Browsing by Author "Deepika Singh"

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Altered expression of NKX3.1 has significant prognostic value in gallbladder cancer
(Elsevier Inc, 2019) Deepika Singh; Amisha Bharti; Dipanjan Biswas; Mallika Tewari; Mumtaz Ahmed Ansari; Sunita Singh; Gopeshwar Narayan
Introduction: NKX3.1, an androgen regulated prostate specific transcription factor, inhibits prostate tumorigenesis. However, its role in GBC is not understood. We aimed to investigate NKX3.1 expression profile to define its role in GBC. Methods: We analyzed the expression of NKX3.1 in 52 GBC and 52 paired adjacent control samples at mRNA level through Real time RT-PCR and validated at protein level through Western blotting. The transcript level data was correlated with clinico-pathological parameters. Promoter hypermethylation was analyzed through methylation specific PCR (MSP). Results: NKX3.1 shows down regulation in 55.8%, up regulation in 25% whereas no change in 19.2% of samples. Its mRNA expression is significantly down regulated in late stage tumors (p =0.0103), in tumors with nodal metastasis (p =0 .0036) and in high grade tumors (p =0 .0173). Interestingly, NKX3.1 is significantly higher in male patients than female patients (p =0 .0057). Kaplan-Meyier analysis reveals prolonged median survival of patients with higher level of NKX3.1 expression compared with patients having low or no change in expression. Conclusion: Our findings suggest that loss or lower expression of NKX3.1 may be a critical in determining the phenotype of GBC. Its expression profile may serve as positive prognostic marker for GBC. © 2019 Elsevier Inc.
Anti-proliferative effect of oyster mushroom, pleurotus from florida (Misnomer) p. florida (agaricomycetes) against hela and siha cervical cancer cells: Mushroom-boon for cancer therapies
(Indian Association of Biomedical Scientists, 2019) Ravi Kant Pathak; Deepika Singh; Krishna Kumar Gupta; Shweta Maurya
Introduction and Aim: Worldwide, people are suffering from the increased risk of cancer due to change in lifestyle, feeding habit and quality of food. To overcome this global problem, Mushroom act as a magic wand. The recent investigations reveal that cancer prevalence is inversely proportional to the intake of mushroom; this is because of its proteins, vitamins, carbohydrate and antioxidants contents. Materials and Methods: Among various species of mushrooms, Pleurotus mushrooms are considered as nutraceuticals i.e. it has nutritional and medicinal values. However, mushroom products and extracts possess immunomodulating and direct cytotoxic effect on cancer cells. Results: The results from the present study shows the potential cytotoxic effect of Pleurotus from Florida against cervical cancer (SIHA) cell line through apoptosis. When SIHA cells were incubated with varying concentration of methanolic extract of Pleurotus from Florida for time (48 hrs). The MTT assay revealed the cytotoxic activity of MME of Pleurotus from Florida in a dose dependent manner. The cell cycle analysis of the SIHA cells revealed that MME of Pleurotus from Florida have anti-cancerous activity. Conclusion: The study could be concluded as the Pleurotus from Florida extract can be useful in the treatment of cervical cancers. The chemical compounds present in the P. from Florida might be useful in the development of drug for the treatment of cancer patients. © 2019, Indian Association of Biomedical Scientists. All rights reserved.
