Browsing by Author "Ruhi Dixit"

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A Study of Arginase Expression in Chronic Non-healing Wounds
(SAGE Publications Inc., 2023) Ruhi Dixit; Abhik Debnath; Suman Mishra; Rajnikant Mishra; Satyanam K. Bhartiya; Arvind Pratap; Vijay K. Shukla
Arginase expression has been recently shown to increase in numerous disease states like neurodegeneration, inflammation, and malignancies. Although it has been found to be functionally important in various disease pathologies, little is known about its role in wound healing. Here, we look at the expression of arginase and its isoforms in chronic non-healing wounds and also study the expression of nitric oxide synthase (NOS) and oxidative stress enzymes in them. Wound tissues and blood samples were collected at the time of index presentation and follow-up from 61 chronic non-healing wound cases. The expression patterns of arginase isoenzymes, NOS, superoxide dismutases (SOD), lactic acid dehydrogenase (LDH), and catalase were examined by using enzyme-linked immunosorbent assay, immunohistochemistry, and western blot analysis at the transcript and protein level. We reported a significant decrease of serum arginase levels in chronic nonhealing wounds in the progress of wound healing. Interestingly, tissue arginase levels were found to be increased with improved wound condition at follow-up. Tissue NOS, LDH, and catalase activity were also found to be increased with the progress of healing, whereas SOD levels were downregulated. Our findings reported increased expression at the transcript level of arginase-I and arginase-II in chronic non-healing wounds for the first time. In conclusion, we observed decreased serum arginase levels in completely healed patients as compared to non-healed cases. Our study findings support the hypothesis that inhibition of the activity of arginase delays wound healing. Arginase and iNOS may also find their place in the future as possible biomarkers for wound healing. © The Author(s) 2021.
A systematic review of proteomic biomarkers in oral squamous cell cancer
(BioMed Central Ltd, 2021) Jyotsnaa Pillai; Tanvi Chincholkar; Ruhi Dixit; Manoj Pandey
Background: Head and neck squamous cell cancer (HNSCC) is the most common cancer associated with chewing tobacco, in the world. As this is divided in to sites and subsites, it does not make it to top 10 cancers. The most common subsite is the oral cancer. At the time of diagnosis, more than 50% of patients with oral squamous cell cancers (OSCC) had advanced disease, indicating the lack of availability of early detection and risk assessment biomarkers. The new protein biomarker development and discovery will aid in early diagnosis and treatment which lead to targeted treatment and ultimately a good prognosis. Methods: This systematic review was performed as per PRISMA guidelines. All relevant studies assessing characteristics of oral cancer and proteomics were considered for analysis. Only human studies published in English were included, and abstracts, incomplete articles, and cell line or animal studies were excluded. Results: A total of 308 articles were found, of which 112 were found to be relevant after exclusion. The present review focuses on techniques of cancer proteomics and discovery of biomarkers using these techniques. The signature of protein expression may be used to predict drug response and clinical course of disease and could be used to individualize therapy with such knowledge. Conclusions: Prospective use of these markers in the clinical setting will enable early detection, prediction of response to treatment, improvement in treatment selection, and early detection of tumor recurrence for disease monitoring. However, most of these markers for OSCC are yet to be validated. © 2021, The Author(s).
Analysis of SET and MYND Domain-Containing Protein 3 (SMYD3) Expression in Gallbladder Cancer: a Pilot Study
(Springer, 2021) Pushkar Chandra; Ruhi Dixit; Arvind Pratap; Suman Mishra; Rajnikant Mishra; Vijay Kumar Shukla
The Suvar, Enhancer of zeste, and Trithorax (SET) and myeloid-Nervy-DEAF-1 (MYND) domain-containing protein 3 (SMYD3) is a histone lysine methyltransferase and has been recently unveiled to play significant roles in the progression of human cancer via regulating various key cancer-associated genes and pathways. The role of SMYD3 in gallbladder cancer (GBC) still needs to be studied. In the present study, we examined the SMYD3 gene expression at mRNA and protein level to look its impact on risk for developing gallbladder carcinogenesis. SMYD3 expression was evaluated by immunohistochemistry and reverse transcriptase PCR (RT-PCR) from 30 cases each of GBC and cholelithiasis patients. The expression was compared with different clinicopathological parameters. The SMYD3 expression was found to be significantly upregulated in GBC than cholelithiasis group (p < 0.05). The SMYD3 with increased expression level was observed in 73.3% of the GBC cases (p < 0.05). Moreover, mRNA SMYD3 expression was observed in 73.3% of GBC and 10% of control (p < 0.05). Our results indicated that the overexpression of SMYD3 plays an important role in the GBC progression, and SMYD3 may represent useful biomarker for gallbladder cancer patients. © 2020, Indian Association of Surgical Oncology.
