen. Nevertheless, these findings need to be validated in large phase 3 RCTs.

Epigenetic reprogramming is the leading mechanism for cell differentiation in early development which gradually takes place upon zygote formation. This is governed by epigenetic modifications of genes involved in cell differen- tiation defined by Waddington’s landscape. Somatic cells have specific gene expression profiles regulated by distinct epigenetic patterns. Therefore, they maintain their identity and specific gene profiles throughout lifetime. Although somatic cells can be induced into stem cell-like structures, the possible transformation of the cells can be associated with disruptions in cell identity leading to carcinogenesis. The epigenetic code for cell identity is the crucial player for maintaining stability and wellness of the cells during their lifespan. This review summarizes the epigenetic regulations involved in establishment of cellular fate and their abnormalities in cancer.

Objectives: Zinc Finger Protein 536 (ZNF536) is a highly conserved zinc finger protein, acting as DNA-binding transcrip- tion suppressor, and negatively regulating neuron differentiation. However, the role of ZNF536 in cancers is still unknown. Methods: In this study, we aim to comprehensively explore the biologic and prognostic implication of ZNF536 in pan- cancer by multi-layered analysis. The mRNA differential expression and DNA methylation of ZNF536 in pan-cancer and normal controls based on The Cancer Genome Atlas (TCGA) and Genotype Tissue-Expression (GTEx) data were inter- preted. Immunohistochemistry was performed on a tissue micro-array to detect the protein expression of ZNF536. The prognostic implication of ZNF536 in pan-cancer was studied by survival analysis. The cBioPortal database was used to display ZNF536 genomic alterations. The co-expression of ZNF536 and immune-related genes in pan-cancer was inves- tigated. Further research was made on the relationship between ZNF536 expression and tumor immune microenviron- ment. CancerSEA was employed to excavate the ZNF536 expression at single cell level with different cancer function. The biological function of ZNF536 in pan-cancer was exhibited by gene enrichment analysis. Results: The ZNF536 mRNA was highly expressed in 4 out of 33 cancers, but lowly expressed in 22 cancers. Immunohis- tochemistry on the tissue micro-array confirmed the high expression of ZNF536 protein in pancreatic adenocarcinoma (PAAD) and low expression in stomach adenocarcinoma (STAD). DNA hypermethylation in prostate adenocarcinoma (PRAD) was observed, which might result in its down-regulated expression. High expression of ZNF536 predicted poor prognosis in 5 cancers, but predicted favorable prognosis in 2 cancers. Genomic alterations of ZNF536 showed mu- tation in 26 cancers and amplification in 20 cancers. The altered group usually had worse prognosis. ZNF536 mRNA expression was correlated with the degree of immune infiltrates in pan-cancer. Single cell sequencing and gene enrich- ment analysis showed that the ZNF536-correlated genes might regulate a variety of biological processes in pan-cancer, mainly via angiogenesis pathway. Conclusion: Our results indicated that ZNF536 might be a prognostic and immune-related biomarker for specific ma- lignancies through the angiogenesis pathway.

Objectives: Cancer development and/or progression can be imputed to telomere shortening or lengthening. The cur- rent research was planned to assess the relation between leucocyte telomere length (LTL) and nasopharyngeal carci- noma (NPC) development, and to evaluate the association between this biomarker and patients' clinical outcomes, mainly response to chemo-radiotherapy, survival and EBV-DNA load. Methods: Leucocyte telomere length was measured using a singleplex quantitative polymerase chain reaction (qPCR) method in 104 NPC patients and 52 healthy controls. The association between LTL and NPC development was assessed using a Khi-deux test. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated by conditional logistic re- gression to evaluate the relationship LTL and patient’s characteristics. The correlation between LTL and 4-years patient’s survival outcomes was assessed by Kaplan–Meier and Cox-regression analyses. Results: Data analysis revealed a significant association between LTL and risk of NPC development (p<0.0001). LTL was also significantly associated with gender (p=0.003), cigarette smoking (p=0.02) and pre-EBV-DNA load (p=0.017) in NPC. However, no significant association was obtained between LTL and age, alcohol consumption, TNM classification, disease stage, response to chemo-radiotherapy and survival outcomes of NPC patients (p>0.05). Conclusion: The study finding highlighted the close association between LTL and NPC development and showed a sig- nificant association with gender, cigarette smoking and pre-EBV-DNA load, suggesting that LTL could be a promising biomarker for better management of NPC in Morocco. Nevertheless, more studies are needed to highlight the value of LTL as a biomarker for the prediction of the response to treatment and prognosis of NPC.

Amniotic fluid stem cells (AFSCs) are one of the prenatal stem cell populations isolated from the amniotic fluid/mem- brane. They include different subpopulations from various sources of origin. AFSCs have important characteristics, including high self-renewal and proliferation capacity, immunocompatibility and anti-inflammatory properties, and differentiation potential into cell types of all three germ layers in vitro. Given the cardiomyogenesis potential of AFSCs and their importance in tissue engineering and regenerative medicine, this review aims to address the current findings regarding the characteristics of the AFSCs. Moreover, we present the strategies and methods used for the differentia- tion of AFSCs into cardiomyocytes in vitro and in vivo. This review also describes and discusses findings regarding the possible signaling pathways, the well-known molecular regulators, and modifications that are important for AFSCs and their differentiation potential into the cardiomyocytes. In general, this review indicates that AFSCs can efficiently differentiate into cardiomyocytes by different methods. Moreover, induction of the ERK signaling pathway, upregula- tion of epigenetic modifiers (GCN5, EZH2, SUZ12, DNMT1/2, and HP-1α) and the cell cycle regulators (p53, p21, Rb, and p130), suppression of HDAC1/2 and stemness markers (OCT4, NANOG, SOX2, KLF4, and REX1), the relative expression of miR-34a and miR-145, and induction of the expression of structural and functional-specific genes of cardiomyocytes (GATA4, Nkx2.5, cTnT, MHC, Myh6, and Tnni3) are the most important molecular changes during the differentiation of AFSCs into the cardiomyocytes.

Objectives: Given the importance of anemia-induced adverse effects on progression of diabetes mellitus (DM), the main aim of this study is to evaluate anemia prevalence amongst diabetic patients hospitalized in a tertiary hospital. The impacts of some critical determinants, including age, gender, duration of diabetes, glycemic status (HbA1c), and lipid profile on anemia comorbidity or progression of DM, were also assessed. Methods: In this cross-sectional study, all diabetic patients with anemia consecutively referred to the hospital in the first six months of 2018 were included. Data collection was performed according to the electronic medical records using a prepared checklist. Data analysis was also performed by SPSS. ver. 26. Results: A total of 212 participants, 142 females (67%) and 70 males (33%), were included, with a mean age of 53.5±14.4. Based on the Hb and hematocrit measurements, anemia was observed in 71 (33.4%) and 76 (35.8%) patients, respectively. In addition, it was found that the prevalence of anemia directly correlates with aging in diabetic patients. Besides, the prevalence of anemia was higher in the patients with a diabetes duration ranging 5 to 10 years, while its prevalence was remarkably less common in those with diabetes duration of ≥20 years. Notably, anemia was reported more frequently in diabetic patients with desirable lipid profiles. Conclusion: Based on our findings, lipid profile measurement should not be considered a reliable indicator to determine anemia prevalence. In this regard, early diagnosis of anemia by applying a simple hematologic test is highly recommended, which can be more helpful in preventing subsequent renal and cardiovascular adverse events.

Objectives: The primary target of this study is to explore a novel therapeutic pathway of nano Diosgenin (DG) by pinpointing the metabolic enzymes that underlies its anti-breast cancer impacts. Methods: A single dosage of 7.12 Dimethyl Benz(a)anthracene (DMBA) (25 mg/kg b.wt) was injected to induce breast cancer. Oral administration of DG (10 mg/kg b.wt) and DG encapsulated chitosan nanoparticle (DG@CS-NP) (5 mg/kg b.wt) was used to medicate DMBA induced tumor bearing rats just after the emergence of a tumor. After the experimental period, biochemical analyses were carried out. Results: Mammary carcinoma bearing rats showed a significant rise in the levels of glycolytic enzymes (hexokinase, phosphoglucoisomerase, and aldolase) and the pentose phosphate pathway enzyme (glucose-6-phosphate dehydrogenase). It also elicits a drop in gluconeogenic enzymes (glucose-6-phosphatase and fructose 1, 6- diphosphatase) and mitochondrial enzymes (succinate dehydrogenase and malate dehydrogenase). Contrarily, nano DG dramatically reverted the rates of glycolytic enzymes, pentose phosphate pathway enzymes, gluconeogenic enzymes, and mitochondrial enzymes in the mammary, liver and kidney tissues to near normal tiers on compared to plain DG treated rats. Thereby, confirming its chemotherapeutic prospects on metabolic rewiring. Conclusion: Thus, our observations suggested that nano DG is a potent therapeutic agent that might have a significant influence on metabolic complications of breast cancer than free DG.

Objectives: Tumor proliferation is guided by neoangiogenesis; microvascular density (MVD) in the tumor micro-environment increases with the action of different immune system stromal cells such as the mast cells (MCs). Methods: We evaluated Ki-67 proliferation rate, MCs positive to tryptase (MCPT), and MVD in a series of 85 gastric cancer (GC) tissue samples from patients undergoing radical surgery. Results: In tumor tissue, a significant correlation between Ki-67 expression, MCPT, and MVD was found through Pearson t-test analysis (p ranged from 0.01 to 0.03). Conclusion: Ki-67 expression and MVD may indicate the survival prognosis of patients and MCPT could repre-sent a biological marker of radical surgery and angiogenesis. Furthermore, MCPT could be consid-ered as a target of novel anti-angiogenic therapies in GC patients.

Objectives: To determine the diagnostic performance of elastography strain ratio (SR) for the diagnosis of malignant thyroid nodules taking fine needle aspiration cytology (FNAC) as the gold standard at a tertiary care hospital in Pakistan. Methods: This is a cross-sectional study. A total of 150 cases aged 20-60 years, of either gender, who presented with palpable/suspected malignant thyroid nodules of any size with Thyroid Imaging Reporting and Data System (TIRADS) category 3 or above on ultrasonography were included. These were further evaluated by elastography and ultrasoundguided fine needle aspiration cytology (FNAC). The elastography SR of the nodules was assessed. Final diagnosis was made using ultrasound-guided FNAC. Relevant clinical and demographic data were obtained from patient charts. The diagnostic sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were calculated for elastography using FNAC as a gold standard. Results: The mean age of all patients was 41.8±8.6 years (range: 20-60 years). There were 97 (64.67%) males and 53 (35.33%) females. The majority of patients, 50 (33.33%), belonged to age category of 41 to 50 years. Taking elastography SR of > 2.32 as the cut-off, 69 (46.0%) nodules were positive, and 81 (54.0%) were negative. The FNAC results showed that 72 (48.0%) were positive, and 78 (52.0%) were negative. The diagnostic sensitivity of SR was 92.31%, specificity, 87.50%, positive predictive value, 88.89% and negative predictive value was 91.30%. The overall diagnostic accuracy was estimated to be 87.5%. Conclusion: The results from this study show that elastography and SR are highly valuable in discriminating benign from malignant thyroid nodules. These may serve as an affordable and reliable alternative diagnostic technique, particularly in the developing world.

Objectives: Primary central nervous system lymphoma (PCNSL) is a rare malignant disease with poor prognosis. Its low incidence leads to challenges in decision-making for treatment. As a matter of fact, there is still no consensus on the appropriate treatment modalities. In this context, the objective of this study is to investigate and comparatively assess the efficacies of several treatment modalities in the treatment of PCNSL. Methods: Thirty-four patients diagnosed with PCNSL at 5 different hematology centers between 2007 and 2021 were included in the study. Patients’ data from all five centers were collected retrospectively. Since ibrutinib is not approved for this indication in Turkey, consent for off-label use of ibrutinib is obtained from each patient. Ethics committee approval was obtained on June 9, 2021 with decision number 2021/18-05. Results: The median age of the patients was 59 (min.: 22, max.: 78) years. The male-to-female ratio was 1.26/1. Nineteen (55.9%) patients had Eastern Cooperative Oncology Group (ECOG) performance score of ≥2. Fifteen (44.1%) patients had normal lactate dehydrogenase (LDH) levels and only 14.7% of the patients had B symptoms at the time of diagnosis. Magnetic resonance imaging (MRI) revealed a single mass lesion in 14 (41.2%) patients. As an induction therapy, methotrexate- based regimen was administered in 29 (85.3%) patients. Only 14 of the 34 patients received 4 or more cycles of high-dose methotrexate (MTX). About 32.4% of the patients received radiation therapy (RT) during follow-up as a part of induction therapy. Five patients received only RT due to poor performance status. Ibrutinib was administered in 5 patients for refractory disease. It was determined that four or more cycles of MTX treatment increased progression-free survival (PFS) (p=0.031) and overall survival (OS) (p=0.012). Moreover, RT improved PFS (p=0.023). Considering that the complete response achieved by induction therapy influences long-term survival, achievement of the best response to the treatment regimens administered in combination with new agents may prolong survival (PFS: p=0.01, OS: p=0.023). Conclusion: The findings of this study indicate that the initial response to treatment is crucial. Additionally, it was found that high-dose MTX treatment should be administered for 4 cycles or more in order to achieve the best results. Furthermore, it was determined that ibrutinib monotherapy was well-tolerated in our patients with relapsed/refractory disease, with excellent clinical benefits. In conclusion, a combination therapy consisting of high-dose MTX, ibrutinib, and rituximab appears to be a promising initial treatment approach in appropriate patients.

