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Sample records for cck-8-stimulated mouse pancreatic

  1. Mouse models of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Marta Herreros-Villanueva; Elizabeth Hijona; Angel Cosme; Luis Bujanda

    2012-01-01

    Pancreatic cancer is one of the most lethal of human malignancies ranking 4th among cancer-related death in the western world and in the United States,and potent therapeutic options are lacking.Although during the last few years there have been important advances in the understanding of the molecular events responsible for the development of pancreatic cancer,currently specific mechanisms of treatment resistance remain poorly understood and new effective systemic drugs need to be developed and probed.In vivo models to study pancreatic cancer and approach this issue remain limited and present different molecular features that must be considered in the studies depending on the purpose to fit special research themes.In the last few years,several genetically engineered mouse models of pancreatic exocrine neoplasia have been developed.These models mimic the disease as they reproduce genetic alterations implicated in the progression of pancreatic cancer.Genetic alterations such as activating mutations in KRas,or TGFb and/or inactivation of tumoral suppressors such as p53,INK4A/ARF BRCA2 and Smad4 are the most common drivers to pancreatic carcinogenesis and have been used to create transgenic mice.These mouse models have a spectrum of pathologic changes,from pancreatic intraepithelial neoplasia to lesions that progress histologically culminating in fully invasive and metastatic disease and represent the most useful preclinical model system.These models can characterize the cellular and molecular pathology of pancreatic neoplasia and cancer and constitute the best tool to investigate new therapeutic approaches,chemopreventive and/or anticancer treatments.Here,we review and update the current mouse models that reproduce different stages of human pancreatic ductal adenocarcinoma and will have clinical relevance in future pancreatic cancer developments.

  2. Development of Orthotopic Pancreatic Tumor Mouse Models

    OpenAIRE

    Qiu, Wanglong; Gloria H. Su

    2013-01-01

    Genetically engineered mouse models of pancreatic cancer that recapitulate human pancreatic tumorigenesis have been established. However, the cost associated with generating and housing these mice can be prohibitive. Tumor latency and progression to invasive diseases in these models are also highly variable. Xenograft mouse models of human pancreatic cancer including heterotopic and orthotopic have been widely used in preclinical studies for their comparatively low cost and rapid, predictable...

  3. Connexins protect mouse pancreatic β cells against apoptosis.

    Science.gov (United States)

    Klee, Philippe; Allagnat, Florent; Pontes, Helena; Cederroth, Manon; Charollais, Anne; Caille, Dorothée; Britan, Aurore; Haefliger, Jacques-Antoine; Meda, Paolo

    2011-12-01

    Type 1 diabetes develops when most insulin-producing β cells of the pancreas are killed by an autoimmune attack. The in vivo conditions modulating the sensitivity and resistance of β cells to this attack remain largely obscure. Here, we show that connexin 36 (Cx36), a trans-membrane protein that forms gap junctions between β cells in the pancreatic islets, protects mouse β cells against both cytotoxic drugs and cytokines that prevail in the islet environment at the onset of type 1 diabetes. We documented that this protection was at least partially dependent on intercellular communication, which Cx36 and other types of connexin channels establish within pancreatic islets. We further found that proinflammatory cytokines decreased expression of Cx36 and that experimental reduction or augmentation of Cx36 levels increased or decreased β cell apoptosis, respectively. Thus, we conclude that Cx36 is central to β cell protection from toxic insults. PMID:22056383

  4. Connexins protect mouse pancreatic β cells against apoptosis

    OpenAIRE

    Klee, Philippe; Allagnat, Florent; Pontes, Helena; Cederroth, Manon; Charollais, Anne; Caille, Dorothée; Britan, Aurore; Haefliger, Jacques-Antoine; Meda, Paolo

    2011-01-01

    Type 1 diabetes develops when most insulin-producing β cells of the pancreas are killed by an autoimmune attack. The in vivo conditions modulating the sensitivity and resistance of β cells to this attack remain largely obscure. Here, we show that connexin 36 (Cx36), a trans-membrane protein that forms gap junctions between β cells in the pancreatic islets, protects mouse β cells against both cytotoxic drugs and cytokines that prevail in the islet environment at the onset of type 1 diabetes. W...

  5. Characterization of the mouse pancreatic islet proteome and comparative analysis with other mouse tissues

    Energy Technology Data Exchange (ETDEWEB)

    Petyuk, Vladislav A.; Qian, Weijun; Hinault, Charlotte; Gritsenko, Marina A.; Singhal, Mudita; Monroe, Matthew E.; Camp, David G.; Kulkarni, Rohit N.; Smith, Richard D.

    2008-08-01

    The pancreatic islets of Langerhans and insulin-producing beta cells in particular play a central role in the maintenance of glucose homeostasis and the islet dysfunction is associated with the pathogenesis of both type 1 and type 2 diabetes mellitus. To contribute to the understanding of the biology of the pancreatic islets we applied proteomic techniques based on liquid chromatography coupled with mass spectrometry. Here as an initial step we present the first comprehensive proteomic characterization of pancreas islets of the mouse, the commonly used animal model for diabetes research. Two-dimensional SCX LC/RP LC-MS/MS has been applied to characterize of the mouse islet proteome, resulting in the confident identification of 17,350 different tryptic peptides covering 2,612 proteins with at least two unique peptide identifications per protein. The dataset also allowed identification of a number of post-translational modifications including several modifications relevant to oxidative stress and phosphorylation. While many of the identified phosphorylation sites corroborates with previous known sites, the oxidative modifications observed on cysteinyl residues potentially reveal novel information related to the role of oxidation stress in islet functions. Comparative analysis of the islet proteome database with 15 available proteomic datasets from other mouse tissues and cells revealed a set of 68 proteins uniquely detected only in the pancreatic islets. Besides proteins with known functions, like islet secreted peptide hormones, this unique set contains a number of proteins with yet unknown functions. The resulting peptide and protein database will be available at ncrr.pnl.gov web site of the NCRR proteomic center (ncrr.pnl.gov).

  6. Effects of CO2, acetylcholine and caerulein on 45Ca efflux from isolated mouse pancreatic fragments

    International Nuclear Information System (INIS)

    Mouse pancreatic fragments were loaded with 45Ca and placed in a flow cell. The concentration of 45Ca in the effluent was measured. The effects of changing the tension of carbon dioxide on 45Ca efflux were observed and compared with effects of pancreatic secretagogues. It is concluded that CO2 releases Ca from pancreatic acinar cells by means of intracellular acidification. This effect may in part be due to H+ displacement of Ca2+ from intracellular membrane binding sites and partly due to release of Ca from compartments (organelles) into which Ca has been actively accumulated. (orig./MG)

  7. Pancreas-specific deletion of mouse Gata4 and Gata6 causes pancreatic agenesis

    OpenAIRE

    Xuan, Shouhong; Borok, Matthew J.; Decker, Kimberly J.; Battle, Michele A.; Duncan, Stephen A.; Hale, Michael A.; MacDonald, Raymond J.; Sussel, Lori

    2012-01-01

    Pancreatic agenesis is a human disorder caused by defects in pancreas development. To date, only a few genes have been linked to pancreatic agenesis in humans, with mutations in pancreatic and duodenal homeobox 1 (PDX1) and pancreas-specific transcription factor 1a (PTF1A) reported in only 5 families with described cases. Recently, mutations in GATA6 have been identified in a large percentage of human cases, and a GATA4 mutant allele has been implicated in a single case. In the mouse, Gata4 a...

  8. MUC1 Selectively Targets Human Pancreatic Cancer in Orthotopic Nude Mouse Models

    OpenAIRE

    Park, Jeong Youp; Hiroshima, Yukihiko; Lee, Jin Young; Maawy, Ali A.; Hoffman, Robert M; Bouvet, Michael

    2015-01-01

    The goal of this study was to determine whether MUC1 antibody conjugated with a fluorophore could be used to visualize pancreatic cancer. Anti-MUC1 (CT2) antibody was conjugated with 550 nm or 650 nm fluorophores. Nude mouse were used to make subcutaneous and orthotopic models of pancreatic cancer. Western blot and flow cytometric analysis confirmed the expression of MUC1 in human pancreatic cancer cell lines including BxPC-3 and Panc-1. Immunocytochemistry with fluorophore conjugated anti-MU...

  9. The structure of two distinct pancreatic amylase genes in mouse strain YBR

    DEFF Research Database (Denmark)

    Mikkelsen, BM; Clark, ME; Christiansen, Gunna;

    1985-01-01

    The amylase complex on mouse chromosome 3 encodes both salivary and pancreatic amylase. It appears that one active gene is present for salivary amylase, whereas pancreatic amylase in some strains is coded by at least 4, and perhaps by more than 10, genes. Strain YBR is different from other strains...... in that it produces twice as much salivary amylase. Pancreatic amylase in YBR is present as two different protein forms, A beta and B beta, the sum of which amounts to only one-third of that in, for instance, strain A/J. YBR chromosomal DNA was cloned in phage gamma, followed by restriction and...... heteroduplex analysis of recombinant phages carrying amylase genes. Among 32 phage isolates, 5 carried parts of the salivary amylase sequence. The remaining phage isolates contained pancreatic amylase-like sequences and represented three nonoverlapping genomic regions, i.e., one of 34 kb containing a complete...

  10. miR-375 Inhibits Proliferation of Mouse Pancreatic Progenitor Cells by Targeting YAP1

    Directory of Open Access Journals (Sweden)

    Zhen-Wu Zhang

    2013-12-01

    Full Text Available Background/Aims: The Hippo signaling pathway regulates expansion and differentiation of stem cells and tissue progenitor cells during organ development and tissue regeneration. Previous studies have shown that YAP1, a potent effector of the Hippo signaling pathway, plays a crucial role in pancreas development, but the function of YAP1 in pancreatic progenitor cells is less known. Methods: The spatio-temporal expression pattern of YAP1 in mouse developing pancreata was detected by in situ hybridization. The effect of silencing YAP1 on the proliferation of pancreatic progenitor cells was analyzed by CCK-8 assay and Ki67 immunostaining. The regulation of miR-375 on YAP1 expression was determined by dual luciferase reporter assay, QRT-PCR and western blot. Finally, the influence of miR-375 on proliferation of pancreatic progenitor cells was analyzed by CCK-8 assay and Ki67 immunostaining. Results: We found that YAP1 was highly expressed in embryonic and adult pancreatic progenitor cells. Knocking down YAP1 by siRNA inhibited the proliferation of pancreatic progenitor cells. The mouse YAP1 was a target gene of miR-375, and miR-375 could target the 3' UTR of YAP1 mRNA to decrease its protein and mRNA levels. Similar to silencing YAP1 by siRNA, the proliferation of pancreatic progenitor cells was inhibited significantly by miR-375. Conclusion: Our results indicate that YAP1 is necessary for the proliferation of pancreatic progenitor cells and miR-375 participates in regulating YAP1 expression during pancreatic progenitor cells differentiation.

  11. MUC1 enhances tumor progression and contributes towards immunosuppression in a mouse model of spontaneous pancreatic adenocarcinoma

    OpenAIRE

    Tinder, Teresa L; Subramani, Durai B.; Basu, Gargi D; Bradley, Judy M.; Schettini, Jorge; Million, Arefayene; Skaar, Todd; Mukherjee, Pinku

    2008-01-01

    MUC1, a membrane tethered mucin glycoprotein, is overexpressed and aberrantly glycosylated in >80% of human ductal pancreatic adenocarcinoma. However, the role of MUC1 in pancreatic cancer has been elusive, partly due to the lack of an appropriate model. We report the characterization of a novel mouse model that expresses human MUC1 as a self molecule (PDA.MUC1 mice). Pancreatic tumors arise in an appropriate MUC1-tolerant background within an immune competent host. Significant enhancement in...

