Browsing by Subject "Pancreatic Neoplasms"
Now showing 1 - 10 of 20
Results Per Page
Sort Options
Item 14-3-3σ regulation of and interaction with YAP1 in acquired gemcitabine resistance via promoting ribonucleotide reductase expression(Impact Journals, LLC, 2016-04-05) Qin, Li; Dong, Zizheng; Zhang, Jian-Ting; Department of Pharmacology and Toxicology, IU School of MedicineGemcitabine is an important anticancer therapeutics approved for treatment of several human cancers including locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). Its clinical effectiveness, however, is hindered by existence of intrinsic and development of acquired resistances. Previously, it was found that 14-3-3σ expression associates with poor clinical outcome of PDAC patients. It was also found that 14-3-3σ expression is up-regulated in gemcitabine resistant PDAC cells and contributes to the acquired gemcitabine resistance. In this study, we investigated the molecular mechanism of 14-3-3σ function in gemcitabine resistance and found that 14-3-3σ up-regulates YAP1 expression and then binds to YAP1 to inhibit gemcitabine-induced caspase 8 activation and apoptosis. 14-3-3σ association with YAP1 up-regulates the expression of ribonucleotide reductase M1 and M2, which may mediate 14-3-3σ/YAP1 function in the acquired gemcitabine resistance. These findings suggest a possible role of YAP1 signaling in gemcitabine resistance.Item Cholecystectomy, gallstones, tonsillectomy, and pancreatic cancer risk: a population-based case-control study in minnesota(Nature Publishing Group, 2014-04-29) Zhang, J; Prizment, A E; Dhakal, I B; Anderson, K E; Department of Epidemiology, Richard M. Fairbanks School of Public HealthBackground: Associations between medical conditions and pancreatic cancer risk are controversial and are thus evaluated in a study conducted during 1994–1998 in Minnesota. Methods: Cases (n=215) were ascertained from hospitals in the metropolitan area of the Twin Cities and the Mayo Clinic. Controls (n=676) were randomly selected from the general population and frequency matched to cases by age and sex. The history of medical conditions was gathered with a questionnaire during in-person interviews. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. Results: After adjustment for confounders, subjects who had cholecystectomy or gallstones experienced a significantly higher risk of pancreatic cancer than those who did not (OR (95% CI): 2.11 (1.32–3.35) for cholecystectomy and 1.97 (1.23–3.12) for gallstones), whereas opposite results were observed for tonsillectomy (0.67 (0.48–0.94)). Increased risk associated with cholecystectomy was the greatest when it occurred ⩽2 years before the cancer diagnosis (5.93 (2.36–15.7)) but remained statistically significant when that interval was ⩾20 years (2.27 (1.16–4.32)). Conclusions: Cholecystectomy, gallstones, and tonsillectomy were associated with an altered risk of pancreatic cancer. Our study suggests that cholecystectomy increased risk but reverse causality may partially account for high risk associated with recent cholecystectomy.Item Confocal Endomicroscopy Characteristics of Different Intraductal Papillary Mucinous Neoplasm Subtypes(2017-05) Kamboj, Amrit K; Dewitt, John M; Modi, Rohan M; Conwell, Darwin L; Krishna, Somashekar G; Medicine, School of MedicineIntraductal papillary mucinous neoplasms are classified into gastric, intestinal, pancreatobiliary, and oncocytic subtypes where morphology portends disease prognosis. The study aim was to demonstrate EUS-guided needle-based confocal laser endomicroscopy imaging features of intraductal papillary mucinous neoplasm subtypes. Four subjects, each with a specific intraductal papillary mucinous neoplasm subtype were enrolled. An EUS-guided needle-based confocal laser endomicroscopy miniprobe was utilized for image acquisition. The mean cyst size from the 4 subjects (2 females; mean age = 65.3±12 years) was 36.8±12 mm. All lesions demonstrated mural nodules and focal dilation of the main pancreatic duct. EUS-nCLE demonstrated characteristic finger-like