Pathways of Progression From Intraductal Papillary Mucinous Neoplasm to Pancreatic Ductal Adenocarcinoma Based on Molecular Features

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Fatty acid ethyl ester (FAEE) associated acute pancreatitis: An ex-vivo study using human pancreatic acini

Background & aimFatty acid ethyl esters (FAEEs), are produced by non-oxidative alcohol metabolism and can cause acinar cell damage and subsequent acute pancreatitis in rodent models. Even though experimental studies have elucidated the FAEE mediated early intra-acinar events, these mechanisms have not been well studied in humans. In the present study, we evaluate the early intra-acinar events and inflammatory response in human pancreatic acinar tissues and cells in an ex-vivo model.MethodsExperiments were conducted using normal human pancreatic tissues exposed to FAEE. Subcellular fractionation was performed on tissue homogenates and trypsin and cathepsin B activities were estimated in these fractions. Acinar cell injury was evaluated by histology and immunohistochemistry. Cytokine release from exposed acinar cells was evaluated by performing Immuno-fluorescence. Serum was collected from patients with AP within the first 72 h of symptom onset for cytokine estimation using FACS.ResultsWe observed significant trypsin activation and acinar cell injury in FAEE treated tissue. Cathepsin B was redistributed from lysosomal to zymogen compartment at 30 min of FAEE exposure. IHC results indicated the presence of apoptosis in pancreatic tissue at 1 & 2hrs of FAEE exposure. We also observed a time dependent increase in secretion of cytokines IL-6, IL-8, TNF-α from FAEE treated acinar tissue. There was also a significant elevation in plasma cytokines in patents with alcohol associated AP within 72 h of symptom onset.ConclusionOur data suggest that alcohol metabolites can cause acute acinar cell damage and subsequent cytokine release which could eventually culminant in SIRS.     

JAK／STAT信号通路与组织器官纤维化的相关性研究进展

Janus激酶／信号转导与转录激活子（JAK／STAT）是一条依靠多种细胞因子和生长因子共同介导的信号通路,广泛参与了细胞的增殖、分化、凋亡及免疫调节等病理生理过程。多项研究表明,JAK／sTAT信号通路对机体不同的组织及器官如肾脏、肝脏、肺、心脏等的纤维化形成过程具有重要的调控作用。该文就近年JAK／sTAT信号通路与机体组织器官纤维化形成的相关性研究作一综述。     

A new in-vitro drug sensitivity test (collagen-gel droplet embedded-culture drug sensitivity test) in carcinomas of pancreas and biliary tract: possible clinical utility

The collagen-gel droplet embedded-culture drug sensitivity test (CD-DST), a chemosensitivity test, evaluate the efficacy of anticancer drugs and to was used clinically to thus plan rational postoperative chemotherapy for patients with pancreatic and biliary tract carcinomas. The CD-DST solves some problems inherent in other conventional assays. This method: (1) allows evaluation of four chemotherapeutic agents, using small quantities of cells (1 × 10⁵ cells), (2) shows high primary culture success rates, (3) maintains the original growth characteristics of the cultured cells, (4) eliminates the effects of fibroblasts by employing image analysis, and (5) permits evaluation using physiologic drug concentrations. Primary cultures of tumor cell samples from all 25 patients with pancreatic or biliary tract carcinomas studied were successful. Against pancreatic carcinomas, the efficacy rates, assessed by CD-DST, of four anticancer drugs evaluated were: 25.0% for mitomycin (MMC), followed by 23.5% for adriamycin, 18.8% for 5-fluorouracil (5-FU), and 11.8% for cisplatin (CDDP). Against biliary tract carcinomas, the rates were highest for 5-FU and MMC (50.0%) and lowest for CDDP (25.0%). The efficacy rates for all four anticancer drugs evaluated were higher against biliary tract carcinomas than against pancreatic carcinomas. Tumor cultures from 10 of 17 patients with pancreatic cancer and 3 of 8 patients with biliary tract cancer showed no sensitivity to any of the drugs tested. The in-vitro results with CD-DST suggest the risk of administering non-selective postoperative chemotherapy to patients with pancreatic and biliary tract carcinomas, and emphasize the importance of carefully selecting effective chemotherapeutic agents based on adequate chemosensitivity testing.     

Optical method for determining the frequency response of pressure-measurement systems in respiratory mechanics

An optical method for measuring the frequency response of pressure transducers is described. The method allows the calculation of the varying pressure of ate pressure. Displacement is measured by a photodetector position sensor with the aid of a laser beam reflected on a mirror attached to the loudspeaker diaphragm. The method is based on the short time response of the optical system and it presents some advantages with regard to the usual dynamic calibration using a microphone reference: (a) it has a good response at low frequencies; (b) it is unaffected by environmental conditions; and (c) the system can easily be recalibrated.     

改良脱细胞异种真皮的制备与动物埋藏实验

目的:研制一种新型异种人工真皮。方法:应用鼠尾胶原和异种(猪)脱细胞真皮复合制备成新型复合真皮,将复合真皮与交联型脱细胞真皮分别埋藏于Balb/C小白鼠皮下,观察新型材料的组织相容性及促胶原代谢能力。结果:所有试验小鼠在早期均有毛发脱失现象,交联型真皮组持续时间长并伴有肉芽组织形成。4周后,新型复合真皮显示组织结构致密有序,降解时间更长;组织相容性及促自体胶原代谢能力均较交联型真皮更为优越。结论:新型材料具有更好的组织相容性和更强的促胶原代谢能力,是良好的皮肤组织工程支架材料。     

No association between XRCC1 and XRCC3 gene polymorphisms and breast cancer risk: Iowa Women's Health Study

BACKGROUND: Genetic variation in DNA repair may contribute to differences in the susceptibility of several cancers. We evaluated two polymorphisms in the base excision repair pathway (BER) (XRCC1; Arg194Trp and Arg399Gln) and one polymorphism in the double strand DNA repair pathway (XRCC3; Thr241Met) for their association with breast cancer risk. METHODS: The association was analyzed in a nested case control study of 460 breast cancer cases and 324 cancer-free controls within the Iowa Women's Health Cohort. DNA was obtained from blood samples or paraffin embedded tissues (PET) and all samples were genotyped by one of three genotyping platforms-PCR-RFLP, PCR-INVADER, or Sequenom. RESULTS: None of the three polymorphisms studied were significantly associated with breast cancer risk (XRCC1: Arg194Trp (OR=1.21, 95% CI: 0.78-1.88); Arg399Gln (OR=1.20, 95% CI: 0.80-1.79); XRCC3: Thr241Met (OR=1.04, 95% CI: 0.76-1.41). CONCLUSIONS: These results suggest that independently these polymorphisms of XRCC1 and XRCC3 genes do not contribute significantly to the genetic susceptibility of breast cancer.     

A study of X chromosome linkage with field dependence and spatial visualization

The purposes of this report are to describe a design for the study of X linkage, to illustrate its application using cognitive test scores, and to offer a linkage hypothesis suggested by these data. Sixty-seven three-son families were examined for two X chromosome marker variables—red-green color vision andXg(a) blood groups—and given a battery of cognitive tests of field dependence and spatial visualization abilities. Evidence was found to suggest that brothers who are identical inXg(a) phenotype are more similar to each other in extent of field dependence than brothers who are different inXg(a) phenotype. This result is tentative because of the small number of informative cases and the many linkage associations examined. If crossvalidated, such a finding would be consistent with the proposition that an X chromosome gene contributes to the field dependence-independence cognitive style.This study was partially supported by NIMH Grant No. 21989.