  12. Oral Administration of Ginseng Ameliorates Cyclosporine-Induced Pancreatic Injury in an Experimental Mouse Model

    OpenAIRE

    Lim, Sun Woo; Doh, Kyoung Chan; Jin, Long; Piao, Shang Guo; Heo, Seong Beom; Zheng, Yu Fen; Bae, Soo Kyung; Chung, Byung Ha; Yang, Chul Woo

    2013-01-01

    Background This study was performed to investigate whether ginseng has a protective effect in an experimental mouse model of cyclosporine-induced pancreatic injury. Methods Mice were treated with cyclosporine (30 mg/kg/day, subcutaneously) and Korean red ginseng extract (0.2 or 0.4 g/kg/day, oral gavage) for 4 weeks while on a 0.01% salt diet. The effect of ginseng on cyclosporine-induced pancreatic islet dysfunction was investigated by an intraperitoneal glucose tolerance test and measuremen...

  13. Dimethylaminoparthenolide and gemcitabine: a survival study using a genetically engineered mouse model of pancreatic cancer

    International Nuclear Information System (INIS)

    Pancreatic cancer remains one of the deadliest cancers due to lack of early detection and absence of effective treatments. Gemcitabine, the current standard-of-care chemotherapy for pancreatic cancer, has limited clinical benefit. Treatment of pancreatic cancer cells with gemcitabine has been shown to induce the activity of the transcription factor nuclear factor-kappaB (NF-κB) which regulates the expression of genes involved in the inflammatory response and tumorigenesis. It has therefore been proposed that gemcitabine-induced NF-κB activation may result in chemoresistance. We hypothesize that NF-κB suppression by the novel inhibitor dimethylaminoparthenolide (DMAPT) may enhance the effect of gemcitabine in pancreatic cancer. The efficacy of DMAPT and gemcitabine was evaluated in a chemoprevention trial using the mutant Kras and p53-expressing LSL-KrasG12D/+; LSL-Trp53R172H; Pdx-1-Cre mouse model of pancreatic cancer. Mice were randomized to treatment groups (placebo, DMAPT [40 mg/kg/day], gemcitabine [50 mg/kg twice weekly], and the combination DMAPT/gemcitabine). Treatment was continued until mice showed signs of ill health at which time they were sacrificed. Plasma cytokine levels were determined using a Bio-Plex immunoassay. Statistical tests used included log-rank test, ANOVA with Dunnett’s post-test, Student’s t-test, and Fisher exact test. Gemcitabine or the combination DMAPT/gemcitabine significantly increased median survival and decreased the incidence and multiplicity of pancreatic adenocarcinomas. The DMAPT/gemcitabine combination also significantly decreased tumor size and the incidence of metastasis to the liver. No significant differences in the percentages of normal pancreatic ducts or premalignant pancreatic lesions were observed between the treatment groups. Pancreata in which no tumors formed were analyzed to determine the extent of pre-neoplasia; mostly normal ducts or low grade pancreatic lesions were observed, suggesting prevention of

  14. A 78-kilobase region of mouse chromosome 3 contains salivary and pancreatic amylase genes and a pseudogene.

    OpenAIRE

    Wiebauer, K; Gumucio, D L; Jones, J M; Caldwell, R M; Hartle, H T; Meisler, M H

    1985-01-01

    Genetic studies have demonstrated that salivary and pancreatic amylase genes are closely linked in human and mouse. To analyze the arrangement of genes within the amylase cluster, a library of YBR mouse genomic DNA was cloned in the cosmid vector pJB8. Clones containing amylase genes were identified by hybridization with amylase cDNA probes. Salivary and pancreatic amylase genes were isolated on separate cosmid clones, but no overlapping clones were evident from the initial screening. A strat...

  15. Complementarity of ultrasound and fluorescence imaging in an orthotopic mouse model of pancreatic cancer

    International Nuclear Information System (INIS)

    Pancreatic cancer is a devastating disease characterized by dismal 5-year survival rates and limited treatment options. In an effort to provide useful models for preclinical evaluation of new experimental therapeutics, we and others have developed orthotopic mouse models of pancreatic cancer. The utility of these models for pre-clinical testing is dependent upon quantitative, noninvasive methods for monitoring in vivo tumor progression in real time. Toward this goal, we performed whole-body fluorescence imaging and ultrasound imaging to evaluate and to compare these noninvasive imaging modalities for assessing tumor burden and tumor progression in an orthotopic mouse model of pancreatic cancer. The human pancreatic cancer cell line XPA-1, engineered for stable, high-level expression of red fluorescent protein (RFP), was implanted into the pancreas of nude mice using orthotopic implantation. The tumors were allowed to grow over a period of one to several weeks during which time the mice were imaged using both fluorescence imaging and ultrasound imaging to measure tumor burden and to monitor tumor growth. Whole-body fluorescence imaging and ultrasound imaging both allowed for the visualization and measurement of orthotopic pancreatic tumor implants in vivo. The imaging sessions were well-tolerated by the mice and yielded data which correlated well in the quantitative assessment of tumor burden. Whole-body fluorescence and two-dimensional ultrasound imaging showed a strong correlation for measurement of tumor size over a range of tumor sizes (R2 = 0.6627, P = 0.003 for an exposure time of 67 msec and R2 = 0.6553, P = 0.003 for an exposure time of 120 msec). Our findings suggest a complementary role for fluorescence imaging and ultrasound imaging in assessing tumor burden and tumor progression in orthotopic mouse models of human cancer

  16. Curcumin Inhibits Tumor Growth and Angiogenesis in an Orthotopic Mouse Model of Human Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Sabrina Bimonte

    2013-01-01

    Full Text Available Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues forming the pancreas. The best chemotherapeutic agent used to treat pancreatic cancer is the gemcitabine. However, gemcitabine treatment is associated with many side effects. Thus novel strategies involving less toxic agents for treatment of pancreatic cancer are necessary. Curcumin is one such agent that inhibits the proliferation and angiogenesis of a wide variety of tumor cells, through the modulation of many cell signalling pathways. In this study, we investigated whether curcumin plays antitumor effects in MIA PaCa-2 cells. In vitro studies showed that curcumin inhibits the proliferation and enhances apoptosis of MIA PaCa-2 cells. To test whether the antitumor activity of curcumin is also observed in vivo, we generated an orthotopic mouse model of pancreatic cancer by injection of MIA PaCa-2 cells in nude mice. We placed mice on diet containing curcumin at 0.6% for 6 weeks. In these treated mice tumors were smaller with respect to controls and showed a downregulation of the transcription nuclear factor NF-κB and NF-κB-regulated gene products. Overall, our data indicate that curcumin has a great potential in treatment of human pancreatic cancer through the modulation of NF-κB pathway.

  17. Effect of Endostar Combined with Gemcitabine on the Mouse Model of Human Pancreatic Cancer

    Institute of Scientific and Technical Information of China (English)

    林清风

    2007-01-01

    Objective To investigate the effects of recombinant human endostatin,that is,endostar combined with gemcitabine on the mouse model of human pancreatic cancer.Methods We use the cell line PANC-1 and the severe combined immune deficient mice to set up the mouse model of human pancreatic cancer,then devide them into three groups,treat them with gemcitabine,gemcitabine combined with endostar,and 0.9% saline water respectively.We observe the change of the tumor volumn,use ELISA method to detect the serum VEGF level,stain the micro vessel in the tumor tissue with immunohistochemistry method,and compare the data among the different groups respectively.Results On the twenty-eighth day,the tumor volume of the control group,the monotherapy group and the combination group,averaged 1 700 mm3,19.2 mm3,10.4 mm3,serum VEGF level 88.6 L,35.5,26.3 pg/mL and MVD 43.9,30.3,19.2 respectively,which had significant difference.Conclusion Endostar can strengthen the lethal effect of gemcitabine on the mouse model of human pancreatic cancer.

  18. Kanglaite combined Gemcitabine inhibits growth of nude mouse subcutaneous transplantation tumor of human PC-3 pancreatic cancer cell

    Institute of Scientific and Technical Information of China (English)

    WANG Wei; JIN Jian-guang; QIN Zhao-yin

    2005-01-01

    Objective:To study the mechanisms of pancreatic cancer treatment with Kanglaite combined Gemcitabine by investigating the relationship between the apoptosis and the expression of bcl-2, Bax and VEGF in pancreatic cancer cells.Methods:Nude mouse subcutaneous transplantation tumor model of Human PC-3 pancreatic cancer was established; the expressions of bcl-2, Bax and VEGF of transplantation tumor cell were determined; the earlier apoptosis rate of pancreatic cancer cell and the gross tumor volume were determined. Results:Kanglaite combined Gemcitabine remarkably decreased the protein expression of bcl-2,raised the expression of Bax,increased the apoptosis rate of the pancreatic cancer and contract the gross tumor volume. Kanglaite greatly decreased the protein expression of VEGF of the tumor cell. Conclusion:Therapeutic efficacy of Kanglaite combined Gemcitabine is far better than separate use of the two medicines in the pancreatic cancer transplantation tumor treatment.

  19. A mouse to human search for plasma proteome changes associated with pancreatic tumor development.

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    Vitor M Faca

    2008-06-01

    Full Text Available BACKGROUND: The complexity and heterogeneity of the human plasma proteome have presented significant challenges in the identification of protein changes associated with tumor development. Refined genetically engineered mouse (GEM models of human cancer have been shown to faithfully recapitulate the molecular, biological, and clinical features of human disease. Here, we sought to exploit the merits of a well-characterized GEM model of pancreatic cancer to determine whether proteomics technologies allow identification of protein changes associated with tumor development and whether such changes are relevant to human pancreatic cancer. METHODS AND FINDINGS: Plasma was sampled from mice at early and advanced stages of tumor development and from matched controls. Using a proteomic approach based on extensive protein fractionation, we confidently identified 1,442 proteins that were distributed across seven orders of magnitude of abundance in plasma. Analysis of proteins chosen on the basis of increased levels in plasma from tumor-bearing mice and corroborating protein or RNA expression in tissue documented concordance in the blood from 30 newly diagnosed patients with pancreatic cancer relative to 30 control specimens. A panel of five proteins selected on the basis of their increased level at an early stage of tumor development in the mouse was tested in a blinded study in 26 humans from the CARET (Carotene and Retinol Efficacy Trial cohort. The panel discriminated pancreatic cancer cases from matched controls in blood specimens obtained between 7 and 13 mo prior to the development of symptoms and clinical diagnosis of pancreatic cancer. CONCLUSIONS: Our findings indicate that GEM models of cancer, in combination with in-depth proteomic analysis, provide a useful strategy to identify candidate markers applicable to human cancer with potential utility for early detection.

  20. Oral administration of ginseng ameliorates cyclosporine-induced pancreatic injury in an experimental mouse model.

    Directory of Open Access Journals (Sweden)

    Sun Woo Lim

    Full Text Available BACKGROUND: This study was performed to investigate whether ginseng has a protective effect in an experimental mouse model of cyclosporine-induced pancreatic injury. METHODS: Mice were treated with cyclosporine (30 mg/kg/day, subcutaneously and Korean red ginseng extract (0.2 or 0.4 g/kg/day, oral gavage for 4 weeks while on a 0.01% salt diet. The effect of ginseng on cyclosporine-induced pancreatic islet dysfunction was investigated by an intraperitoneal glucose tolerance test and measurements of serum insulin level, β cell area, macrophage infiltration, and apoptosis. Using an in vitro model, we further examined the effect of ginseng on a cyclosporine-treated insulin-secreting cell line. Oxidative stress was measured by the concentration of 8-hydroxy-2'-deoxyguanosine in serum, tissue sections, and culture media. RESULTS: Four weeks of cyclosporine treatment increased blood glucose levels and decreased insulin levels, but cotreatment with ginseng ameliorated the cyclosporine-induced glucose intolerance and hyperglycemia. Pancreatic β cell area was also greater with ginseng cotreatment compared with cyclosporine monotherapy. The production of proinflammatory molecules, such as induced nitric oxide synthase and cytokines, and the level of apoptotic cell death also decreased in pancreatic β cell with ginseng treatment. Consistent with the in vivo results, the in vitro study showed that the addition of ginseng protected against cyclosporine-induced cytotoxicity, inflammation, and apoptotic cell death. These in vivo and in vitro changes were accompanied by decreases in the levels of 8-hydroxy-2'-deoxyguanosine in pancreatic β cell in tissue section, serum, and culture media during cotreatment of ginseng with cyclosporine. CONCLUSIONS: The results of our in vivo and in vitro studies demonstrate that ginseng has a protective effect against cyclosporine-induced pancreatic β cell injury via reducing oxidative stress.