Objectives: There is a great variability of inter-observer disagreements for central stenosis diagnostics depending on the used classification. This study investigates the level of agreement between lumbar magnetic resonance imaging (MRI) reports created by a deep learning neural network (CoLumbo) and the radiologists’ reading. Methods: A total of 382 (53.4 % females, 46.6 % males and average age 49.52±13.20) prospective consecutive patients in 3 different healthcare centers referred to L-spine MRI for back or leg pain were analyzed by the software CoLumbo for the presence of stenosis on all lumbar levels, by radiologists using it and radiologists not using the dedicated software. In case of disagreement between radiologists, a radiologist-arbiter opinion was used to establish majority opinion. The total number of evaluated levels was 1762. Results: There were 156 debatable cases of disagreements between radiologists using the software, and radiologists, not using CoLumbo, for the presence of central stenosis. In 18 cases, the arbiter opinion has coincided with that of the radiologist not using the software. In 138 cases, the former has coincided with that of the radiologist using the software CoLumbo. Most of the cases of disagreement are borderline cases. The reported sensitivity and specificity of CoLumbo was 92.70% and 99.04%, respectively. Conclusion: The study showed that the radiologist using the CoLumbo software achieved best results. The results of the algorithm were inferior but still better than radiologists not using the software in any published study.

Objectives: Enzalutamide(ENZ) is an effective hormonal treatment modality in mCRPC. It can be used before or after docetaxel(DTX) in this setting. Herein, we aimed to show the efficacy of ENZ before or after DTX use and the factors predicting the efficacy. Methods: We retrospectively collected the data of 320 patients from 12 centers who were treated with ENZ in mCRPC. The initial stage, age, line of treatment, serum prostate-specific antigen (PSA) levels before ENZ treatment and at nadir, site of metastasis, gleason score were evaluated. Results: Median age of 320 patients were 69. At a median follow-up of 56 months, 271/320 (84.7%) disease progression and 230/320(71.9%) death had been observed. Median PFS was 11(8.9-13)) and median OS was 25(22.1-27.8) months in all patients group. Median PFS was 10(7.4-12.5) months, 11(8-13.9) months in pre-DTX and post-DTX groups respectively. Median OS was higher in the post-DTX group than the pre-DTX group (28(25.7-30.2) vs 19(15.0-22.9-46.6) (p:0.000). Gleason score≥8 (HR 0.59, 95%CI 0.46-0.77, p=0.00), presence of non-visceral metastasis (HR 0.72, 95%CI 0.53-0.97, p=0.031), initial PSA value<43(median) (HR 0.70, 95%CI 0.54-0.91, p=0.009), PSA at nadir <2 (HR 0.61, 95%CI 0.44-0.85, p=0.004), >50% decline in PSA (HR 0.27, 95%CI 0.19-0.36, p=0.000) significantly predicted ENZ response regarding rPFS. Conclusion: ENZ has shown equal efficacy before and after DTX treatment in mCRPC regarding rPFS. But OS rate was significantly better in the pre-DTX group. Therefore, we recommend starting with DTX in patients who can tolerate chemotherapy in mCRPC setting.

Objectives: A member of the flavonoid family, chalcones are natural compounds known to have anticancer effects. Chalcones and their synthetic derivatives have become an important field of interest for cancer research. In this study, we aimed to investigate the anticancer activity of a new Chalcone derivative compound [(2E,4E)-1-(7-ethoxy-1-benzofuran- 2-yl)-5-(4-hydroxy-3-methoxyphenyl)penta-2,4-dien-1-one] synthesized by the Claisen-Schmidt reaction based on the curcumin structure in human lung (A549, H1299) and colon cancer (HCT116, HT29) cells. Methods: The effect of Chalcone compound on cell viability was evaluated with the SRB test. In addition, combination studies with 5-FU, which is used as a chemotherapy drug, was performed. The cell death mode was determined by fluorescence imaging method with Hoechst 33342, Annexin-V-FITC and Propidium iodide (PI) triple staining. Results: IC50 values of the Chalcone compound were found as 2.85, 1.46, 0.59, 0.35 μM for A549, H1299, HCT116, HT29, respectively. As a result of fluorescence imaging, pycnotic nuclei and chromatin condensation were observed in the cells in addition to positive staining with Annexin-V-FITC (green). Conclusion: The results showed that the newly synthesized Chalcone derivative compound has a significant cytotoxic effect on cancer cells and induce apoptosis.

In the world nowadays, cancer gradually becomes the first problem to public health and seriously threatens human life due to the high mortality and recurrence. In modern medical theory, cancer is considered as a genetic disease presenting either oncogene activation (OCG) or tumor suppressor gene (TSG) inactivation. Many clinical observations showed that the existing standard chemotherapies which target oncogenes and their related molecules have little benefit in improving survival, prognosis, recurrence and metastasis despite tumor size shrinkage. Compared with these routine treatment methods, the traditional Chinese medicine (TCM) cancer therapy based on TCM theory, in which the cancer initiation is regarded as disorder of human body system, focuses on the events impacting the gene rather than the gene itself. In fact, it is necessary but not sufficient for cancer initiation and progression to activate OCG or inactivate TSG, which exhibit oncogene or tumor-suppressor property depending on the biological context. In TCM theory, lung and large intestine are external-internal relations of each other, which are physiologically related and pathologically affected each other. Hence, the use of a classical laxative medicine rhubarb for lung cancer treatment is in line with TCM theory. Emodin as the major component of rhubarb represents the multi-targeting therapeutic mechanisms of TCM in multiple disease treatment including anti-cancer. There are some reviews on microscopic and inner mechanisms of emodin in cancer treatment, our previous study confirmed lung cancer-preventing effect of lung cancer. Here, we summarize the real mechanisms of emodin treating lung cancer based on system pharmacology, mainly focusing on the resolution of intrinsic pathological inducers, which will provide a solid foundation to understand cancer pathogenesis and formulate cancer therapy.

Autophagy is a process in which lysosome-mediated intracellular damage or aging organelles and proteins are degraded to produce amino acids, fatty acids, ATP, etc., and then reused by cells. Under normal physiological conditions, cardiomyocytes maintain low levels of autophagy. However, autophagy is activated during myocardial ischemia-reperfusion (MI/R), and autophagosomes increase significantly, indicating that autophagy plays an important role in myocardial ischemia-reperfusion injury (MI/RI). Studies have shown that autophagy has protective and detrimental effects on MI/RI and is regulated by a variety of factors. This article reviews the relationship between autophagy and MI/RI.

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Here, we present the case of a 74-year-old woman with clinically prominent hirsutism and a large adrenal mass where the clinical diagnosis was inconsistent with the histological appearance. Her hormonal evaluation showed normal androgens with slightly inadequate cortisol suppression upon dexamethasone test but normal 24-h urinary free cortisol. Abdominal computed tomography (CT) imaging showed a large inhomogeneous mass of the left adrenal and the FDG PET/CT scan revealed hypermetabolic foci in the right upper lobe of the lung, in hilum lymph nodes, and in the soft tissue in proximity to the right femoral neck. The cytological examination of a biopsy from the pulmonary lesion showed a highly malignant neoplasm of unknown origin, and left adrenalectomy, nephrectomy, and splenectomy were performed. The pathologists reported infiltration of the adrenal by an undifferentiated carcinoma of unknown origin. Due to the clinical suspicion of adrenocortical carcinoma (ACC), a mitotane therapy along with hydrocortisone substitution was directly initiated, and the patient also received 6 cycles of chemotherapy. However, the patient’s condition deteriorated quickly, and she died. Upon availability of steroidogenic factor-1 staining, the positivity of the resected tumor could be documented postmortem, confirming the diagnosis of an ACC. Taken together, this case underlines the difficulties in the differential diagnosis of aggressive adrenal masses.

Soft tissue sarcoma is a heterogeneous disease and treatment options are limited in advanced stage settings. Brivudine is a thymidine-nucleoside analog and inhibits DNA polymerase in VZV infection. We demonstrated a case of a patient who was diagnosed with both VZV infection and advanced stage sarcoma, and unexpected anti-tumoral response after brivudine therapy.

Microtubule-targeting agents often have limitations to the development of resistance. Colchicine binding site (CBS) agents have several advantages compared with other tubulin inhibitors. Numerous medications in this class are less susceptible to multidrug resistance that restricts the viability of different inhibitors. In the present study, molecules that bind to the CBS of tubulin are collected from PubMed literature against the A549 cancer cell line. Regression models were established between the descriptor and IC50 value of all the compounds present in the training set based on significant molecular fingerprints using multiple linear regression (MLR). Fifteen most significant descriptors selected include Burden modified eigenvalue descriptors, PaDEL-weighted path descriptor, autocorrelation descriptor, topological distance matrix descriptor, MLFER descriptor, Barysz matrix descriptor, chi path cluster descriptor, and validated using internal and external validation parameters. The selected MLR-GA model has R2adjusted = 0.7895, Q2 CV = 0.76577, R2 pred = 0.7419, and R2 tes = 0.77373. An applicability domain is also defined so that it defines the chemical space that the model can predict. The above details suggest a good predictive model for CBS inhibitors that can predict the IC50 value of the unknown chemical compound.

Objectives: Analysis of multi-molecular interactions and detection of combinatorial transcriptomic signatures are emerging as important research topics in disease analytics. Currently, a combination of gene and miRNA expression profiling in bioinformatic analysis enables us to comprehensively detect molecular changes in cancer and thereafter to identify integrated signatures and pathways that exist in the miRNA and gene interaction networks. Although many methodologies and applications have been suggested in recent literature, efficient techniques that can integrate the complex gene as well as miRNA expression profiles, and identify the most relevant signatures are required. Methods: In this article, we presented a new framework of multi-molecular data integration to identify combinatorial transcriptomic signatures through the strategy of unsupervised learning and target detection. Later, we evaluated their utility in survival analysis through a multi-variate Cox regression study. We used a cervical cancer data repository to conduct our experiment. To construct the miRNA-mRNA interaction network, we selected the downregulated mRNAs that were negatively correlated with the upregulated miRNAs. Thereafter, we identified dense modules by using an unsupervised learning technique. The silhouette index value was computed for each cluster. Results: By considering the network centrality of each molecule belonging to each cluster we identified top 3 combined signatures We also highlighted cluster-2 (hsa-mir-944, CFTR, GABRB2, HNF4G, TAC1, and C7orf57) for its high cohesiveness and contained a combined signature. We then applied three well-known classifiers (viz., SVM, KNN, and random forest) using 10-fold cross-validation, and obtained a high AUC score for cluster-2. Finally, we conducted a survival study with each molecule of the same cluster. Conclusion: Finally, we conducted a survival study with each molecule of the same cluster. Our proposed combined signature detection strategy can determine the signature(s) for any microarray or RNA-Seq profile. The code is available at https://github.com/sahasuparna/DeMoS

Objectives: To investigate the immune inflammatory profile in patients affected by benign salivary gland tumors (SGTs) by evaluating the blood inflammatory biomarkers. Methods: A retrospective chart review was performed between January 2015 and April 2020, collecting the data of all patients admitted for benign SGTs in our maxillofacial surgery unit. A total of 191 patients were divided into two groups: 94 with Warthin’s tumor (WT group) and 97 with pleomorphic adenoma (PA group) at histological diagnosis. The third group consisted of 90 patients randomly selected as the control group (C group). Results: The most relevant correlations were found by analyzing the values of some inflammatory biomarkers among the three groups. The neutrophil-to-lymphocyte ratio was found significantly higher in patients in the PA (p<0.005) and WT (p<0.001) groups than in patients in the C group. Similarly, the systemic immune-inflammation index was found significantly higher in patients in the PA and WT (p<0.005) groups than in patients in the C group. The platelet-tolymphocyte ratio was significantly higher in patients in the PA group than in patients in the WT (p<0.05) and C groups (p<0.05). Conclusion: In both WT and PA groups, the inflammatory status of the patients was found altered. Thus, inflammation and the immune system seem to have a role in the genesis of these benign salivary neoplasms whose etiopathogenesis is still debated.

Objectives: Breast cancer (BCa) remains the world’s second biggest cause of cancer death. This occurs as a result of unregulated cell development and can be metastasized to other parts of the human. Estrogen receptor alpha is the renowned target that has piqued the interest of researchers to target BCa. FlexX molecular docking technique was used to predict the aspects of interaction, affinities energy, and orientation of natural compounds in the protein site. Phytoconstituents have a vital role in anticancer activities due to their important scaffolds, which may offer more effective and reduced costs and side effects than synthetic drugs. The present study aims to identify new anticancer agents from natural and dietary compounds with lesser adverse effects. Methods: To accomplish this, we implemented with the help of molecular docking approaches using FlexX for predicting the features of bioactive phytocompounds from natural products and evaluating targeted binding affinity energy. Results: Our results confirm that among various natural compounds, daidzein has the best docking score in the ten compounds compared with the standard drug cytarabine. Conclusion: Our study suggests that daidzein is a potent ligand for ERα BCa among all and can be further investigated through in vitro and in vivo studies.

