24 results on '"Surinder K. Batra"'
Search Results
2. Malondialdehyde-Acetaldehyde Extracellular Matrix Protein Adducts Attenuate Unfolded Protein Response During Alcohol and Smoking–Induced Pancreatitis
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Rakesh, Bhatia, Christopher M, Thompson, Emalie J, Clement, Koelina, Ganguly, Jesse L, Cox, Sanchita, Rauth, Jawed Akhtar, Siddiqui, Simran S, Mashiana, Maneesh, Jain, Todd A, Wyatt, Harmeet S, Mashiana, Shailender, Singh, Nicholas T, Woods, Kusum K, Kharbanda, Surinder K, Batra, and Sushil, Kumar
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Proteomics ,Aldehydes ,Extracellular Matrix Proteins ,Ethanol ,Proteome ,Hepatology ,Smoking ,Gastroenterology ,Acetaldehyde ,Cyclin-Dependent Kinases ,Mice ,Malondialdehyde ,Pancreatitis, Chronic ,Acute Disease ,Unfolded Protein Response ,Animals ,Ceruletide - Abstract
Epidemiological studies have established alcohol and smoking as independent risk factors for recurrent acute pancreatitis and chronic pancreatitis. However, the molecular players responsible for the progressive loss of pancreatic parenchyma and fibroinflammatory response are poorly characterized.Tandem mass tag-based proteomic and bioinformatics analyses were performed on the pancreata of mice exposed to alcohol, cigarette smoke, or a combination of alcohol and cigarette smoke. Biochemical, immunohistochemistry, and transcriptome analyses were performed on the pancreatic tissues and primary acinar cells treated with cerulein in combination with ethanol (50 mmol/L) and cigarette smoke extract (40 μg/mL) for the mechanistic studies.A unique alteration in the pancreatic proteome was observed in mice exposed chronically to the combination of alcohol and cigarette smoke (56.5%) compared with cigarette smoke (21%) or alcohol (17%) alone. The formation of toxic metabolites (P.001) and attenuated unfolded protein response (P.04) were the significantly altered pathways on combined exposure. The extracellular matrix (ECM) proteins showed stable malondialdehyde-acetaldehyde (MAA) adducts in the pancreata of the combination group and chronic pancreatitis patients with a history of smoking and alcohol consumption. Interestingly, MAA-ECM adducts significantly suppressed expression of X-box-binding protein-1, leading to acinar cell death in the presence of alcohol and smoking. The stable MAA-ECM adducts persist even after alcohol and smoking cessation, and significantly delay pancreatic regeneration by abrogating the expression of cyclin-dependent kinases (CDK7 and CDK5) and regeneration markers.The combined alcohol and smoking generate stable MAA-ECM adducts that increase endoplasmic reticulum stress and acinar cell death due to attenuated unfolded protein response and suppress expression of cell cycle regulators. Targeting aldehyde adducts might provide a novel therapeutic strategy for the management of recurrent acute pancreatitis and chronic pancreatitis.