  1. Pancreatitis

    Science.gov (United States)

    ... the hormones insulin and glucagon into the bloodstream. Pancreatitis is inflammation of the pancreas. It happens when digestive enzymes start digesting the pancreas itself. Pancreatitis can be acute or chronic. Either form is ...

  2. A mouse model of severe acute pancreatitis induced with caerulein and lipopolysaccharide

    Institute of Scientific and Technical Information of China (English)

    Shi-Ping Ding; Ji-Cheng Li; Chang Jin

    2003-01-01

    AIM: To establish a non-traumatic, easy to induce and reproducible mouse model of severe acute pancreatitis (SAP)induced with caerulein and lipopolyasccharide (LPS).METHODS: Thirty-two healthy mature NIH female mice were selected and divided at random into four groups (each of 8 mice), i.e., the control group (NS group), the caerulein group (Ch group), the lipopolysaccharide group (LPS group),and the caerulein+LPS group (Cn+LPS group). Mice were injected intraperitoneally with caerulein only, or LPS only,and caerulein and LPS in combination. All the animals were then killed by neck dislocation three hours after the last intraperitoneal injection. The pancreas and exo-pancreatic organs were then carefully removed for microscopic examination. And the pancreatic acinus was further observed under transmission electron microscope (TEM). Pancreatic weight, serum amylase, serum nitric oxide (NO)concentration, superoxide dismutase (SOD) and malondialdehyde (MDA) concentration of the pancreas were assayed respectively.RESULTS: (1) NS animals displayed normal pancreatic structure both in the exocrine and endocrine. In the LPS group, the pancreas was slightly edematous, with the infiltration of a few inflammatory cells and the necrosis of the adjacent fat tissues. All the animals of the Cn group showed distinct signs of a mild edematous pancreatitis characterized by interstitial edema, infiltration of neutrophil and mononuclear cells, but without obvious parenchyma necrosis and hemorrhage. In contrast, the Cn+LPS groupshowed more diffuse focal areas of nonviable pancreatic and hemorrhage as well as systemic organ dysfunction.According to Schmidt's criteria, the pancreatic histologic score showed that there existed significant difference in the Cn+LPS group in the interstitial edema, inflammatory infiltration,parenchyma necrosis and parenchyma homorrhage in comparison with those of the Cn group, LPS group and NS group (P<0.01 or P<0.05). (2) The ultrasturcture of acinar

  3. An optimised mouse model of chronic pancreatitis with a combination of ethanol and cerulein

    Science.gov (United States)

    Ahmadi, Abbas; Nikkhoo, Bahram; Mokarizadeh, Aram; Rahmani, Mohammad-Reza; Fakhari, Shohreh; Mohammadi, Mehdi

    2016-01-01

    Introduction Chronic pancreatitis (CP) is an intractable and multi-factorial disorder. Developing appropriate animal models is an essential step in pancreatitis research, and the best ones are those which mimic the human disorder both aetiologically and pathophysiologically. The current study presents an optimised protocol for creating a murine model of CP, which mimics the initial steps of chronic pancreatitis in alcohol chronic pancreatitis and compares it with two other mouse models treated with cerulein or ethanol alone. Material and methods Thirty-two male C57BL/6 mice were randomly selected, divided into four groups, and treated intraperitoneally with saline (10 ml/kg, control group), ethanol (3 g/kg; 30% v/v), cerulein (50 µg/kg), or ethanol + cerulein, for six weeks. Histopathological and immunohistochemical assays for chronic pancreatitis index along with real-time PCR assessments for mRNA levels of inflammatory cytokines and fibrogenic markers were conducted to verify the CP induction. Results The results indicated that CP index (CPI) was significantly increased in ethanol-cerulein mice compared to the saline, ethanol, and cerulein groups (p < 0.001). Interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), transforming growth factor β (TGF-β), α-smooth muscle actin (α-SMA), and myeloperoxidase activity were also significantly greater in both cerulein and ethanol-cerulein groups than in the saline treated animals (p < 0.001). Immunohistochemical analysis revealed enhanced expression of TGF-β and α-SMA in ethanol-cerulein mice compared to the saline group. Conclusions Intraperitoneal (IP) injections of ethanol and cerulein could successfully induce CP in mice. IP injections of ethanol provide higher reproducibility compared to ethanol feeding. The model is simple, non-invasive, reproducible, and time-saving. Since the protocol mimics the initial phases of CP development in alcoholics, it can be used for investigating basic mechanisms and testing

  4. The effect of sulindac, a non-steroidal anti-inflammatory drug, attenuates inflammation and fibrosis in a mouse model of chronic pancreatitis

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    Bai Han

    2012-08-01

    Full Text Available Abstract Background Chronic pancreatitis is characterized by progressive fibrosis, pain and loss of exocrine and endocrine functions. The long-standing chronic pancreatitis and its associated pancreatic fibrosis are the most common pathogenic events involved in human pancreatic carcinogenesis, but the therapeutic strategies to chronic pancreatitis and the chemoprevention of pancreatic carcinogenesis are very limited. Methods We investigated the effect of sulindac, a non-steroidal anti-inflammatory drug (NSAID, on inhibition of chronic pancreatitis in a caerulein induced chronic pancreatitis mouse model. Results Sulindac significantly reduced the severity of chronic pancreatitis including the extent of acini loss, inflammatory cell infiltration and stromal fibrosis. The protein expression of phosphorylation of MEK/ERK was inhibited in the chronic pancreatic tissues by sulindac treatment as measured by Western blot assay. The levels of inflammatory cytokines including TNF-α and MCP-1 were also significantly decreased with sulindac treatment, as well as the expression of TGF-β, PDGF-β, SHH and Gli in the chronic pancreatic tissue detected by qPCR assay and confirmed by western blot assay. The activation of pancreatic satellet cells was also inhibited by sulindac as measured by the activity of α-smooth muscle actin (α-SMA in the pancreatic tissue of chronic pancreatitis. Conclusions Sulindac is a promising reagent for the treatment of chronic pancreatitis via inhibition of inflammatory cell infiltration and stromal fibrosis, the inhibitory effect of sulindac on chronic pancreatitis may through targeting the activation ERK/MAPK signaling pathway.

  5. Characterization of the bombesin receptor on mouse pancreatic acini by chemical cross-linking

    International Nuclear Information System (INIS)

    Bombesin (BN), gastrin-releasing peptide (GRP) and GRP(18-27) (neuromedin C) were equipotent and 30-fold more potent than neuromedin B (NMB) in inhibiting binding of 125I-GRP to and in stimulating amylase release from mouse pancreatic acini. In the present study we used 125I-GRP and chemical cross-linking techniques to characterize the mouse pancreatic BN receptor. After binding of 125I-GRP to membranes, and incubation with various chemical cross-linking agents, cross-linked radioactivity was analyzed by SDS-PAG electrophoresis and autoradiography. With each of 4 different chemical cross-linking agents, there was a single broad polypeptide band of Mr 80,000. Cross-linking did not occur in the absence of the cross-linking agent. Cross-linking was inhibited only by peptides that interact with the BN receptor such as GRP, NMB, GRP(18-27) or BN. Dose-inhibition curves for the ability of BN or NMB to inhibit binding of 125I-GRP to membranes or cross-linking to the 80,000 polypeptide demonstrated for both that BN was 15-fold more potent than NMB. The apparent molecular weight of the cross-linked polypeptide was unchanged by adding dithiothreitol. N-Glycanase treatment reduced the molecular weight of the cross-linked peptide to 40,000. The present results indicate that the BN receptor on mouse pancreatic acinar cell membranes resembles that recently described on various tumor cells in being a single glycoprotein with a molecular weight of 76,000. Because dithiothreitol had no effect, this glycoprotein is not a subunit of a larger disulfide-linked structure

  6. Characterization of the bombesin receptor on mouse pancreatic acini by chemical cross-linking

    Energy Technology Data Exchange (ETDEWEB)

    Huang, S.C.; Yu, D.H.; Wank, S.A.; Gardner, J.D.; Jensen, R.T. (National Institutes of Health, Bethesda, MD (USA))

    1990-11-01

    Bombesin (BN), gastrin-releasing peptide (GRP) and GRP(18-27) (neuromedin C) were equipotent and 30-fold more potent than neuromedin B (NMB) in inhibiting binding of {sup 125}I-GRP to and in stimulating amylase release from mouse pancreatic acini. In the present study we used {sup 125}I-GRP and chemical cross-linking techniques to characterize the mouse pancreatic BN receptor. After binding of {sup 125}I-GRP to membranes, and incubation with various chemical cross-linking agents, cross-linked radioactivity was analyzed by SDS-PAG electrophoresis and autoradiography. With each of 4 different chemical cross-linking agents, there was a single broad polypeptide band of Mr 80,000. Cross-linking did not occur in the absence of the cross-linking agent. Cross-linking was inhibited only by peptides that interact with the BN receptor such as GRP, NMB, GRP(18-27) or BN. Dose-inhibition curves for the ability of BN or NMB to inhibit binding of {sup 125}I-GRP to membranes or cross-linking to the 80,000 polypeptide demonstrated for both that BN was 15-fold more potent than NMB. The apparent molecular weight of the cross-linked polypeptide was unchanged by adding dithiothreitol. N-Glycanase treatment reduced the molecular weight of the cross-linked peptide to 40,000. The present results indicate that the BN receptor on mouse pancreatic acinar cell membranes resembles that recently described on various tumor cells in being a single glycoprotein with a molecular weight of 76,000. Because dithiothreitol had no effect, this glycoprotein is not a subunit of a larger disulfide-linked structure.

  7. MUC1 enhances tumor progression and contributes towards immunosuppression in a mouse model of spontaneous pancreatic adenocarcinoma

    Science.gov (United States)

    Tinder, Teresa L.; Subramani, Durai B.; Basu, Gargi D.; Bradley, Judy M.; Schettini, Jorge; Million, Arefayene; Skaar, Todd

    2008-01-01

    MUC1, a membrane tethered mucin glycoprotein, is overexpressed and aberrantly glycosylated in >80% of human ductal pancreatic adenocarcinoma. However, the role of MUC1 in pancreatic cancer has been elusive, partly due to the lack of an appropriate model. We report the characterization of a novel mouse model that expresses human MUC1 as a self molecule (PDA.MUC1 mice). Pancreatic tumors arise in an appropriate MUC1-tolerant background within an immune competent host. Significant enhancement in the development of pancreatic intraepithelial pre-neoplastic lesions (PanINs) and progression to adenocarcinoma is observed in PDA.MUC1 mice, possibly due to increased proliferation. Tumors from PDA.MUC1 mice express higher levels of cyclooxygenase-2 and indoleamine 2,3, dioxygenase compared to PDA mice lacking MUC1, especially during early stages of tumor development. The increased pro-inflammatory milieu correlates with an increased percentage of regulatory T cells and myeloid suppressor cells in the pancreatic tumor and tumor draining lymph nodes. Data shows that during pancreatic cancer progression, MUC1-mediated mechanisms enhance the onset and progression of the disease which in turn regulate the immune responses. Thus, the mouse model is ideally-suited for testing novel chemopreventive and therapeutic strategies against pancreatic cancer. PMID:18713982

  8. MUC1 enhances tumor progression and contributes toward immunosuppression in a mouse model of spontaneous pancreatic adenocarcinoma.