Antisense RNAs (asRNAs) as key players in gallbladder cancer progression: a bioinformatics analysis
(Research Institute for Gastroenterology and Liver Diseases, 2025) Monika Rajput; Ruhi Dixit; Manoj Pandey; Vijay Kumar Shukla
Aim: This study reports differential expression of Antisense RNAs (asRNAs) by analyzing transcriptomic profiles in gallbladder cancer (GBC). Background: asRNAs play crucial roles in developing various tumors. However, the presence and biological mechanism of asRNAs in GBC development are still unknown. Methods: Differentially expressed asRNAs (DE-asRNAs) were systematically identified from RNA sequencing data \ from ten GBC patients. Functional enrichment analysis was performed, followed by the identification of mRNAs targeted by asRNAs and the construction of a gene regulatory network of asRNAs targeting mRNAs. Results: Of the 891 asRNAs identified, 17 DE-asRNAs were statistically significant. Out of 17, 12 asRNAs were upregulated, and five asRNAs were downregulated. Functional enrichment analysis showed their role in methylation and developmental processes. Of the 17 asRNAs, 14 are novel (UNC5B-AS1, SLC2A1-AS1, BBOX1-AS1, SOX21-AS1, ELFN1-AS1, TRPM2-AS, DNAH17-AS1, DCST1AS1, VPS9D1-AS1, MIR1-1HG-AS1, HAND2-AS1, PGM5P4-AS1, PGM5P3-AS1, and MAGI2-AS). Enrichment analysis of asRNAs with target mRNAs showed enrichment in biological regulation and developmental processes involved in the PI3K, p53, apoptosis, and VEGF signaling pathways. Conclusion: This study identified 14 asRNAs for the first time and showed that asRNAs targeting mRNAs strongly associated with tumor development in GBC through the PI3KCA and TP53 pathways. © 2025, Gastroenterology and Hepatology From Bed to Bench (GHFBB). This is an open-access article, distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by nc/4.0/) which permits others to copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
Association of Methylenetetrahydrafolate Reductase Gene Polymorphism (MTHFR) in Patients with Gallbladder Cancer
(Humana Press Inc., 2016) Ruhi Dixit; Gyanendra Singh; Manoj Pandey; Somprakas Basu; Satyanam Kumar Bhartiya; K.K. Singh; Vijay Kumar Shukla
Purpose: 5,10-Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism and plays a major role in DNA methylation. There are two popular MTHFR polymorphisms known as C677T and A1298C which are found to be involved in folate metabolism and lowering the enzyme activity, thus may be linked with cancer development. This study aims to look at the association of these polymorphisms in gallbladder cancer. Methods: Thirty patients each with gallbladder cancer, cholelithiasis, and normal gallbladder were genotyped for the above-given polymorphisms by PCR-restriction fragment length polymorphism (RFLP) method. Results: C677T MTHFR polymorphism was not associated (χ2 = 2.44, p = 0.85) with an increased likelihood of having gallbladder cancer. A1298C was significantly associated (χ2 = 28.87, p < 0.001) with risk of developing gallbladder cancer. A1298C was significantly correlated with grade (r = 0.337, p < 0.001) and histopathology (r = 0.446, p < 0.001). Conclusion: This study proposed that MTHFR A1298C polymorphism may be associated with risk of developing gallbladder cancer, and there is no association between C677T polymorphism and gallbladder cancer. © 2015, Springer Science+Business Media New York.