Objectives: The objective of the study is to evaluate the expression of CD10 in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC) and to determine its role as a potential biomarker in OSCC. Methods: Immunohistochemical evaluation of 40 archival paraffin-embedded tissue specimens grouped into oral epithelial dysplasia and early invasive, well-differentiated, and moderately differentiated OSCC was conducted to determine and compare the CD10 expression among the groups. Stromal positivity of the CD10 expression was calculated and statistically analyzed at p<0.05. Results: The results of the study showed that there was a statistically significant increase in the mean CD10 expression among the four groups. Intergroup comparison showed a statistically significant difference between oral epithelial dysplasia and OSCC while statistical significance was not observed in the various grades of OSCC. Conclusion: CD10 expression could be used as an important biomarker for determining the progression of oral epithelial dysplasia and the overall prognosis of OSCC.

Objectives: Composite lymphomas (CL), which are a combination of different types of lymphomas in a single patient can occur simultaneously or sequentially. Diagnosis and treatment of CL require a full range of modern approaches. Methods: The study included 37 cases of CL (M:F=2:1), the median age of patients was 64 (38-83 years). All patients underwent a full range of diagnostic procedures, including histopathological, immunohistochemical/immunophenotypic (flow cytometry), cytogenetic/FISH, and molecular tests at the National Research Centre for Hematology, Moscow. Results: Metachronous CL were observed in 17 cases and the most common type of the second lymphoma was diffuse large B-cell lymphoma (DLBCL) or Hodgkin's lymphoma (HL). In 30% of cases, DLBCL developed after HL therapy, and in 30% - after therapy of angioimmunoblastic T-cell lymphoma (AITL). In 20 cases of synchronous CL the most common was B-cell chronic lymphocytic leukemia (B-CLL) combined with hairy cell leukemia (HCL) - 54.5%, large granular lymphocytic leukemia, marginal zone lymphoma (MZL), follicular lymphoma, multiple myeloma, or mycosis fungoides. A combination of HL with other lymphoma was observed in 25% of cases (HL+MZL represent 60% of cases). Conclusion: CL are excellent models for studying the complex process of tumor cells evolution during the course of the disease. Treatment of CL is a non-trivial task and aims to control both diseases.

Objectives: Worldwide, Non-Muscle-Invasive Bladder Cancer (NMIBC) patients are characterized by a high rate of recurrence and progression highlighting the need for a valuable prognostic estimation for better management of this disease. Thus, the present preliminary study was planned to evaluate the validation of the European Organization for Research and Treatment of Cancer (EORTC) and the Spanish Urological Club for Oncological Treatment (CUETO) risk tables to predict recurrence and progression in Moroccan patients with NMIBC. Methods: A total of 56 NMIBC patients that have undergone transurethral resection of bladder tumor (TURBT), between January 2017 and May 2021, were recruited. The recurrence and progression rates at 1 and 5 years were calculated for each patient using EORTC and CUETO scoring models and compared to EORTC and CUETO risk tables. KaplanMeier was performed to validate stratification and difference between the four groups obtained. A univariate analysis using the Cox regression test was realized to evaluate the association between prognostic factors with recurrence and progression of the disease. Results: For the 56 NMIBC patients, the median follow-up duration was 49.68 months. In this cohort, 43 patients had recurrent tumors, and 27 showed progression to an advanced stage and/or grade. At 1-year progression and recurrence rates were higher than the values predicted by the EORTC and CUETO risk tables, while both tables overestimate the long-term risk probabilities of recurrence and progression. Only the CUETO model successfully stratified our patients with statistically significant differences between the four groups of recurrence (p=0.005). Of particular interest, univariate Cox analysis indicated that only prior recurrence rate had a significant effect on both recurrence-free survival (p=0.04) and progression-free survival (p=0.037). Conclusion: CUETO scoring model is better than EORTC for recurrence stratification in Moroccan patients with NMIBC. Both models overestimate risk in 1-year and underestimate risk in 5-years. A prospective study should be realized in large cohorts to establish an ideal prognosis model for Moroccan NMIBC patients.

Objectives: Human Papillomavirus (HPV) is the main contributor to the development of cervical cancer. This study aimed to investigate the biological significance of changes in the expression of lncRNAs induced by HPV oncoproteins in cervical oncogenesis mechanisms. Methods: We performed a review using online databases. The alterations were associated with some molecular and/or cellular characteristics that could be involved in the pathogenesis of cervical cancer. The molecular targets of the RNAs were identified using the Gene Expression Profiling Interactive Analysis (GEPIA) bioinformatics sites/tools, GeneCards®, OMIM, and Lnc2Cancer 3.0. Results: Sixty-one altered lncRNAs were identified. The alterations contribute to the higher staging of cervical cancer and a worse prognosis. These lncRNAs can act by competing for miRNAs for response elements, influencing the regulation of target genes and, ultimately, participating in the cancer regulation process and exhibit multiple biological functions, such as chromatin modification, transcription, translation, splicing, and epigenetic regulation. Conclusion: Changes in lncRNA expression have been associated with the onset, progression, and prognosis of cervical cancer. These changes can contribute to several features of cervical oncogenesis, and their identification has the potential to provide new biomarkers and therapeutic targets for the treatment of this cancer.

Currently, cancer is an important health problem, and virus-related infections have a large share among the factors that have been confirmed to play a role in the etiology of cancer. Until now, virus-associated cancers and nonvirusassociated cancers are treated with the same therapeutic agents. The answer to the question of whether the treatment of virus-associated tumors should be different from the treatment of other tumors has not yet been clearly answered. In addition to protective methods such as vaccination and pretransfusion serological tests, the immune system also plays an important role in eliminating the virus from the body. Besides, viruses escape from the immune system in various ways. Immunotherapies, which have been used in recent years, have brought a different dimension to cancer treatment by eliminating the inhibition of the immune checkpoint and activating T lymphocytes, thus showing an immunostimulating effect. The data showing that these agents, which are used in many types of cancer, may also be effective in virus-related cancers are increasing day by day. In this review, we aimed to evaluate the results of immunotherapies in randomized controlled trials in virus-associated cancers. Immunotherapies can play a role in many issues such as treatment of premalignant lesions and elimination of suppression or immunity after malignancy develops. As we summarized in our study, many randomized controlled clinical studies are ongoing to investigate the effectiveness of immunotherapies in virus-related cancers, and the results of these studies will answer many questions.

While humanity has not been able to end the fight against the COVID-19 pandemic, newly reported cases of monkeypox have caused unease. The current review sheds light on the transmission routes, pathogenesis, clinical presentation, treatment, and prevention of the disease in this early stage of the ongoing monkeypox epidemic.

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Sarcoid like reaction is an interesting entity in cases treated by checkpoint inhibitor treatment and suggests a good response to therapy. Here a case with granulomatous reaction has been reported in a case with malignant mesothelioma treated by nivolumab. This entity may simulate disease progression by imaging modalities especially in PET/CT.

Objectives: Breast cancer is among the most commonly diagnosed cancers and one of the main causes of cancerrelated deaths in females. Long noncoding RNAs (lncRNA) are vital regulators of both oncogenesis and tumor suppression involved in crucial cancer pathways. Recent studies have demonstrated that LINC01296 and LINC00152 were aberrantly upregulated in different tumor types. In this study, we aimed to assess the expression levels of LINC01296 and LINC00152 in breast cancer and its adjacent tissues. Methods: Sample tissues were collected from 49 women with breast cancer referred to Shahid Faghihi Hospital in Shiraz for surgery from 2017 to 2018. Total RNA was extracted from fresh tumor and normal breast cancer tissues and expression of lncRNAs was assessed using real-time polymerase chain reaction. Results: A significant upregulation of LINC01296 and LINC00152 in breast cancer tissues compared with the adjacent normal tissues was observed (p<0.01). The Mann–Whitney analysis showed a significant relationship between the upregulation of LINC01296 and the use of oral contraceptives in luminal B breast cancer subjects (p=0.028). No significant relationship was found between the expression of LINC01296 and quantitative variables. Conclusion: This study showed an upregulation of LINC01296 and LINC00152 in breast cancer tissues compared with the adjacent normal tissues.

Objectives: Cancer patients were found to be at higher risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and experienced more adverse outcomes. The objective of this meta-analysis was to estimate the prevalence of lung cancer patients with SARS-CoV-2 infection during the COVID-19 pandemic. Methods: A comprehensive search was carried out on PubMed, Web of Science, Scopus, MedRxiv, SciELO, SID, CNKI, and Wanfang databases to retrieve all relevant publications. All cross-sectional studies and consecutive case series on cancer patients with SARS-CoV-2 infection were selected. A total of 28 studies including 5400 infected cancer patients and 767 lung cancer patients with COVID-19 were included. Results: Combined data indicated that the prevalence of lung cancer patients with SARS-CoV-2 infection was 15.2% (95% CI, 0.111–0.205) overall. Stratified analysis by ethnicity showed that the prevalence was 16.4% and 15.4% in Asian and Caucasian lung cancer patients with COVID-19, respectively. Moreover, subgroup analysis by country of origin showed that the prevalence was highest in China (19.3.0%) followed by France (12.6%), the UK (10.7%), and the USA (8.3%). Conclusion: This meta-analysis revealed that the prevalence of lung cancer patients with SARS-CoV-2 infection during the COVID-19 pandemic was 15.2%.

Objectives: Radio-resistance poses a major challenge in nasopharyngeal carcinoma (NPC) treatment. Due to individual variations in radio-sensitivity, biomarkers are needed to tailor radiation treatment. Within this frame, the identification of series of genetic signatures mainly SNPs for NPC patients treated with radiotherapy may help to predict treatment outcome and deliver personalized therapy. The aim of this study was to evaluate the possible association between the GSTP1 Ile105Val and GPX1 Pro198Leu polymorphisms and response to radiotherapy in NPC patients. Methods: From September 2016 to October 2018, a total of 101 patients with confirmed NPC, recruited at Mohammed IV Center for Treatment of Cancer of Casablanca, underwent radiotherapy. DNA was extracted from peripheral blood. Genotyping of the GPX1 Pro198Leu and GPX1 Val105Leu polymorphisms was carried out by PCR amplification and DNA sequencing. SPSS was used to analyse the association of GSTP1 and GPX1 genotypes with clinico-pathological features and response to radiotherapy. Results: The genotyping data revealed the presence of only two genotypes namely Pro/Pro (57.4%) and Pro/Leu (40.6%) for GPX1 gene. The allelic frequencies of C and T alleles were 78.7% and 21.3% respectively. For GSTP gene, the homozygous genotypes Val/Val and Leu/Leu were detected in 35.6% and 12.9% of patients respectively. The heterozygous genotype Val/Leu prevailed (51.5%). Allelic frequencies showed the presence of the two alleles A and G in 57.1% and 42.9% patients respectively. Statistical analysis failed to find any significant association between GSTP Val105Ile and GPX1 Pro198Leu genetic polymorphisms and socio-demographic and clinico-pathological features as well as response to radiotherapy (p>0.05). Conclusion: Further research is warranted on the potential role of SNPs within antioxidant defines genes in radiotherapy response and to identify reliable predictive and non-invasive biomarkers for radio-resistance among NPC patients for personalised therapies.

Objectives: Although immune checkpoint inhibitors (ICIs) became a vital part of cancer care, many patients do not respond to treatment. In this group, a few of the patients with a hyperprogressive disease (HPD) have shorter overall survival (OS) compared with those having a progressive disease (PD). Therefore, biomarkers are needed to differentiate HPD and PD. Methods: Ninety-five patients treated with ICIs with progression according to response evaluation criteria ın solid tumors criteria in the first control imaging were included. HPD was defined according to Russo's work. The PILE scoring system, which includes pan-immune-inflammation value, lactate dehydrogenase, and Eastern Cooperative Oncology Group PS, was followed. The relationship between PILE score and HPD was analyzed. Results: The median OS of all cohorts was 11.18 months. The patients in the HPD group had decreased OS (4.77 vs. 13.94 months, p<0.001) and progression-free survival (PFS) (1.89 vs. 3.16 months, p<0.001) compared with those in the PD group. The risk of HPD was higher than the risk of PD in patients with a high PILE score (p=0.001). Conclusion: In this study, we showed that patients treated with ICI with a higher PILE score are at greater risk for HPD. The PILE score may be a biomarker to differentiate HPD from PD.