    Science.gov (United States)

    Tinder, Teresa L; Subramani, Durai B; Basu, Gargi D; Bradley, Judy M; Schettini, Jorge; Million, Arefayene; Skaar, Todd; Mukherjee, Pinku

    2008-09-01

    MUC1, a membrane tethered mucin glycoprotein, is overexpressed and aberrantly glycosylated in >80% of human ductal pancreatic adenocarcinoma. However, the role of MUC1 in pancreatic cancer has been elusive, partly due to the lack of an appropriate model. We report the characterization of a novel mouse model that expresses human MUC1 as a self molecule (PDA.MUC1 mice). Pancreatic tumors arise in an appropriate MUC1-tolerant background within an immune-competent host. Significant enhancement in the development of pancreatic intraepithelial preneoplastic lesions and progression to adenocarcinoma is observed in PDA.MUC1 mice, possibly due to increased proliferation. Tumors from PDA.MUC1 mice express higher levels of cyclooxygenase-2 and IDO compared with PDA mice lacking MUC1, especially during early stages of tumor development. The increased proinflammatory milieu correlates with an increased percentage of regulatory T cells and myeloid suppressor cells in the pancreatic tumor and tumor draining lymph nodes. Data shows that during pancreatic cancer progression, MUC1-mediated mechanisms enhance the onset and progression of the disease, which in turn regulate the immune responses. Thus, the mouse model is ideally suited for testing novel chemopreventive and therapeutic strategies against pancreatic cancer. PMID:18713982

  9. Inhibition of the ATP-sensitive potassium channel from mouse pancreatic β-cells by surfactants

    OpenAIRE

    Smith, Paul A.; Proks, Peter

    1998-01-01

    We have used patch-clamp methods to study the effects of the detergents, Cremophor, Tween 80 and Triton X100 on the KATP channel in the pancreatic β-cell from mouse.All three detergents blocked KATP channel activity with the following order of potency: Tween 80 (KiTriton X100 (Ki=350 nM)>Cremophor. In all cases the block was poorly reversible.Single-channel studies suggested that at low doses, the detergents act as slow blockers of the KATP channel.Unlike the block produced by tolbutamide, th...

  10. Permeation and gating properties of the L-type calcium channel in mouse pancreatic beta cells

    OpenAIRE

    1993-01-01

    Ba2+ currents through L-type Ca2+ channels were recorded from cell- attached patches on mouse pancreatic beta cells. In 10 mM Ba2+, single- channel currents were recorded at -70 mV, the beta cell resting membrane potential. This suggests that Ca2+ influx at negative membrane potentials may contribute to the resting intracellular Ca2+ concentration and thus to basal insulin release. Increasing external Ba2+ increased the single-channel current amplitude and shifted the current-voltage relation...

  11. Utilizing Past and Present Mouse Systems to Engineer More Relevant Pancreatic Cancer Models

    Directory of Open Access Journals (Sweden)

    Brian T DeCant

    2014-12-01

    Full Text Available The study of pancreatic cancer has prompted the development of numerous mouse models that aim to recapitulate the phenotypic and mechanistic features of this deadly malignancy. This review accomplishes two tasks. First, it provides an overview of the models that have been used as representations of both the neoplastic and carcinoma phenotypes. Second, it presents new modeling schemes that ultimately will serve to more faithfully capture the temporal and spatial progression of the human disease, providing platforms for improved understanding of the role of non-epithelial compartments in disease etiology as well as evaluating therapeutic approaches.

  12. Pancreatitis

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    2010355 Oxymatrine enhances the expression of collagen I and α-SMA in rat chronic pancreatitis. WANG Yuliang(王昱良),et al. Dept Gastroenterol ,Huanghe Hosp,Sanmenxia 472000. World Chin J Digestol 2010;18(13):1331-36. Objective To investigate the treatment effects of oxymatrine (OM) against chronic pancreatitis in rats and to explore the potential

  13. Effects of Compounded Human Ghrelin in a Mouse Model of Pancreatic Carcinoma

    Directory of Open Access Journals (Sweden)

    Atsushi Nanashima

    2016-08-01

    Full Text Available Ghrelin is a peptide that is secreted from the stomach and plays a role in appetite, weight gain, and skeletal muscle composition. Thus, compounded human ghrelin is a candidate drug for improving nutritional status after pancreatic surgery. However, in patients with pancreatic carcinomas, adverse influences on the occult tumor growth of ghrelin-induced secretion are a concern. The present study describes the effects of the administration of compounded human ghrelin on weight gain and pancreatic cancer cell growth in a mouse model. Changes in body weight and tumor growth in a subcutaneously transplanted pancreatic carcinoma cell line in vivo (5-week-old BALB/c-nu/nu mice were examined with or without the administration of compounded human ghrelin. Compounded human ghrelin was administered at 44 days after post-transplantation” Changes in weight were not significantly different between the control and compounded human ghrelin groups 8 days after compounded human ghrelin administration, and no association between weight and concentration of compounded human ghrelin was identified. Tumor growth after the administration of compounded human ghrelin was significantly lower than that of the control group, with the magnitude of the decrease being associated with increasing compounded human ghrelin concentration (p<0.05. At 6 and 8 days after compounded human ghrelin administration, increases in tumor weights of the control groups (0.5±0.3 g and 0.9±0.2 g, respectively were significantly greater than those observed for groups receiving 3, 15, and 30 nmol per kg of compounded human ghrelin (0.1 and 0.2, 0.2 and 0.3, and 0.2 and 0.3, respectively. There were no adverse effects of compounded human ghrelin administration. Plasma leptin levels were significantly lower in cancer cells compared with the control vehicle (p<0.05, which was decreased in mice receiving 30nmol per kg of compounded human ghrelin in comparison with those receiving vehicle (p<0

  14. The Cyan Fluorescent Protein (CFP Transgenic Mouse as a Model for Imaging Pancreatic Exocrine Cells

    Directory of Open Access Journals (Sweden)

    Hop S Tran Cao

    2009-03-01

    Full Text Available The use of fluorescent proteins for in vivo imaging has opened many new areas of research. Among the important advances in the field have been the development of transgenic mice expressing various fluorescent proteins. Objective To report whole-body and organ-specific fluorescence imaging to characterize the transgenic cyan fluorescent protein mouse. Design Mice were imaged using two devices. Brightfield images were obtained with the OV100 Small Animal Imaging System (Olympus Corp., Tokyo, Japan. Fluorescence imaging was performed under the cyan fluorescent protein filter using the iBox Small Animal Imaging System (UVP, Upland, CA, USA. Intervention All animals were sacrificed immediately before imaging. They were imaged before and throughout multiple steps of a complete necropsy. Harvested organs were also imaged with both devices. Selected organs were then frozen and processed for histology, fluorescence microscopy, and H&E staining. Fluorescence microscopy was performed with an Olympus IMT-2 inverted fluorescence microscope. Main outcome measure Determination of fluorescence intensity of different organs. Results Surprisingly, we found that there is differential enhancement of fluorescence among organs; most notably, the pancreas stands out from the rest of the gastrointestinal tract, displaying the strongest fluorescence of all organs in the mouse. Fluorescence microscopy demonstrated that the cyan fluorescent protein fluorescence resided in the acinar cells of the pancreas and not the islet cells. Conclusions The cyan fluorescent protein mouse should lead to a deeper understanding of pancreatic function and pathology, including cancer.

  15. Chaotic electrical activity of living β-cells in the mouse pancreatic islet

    Science.gov (United States)

    Kanno, Takahiro; Miyano, Takaya; Tokuda, Isao; Galvanovskis, Juris; Wakui, Makoto

    2007-02-01

    To test for chaotic dynamics of the insulin producing β-cell and explore its biological role, we observed the action potentials with the perforated patch clamp technique, for isolated cells as well as for intact cells of the mouse pancreatic islet. The time series obtained were analyzed using nonlinear diagnostic algorithms associated with the surrogate method. The isolated cells exhibited short-term predictability and visible determinism, in the steady state response to 10 mM glucose, while the intact cells did not. In the latter case, determinism became visible after the application of a gap junction inhibitor. This tendency was enhanced by the stimulation with tolbutamide. Our observations suggest that, thanks to the integration of individual chaotic dynamics via gap junction coupling, the β-cells will lose memory of fluctuations occurring at any instant in their electrical activity more rapidly with time. This is likely to contribute to the functional stability of the islet against uncertain perturbations.

  16. Use of the Fluidigm C1 platform for RNA sequencing of single mouse pancreatic islet cells.

    Science.gov (United States)

    Xin, Yurong; Kim, Jinrang; Ni, Min; Wei, Yi; Okamoto, Haruka; Lee, Joseph; Adler, Christina; Cavino, Katie; Murphy, Andrew J; Yancopoulos, George D; Lin, Hsin Chieh; Gromada, Jesper

    2016-03-22

    This study provides an assessment of the Fluidigm C1 platform for RNA sequencing of single mouse pancreatic islet cells. The system combines microfluidic technology and nanoliter-scale reactions. We sequenced 622 cells, allowing identification of 341 islet cells with high-quality gene expression profiles. The cells clustered into populations of α-cells (5%), β-cells (92%), δ-cells (1%), and pancreatic polypeptide cells (2%). We identified cell-type-specific transcription factors and pathways primarily involved in nutrient sensing and oxidation and cell signaling. Unexpectedly, 281 cells had to be removed from the analysis due to low viability, low sequencing quality, or contamination resulting in the detection of more than one islet hormone. Collectively, we provide a resource for identification of high-quality gene expression datasets to help expand insights into genes and pathways characterizing islet cell types. We reveal limitations in the C1 Fluidigm cell capture process resulting in contaminated cells with altered gene expression patterns. This calls for caution when interpreting single-cell transcriptomics data using the C1 Fluidigm system. PMID:26951663

  17. The early effects of ionizing radiation on pancreatic endocrine cells in mouse: an immunocytochemistry study

    International Nuclear Information System (INIS)

    Prodromal radiation sickness can occur within 30 minutes following irradiation. The early sign is a fatigue, accompanied by other symptoms including diarrhoea, intestinal cramps, nausea and vomiting. This event is often very significant. The contribution of pancreatic damage towards these post-irradiation symptoms is not clear. This study is to assess the volume density, by using the point counting method, of insulin-, glucagon-, somatostatin-, and pancreatic polypeptide-containing cells of mouse pancreas following X-irradiation with doses of 5 and 10 Gy. It uses an in vitro system sampled at 30 minutes, 1 and 3 hours. A radiation dose of 10 Gy significantly decreased the volume density of glucagon-containing cells at 1 hour incubation time and radiation doses of 5 and 10 Gy slightly decreased the volume density of somatostatin-containing cells at all time points. These changes may result in disturbances in metabolism of nutrients, which possibly lead to several symptoms (e.g. fatigue and weight loss) associated with prodromal radiation sickness

  18. X-ray phase-contrast CT of a pancreatic ductal adenocarcinoma mouse model.

    Directory of Open Access Journals (Sweden)

    Arne Tapfer

    Full Text Available To explore the potential of grating-based x-ray phase-contrast computed tomography (CT for preclinical research, a genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDAC was investigated. One ex-vivo mouse specimen was scanned with different grating-based phase-contrast CT imaging setups covering two different settings: i high-resolution synchrotron radiation (SR imaging and ii dose-reduced imaging using either synchrotron radiation or a conventional x-ray tube source. These experimental settings were chosen to assess the potential of phase-contrast imaging for two different types of application: i high-performance imaging for virtual microscopy applications and ii biomedical imaging with increased soft-tissue contrast for in-vivo applications. For validation and as a reference, histological slicing and magnetic resonance imaging (MRI were performed on the same mouse specimen. For each x-ray imaging setup, attenuation and phase-contrast images were compared visually with regard to contrast in general, and specifically concerning the recognizability of lesions and cancerous tissue. To quantitatively assess contrast, the contrast-to-noise ratios (CNR of selected regions of interest (ROI in the attenuation images and the phase images were analyzed and compared. It was found that both for virtual microscopy and for in-vivo applications, there is great potential for phase-contrast imaging: in the SR-based benchmarking data, fine details about tissue composition are accessible in the phase images and the visibility of solid tumor tissue under dose-reduced conditions is markedly superior in the phase images. The present study hence demonstrates improved diagnostic value with phase-contrast CT in a mouse model of a complex endogenous cancer, promoting the use and further development of grating-based phase-contrast CT for biomedical imaging applications.