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- 2022
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3. Reply
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Surinder K. Batra, Saswati Karmakar, and Moorthy P. Ponnusamy
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Text mining ,Hepatology ,business.industry ,Pancreatic cancer ,Gastroenterology ,Cancer research ,medicine ,Stem cell ,Biology ,business ,medicine.disease - Published
- 2021
4. Pancreatic Tumor Microenvironment Factor Promotes Cancer Stemness via SPP1-CD44 Axis
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Corinn E. Grabow, Maneesh Jain, Palanisamy Nallasamy, Imayavaramban Lakshmanan, Frank Leon, Moorthy P. Ponnusamy, Molly S. Myers, Rama Krishna Nimmakayala, Satyanarayana Rachagani, Surinder K. Batra, Quan P. Ly, Parthasarathy Seshacharyulu, Shailendra K. Gautam, Subodh M. Lele, Chunmeng Zhang, Sushil Kumar, Lindenberger Josh, Kavita Mallya, and Saswati Karmakar
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Male ,Epithelial-Mesenchymal Transition ,Population ,Mice, Nude ,Mice, Transgenic ,Cancer-Associated Fibroblasts ,Cancer stem cell ,Cell Movement ,Pancreatic cancer ,Cell Line, Tumor ,Paracrine Communication ,medicine ,Tumor Microenvironment ,Animals ,Humans ,Neoplasm Invasiveness ,Epithelial–mesenchymal transition ,Osteopontin ,education ,Cell Proliferation ,education.field_of_study ,Tumor microenvironment ,Hepatology ,biology ,Chemistry ,CD44 ,Gastroenterology ,medicine.disease ,Coculture Techniques ,Gene Expression Regulation, Neoplastic ,Pancreatic Neoplasms ,Hyaluronan Receptors ,Phenotype ,Phosphoprotein ,Cancer research ,biology.protein ,Neoplastic Stem Cells ,Carcinoma, Pancreatic Ductal ,Signal Transduction - Abstract
Background & Aims Tumor-microenvironment factors and cancer stem cells (CSCs) play a critical role in the aggressiveness of pancreatic cancer (PC). However, the degree to which tumor-microenvironment factors promote stemness remains unexplored. Here, we examined whether cancer-associated fibroblasts (CAFs) promote CSC features in PC. Methods PC cells were treated long-term (30, 60, and 90 days) with conditioned media (CM)-derived from normal human fibroblasts (NFs) and CAFs. The stemness features of tumorsphere formation and stemness populations, along with CSCs markers, were analyzed using 2-dimensional and 3-dimensional sodium alginate bead-based co-culture models. Immunohistochemistry and immunofluorescence staining were performed for CSCs and fibroblast markers in autochthonous KrasG12D/+; Trp53R172H/+; Pdx1-Cre mice and human pancreatic tumors. Polymerase chain reaction array and gene knockdown were performed to identify the mechanism of stemness enrichment. Results Long-term treatment of PC cells with CAF-CM enriched stemness, as indicated by significantly higher CD44+, ALDH+, and AF+ populations in PC cells. Increased tumorsphere formation and elevated CSC, self-renewal, and drug-resistance markers in CAF-CM–treated PC cells were observed. In addition, CAFs co-cultured with PC cells in the 3-dimensional model showed a substantial increase in stemness features. CD44 and α–smooth muscle actin were positively correlated and their expressions progressively increased from the early to late stages of KrasG12D/+; Trp53R172H/+; Pdx1-Cre mouse and human pancreatic tumors. Osteopontin/secreted phosphoprotein 1 was identified as the top differentially overexpressed gene in CAF-CM–treated PC cells and knockdown of osteopontin/secreted phosphoprotein 1 significantly reduced stemness characteristics in CAF-CM–treated PC cells. Conclusions Our data uncovered novel insight into the interplay between CAF and enrichment of stemness population through the osteopontin/secreted phosphoprotein 1–CD44 axis in PC.
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- 2021
5. Mucin 5AC–Mediated CD44/ITGB1 Clustering Mobilizes Adipose-Derived Mesenchymal Stem Cells to Modulate Pancreatic Cancer Stromal Heterogeneity
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Koelina Ganguly, Jesse L. Cox, Dario Ghersi, Paul M. Grandgenett, Michael A. Hollingsworth, Maneesh Jain, Sushil Kumar, and Surinder K. Batra
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Hepatology ,Integrin beta1 ,Gastroenterology ,Mesenchymal Stem Cells ,Mucin 5AC ,Article ,Actins ,Pancreatic Neoplasms ,Proto-Oncogene Proteins p21(ras) ,Mice ,Hyaluronan Receptors ,Animals ,Cluster Analysis ,Heterografts ,Humans - Abstract