Objectives: In cancer centers, various factors influence the type of organism causing bloodstream infection (BSI). Our premise includes the indirect benefits of hand hygiene of healthcare personnel, masking, and distancing practices during lockdown/post-lockdown period on the type of BSI among cancer patients and their antibiotic sensitivity patterns. Methods: The retrospective cohort study was conducted from November 2020 to July 2021, among cancer patients admitted to Healthcare Global cancer center. Blood culture reports of patients presenting with symptoms of BSI were retrieved and analyzed in the Department of Preventive Oncology, Healthcare Global. Our data were stratified from pre-lockdown (November 2019 to March 24, 2020) and lockdown/post-lockdown (March 25, 2020, to Jul 2020) periods. Results: The proportion of culture positives during the pre-lockdown (Nov 2019 to March 24, 2020) and post-lockdown period (March 25, 2020, to July 2020) are 21.7% and 21.1%, respectively. However, this small difference did not show a significant association with the difference in hand hygiene during the two periods (<80% and ≥80%). In our study, Escherichia coli (23.8%), Staphylococcus epidermidis (10.9 %), and Klebsiella pneumoniae (17.8%) were the most common BSI during the pre-lockdown period. A similar analysis during the post-lockdown period shows a higher prevalence of E. coli (20.7%), Staphylococcus haemolyticus (12.1%), and K. pneumoniae (15.5%). In our study, the isolates showed a greater proportion of resistance (>50%) to Gentamicin, Ciprofloxacin, Tigecycline, and Cephalosporin group of drugs. Conclusion: During COVID times, some of the preventive interventions which were implemented for reducing the transmission of SARS-CoV-2 could contribute to the reduction of BSI in the hospital setting. For the management of BSI, it is imperative to initiate appropriate antimicrobial treatment at an early stage. It is imperative for customizing the antimicrobial stewardship strategies as per the geographic location.

Objectives: Сutаnеоus mеlаnоmа (CM) is characterized bу molecular heterogeneity. The aim of the study was to clarify clinical and pathological characteristics associated with gene mutations in the MAPK signaling pathway in Russian CM patients. Methods: BRAF, NRAS, KIT, and PDGFRA mutations were evaluated in tumor DNA from 214 CM patients with Sanger sequencing of PCR products. Results: Analysis of 173 non-acral CM revealed somatic mutations in BRAF (61.3%), NRAS (15.0%), KIT (1.1%), PDGFRA (1.1%), while 41 metastatic melanomas with unknown primary sites demonstrated a lower frequency of BRAF (46.3%) and NRAS (12.2%) mutations. The spectrum of BRAF and NRAS mutations differs among CM specimens, depending on tumor location and UV exposure. BRAFV600E was found in 90.4% of BRAF+ melanomas, that is, 52.8% of all CM cases, among them in 70% of patients aged under 30 years. KIT exon 11 mutations (p.V559A and p.Q556_W557del) were detected in CM, affecting the skin areas exposed to UV insolation (lower lip and shoulder). Somatic PDGFRA mutations (p.R558C and p.S847L) were found in patients with metastatic nodular CM of shin and back. Substitution c.2472C>T PDGFRA (silent mutation p.V824V or functional synonymous SNP rs2228230:C>T) was detected in CM cases with low expression of immunohistochemical diagnostic markers (poorly differentiated CM). Conclusion: Molecular genetic study has revealed the prevalence of BRAF, NRAS and KIT (italics) gene mutations which were associated with primary non-acral CM location, whereas PDGFRA (italics) alterations were detected in a few metastatic poorly differentiated CM cases.

Objectives: The aim was to point out the importance of the diagnosis rate of breast cancer (BC) by analyzing the cancer predisposition genes except BRCA1/2 with multigene testing. Methods: In this study, 232 non-BRCA cases with BC and/or BC family history (FH) were analyzed using the next-generation sequencing method. Results: Twenty-two different pathogenic/likely pathogenic variants were determined in 24 (10.34%) of cases, and these variants were detected in the CHEK2 (7/24, 29.1%), ATM (5/24, 20.8%), MUTYH (3/24, 12.5%), BLM (2/24, 8.3%), WRN (2/24, 8.3%), TP53 (1/24, 4.1%), BRIP1 (1/24, 4.1%), MSH2 (1/24, 4.1%), NBN (1/24, 4.1%), and PTEN (1/24, 4.1%) genes including three novel variants which were identified in the BLM, ATM, and MSH2 (3/22, 13.6%) genes. Fourteen of 24 (58.3%) cases had BC diagnosis, and 10 of 24 (41.6%) cases had a FH of BC. Conclusion: Among non-BRCA BC and/or BC FH cases, cancer susceptibility gene frequency was 10.34% in this study. CHEK2 and ATM genes had relatively high mutation rates.

Objectives: Targeted agents combined with immune checkpoint inhibitors (ICIs) for advanced hepatocellular carcinoma (HCC) may improve survival for some patients. This study aims to identify the patients who are most likely to benefit from combination therapy. Methods: The study included 45 patients receiving lenvatinib while other 65 patients receiving lenvatinib plus ICIs between January 2019 and August 2020. Clinical and laboratory data were evaluated and compared. Results: The median follow-up was 20.5 months in the lenvatinib and 18.0 months in the combination group. The corresponding median overall survival was 9.3 and 13.0 months (p=0.004), respectively. Subgroup analyses found that lenvatinib plus ICIs was associated with better overall survival in patients younger than 60 years, males, without MAFLD as well as with BMI <23 kg/m2, cirrhosis, HBV infection, total tumor volume ≥982 cm3, tumor burden score of ≥10.4 or α-fetoprotein ≥200 ng/ml. Conclusion: Lenvatinib plus ICIs therapy seems to be more effective in advanced HCC patients with viral etiology, low BMI, or high tumor load.

Cancer cell plasticity includes their interconversion into various subtypes or entirely different cells through transdifferentiation. This allows the cells to survive in difficult microenvironments while remaining unresponsive to treatment. Plastic characteristics of cancer cells include increased metastasis, tumorigenesis, and chemoresistance. Though many pathways regulate these activities, this paper focuses on the Wnt signaling pathway. When Wnt is activated, the Axin is dephosphorylated, allowing the phosphorylation of β-catenin (β-Cat) and the degradation of antigen-presenting cell (APC). This degradation is important because APC is classified as a tumor suppressor; therefore, when Wnt is on, tumorigenesis is more likely to occur. Lung cancer contains a subpopulation of cancer stem-like cells (CS-LCs), which are highly resistant to anticancer drugs and are a major catalyst for tumor recurrence. The Wnt signaling pathway, in conjunction with other pathways, is a key player in the development and maintenance of cancer stem cells, catalyzing increased chemoresistance and metastasis. The Wnt signaling pathway can sustain these CS-LCs with β-Cat present in the pathway. In this review, we summarize the current knowledge surrounding the Wnt signaling pathway as well as its crosstalk with other pathways and their implications for cancer cell plasticity.

Immunotherapies (ICI) are used alone, in combination with chemotherapy (CT) or targeted therapy in many cancers. All current developments will be reviewed in gastrointetsinal tract tumor treatment.

The disease that poses a major threat to human life is cancer. Although different treatment techniques such as chemotherapy, radiotherapy, and chemically driven drugs are used, they do not show expected results and cause many side effects, eventually leading to the death of patients. However, there is one approach that is promising is the consolidation of cancer vaccines and immunotherapy, in which tumor-specific antigens, tumor-associated antigens, antigen-presenting cells, and toll-like receptors play a major role. The approach involves vaccines that are approved by the FDA and has shown good results in the latest research studies.

Objectives: Hepatocellular carcinoma (HCC) is a common liver cancer accounting with high mortality rate owing to metastasis. Anti-metastatic treatment is scant while proposed mechanisms are in excess, yet specific molecular drivers of HCC remain at large. Therefore, our study aims to identify drivers of HCC metastasis using protein-protein interaction (PPI) networks to identify key driver genes associated with HCC metastasis. Methods: From differential expression genes (DEGs) analysis using GSE45114 microarray dataset, four main hub genes that correlated with patient survival were identified. The first hub gene, SERPINC1 had the highest centrality parameter in impeding HCC metastasis, implicating thrombin mediation through thrombin-induced tumor growth and angiogenesis. Results: Our study reveals that thrombin was not differentially expressed, hence, suggesting the involvement of other, less-well studied pathways in impeding metastasis, such as KNG1, PAH, AMBP, and TTR. Findings for CD44 were con- sistent with existing literature. Meanwhile, FGG and APOA5, both less studied genes in the context cancer metastasis studies, were found to be crucial in impeding HCC metastasis. Conclusion: This study identified four potential proteins (SERPINC1, CD44, FGG and APOA5) to be therapeutic targets or biomarkers and demonstrates the use of PPI networks for understanding HCC metastasis at a more profound level.

Objectives: Necrotizing enterocolitis (NEC) is a severe neonatal condition. This study aimed to assess predictive factors for surgical treatment in preterm neonates with NEC in a Tunisian center. Methods: We present a retrospective study including all neonates treated for NEC between January 01, 2010 and March 31, 2022. Results: Within the study period, 102 patients were included, with an overall survival of 47%. Most of our patients were male (64.7%), with low birth weight or less (100%), 5-min Apgar score ≥8 (79.4%), and Bell’s stage II (66.7%). Multivariate logistic analyses demonstrated that gestational age <30 weeks (p=0.002, odds ratio [OR]=4.544), birth weight <1000 g (p=0.001, OR=5.750), NEC onset <7 days (p<0.001, OR=5.667), not being breastfed (p=0.019, OR=3.026), and C-reactive protein level >20 mg/L (p=0.020, OR=2.942) were associated with the need for surgical treatment in neonates with NEC. Conclusion: Our findings would be helpful in refining treatment modalities for better disease outcomes.

Objectives: The aim of this study is to evaluate the risk factors which lead to post-trans arterial chemoembolization (TACE) hepatic decompensation. Methods: This was a prospective study took place between December 2021 and August 2022 at PEMH, Rawalpindi. After informed consent, 122 patients suffering from hepatocellular carcinoma secondary to chronic hepatitis C were in- cluded who were eligible for TACE as per Barcelona Liver Cancer Algorithm. The baseline variables and post-treatment 30-day variables were noted. Decompensation was assessed using the Child Pugh Score and the ECOG performance score. Baseline variables and demographic variables were compared in patients who developed and did not develop hepatic decompensation. Results: Among the total 122 patients in the study, 95 were males and 64 were older than the age of 50 years. Hepatic decompensation was reported in 54.1% of the total participants. Analysis showed significant association of hepatic decompensation with pre-TACE bilirubin levels, age >50, and pre-TACE alpha-fetoprotein levels. A patient with alpha- fetoprotein (AFP) levels >3200 ng/mL is 2.043 times likely and a patient with age >50 is 4.173 times more likely to have hepatic decompensation after TACE. After TACE, there is increased incidence of ascites and encephalopathy. Conclusion: Hepatic decompensation is commonly encountered in patient’s post-TACE. The predictive factors are age >50, raised bilirubin levels and AFP. >3200 ng/dL.

Objectives: Breast cancer shows the highest incidence and cancer-related deaths among women worldwide. Radio- therapy is used for treating different stages of breast cancer. Several polyphenols have increased the effectiveness of radiotherapy. Wogonin is a flavone compound abundant in the root of Chinese skullcap. This compound induced apop- tosis and inhibited proliferation distinctively in cancer cells. We studied effect of wogonin on the response of a typical breast cancer cell line to ionizing radiation. Methods: MCF-7 cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell counting and double staining apoptosis assays were also used to find suitable physiologically relevant concentra- tions of wogonin. Cells treated with wogonin were exposed to different doses of X-ray and clonogenic survival assay was utilized to determine the effect of wogonin on survival from radiation. Results: Wogonin treatment decreased the viability of MCF-7 cells in a dose- and time-dependent manner. It de - creased number of cells and increased percent of apoptotic cells dose dependently. Cells pretreated with 5 and 10 μM concentrations of wogonin 3 days before radiation showed increased radioresistance compared with cells that were not treated with wogonin. Conclusion: Treatment of MCF-7 breast cancer cells with wogonin made them more resistant to ionizing radiation.

Objectives: Triple negative breast cancer cells are estrogen, progesterone, and HER receptor negative, malign breast cancer cells. These cells have high telomerase activity, and this activity gives these cells high proliferation and evading apoptosis abilities. In this study, we aimed to determine the affect piR-823 on genetic parameters of proliferation and ERα status in MDA-MB-231 cells. Methods: After anti-piR-823 transfection, proliferation of cells was tested by XTT. Gene expressions were determined by RT-PCR. Protein expressions were determined by ELISA. Results: The proliferation decreased after inhibition (p<0.001). Gene and protein expressions of ERα were upregulated while hTERT was downregulated after inhibition (p<0.001). Furthermore, piR-823 inhibition cause to decrease PI3K/ AKT/mTOR gene expressions and miR-126 expression (p<0.001). Conclusion: Obtained data indicates that piR-823 inhibition lead MDA-MB-231 cells to increase ERα expression. De- creased expressions of hTERT and PI3K/AKT/mTOR pathway affect cell proliferation. Moreover, miR-126 decrease in- dicates that piRNAs and miRNAs can share the same target molecules and piRNA expression changes might have an impact on miRNA expressions. All obtained data is important on the perspective of piRNAs and their effect on cellular characteristics of triple negative breast cancer cells.

