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Background: Stomach adenocarcinoma (STAD) is a common cancer with poor clinical outcomes globally. Due to a lack of early diagnostic markers of disease, the majority of patients are diagnosed at an advanced stage. Objective: The aim of the present study is to provide some new insights into the available biomarkers for patients with STAD using bioinformatics. Methods: RNA-Sequencing and other relevant data of patients with STAD from The Cancer Genome Atlas (TCGA) database were evaluated to identify differentially expressed genes (DEGs). Then, Machine Learning algorithms were undertaken to predict biomarkers. Additionally, Kaplan–Meier analysis was used to detect prognostic biomarkers. Furthermore, the Gene Ontology and Reactome pathways, protein-protein interactions (PPI), multiple sequence alignment, phylogenetic mapping, and correlation between clinical parameters were evaluated. Results: The results showed 61 DEGs, and the key dysregulated genes associated with STAD are MTHFD1L (Methylenetetrahydrofolate dehydrogenase 1-like), ZWILCH (Zwilch Kinetochore Protein), RCC2 (Regulator of chromosome condensation 2), DPT (Dermatopontin), GCOM1 (GRINL1A complex locus 1), and CLEC3B (C-Type Lectin Domain Family 3 Member B). Moreover, the survival analysis reported ASPA (Aspartoacylase) as a prognostic marker. Conclusion: Our study provides a proof of concept of the potential value of ASPA as a prognostic factor in STAD, requiring further functional investigations to explore the value of emerging markers.

Abstract: Colorectal cancer (CRC) is currently the second most prevalent cancer diagnosed in women and the third most common kind of cancer in men. Despite tremendous efforts and advancements in diagnostic approaches and treatment options, the mortality rate of CRC accounts for around one million each year globally. The five-year survival rate of CRC is reported to be approximately 14 percent for patients diagnosed at an advanced stage. Due to its significant associated mortality and morbidity, diagnostic tools to identify the disease at its early stages are urgently required. Early diagnosis may lead to better outcomes. The gold standard approach for CRC diagnosis is colonoscopy with biopsy. However, it is an invasive process with a risk of complications and discomfort for the patient. Moreover, it is usually performed in symptomatic or high-risk individuals and therefore, asymptomatic patients might be missed. Thus, alternative non-invasive diagnostic techniques are required to improve CRC outcomes. The new era of personalized medicine is identifying novel biomarkers associated with overall survival and clinical outcomes. Recently, liquid biopsy, a minimally invasive analysis of body fluid biomarkers, has gained attention for diagnosis, evaluation of prognosis, and follow-up of patients with CRC. Several previous studies have demonstrated that this novel approach allows for better understanding of CRC tumor biology and leads to an improvement in clinical outcomes. Here, we explain the enrichment and detection methods of circulating biomarkers, including CTCs, ctDNA, miRNA, lncRNA, and circRNA. Furthermore, we provide an overview on their clinical potential as diagnostic, prognostic, and predictive biomarkers for CRC.

Abstract: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder associated with obesity, diabetes mellitus, dyslipidemia, and cardiovascular disease. A “multiple hit” model has been a widely accepted explanation for the disease's complicated pathogenesis. Despite advances in our knowledge of the processes underlying NAFLD, no conventional pharmaceutical therapy exists. The only currently approved option is to make lifestyle modifications, such as dietary and physical activity changes. The use of medicinal plants in the treatment of NAFLD has recently gained interest. Thus, we review the current knowledge about these agents based on clinical and preclinical studies. Moreover, the association between NAFLD and colorectal cancer (CRC), one of the most common and lethal malignancies, has recently emerged as a new study area. We overview the shared dysregulated pathways and the potential therapeutic effect of herbal medicines for CRC prevention in patients with NAFLD.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a painful condition, experienced by patients undergoing chemotherapy with some specific drugs, such as platinum-based agents, taxanes, and vinca alkaloids. Painful CIPN may lead to dose interruptions and discontinuation of chemotherapy and can negatively impact on the quality of life and clinical outcome of these patients. Due to a lack of a practical medical therapy for CIPN, it is necessary to further explore and identify novel therapeutic options. Methods: We have reviewed PubMed and EMBASE libraries to gather data on the mechanism-based pharmacological management of chemotherapy-induced neuropathic pain. Result: This review has focused on the potential mechanisms by which these chemotherapeutic agents may be involved in the development of CIPN, and explains how this may be translated into clinical management. Additionally, we have presented an overview of emerging candidates for the prevention and treatment of CIPN in preclinical and clinical studies. Conclusion: Taken together, due to the debilitating consequences of CIPN for the quality of life and clinical outcome of cancer survivors, future studies should focus on identifying underlying mechanisms contributing to CIPN as well as developing effective pharmacological interventions based on these mechanistic insights.

