16 results on '"Niharika Badi"'
Search Results
2. Supplemental Table 1 from Lipocalin-2 Promotes Pancreatic Ductal Adenocarcinoma by Regulating Inflammation in the Tumor Microenvironment
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Zobeida Cruz-Monserrate, Craig D. Logsdon, Ralph B. Arlinghaus, Xiaohong Leng, Huamin Wang, Deyali Chatterjee, Todd Moore, Liran Zhou, Rosa F. Hwang, Defeng Deng, Yan Liu, Carl Schmidt, Thomas A. Mace, Matthew R. Farren, Tanios Bekaii-Saab, Gregory B. Lesinski, Myrriah Chavez-Tomar, Niharika Badi, Agnieszka Katarzyna Swidnicka-Siergiejko, and Sobeyda B. Gomez-Chou more...
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Supplementary Table 1. List of antibodies used for immunohistochemical staining of mouse pancreas.
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- 2023
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Catalog
3. Data from Lipocalin-2 Promotes Pancreatic Ductal Adenocarcinoma by Regulating Inflammation in the Tumor Microenvironment
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Zobeida Cruz-Monserrate, Craig D. Logsdon, Ralph B. Arlinghaus, Xiaohong Leng, Huamin Wang, Deyali Chatterjee, Todd Moore, Liran Zhou, Rosa F. Hwang, Defeng Deng, Yan Liu, Carl Schmidt, Thomas A. Mace, Matthew R. Farren, Tanios Bekaii-Saab, Gregory B. Lesinski, Myrriah Chavez-Tomar, Niharika Badi, Agnieszka Katarzyna Swidnicka-Siergiejko, and Sobeyda B. Gomez-Chou more...
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Lipocalin-2 (LCN2) promotes malignant development in many cancer types. LCN2 is upregulated in patients with pancreatic ductal adenocarcinoma (PDAC) and in obese individuals, but whether it contributes to PDAC development is unclear. In this study, we investigated the effects of Lcn2 depletion on diet-induced obesity, inflammation, and PDAC development. Mice with acinar cell–specific expression of KrasG12D were crossed with Lcn2-depleted animals and fed isocaloric diets with varying amounts of fat content. Pancreas were collected and analyzed for inflammation, pancreatic intraepithelial neoplasia (PanIN), and PDAC. We also used a syngeneic orthotopic PDAC mouse model to study tumor growth in the presence or absence of Lcn2 expression. In addition, to understand the mechanistic role of how LCN2 could be mediating PDAC, we studied LCN2 and its specific receptor solute carrier family 22 member 17 (SLC22A17) in human pancreatic cancer stellate cells (PSC), key mediators of the PDAC stroma. Depletion of Lcn2 diminished extracellular matrix deposition, immune cell infiltration, PanIN formation, and tumor growth. Notably, it also increased survival in both obesity-driven and syngeneic orthotopic PDAC mouse models. LCN2 modulated the secretion of proinflammatory cytokines in PSC of the PDAC tumor microenvironment, whereas downregulation of LCN2-specific receptor SLC22A17 blocked these effects. Our results reveal how LCN2 acts in the tumor microenvironment links obesity, inflammation, and PDAC development. Cancer Res; 77(10); 2647–60. ©2017 AACR more...
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- 2023
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4. Supplementary Methods from Lipocalin-2 Promotes Pancreatic Ductal Adenocarcinoma by Regulating Inflammation in the Tumor Microenvironment
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Zobeida Cruz-Monserrate, Craig D. Logsdon, Ralph B. Arlinghaus, Xiaohong Leng, Huamin Wang, Deyali Chatterjee, Todd Moore, Liran Zhou, Rosa F. Hwang, Defeng Deng, Yan Liu, Carl Schmidt, Thomas A. Mace, Matthew R. Farren, Tanios Bekaii-Saab, Gregory B. Lesinski, Myrriah Chavez-Tomar, Niharika Badi, Agnieszka Katarzyna Swidnicka-Siergiejko, and Sobeyda B. Gomez-Chou more...