BACKGROUND: Secreted mucin 5AC (MUC5AC) promotes pancreatic cancer (PC) progression and chemoresistance, suggesting its clinical association with poor prognosis. RNA sequencing analysis from the autochthonous pancreatic tumors showed a significant stromal alteration upon genetic ablation of Muc5ac. Previously, depletion or targeting the stromal fibroblasts showed an ambiguous effect on PC pathogenesis. Hence, identifying the molecular players and mechanisms driving fibroblast heterogeneity is critical for improved clinical outcomes. METHODS: Autochthonous murine models of PC [Kras(G12D), Pdx1-Cre (KC); Kras(G12D), Pdx1-Cre, Muc5ac(−/−) (KCM)] and co-implanted allografts of murine PC cell lines (Muc5ac-WT and CRISPR/Cas-KO) with adipose-derived mesenchymal stem cells (AD-MSCs) were used to assess the role of Muc5ac in stromal heterogeneity. Proliferation, migration, surface expression of cell-adhesion markers on AD-MSCs were measured using live-cell imaging and flow cytometry. MUC5AC-interactome was investigated using mass-spectrometry and ELISA. RESULTS: The KCM tumors showed a significant decrease in the expression of α-smooth muscle actin, and fibronectin, as compared to histology-matched KC tumors. Our study showed that MUC5AC, carrying tumor secretome, gets enriched in the adipose tissues of tumor-bearing mice and patients, where it promotes CD44/CD29 (integrin-β1) clustering leading to Rac1 activation and migration of AD-MSCs. Further, treatment with KC-derived serum enhanced proliferation and migration of AD-MSCs, which was abolished upon Muc5ac-depletion or pharmacological inhibition of CXCR2 and Rac1, respectively. The AD-MSCs significantly contribute towards α-SMA-positive CAFs population in Muc5ac-dependent manner, as suggested by autochthonous tumors, co-implantation xenografts, and patient tumors. CONCLUSION: MUC5AC, secreted during PC progression, enriches in adipose and enhances the mobilization of AD-MSCs. Upon recruitment to pancreatic tumors, AD-MSCs proliferate and contribute towards stromal heterogeneity.
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- 2022
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6. 152d: FLUORESCENT MUCIN 5AC ANTIBODY BRIGHTLY LABELS COLONIC POLYPS CONTAINING INTRAMUCOSAL ADENOCARCINOMA IN CPC-APC MICE: TECHNOLOGY FOR IMPROVED COLONOSCOPY
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Michael A. Turner, Siamak Amirfakhri, Hiroto Nishino, Nicholas Neel, Mojgan Hosseini, Joshua A. Alcantara, Thinzar M. Lwin, Sukhwinder Kaur, Kavita Mallya, Joseph R. Pisegna, Satish K. Singh, Pradipta Ghosh, Robert M. Hoffman, Surinder K. Batra, and Michael Bouvet
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Hepatology ,Gastroenterology - Published
- 2022
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7. Liquid Biopsy for Identification of High-Risk Cystic Lesions of Pancreas
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Sukhwinder Kaur, Surinder K. Batra, and Maneesh Jain
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Pathology ,medicine.medical_specialty ,Hepatology ,business.industry ,Gastroenterology ,Liquid Biopsy ,Article ,Cystic lesion ,medicine.anatomical_structure ,medicine ,Humans ,Identification (biology) ,Liquid biopsy ,Pancreatic Cyst ,Pancreas ,business - Abstract
BACKGROUND & AIMS: Advances in cross-sectional imaging have resulted in increased detection of intraductal papillary mucinous neoplasms (IPMNs) and their management remains controversial. At present, there is no reliable non-invasive method to distinguish between indolent and high risk IPMNs. We performed extracellular vesicle (EV) analysis to identify markers of malignancy in an attempt to better stratify these lesions. METHODS: Using a novel ultrasensitive digital extracellular vesicle screening technique (DEST) we measured putative biomarkers of malignancy (MUC1, MUC2, MUC4, MUC5AC, MUC6, Das-1, STMN1, TSP1, TSP2, EGFR, EpCAM, GPC1, WNT-2, EphA2, S100A4, PSCA, MUC13, ZEB1, PLEC1, HOOK1, PTPN6, and FBN1) in EV from patient-derived cell lines and then on circulating EV obtained from peripheral blood drawn from patients with IPMNs. We enrolled a total of 133 patients in two separate cohorts: a clinical discovery cohort (n=86) and a validation cohort (n=47). RESULTS: From 16 validated EV proteins in plasma samples collected from the discovery cohort, only MUC5AC showed significantly higher levels in high grade lesions. Of the 11 patients with invasive IPMN (inv/HG), 9 had high MUC5AC expression in plasma EV and of the 11 patients with high grade dysplasia alone, only 1 had high MUC5AC expression (specificity of 82%, sensitivity of 100%). These findings were corroborated in a separate validation cohort. The addition of MUC5AC as a biomarker to imaging and high risk stigmata allowed detection of all cases requiring surgery, whereas imaging and high risk stigmata alone would have missed 5/14 cases (36%). CONCLUSIONS: MUC5AC in circulating EV can predict the presence of invasive carcinoma within IPMN. This approach has the potential to improve the management and follow-up of patients with IPMN including avoiding unnecessary surgery.