Abstract: Colorectal cancer (CRC) is a growing concern worldwide. In recent decades, the incidence of CRC has increased, and this has been attributed to changes in lifestyle. The lack of physical activity, smoking habits, and a diet high in red meat and fat and low in fiber are important aspects of these deleterious changes in lifestyle. The increase in the incidence of CRC has impelled researchers to investigate methods for preventing and treating CRC with greater efficacy and fewer complications. Probiotics are an attractive and potentially promising therapeutic approach. They have been evaluated by a large number of preclinical and clinical studies in recent years, and it has been found that they can play a role in the prevention, treatment, and management of complications of CRC. This review provides a concise summary of the mechanisms of action of probiotics. Furthermore, it focuses on the results of clinical and preclinical studies that evaluated probiotics' effects on CRC management. It also discusses the effects of different strains of probiotics and their combination in CRC treatment.

Background\ud Cervical cancer is one of the most prevalent cancers among women and is associated with high morbidity and mortality. Several factors are involved in the pathogenesis of cervical cancer including viral infections and/or genetic modifications that include single nucleotide polymorphisms (SNPs). \ud \ud Methods\ud We aimed to investigate the association of genetic variants in ATP Binding Cassette Subfamily B Member 1 (ABCB1) (rs1128503) and Fc Gamma Receptor IIIa (FCGR3A) (rs396991) genes and susceptibility to cervical cancer in 263 individuals with or without this form of cancer. DNA samples were isolated and genotyped using a TaqMan based real-time (RT-) PCR method. \ud \ud Results\ud The rs1128503 was found to be associated with an increased risk of cervical cancer (recessive model: OR=2.6, CI: 1.1-5.8, p=0.02). whilst there was no association between the rs396991 and susceptibility to cervical cancer.\ud \ud Conclusion\ud Our results showed that there is an association between the ABCB1 polymorphism and susceptibility for cervical cancer suggesting its potential as a risk stratification marker for cervical neoplasia.

Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with a very poor prognosis. Therefore, there has been a focus on the identification of new biomarkers for the early diagnosis of PDAC and prediction of patient survival. Genome-wide RNA and microRNA sequencing were used using bioinformatics and Machine Learning approaches to identify differentially expressed genes (DEGs) followed by validation in additional cohort of PDAC patients. Methods: genome RNA sequencing and clinical data from pancreatic cancer patients were extracted from The Cancer Genome Atlas Database (TCGA) to identify DEGs. We used Kaplan-Meier analysis of survival curves was used to assess prognostic biomarkers. Ensemble learning, Random Forest, (RF), Max Voting, Adaboost, Gradient boosting machines (GBM) and Extreme Gradient Boosting (XGB) techniques were used and Gradient boosting machines (GBM) were selected with 100 % accuracy for analysis. Moreover, protein-protein interaction (PPI), molecular pathways, concomitant expression of DEGs, and correlations between DEGs and clinical data were analyzed. We have evaluated candidate genes, miRNAs and a combination of these obtained from machine learning algorithms and survival analysis. Results: Machine learning results showed 23 genes with negative regulation, 5 genes with positive regulation, 7 microRNAs with negative regulation and 20 microRNAs with positive regulation in PDAC. Key genes BMF, FRMD4A, ADAP2, PPP1R17, and CACNG3 had the highest coefficient in the advanced stages of disease. In addition, the survival analysis results showed decreased expression of hsa.miR.642a, hsa.mir.363, CD22, BTNL9 and CTSW and overexpression of hsa.miR.153.1, hsa.miR.539, hsa.miR.412 reduced survival rate. CTSW was identified as a novel genetic marker and this was validated using RT-PCR. Conclusion: Machine learning algorithms may be used to Identify key dysregulated genes/miRNAs involved in pathogenesis of the diseases can be used for detection of patients in earlier stages. Our data also demonstrated the prognostic and diagnostic value of CTSW in PDAC.