  19. Rab27A Is Present in Mouse Pancreatic Acinar Cells and Is Required for Digestive Enzyme Secretion.

    Directory of Open Access Journals (Sweden)

    Yanan Hou

    Full Text Available The small G-protein Rab27A has been shown to regulate the intracellular trafficking of secretory granules in various cell types. However, the presence, subcellular localization and functional impact of Rab27A on digestive enzyme secretion by mouse pancreatic acinar cells are poorly understood. Ashen mice, which lack the expression of Rab27A due to a spontaneous mutation, were used to investigate the function of Rab27A in pancreatic acinar cells. Isolated pancreatic acini were prepared from wild-type or ashen mouse pancreas by collagenase digestion, and CCK- or carbachol-induced amylase secretion was measured. Secretion occurring through the major-regulated secretory pathway, which is characterized by zymogen granules secretion, was visualized by Dextran-Texas Red labeling of exocytotic granules. The minor-regulated secretory pathway, which operates through the endosomal/lysosomal pathway, was characterized by luminal cell surface labeling of lysosomal associated membrane protein 1 (LAMP1. Compared to wild-type, expression of Rab27B was slightly increased in ashen mouse acini, while Rab3D and digestive enzymes (amylase, lipase, chymotrypsin and elastase were not affected. Localization of Rab27B, Rab3D and amylase by immunofluorescence was similar in both wild-type and ashen acinar cells. The GTP-bound states of Rab27B and Rab3D in wild-type and ashen mouse acini also remained similar in amount. In contrast, acini from ashen mice showed decreased amylase release induced by CCK- or carbachol. Rab27A deficiency reduced the apical cell surface labeling of LAMP1, but did not affect that of Dextran-Texas Red incorporation into the fusion pockets at luminal surface. These results show that Rab27A is present in mouse pancreatic acinar cells and mainly regulates secretion through the minor-regulated pathway.

  20. The c-myc and PyMT oncogenes induce different tumor types in a somatic mouse model for pancreatic cancer

    OpenAIRE

    Lewis, Brian C.; Klimstra, David S.; Varmus, Harold E

    2003-01-01

    We have generated a mouse model for pancreatic cancer through the somatic delivery of oncogene-bearing avian retroviruses to mice that express TVA, the receptor for avian leukosis sarcoma virus subgroup A (ALSV-A), under the control of the elastase promoter. Delivery of ALSV-A-based RCAS vectors encoding either mouse polyoma virus middle T antigen (PyMT) or c-Myc to elastase-tv-a transgenic, Ink4a/Arf null mice induced the formation of pancreatic tumors. RCAS-PyMT induced pancreatic tumors wi...

  1. Degradation of insulin by isolated mouse pancreatic acini. Evidence for cell surface protease activity

    International Nuclear Information System (INIS)

    In the present study, we have used isolated mouse pancreatic acini were used to investigate the relationship between 125I-insulin binding and its degradation in order to probe the nature and cellular localization of the degradative process. In these cells, the proteolysis of 125I-insulin was dependent on time and cell concentration, and was saturated by unlabeled insulin with a Km of 290 nM. Since this value was much higher than the Kd for insulin binding to its receptor (1.1 nM), the data indicated that 125I-insulin degradation by acini occurred primarily via nonreceptor mechanisms. Several lines of evidence suggested that insulin was being degraded by the neutral thiol protease, insulin degrading enzyme (IDE). First, insulin degradation was inhibited by thiolreacting agents such as N-ethylmaleimide and p-chloromercuribenzoate. Second, the Km for degradation in acini was similar to the reported Km for IDE in other tissues. Third, the enzyme activity had a relative mol wt of approximately 130,000 by gel filtration, a value similar to that reported for purified IDE. Fourth, the degrading activity was removed with a specific antibody to IDE. Other lines of evidence suggested that enzymes located on the cell surface played a role in insulin degradation by acini. First, the nonpenetrating sulfhydryl reacting agent 5,5' dithiobis-2-nitrobenzoic acid blocked 125I-insulin degradation. Second, a specific antibody to IDE identified the presence of the enzyme on the cell surface. Third, chloroquine, leupeptin and antipain, agents that inhibit lysosomal function, did not influence 125I-insulin degradation. Fourth, highly purified pancreatic plasma membranes degraded 125I-insulin

  2. Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca2+ oscillations in mouse pancreatic acinar cells

    Science.gov (United States)

    Huang, Zebing; Wang, Haiyan; Wang, Jingke; Zhao, Mengqin; Sun, Nana; Sun, Fangfang; Shen, Jianxin; Zhang, Haiying; Xia, Kunkun; Chen, Dejie; Gao, Ming; Hammer, Ronald P.; Liu, Qingrong; Xi, Zhengxiong; Fan, Xuegong; Wu, Jie

    2016-01-01

    Emerging evidence demonstrates that the blockade of intracellular Ca2+ signals may protect pancreatic acinar cells against Ca2+ overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB2Rs modulate intracellular Ca2+ signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca2+ oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB2Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca2+ oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca2+ oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB2Rs eliminates ACh-induced Ca2+ oscillations and L-arginine-induced enhancement of Ca2+ signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis. PMID:27432473

  3. Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca(2+) oscillations in mouse pancreatic acinar cells.

    Science.gov (United States)

    Huang, Zebing; Wang, Haiyan; Wang, Jingke; Zhao, Mengqin; Sun, Nana; Sun, Fangfang; Shen, Jianxin; Zhang, Haiying; Xia, Kunkun; Chen, Dejie; Gao, Ming; Hammer, Ronald P; Liu, Qingrong; Xi, Zhengxiong; Fan, Xuegong; Wu, Jie

    2016-01-01

    Emerging evidence demonstrates that the blockade of intracellular Ca(2+) signals may protect pancreatic acinar cells against Ca(2+) overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB2Rs modulate intracellular Ca(2+) signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca(2+) oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB2Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca(2+) oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca(2+) oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB2Rs eliminates ACh-induced Ca(2+) oscillations and L-arginine-induced enhancement of Ca(2+) signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis. PMID:27432473

  4. Pancreatitis

    Science.gov (United States)

    ... campuses in Maryland and Arizona Research Resources Protocols, repositories, mouse models, plasmids, and more Technology Advancement & Transfer ... through its clearinghouses and education programs to increase knowledge and understanding about health and disease among patients, ...

  5. Mouse Muscle As an Ectopic Permissive Site for Human Pancreatic Development

    OpenAIRE

    Capito, C.; Simon, M.-T.; Aiello, V; Clark, A; Aigrain, Y; Ravassard, P.; Scharfmann, R.

    2013-01-01

    While sporadic human genetic studies have permitted some comparisons between rodent and human pancreatic development, the lack of a robust experimental system has not permitted detailed examination of human pancreatic development. We previously developed a xenograft model of immature human fetal pancreas grafted under the kidney capsule of immune-incompetent mice, which allowed the development of human pancreatic β-cells. Here, we compared the development of human and murine fetal pancreatic ...

  6. Diminished agonist-stimulated inositol trisphosphate generation blocks stimulus-secretion coupling in mouse pancreatic acini during diet-induced experimental pancreatitis

    International Nuclear Information System (INIS)

    Young female mice fed a choline-deficient, ethionine-supplemented (CDE) diet rapidly develop acute hemorrhagic pancreatitis. We have observed that pancreatic acini prepared from these mice are unable to secrete amylase in response to addition of the cholinergic agonist carbachol, although they retain the ability to secrete amylase in response to the Ca2+ ionophore A23187. The CDE diet does not alter the binding characteristics (Kd or the maximal number of binding sites) for muscarinic cholinergic receptors as tested using the antagonist [3H]N-methylscopolamine nor the competition for this binding by carbachol. Addition of carbachol to acini prepared from mice fed the CDE diet does not result in as marked an increase in cytosolic free Ca2+ levels as that noted in control samples (evaluated using quin2 fluorescence). These observations indicate that the CDE diet interferes with stimulus-secretion coupling in mouse pancreatic acini at a step subsequent to hormone-receptor binding and prior to Ca2+ release. This conclusion is confirmed by our finding that the hormone-stimulated generation of [3H]inositol phosphates (inositol trisphosphate, inositol bisphosphate, and inositol monophosphate) from acini labeled with [3H]myoinositol is markedly reduced in acini prepared from mice fed the CDE diet. This reduction is not due to a decrease in phosphatidylinositol-4,5-bisphosphate. This communication represents the first report of a system in which a blockade of inositol phosphate generation can be related to a physiologic defect and pathologic lesion

  7. Glucose decouples intracellular Ca2+ activity from glucagon secretion in mouse pancreatic islet alpha-cells.

    Directory of Open Access Journals (Sweden)

    Sylvain J Le Marchand

    Full Text Available The mechanisms of glucagon secretion and its suppression by glucose are presently unknown. This study investigates the relationship between intracellular calcium levels ([Ca(2+](i and hormone secretion under low and high glucose conditions. We examined the effects of modulating ion channel activities on [Ca(2+](i and hormone secretion from ex vivo mouse pancreatic islets. Glucagon-secreting α-cells were unambiguously identified by cell specific expression of fluorescent proteins. We found that activation of L-type voltage-gated calcium channels is critical for α-cell calcium oscillations and glucagon secretion at low glucose levels. Calcium channel activation depends on K(ATP channel activity but not on tetrodotoxin-sensitive Na(+ channels. The use of glucagon secretagogues reveals a positive correlation between α-cell [Ca(2+](i and secretion at low glucose levels. Glucose elevation suppresses glucagon secretion even after treatment with secretagogues. Importantly, this inhibition is not mediated by K(ATP channel activity or reduction in α-cell [Ca(2+](i. Our results demonstrate that glucose uncouples the positive relationship between [Ca(2+](i and secretory activity. We conclude that glucose suppression of glucagon secretion is not mediated by inactivation of calcium channels, but instead, it requires a calcium-independent inhibitory pathway.

  8. Efflux of radioactive nucleotides from mouse pancreatic islets prelabelled with 2-3H-adenosine

    International Nuclear Information System (INIS)

    Cultured mouse pancreatic islets were prelabelled with 2-3H-adenosine in order to monitor the efflux pattern of radioactivity and insulin. The outflow of radioactivity decreased continuously when the islets were perifused with glucose (1.67 mmol/l). When raising the glucose concentration to 16.7 mmol/l, there was a prompt inhibition of the radioactive efflux concomitant with an increased rate of insulin release. These effects were reversed when the high glucose challenge was withdrawn. Similar radioactive efflux patterns were obtained after addition of α-ketoisocaproic acid, leucine or pyruvate to the perifusion medium, and also when the islets were challenged with high glucose concentrations in the absence of calcium. Both antimycin A and glipizide stimulated the efflux of radioactivity, although only the addition of glipizide was accompanied by a stimulation of the insulin release. Nucleotides constituted approximately 90% of the total effluent radioactivity. Decrease in the radioactive AMP and ADP efflux due to high glucose was furthermore found to be the cause of the observed inhibition of the total radioactive efflux. The changes in radioactive efflux induced by glucose probably reflect changes in the intracellular concentrations of AMP and ADP. It is concluded that no simple correlation exists between radioactive efflux and insulin release and that changes in the intracellular concentrations of nucleotides may be an early event in the stimulus-secretion coupling of glucose-induced insulin release. (orig.)

  9. Efflux of radioactive nucleotides from mouse pancreatic islets prelabelled with 2-/sup 3/H-adenosine

    Energy Technology Data Exchange (ETDEWEB)

    Welsh, M.