Clinical Significance of Overexpression of Oct4 in Advanced Stage Gallbladder Carcinoma
(Springer, 2023) Deepika Singh; Dipanjan Biswas; Mallika Tewari; Amrita Ghosh Kar; Mumtaz Ahmad Ansari; Sunita Singh; Gopeshwar Narayan
Background: Oct4 has critical role in maintaining pluripotency, proliferative potential, and self-renewal capacity in embryonic stem and germ cells. Although Oct4 has been shown to be upregulated in many cancers, its clinical significance in gallbladder carcinoma is poorly understood. Methods: We studied the expression profile of Oct4 in 61 GBC and 30 chronic cholecystitis (as control) using real time RT-PCR, western blotting, and immunohistochemistry. The expression data was correlated with clinico-pathological parameters. The diagnostic utility was assessed through ROC curve, and prognostic value was analyzed by Kaplan–Meier method. Results: Oct4 was significantly upregulated at mRNA as well as protein levels. The higher mRNA expression shows significant association with late stage, late T stage, and higher grade of tumor. A significant positive correlation was also observed with stage, T stage, and tumor grade. Sum score analysis of protein expression shows positive correlation with stage and the presence or absence of gallstone in tumor samples. The ROC curve analysis revealed the moderate diagnostic potential of Oct4. Kaplan–Meier analysis showed that patients having higher expression of Oct4 were having low mean survival compared with the patients with lower Oct4 expression. Conclusion: In conclusion, our data suggests that higher expression of Oct4 may serve as potential biological indicator for tumor aggressiveness and poor prognosis of GBC. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
DNA Damage Response: A Therapeutic Landscape For Breast Cancer Treatment
(Bentham Science Publishers, 2022) Deepika Singh; Chandra Bhushan Prasad
Breast cancer is responsible for cancer-related death among women globally. The known causes of breast cancer include genetic predisposition, dysregulated hormonal signaling due to psychological stress, and aging and lifestyle factors, such as smoking and alcohol consumption. Due to improved treatment strategies, the overall survival is significantly increased; however, it is still significantly associated with death worldwide. Breast cancer's initiation and progression are strongly influenced by genomic instability. Defect in DNA damage response (DDR) pathways, which enable cells to survive, help in the accumulation of mutation, clonal selection, and expansion of cancer cells. Germline mutation in breast cancer susceptibility genes, BRCA1 and BRCA2, TP53, and PTEN, increases the risk of early onset of disease. During the initial and clonal selection of cancer cells, a defect in one DNA repair pathway could potentially be compensated by another pathway. Therefore, cancer cells with defective DNA repair pathways could be easily killed by targeting the compensatory pathways by inducing synthetic lethality. Evidently, cancer cells with defective DDR or decreased DNA repair capacity show synthetic lethality in monotherapy when the backup DNA repair pathway is inhibited. For instance, tumors with defective homologous recombination (HR) can be targeted by inhibitors of double-strand break repair enzymes. Here, we briefly addressed the relevant factors associated with the development of breast cancer and the role of the DDR factor in the development of breast cancer. In addition, recent treatment strategies targeting genomic instability in breast cancer will be summarized as well as how the genomic instability and defective DDR can be targeted for the treatment of breast cancer. © 2022, Bentham Books imprint.
Frequent Downregulation and Promoter Hypermethylation of DLC1: Relationship with Clinical Outcome in Gallbladder Cancer
(Springer, 2022) Deepika Singh; Amisha Bharti; Dipanjan Biswas; Mallika Tewari; Amrita Ghosh Kar; Mumtaz Ahmed Ansari; Sunita Singh; Gopeshwar Narayan
Introduction: Down regulation of DLC1 is associated with poor prognosis in many cancers, however, its role in gallbladder cancer (GBC) is still unclear. In present study, we investigated the expression profile and promoter methylation status of DLC1. Methods: Expression profiles of DLC1 in 55 GBC and their paired adjacent control samples were analyzed through real time RT-PCR and immunohistochemistry. The mRNA data was correlated with clinico-pathological parameters. Promoter hypermethylation was analyzed through MSP. Results: DLC1 shows downregulation in 76.4%, upregulation in 10.9% whereas no change in 12.7% of GBC samples. Its underexpression shows significant correlation with tumor grade and nodal spread. IHC shows cytoplasmic expression of DLC1 in normal as well as tumor samples. IHC result was concordant to mRNA result. Samples having downregulated DLC1 expression show heterozygous methylation in 83.3% of samples and homozygous methylation in 9.5% of samples whereas 7% of samples have no methylation. Kaplan–Meier analysis shows patient with decreased mRNA of DLC1 have significant low mean survival compared to patients with higher mRNA expression of DLC1. Conclusion: Our findings suggested that dysregulated expression of DLC1 and its hypermethylation may be one of the events playing roles in tumorigenesis of GBC and may serve as a potential target for development of future GBC gene therapy. © 2021, Springer Science+Business Media, LLC, part of Springer Nature.