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Additional Experimental Methods
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- 2023
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5. Changes in Plasma Fatty Acid Abundance Related to Chronic Pancreatitis: A Pilot Study
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Kristyn Gumpper-Fedus, Olivia Crowe, Phil A. Hart, Valentina Pita-Grisanti, Ericka Velez-Bonet, Martha A. Belury, Mitchell Ramsey, Rachel M Cole, Niharika Badi, Stacey Culp, Alice Hinton, Luis Lara, Somashekar G. Krishna, Darwin L. Conwell, and Zobeida Cruz-Monserrate more...
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Article - Abstract
ObjectivesChronic pancreatitis (CP) is an inflammatory disease that affects the absorption of nutrients like fats. Molecular signaling in pancreatic cells can be influenced by fatty acids (FAs) and changes in FA abundance could impact CP-associated complications. Here, we investigated FA abundance in CP compared to controls and explored how CP-associated complications and risk factors affect FA abundance.MethodsBlood and clinical parameters were collected from subjects with (n=47) and without CP (n=22). Plasma was analyzed for relative FA abundance using gas chromatography and compared between controls and CP. Changes in FA abundance due to clinical parameters were also assessed in both groups.ResultsDecreased relative abundance of polyunsaturated fatty acids (PUFAs) and increased monounsaturated fatty acids (MUFAs) were observed in subjects with CP in a sex-dependent manner. The relative abundance of linoleic acid increased, and oleic acid decreased in CP subjects with exocrine pancreatic dysfunction and a history of substance abuse.ConclusionsPlasma FAs like linoleic acid are dysregulated in CP in a sex-dependent manner. Additionally, risk factors and metabolic dysfunction further dysregulate FA abundance in CP. These results enhance our understanding of CP and highlight potential novel targets and metabolism-related pathways for treating CP. more...
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- 2023
6. Physical Activity Delays Obesity-Associated Pancreatic Ductal Adenocarcinoma in Mice and Decreases Inflammation
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Valentina Pita-Grisanti, Kelly Dubay, Ali Lahooti, Niharika Badi, Olivia Ueltschi, Kristyn Gumpper-Fedus, Hsiang-Yin Hsueh, Ila Lahooti, Myrriah Chavez-Tomar, Samantha Terhorst, Sue E. Knoblaugh, Lei Cao, Wei Huang, Christopher C. Coss, Thomas A. Mace, Fouad Choueiry, Alice Hinton, Jennifer M Mitchell, Rosemarie Schmandt, Michaela Onstad Grinsfelder, Karen Basen-Engquist, and Zobeida Cruz-Monserrate more...
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BACKGROUND & AIMSObesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC), a deadly disease with limited preventive strategies. Lifestyle interventions to decrease obesity might prevent obesity-associated PDAC. Here, we examined whether decreasing obesity by increased physical activity (PA) and/or dietary changes would decrease inflammation in humans and prevent PDAC in mice.METHODSCirculating inflammatory-associated cytokines of overweight and obese subjects before and after a PA intervention were compared. PDAC pre-clinical models were exposed to PA and/or dietary interventions after obesity-associated cancer initiation. Body composition, tumor progression, growth, fibrosis, inflammation, and transcriptomic changes in the adipose tissue were evaluated.RESULTSPA decreased the levels of systemic inflammatory cytokines in overweight and obese subjects. PDAC mice on a diet-induced obesity (DIO) and PA intervention, had delayed weight gain, decreased systemic inflammation, lower grade pancreatic intraepithelial neoplasia lesions, reduced PDAC incidence, and increased anti-inflammatory signals in the adipose tissue compared to controls. PA had additional cancer prevention benefits when combined with a non-obesogenic diet after DIO. However, weight loss through PA alone or combined with a dietary intervention did not prevent tumor growth in an orthotopic PDAC model. Adipose-specific targeting of interleukin (IL)-15, an anti-inflammatory cytokine induced by PA in the adipose tissue, slowed PDAC growth.CONCLUSIONSPA alone or combined with diet-induced weight loss delayed the progression of PDAC and reduced systemic and adipose inflammatory signals. Therefore, obesity management via dietary interventions and/or PA, or modulating weight loss related pathways could prevent obesity-associated PDAC in high-risk obese individuals.Graphical Abstract more...