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- 2020
8. Disruption of C1galt1 Gene Promotes Development and Metastasis of Pancreatic Adenocarcinomas in Mice
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Ramesh Pothuraju, Sidharth Mahapatra, Srikanth Barkeer, Lynette M. Smith, Moorthy P. Ponnusamy, Seema Chugh, Pranita Atri, Lijun Xia, Sriram Neelamegham, Rama Krishna Nimmakayala, Ishwor Thapa, Geoffrey A. Talmon, Surinder K. Batra, Satyanarayana Rachagani, Jianxin Fu, Naveenkumar Perumal, and Xinheng Yu
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0301 basic medicine ,Glycosylation ,endocrine system diseases ,Pancreatic Intraepithelial Neoplasia ,Adenocarcinoma ,Biology ,medicine.disease_cause ,Article ,Metastasis ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Stroma ,medicine ,Animals ,Humans ,Epithelial–mesenchymal transition ,Sirius Red ,Cell Proliferation ,Hepatology ,Gastroenterology ,Galactosyltransferases ,medicine.disease ,Mice, Inbred C57BL ,Pancreatic Neoplasms ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Cancer research ,Immunohistochemistry ,CRISPR-Cas Systems ,Pancreas ,Carcinogenesis ,Carcinoma, Pancreatic Ductal - Abstract
BACKGROUND & AIMS: Pancreatic ductal adenocarcinomas (PDACs) produce higher levels of truncated O-glycan structures (such as Tn and sTn) than normal pancreata. Dysregulated activity of core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase 1 (C1GALT1) leads to increased expression of these truncated O-glycans. We investigated whether and how truncated O-glycans contributes to development and progression of PDAC using mice with disruption of C1galt1. METHODS: We crossed C1galt1 floxed mice (C1galt1(loxP/loxP)) with Kras(G12D/+); Trp53(R172H/+); Pdx1- Cre mice (KPC mice) to create KPCC mice. Growth and progression of pancreatic tumors were compared between KPC and KPCC mice; pancreatic tissues were collected and analyzed by immunohistochemistry; immunofluorescence; and Sirius red, alcian blue, and lectin staining. We used the CRISPR/Cas9 system to disrupt C1GALT1 in human PDAC cells (T3M4 and CD18/HPAF) and levels of O-glycans were analyzed by lectin blotting, mass spectrometry and lectin-pull down assay. Orthotopic studies and RNA sequencing analyses are performed with control and C1GALT1 knockout PDAC cells. C1GALT1 expression was analyzed in well differentiated (n=36) and poorly differentiated (n=23) PDAC samples by immunohistochemistry. RESULTS: KPCC mice had significantly shorter survival times (median, 102 days) than KPC mice (median, 200 days), and developed early pancreatic intraepithelial neoplasias at 3 weeks, PDAC at 5 weeks, and metastases at 10 weeks compared to KPC. Pancreatic tumors that developed in KPCC mice were more aggressive than those of KPC mice (more invasive and metastases), had a decreased amount of stroma, and had increased production of Tn. Poorly differentiated PDAC specimens had significantly lower levels of C1GALT1 than welldifferentiated PDACs. Human PDAC cells with knockout of C1GALT1 had aberrant glycosylation of MUC16 compared with control cells, and increased expression of genes that regulate tumorigenesis and metastasis. CONCLUSIONS: In studies of KPC mice with disruption of C1galt1, we found that loss of C1galt1 promotes development of aggressive PDACs and increased metastasis. Knockout of C1GALT1 leads to increased tumorigenicity and truncation of O-glycosylation on MUC16, which could contribute to increased aggressiveness.