Frequent promoter hypermethylation and down regulation of BNIP3: An early event during gallbladder cancer progression
(Elsevier B.V., 2022) Amisha Bharti; Amrita Ghosh Kar; Deepika Singh; Mumtaz Ahmad Ansari; Mallika Tewari; Gopeshwar Narayan; Sunita Singh
Background: Epigenetic alterations have been reported as one of the risk factors of gallbladder cancer. Promoter hypermethylation is associated with high incidence and poor prognosis of GBC. Bcl-2/adenovirus E1B 19 kDa interacting protein 3 is a pro-apoptotic protein member of Bcl-2 family. Aims: Present study was aimed to investigate expression profile and promoter methylation status of BNIP3 in GBC and its correlation with clinico-pathological parameters. Methods: The expression analysis and methylation status of BNIP3 was performed by semi-quantitative reverse transcription polymerase chain reaction and Methylation-specific polymerase chain reaction respectively in 84 GBC patients and 29 gallstone tissues (used as normal controls). Results: We demonstrate down regulation of BNIP3 in 56% of the GBC samples. BNIP3 promoter is also frequently hypermethylated (69%) in GBC samples. Interestingly, we found that 69% (40/58) of the BNIP3 promoter hypermethylated samples had also reduced expression of BNIP3. Our data demonstrate significant correlation of the mRNA expression and promoter hypermethylation with late stage and nodal metastasis. Hypermethylation of BNIP3 promoter is associated with low overall survival period. Conclusion: Our results suggest that promoter hypermethylation is an early event and can be a frequent mechanism for downregulation of BNIP3 in GBC. © 2022
PARP1 rs1136410 (A/G) polymorphism is associated with early age of onset of gallbladder cancer
(Lippincott Williams and Wilkins, 2022) Kumari Anjali; Deepika Singh; Puneet Kumar; Tarun Kumar; Gopeshwar Narayan; Sunita Singh
Objectives Evaluation of the association of PARP1 rs1136410 (A/G) polymorphism with gallbladder cancer susceptibility and its prognosis in the Indian population of eastern Uttar Pradesh and western Bihar. Methods PARP1 rs1136410 was genotyped by PCR-RFLP and its association with the prognosis of gallbladder cancer patients were analyzed using Kaplan-Meier plot and log-rank tests. Results Our results demonstrate that minor allele G is more frequent in gallbladder cancer patients than controls. The frequencies of minor allele G and GG genotype are significantly associated with increased risk of gallbladder cancer. Our data suggest that the minor allele G and homozygous genotype GG are significant predisposing factors for the early age of onset of gallbladder cancer. Similarly, women patients having AG and GG genotypes demonstrate an increased risk of gallbladder cancer. The risk group genotypes (AG + GG) are significantly more frequent in patients with thick gallbladder wall, with jaundice and with the presence of lymph node than in patients with normal gallbladder wall thickness, without jaundice and absence of lymph node involvement. Survival analysis data suggest that patients with risk group genotype (AG + GG) presenting jaundice have shorter overall survival. Conclusion Our study suggests that the minor allele G of PARP1 rs1136410 (A/G) is a predisposing factor for gallbladder carcinogenesis and is significantly associated with early onset of the disease. Interestingly, the minor allele G is significantly more frequent in the patients with jaundice, lymph node metastasis and gallbladder wall thickness. © 2022 Lippincott Williams and Wilkins. All rights reserved.
