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Bhabani Mohanty

Bio: Bhabani Mohanty is an academic researcher from Cancer Research Institute. The author has contributed to research in topic(s): Gallbladder cancer & Gallbladder. The author has an hindex of 6, co-authored 9 publication(s) receiving 87 citation(s).
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Journal ArticleDOI
Ambuja Navalkar1, Satyaprakash Pandey1, Namrata Singh1, Komal Patel1  +5 moreInstitutions (3)
Abstract: Tumor suppressor p53 mutations are associated with more than 50% of cancers. Aggregation and amyloid formation of p53 is also implicated in cancer pathogenesis, but direct evidence for aggregated p53 amyloids acting as an oncogene is lacking. Here, we conclusively demonstrate that wild-type p53 amyloid formation imparts oncogenic properties to non-cancerous cells. p53 amyloid aggregates were transferred through cell generations, contributing to enhanced survival, apoptotic resistance with increased proliferation and migration. The tumorigenic potential of p53 amyloid-transformed cells was further confirmed in mouse xenografts, wherein the tumors showed p53 amyloids. p53 disaggregation rescued the cellular transformation and inhibited tumor development in mice. We propose that wild-type p53 amyloid formation contributes to tumorigenesis and can be a potential target for therapeutic intervention. This article has an associated First Person interview with the first author of the paper.

1 citations

Journal ArticleDOI
Dheeraj Kumar, Navin Sakhare, Soumen Das, Pooja Kale  +7 moreInstitutions (1)
TL;DR: In vivo pharmacokinetics envisaged in the present design was achieved using the present gold functionalized NP preparation, which showed affinity towards FR positive KB cancer cell lines.
Abstract: Introduction Strategic design and synthesis of nanoparticle based preparations could improve diagnostic screening of several cancer types, thereby facilitating better clinical management of the disease. Towards this, the present work aims to develop and evaluate a radioactive technetium-99m (99mTc) labeled gold nanoparticle (NP) preparation modified with folic acid, so as to diagnose folate receptor positive cancers viz. ovarian, breast, etc. Methods 11-Bromoundecanoic acid (UA) was synthetically modified both with folic acid and Hydrazinonicotinic acid (HYNIC) chelate at the carboxylic acid end and subsequently converted to thiol functionality at the bromo terminal to yield folic acid-UA-SH and HYNIC-UA-SH ligands respectively. Gold NPs modified with folic acid and HYNIC chelator were obtained on direct addition of folic acid-UA-SH and HYNIC-UA-SH to chloroauric acid in polysorbate 80 solution under reducing conditions. These NPs were then radiolabeled with 99mTc following HYNIC labeling approach. Both the inactive and 99mTc-labeled gold NPs were then tested for their biological efficacy in folate receptor (FR) positive KB cancer cell lines. Also, biodistribution studies of 99mTc-labeled gold NPs were carried in KB tumor xenografts to ascertain the efficacy towards FR in in vivo system. Results Polysorbate 80 could stabilize the gold NP preparation with average size Conclusions Biological evaluation of functionalized gold NP showed affinity towards FR positive cancer cell lines. 99mTc-labeled NP exhibited target uptake in both in vitro and in vivo models, but folic acid inhibition could not establish the target specificity. Nevertheless, in vivo pharmacokinetics envisaged in the present design was achieved using the present gold functionalized NP preparation.