Association of mustard oil as cooking media with carcinoma of the gallbladder
(2013) Ruhi Dixit; Piyush Srivastava; Somprakas Basu; Pradeep Srivastava; Pradeep Kumar Mishra; Vijay Kumar Shukla
Purpose Carcinoma of the gallbladder (CaGB) is a common health problem in Northern India. Exact causative factors are still obscure. Dietary habits are also known to be a major factor in the gallbladder carcinogenesis. Mustard oil is mostly used as cooking media, which is adulterated by sanguinarine, diethylnitrosamine and repeated frying. We tried to find out the association of mustard oil as cooking media with CaGB. Methods Twenty patients each of CaGB (group I) and cholelithiasis (group II) were included in the study. Sanguinarine and diethylnitrosamine (DEN) were extracted from the tissue and blood samples from both groups. Mean and standard error of mean of the concentration of the sanguinarine and DEN were calculated. Mann-Whitney U test was applied to test the level of significance between the two groups. Results The mean concentration of tissue sanguinarine in both groups (I and II) was 195.18 ng/mg and 24.05 ng/mg, respectively, and the difference was statistically highly significant (p<0.001). The estimated concentration of blood sanguinarine was 230.96 ng/mL and 14.0 ng/mL in group I and II, respectively, and the difference was statistically highly significant (p<0.001). The concentration of DEN in the tissue sample was 38.08 ng/mg in CaGB and 2.51 ng/mg in cholelithiasis patient, and these values were statistically highly significant (p<0.001). Similarly, blood DEN concentration was 119.05 ng/mL and 4.22 ng/mL in group I and II, respectively, and the difference was statistically highly significant (p<0.001). Conclusion There is an increase in concentration of sanguinarine and diethylnitrosamine in CaGB blood and tissue in comparison to the cholelithiasis group suggesting an association with carcinoma of the gallbladder. © Springer Science+Business Media New York 2012.
Bioprospecting potential genetic biomarkers of gallbladder cancer
(Springer Science and Business Media B.V., 2025) Ruhi Dixit; Manoj Pandey; Vijay Kumar Shukla
Background: Gallbladder cancer (GBC) is a rare and aggressive cancer of the biliary tract with a very low survival rate. The availability of diagnostic biomarkers and targeted therapies for its management is limited. The study identifies potential genetic biomarkers of GBC by analyzing differentially expressed genes (DEGs) through microarray profiling and constructing regulatory networks using systems biology techniques. Methods: We used Clariom™ D Array in gallbladder cancer, cholelithiasis, and normal tissues (10 cases in each group), identifying DEGs and key biological pathways. Functional analysis via Metascape, DisGeNET, and KEGG-SIGNOR network mapping revealed gene-disease relationships and protein interactions. Results: There were 3,898 significant DEGs (|Fold Change| > 2.0, p < 0.05) identified in GBC compared to normal gallbladder tissue, with 2,575 genes upregulated and 1,323 downregulated. On comparison with cholelithiasis, 2523 DEGs (|Fold Change|>2.0, p < 0.05) were upregulated and 1451 downregulated. The functional analyses have shown that these DEGs were mainly involved in anatomical structure maturation and cell-cycle regulation. Top ten identified hub genes were XAB2, XPA, RPA1, RAD51B, RPS27A, BRCA2, ATR, PDS5B, CCNB2 and RANBP2. The top 3 related pathways were mismatch repair pathway, nucleotide excision repair and homologous recombination. Conclusion: A significantly high differential gene expression was identified in gallbladder cancer compared to control groups. For the first time, we identified key genes—XAB2, XPA, RPA1, RAD51B, RPS27A, BRCA2, ATR, PDS5B, CCNB2, and RANBP2—as crucial players in homologous recombination, mismatch repair, DNA damage repair, and DNA replication processes that contribute to gallbladder carcinogenesis. © The Author(s), under exclusive licence to Springer Nature B.V. 2025.