Revisiting the role of TRAIL/TRAIL-R in cancer biology and therapy
(Future Medicine Ltd., 2021) Deepika Singh; Mallika Tewari; Sunita Singh; Gopeshwar Narayan
TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, can induce apoptosis in cancer cells, sparing normal cells when bound to its associated death receptors (DR4/DR5). This unique mechanism makes TRAIL a potential anticancer therapeutic agent. However, clinical trials of recombinant TRAIL protein and TRAIL receptor agonist monoclonal antibodies have shown disappointing results due to its short half-life, poor pharmacokinetics and the resistance of the cancer cells. This review summarizes TRAIL-induced apoptotic and survival pathways as well as mechanisms leading to apoptotic resistance. Recent development of methods to overcome cancer cell resistance to TRAIL-induced apoptosis, such as protein modification, combination therapy and TRAIL-based gene therapy, appear promising. We also discuss the challenges and opportunities in the development of TRAIL-based therapies for the treatment of human cancers. © 2021 Future Medicine Ltd
TRAIL receptors are differentially regulated and clinically significant in gallbladder cancer
(Elsevier B.V., 2020) Deepika Singh; Chandra Bhushan Prasad; Dipanjan Biswas; Mallika Tewari; Amrita Ghosh Kar; Mumtaz Ahmed Ansari; Sunita Singh; Gopeshwar Narayan
Deregulation of the receptors of TNF-related apoptosis inducing ligand (TRAIL) has been reported in various cancers. In an effort to define the role of these receptors we profiled their expression in gallbladder cancer (GBC) and explored their clinical significance. Expression of TRAIL receptors' mRNA in GBC was analysed through reverse transcriptase polymerase chain reaction (RT-PCR), and protein through western blotting, immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). mRNA data show frequent higher expression of TRAIL receptors in GBC samples. Death receptors DR4 and DR5 showed significant negative correlation with tumour stage, T stage and tumour grade; DcR1 transcript showed positive correlation with tumour stage, N stage, M stage and tumour grade. Similarly, IHC showed frequent positive staining for DR4, DR5 and DcR1in GBC samples. Cytoplasmic and nuclear DR4 protein showed negative correlation with T stage and tumour grade, whereas cytoplasmic DcR1 protein showed positive correlation with tumour stage and N stage. Nuclear DcR1 showed positive correlation with N stage. ELISA results showed significantly higher expression of secretory DcR1 in GBC patients. Kaplan–Meier analysis demonstrated significantly decreased mean survival of patients with positive staining of cytoplasmic DcR1. High level of death receptors identified the patients with early gallbladder cancer, whereas high DcR1 expression served as a prognostic factor for poor outcome. © 2020 Royal College of Pathologists of Australasia
VEGFa/VEGFR2 autocrine and paracrine signaling promotes cervical carcinogenesis via β-catenin and snail
(Elsevier Ltd, 2022) Chandra Bhushan Prasad; Deepika Singh; Laxmi Kant Pandey; Satyajit Pradhan; Sunita Singh; Gopeshwar Narayan
VEGF secretion into the tumor microenvironment by cancer cells regulates several oncogenic signaling pathways and cancer-regulated angiogenesis. VEGFR receptors are exclusively present on endothelial cells to maintain their biological homeostasis. The acquisition of unique VEGFR2 receptor and VEGFa in cervical cancer (CC) cells reflects VEGFa/VEGFR2 autocrine machinery. Given the critical role of VEGFR2 in endothelial cell proliferation, migration, and angiogenesis, we explored its function in CC epithelial-mesenchymal transition (EMT) and stemness. Here we report that VEGFR2 regulates cancer-induced angiogenesis and EMT-linked stemness in CC cells via AKT/GSK3β/β-catenin and Snail pathway. Receptor tyrosine kinase inhibitor (RTKi) of VEGFR, Pazopanib (PAZ), shows potential anti-VEGFR2 activity and inhibits VEGFa induced metastatic events such as migration, invasion, and anoikis resistance in CC cells. Similarly, PAZ also attenuates cancer-regulated angiogenesis by inhibiting VE-cadherin internalization in endothelial cells followed by inhibition of endothelial cell migration. Selective depletion of VEGFR2 ligand VEGFa in CC cells also attenuates EMT, metastatic events, and inhibition of cancer-induced angiogenesis. In addition, blocking of VEGFR2 signaling in CC cells via PAZ or shRNA alters the formation of cervical tumorspheres (TS) and their successive generation. Collectively, inhibition of functional VEGFa/VEGFR2 autocrine and paracrine axis ceases the cancer-promoting events in cervical cancer cells. Based on the finding in this study, this oncogenic pathways could be used as a potential therapeutic target in a clinical setting with conventional radio-chemotherapy to achieve synergistic killing of CC cells. © 2021 Elsevier Ltd