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- 2023
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7. Delayed Processing of Secretin-Induced Pancreas Fluid Influences the Quality and Integrity of Proteins and Nucleic Acids
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Stephen J. Pandol, Amy L. McElhany, Darwin L. Conwell, Samantha Terhorst, Gregory B. Lesinski, Somashekar G. Krishna, William E. Fisher, Lilibeth Ortega-Pineda, Benoit Fatou, Saima Ahmed, Luis F. Lara, Kelly Dubay, Sabrina Kaul, Niharika Badi, Alice Hinton, Michael A. Freitas, Phil A. Hart, Hanno Steen, Dhiraj Yadav, Kristyn Gumpper, Natalia Higuita-Castro, Zobeida Cruz-Monserrate, and Thomas A. Mace more...
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Time Factors ,RNase P ,RNA Stability ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Protein degradation ,Article ,Specimen Handling ,Workflow ,Secretin ,03 medical and health sciences ,chemistry.chemical_compound ,Ribonucleases ,0302 clinical medicine ,Endocrinology ,Pancreatic Juice ,Predictive Value of Tests ,Nucleic Acids ,Freezing ,Internal Medicine ,medicine ,Humans ,Protease Inhibitors ,Endoscopy, Digestive System ,Protease ,Hepatology ,Protein Stability ,Chemistry ,Pancreatic Diseases ,Proteins ,RNA ,Cold Temperature ,Pancreatic Function Tests ,medicine.anatomical_structure ,Biochemistry ,030220 oncology & carcinogenesis ,Proteolysis ,Nucleic acid ,030211 gastroenterology & hepatology ,Pancreas ,Biomarkers ,DNA ,DNA Damage - Abstract
OBJECTIVES: Endoscopic pancreatic function tests are used to diagnose pancreatic diseases and are a viable source for the discovery of biomarkers to better characterize pancreatic disorders. However, pancreatic fluid (PF) contains active enzymes that degrade biomolecules. Therefore, we tested how preservation methods and time to storage influences the integrity and quality of proteins and nucleic acids. METHODS: We obtained PF from 9 subjects who underwent an endoscopic pancreatic function test. Samples were snap frozen at the time of collection, after 1, 2, 4 hours on ice, or after storage overnight at 4°C with or without RNase or protease inhibitors. Electrophoresis and mass spectrometry analysis determined protein abundance and quality while nucleic acid integrity values determined DNA and RNA degradation. RESULTS: Protein degradation increased after 4 hours on ice and DNA degradation after 2 hours on ice. Adding protease inhibitors delayed degradation. RNA was significantly degraded under all conditions compared to the snap frozen samples. Isolated RNA from PF-derived exosomes exhibited similar poor quality as RNA isolated from matched PF samples. CONCLUSIONS: Adding protease inhibitors immediately after collecting PF and processing the fluid within 4 hours of collection maintains the protein and nucleic acid integrity for use in downstream molecular analyses. more...
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- 2021
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8. Altered Plasma Fatty Acid Abundance Is Associated with Cachexia in Treatment-Naïve Pancreatic Cancer
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Kristyn Gumpper-Fedus, Phil A. Hart, Martha A. Belury, Olivia Crowe, Rachel M. Cole, Valentina Pita Grisanti, Niharika Badi, Sophia Liva, Alice Hinton, Christopher Coss, Mitchell L. Ramsey, Anne Noonan, Darwin L. Conwell, and Zobeida Cruz-Monserrate more...
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Pancreatic Neoplasms ,Cachexia ,Linoleic Acids ,digestive, oral, and skin physiology ,Fatty Acids ,Humans ,General Medicine ,Adenocarcinoma ,musculoskeletal system ,pancreatic cancer ,fatty acids ,sarcopenia ,diabetes ,hemoglobin ,albumin ,oleic acid ,linoleic acid ,Carcinoma, Pancreatic Ductal ,Oleic Acid - Abstract
Cachexia occurs in up to 80% of pancreatic ductal adenocarcinoma (PDAC) patients and is characterized by unintentional weight loss and tissue wasting. To understand the metabolic changes that occur in PDAC-associated cachexia, we compared the abundance of plasma fatty acids (FAs), measured by gas chromatography, of subjects with treatment-naïve metastatic PDAC with or without cachexia, defined as a loss of > 2% weight and evidence of sarcopenia (n = 43). The abundance of saturated, monounsaturated, and polyunsaturated FAs was not different between subjects with cachexia and those without. Oleic acid was significantly higher in subjects with cachexia (p = 0.0007) and diabetes (p = 0.015). Lauric (r = 0.592, p = 0.0096) and eicosapentaenoic (r = 0.564, p = 0.015) acids were positively correlated with age in cachexia patients. Subjects with diabetes (p = 0.021) or both diabetes and cachexia (p = 0.092) had low palmitic:oleic acid ratios. Linoleic acid was lower in subjects with diabetes (p = 0.018) and correlated with hemoglobin (r = 0.519, p = 0.033) and albumin (r = 0.577, p = 0.015) in subjects with cachexia. Oleic or linoleic acid may be useful treatment targets or biomarkers of cachexia in patients with metastatic PDAC, particularly those with diabetes. more...