Cancer prevention through lifestyle modification
(Scientific Scholar LLC, 2025) Devi Nandakumar; Ruhi Dixit; Manoj Pandey
[No abstract available]
Chemotherapeutic drugs and gallbladder cancer: Market potential in India
(Springer Singapore, 2019) Ruhi Dixit; Manoj Pandey; Punam Pandey; V.K. Shukla
Gallbladder cancer (GBC) is the most fatal cancer of the biliary tract with poor prognosis. Silent in its infancy, this malignancy remains asymptomatic until aggressive disease has progressed to an advanced and non-curative stage. The overall mean survival rate for patients with GBC is less than 6 months, with a 5-year survival rate of approximately 5% with a high relapse rate. Treatment depends upon the stage of disease, patient’s age, nutritional status, performance status, and cardiopulmonary, hepatic, and renal functions. Complete surgical resection is considered the most curative modality for GBC. Chemotherapy has recently shown its effect on gallbladder cancer. Therapeutic agents, targeting cellular and molecular pathways, can effectively impede tumor growth. Newer drugs are being developed that work which target specific parts of cancer cells or their surrounding environments like tumor blood vessels. This chapter discusses market of chemotherapeutic drugs in India and market drives and government initiatives for the promotion of pharmaceutical sector in India with special emphasis on GBC. © Springer Nature Singapore Pte Ltd. 2020.
Chromosomal structural analysis in carcinoma of the gallbladder
(2012) Ruhi Dixit; Prabhat Kumar; Ratnakar Tripathi; Somprakash Basu; Rajnikanth Mishra; V.K. Shukla
Background: The etiopathogenesis of gallbladder cancer is still unknown. Both environmental and patient factors have been incriminated in its cause. That it is found in pockets of epidemiological distribution raises an issue of genetic changes associated with it. The aim of this study was to find out the chromosomal changes in gallbladder cancer.Methods: Lymphocyte cell culture was carried out on blood of gallbladder cancer patients to determine chromosomal banding abnormalities. Native PAGE was also evaluated to analyze lactate dehydrogenase (LDH), superoxide dismutase (SOD) and catalase enzyme activity from the same blood of gallbladder cancer patients.Results: Out of 30 gallbladder cancer patients, 4 male showed breakage on the long arm of chromosome 1 while only one male patient showed the translocation from the long arm of chromosome 4 to the long arm of chromosome 6 in a male patient.Conclusion: The aberrations found in our study may suggest underlying genetic predisposition for the development of gallbladder cancer. They can act as a marker for gallbladder cancer, which needs further study. © 2012 Dixit et al.; licensee BioMed Central Ltd.
Comparative Analysis of Mutational Profile of Sonic hedgehog Gene in Gallbladder Cancer
(Springer New York LLC, 2017) Ruhi Dixit; Manoj Pandey; Sunil Kumar Tripathi; Amit Nandan Dhar Dwivedi; Vijay Kumar Shukla
Background: Gallbladder cancer has high incidence in northeastern India; mortality too is high as the disease is often diagnosed late. Numerous studies have shown the role of sonic hedgehog (shh) in different cancers, an important ligand of the hedgehog signaling pathway. Aim: This study was carried out to evaluate the shh gene mutations in gallbladder cancer patients. Methods: PCR-SSCP was performed for shh gene in 50 samples each of gallbladder cancer, cholelithiasis, and control. The samples showing aberration in banding pattern were sequenced. Results: Variation in banding pattern was observed in 20% gallbladder cancer cases, 10% in cholelithiasis, and none of the control (χ2 = 11.111; p < 0.05). Sequencing results revealed seven novel point mutations in GBC cases. These novel mutations were found to be associated with histopathology (p < 0.05) and stage (p < 0.05) of gallbladder cancer. Conclusion: This study reveals several novel individual and repetitive mutations of shh gene in GBC and cholelithiasis samples that may be used as diagnostic markers for gallbladder carcinogenesis. © 2017, Springer Science+Business Media New York.