4 citations

Journal ArticleDOI
TL;DR: The findings of the present study confirm that osteogenic nanofibrous coating significantly increases the magnitude of osteogenesis in the peri-implant zone and favours the dynamics of osseointegration.
Abstract: Anchoring of endosseous implant through osseointegration continues to be an important clinical need. Here, we describe the development of superior endosseous implant demonstrating enhance osseointegration, achieved through surface modification via coating of osteogenic nanofibres. The randomized bio-composite osteogenic nanofibres incorporating polycaprolactone, gelatin, hydroxyapatite, dexamethasone, beta-glycerophosphate and ascorbic acid were electrospun on titanium implants mimicking bone extracellular matrix and subsequently induced osteogenesis by targeting undifferentiated mesenchymal stem cells present in the peri-implant niche to regenerate osseous tissue. In proof-of-concept experiment on rabbit study models (n = 6), micro-computed tomography (Micro-CT), histomorphometric analysis and biomechanical testing in relation to our novel osteogenic nanofibrous coated implants showed improved results when compared to uncoated controls. Further, no pathological changes were detected during gross examination and necropsy on peri-implant osseous tissues regenerated in response to such coated implants. The findings of the present study confirm that osteogenic nanofibrous coating significantly increases the magnitude of osteogenesis in the peri-implant zone and favours the dynamics of osseointegration.

10 citations

Journal ArticleDOI
K.A. Gandhi, Jayant Sastri Goda1, V.V. Gandhi1, A. Sadanpurwala  +12 moreInstitutions (2)
TL;DR: DSePA offers protection to normal lung against RP without affecting radiation sensitivity of tumors, and has the potential to be developed as an oral agent for preventing RP.
Abstract: The incidence of symptomatic radiation induced lung pneumonitis (RILP), a major dose limiting side effect of thoracic radiotherapy, is in the range of 15-40%. Therapeutic options for the prevention and treatment of RILP are limited. Hence there is a need for developing novel radioprotectors to prevent RILP which can be patient compliant. This study sought to evaluate the efficacy of oral 3,3′-diselenodipropionic acid (DSePA), a novel selenocystine derivative to prevent RILP. C3H/HeJ (pneumonitis responding) mice received a single dose of 18 Gy, whole thorax irradiation and a subset were treated with DSePA orally (2.5 mg/kg), three times per week beginning 2 h post irradiation and continued till 6 months. DSePA delayed onset of grade ≥ 2 RILP by 45 days compared to radiation control (~105 versus ~60 days). It also reversed the severity of pneumonitis in 3/10 radiation treated mice leading to significant improvement in asymptomatic survival compared to radiation control (~180 versus ~102 days). DSePA significantly (p

9 citations

Journal ArticleDOI
Prajish Iyer1, Shailesh V. Shrikhande1, Malika Ranjan, Asim Joshi1  +21 moreInstitutions (1)
TL;DR: Overall, besides implicating ERBB2 as an important therapeutic target under neo‐adjuvant or adjuvant settings, this work presents the first evidence that the presence of KRAS mutations may preclude gallbladder cancer patients to respond to anti‐ EGFR treatment, similar to a clinical algorithm commonly practiced to opt for anti‐EGFR treatment in colorectal cancer.
Abstract: The uncommonness of gallbladder cancer in the developed world has contributed to the generally poor understanding of the disease. Our integrated analysis of whole exome sequencing, copy number alterations, immunohistochemical, and phospho-proteome array profiling indicates ERBB2 alterations in 40% early-stage rare gallbladder tumors, among an ethnically distinct population not studied before, that occurs through overexpression in 24% (n = 25) and recurrent mutations in 14% tumors (n = 44); along with co-occurring KRAS mutation in 7% tumors (n = 44). We demonstrate that ERBB2 heterodimerizes with EGFR to constitutively activate the ErbB signaling pathway in gallbladder cells. Consistent with this, treatment with ERBB2-specific, EGFR-specific shRNA or with a covalent EGFR family inhibitor Afatinib inhibits tumor-associated characteristics of the gallbladder cancer cells. Furthermore, we observe an in vivo reduction in tumor size of gallbladder xenografts in response to Afatinib is paralleled by a reduction in the amounts of phospho-ERK, in tumors harboring KRAS (G13D) mutation but not in KRAS (G12V) mutation, supporting an essential role of the ErbB pathway. In overall, besides implicating ERBB2 as an important therapeutic target under neo-adjuvant or adjuvant settings, we present the first evidence that the presence of KRAS mutations may preclude gallbladder cancer patients to respond to anti-EGFR treatment, similar to a clinical algorithm commonly practiced to opt for anti-EGFR treatment in colorectal cancer.

