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.