Effect of neoadjuvant chemotherapy and its correlation with HPV status, EGFR, Her-2-neu, and GADD45 expression in oral squamous cell carcinoma
(BioMed Central Ltd., 2018) Manoj Pandey; Krishna Kiran Kannepali; Ruhi Dixit; Mohan Kumar
Background: Head and neck cancers are the commonest cancer in Southeast Asia. Despite being a surface cancer, it is associated with significant morbidity as despite early detection by the patients they often report for treatment late and hence are associated with poor prognosis. The role of neoadjuvant chemotherapy in head and neck cancer is still under evaluation; there is a large subgroup of population that does not respond to chemotherapy, and hence, most studies have failed to show any survival benefit. This study evaluated the role of neoadjuvant therapy with docetaxel and carboplatin in patients with oral cancer and correlated the response to human papilloma virus, EGFR1, EGFR2, and GADD45 expression. Methods: A total of 24 locally advanced, non-metastatic oral cancer patients were included in the study. Tumor biopsies were taken prior to the start of neoadjuvant therapy for expression of EGFR, Her-2-Neu, and GADD45 by immunohistochemistry and for HPV by PCR. The response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria after three cycles of chemotherapy. Statistical analysis was performed using correlation and Kaplan-Meier analysis; the difference in survival was calculated with log rank test. Results: A total of 21 male and 3 female with a mean age of 53.12years were enrolled. Sixty-five percent of these received three cycles of chemotherapy. Five patients were positive for HPV 16 and none for HPV 18. Twenty-two of 24 patients showed GADD45 expression, 3 showed expression of Her-2-Neu while all 24 showed expression for EGFR1 protein. Two-year overall survival was 81%; GADD45 expressions were found to significantly affect the overall and disease-free survival, while any of the other protein expression studied and HPV status was not significant. Conclusion: The result of the present study shows significant downgrading of the oral cancers with neoadjuvant chemotherapy suggesting its utility in borderline operable cases. However, the response of chemotherapy does not appear to be related to the expression of EGFR, Her-2-Neu, and GADD45 protein or presence of HPV. Bone involvement, perineural invasion, and GADD45 expression significantly predict OS and DFS. All patients who did not express Gadd45 died before 2years. Study with more subjects and longer follow-up should be carried out to elucidate this relation further. © 2018 The Author(s).
Efficacy and safety of cetuximab-based versus platinum-based chemoradiation in HNSCC: evidence from a meta-analysis of 10 randomized controlled trials
(Springer Science and Business Media Deutschland GmbH, 2025) Tarun Kumar; Nishu Kesh; Atindra Kumar Pandey; Ankita Chakrawal; Bhavana Singh; Manjusha Pal; Monika Rajput; Ruhi Dixit; Esha Pai; Manoj Pandey
Background: Platinum-based chemoradiotherapy (CTRT) is the standard treatment for head and neck squamous cell carcinoma (HNSCC). While cetuximab-based radiotherapy (CxRT) has been proposed as an alternative, its efficacy remains controversial. Multiple meta-analyses have compared CxRT with CTRT for HNSCC though they combined randomized controlled trials (RCTs) with lower-evidence studies, compromising result validity. This study presents the first meta-analysis using exclusively RCT data, providing the highest level of evidence for clinical decision-making. Methods: We systematically searched MEDLINE, Embase, Cochrane, and SCOPUS, identifying 10 RCTs (n = 2,557 patients). Primary outcomes included overall survival (OS), disease-free survival (DFS), and all-cause mortality; secondary outcomes were Grade ≥ 3 toxicities. Hazard ratios (HRs) and odds ratios (ORs) were pooled using random effect models. Results: CxRT was associated with a 50% higher recurrence risk (HR 1.50, 95% CI 1.07–2.10) and 27% increased all-cause mortality (OR 1.27, 95% CI 1.05–1.55) compared to CTRT. OS did not differ significantly (HR 1.33, 95% CI 0.79–2.22). Toxicity profiles varied: CxRT had higher mucositis (OR 1.17, 95% CI 1.04–1.32) and skin rash (OR 3.46, 95% CI 1.28–9.36), while CTRT showed more anemia (OR 0.15, 95% CI 0.05–0.52) and nausea/vomiting (OR 0.31, 95% CI 0.19–0.53). Conclusion: CxRT is inferior to CTRT in HNSCC, with poorer disease control and survival outcomes. The lack of biomarker (EGFR/RAS) stratification in trials may have contributed to suboptimal patient selection. While CxRT may be an option for cisplatin-ineligible patients, platinum-based therapy appears to be the standard. Future research should optimize cetuximab’s role through biomarker-driven selection. © The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2025.