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- 2022
9. Murine Model of Obesity-Induced Cancer
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Niharika, Badi and Zobeida, Cruz-Monserrate
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Disease Models, Animal ,Mice ,Neoplasms ,Animals ,Obesity ,Diet, High-Fat ,Weight Gain - Abstract
Obesity is a major risk factor for the development of multiple cancers. In efforts to develop models that will assist the scientific community in studying the mechanisms of this risk, a diet-induced obesity model of obesity is often utilized. Here we describe the use of diet-induced obesity (DIO) diets to study the effects of high-fat diet weight gain in the context of cancer mouse models. more...
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- 2022
10. Murine Model of Obesity-Induced Cancer
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Niharika Badi and Zobeida Cruz-Monserrate
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- 2022
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11. Reduction of Inflammation in Chronic Pancreatitis Using a Soy Bread Intervention: a Feasibility Study
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K. Roberts, Zobeida Cruz-Monserrate, Jennifer Ahn-Jarvis, Mitchell L. Ramsey, Phil A. Hart, Sabrina Kaul, Olivia Crowe, Niharika Badi, Yael Vodovotz, Darwin L. Conwell, Erin Marie Lombardo, Somashekar G. Krishna, Kyle R. Stinehart, Hannah Komar, Thomas A. Mace, Madelyn Traczek, and Gregory B. Lesinski more...
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Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Urinary system ,Pilot Projects ,Gastroenterology ,Article ,Excretion ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Fibrosis ,Internal medicine ,Pancreatitis, Chronic ,medicine ,Humans ,Interleukin 6 ,Aged ,Inflammation ,Hepatology ,biology ,Dose-Response Relationship, Drug ,business.industry ,Tumor Necrosis Factor-alpha ,Bread ,Isoflavones ,Middle Aged ,medicine.disease ,Compliance (physiology) ,Tolerability ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,Pancreatitis ,Cytokines ,Feasibility Studies ,Patient Compliance ,030211 gastroenterology & hepatology ,Female ,Soybeans ,Inflammation Mediators ,business - Abstract
Introduction Chronic pancreatitis is a chronic inflammatory disease, which progresses to fibrosis. Currently there are no interventions to delay or stop the progression to irreversible organ damage. In this study, we assessed the tolerability and feasibility of administering soy bread to reduce circulating inflammatory mediators. Methods Subjects with chronic pancreatitis diagnosed using the American Pancreatic Association diagnostic guidelines were enrolled. During the dose escalation (DE) phase, subjects received one week of soy bread based using a 3 + 3 dose-escalation design, which was then followed by a maximally tolerated dose (MTD) phase with four weeks of intervention. Dose-limiting toxicities (DLTs) were monitored. Plasma cytokine levels were measured using a Meso Scale Discovery multiplex assay kit. Isoflavonoid excretion in 24-h urine collection was used to measure soy bread compliance. Results Nine subjects completed the DE phase, and one subject completed the MTD phase without any DLTs at a maximum dosage of three slices (99 mg of isoflavones) per day. Reported compliance to soy bread intervention was 98%, and this was confirmed with urinary isoflavones and their metabolites detected in all subjects. There was a significant decline in the TNF-α level during the DE phase (2.667 vs 2.382 pg/mL, p = 0.039); other levels were similar. Conclusions In this feasibility study, there was excellent compliance with a short-term intervention using soy bread in chronic pancreatitis. Reduction was seen in at least one pro-inflammatory cytokine with short-term intervention. Larger cohorts and longer interventions with soy are warranted to assess the efficacy of reducing pro-inflammatory mediators of disease. more...