Objectives: Monoglyceride lipase (MGLL), as a prominent metabolic hub, is known to be actively involved in the devel- opment of the lipogenic phenotype, which promotes de novo lipid biosynthesis, allowing cancer cells to maintain their growth advantage, continuous proliferation, and metastasis. In this study, we aim to investigate mRNA MGLL expres- sion levels and its sub-cellular localization in non-small cell lung cancer (NSCLC) cell lines, as well as examine the effect of two chemotherapy/targeted therapy agents, cisplatin and crizotinib, on the expression levels of MGLL. Methods: pcDNA3.1(-)-MGLL and pEGFPN1-MGLL constructs were sub-cloned into E.coli DH5a and transfected into NSCLC cell lines for MGLL expression evaluation and sub-cellular localization, using polymerase chain reaction (PCR) and quantitative PCR (qPCR) and fluorescence microscopy, respectively. Parent and cisplatin/crizotinib-resistant cell lines were grown and maintained in adequate media for subsequent MGLL expression analysis. Results: PCR and qPCR results revealed that MGLL was successfully transfected into the H1299 cells and efficiently expressed. Fluorescence microscopy of the pEGFPN1-MGLL transfected cells revealed a cytosolic expression of MGLL. As per the analysis on the effect of cisplatin and crizotinib on MGLL expression, a notable downregulation of MGLL expression was noted in the resistant cell lines. Conclusion: These results provide groundwork for further research on molecules modulating MGLL expression, which may be deemed helpful to provide therapy options targeting MGLL in NSCLC treatment.

Objectives: Peritoneal metastasis (PM) is a poor prognostic factor for all malignancies and remains difficult to treat with systemic chemotherapy because of poor peritoneal vascularization, resulting in limited drug delivery and penetration into tissues. Our study aims to investigate the efficacy and safety of different locoregional treatment protocols with hy- perthermic intraperitoneal chemotherapy (HIPEC), Early Peritoneal Chemotherapy (EPIC), Pressurized Intraperitoneal Chemotherapy (PIPAC) in the management of advanced colorectal cancer with metachronous PM. Methods: A total of 42 patients were divided into three groups, as follows. Group A: After neoadjuvant systemic che- motherapy, 15 patients received cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) and then adjuvant systemic chemotherapy. Group B: After neoadjuvant systemic chemotherapy, 12 patients received CRS + HIPEC + early postoperative intraperitoneal chemotherapy for 5 postoperative days and then adjuvant systemic chemotherapy. Group C: After neoadjuvant chemotherapy, 15 patients received CRS + HIPEC and then an adjuvant bedside HIPEC on the 10th postoperative day combined with postoperative adjuvant chemotherapy. Results: Patients in group A had a median overall survival (OS) of 33 months; however, log-rank tests showed that sur- vival distributions of the three groups were not statistically significant different for both OS and disease-free survival. Conclusion: In conclusion, CRS plus HIPEC remains an alternative to locoregional treatment in well-selected patients with PM in combination with systemic neoadjuvant and adjuvant chemotherapy.

Objectives: To assess the correlation between imaging findings and Cancer Antigen (CA) 125 serum value in the fol- low-up of ovarian cancer. Methods: We included 41 consecutive patients with malignant ovarian epithelial cancer who underwent surgical de- bulking at our institution (Jan 2014–Dec 2018). Computed Tomography (CT) / Positron Emission Tomography (PET)-CT images obtained during follow-up were reviewed for the presence of disease (yes/no). Imaging findings were com- pared with the CA 125 serum values at the time of examination. Results: Of the 211 imaging studies, 117 (55.5%) were negative for the presence of disease, whereas 94 (44.5%) were positive. The median CA 125 value was 87 U/mL in patients with positive imaging findings and 10 U/mL in patients with negative ones (Mann-Whitney U test, p<0.0001). Of the 129 examinations performed in patients with normal CA 125 serum value, 110 (85.3%) were negative for disease, whereas 19 (14.7%) were positive; the median CA 125 serum value of the latter were 10 U/mL in patients with negative imaging findings and 23 U/mL in patients with positive ones (Mann-Whitney U test, p<0.0001). Only 3/129(2.3%) patients with normal CA 125 serum value, no CA 125 increasing trend and no clinical suspicion of progression showed positive imaging findings. Conclusion: A strict correlation between CA 125 serum value and imaging finding was observed. Imaging should be avoided in patients with normal CA 125 serum value and no clinical suspicion of disease progression.

Objectives: To discover micro ribonucleic acids (miRNAs) involved in the regulation of DDX3 expression using sexual hormones in combination with the well-known anticancer medication cisplatin. Methods: SiHa cells were treated with estradiol, dihydrotestosterone, and cisplatin and evaluated the expression of ER beta, Ki67, and DDX3 via quantitative reverse transcription–polymerase chain reaction. We generated a chimeric fusion construct five untranslated region (UTR)–hLUC–3UTR in the pEZX-MT06 miRNA vector under the control of the SV40 promoter. Reporter activity is measured with/without hormones, and their activity is compared with 5'- and 3'-UTR respectively. Various reporter deletion constructs were generated to identify the minimal UTR region in regulating the expression of DDX3. We identified the potential miRNA binding sites on the DDX3 UTR region, and their expression is monitored in cancer patients and cisplatin-treated SiHa cells. Results: Hormones increased the proliferation of SiHa cells and expression of DDX3. The 3'-UTR region 2135–4307bp contains miRNA sites that regulate DDX3 expression. miRNAs hsa-miR-671-5p, hsa-miR-361-5p, hsa-miR-140-5p, hsa- miR-564, and hsa-miR-769-5p downregulated in patient samples but upregulated in cisplatin-treated cells. miRNA hsa- miR-671-5p and hsa-miR-564 were associated with patient data and cisplatin-treated cancer cells. Conclusion: We discovered that sexual hormones enhanced DDX3 expression in SiHa cells. MiR-671-5p and miR-564 are two potential therapeutic miRNAs that can be used to treat DDX3-related malignancies.

Objectives: The present study aims to evaluate the relationship between microribonucleic acid (miRNA) and target gene expressions with clinical and histopathological data in ovarian cancer. Methods: We evaluated 96 archival samples of paraffin-embedded tissue. Some potentially significant miRNA and target gene expressions were evaluated in different histopathological characteristics. These were quantified using real- time–polymerase chain reaction (RT–PCR) in tumor and normal tissue. In miRNA expressions, twofold changes are ac- cepted as significant. Results: According to histopathological groups, 38 (39.6%) were endometroid adenocarcinoma, 11 (11.5%) were bor- derline serous, 29 (30.2%) were serous, and 18 (18.8%) were mucinous carcinoma. When evaluated according to their stages, 26 (27.1%) patients were stage 1A/1B. A relationship was found between miR200a and miR200c and histopatho- logic groups, between miR141 and estrogen receptors, between CXCL1 and survival status, and between KEAP1 and ki67. Additionally, miR200a in endometrial and miR200c in mucinous adenocarcinoma were overexpressed. When the relationship between all miRNAs and histopathological groups was evaluated, a significant change was found only in miR200c expression. It was significantly higher in serous than endometrial tumors and significantly higher in mucinous than endometroid tumors. Conclusion: These suggested that miR200a and 200c expressions might be useful for the evaluation of histopathologi- cal subgroups of ovarian cancer.

Human papillomaviruses (HPV) are one of the first viral organisms acknowledged to causing carcinogenesis. Among gynecologic cancers, Pap smear represents a gold standard diagnostic procedure for precancerous cervical lesions. It is efficiently interpreted through a standardized reporting system; The Bethesda System, which aids in distinguishing squamous categories from other entities. Co-infections with other sexually transmitted infections (STIs) could exacer- bate cervical lesion severity caused by initial HPV infection as co-infections can lead to distinct reprogramming of host cells and genome integrity. The intricate pathways and effect of the unique cellular microenvironment that HPV and co-infecting STIs create that cause local inflammation and eventually cervical lesion progression will be reviewed in this manuscript. Besides, it is also crucial to consider HPV viral load and distinguish its correlation with cervical lesion severity. Varying amounts of viral titer and its impact on cervical lesions could indicate a mutagenic transformation of the human host cells and HPV. Thus, this review aims to discuss the correlation of co-infections and viral titer on cervical lesion severity and its progression to cancer. Based on these factors, clear clinical reasoning with more effective treat- ment plans and specific diagnostics can be achieved.

Immunotherapy is a recently developed treatment against most forms of cancer. Although since the early 1990s, many advances have been made with the finding of new drugs as chemotherapy and molecular targeted therapies, the latest drugs approved for cancer treatment are mostly immunotherapy. These immunotherapies, including drugs directed against immune checkpoint Programmed cell death protein 1 (PD- 1), Programmed cell death protein 1 ligand (PD-L) 1, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have become a consolidated treatment strategy regarding various kinds of tumors, with an effective response, and good tolerability towards patients. Patients over 65 years old constitute a large portion of the neoplastic population, and are increasingly represented in medical oncology clinics. Unfortunately, however, these patients are underrepresented in randomized clinical trials. We also know that with aging, the microenvironment and immune cells undergo marked changes that are defined by the term immunosenescence. In this review, we will consider the various studies on im- munotherapy in elderly patients, while evaluating the subgroup analyses to better clarify the efficacy and safety that immunotherapy shows in this frail population in which the treatment strategy must be carefully selected.

Endothelial cells (EC) are key elements of vascularized tissues that form a single-cell layer that connects the vessels to the surrounding tissues. EC participate in the regulation of blood hemostasis, leukocyte homing, acute inflammation, wound healing, and antigen presentation. EC subpopulations are characterized by diverse structures, functions, and molecular profiles. In bone marrow, EC are part of the hematopoietic stem cell vascular and endosteal niche, where they play well-defined roles in hematopoietic stem cell functioning and maintenance, and reside surrounding sinu- soids and blood vessels. In the past years, the clinical and pathophysiological roles of EC have been explored due to their contribution to neoangiogenesis and alterations in the vascular endothelium functions in hematological diseases. The present review discusses the EC contribution to pathogenesis of hematological malignancies and their potential use as therapeutic target in these diseases.

Faced with the complexity of emergency surgery and the aging of the population, it is increasingly common to have to deal with critically ill patients who require intensive care postoperatively. Surgical stress amplifies senescence mecha- nisms where the organism is called to face the establishment of both early and late pathophysiological mechanisms disrupting homeostasis. In this scenario, sarcopenia represents a prognostic factor with a multifactorial etiology that can lead to fearful com- plications in the early postoperative period. As an octogenarian adaptation, its multifactorial genesis allows to act and counterbalance the action of concomitant modifiable factors through post-operative optimization strategies.

Objectives: Colorectal cancer is the most frequent and mortal cancer in Portugal. Both angiogenesis and cellular prolif- eration are core mechanisms to tumoral progression, with VEGF (Vascular Endothelial Growth Factor) and Ki-67, respec- tively, being widely known markers of those two processes. The purposes of this study are to comprehend VEGF and Ki-67’s impact on colorectal cancer prognosis which include assessing its expression in primary colorectal cancer of pa- tients who underwent surgery, establishing associations between the expression of VEGF and Ki-67 and discovering hy- pothetical associations between these biomarkers and clinicopathological aspects, relapse, and mortality of patients. Methods: A retrospective study was conducted in our hospital by including 512 patients submitted to surgery, from 2005 to 2010, with a post-operatory diagnosis of colorectal adenocarcinoma. The evaluation of expression of VEGF and Ki-67 in the obtained tissue was made through immunohistochemistry technique. The statistical analysis resourced to association tests and survival analysis. Results: VEGF-A showed association with the variable gender (p-value of 0.016), with its expression being more fre- quent in men. VEGF-C expression is more common in colon than in rectum (p- value of 0.042). VEGF-C is significantly associated with Ki-67 (p-value of 0.036), with 69.7% of cases where both are positive. All markers are significantly as- sociated with the grade of differentiation, with the VEGF family generally more present in well or moderately differenti- ated tumours and Ki-67 in the poorly differentiated. While the survival time was generally lower in the presence of any marker or combination, no significant differences were found among the survival analysis. Conclusion: VEGF-A, VEGF-C and Ki-67 expression did not show impact on the prognosis of this sample of patients. There was no significant association with a poorer overall survival or a reduced disease-free survival.

Objectives: This simulated study has mechanistically evaluated the molecular dynamics effects of rutin on CDKs 2, 4, and 6 in cell cycling. Methods: Protein Data Bank (http://www.rcsb.org) was used to obtain the PDB file of CDK 2, 4, and 6. After simulation of CDKs in Gromacs software, AutoDock 4.2 was used to run 200 stages of molecular docking of CDKs in the presence of the rutin. CDK 2, 4, and 6 were simulated in the presence of rutin after docking. Results: Rutin had the highest tendency to bind the CDK-2 and CDK-6 via binding 16 and 18 residues in the binding site with hydrogen and hydrophobic bonds (respectively). Also, they had the highest amount of binding energy released. Rutin decreased total energy in CDKs and reduced the radius of gyration in CDK-2 and CDK-6 after docking. The second- ary coil structure increased in CDK-2 and decreased in CDK-4 and 6. Conclusion: Conformational changes in CDK2 and 6 via rutin can inhibit the activity of these proteins and subsequent- ly arrest the cell cycle in phases G1, S, and G2, which can lead the damaged cell to cell repair or Apoptosis.