Expression analysis of aryl hydrocarbon receptor repressor (AHRR) gene in gallbladder cancer
(NLM (Medline), 2021) Puneet Kumar; Manoj Yadav; Khushi Verma; Ruhi Dixit; Juhi Singh; Satyendra K. Tiwary; Gopeshwar Narayan; V.K. Dixit
Background: The aryl hydrocarbon receptor repressor (AHRR), a member of the growing superfamily, is a basic helix-loop-helix/PerAHR nuclear translocator (ARNT)-Sim (bHLH-PAS) protein. AHRR has been proposed to function as a putative new tumor suppressor gene based on studies in multiple types of human cancers. This current study aims to investigate AHHR expression and its prognostic significance in gallbladder cancer. Methods: The study includes 48 gallbladder cancer and 34 chronic cholecystitis cases as controls. The expression level of AHRR was analyzed by using semi-quantitative PCR and immunohistochemical staining. The results were correlated with different clinical parameters. Results: We demonstrate that the expression of AHRR is significantly down-regulated in gallbladder cancer tissue samples as compared to that in chronic cholecystitis tissue samples by reverse transcriptase PCR (RT-PCR) (P = 0.017) and immunohistochemistry analysis (P = 0.002). Interestingly, our RT-PCR data revealed that AHRR mRNA expression is frequently down-regulated (45.8%; 22/48) in cases as compared to 14.7% (5/34) in controls. Similarly, immunohistochemical analysis data show significant down-regulation of AHRR expression in 77.1% (37/48) of gallbladder cancer cases than 44.1% (15/34) in controls (P < 0.017). Reduced mRNA and protein expression is significantly associated with advanced T-stage (P = 0.001), histological differentiation (P = 0.001), and tumors with nodal metastasis (P = 0.001). Decreased expression of AHRR is significantly associated with poor prognosis in gallbladder cancer patients. Conclusion: In conclusion, the present study suggests that low AHRR expression may be critical in gallbladder cancer development. Our data suggests that AHRR may act as a tumor suppressor gene and its expression profile may be useful as a diagnostic marker in gallbladder cancer.
Expression analysis of survivin and XIAP in gallbladder cancer: A case-control study in indo-gangetic plain
(Humana Press Inc., 2018) Ruhi Dixit; Mohd Raza; Mohan Kumar; S. Basu; V.K. Shukla
Purpose Gallbladder cancer is a highly mortal disease with poor prognosis because of late presentation of disease. Survivin and X-linked inhibitor of apoptosis (XIAP) are one of the two important members of inhibitors of apoptosis. Thus, this study aimed to look at the expression of Survivin and XIAP in gallbladder cancer patients. Methods Survivin and XIAP expression were investigated in tissues of gallbladder cancer patients (40 cases) and compared with cholelithiasis as control (40 cases) by using immunohistochemistry. Their expression was correlated with clinicopathological parameters. Results Significantly higher (p < 0.05), Survivin protein was expressed in gallbladder cancer (n = 67.5%) than control (n = 35%). But it did not show any significant association with any of the clinicopathological parameter while XIAP was not expressed in the GBC patients (p > 0.05). Conclusion Overexpression of Survivin in gallbladder cancer suggests its possible role and association with poor prognosis. But XIAP has not been found to be associated with gallbladder carcinogenesis. © Springer Science+Business Media, LLC 2017.