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- 2018
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9. RNA Polymerase II-Associated Factor 1 Regulates Stem Cell Features of Pancreatic Cancer Cells, Independently of the PAF1 Complex, via Interactions With PHF5A and DDX3
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Ramakanth Chirravuri Venkata, Sanchita Rauth, Rama Krishna Nimmakayala, Rohitesh Gupta, Saswati Karmakar, Palanisamy Nallasamy, Naveenkumar Perumal, Satyanarayana Rachagani, Venu Raman, Surinder K. Batra, Srikanth Barkeer, Frank Leon, and Moorthy P. Ponnusamy
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0301 basic medicine ,Homeobox protein NANOG ,Mice, Nude ,Biology ,Article ,DEAD-box RNA Helicases ,Small hairpin RNA ,03 medical and health sciences ,0302 clinical medicine ,Side population ,Cell Movement ,Cancer stem cell ,Pancreatic tumor ,Cell Line, Tumor ,Pancreatic cancer ,medicine ,Animals ,Humans ,Cell Self Renewal ,Neoplasm Metastasis ,Side-Population Cells ,Cell Proliferation ,Gene knockdown ,Hepatology ,Gastroenterology ,RNA-Binding Proteins ,Nanog Homeobox Protein ,medicine.disease ,Tumor Burden ,Gene Expression Regulation, Neoplastic ,Pancreatic Neoplasms ,Phenotype ,030104 developmental biology ,Neoplastic Stem Cells ,Trans-Activators ,Cancer research ,030211 gastroenterology & hepatology ,Stem cell ,Signal Transduction ,Transcription Factors - Abstract
Background & Aims It is not clear how pancreatic cancer stem cells (CSCs) are regulated, resulting in ineffective treatments for pancreatic cancer. PAF1, a RNA polymerase II-associated factor 1 complex (PAF1C) component, maintains pluripotency of stem cells, by unclear mechanisms, and is a marker of CSCs. We investigated mechanisms by which PAF1 maintains CSCs and contributes to development of pancreatic tumors. Methods Pancreatic cancer cell lines were engineered to knockdown PAF1 using inducible small hairpin RNAs. These cells were grown as orthotopic tumors in athymic nude mice and PAF1 knockdown was induced by administration of doxycycline in drinking water. Tumor growth and metastasis were monitored via IVIS imaging. CSCs were isolated from pancreatic cancer cell populations using flow cytometry and characterized by tumor sphere formation, tumor formation in nude mice, and expression of CSC markers. Isolated CSCs were depleted of PAF1 using the CRISPR/Cas9 system. PAF1-regulated genes in CSCs were identified via RNA-seq and PCR array analyses of cells with PAF1 knockdown. Proteins that interact with PAF1 in CSCs were identified by immunoprecipitations and mass spectrometry. We performed chromatin immunoprecipitation sequencing of CSCs to confirm the binding of the PAF1 sub-complex to target genes. Results Pancreatic cancer cells depleted of PAF1 formed smaller and fewer tumor spheres in culture and orthotopic tumors and metastases in mice. Isolated CSCs depleted of PAF1 downregulated markers of self-renewal (NANOG, SOX9, and β-CATENIN), of CSCs (CD44v6, and ALDH1), and the metastasis-associated gene signature, compared to CSCs without knockdown of PAF1. The role of PAF1 in CSC maintenance was independent of its RNA polymerase II-associated factor 1 complex component identity. We identified DDX3 and PHF5A as proteins that interact with PAF1 in CSCs and demonstrated that the PAF1–PHF5A–DDX3 sub-complex bound to the promoter region of Nanog, whose product regulates genes that control stemness. Levels of the PAF1–DDX3 and PAF1–PHF5A were increased and co-localized in human pancreatic tumor specimens, human pancreatic tumor-derived organoids, and organoids derived from tumors of KPC mice, compared with controls. Binding of DDX3 and PAF1 to the Nanog promoter, and the self-renewal capacity of CSCs, were decreased in cells incubated with the DDX3 inhibitor RK-33. CSCs depleted of PAF1 downregulated genes that regulate stem cell features (Flot2, Taz, Epcam, Erbb2, Foxp1, Abcc5, Ddr1, Muc1, Pecam1, Notch3, Aldh1a3, Foxa2, Plat, and Lif). Conclusions In pancreatic CSCs, PAF1 interacts with DDX3 and PHF5A to regulate expression of NANOG and other genes that regulate stemness. Knockdown of PAF1 reduces the ability of orthotopic pancreatic tumors to develop and progress in mice and their numbers of CSCs. Strategies to target the PAF1–PHF5A–DDX3 complex might be developed to slow or inhibit progression of pancreatic cancer.