papillae with inner vascular core for all subtypes. The image patterns of the papillae for the gastric, intestinal, and pancreatobiliary subtypes were similar. However, the papillae in the oncocytic subtype were thick and demonstrated a fine scale-like or honeycomb pattern with intraepithelial lumina correlating with histopathology. There was significant overlap in the needle-based confocal laser endomicroscopy findings for the different intraductal papillary mucinous neoplasm subtypes; however, the oncocytic subtype demonstrated distinct patterns. These findings need to be replicated in larger multicenter studies.Item Diabetes, Pancreatogenic Diabetes, and Pancreatic Cancer(American Diabetes Association, 2017-05) Andersen, Dana K.; Korc, Murray; Petersen, Gloria M.; Eibl, Guido; Li, Donghui; Rickels, Michael R.; Chari, Suresh T.; Abbruzzese, James L.; Medicine, School of MedicineThe relationships between diabetes and pancreatic ductal adenocarcinoma (PDAC) are complex. Longstanding type 2 diabetes (T2DM) is a risk factor for pancreatic cancer, but increasing epidemiological data point to PDAC as also a cause of diabetes due to unknown mechanisms. New-onset diabetes is of particular interest to the oncology community as the differentiation of new-onset diabetes caused by PDAC as distinct from T2DM may allow for earlier diagnosis of PDAC. To address these relationships and raise awareness of the relationships between PDAC and diabetes, a symposium entitled Diabetes, Pancreatogenic Diabetes, and Pancreatic Cancer was held at the American Diabetes Association's 76th Scientific Sessions in June 2016. This article summarizes the data presented at that symposium, describing the current understanding of the interrelationships between diabetes, diabetes management, and pancreatic cancer, and identifies areas where additional research is needed.Item Dosimetric impact of gastrointestinal air column in radiation treatment of pancreatic cancer(British Institute of Radiology, 2018-02) Estabrook, Neil C.; Corn, Jonathan B.; Ewing, Marvene M.; Cardenes, Higinia R.; Das, Indra J.; Radiation Oncology, School of MedicineOBJECTIVE: Dosimetric evaluation of air column in gastrointestinal (GI) structures in intensity modulated radiation therapy (IMRT) of pancreatic cancer. METHODS: Nine sequential patients were retrospectively chosen for dosimetric analysis of air column in the GI apparatus in pancreatic cancer using cone beam CT (CBCT). The four-dimensional CT (4DCT) was used for target and organs at risk (OARs) and non-coplanar IMRT was used for treatment. Once a week, these patients underwent CBCT for air filling, isocentre verification and dose calculations retrospectively. RESULTS: Abdominal air column variation was as great as ±80% between weekly CBCT and 4DCT. Even with such a large air column in the treatment path for pancreatic cancer, changes in anteroposterior dimension were minimal (2.8%). Using IMRT, variations in air column did not correlate dosimetrically with large changes in target volume. An average dosimetric deviation of mere -3.3% and a maximum of -5.5% was observed. CONCLUSION: CBCT revealed large air column in GI structures; however, its impact is minimal for target coverage. Because of the inherent advantage of segmentation in IMRT, where only a small fraction of a given beam passes through the air column, this technique might have an advantage over 3DCRT in treating upper GI malignancies where the daily air column can have significant impact. Advances in knowledge: Radiation treatment of pancreatic cancer has significant challenges due to positioning, imaging of soft tissues and variability of air column in bowels. The dosimetric impact of variable air column is retrospectively studied using CBCT. Even though, the volume of air column changes by ± 80%, its dosimetric impact in IMRT is minimum.Item Endoscopic papillectomy: risk factors for incomplete resection and recurrence during long-term follow-up(Elsevier, 2014-02) Ridtitid, Wiriyaporn; Tan, Damien; Schmidt, Suzette E.; Fogel, Evan L.; McHenry, Lee; Watkins, James