Expression of Mucoproteins in Gallbladder Cancer
(Springer, 2022) Puneet Kumar; Priyesh Shukla; Soni Kumari; Ruhi Dixit; Gopeshwar Narayan; V.K. Dixit; A.K. Khanna
This study was designed to evaluate the correlation of expression profiles of MUC2, MUC4, and MUC5AC to the clinico-pathological parameters in gallbladder cancer. We recruited biopsies of a total of 60 subjects including 50 primary tumor biopsies from histopathologically proven gallbladder cancer and 10 cases of chronic cholecystitis as control. We have investigated the expression levels of MUC2, MUC4, and MUC5AC by semi-quantitative RT-PCR and immune-histochemistry in gallbladder cancer biopsies, and chronic cholecystitis as a control. Clinical correlation of the differential expression of MUC2, MUC4, and MUC5AC was determined using appropriate statistical methods. Our results demonstrated that MUC2 was significantly (p = 0.004) upregulated in 16%, MUC4 was significantly (p = 0.0004) upregulated in 24%, and MUC5AC was significantly (p = 0.003) upregulated in 32% samples at transcript levels in primary gallbladder cancer biopsies in comparison to the control. Similar to RT-PCR data, MUC2 was significantly (p = 0.001) upregulated in 30%, MUC4 was significantly (p = 0.047) upregulated in 48%, and MUC5AC was significantly (p = 0.002) upregulated in 52% samples at proteome levels in primary gallbladder cancer biopsies in comparison to the control. In conclusion, the MUC2, MUC4, and MUC5AC expression were found to be significantly upregulated in gallbladder cancer group than control. The overexpression of MUC2, MUC4, and MUC5AC suggested their association with gallbladder cancer. © 2021, Association of Surgeons of India.
Gallbladder Cancer: Current Treatment Options
(Springer Nature, 2023) Vijay Kumar Shukla; Manoj Pandey; Ruhi Dixit
The book discusses the recent progress in understanding the therapeutic targets for gallbladder cancer to provide opportunities for research and for developing innovative strategies that may enhance the benefit of conventional chemotherapy.The book focuses on identifying candidate molecules and the overall status of the targeted therapies available for gallbladder cancer, as there is an urgent need to discover new molecular targets that can guide the emergence of new treatment strategies to improve patient outcomes and act as biomarkers for the early detection of diseases. Recently, new treatment therapeutics targets for gallbladder cancer patients have been identified and the field is evolving rapidly.The book is relevant for the clinical researcher, surgeon, scientist and academician. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.
Genetic mutational analysis of β-catenin gene affecting GSK-3β phosphorylation plays a role in gallbladder carcinogenesis: Results from a case control study
(Elsevier Ltd, 2020) Ruhi Dixit; Manoj Pandey; Sunil Kumar Tripathi; Amit Nandan Dhar Dwivedi; Vijay Kumar Shukla
This manuscript has reported different mutations of β-catenin gene in gallbladder cancer patients which affect GSK-3β phosphorylation site. Purpose: Gallbladder carcinoma (GBC) is a relatively rare and fatal cancer with poor prognosis. The molecular mechanism of gallbladder carcinogenesis is still not clear. Wnt signaling pathway is a highly conserved pathway that regulates proliferation, differentiation, migration, genetic stability, apoptosis, and stem cell renewal. β-catenin plays major role in Wnt signaling and aberrations in β-catenin has found to be involved in several cancers pathogenesis. This study was carried out to document the mutations of β-catenin gene in gallbladder cancer and to evaluate its possible role in gallbladder carcinogenesis. Methods: PCR-SSCP (Single Stranded Conformation Polymorphism) for ctnnb1 was performed in 50 patients each of gallbladder cancer, cholelithiasis and 50 healthy controls. Samples that showed variation in banding pattern were sequenced. Results: Variation in banding pattern was observed in 9 (18%) samples of GBC, 4 (8%) of cholelithiasis and 2 (4%) of control. Sequencing analysis showed 9 novel mutations of ctnnb1 in exon 3 in 18% of gallbladder cancer (χ2 = 5.778; p < 0.05). Six point mutations, 1 deletion and 1 insertion mutation