Molecular aberrations in Endometriosis were known to be associated with an increased risk of epithelial ovarian cancer (EOCs), especially endometrioid ovarian cancer (ENOC) and ovarian clear cell carcinoma (OCCC). Causal genetic evidence currently remains elusive. The integrated study of related prognostic markers will help to identify the tumorigenesis pathways in endometriosis-associated ovarian cancer (EAOC). The objective of this study was to gain a better understanding of the tumorigenesis mechanisms that occur in the endometriosis-associated genetic variation-progressed ovarian cancer risk. We found 172 overlapping genes that changed both at the DNA and RNA levels from the literature summary of whole exome sequencing and RNA expression from GEO databases. Furthermore, we use KEGG pathways to determine a significant pathway among the gene variants. KEGG includes 50 genes that have significant enrichment pathways. In order to find genes that are specifically expressed in ovary tissue, we prioritize genes using the GTEx database. Based on their TPKM levels, we found 7 genes that were highly expressed in ovary tissue. The genes found were COL12A1, PDGFRA, C7, MYH11, MMP2, C3, and FOS. Interestingly, MYH11 was found in each sample histotype and involved in the role of the actin cytoskeleton. Several proteins influence the migratory and metastatic phenotype of tumor cells, directly or indirectly, as well as myosin protein, suggesting an explanation of tumorigenesis progression in endometriosis to ovarian cancer. Through this analysis, it has attempted to provide variants fortified for future in vivo research through this analysis. More importantly, a comprehensive study of endometriosis-associated diseases associated with ovarian cancer may open new possibilities for identifying and treating these diseases.

Lung Cancer has taken over all cancers in terms of diagnosis and mortality worldwide, which is why it is on the World Health Organisation’s (WHO) priority list. As per the data reported by the WHO, cancer has caused 10 million death each year, and lung cancer alone caused 1.80 million deaths in 2020. Also, the FDA has approved almost 100 drugs against lung cancer, but it is not curable as most drugs target a single protein or block a single pathway. In this study, we screened the Drug Bank library against three major proteins- Ribosomal protein S6 kinase alpha-6, Cyclic-dependent protein kinase-2, and Insulin-like growth factor-1 of lung cancer- and identified the compound 5-Nitroindazole as a multitargeted inhibitor that potentially can treat lung cancer. For the screening, we deployed multisampling algorithms such as HTVS, SP and XP, followed by the MM\GBSA calculation, and the study was extended to molecular fingerprinting analysis, ADMET calculations and Molecular Dynamics simulation analysis to understand the complex’s stability. The docking scores against the proteins 6G77, 1AQ1 and 1K3A were -6.884 Kcal/mol, -7.515 Kcal/mol and -6.754 Kcal/mol, respectively, considered in a good scoring category. Also, the compound has shown all the values satisfying the ADMET criteria, and the fingerprint analysis has shown wide similarities. The molecular dynamics of each complex have shown a cumulative deviation of less than 2 Å, which is considered best for the biomolecules, especially for the protein-ligand complexes. The best feature of the proposed drug candidate is that it targets multiple proteins of lung cancer at the same time, the chance of developing resistance is relatively less, and it drastically can reduce the burden of the pharma industry.

Decitabine (DAC) is an anti-cancer hypomethylating drug used to activate silenced genes by promoter demethylation. DAC induced the expression of the New York esophageal squamous cell carcinoma (NY-ESO-1), a highly immunogenic cancer testis antigen known to induce both humoral and cellular immune responses. However, DAC would increase Programmed Death Ligand-1 (PD-L1) expression in tumor cells leading to resistance to cancer therapy. Vitamin C (Vit-C) is a novel epigenetic regulator of DNA demethylation and is capable of downregulating transcription factors involved in the modulation of PD-L1 expression. Therefore, our major aim is to investigate whether Vit-C could improve the effect of DAC by reducing PD-L1 and to determine the effect of a combination of Vit-C and DAC in colorectal cancer cells.

We treated the HCT-116 colon cancer cell line with DAC (20 µM) and Vit-C (1 mM) alone or in combination for 48h, then cell proliferation was assessed using CCK-8. The differential expression of immune-regulatory and pro-apoptotic markers was quantified using Western Blotting and quantitative real-time PCR. Cell apoptosis and cell cycle profile were analyzed using flow cytometry.