    1982-07-01

    Cultured mouse pancreatic islets were prelabelled with 2-/sup 3/H-adenosine in order to monitor the efflux pattern of radioactivity and insulin. The outflow of radioactivity decreased continuously when the islets were perifused with glucose (1.67 mmol/l). When raising the glucose concentration to 16.7 mmol/l, there was a prompt inhibition of the radioactive efflux concomitant with an increased rate of insulin release. These effects were reversed when the high glucose challenge was withdrawn. Similar radioactive efflux patterns were obtained after addition of ..cap alpha..-ketoisocaproic acid, leucine or pyruvate to the perifusion medium, and also when the islets were challenged with high glucose concentrations in the absence of calcium. Both antimycin A and glipizide stimulated the efflux of radioactivity, although only the addition of glipizide was accompanied by a stimulation of the insulin release. Nucleotides constituted approximately 90% of the total effluent radioactivity. Decrease in the radioactive AMP and ADP efflux due to high glucose was furthermore found to be the cause of the observed inhibition of the total radioactive efflux. The changes in radioactive efflux induced by glucose probably reflect changes in the intracellular concentrations of AMP and ADP. It is concluded that no simple correlation exists between radioactive efflux and insulin release and that changes in the intracellular concentrations of nucleotides may be an early event in the stimulus-secretion coupling of glucose-induced insulin release.

  10. A bioluminescent mouse model of proliferation to highlight early stages of pancreatic cancer: A suitable tool for preclinical studies.

    Science.gov (United States)

    de Latouliere, Luisa; Manni, Isabella; Iacobini, Carla; Pugliese, Giuseppe; Grazi, Gian Luca; Perri, Pasquale; Cappello, Paola; Novelli, Franco; Menini, Stefano; Piaggio, Giulia

    2016-09-01

    Transgenic mouse models designed to recapitulate genetic and pathologic aspects of cancer are useful to study early stages of disease as well as its progression. Among several, two of the most sophisticated models for pancreatic ductal adenocarcinoma (PDAC) are the LSL-Kras(G12D/+);Pdx-1-Cre (KC) and LSL-Kras(G12D/+);LSL-Trp53(R172H/+);Pdx-1-Cre (KPC) mice, in which the Cre-recombinase regulated by a pancreas-specific promoter activates the expression of oncogenic Kras alone or in combination with a mutant p53, respectively. Non-invasive in vivo imaging offers a novel approach to preclinical studies introducing the possibility to investigate biological events in the spatio/temporal dimension. We recently developed a mouse model, MITO-Luc, engineered to express the luciferase reporter gene in cells undergoing active proliferation. In this model, proliferation events can be visualized non-invasively by bioluminescence imaging (BLI) in every body district in vivo. Here, we describe the development and characterization of MITO-Luc-KC- and -KPC mice. In these mice we have now the opportunity to follow PDAC evolution in the living animal in a time frame process. Moreover, by relating in vivo and ex vivo BLI and histopathological data we provide evidence that these mice could represents a suitable tool for pancreatic cancer preclinical studies. Our data also suggest that aberrant proliferation events take place early in pancreatic carcinogenesis, before tumour appearance. PMID:26704357

  11. Three-dimensional image study on the vascular structure after angiopoietin-1 transduction in isolated mouse pancreatic islets

    Science.gov (United States)

    He, Jing; Su, Dongming; Trucco, Massimo

    2008-02-01

    Angiopoietin-1 (Ang-1) is essential for remodeling the primitive vascular plexus during embryonic development and for reducing plasma leakage in inflammation of adult vasculature. However, the role for Ang-1 in maintenance of vascular stability in isolated pancreatic islets is not fully understood. In this study, we compared the difference of vascular morphology between Ang-1 treated (n=5) and control mouse islets (n=5) using both two- and three-dimensional optical image analysis. Isolated mouse islets were transduced with Ang-1 or Lac Z (control) vector at 37°C for 16 hours. Islets were incubated with both rat anti-CD31 antibody and rabbit anti-insulin antibody followed by incubation with Rhodamine-conjugated goat anti-rat IgG and Alexa-488 conjugated goat anti-rabbit IgG. Islets were viewed under a Nikon confocal microscope. Serial optical section images were captured and reconstructed using Nikon EZ-C1 software. Individual two-D and reconstructed three-D images were analyzed using MetaMorph Image Analysis software. Islet vascular density was determined. In two-D images, there was no significant difference of vascular density between the two groups. The vascular morphology didn't show any obvious differences in two-D images either. However, in the three-D images, we found higher vascular density and more vascular branches in the Ang-1 transducted islets and vascular dilation in control group. In conclusion, using three-D image analysis, Ang-1 displayed functions in maintenance of vascular stability and in stimulating growth of vascular branches in isolated mouse pancreatic islets. In order to study further the regeneration of different cell contents in the spherical pancreatic islet, three-D image analysis is an effective method to approach this goal.

  12. A mutation in the insulin 2 gene induces diabetes with severe pancreatic β-cell dysfunction in the Mody mouse

    OpenAIRE

    Jie WANG; Takeuchi, Toshiyuki; Tanaka, Shigeyasu; Kubo, Suely-Kunimi; Kayo, Tsuyoshi; Lu, Danhong; Takata, Kuniaki; Koizumi, Akio; Izumi, Tetsuro

    1999-01-01

    The mouse autosomal dominant mutation Mody develops hyperglycemia with notable pancreatic β-cell dysfunction. This study demonstrates that one of the alleles of the gene for insulin 2 in Mody mice encodes a protein product that substitutes tyrosine for cysteine at the seventh amino acid of the A chain in its mature form. This mutation disrupts a disulfide bond between the A and B chains and can induce a drastic conformational change of this molecule. Although there was no gross defect in the ...

  13. Direct effect of gonadal and contraceptive steroids on insulin release from mouse pancreatic islets in organ culture

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis

    1984-01-01

    Sex steroids are supposed to contribute to the normal glucose homeostasis and to the altered glucose and insulin metabolism in pregnancy and during contraception. In the present study isolated mouse pancreatic islets were maintained in tissue culture medium RPMI 1640 supplemented with 0.5% newborn...... calf serum and 100 ng/ml of one of the following steroids: oestradiol, progesterone, testosterone, megestrol acetate, medroxyprogesterone, chlormadinone acetate, norethynodrel, norethindrone acetate, and ethynyloestradiol. Release of insulin to the culture medium was measured during a 2 week culture...

  14. Lactisole inhibits the glucose-sensing receptor T1R3 expressed in mouse pancreatic β-cells.

    Science.gov (United States)

    Hamano, Kunihisa; Nakagawa, Yuko; Ohtsu, Yoshiaki; Li, Longfei; Medina, Johan; Tanaka, Yuji; Masuda, Katsuyoshi; Komatsu, Mitsuhisa; Kojima, Itaru

    2015-07-01

    Glucose activates the glucose-sensing receptor T1R3 and facilitates its own metabolism in pancreatic β-cells. An inhibitor of this receptor would be helpful in elucidating the physiological function of the glucose-sensing receptor. The present study was conducted to examine whether or not lactisole can be used as an inhibitor of the glucose-sensing receptor. In MIN6 cells, in a dose-dependent manner, lactisole inhibited insulin secretion induced by sweeteners, acesulfame-K, sucralose and glycyrrhizin. The IC50 was ∼4 mmol/l. Lactisole attenuated the elevation of cytoplasmic Ca2+ concentration ([Ca2+]c) evoked by sucralose and acesulfame-K but did not affect the elevation of intracellular cAMP concentration ([cAMP]c) induced by these sweeteners. Lactisole also inhibited the action of glucose in MIN6 cells. Thus, lactisole significantly reduced elevations of intracellular [NADH] and intracellular [ATP] induced by glucose, and also inhibited glucose-induced insulin secretion. To further examine the effect of lactisole on T1R3, we prepared HEK293 cells stably expressing mouse T1R3. In these cells, sucralose elevated both [Ca2+]c and [cAMP]c. Lactisole attenuated the sucralose-induced increase in [Ca2+]c but did not affect the elevation of [cAMP]c. Finally, lactisole inhibited insulin secretion induced by a high concentration of glucose in mouse islets. These results indicate that the mouse glucose-sensing receptor was inhibited by lactisole. Lactisole may be useful in assessing the role of the glucose-sensing receptor in mouse pancreatic β-cells. PMID:25994004

  15. Pharmacokinetics in Mouse and Comparative Effects of Frondosides in Pancreatic Cancer

    OpenAIRE

    Al Shemaili, Jasem; Parekh, Khatija A.; Newman, Robert A; Hellman, Björn; Woodward, Carl; Adem, Abdu; Collin, Peter; Thomas E Adrian

    2016-01-01

    The frondosides are triterpenoid glycosides from the Atlantic sea cucumber Cucumaria frondosa. Frondoside A inhibits growth, invasion, metastases and angiogenesis and induces apoptosis in diverse cancer types, including pancreatic cancer. We compared the growth inhibitory effects of three frondosides and their aglycone and related this to the pharmocokinetics and route of administration. Frondoside A potently inhibited growth of pancreatic cancer cells with an EC50 of ~1 µM. Frondoside B was ...

  16. Imaging-Guided Curative Surgical Resection of Pancreatic Cancer in a Xenograft Mouse Model

    OpenAIRE

    Ni, Xiaoling; Yang, Jingxuan; Min LI

    2012-01-01

    Pancreatic cancer is the fourth leading cause of cancer related deaths in North America. The poor survival statistics are due to the fact that there are no reliable tests for early diagnosis and no effective therapies once metastasis has occurred. Surgical resection is the only curative treatment for pancreatic cancer; however, only less than 15% of the patients are eligible for surgery at diagnosis. New therapies are urgently needed for this malignant disease. And combinational therapy inclu...

  17. Metabonomic studies of pancreatic cancer response to radiotherapy in a mouse xenograft model using magnetic resonance spectroscopy and principal components analysis

    Directory of Open Access Journals (Sweden)

    Xin-Hong He

    2013-01-01

    Full Text Available AIM: To investigate the metabolic profiles of xenograft pancreatic cancer before and after radiotherapy by high-resolution magic angle spinning proton magnetic resonance spectroscopy (HRMAS 1H NMR combined with principal components analysis (PCA and evaluate the radiotherapeutic effect. METHODS: The nude mouse xenograft model of human pancreatic cancer was established by injecting human pancreatic cancer cell SW1990 subcutaneously into the nude mice. When the tumors volume reached 800 mm3, the mice received various radiation doses. Two weeks later, tumor tissue sections were prepared for running the NMR measurements. 1H NMR and PCA were used to determine the changes in the metabolic profiles of tumor tissues after radiotherapy. Metabolic profiles of normal pancreas, pancreatic tumor tissues, and radiation- treated pancreatic tumor tissues were compared. RESULTS: Compared with 1H NMR spectra of the normal nude mouse pancreas, the levels of choline, taurine, alanine, isoleucine, leucine, valine, lactate, and glutamic acid of the pancreatic cancer group were increased, whereas an opposite trend for phosphocholine, glycerophosphocholine, and betaine was observed. The ratio of phosphocholine to creatine, and glycerophosphocholine to creatine showed noticeable decrease in the pancreatic cancer group. After further evaluation of the tissue metabolic profile after treatment with three different radiation doses, no significant change in metabolites was observed in the 1H NMR spectra, while the inhibition of tumor growth was in proportion to the radiation doses. However, PCA results showed that the levels of choline and betaine were decreased with the increased radiation dose, and conversely, the level of acetic acid was dramatically increased. CONCLUSION: The combined methods were demonstrated to have the potential for allowing early diagnosis and assessment of pancreatic cancer response to radiotherapy.