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- 2020
12. Circulating interleukin-6 is associated with disease progression, but not cachexia in pancreatic cancer
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Anne M. Noonan, Gregory B. Lesinski, Mitchell L. Ramsey, Mary Dillhoff, Priyani V. Rajasekera, Tanios Bekaii-Saab, P. Mark Bloomston, Matthew R. Farren, Darwin L. Conwell, Somashekar G. Krishna, Carl Schmidt, Alice Hinton, Zobeida Cruz-Monserrate, Erin E. Talbert, Andrei Manilchuk, Timothy M. Pawlik, Daniel H. Ahn, Denis C. Guttridge, Niharika Badi, Phil A. Hart, and Thomas A. Mace more...
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Male ,medicine.medical_specialty ,Cachexia ,Endocrinology, Diabetes and Metabolism ,Population ,Gastroenterology ,Article ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Weight loss ,Pancreatic cancer ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Wasting Syndrome ,education ,Aged ,Retrospective Studies ,education.field_of_study ,Hepatology ,Interleukin-6 ,business.industry ,Cancer ,Middle Aged ,medicine.disease ,Pancreatic Neoplasms ,030220 oncology & carcinogenesis ,Disease Progression ,Biomarker (medicine) ,Female ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,Carcinoma, Pancreatic Ductal - Abstract
BACKGROUND: Cachexia is a wasting syndrome characterized by involuntary loss of >5% body weight due to depletion of adipose and skeletal muscle mass. In cancer, the pro-inflammatory cytokine interleukin-6 (IL-6) is considered a mediator of cachexia and a potential biomarker, but the relationship between IL-6, weight loss, and cancer stage is unknown. In this study we sought to evaluate IL-6 as a biomarker of cancer cachexia while accounting for disease progression. METHODS: We retrospectively studied 136 subjects with biopsy-proven pancreatic ductal adenocarcinoma (PDAC), considering the high prevalence of cachexia is this population. Clinical data were abstracted from subjects in all cancer stages, and plasma IL-6 levels were measured using a multiplex array and a more sensitive ELISA. Data were evaluated with univariate comparisons, including Kaplan-Meier survival curves, and multivariate Cox survival models. RESULTS: On multiplex, a total of 43 (31.4%) subjects had detectable levels of plasma IL-6, while by ELISA all subjects had detectable IL-6 levels. We found that increased plasma IL-6 levels, defined as detectable for multiplex and greater than median for ELISA, were not associated with weight loss at diagnosis, but rather with the presence of metastasis (p5% weight loss was not associated with worse survival, increased plasma IL-6 by either methodology was. CONCLUSION: Circulating IL-6 levels do not correlate with weight loss (i.e., cachexia), but rather with advanced cancer stage. This suggests that IL-6 may mediate wasting, but should not be considered a diagnostic biomarker for PDAC-induced cachexia. more...
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- 2019
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13. Lipocalin-2 Promotes Pancreatic Ductal Adenocarcinoma by Regulating Inflammation in the Tumor Microenvironment
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Liran Zhou, Carl Schmidt, Zobeida Cruz-Monserrate, Gregory B. Lesinski, Thomas A. Mace, Rosa F. Hwang, Sobeyda B. Gomez-Chou, Matthew R. Farren, Yan Liu, Huamin Wang, Todd Moore, Tanios Bekaii-Saab, Craig D. Logsdon, Niharika Badi, Defeng Deng, Xiaohong Leng, Deyali Chatterjee, Agnieszka Katarzyna Swidnicka-Siergiejko, Ralph B. Arlinghaus, and Myrriah Chavez-Tomar more...