17 citations

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Abstract: Mercury is one of the most toxic heavy metal for mammals particularly in inorganic form. In present study, 3,3′-diselenodipropionic acid (DSePA), a well-known pharmacological diselenide was evaluated for its interaction with HgCl2 and ability to prevent HgCl2-induced toxicity in experimental cellular and mice models. UV–visible, stopped flow, Fourier-transform infrared spectroscopy and 1H nuclear magnetic resonance spectroscopy studies confirmed that DSePA sequestered Hg (II) ions with stoichiometry of 1:1 and binding constant of ~104 M−1. X-ray photoelectron spectroscopy and X-ray powder diffraction analysis suggested that diselenide group of DSePA was involved in the complexation with Hg (II) ions. Further, Hg-DSePA complex degraded within 10 days to form excretable HgSe. The binding constant of DSePA and Hg (II) was comparable with that of dihydrolipoic acid, a standard disulfide compound used in heavy metal detoxification. Corroborating these observations, pre-treatment of DSePA (10 μM) significantly prevented the HgCl2 (50 μM)-induced glutathione oxidation (GSH/GSSG), decrease of thioredoxin reductase (TrxR) and glutathione peroxidase (GPx) activities and cell death in Chinese Hamster Ovary (CHO) cells. Similarly, intraperitoneal administration of DSePA at a dosage of 2 mg/kg for 5 consecutive days prior to exposure of HgCl2 (1 mg/kg) significantly suppressed oxidative stress in renal and hepatic tissues of C57BL/6 mice. In conclusion, the protective effect of DSePA against Hg induced oxidative stress is attributed to its ability to rescue the activities of GPx, TrxR and GSH by sequestering Hg (II) ions. DSePA being a relatively safer selenium-compound for in vivo administration can be explored for mercury detoxification.

Journal ArticleDOI
Abstract: Methotrexate (MTX) is a common drug used for rheumatoid arthritis (RA) treatment; however, a series of adverse effects associated with its oral or subcutaneous administration is reported. Transdermal delivery of MTX is an alternative to abate these issues, and the use of drug delivery systems (DDS) based on polymeric films presents an impressive potential for this finality. Based on this, in this study, we report the preparation of films made by cationic starch (CSt), poly(vinyl alcohol) (PVA), and chondroitin sulfate (ChS) to incorporate and release MTX, as well as the in vivo evaluation in model of rheumatoid arthritis in mice. CSt/PVA and CSt/PVA/ChS-based films (with and without MTX) were prepared using a simple protocol under mild conditions. The films loaded with 5 w/w-% of MTX exhibited appreciable drug loading efficiency and distribution. The MTX permeation through the layers of porcine skin demonstrated that most of the drug permeated was detected in the medium, suggesting that the formulation can provide a systemic absorption of the MTX. In vivo studies performed in an arthritis-induced model in mice demonstrated that the MTX-loaded films were able to treat and attenuate the symptoms and the biochemical alterations related to RA (inflammatory process, oxidative stress, and nociceptive behaviors). Besides, the pharmacological activity of MTX transdermally delivery by the CSt/PVA and CSt/PVA/ChS films was comparable to the MTX orally administered. Based on these results, it can be inferred that both films are prominent materials for incorporation and transdermal delivery of MTX in a practical and non-invasive manner.