Gastric cancer (GC) is the fourth most common cause of mortality and the fifth for incidence, globally. Diagnosis, early prognosis, and therapy remains challenging for this condition, and new tumor-associated antigens are required for its detection and immunotherapy. Cancer-testis antigens (CTAs) are a subfamily of tumor-associated antigens (TAAs) that have been identified as potential biomarkers and targets for cancer immunotherapy. The CTAs-restricted expression pattern in tumor cells and their potential immunogenicity identify them as attractive target candidates in CTA-based diagnosis or prognosis or immunotherapy. To date, numerous studies have reported the dysregulation of CTAs in GC. Several clinical trials have been done to assess CTA-based immunotherapeutic potential in the treatment of GC patients. NY-ESO-1, MAGE, and KK-LC-1 have been used in GC clinical trials. We review recent studies that have investigated the potential of the CTAs in GC regarding the expression, function, aggressive phenotype, prognosis, and immunological responses as well as their possible clinical significance as immunotherapeutic targets with a focus on challenges and future interventions.

Background\ud Colorectal-cancer (CRC) is amongst the most lethal-cancers, mainly due to its metastatic spread and drug chemoresistance. Hence there is a need for new approaches to either increase the efficacy of current therapy or introduce new therapies that have greater efficacy. There is increasing evidence that dysregulation of WNT-signaling-pathway plays an essential role in the development and prognosis of CRC. Here we have investigated the therapeutic potential of targeting the WNT/b-catenin pathway using a novel Wnt/b-catenin inhibitor, PNU-74654, in combination with 5-FU in CRC.\ud \ud Methods\ud The anti-proliferative-effect of PNU-74654 was evaluated in two-/three-dimensional cell models. The activity of agents on cell growth, migration, invasion, cell cycle and apoptosis was evaluated by MTT, wound healing assay, invasion, FACS, and annexin V staining, respectively. The oxidant/antioxidant levels were also assessed by determining the level of MDA, SOD, as well as using the DCFH-DA assay. We used a xenograft model of CRC to investigate PNU-74654 activity alone and in combination with 5-FU follow by histological staining and biochemical and gene expression analyses by RT-PCR and western blot.\ud \ud Results\ud PNU-74654 inhibited cell-growth and synergistically affected the anti-tumor properties of 5-FU via modulation of Cyclin D1 and survivin. This agent inhibited the migration/invasion of colorectal cancer cells via perturbation of E-cadherin. Furthermore, PNU-74654 inhibited the tumor growth, which was more pronounced using the PNU-74654 plus 5-FU combination via induction of reactive oxygen species, down-regulation of SOD and modulation of MCP-1, P53, TNF-α.\ud \ud Conclusions\ud Our finding demonstrated that PNU-74654 can target Wnt-pathway, interfere with cell-proliferation, induced-cell death, reduced-migration and interact with 5-FU, supporting further investigations on this therapeutic-approach for colorectal cancer.

Mutations in the Wilm's tumor 1 (WT1) gene are associated with a wide spectrum of renal manifestations, ultimately leading to end-stage kidney failure. There is an inadequate understanding of the molecular functions of WT1 in renal development, and this has limited the potential for therapeutic interventions in WT1-related diseases. In this review, we discuss the existing data on the genetic and epigenetic abnormalities that have been described in WTs and their potential utility as biomarkers for risk stratification, prediction and prognosis in patients with WTs.