were found in 9 cases of gallbladder cancer. All point mutations were mis-sense mutation that affected highly conserved serine or threonine region that is important for GSK-3β phosphorylation. Conclusion: Findings of the study suggests that high frequency of non synonymous mutations of β-catenin gene (ctnnb1) occurs in patients with gallbladder cancer. As these mutations mainly effect GSK 3β phosphorylation, it may be concluded that this might be an important step in gallbladder carcinogenesis. These β-catenin mutations lead to Wnt pathway activation and appear to have a role in progression from inflammation to cancer in gallbladder. © 2020 The Author(s)
Helicobacter bilis in Human gallbladder cancer: Results of a case-control study and a meta-analysis
(Asian Pacific Organization for Cancer Prevention, 2010) Manoj Pandey; Raghvendra R Mishra; Ruhi Dixit; Rashmi Jaiswal; Mridula Shukla; Gopal Nath
Introduction: Gallbladder cancer is an uncommon neoplasm of uncertain etiology and poor survival. Recently, interest has been generated in bacterial infections and cancers. Helicobacter is one such bacterium found to be associated with gastric MALToma, gastric adenocarcinoma and hepatobiliary neoplasms. Patients and methods: Fifty four gallbladder cancer and 55 controls with cholelithiasis were studied. Helicobacter bilis was identified using 16S rRNA PCR. Relative risk and odds ratio with 95% CI were estimated. A detailed search of literature was carried out and selected relevant articles were extracted. A meta analysis was carried out using a random effect model. Results: Helicobacter bilis was identified in 32/54 patients and 32/55 controls, The relative risk of gallbladder cancer in H. bilis positive cases was 1.05 (95% CI 0.49 to 2.24). Of the 10 identified case control studies on Helicobacter in the hepatobiliary tract 3 each were on gallbladder cancer and H. bilis. In meta analysis a pooled odds ratio of 4.13 (95% CI 2.68-6.36) favoring Helicobacter was observed. Pooled analysis of published studies on gallbladder cancer showed an odds ratio of 1.24 (95% CI 0.63-2.44). Conclusions: The present study failed to demonstrate any increase in risk of gallbladder cancer in presence of Helicobacter bilis. It may be hypothesized that increased risk observed in earlier studies may be indirectly due to increase in the risk of gallstones, although lack of any study specifically looking at this aspect and absence of normal controls in the present study makes this assumption superfluous.
Human long non-coding RNAs acquired from bacteria via horizontal gene transfer promote gallbladder cancer
(Springer Science and Business Media B.V., 2025) Manoj Pandey; Monika Rajput; Pooja Singh; Vijay Kumar Shukla; Ruhi Dixit
Background: Gallbladder cancer, the most common malignancy of the bile duct, has a poorly understood etiopathogenesis. Non-coding RNAs are implicated in various cancers, but their role in gallbladder carcinogenesis remains unclear. Methods: Transcriptomic data from gallbladder cancer patients were analyzed to identify differentially expressed long non-coding RNAs (lncRNAs). These data underwent cross-species phylogenetic analysis and BLAST comparison with bacterial and ancient human genomes, including Homo heidelbergensis and Homo neanderthalensis. Pathway analysis, gene-gene interactions, and data and text mining were performed for non-conserved, non-coding genes. Results: Of 16 differentially expressed lncRNAs, seven showed phylogenetic links to bacterial genomes, suggesting acquisition through horizontal gene transfer (HGT) during human evolution. These lncRNAs were present in ancient human species with sequence variations. Functional analysis revealed their role in regulating biological and genetic processes, potentially promoting gallbladder carcinogenesis. Conclusions: This is the first study to propose that seven human lncRNAs, likely of bacterial origin, were acquired through HGT during evolution. These lncRNAs regulate transcriptional and post-transcriptional processes, potentially inducing gallbladder carcinogenesis, thus highlighting a novel link between evolutionary genetics and cancer. © The Author(s), under exclusive licence to Springer Nature B.V. 2025.