Objectives: Current literature regarding the assessment of changes in gall bladder polyps is minimal in Pakistan, which is known to have one of the highest risk of developing gall bladder carcinoma. The aim of this study is to determine the occurrence of cancer in incidentally detected Gall Bladder (GB) polyps identified by sonography and to propose surveil- lance guidelines in high risk population for gall bladder cancer. Methods: Radiological data of all “gall bladder polyps” detected on ultrasounds done between January 2001 and Feb- ruary 2015 was taken at a tertiary care institution and it was evaluated to see changes in the size of GB polyps. Patho- logic and clinical follow-up was reviewed from the medical record files. Results: GB polyps from 155 patients (Age range, 18–92 years) were included. US follow-up was performed with minimum follow-up duration of 2 years. The polyps ranged in size from 2-19 mm (mean size, 4 mm). Polyp size remained unchanged in 65 (42 %) polyps, decreased in 25 (16 %), increased in 12 (7 %) and resolved in 53 (34%). None of the polyps ranging in size from 1-6 mm turned out to be neoplastic. One polyp of 7 mm showed increase in size and progressed to carcinoma. Conclusion: The risk of malignancy of gall bladder resulting from incidentally detected polyps is very low. Hence, gall bladder polyps measuring upto 6 mm require no additional follow-up. Follow up may be indicated for polyps that are greater than or equal to 7 mm in size.

Objectives: Interleukin-10 (IL10) is a pro-inflammatory cytokine that plays a pivotal role in inflammatory diseases as well as in the pathogenesis of diverse tumors, including nasopharyngeal carcinoma (NPC). The present study was de- signed to evaluate the importance of the functional promoter polymorphisms of IL10 (-1082 A>G and -592 A>C) in the development of NPC. Methods: A total of 384 patients with NPC were recruited into this study, together with 375 matched control subjects. Polymorphisms within the promoter region of IL10 gene were analysed using PCR-RFLP method. Results: We report a lack of association between IL10 polymorphisms and NPC in the overall population (P>0.05). How- ever, the 1082 A>G polymorphism was significantly associated with the susceptibility to NPC among young patients (age ≤30 years). The GG genotype was found to be associated with a significantly higher risk of NPC as compared with the AA genotype among young patients (OR=2.534; 95% CI, 1.189–5.398, P=0.016). Conclusion: The results of the present study indicate an association between IL10 -1082 GG genotype and NPC among young North African subjects. This difference in IL10 polymorphism association with different ages at the onset of NPC suggests that the younger and older onset patients are genetically different and may involve different mechanisms.

Objectives: Treatment of multiple brain metastases more than 10 is challenging. Whole brain radiotherapy (WBRT) is generally believed to be the first treatment choice. In order to escape from mental deterioration after WBRT, we have performed Gamma Knife stereotactic radiosurgery (GKS) for numerous small brain metastases. Methods: Twelve cases of numerous (more than 30) brain metastases were treated by GKS. Mean total session number was 5.42 times, ranging 2 to 17. Each tumor was treated with the margin dose between 14 to 20 Gy. The tumor number treated in whole sessions was ranged from 31 to 144 (mean, 70.8). Results: Almost all the irradiated tumors either disappeared or shrank at the patient’s death or at the last follow-up, though new metastatic tumors were subsequently developed in some cases which required an additional treatment with GKS. At the last follow-up (3 to 51 months after GKS), nine cases were alive and well and three were dead. As adverse effects, two cases demonstrated seizures by radiation brain injury and another showed a gait disturbance. No apparent mental deterioration was observed during follow-up. Conclusion: Radiosurgery for numerous small brain metastases may be preferable rather than WBRT.

Objectives: We performed a planning study to evaluate the dosimetric differences between Volumetric Modulated Arc Therapy (VMAT) and Intensity Modulated Radiation Therapy (IMRT) using simultaneous Integrated Boost (SIB) for prostate cancer cases. Methods: 20 prostate cancer patients scheduled for SIB-VMAT treatment on the HalcyonTM 2.0 linear accelerator were recruited for this study and SIB-IMRT plans were generated for comparison purpose. The pelvic lymph nodes (PTV46), the seminal vesicle (PTV50), and the prostate (PTV60) were simultaneously treated to 46 Gy 50 Gy, and 60 Gy delivered in 20 fractions respectively. Results: SIB-VMAT was better due to its higher (1.41%) CI, lower (2.7%) HI, and lower (26%) GI than SIB-IMRT for PTV60. For PTV50, a higher (7.3%) CI, lower (48%) HI, and a lower (31.73%) GI for SIB-VMAT compared to SIB-IMRT. Also, for PTV46, a higher (9.4%) CI, lower (2.5%) HI, and a lower (16.4%) GI were achieved by SIB-VMAT compared to SIB-IMRT. Conclusion: Better conformal and slightly similar homogeneous dose distribution were noticed in SIB-VMAT plans compared to SIB-IMRT plans. However, SIB-IMRT provided better OARs sparing of the bladder and the femoral heads while SIB-VMAT had better sparing for rectum.

Numerous epidemiological studies examining the etiology of ovarian cancer and the role of pregnancy related factors in ovarian cancer has been one of the topics of interest to many researchers. Various articles have only mentioned the link between some risk factors and ovarian cancer, but no study has addressed the various dimensions of this issue to this day. Therefore, due to the important position of ovarian cancer among gynecological cancers, this study was con- ducted to investigate the pregnancy-related risk factors for ovarian cancer. To determine the relationship between pregnancy characteristic and ovarian cancer, a comprehensive search was car- ried out in English databases such as; Medline, Web of Science Core Collection, and Scopus using keywords; pregnancy, ovarian cancer (or 'carcinoma of the ovary' or 'ovarian neoplasm' or 'ovarian tumor'), risk factor, pregnancy characteris- tic terms and a combination of these terms. Full-text, English language, and original articles were included in this study. In total, 35 articles were entered into the study. The relationship between pregnancy related factors and ovarian cancer were studied. Although there was a weak association between some factors such as preterm birth and the risk of ovar- ian cancer, only the strong protective effect of parity was seen in the articles. The results of this study did not show that pregnancy related factors increase the risk of ovarian cancer. In summary, the findings are inadequate regarding some risk factors such as gender of fetus, multiple pregnancy, placental and fetal weight, parity, miscarriage, preeclampsia, and gestational diabetes, and raised questions for future research.

Objectives: DKK-1, a negative regulator of β-catenin in the Wnt pathway is commonly upregulated in cancer cells but its expression and association to chemoresistance have not been investigated extensively. Our aim was to evaluate the expression of DKK-1 and β-catenin as well as the effect of the Wnt pathway modulators iCRT-14 (iCRT) and WAY626611 (WAY) alone or in combination with Nigericin (NIG) on the viability of cancer cells grown under routine conditions (RC) or as floating spheroids (FSs). Methods: RC or FSs from human prostate (PC3 and LnCAP) and breast (MCF-7 and MDA-MB231) cells were treated for 72 hs with WAY or iCRT. Cell viability was determined by the MTT or the CCK-8 assays and protein expression was determined by western blot analysis. Results: DKK-1 was expressed at different basal levels in RC but was undetectable in FSs. β-catenin expression was in- creased in FSs. RC of PC3 and MCF-7 were sensitive to both iCRT and WAY but FSs generated from these cell lines were resistant to both drugs. NIG potentiated the effect of both Wnt inhibitors in FSs. Conclusion: Marked changes in the expression of Wnt pathway proteins, DKK-1 and β-catenin in FSs are associated with resistance to WAY and iCRT.

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Objectives: To aim to show the survival outcomes of ifosfamide, carboplatin and etoposide (ICE) therapy and the characteristics of treatment-related hematological side effects in patients with relapsed/refractory bone sarcomas (BSs) andsoft tissue sarcomas (STSs). Methods: Patients who were treated at the Department of Medical Oncology, Gulhane School of Medicine betweenJanuary 2017 and June 2021 were included. Post-ICE progression-free survival (PFS), overall survival (OS) rates and treatment-related hematological side effects were determined. Results: Fifty-six adult patients were included (thirty-four of them BSs). PFS was determined as 6.7 ± 4.4 months and 7.1±3.6 months for STSs and BSs, respectively. OS was 11.4±5.6 monhts and 12.6±7.1 for STSs and BSs, respectively. PFS and OS were not found to be better between groups (p=0.84 and p=0.517, respectively). The median OS and PFS after ICE protocol in patients with two or less systemic chemotherapy lines were significantly higher than those who received three or more lines (7.85±1.66 vs 3.74 ±2.89, p=0.001 and 13.80±8.45 vs 6.73, p=0.001). Conclusion: In addition to its contribution for all patients, ICE may contribute to longer survival, especially in patients receiving ≤2 lines of systemic chemotherapy.

Objectives: The aim of this study is to investigate the incidence of asymptomatic COVID 19 patients who underwent CT and PET/CT for oncological indications and to detect lung changes in CT and PET/CT in these patients. Methods: Between March 2020 and September 2021, 3135 patients admitted to the nuclear medicine department were retrospectively analyzed. Our study involved the oncology patients with a history of contact, clinical and labora- tory findings and possible COVID-19 disease, whose radiological findings at PET/CT and CT were compatible with viral pneumonia and confirmed by PCR testing. Results: Lung imaging findings suspicious of SARS-Co V-2 infection were found in 78 of 3135 patients (2,48%) included. The most frequent finding was multiple ground glass opacities (GGOs). In our study, we found characteristic peripheral ground-glass opacities with high FDG activitiy with increased nodal FDG uptake in favor of reactive lymphadenitis in FDG-PET/CT. Conclusion: Chest CT is used in the initial diagnosis and monitoring of COVID-19 progression as well as in the evalu- ation of complications. Although PET imaging is not typically considered among the primary research methods for the diagnosis of lower respiratory tract infections, it has made a significant contribution to the incidental diagnosis of especially asymptomatic COVID-19 oncological cases

Objectives: The knowledge of the possible differences in the clinical course of COVID-19 infection in cancer patients receiving treatment has not been sufficient to conclude. In this study, we retrospectively evaluated lymphocyte counts, LDH levels, neutrophil/lymphocyte ratios (NLR), platelet lymphocyte ratios (PLR), CRP albumin ratios (CRP/Alb), LDH/ albumin ratios in COVID-19 infected cancer patients actively treated in our clinic. Methods: Cancer patients who were currently under treatment in Department of Medical Oncology, Faculty of Medicine, Pamukkale University during the period between September 2020 and April 2021 were included in the study. During the period, 1363 stage 3-4 patients were received parenteral treatment and 60 patients were diagnosed with COVID-19 infection. Results: The median age of the patients was 60 years (range 19-82 years). Stage of cancer (p=0.028), lymphopenia (p<0.001), elevated LDH (p=0.002), elevated NLR (p<0.001); and elevated LDH/Alb ratios (p<0.001) were identified as the factors affecting mortality. Conclusion: In patients actively under treatment for cancer, clinical course of COVID-19 infection was found to be af- fected by the stage of the cancer, neutrophil lymphocyte ratios and by LDH/albumin ratios. We think that neutrophil lymphocyte ratios and LDH/albumin ratios are the important prognostic markers in the course of COVID-19 infection in cancer patients.

Many dental procedures invariably include a "bleeding event." The chance and severity of such events should be assessed on a relative risk rather than absolute risk. For example, when patients using antithrombotic agents for the management of their systemic illness (like coronary artery disease, cerbero vascular disease and major surgeries like hip joint /knee joint replacement) require any dental treatment, the dentist should weigh bleeding risk associated with the particular dental procedure together with the thrombotic risk. The dentist should also engage with the patient as well as patient`s consulting physician to decide whether the antithrombotic agent needs temporary withdrawal

For more than a decade, the targeted drug sorafenib[1, 2] has been the dominant first-line treatment for patients with advanced hepatocellular carcinoma (HCC). However, due to the low overall response rate and high drug resistance rate, many new targeted drugs have been developed, including sunitinib, brivanib, linifanib, nintedanib, dovitinib, sorafenib plus erlotinib, lenvatinib, and donafenib. On the other hand, with the increasing use of immune checkpoint inhibitors in solid tumors, several trials investigated the efficacy and safety of immune checkpoint inhibitors in advanced HCC. Among these trials, only lenvatinib and donafenib as monotherapy were non-inferior to sorafenib in overall survival in untreated advanced HCC. Most of other trials did not meet their primary end point of overall survival. However, the efficacy of the combination therapy with PD-1 or PD-L1 inhibitor plus bevacizumab (VEGF inhibitor) is amazing.[3, 4] An expert panel convened by the American Association for the Study of Liver Diseases recommended time to progression as the primary endpoint in randomized phase 2 trials and overall survival as the main endpoint to measure effectiveness in phase 3 trials.[5, 6] In real world clinical practice, subsequent antitumor therapies after tumor progression and/or therapies for concurrent liver disease can confound the assessment of clinical benefit. In the recent issue of Journal of Hepatology, on behalf of EASL, Bruix and coworkers updated the recommendations of systemic treatment of HCC.7 This review proposed that “overall survival is the sole robust endpoint to assess the benefit from any intervention in advanced HCC” and “all proposed surrogates lack adequate validation”. Here, we tried to reveal the relationship among objective response rate (ORR), median overall survival (OS) time and median progression-free survival (PFS) time by presenting them in a same curve graph. The potential relationship between PFS and OS is revealed by representing the hazard ratio (with 95% confidence interval) of PFS and OS with a forest plot. We systematically searched PubMed and EMBASE databases and analyzed phase 3 clinical trials with large sample size. A total of 11 trials about first-line systemic therapies for advanced HCC published from 2008 to 2021 were included into analysis. All these 11 trials included a group of patients treated with sorafenib. In addition, 7 trials about second-line systemic therapies published from 2015 to 2021 were also included into analysis. The control group received placebo treatment in all these 7 trials. All these 18 trials reported ORR, median PFS and OS time. The ORR according to RECIST 1.1 in the sorafenib group ranged from 0.7% to 11.9% (median 6.1%). Among patients with sorafenib therapy, the median PFS and OS time was 3.75 (range 2.8 to 5.5) and 10.4 (range 6.5 to 14.7) months, respectively.