  18. Assessment and optimization of electroporation-assisted tumoral nanoparticle uptake in a nude mouse model of pancreatic ductal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    West DL

    2014-09-01

    nanoparticles as a function of electroporation voltage and timing of administration in pancreatic adenocarcinoma cells. Our studies demonstrated that addition of electroporation to administration of nanoparticles significantly increased the amount of intracellular iron oxide nanoparticle uptake by a PANC-1 cell line in an athymic nude mouse model of PDAC. Further, electroporation-assisted nanoparticle uptake could be significantly altered by changing the timing of application of electroporation. Keywords: electroporation, nanoparticles, tumoral uptake, pancreatic adenocarcinoma, in vivo

  19. ATP-consuming and ATP-generating enzymes secreted by pancreas

    DEFF Research Database (Denmark)

    Yegutkin, Gennady G; Samburski, Sergei S; Jalkanen, Sirpa;

    2006-01-01

    -generating enzymes in pancreatic juice, adenylate kinase, and NDP kinase, capable of sequentially phosphorylating AMP via ADP to ATP. Activities of nonspecific phosphatases, nucleotide pyrophosphatase/phosphodiesterases, and adenosine deaminase were negligible. Taken together, CCK-8 stimulation of pancreas causes...

  20. Genetic deletion of the desmosomal component desmoplakin promotes tumor microinvasion in a mouse model of pancreatic neuroendocrine carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Matthew G H Chun

    2010-09-01

    Full Text Available We used the RIP1-Tag2 (RT2 mouse model of islet cell carcinogenesis to profile the transcriptome of pancreatic neuroendocrine tumors (PNET that were either non-invasive or highly invasive, seeking to identify pro- and anti-invasive molecules. Expression of multiple components of desmosomes, structures that help maintain cellular adhesion, was significantly reduced in invasive carcinomas. Genetic deletion of one of these desmosomal components, desmoplakin, resulted in increased local tumor invasion without affecting tumor growth parameters in RT2 PNETs. Expression of cadherin 1, a component of the adherens junction adhesion complex, was maintained in these tumors despite the genetic deletion of desmoplakin. Our results demonstrate that loss of desmoplakin expression and resultant disruption of desmosomal adhesion can promote increased local tumor invasion independent of adherens junction status.

  1. The Influence of Bone Marrow-Secreted IL-10 in a Mouse Model of Cerulein-Induced Pancreatic Fibrosis

    Science.gov (United States)

    Lin, Wey-Ran; Lim, Siew-Na; Yen, Tzung-Hai; Alison, Malcolm R.

    2016-01-01

    This study aimed to understand the role of IL-10 secreted from bone marrow (BM) in a mouse model of pancreatic fibrosis. The severity of cerulein-induced inflammation, fibrosis, and the frequency of BM-derived myofibroblasts were evaluated in the pancreas of mice receiving either a wild-type (WT) BM or an IL-10 knockout (KO) BM transplantation. The area of collagen deposition increased significantly in the 3 weeks after cerulein cessation in mice with an IL-10 KO BM transplant (13.7 ± 0.6% and 18.4 ± 1.1%, p < 0.05), but no further increase was seen in WT BM recipients over this time. The percentage of BM-derived myofibroblasts also increased in the pancreas of the IL-10 KO BM recipients after cessation of cerulein (6.7 ± 1.1% and 11.9 ± 1.3%, p < 0.05), while this figure fell in WT BM recipients after cerulein withdrawal. Furthermore, macrophages were more numerous in the IL-10 KO BM recipients than the WT BM recipients after cerulein cessation (23.2 ± 2.3 versus 15.3 ± 1.7 per HPF, p < 0.05). In conclusion, the degree of fibrosis, inflammatory cell infiltration, and the number of BM-derived myofibroblasts were significantly different between IL-10 KO BM and WT BM transplanted mice, highlighting a likely role of IL-10 in pancreatitis. PMID:27314021

  2. Convergence of bone morphogenetic protein and laminin-1 signaling pathways promotes proliferation and colony formation by fetal mouse pancreatic cells

    International Nuclear Information System (INIS)

    We previously reported that bone morphogenetic proteins (BMPs), members of the transforming growth factor superfamily, together with the basement membrane glycoprotein laminin-1 (Ln-1), promote proliferation of fetal pancreatic cells and formation of colonies containing peripheral insulin-positive cells. Here, we further investigate the cross-talk between BMP and Ln-1 signals. By RT-PCR, receptors for BMP (BMPR) (excepting BMPR-1B) and Ln-1 were expressed in the fetal pancreas between E13.5 and E17.5. Specific blocking antibodies to BMP-4 and -6 and selective BMP antagonists partially inhibited colony formation by fetal pancreas cells. Colony formation induced by BMP-6 and Ln-1 was completely abolished in a dose-dependent manner by blocking Ln-1 binding to its α6 integrin and α-dystroglycan receptors or by blocking the Ln-1 signaling molecules, phosphatidyl-inositol-3-kinase (P13K) and MAP kinase kinase-1. These results demonstrate a convergence of BMP and Ln-1 signaling through P13K and MAP kinase pathways to induce proliferation and colony formation in E15.5 fetal mouse pancreatic cells

  3. Ca2+ controls slow NAD(P)H oscillations in glucose-stimulated mouse pancreatic islets

    DEFF Research Database (Denmark)

    Luciani, Dan Seriano; Misler, S.; Polonsky, K.S.

    2006-01-01

    Exposure of pancreatic islets of Langerhans to physiological concentrations of glucose leads to secretion of insulin in an oscillatory pattern. The oscillations in insulin secretion are associated with oscillations in cytosolic Ca2+ concentration ([Ca2+](c)). Evidence suggests that the oscillations...

  4. An adenylate kinase is involved in KATP channel regulation of mouse pancreatic beta cells.

    NARCIS (Netherlands)

    Schulze, D.U.; Dufer, M.; Wieringa, B.; Krippeit-Drews, P.; Drews, G.

    2007-01-01

    AIMS/HYPOTHESIS: In a previous study, we demonstrated that a creatine kinase (CK) modulates K(ATP) channel activity in pancreatic beta cells. To explore phosphotransfer signalling pathways in more detail, we examined whether K(ATP) channel regulation in beta cells is determined by a metabolic intera

  5. Abnormal mitochondrial function impairs calcium influx in diabetic mouse pancreatic beta cells

    Institute of Scientific and Technical Information of China (English)

    LI Fei; D. Marshall Porterfield; ZHENG Xi-yan; WANG Wen-jun; XU Yue; ZHANG Zong-ming

    2012-01-01

    Background Abnormal insulin secretion of pancreatic beta cells is now regarded as the more primary defect than the insulin function in the etiology of type 2 diabetes.Previous studies found impaired mitochondrial function and impaired Ca2+ influx in beta cells in diabetic patients and animal models,suggesting a role for these processes in proper insulin secretion.The aim of this study was to investigate the detailed relationship of mitochondrial function,Ca2+ influx,and defective insulin secretion.Methods We investigated mitochondrial function and morphology in pancreatic beta cell of diabetic KK-Ay mice and C57BL/6J mice.Two types of Ca2+ channel activities,L-type and store-operated Ca2+ (SOC),were evaluated using whole-cell patch-clamp recording.The glucose induced Ca2+ influx was measured by a non-invasive micro-test technique (NMT).Results Mitochondria in KK-Ay mice pancreatic beta cells were swollen with disordered cristae,and mitochondrial function decreased compared with C57BL/6J mice.Ca2+ channel activity was increased and glucose induced Ca2+ influx was impaired,but could be recovered by genipin.Conclusion Defective mitochondrial function in diabetic mice pancreatic beta cells is a key cause of abnormal insulin secretion by altering Ca2+ influx,but not via Ca2+ channel activity.

  6. Ultrasound-guided direct delivery of 3-bromopyruvate blocks tumor progression in an orthotopic mouse model of human pancreatic cancer.

    Science.gov (United States)

    Ota, Shinichi; Geschwind, Jean-Francois H; Buijs, Manon; Wijlemans, Joost W; Kwak, Byung Kook; Ganapathy-Kanniappan, Shanmugasundaram

    2013-06-01

    Studies in animal models of cancer have demonstrated that targeting tumor metabolism can be an effective anticancer strategy. Previously, we showed that inhibition of glucose metabolism by the pyruvate analog, 3-bromopyruvate (3-BrPA), induces anticancer effects both in vitro and in vivo. We have also documented that intratumoral delivery of 3-BrPA affects tumor growth in a subcutaneous tumor model of human liver cancer. However, the efficacy of such an approach in a clinically relevant orthotopic tumor model has not been reported. Here, we investigated the feasibility of ultrasound (US) image-guided delivery of 3-BrPA in an orthotopic mouse model of human pancreatic cancer and evaluated its therapeutic efficacy. In vitro, treatment of Panc-1 cells with 3-BrPA resulted in a dose-dependent decrease in cell viability. The loss of viability correlated with a dose-dependent decrease in the intracellular ATP level and lactate production confirming that disruption of energy metabolism underlies these 3-BrPA-mediated effects. In vivo, US-guided delivery of 3-BrPA was feasible and effective as demonstrated by a marked decrease in tumor size on imaging. Further, the antitumor effect was confirmed by (1) a decrease in the proliferative potential by Ki-67 immunohistochemical staining and (2) the induction of apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphospate nick end labeling staining. We therefore demonstrate the technical feasibility of US-guided intratumoral injection of 3-BrPA in a mouse model of human pancreatic cancer as well as its therapeutic efficacy. Our data suggest that this new therapeutic approach consisting of a direct intratumoral injection of antiglycolytic agents may represent an exciting opportunity to treat patients with pancreas cancer. PMID:23529644

  7. Embryonic mouse blood flow and oxygen correlate with early pancreatic differentiation

    OpenAIRE

    Shah, Sohail R.; ESNI, FARZAD; Jakub, Adam; Paredes, Jose; Lath, Nikesh; Malek, Marcus; Potoka, Douglas A.; Prasadan, Krishna; Mastroberardino, Pier G.; Shiota, Chiyo; Guo, Ping; Miller, Kelly A.; Hackam, David J.; Burns, R. Cartland; Tulachan, Sidhartha S.

    2010-01-01

    The mammalian embryo represents a fundamental paradox in biology. Its location within the uterus, especially early during development when embryonic cardiovascular development and placental blood flow are not well-established, leads to an obligate hypoxic environment. Despite this hypoxia, the embryonic cells are able to undergo remarkable growth, morphogenesis, and differentiation. Recent evidence suggests that embryonic organ differentiation, including pancreatic β-cells, is tightly regulat...