L.; Lehman, Glen A.; Sherman, Stuart; Coté, Gregory A.; Department of Medicine, IU School of MedicineBackground Endoscopic papillectomy is increasingly used as an alternative to surgery for ampullary adenomas and other noninvasive ampullary lesions. Objective To measure short-term safety and efficacy of endoscopic papillectomy, define patient and lesion characteristics associated with incomplete endoscopic resection, and measure adenoma recurrence rates during long-term follow-up. Design Retrospective cohort study. Setting Tertiary-care academic medical center. Patients All patients who underwent endoscopic papillectomy for ampullary lesions between July 1995 and June 2012. Intervention Endoscopic papillectomy. Main Outcome Measurements Patient and lesion characteristics associated with incomplete endoscopic resection and ampullary adenoma-free survival analysis. Results We identified 182 patients who underwent endoscopic papillectomy, 134 (73.6%) having complete resection. Short-term adverse events occurred in 34 (18.7%). Risk factors for incomplete resection were jaundice at presentation (odds ratio [OR] 0.21, 95% confidence interval [CI] 0.07–0.69; P = .009), occult adenocarcinoma (OR 0.06, 95% CI, 0.01–0.36; P = .002), and intraductal involvement (OR 0.29, 95% CI, 0.11–0.75; P = .011). The en bloc resection technique was strongly associated with a higher rate of complete resection (OR 4.05, 95% CI, 1.71–9.59; P = .001). Among patients with ampullary adenoma who had complete resection (n = 107), 16 patients (15%) developed recurrence up to 65 months after resection. Limitations Retrospective analysis. Conclusion Jaundice at presentation, occult adenocarcinoma in the resected specimen, and intraductal involvement are associated with a lower rate of complete resection, whereas en bloc papillectomy increases the odds of complete endoscopic resection. Despite complete resection, recurrence was observed up to 5 years after papillectomy, confirming the need for long-term surveillance.Item Epithelial Splicing Regulatory Protein 1 is a Favorable Prognostic Factor in Pancreatic Cancer that Attenuates Pancreatic Metastases(Nature Publishing Group, 2014-09-04) Ueda, Junji; Matsuda, Yoko; Yamahatsu, Kazuya; Uchida, Eiji; Naito, Zenya; Korc, Murray; Ishiwata, Toshiyuki; Department of Medicine, IU School of MedicineEpithelial splicing regulatory protein 1 (ESRP1) binds the FGFR-2 auxiliary cis-element ISE/ISS-3, located in the intron between exon IIIb and IIIc, and primarily promotes FGFR-2 IIIb expression. Here we assessed the role of ESRP1 in pancreatic ductal adenocarcinoma (PDAC). Immunohistochemical analysis was performed using anti-ESRP1, FGFR-2 IIIb and FGFR-2 IIIc antibodies in 123 PDAC cases. ESRP1-expression vector and small interference RNA (siRNA) targeting ESRP1 were transfected into human PDAC cells, and cell growth, migration and invasion were analyzed. In vivo heterotopic and orthotopic implantations using ESRP1 overexpression clones were performed and effects on pancreatic tumor volumes and hepatic and pulmonary metastases determined. ESRP1 immunoreactivity was strong in the nuclei of cancer cells in well-to-moderately differentiated PDACs, but weak in poorly-differentiated cancers. Well-to-moderately differentiated cancers also exhibited high FGFR-2 IIIb and low FGFR-2 IIIc expression, whereas this ratio was reversed in the poorly-differentiated cancers. Increased ESRP1 expression was associated with longer survival by comparison with low-ESRP1 expression, and PANC-1 cells engineered to express ESRP1 exhibited increased FGFR-2 IIIb expression and decreased migration and invasion in vitro, whereas ESRP1 siRNA-transfected KLM-1 cells exhibited increased FGFR-2 IIIc expression and increased cell growth, migration and invasion. In vivo, ESRP1-overexpressing clones formed significantly fewer liver metastases as compared with control clones. ESRP1 regulates the expression pattern of FGFR-2 isoforms, attenuates cell growth, migration, invasion, and metastasis, and is a favorable prognostic factor in PDAC. Therefore, devising