Journal ArticleDOI
Abstract: The aim of present study was to investigate the anticancer mechanisms of 3,3′-diselenodipropionic acid (DSePA), a redox-active organodiselenide in human lung cancer cells. DSePA elicited a significant concentration and time-dependent cytotoxicity in human lung cancer cell line A549 than in normal WI38 cells. The cytotoxic effect of DSePA was preceded by an acute decrease in the level of basal reactive oxygen species (ROS) and a concurrent increase in levels of reducing equivalents (like GSH/GSSG and NADH/NAD) within cells. Further, a series of experiments were performed to measure the markers of intrinsic (Bax, cytochrome c and caspase-9), extrinsic (TNFR, FADR and caspase-8) and endoplasmic reticulum (ER) stress (protein ubiquitylation, calcium flux, Bip, CHOP and caspase-12) pathways in DSePA treated cells. DSePA treatment significantly increased the levels of all the above markers. Moreover, DSePA did not alter the expression and phosphorylation (Ser15) of p53 but caused a significant damage to mitochondria. Pharmacological modulation of GSH level by BSO and NAC in DSePA treated cells led to partial abrogation and augmentation of cell kill respectively. This established the role of reductive stress as a trigger for the apoptosis induced by DSePA treatment. Finally, in vitro anticancer activity of DSePA was also corroborated by its in vivo efficacy of suppressing the growth of A549 derived xenograft tumor in SCID mice. In conclusion, above results suggest that DSePA induces apoptosis in a p53 independent manner by involving extrinsic and intrinsic pathways together with ER stress which can an interesting strategy for lung cancer therapy.

Journal ArticleDOI
20 Oct 2021-Cancers
Abstract: Due to the fast progression in molecular technologies such as next-generation sequencing, knowledge of genetic alterations in gallbladder cancer (GBC) increases. This systematic review provides an overview of frequently occurring genetic alterations occurring in GBC and their possible therapeutic implications. A literature search was performed utilizing PubMed, EMBASE, Cochrane Library, and Web of Science. Only studies reporting genetic alterations in human GBC were included. In total, data were extracted from 62 articles, describing a total of 3893 GBC samples. Frequently detected genetic alterations (>5% in >5 samples across all studies) in GBC for which targeted therapies are available in other cancer types included mutations in ATM, ERBB2, and PIK3CA, and ERBB2 amplifications. High tumor mutational burden (TMB-H) and microsatellite instability (MSI-H) were infrequently observed in GBC (1.7% and 3.5%, respectively). For solid cancers with TMB-H or MSI-H pembrolizumab is FDA-approved and shows an objective response rates of 50% for TMB-H GBC and 41% for MSI-H biliary tract cancer. Only nine clinical trials evaluated targeted therapies in GBC directed at frequently altered genes (ERBB2, ARID1A, ATM, and KRAS). This underlines the challenges to perform such clinical trials in this rare, heterogeneous cancer type and emphasizes the need for multicenter clinical trials.

Posted ContentDOI
07 Oct 2021-bioRxiv
Abstract: Hepatobiliary cancers (HBCs) are the most aggressive and sixth most diagnosed cancers globally. Biomarkers for timely diagnosis and targeted therapy in HBCs are still limited. Considering the gap, our objective is to identify unique and overlapping molecular signatures associated with HBCs. We analyzed publicly available transcriptomic datasets on Gallbladder cancer (GBC), Hepatocellular carcinoma (HCC), and Intrahepatic cholangiocarcinoma (ICC) to identify potential biomarkers using integrative systems approaches. An effective Common and Unique Molecular Signature Identification (CUMSI) approach has been developed, which contains analysis of differential gene expression (DEG), gene co-expression networks (GCN), and protein-protein interactions (PPIs) networks. Functional analysis of the DEGs unique for GBC, HCC, and ICC indicated that GBC is associated with cellular processes, HCC is associated with immune signaling pathways, and ICC is associated with lipid metabolic pathways. Our findings shows that the hub genes and pathways identified for each individual cancer type of the HBS are related with the primary function of each organ and each cancer exhibit unique expression patterns despite being part of the same organ system.

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Related Authors (1)
Pradip Chaudhari

52 papers, 711 citations

77% related

Author's H-index: 6

No. of papers from the Author in previous years