Chromophobe renal cell carcinoma (ChRCC) accounts for 4-6% of RCC1. Most of ChRCC have good prognosis, but sarcomatoid transformation implies poor prognosis factor2. Although sarcomatoid RCC was initially described as an own histological entity3, despite the fact that its transformation mechanism is not known, it is nowadays recognized that this histology represents a transformation or dedifferentiation of a high-grade malignant neoplasia originating from any other histological subtype of RCC2. ChRCC with sarcomatoid differentiation is very rare, with a few reported cases and there is no consensus about the treatment of patients affected by this variant of RCC in the guidelines. Therefore, we consider appropriate to present these two cases and review the literature, focusing on the incidence and the current therapeutic options.

Atypical chronic myeloid leukemia (aCML) is a BCR-ABL1 negative myelodysplastic/myeloproliferative (MDS/MPN) neoplasm. Patients typically present with elevated neutrophil counts and hypercellular bone marrow, but there are no specific genetic or molecular markers available to diagnose aCML and it is therefore a diagnosis of exclusion. Atypical CML is rare and carries a poor prognosis, and there is currently no standard of care for treatment. In the absence of an available clinical trial, current consensus is for patients with a suitable donor to undergo allogeneic stem cell transplantation, and a comprehensive evaluation for driver mutations should be performed to screen for the potential use of targeted agents. Without an actionable driver mutation, hypomethylating agents are an emerging treatment option based on four reports showing complete hematologic remission in 7 of 8 patients treated with decitabine.

Objectives: Breast cancer is a dreadful public health issue that kills plenty of women all around the world. The peril of breast cancer is strongly linked to lipids, lipoproteins, and glycoproteins. Capsaicin (CAP), a natural alkaloid isolated from chilies, has been reported to possess excellent anti-cancer activity. Unfortunately, the clinical application of this compound is strictly limited due to its low solubility and poor bioavailability. Nanoparticle-based drug delivery systems have set the path for a revolution in cancer therapy by improving its therapeutic value. The aim of the present study was to investigate the effect of CAP encapsulated chitosan nanoparticles (CAP@CS-NP) on lipids, lipoproteins and glycoproteins abnormalities in 7,12-dimethylbenz(a)anthracene (DMBA) induced mammary carcinogenesis. Methods: A mammary tumor was induced by a single dose of DMBA 25mg/kg b.wt injected subcutaneously near the mammary gland. The levels of lipid profile, lipoproteins and glycoprotein components were analyzed in the plasma, liver and mammary tissues. Results: We observed higher levels of total cholesterol (TC), triglycerides (TG), phospholipids (PL), free fatty acids (FFA), hexose, hexosamine and sialic acid in DMBA induced tumor-bearing rats. Moreover, low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C) levels were raised and high-density lipoprotein cholesterol (HDL-C) levels were dropped in tumor-bearing rats. The result shows that, CAP@CS-NP 4mg/kg b.wt administration significantly recouped abnormal levels to near-normal levels. It was additionally verified by histological staining in mammary tissues. Conclusion: Our findings suggest that nanoencapsulation of CAP@CS-NP successfully regulates lipid profile, lipoproteins, and glycoproteins levels.

Objectives: This study examined the effect of a health literacy training intervention on self-care behaviors and treatment adherence in patients with ischemic heart disease (IHD). Methods: A quasi-experimental study was conducted in 2020, on 50 patients with IHD referred to a medical center in Kashan, Iran. The patients were assigned to a control group (n=25) and an intervention (n=25) group via a block randomization method. The intervention group received a health literacy training intervention, while the control group did not. The "Adherence to Treatment Questionnaire" and the "Self-Care Behavior Questionnaire" were used to gather the data at the start and the end of the study. Results: The mean baseline self-care behaviors in the intervention and the control groups were 61.56±10.99 and 56.25±8.42 (p=0.061) out of 100, which then changed to 85.24±4.06 and 53.01±4.86 (p<0.001). Also, the mean baseline treatment adherence in the intervention and the control groups were 84.77±29.19 and 84.40±13.89 (p=0.315) out of 200, which then changed to 179.08±8.59 and 95.76±9.24 (p<0.001). Conclusion: The health literacy training intervention could improve self-care behaviors and treatment adherence in patients with IHD. Nurses and the medical team are recommended to implement similar packages to improve the health literacy of patients with IHD.

Objectives: The objectives of the study were to compare the wound complication rate, postoperative pain and overall patient satisfaction between adhesive glue and subcuticular suture in women undergoing elective Caesarean Section (CS). Methods: A double blind Randomized Controlled trial was conducted among pregnant women undergoing an elective CS, who were randomly assigned to skin closure with adhesive glue or with a Polyglactin 3-0 subcuticular suture. In both groups after closure of the rectus fascia, the subcutaneous fat layer was closed with 3-4 interrupted catgut or Vicryl 1-0. In the adhesive glue group, 2 layers of adhesive glue were used to close the outer skin layer. In the suture group, the skin was closed with Polyglactin 3-0 suture under the skin using a continuous suture technique. A sample of 52 in each group was needed to achieve any significant finding with a power of 80%. Primary outcome assessed were parenteral analgesic use, daily subjective pain scores while in hospital, 6 week postoperative subjective pain score and scar cosmetic score 6 weeks post-operatively. Secondary outcome assessed were surgeons satisfaction, duration of surgery, duration of hospitalization after the caesarean, and wound complications. Results: Two hundred pregnant women at term for elective caesarean were assessed for eligibility of which 132 fulfilled the criteria and were randomized into two groups. Sixty women in each group completed the required follow up. Patients’ baseline demographic and clinical backgrounds were similar in both the groups. Postoperative day 3 subjective pain score was significantly lower in adhesive glue group (p=0.023) compared to suture group. Skin closure time with glue required less time compared to suture (glue 2.57±.67 minute vs suture 3.2±1.18 minute, p=0.001). Total operative time was also less in adhesive glue group though the difference was not significant (39.52±8.24 minute vs 42.1±6.10, p=0.054). Scar assessment by the modified patient and observer scar assessment scale (POSAS) at 6 weeks postpartum showed similar cosmetic outcome between the two groups. Patient Scar cosmetic score was 11.8 for glue group and 12.7 for suture group (p=0.330) while the Observer Scar cosmetic score was 10.8 for glue group and 11.7 for suture (p=0.252). No significant differences were observed between the groups in blood loss, surgical site infection, length of hospitalization, or wound breakdown. Conclusion: Adhesive glue may be a useful option for skin closure of Pfannenstiel skin incisions after caesarean delivery. It has the advantages like shorter skin closure and operating time, less postoperative pain and similar cosmesis and satisfaction among surgeons with no increases in wound complication rates.

Objectives: Dual specificity phosphatase 22 (DUSP22) is a novel phosphatase and has been demonstrated to be a cancer suppressor gene associated with various biological and pathological processes. The aim of this study is to evaluate the prognostic importance of DUSP22 expression in low-grade lymphomas. Methods: Fluorescence in situ hybridization (FISH) was used to detect DUSP22 and 76 cases with indolent lymphoma were evaluated for DUSP22 expression. Thirty-nine had follicular lymphoma (FL), 30 had marginal zone lymphoma (MZL) and 7 had chronic lymphocytic leukemia (CLL). Results: DUSP22 expression was detected in 17 cases (22.3%). The mean overall survival (OS) was found to be longer in cases without DUSP22 compared to cases with DUSP22 expression while event-free survival (EFS) was not different between the cases according to the DUSP22 expression. In univariate analysis, stage (early-stage disease p=0.0001), gender (female p=0.009) and DUSP22 expression (p=0.018) were found to be independent prognostic factors according to Cox regression analysis. . Conclusion: There is no sufficient data about the clinical and/or prognostic significance of DUSP22 rearrangement in lymphomas except ALK (-) anaplastic large cell lymphoma. We found that DUSP22 is poor prognostic indicator in cases with low grade lymphomas.

Objectives: The dysregulation of angiotensin-converting enzyme inhibitor (ACE-I) and its pathway has been reported to be associated with oncogenesis and poor prognosis in colorectal cancer (CRC). Methods: We explored the therapeutic potential of targeting ACE-I through the use of enalapril and investigated its pharmacological interaction with 5-FU in CT26, HT29, and SW480 cells. The anti-proliferative and anti-migratory effects as well as apoptotic activity of this agent on cell cycle have been evaluated by MTT, wound healing assay, and FACS, while the expression of genes was determined through mRNA or protein levels. Results: According to the observations, enalapril has inhibited cell proliferation in a dose-dependent manner and affected the anti-tumor properties of 5-FU via increasing the levels of apoptosis and ROS, as well as through the modulation of antioxidant/oxidant markers. Enalapril has also suppressed cell migration by the perturbation of MMP3/MMP-9 and E-cadherin. The combination of enalapril and 5FU has resulted in decrease in the expression levels of ACE, AT1R, and SMAD-3. Conclusion: Our findings suggested that targeting ACE-I by applying the modulation of angiotensin pathway could increase the activity of 5-FU due to interfering with cell-proliferation, apoptosis, and inflammatory markers, which is indicative of its potential value as a therapeutic option for the treatment of CRC.

Objectives: Preoperative diagnostic investigation of salivary neoplasms leaves a fair share of doubtful cases that complicate the therapeutic choices. The aim of our study was to look for new means to support the decision-making process for their management. Inflammatory biomarkers could play an important role in this process. Methods: A retrospective chart review of salivary glands tumors was performed between January 2016 and September 2020 in our Department. The samples were divided in 2 groups basing on the histological result after surgery: 191 patients with benign salivary glands tumors (SGbt), and 47 with salivary glands cancer (SGc). 90 patients were randomly selected to form the control group (C group). Results: Statistically significant increase of platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocite ratio (NLR) and systemic immune-inflammation index (SII) was reported in SGc group compared to SGbt group and control group (p<0.001). Statistical evaluation estabilished optimal threshold for PLR (164,2), NLR (3,11) and SII (517.5) that can discriminate the doubtful cases with specificity of 85-86% and 62% respectively, and sensitivity of 40-45% and 64% respectively. Conclusion: Inflammatory biomarkers can have a relevant role as diagnostic tools in doubtful cases. They could be performed in the clinical setting for guiding the treatment of these neoplasms.

Objectives: To analyze the added value of a new CXR scoring system in the evaluation of the COVID-19 pneumonia severity. Methods: This retrospective study included, from March to April 2020, 169 (132M/37F) hospitalized COVID-19 patients, mean age 65.6±10.8 years; 57 had low-pressure ventilation (Group A), 50 positive-pressure ventilation (Group B) and 62 invasive ventilation (Group C). Two radiologists in consensus evaluated the CXRs using an 18-points scoring system. CXR scores were compared in each Group and among the three Groups. Then in each Group CXR scores were correlated with Pa02/Fi02 and, in Group C, with Simplified Acute Physiology Score (SAPS). Non-parametric tests were used. Results: In Group A the median score at admission was 8 [Interquartile range (IR) 7-9] and the median of the highest scores was 9 [IR 8-10](p=0.0738). Median scores at admission and before the start of the ventilation (pre-ventilation) are resulted, in Group B, 10 [IR 8-10] and 11 [IR 10-14](p<0.0001) and, in Group C, 10 [IR 8-11] and 12 [IR 11-13](p<0.0001). In Group A the CXR scores at admission were lower than in Group C (p=0.0257), and the highest scores were lower than the pre-ventilation ones of Groups B (p=0.0018) and C (p=0.0001). The CXR scores correlated negatively with Pa02/Fi02 and positively with SAPS. Conclusion: CXR scoring system could be an added value in the evaluation of COVID-19 pneumonia severity. With lowpressure ventilation, the CXR scores were lower than with positive-pressure and invasive ventilation. Furthermore, CXR scores showed negative correlation with Pa02/Fi02 and positive with SAPS. Implications for practice: This new CXR scoring system could be a useful diagnostic tool to quantify the COVID-19 pneumonia severity and to guide to choice of the correct ventilation support.

Objectives: Cancer stem cells (CSCs), a small subpopulation of tumors, are responsible for chemo-radioresistance, metastasis, and cancer recurrence. The main aim of the present study is to investigate the potential effects of metformin on prostate CSCs (PCSCs). Methods: Flow cytometry was used to isolate cells with co-expression of CD133 and CD44. Sorted PCSCs were treated with different concentrations of metformin to determine the effects of metformin on cell viability using MTT assay. The association of cells exposure to metformin with apoptotic cell death and caspase activity, as well as cell cycle, were performed using the Muse Cell Analyzer. Results: In our study, for the first time we demonstrated the anti-cancer effects of metformin on PCSCs. Our results revealed that treatment with metformin reduced cell viability in CD133high/CD44high cells in a dose- and time-dependent manner. Metformin significantly induced early apoptosis and triggered the activity of several caspases associated with the apoptotic process. Metformin significantly altered the cell cycle distribution in CD133high/CD44high cells, leading to G0/G1 phase arrest. Conclusion: The results of the study revealed that metformin triggers cell death and apoptosis and modulates cell cycle distribution in CD133high/CD44high PCSCS. The present study raises the possibility that metformin is a potential anti-cancer agent for targeting PCSCs.