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- 2020
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10. Insights Into the Role of Nicotine in Pancreatic Stem Cell Activation and Acinar Dedifferentiation
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Surinder K. Batra and Moorthy P. Ponnusamy
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Nicotine ,Acinar Cells ,Proto-Oncogene Proteins p21(ras) ,GATA6 Transcription Factor ,medicine ,Carcinoma ,Animals ,Humans ,Nicotinic Agonists ,Pancreas ,Cell dedifferentiation ,Hepatology ,business.industry ,Gastroenterology ,Cell Dedifferentiation ,medicine.disease ,Pancreatic Neoplasms ,medicine.anatomical_structure ,Nicotinic agonist ,Cancer research ,Stem cell ,business ,Carcinoma, Pancreatic Ductal ,medicine.drug - Published
- 2014
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11. Interleukin-22 Connects Smoking and Pancreatic Fibrosis During Chronic Pancreatitis
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Surinder K. Batra and Sushil Kumar
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0301 basic medicine ,medicine.medical_specialty ,Gastroenterology ,Article ,Interleukin 22 ,03 medical and health sciences ,0302 clinical medicine ,Fibrosis ,Internal medicine ,Pancreatitis, Chronic ,medicine ,Humans ,Pancreas ,Hepatology ,business.industry ,General surgery ,Interleukins ,Smoking ,Interleukin ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Chronic disease ,Pancreatitis ,Chronic Disease ,030211 gastroenterology & hepatology ,business ,Pancreatic fibrosis - Published
- 2016
12. Cigarette Smoke Induces Stem Cell Features of Pancreatic Cancer Cells via PAF1
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Raghupathy Vengoji, Subodh M. Lele, Sanchita Rauth, Parthasarathy Seshacharyulu, Seema Chugh, Pranita Atri, Saswati Karmakar, Ishwor Thapa, Geoffrey A. Talmon, Michel M. Ouellette, Dhundy R. Bastola, Satyanarayana Rachagani, Moorthy P. Ponnusamy, Rama Krishna Nimmakayala, Imayavaramban Lakshmanan, Surinder K. Batra, and Lynette M. Smith
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0301 basic medicine ,alpha7 Nicotinic Acetylcholine Receptor ,Stem cell marker ,Article ,Cigarette Smoking ,Flow cytometry ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Pancreatic cancer ,medicine ,Animals ,Humans ,Epithelial–mesenchymal transition ,Pancreas ,Hepatology ,medicine.diagnostic_test ,Chemistry ,Gastroenterology ,medicine.disease ,Embryonic stem cell ,Pancreatic Neoplasms ,Reverse transcription polymerase chain reaction ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer cell ,Neoplastic Stem Cells ,Cancer research ,Stem cell ,Carrier Proteins ,Proto-Oncogene Proteins c-fos ,Carcinoma, Pancreatic Ductal ,Signal Transduction - Abstract
Background & Aims Cigarette smoking is a major risk factor for pancreatic cancer. Aggressive pancreatic tumors contain cancer cells with stem cell features. We investigated whether cigarette smoke induces stem cell features in pancreatic cancer cells. Methods KrasG12D; Pdx1-Cre mice were exposed to cigarette smoke or clean air (controls) for up to 20 weeks; pancreata were collected and analyzed by histology, quantitative reverse transcription polymerase chain reaction, and confocal immunofluorescence microscopy. HPNE and Capan1 cells were exposed to cigarette smoke extract (CSE), nicotine and nicotine-derived carcinogens (NNN or NNK), or clean air (controls) for 80 days and evaluated for stem cell markers and features using flow cytometry–based autofluorescence, sphere formation, and immunoblot assays. Proteins were knocked down in cells with small interfering RNAs. We performed RNA sequencing analyses of CSE-exposed cells. We used chromatin immunoprecipitation assays to confirm the binding of FOS-like 1, AP-1 transcription factor subunit (FOSL1) to RNA polymerase II-associated factor (PAF1) promoter. We obtained pancreatic ductal adenocarcinoma (PDAC) and matched nontumor tissues (n = 15) and performed immunohistochemical analyses. Results Chronic exposure of HPNE and Capan1 cells to CSE caused them to increase markers of stem cells, including