mechanisms to up-regulate ESRP1 may exert a beneficial therapeutic effect in PDAC.Item Genetic variability in energy balance and pancreatic cancer risk in a population-based case-control study in Minnesota(Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins, 2014-03) Zhang, Jianjun; Dhakal, Ishwori B.; Zhang, Xuemei; Prizment, Anna E.; Anderson, Kristin E.; Department of Epidemiology, Richard M. Fairbanks School of Public HealthOBJECTIVES: Accumulating evidence suggests that energy imbalance plays a role in pancreatic carcinogenesis. However, it remains unclear whether single-nucleotide polymorphisms (SNPs) in genes regulating energy homeostasis influence pancreatic cancer risk. We investigated this question in a case-control study conducted from 1994 to 1998. METHODS: Patients (n = 173) were ascertained from hospitals in the Twin Cities and Mayo Clinic, Minnesota. Control subjects (n = 476) were identified from the general population and frequency matched to patients by age and sex. Seven SNPs were evaluated in relation to pancreatic cancer using unconditional logistic regression. RESULTS: After adjustment for confounders, the leucine/proline or proline/proline genotype of the neuropeptide Y (NPY) gene rs16139 was associated with a lower risk than the leucine/leucine genotype (odds ratio, 0.40 [95% confidence interval, 0.15-0.91]). Conversely, an increased risk was observed for the glycine/arginine or arginine/arginine genotype of the adrenoceptor β2, surface (ADRB2) gene rs1042713 as compared with the glycine/glycine genotype (odds ratio, 1.52 [95% confidence interval, 1.01-2.31]). CONCLUSIONS: This study first reveals that SNPs in genes modulating energy intake (NPY) and energy expenditure (ADRB2) altered pancreatic cancer risk. If confirmed by other studies, our findings may shed new light on the etiology and prevention of pancreatic cancer.Item Highly specific plasmonic biosensors for ultrasensitive microRNA detection in plasma from pancreatic cancer patients(American Chemical Society, 2014-12-10) Joshi, Gayatri K.; Deitz-McElyea, Samantha; Johnson, Merrell; Mali, Sonali; Korc, Murray; Sardar, Rajesh; Department of Chemistry & Chemical Biology, School of ScienceMicroRNAs (miRs) are small noncoding RNAs that regulate mRNA stability and/or translation. Because of their release into the circulation and their remarkable stability, miR levels in plasma and other biological fluids can serve as diagnostic and prognostic disease biomarkers. However, quantifying miRs in the circulation is challenging due to issues with sensitivity and specificity. This Letter describes for the first time the design and characterization of a regenerative, solid-state localized surface plasmon resonance (LSPR) sensor based on highly sensitive nanostructures (gold nanoprisms) that obviates the need for labels or amplification of the miRs. Our direct hybridization approach has enabled the detection of subfemtomolar concentration of miR-X (X = 21 and 10b) in human plasma in pancreatic cancer patients. Our LSPR-based measurements showed that the miR levels measured directly in patient plasma were at least 2-fold higher than following RNA extraction and quantification by reverse transcriptase-polymerase chain reaction. Through LSPR-based measurements we have shown nearly 4-fold higher concentrations of miR-10b than miR-21 in plasma of pancreatic cancer patients. We propose that our highly sensitive and selective detection approach for assaying miRs in plasma can be applied to many cancer types and disease states and should allow a rational approach for testing the utility of miRs as markers for early disease diagnosis and prognosis, which could allow for the design of effective individualized therapeutic approaches.Item Improving the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration using microRNAs(ScienceDirect, 2014-10) Sina, Marsela; Cote, Gregory A.; Korc, Murray; Department of Medicine, IU School of MedicineComment on: A microRNA-based test improves endoscopic ultrasound-guided cytologic diagnosis of pancreatic cancer.