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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.

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