autofluorescence and sphere formation, compared with control cells. These cells increased expression of ABCG2, SOX9, and PAF1, via cholinergic receptor nicotinic alpha 7 subunit (CHRNA7) signaling to mitogen-activated protein kinase 1 and FOSL1. CSE-exposed pancreatic cells with knockdown of PAF1 did not show stem cell features. Exposure of cells to NNN and NNK led to increased expression of CHRNA7, FOSL1, and PAF1 along with stem cell features. Pancreata from KrasG12D; Pdx1-Cre mice exposed to cigarette smoke had increased levels of PAF1 mRNA and protein, compared with control mice, as well as increased expression of SOX9. Levels of PAF1 and FOSL1 were increased in PDAC tissues, especially those from smokers, compared with nontumor pancreatic tissue. CSE exposure increased expression of PHD-finger protein 5A, a pluripotent transcription factor and its interaction with PAF1. Conclusions Exposure to cigarette smoke activates stem cell features of pancreatic cells, via CHRNA7 signaling and FOSL1 activation of PAF1 expression. Levels of PAF1 are increased in pancreatic tumors of humans and mice with chronic cigarette smoke exposure.
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- 2018
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13. Su1610 Membrane-Bound Mucins Expression in Helicobacter pylori, NSAID, and Idiopathic Peptic Ulcers
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Marisa Halpern, Alex Vilkin, Surinder K. Batra, Sara Morgenstern, Pascal Gagneux, Zohar Levi, Samuel B. Ho, Yaron Niv, Doron Boltin, and Miriam Cohen
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Hepatology ,biology ,Membrane bound ,Chemistry ,Peptic ,Mucin ,Gastroenterology ,Helicobacter pylori ,biology.organism_classification ,Microbiology - Published
- 2012
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14. Aberrant Expression of MUC17 Correlates With Survival in Advanced Stage Colorectal Adenocarcinomas
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Michael R. Peterson, Ke Li, Surinder K. Batra, Vahig Manugian, Brandon Kandarian, Aaron Lee, and Samuel B. Ho
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Hepatology ,Expression (architecture) ,business.industry ,Advanced stage ,Gastroenterology ,Cancer research ,Medicine ,business - Published
- 2011
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15. S1673 Mechanisms of CDx2 Suppression in Colorectal Carcinogenesis: Role of Deoxycholate-MUC 4 Signaling Cascade
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Tina P. Ward, Ashish K. Tiwari, Dhananjay Kunte, Ramesh K. Wali, Seema R. Gandhi, Hemant K. Roy, Mart DeLaCruz, and Surinder K. Batra
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Hepatology ,Cascade ,Chemistry ,Gastroenterology ,Cancer research ,Colorectal carcinogenesis ,CDX2 - Published
- 2010
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16. W1747 MUC4 and AKT/β-Catenin Mediated Control of Cell Proliferation in Early Colon Carcinogenesis
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Tina P. Ward, Ashish K. Tiwari, Yolanda Stypula, Seema R. Gandhi, Dhananjay Kunte, Ramesh K. Wali, Hemant K. Roy, Srustidhar Das, Shantibhushan Senapati, Mart DeLaCruz, and Surinder K. Batra
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Hepatology ,Chemistry ,Cell growth ,Catenin ,Gastroenterology ,Cancer research ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Colon carcinogenesis - Published
- 2010
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17. S1681 Expression of Intestinal MUC17 Membrane-Bound Mucin in Inflammatory and Neoplastic Diseases of the Colon
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Samuel B. Ho, Poonam Sharma, Senapati Shantibhusan, Surinder K. Batra, Sukhwinder Kaur, Subhankar Chakraborty, Srustidhar Das, Silvia C. Resta, and Brandon Kandarian
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Hepatology ,Chemistry ,Membrane bound ,Mucin ,Gastroenterology ,Molecular biology - Published
- 2010
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18. S1951 MUC 4 Suppression is an Early Event in Colorectal Carcinogenesis (CRC): Potential Biomarker for Screening and Chemoprevention