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0301 basic medicine ,Cancer Research ,endocrine system diseases ,Pancreatic Intraepithelial Neoplasia ,Mice, Transgenic ,Inflammation ,Kaplan-Meier Estimate ,Biology ,Article ,Proinflammatory cytokine ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Lipocalin-2 ,Downregulation and upregulation ,Pancreatic cancer ,Tumor Microenvironment ,medicine ,Animals ,Humans ,RNA, Small Interfering ,Mice, Knockout ,Tumor microenvironment ,Cancer ,Prognosis ,medicine.disease ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,Pancreatic Neoplasms ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Gene Knockdown Techniques ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,Cytokines ,Inflammation Mediators ,medicine.symptom ,Pancreas ,Carcinoma, Pancreatic Ductal - Abstract
Lipocalin-2 (LCN2) promotes malignant development in many cancer types. LCN2 is upregulated in patients with pancreatic ductal adenocarcinoma (PDAC) and in obese individuals, but whether it contributes to PDAC development is unclear. In this study, we investigated the effects of Lcn2 depletion on diet-induced obesity, inflammation, and PDAC development. Mice with acinar cell–specific expression of KrasG12D were crossed with Lcn2-depleted animals and fed isocaloric diets with varying amounts of fat content. Pancreas were collected and analyzed for inflammation, pancreatic intraepithelial neoplasia (PanIN), and PDAC. We also used a syngeneic orthotopic PDAC mouse model to study tumor growth in the presence or absence of Lcn2 expression. In addition, to understand the mechanistic role of how LCN2 could be mediating PDAC, we studied LCN2 and its specific receptor solute carrier family 22 member 17 (SLC22A17) in human pancreatic cancer stellate cells (PSC), key mediators of the PDAC stroma. Depletion of Lcn2 diminished extracellular matrix deposition, immune cell infiltration, PanIN formation, and tumor growth. Notably, it also increased survival in both obesity-driven and syngeneic orthotopic PDAC mouse models. LCN2 modulated the secretion of proinflammatory cytokines in PSC of the PDAC tumor microenvironment, whereas downregulation of LCN2-specific receptor SLC22A17 blocked these effects. Our results reveal how LCN2 acts in the tumor microenvironment links obesity, inflammation, and PDAC development. Cancer Res; 77(10); 2647–60. ©2017 AACR more...
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- 2017
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14. Iron and Lipocalin-2 Modulate Cellular Responses in the Tumor Micro-environment of Pancreatic Ductal Adenocarcinoma
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Maciej Pietrzak, Andrea Ludwig, Madelyn Traczek, Zobeida Cruz-Monserrate, Rosa F. Hwang, Amy Webb, Olivia Ueltschi, Xiaokui Mo, Valentina Pita-Grisanti, Niharika Badi, Kristyn Gumpper, and Andrew W. Dangel more...
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endocrine system diseases ,Chemistry ,Cell growth ,Cell migration ,Lipocalin ,medicine.disease ,digestive system diseases ,Metastasis ,Extracellular matrix ,Cancer research ,Hepatic stellate cell ,medicine ,Receptor ,Gene - Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease with poor outcomes. Iron is known to signal cellular responses, and its levels are regulated by lipocalin-2 (LCN2) expression, a PDAC pro-tumorigenic molecule. However, how iron and LCN2 function in PDAC is unclear. Here we demonstrate that iron levels regulate PDAC cell proliferation, invasion, expression of epithelial to mesenchymal tumor markers, and pro-inflammatory cytokines. Iron chelation increased the expression of the LCN2 receptorSLC22A17in pancreatic stellate cells and the anti-metastatic geneNDRG1in PDAC cells. Deletion ofLcn2in mouse tumor cells modulated the expression of genes involved in extracellular matrix deposition and cell migration. Moreover, cellular iron responses were dependent on theKrasmutation status of cells, andLCN2expression levels. Deletion ofLcn2expression in PDAC suggests a protective role against metastasis. Thus, iron modulation and LCN2 blockade could serve as potential therapeutic approaches against PDAC. more...