Objectives: The associations of Matrilin-3 (MATN3) and Adiponectin (ADIPOQ) polymorphisms with knee osteoarthritis (OA) risk have been reported, but it is currently the conclusions have been divergent. Thus, this study was performed to evaluate the association of MATN3 and ADIPOQ polymorphisms with susceptibility to knee OA. Methods: We carried out this case-control study involving 105 cases with knee OA and 120 healthy subjects to evaluate the association of MATN3 rs8176070, ADI POQ rs1501299, rs822396, and rs2241766 polymorphisms with knee OA using RFLP-PCR assay. Results: There was a significant association between MATN3 rs8176070 polymorphism and KOA risk. However, there was no significant association between rs1501299, rs822396, and rs2241766 polymorphisms at ADIPOQ gene and knee OA risk. Conclusion: This piece of evidence revealed that the MATN3 rs8176070 polymorphism was serving as risk factor for development of knee OA, but not ADI POQ rs1501299, rs822396, and rs2241766 polymorphisms. However, well-designed and large-scale clinical studies are necessary to further validate our results.

Objectives: Intraoperative radiotherapy (IORT) is the delivery of ionizing radiation to the tumor or tumor bed during surgery. It is being explored as a treatment modality for brain metastases (BrMs). We aimed to determine the safety and efficacy of IORT for BrMs by reviewing the current evidence. Methods: We performed a systematic review of the online databases for studies on IORT for BrMs. Data on clinical features, treatment modalities, and outcomes were collected. Results: Five studies (n=179) were included. Mean age was 60.4 years, 43% were women. The most common etiology of BrMs were lung, melanoma, breast, and renal cancer. Ninety-five patients underwent IORT with the Photon Radiosurgery System (PRS) while 84 were treated with the INTRABEAM system. Follow-up ranged from 5 days to 94 months. The most frequent complication was radiation necrosis. Local recurrence and distal progression were seen in 11-77% and 0-82%, respectively. The 6- and 12-month overall survival ranged from 60-86% and 34-73%, respectively. Conclusion: The results of the systematic review on the safety and efficacy of IORT on BrMs were inconclusive, due to heterogeneity of the studies. Larger prospective studies are needed to determine the optimal dose, efficacy, and safety of IORT for BrMs.

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Due to phenotypic variability, age-related penetrance, and variety of targeted organs, many families with an inheritedcancer syndrome will not meet syndrome-specific criteria. We report hereditary breast cancer case in a family withgastric cancer, pancreatic cancer, lung sarcoma and penile cancer, suggesting several alternative hereditary cancersyndromes. Mutation screening by NGS was performed using three panels with BRCA1, BRCA2, TP53, BMPR1A, SMAD4, CDH1,STK11, PTEN genes and 409 genes from Ion AmpliSeq Comprehensive Cancer Panel.In maternal lineage we found a novel mutation c.5193_5194del:p.H1731fs in BRCA2 resulted in HBOC. 7 of 8 tested fam ily members (87.5%) were carriers of the mutation; 4 would have been expected from mendelian ratio of 50%. In orderto find out whether the paternal lineage could have another hereditary cancer syndrome we tested paternal uncle withpenile carcinoma. 409 gene panel revealed no pathogenic mutations. VUS’s identified in this study cannot be used tomake clinical decisions.A positive cancer family history in itself is usually not enough to diagnose a cancer syndrome, especially when com mon type cancers are involved. Chance alone may cause the clustering of cancer (especially in large families) and thenumber of possible unaffected relatives.

Objectives: Dialister is the genus classified within Veillonellaceae family in Firmicutes phylum. Dialister genus has beendetected in patients with oral infections and healthy people in their oral cavity, as well as in clinical samples in differentparts of the body. Cancers are complex and multifactorial diseases and considered a global problem. End products ofDialister such as acetate, lactate and propionate seem to be important in the mechanism of carcinogenesis. Althoughit is reported that the composition of Dialister has changed in articles investigating the microbiome relationship withcancer patients, it is seen that it is not taken into consideration. The aim of this review was to investigate cancer studiesin humans on the association of microbiome with composition changes in Dialister. Methods: A systematic literature search was performed using in Pubmed. In vitro and animal studies were excluded.After database search, 510 articles were found. 484 article were excluded based on the exclusion criteria. The remain ing 26 articles were identified and analysed for Dialister. Meta-Mar online software was used for metaanalysis results. Results: The meta-analysis included 26 studies with 1649 control samples and 1961 cancer samples. Compared tohealthy controls, Dialister were significantly elevated in samples from cancer patients (Hedges’g=0.907, p<0.05, 95%CI[13.19 - 16.746]. Statistical heterogeneity was found hihg (I2 =99.6%). Conclusion: This review showed that a relationship between different cancer types and Dialister composition of mi crobiome. however, these data still seem very weak to reveal the Dialister and cancer relationship. Dialister can be animportant genus especially in solid tumors but, more comprehensive and wider studies are needed to understand therelationship between Dialister and cancer. In addition, due to rapidly developing new bioinformatics analysis tech niques, massive data should be added to public databases by the authors in studies of microbiome or microbiotadisease relationship. Thus, it is valuable in terms of detecting different strains such as Dialister, which can be ignored byre-evaluating these data in the future.

Objectives: Alteration in the Glutathione (GSH) and Glutathione S-Transferase (GST) family lead to various disordersincluding breast cancer. However, the role of GSH and GSTM1 in the onset of breast cancer is still not fully elucidated. Inthe present study we observed considerable deficiency in the levels of glutathione and genetic mutation in the GSTM1enzyme that influence susceptibility to breast cancer metastasis and invasion via EMT pathway.Methods: GSTM1 genotype was identified by multiplex polymerase chain reaction (PCR), real time (RT)-PCR and west ern blotting in breast tumor samples and adjacent normal control tissue (ANCT) samples. The endogenous glutathi one levels were determined by high performance liquid chromatography (HPLC).The tumor metastasis, invasion andepithelial-mesenchymal transition (EMT) biomarkers were determined by RT-PCR. Results: In present study genotyping analysis of GST investigated that genetic mutation in GSTM1 was detected inbreast cancer tissue samples. mRNA and protein expression of GSTM1 was significantly downregulated in tumor sam ples as compared to adjacent normal control tissue (ANCT) samples in breast cancer patients. Significant reductionof total glutathione (GSHt P<0.05) was observed among correlation with patient ages, stages and histological gradesof breast cancer patients. Additionally, downregulation of GSTM1 promotes EMT pathway that leads to enhanced theexpression of tumor proliferation, invasion and metastasis in breast cancer patients (p<0.05). Conclusion: The present findings suggest that GSTM1 genotype could be a potential biomarker for breast cancer pathogenesis.

Objectives: Artificial Intelligence (AI) and Machine Learning (ML) are innovations contributing to the diagnosis andtreatment of cancer. The aim is to present an overview of AI and ML application in oncology research. Methods: Data was retrieved from the web of science. Bibliometrics and R packages and VOSviwer software was usedfor mapping and network analysis. Results: 214 publications were retrieved written by 1161 authors and published in 133 journals from 1988 to 2021.There has been a steadily increasing trend of research over the past years. AI and ML in oncology research have at tracted the interest of the scientific community and the readership. The first ranked documents received a 173 citationsscore. It covers hot topics related to common mistakes in diagnostic classification in clinical and the potential futureopportunities for precision oncology using AI. Aneja S and Thompson RF from the USA are the most productive author.Frontiers in Oncology is the most productive Journal. The United States is leading the research effort on the topics, fol lowed by Korea. The collaboration and network between countries in AL or ML in oncology research were documented. Conclusion: AI and ML in oncology research have attracted the interest of of the scientific community and readership.The trend of research has been steadily increasing globally.

A number of studies have evaluated the association of cyclooxygenase-2 (COX-2) polymorphisms with prostate cancerrisk. However, the results still remain controversial. We carried out this meta-analysis to clarify the association of COX-2polymorphisms and prostate cancer risk. An universal search in PubMed, Web of Knowledge and Google Scholar wasperformed to identify relevant studies up to January 2021. A total of 34 case-control studies including 11 studies with13,248 cases and 14,768 controls were on -765G>C, 7 studies with 9,720 cases and 10,695 controls on -1195G>A, 9studies with 11,476 cases and 11,761 controls on +202C>T, and 7 studies with 12,220 cases and 12,496 controls wereon +8473T>C were selected. Pooled data showed that the COX-2 +202C>T polymorphism (T vs. C: OR= 1.305, 95%CI: 1.849-9.490; p= 0.001; TT+TC vs. CC: OR= 0.781, 95% CI: 0.669-0.913; p=0.002) was associated with risk of prostatecancer, but not the -765G>C, -1195G>A and +8473T>C polymorphisms. Stratified analyses showed that the -765G>C,-1195G>A and +202C>T polymorphisms were associated with prostate cancer risk by ethnicity. To sum up, our re sults indicated that the COX-2 +202C>T polymorphism was associated with risk of prostate cancer, while the -765G>C,-1195G>A and +8473T>C polymorphisms were not associated.

Objectives: Sex differences are ascribed to the risk of hepatocellular carcinoma (HCC); however, whether gender dis parity also exists in the prognosis of palliative therapy is yet unclear. A retrospective cohort study was performed toassess the prognostic predictors after palliative therapy of HCC, focusing on sex differences. Methods: This retrospective cohort study consisted of 2356 patients (270 women and 2086 men) with a diagnosis ofHCC between 2006 and 2011. The patients received palliative care. Clinical and laboratory data were evaluated andcompared. Results: Overall, the two groups did not have significant sex-related differences in prognosis for overall survival (OS)of palliative care, including transarterial chemoembolization (TACE), chemotherapy, and best supportive care (BSC).Using multivariate analysis, the following were identified as independent risk factors of survival (P<0.05): smoking, livercirrhosis, vascular invasions, tumor size, absolute value of neutrophils, and glutamyltransferase. Transarterial chemo embolization was regarded as protective factor of OS. Conclusion: No significant differences were observed in the prognosis of male or female HCC patients after palliativecare. The gender factor was not an independent predictor for OS.

Surgical resection followed by concurrent radiation therapy and temozolomide (TMZ) chemotherapy then adjuvantTMZ is the current standard treatment for glioblastoma multiforme (GBM). There is a lot of controversy regarding theduration of adjuvant TMZ. The standard guidelines recommend 6 months of adjuvant treatment, however in clinicalpractice in a lot of centers around the world, TMZ therapy is continued beyond 6 months duration. In this reviewarticle we will discuss both favorable and unfavorable trials regarding extended TMZ therapy and try to analyze inwhom extended TMZ therapy is beneficial and whether or not it should be offered.

It is known that the pathophysiology and treatment strategies of cancer pain, acute and chronic pain, which are notclearly classified in the traditional approach to pain management, are different. Cancer pain is the most common symp tom seen after cancer diagnosis and 40% of cancer patients who have completed curative treatment experience chron ic pain. Many physicians who encounter patients with intractable pain are known to be concerned about using potentopioids due to their potential side effects.To be more successful against cancer pain, educational strategies to address concerns about treating pain with strongopioids should be planned and implemented regularly.Palliative Care Centers in our country are key in the care of cancer patients and in the treatment of cancer pain. First ofall, it is more appropriate that these centers are preferably under the responsibility of Anesthesiology and Reanimationspecialists as stated in the law, and their knowledge and experience about the use of all analgesics, especially opioids,and their side effects will also provide a significant advantage. In this article, we offer some recommendations for the implementation of the standards established by EFIC (The Euro pean Pain Federation) on the management of cancer pain in our country.

Tetraploidy constitutes a genomically metastable state that drives oncogenesis by leading aneuploidy. Tetraploidsub-population is frequently found in pre-neoplastic lesions. This particular population is relatively more resistantagainst DNA damaging agents and in consequence, it is important to selectively target tetraploid cancer cells. Here,we listed all the studies that targeted preferentially tetraploid tumors cells focusing on mitosis machinery, essentiallythe spindle pole apparatus and the spindle assembly checkpoint pathways..

Several thrombotic complications in patients affected with SARS-CoV-2 have been reported. Single-centre pilot study aimed to analyse the coexistence of antiphospholipid antibodies and thrombotic events onSARS-CoV-2 infected patients. Antiphospholipid antibodies were measured by solid phase enzyme immunoassay. Clinical data were collected fromelectronic history and clinical records. Over 25 patients studied we report four cases of COVID-19 patients who presented circulating antiphospholipid anti bodies and arterial or venous thrombotic events. No patient had a previous history of thrombosis. Two cases presentedwith pulmonary embolism, one with pulmonary embolism and pulmonary infarction and one with a stroke. All of themshowed positive anti-cardiolipin antibodies. One patient died and three were discharged. The presence of antiphospholipid antibodies in these patients might represent an epiphenomenon secondary tothe immune stimulation by the virus. It could be reasonable to consider measuring antiphospholipid antibodies aspart of the study of a thrombotic event in COVID-19 patients to better understand the impact of these antibodies inthe development of thrombotic events and we highlight the value of a periodic determination to define the need oflong-term anticoagulant therapy.