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Dhananjay Kunte, Hemant K. Roy, Seema R. Gandhi, Tina P. Ward, Srustidhar Das, Ramesh K. Wali, Shantibhushan Senapati, Mart DeLaCruz, Surinder K. Batra, and Ashish K. Tiwari
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Oncology ,medicine.medical_specialty ,Hepatology ,business.industry ,Internal medicine ,Event (relativity) ,Potential biomarkers ,Gastroenterology ,medicine ,Colorectal carcinogenesis ,business - Published
- 2010
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19. T1300 Serum Neutrophil-Associated Gelatinase Lipocalcin (NGAL) Levels As An Early Biomarker of Severe Acute Pancreatitis
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Randall E. Brand, Sukhwinder Kaur, David C. Whitcomb, Georgios I. Papachristou, Surinder K. Batra, Venkata Muddana, Neil Sharma, and Subhankar Chakraborty
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medicine.medical_specialty ,Hepatology ,business.industry ,Internal medicine ,Gastroenterology ,Medicine ,Gelatinase ,Biomarker (medicine) ,Acute pancreatitis ,business ,medicine.disease - Published
- 2009
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20. S2044 MUC17: A Novel Tumor Suppressor Gene in Colon Carcinogenesis?
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Srustidhar Das, Surinder K. Batra, Jennifer L. Koetsier, Hemant K. Roy, Shantibhushan Senapati, Dhananjay Kunte, Christopher R. Weber, and Ramesh K. Wali
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Hepatology ,Tumor suppressor gene ,Gastroenterology ,Cancer research ,Cyclin-dependent kinase 8 ,Biology ,Colon carcinogenesis - Published
- 2009
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21. M1697 The Membrane Bound MUC17 Mucin Protects Cell Integrity in Response to Short Term Infection with Enteroinvasive E. coli
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Silvia C. Resta, Samuel B. Ho, Satyanarayana Rachagani, Erik D. Moore, Wade M. Junker, Ying H. Luu, and Surinder K. Batra
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Hepatology ,Membrane bound ,Mucin ,Cell integrity ,Gastroenterology ,Biology ,Enteroinvasive E. coli ,Microbiology - Published
- 2009
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22. W1878 Muc4: A Novel Tumor Suppressor Gene Impacts Upon Initiation and Progression Phases of Colorectal Carcinogenesis
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Jennifer L. Koetsier, Hemant K. Roy, Surinder K. Batra, Christopher R. Weber, Dhananjay Kunte, Ramesh K. Wali, Srustidhar Das, and Shantibhushan Senapati
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Oncology ,medicine.medical_specialty ,Hepatology ,Tumor suppressor gene ,business.industry ,Internal medicine ,Gastroenterology ,medicine ,Cyclin-dependent kinase 8 ,Colorectal carcinogenesis ,business - Published
- 2009
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23. W1097 Muc4: A Potential Tumor Suppressor Gene in Colon Carcinogenesis
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Hemant K. Roy, Geoffrey Kraker, Surinder K. Batra, Dhananjay Kunte, Thomas C. Smyrk, Ramesh K. Wali, and Jennifer L. Koetsier
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Hepatology ,Tumor suppressor gene ,Gastroenterology ,medicine ,Cancer research ,Cyclin-dependent kinase 8 ,Biology ,Carcinogenesis ,medicine.disease_cause ,Colon carcinogenesis - Published
- 2008
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24. The combination of CA 19-9 and MUC4 mRNA in peripheral blood mononuclear cells improves the sensitivity of either marker alone for the diagnosis of pancreatic adenocarcinoma
- Author
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Jöerg Ringel, Grit Faulmann, Nicolas Moniaux, Randall E. Brand, Matthias Löhr, and Surinder K. Batra
- Subjects
Messenger RNA ,Hepatology ,business.industry ,Immunology ,Gastroenterology ,Medicine ,Adenocarcinoma ,CA19-9 ,business ,medicine.disease ,Peripheral blood mononuclear cell ,Molecular biology - Published
- 2001
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