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- 2020
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15. Abstract PO-022: Plasma fatty acid levels in treatment-naïve metastatic pancreatic cancer patients are associated with clinical indicators of cachexia
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Anne M. Noonan, Martha A. Belury, Kristyn Gumpper, Mitchell L. Ramsey, Rachel M. Cole, Olivia Crowe, Phil A. Hart, Niharika Badi, Zobeida Cruz-Monserrate, Alice Hinton, and Darwin L. Conwell
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chemistry.chemical_classification ,Oncology ,Cancer Research ,Chemotherapy ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Fatty acid ,Cancer ,medicine.disease ,Cachexia ,chemistry ,Weight loss ,Internal medicine ,Pancreatic cancer ,Diabetes mellitus ,Medicine ,medicine.symptom ,business ,Wasting - Abstract
Cachexia is a multifactorial syndrome characterized by weight loss and tissue wasting, which is associated with reduced quality of life, responsiveness to chemotherapy, and decreased survival. We aim to determine whether changes in plasma fatty acid content in pancreatic ductal adenocarcinoma (PDAC): 1) are predictive of developing cachexia, and 2) whether these changes are influenced by other clinical parameters, like diabetes, that could contribute to malnutrition. Treatment-naïve metastatic PDAC subjects (n=51) were enrolled in NCT01280058 in which plasma samples and clinical data were collected prior to treatment. Subjects were assigned to either weight stable ( Citation Format: Kristyn Gumpper, Phil A. Hart, Martha Belury, Olivia Crowe, Rachel M. Cole, Niharika Badi, Alice Hinton, Mitchell L. Ramsey, Anne Noonan, Darwin L. Conwell, Zobeida Cruz-Monserrate. Plasma fatty acid levels in treatment-naïve metastatic pancreatic cancer patients are associated with clinical indicators of cachexia [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-022. more...
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- 2020
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16. Abstract PO-034: Increased physical activity delays development of obesity-induced pancreatic ductal adenocarcinoma in mice and modulates inflammation
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Samantha Terhorst, Niharika Badi, Jennifer M. Mitchell, Karen Basen-Engquist, Alice Hinton, Kelly Dubay, Myrriah Chavez-Tomar, Thomas A. Mace, Valentina Pita-Grisanti, Fouad Choueiry, Zobeida Cruz-Monserrate, Ali Lahooti, Olivia Ueltschi, Christopher C. Coss, and Sue E. Knoblaugh more...
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Oncology ,Cancer Research ,medicine.medical_specialty ,Cluster of differentiation ,business.industry ,Cancer ,Inflammation ,medicine.disease ,Immune system ,Fibrosis ,Tumor progression ,Weight loss ,Internal medicine ,Pancreatic cancer ,medicine ,medicine.symptom ,business - Abstract
Background: Obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC), a deadly disease with no preventive strategies. Lifestyle interventions to decrease obesity might serve to prevent obesity-induced PDAC. We examined whether decreasing obesity via increased physical activity (PA) and/or diet-induced weight loss could prevent PDAC in mice and compared the levels of systemic inflammatory-associated cytokines in human subjects undergoing a PA intervention. Methods: Obesity-induced PDAC mouse models were exposed to various interventions before and after cancer initiation, that included increased PA, diet-induced weight loss, and/or chemotherapy. We evaluated body composition, tumor progression, growth, fibrosis, and inflammation. Circulating inflammatory-associated cytokines of overweight/obese human subjects before and after a PA intervention were also compared. Results: Genetically engineered PDAC mice on a PA intervention while on a HFD, gained less weight, displayed lower grade pancreatic intraepithelial neoplasias lesions, and fewer mice developed PDAC compared to controls. Similar results were observed in PDAC mice given a HFD to induce obesity, prior to a control diet (CD) and PA intervention, compared to mice given a CD after the HFD. PA alone or with a CD intervention decreased body weight but did not prevent tumor growth in an orthotopic mouse model of PDAC. PA combined with chemotherapy increased the percentage of splenic cluster of differentiation 8+ (CD8+) T cells in PDAC mice. Finally, PA prevented the increase of systemic inflammatory-associated cytokines in PDAC mice and in overweight/obese control human subjects. Conclusions: PA alone or with diet-induced weight loss delayed the progression of PDAC in genetically engineered mice and reduced inflammation. While these interventions did not prevent tumor growth in the orthotopic mouse model, it did modulate immune responses. Reducing obesity by increasing PA and decreasing dietary fat intake could be a way of reducing the incidence of PDAC in high-risk obese individuals. Citation Format: Valentina Pita-Grisanti, Kelly Dubay, Ali Lahooti, Niharika Badi, Olivia Ueltschi, Myrriah Chavez-Tomar, Samantha Terhorst, Sue Knoblaugh, Christopher Coss, Thomas Mace, Fouad Choueiry, Alice Hinton, Jennifer M Mitchell, Karen Basen-Engquist, Zobeida Cruz-Monserrate. Increased physical activity delays development of obesity-induced pancreatic ductal adenocarcinoma in mice and modulates inflammation [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-034. more...
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- 2020
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