Treatment with DAC alone induces the expression of NY-ESO-1 and upregulates the expression of PD-L1 at mRNA and protein levels compared to untreated cells. Interestingly, the combination of Vit-C with DAC decreased significantly PD-L1 expression compared to DAC alone. Further, the cytotoxic effect of DAC was primarily due to apoptosis shown by overexpression of caspase 8 and cleavage of PARP and caspase 3. This apoptotic effect was confirmed by FACS and was enhanced when Vit-C was used in combination with DAC.

Vit-C prevented the upregulation of PD-L1 and enhanced the cytotoxic effect of the chemotherapeutic drug DAC. Our findings suggest Vit-C as an attractive adjuvant therapy that will promote the immune response and help to overcome immune resistance to DAC in colon cancer patients.

Adipose-derived stem cells (rADSC) play a multifaceted role in cancer metabolism and constitute a potential target for oncologic therapies. Local delivery of TNF-related apoptosis-inducing ligand (TRAIL) can limit tumour growth by selective binding to the death receptor (DR5) in cancer cells. In most healthy cells this pathway is blocked by decoy antagonists such as osteoprotegerin (OPG). This in-vitro study aimed to evaluate an oncologic treatment based on the delivery of TRAIL-transduced rADSC to the vicinity of breast adenocarcinoma cells.

A plasmid containing transgene was produced using the Cloning HD system(TakaraBio) based on Plvx-EF1a-IRES-PURO plasmid and amplified TRAIL gene from the Sprague-Dawley rat kidney. Lentiviral particles were produced using VSV-G Single Shots(TakaraBio) in HEK293T cells. Cytotoxicity of TRAIL against rADSC and RBA (rat adenocarcinoma of the mammary gland) was measured using MTS Assay. Quantitative PCR and Western Blot analyses were conducted to confirm transgene overexpression and measure OPG and DR5 expression in both cell lines. Direct cytotoxicity of RBA cells to transduced rADSC was measured using exposure to a supernatant of TRAIL-expressing rADSC. Data analysis was done using the student’s t-test.

Cells were successfully transduced, and TRAIL expression was 400-fold higher in transduced cells (P<0.01) than in controls. The expression of TRAIL-dependent receptors was higher in rADSC (OPG – 30-fold (P<0.01) and DR5 - 6-fold (P<0.05)). RBA cells were susceptible to exogenous TRAIL and the cell supernatant – IC50 was equal to 200 ng/ml, while rADSC were resistant to TRAIL.

The results show that TRAIL-transduced rADSC are cytotoxic against adenocarcinoma cells. Overexpression of TRAIL by rADSC also stimulates their growth leading to an increased cancer microenvironment penetration. Such active surveillance based on stable local production of anticancer cytokine can limit cancer recurrence when transplanted into the vicinity of cancer tissue.

Glioblastoma multiforme (GBM) is the most common aggressive malignant primary brain tumor afflicting approximately 3.19 per 100,000 persons in the United States with an incidence 1.6 times higher in males compared to females. GBM usually arises from the glial cells known as astrocytes and it is commonly located in the supratentorial region (cortical lobes),usually affecting the frontal lobe. A unique feature of this tumor is its rapid local growth and spread making the prognosis very poor with a 5-year survival rate less than 5 %.Treatment of GBM remains challenging. Multiple therapeutic interventions are used for GBM including surgical resection of the tumor, radiotherapy and chemotherapy. Other experimental methods for the treatment of GBM include immune therapy, gene therapy, simulated microgravity therapy, and oncolytic viral therapy. We propose a combination therapy of simulated microgravity using a clinostat-based three-dimensional culture system with an oncolytic viral therapy using an autonomous rat parvovirus H-1 (H-1PV). Our hypothesis combines the beneficial effects of simulated microgravity and oncolytic viral therapy to lyse tumor cells through induction of apoptosis, decreased cell proliferation and or induction of an immune response. This proposal provides the foundations to construct novel breakthroughs in the treatment of GBM.