  8. Targeting the insulin growth factor-1 receptor with fluorescent antibodies enables high resolution imaging of human pancreatic cancer in orthotopic mouse models

    Science.gov (United States)

    Park, Jeong Youp; Lee, Jin Young; Zhang, Yong; Hoffman, Robert M.; Bouvet, Michael

    2016-01-01

    The goal of the present study was to determine whether insulin-like growth factor-1 receptor (IGF-1R) antibodies, conjugated with bright fluorophores, could enable visualization of pancreatic cancer in orthotopic nude mouse models. IGF-1R antibody (clone 24-31) was conjugated with 550 nm or 650 nm fluorophores. Western blotting confirmed the expression of IGF-1R in Panc-1, BxPC3, and MIAPaCa-2 human pancreatic cancer cell lines. Labeling with fluorophore-conjugated IGF-1R antibody demonstrated fluorescent foci on the membrane of the pancreatic cancer cells. Subcutaneous Panc-1, BxPC-3, and MIA PaCa-2 tumors became fluorescent after intravenous administration of fluorescent IGF-1R antibodies. Orthotopically-transplanted BxPC-3 tumors became fluorescent with the conjugated IGF-1R antibodies, and were easily visible with intravital imaging. Gross and microscopic ex vivo imaging of resected pancreatic tumor and normal pancreas confirmed that fluorescence indeed came from the membrane of cancer cells, and it was stronger from the tumor than the normal tissue. The present study demonstrates that fluorophore-conjugated IGF-1R antibodies can visualize pancreatic cancer and it can be used with various imaging devices such as endoscopy and laparoscopy for diagnosis and fluorescence-guided surgery. PMID:26919100

  9. Pharmacokinetics in Mouse and Comparative Effects of Frondosides in Pancreatic Cancer.

    Science.gov (United States)

    Al Shemaili, Jasem; Parekh, Khatija A; Newman, Robert A; Hellman, Björn; Woodward, Carl; Adem, Abdu; Collin, Peter; Adrian, Thomas E

    2016-01-01

    The frondosides are triterpenoid glycosides from the Atlantic sea cucumber Cucumaria frondosa. Frondoside A inhibits growth, invasion, metastases and angiogenesis and induces apoptosis in diverse cancer types, including pancreatic cancer. We compared the growth inhibitory effects of three frondosides and their aglycone and related this to the pharmocokinetics and route of administration. Frondoside A potently inhibited growth of pancreatic cancer cells with an EC50 of ~1 µM. Frondoside B was less potent (EC50 ~2.5 µM). Frondoside C and the aglycone had no effect. At 100 µg/kg, frondoside A administered to CD₂F₁ mice as an i.v. bolus, the Cpmax was 129 nM, Cltb was 6.35 mL/min/m², and half-life was 510 min. With i.p. administration the Cpmax was 18.3 nM, Cltb was 127 mL/min/m² and half-life was 840 min. Oral dosing was ineffective. Frondoside A (100 µg/kg/day i.p.) markedly inhibited growth cancer xenografts in nude mice. The same dose delivered by oral gavage had no effect. No evidence of acute toxicity was seen with frondoside A. Frondoside A is more potent inhibitor of cancer growth than other frondosides. The glycoside component is essential for bioactivity. Frondoside A is only effective when administered systemically. Based on the current and previous studies, frondoside A appears safe and may be valuable in the treatment of cancer. PMID:27322291

  10. Pharmacokinetics in Mouse and Comparative Effects of Frondosides in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Jasem Al Shemaili

    2016-06-01

    Full Text Available The frondosides are triterpenoid glycosides from the Atlantic sea cucumber Cucumaria frondosa. Frondoside A inhibits growth, invasion, metastases and angiogenesis and induces apoptosis in diverse cancer types, including pancreatic cancer. We compared the growth inhibitory effects of three frondosides and their aglycone and related this to the pharmocokinetics and route of administration. Frondoside A potently inhibited growth of pancreatic cancer cells with an EC50 of ~1 µM. Frondoside B was less potent (EC50 ~2.5 µM. Frondoside C and the aglycone had no effect. At 100 µg/kg, frondoside A administered to CD2F1 mice as an i.v. bolus, the Cpmax was 129 nM, Cltb was 6.35 mL/min/m2, and half-life was 510 min. With i.p. administration the Cpmax was 18.3 nM, Cltb was 127 mL/min/m2 and half-life was 840 min. Oral dosing was ineffective. Frondoside A (100 µg/kg/day i.p. markedly inhibited growth cancer xenografts in nude mice. The same dose delivered by oral gavage had no effect. No evidence of acute toxicity was seen with frondoside A. Frondoside A is more potent inhibitor of cancer growth than other frondosides. The glycoside component is essential for bioactivity. Frondoside A is only effective when administered systemically. Based on the current and previous studies, frondoside A appears safe and may be valuable in the treatment of cancer.

  11. Predictive imaging of chemotherapeutic response in a transgenic mouse model of pancreatic cancer.

    Science.gov (United States)

    Wang, Ping; Yoo, Byunghee; Sherman, Sarah; Mukherjee, Pinku; Ross, Alana; Pantazopoulos, Pamela; Petkova, Victoria; Farrar, Christian; Medarova, Zdravka; Moore, Anna

    2016-08-01

    The underglycosylated mucin 1 tumor antigen (uMUC1) is a biomarker that forecasts the progression of adenocarcinomas. In this study, we evaluated the utility of a dual-modality molecular imaging approach based on targeting uMUC1 for monitoring chemotherapeutic response in a transgenic murine model of pancreatic cancer (KCM triple transgenic mice). An uMUC1-specific contrast agent (MN-EPPT) was synthesized for use with magnetic resonance imaging (MRI) and fluorescence optical imaging. It consisted of dextran-coated iron oxide nanoparticles conjugated to the near infrared fluorescent dye Cy5.5 and to a uMUC1-specific peptide (EPPT). KCM triple transgenic mice were given gemcitabine as chemotherapy while control animals received saline injections following the same schedule. Changes in uMUC1 levels following chemotherapy were monitored using T2-weighted MRI and optical imaging before and 24 hr after injection of the MN-EPPT. uMUC1 expression in tumors from both groups was evaluated by histology and qRT-PCR. We observed that the average delta-T2 in the gemcitabine-treated group was significantly reduced compared to the control group indicating lower accumulation of MN-EPPT, and correspondingly, a lower level of uMUC1 expression. In vivo optical imaging confirmed the MRI findings. Fluorescence microscopy of pancreatic tumor sections showed a lower level of uMUC1 expression in the gemcitabine-treated group compared to the control, which was confirmed by qRT-PCR. Our data proved that changes in uMUC1 expression after gemcitabine chemotherapy could be evaluated using MN-EPPT-enhanced in vivo MR and optical imaging. These results suggest that the uMUC1-targeted imaging approach could provide a useful tool for the predictive assessment of therapeutic response. PMID:26996122

  12. Beneficial renal and pancreatic phenotypes in a mouse deficient in FXYD2 regulatory subunit of Na,K-ATPase

    Directory of Open Access Journals (Sweden)

    Elena eArystarkhova

    2016-03-01

    Full Text Available The fundamental role of Na,K-ATPase in eukaryotic cells calls for complex and efficient regulation of its activity. Besides alterations in gene expression and trafficking, kinetic properties of the pump are modulated by reversible association with single span membrane proteins, the FXYDs. Seven members of the family are expressed in a tissue-specific manner, affecting pump kinetics in all possible permutations. This mini-review focuses on functional properties of FXYD2 studied in transfected cells, and on noteworthy and unexpected phenotypes discovered in a Fxyd2-/- mouse. FXYD2, the gamma subunit, reduces activity of Na,K-ATPase either by decreasing affinity for Na+, or reducing Vmax. FXYD2 mRNA splicing and editing provide another layer for regulation of Na,K-ATPase. In kidney of knockouts, there was elevated activity for Na,K-ATPase and for NCC and NKCC2 apical sodium transporters. That should lead to sodium retention and hypertension, however, the mice were in sodium balance and normotensive. Adult Fxyd2-/- mice also exhibited a mild pancreatic phenotype with enhanced glucose tolerance, elevation of circulating insulin, but no insulin resistance. There was an increase in beta cell proliferation and beta cell mass that correlated with activation of the PI3K-Akt pathway. The Fxyd2-/- mice are thus in a highly desirable state: the animals are resistant to Na+ retention, and showed improved glucose control, i.e. they display favorable metabolic adaptations to protect against development of salt-sensitive hypertension and diabetes. Investigation of the mechanisms of these adaptations in the mouse has the potential to unveil a novel therapeutic FXYD2-dependent strategy.

  13. Piperlongumine Suppresses Growth and Sensitizes Pancreatic Tumors to Gemcitabine in a Xenograft Mouse Model by Modulating the NF-kappa B Pathway.

    Science.gov (United States)

    Wang, Yongwei; Wu, Xiangsong; Zhou, Yinan; Jiang, Hongchi; Pan, Shangha; Sun, Bei

    2016-03-01

    Pancreatic cancer is an aggressive malignancy, which generally respond poorly to chemotherapy. Hence, novel agents that are safe and effective are highly needed. The aim of this study was to investigate whether piperlongumine, a natural product isolated from the fruit of the pepper Piper longum, has any efficacy against human pancreatic cancer when used either alone or in combination with gemcitabine in vitro and in a xenograft mouse model. In vitro, piperlongumine inhibited the proliferation of pancreatic cancer cell lines, potentiated the apoptotic effects of gemcitabine, inhibited the constitutive and inducible activation of NF-κB, and suppressed the NF-κB-regulated expression of c-Myc, cyclin D1, Bcl-2, Bcl-xL, Survivin, XIAP, VEGF, and matrix metalloproteinase-9 (MMP-9). Furthermore, in an in vivo xenograft model, we found piperlongumine alone significantly suppressed tumor growth and enhanced the antitumor properties of gemcitabine. These results were consistent with the downregulation of NF-κB activity and its target genes, decreased proliferation (PCNA and Ki-67), decreased microvessel density (CD31), and increased apoptosis (TUNEL) in tumor remnants. Collectively, our results suggest that piperlongumine alone exhibits significant antitumor effects against human pancreatic cancer and it further enhances the therapeutic effects of gemcitabine, possibly through the modulation of NF-κB- and NF-κB-regulated gene products. PMID:26667450

  14. Bipotential mouse embryonic liver (BMEL cells spontaneously express Pdx1 and Ngn3 but do not undergo further pancreatic differentiation upon Hes1 down-regulation

    Directory of Open Access Journals (Sweden)

    Martignat Lionel

    2008-12-01

    Full Text Available Abstract Background Liver-to-pancreas conversion offers new possibilities for β-cell engineering for type 1 diabetes therapy. Among conceivable sources of liver cells, we focused on BMEL cells. These untransformed mouse embryonic liver cells have been reproducibly isolated from different inbred mice strains and have the potential to differentiate into hepatocytes and cholangiocytes in vitro and in vivo. Findings Strikingly, we find here that adherent BMEL cells display functional similarities with multipotent pancreatic precursor cells, namely Pdx1 and Ngn3 expression, and further express Hnf6 in floating aggregate culture. Hes1, a direct repressor of Ngn3 and pancreatic endocrine commitment, is expressed in adherent BMEL cells and decreases with time in aggregate culture. However, Hes1 decrease fails to initiate activation of late-stage pancreatic endocrine transcription factors. Conclusion Here we report that BMEL cells present features of pancreatic endocrine progenitor cells. In the field of diabetes research, BMEL cells are of potential interest for the study of inductive signals critical for in vitro β-cell maturation in-liver-to-pancreas conversion.

  15. A Novel Chimeric Antigen Receptor Against Prostate Stem Cell Antigen Mediates Tumor Destruction in a Humanized Mouse Model of Pancreatic Cancer

    Science.gov (United States)

    Lagisetty, Kiran H.; Tran, Eric; Zheng, Zhili; Gattinoni, Luca; Yu, Zhiya; Burns, William R.; Miermont, Anne M.; Teper, Yaroslav; Rudloff, Udo; Restifo, Nicholas P.; Feldman, Steven A.; Rosenberg, Steven A.; Morgan, Richard A.

    2014-01-01

    Abstract Despite advances in the understanding of its molecular pathophysiology, pancreatic cancer remains largely incurable, highlighting the need for novel therapies. We developed a chimeric antigen receptor (CAR) specific for prostate stem cell antigen (PSCA), a glycoprotein that is overexpressed in pancreatic cancer starting at early stages of malignant transformation. To optimize the CAR design, we used antigen-recognition domains derived from mouse or human antibodies, and intracellular signaling domains containing one or two T cell costimulatory elements, in addition to CD3zeta. Comparing multiple constructs established that the CAR based on human monoclonal antibody Ha1-4.117 had the greatest reactivity in vitro. To further analyze this CAR, we developed a human pancreatic cancer xenograft model and adoptively transferred CAR-engineered T cells into animals with established tumors. CAR-engineered human lymphocytes induced significant antitumor activity, and unlike what has been described for other CARs, a second-generation CAR (containing CD28 cosignaling domain) induced a more potent antitumor effect than a third-generation CAR (containing CD28 and 41BB cosignaling domains). While our results provide evidence to support PSCA as a target antigen for CAR-based immunotherapy of pancreatic cancer, the expression of PSCA on selected normal tissues could be a source of limiting toxicity. PMID:24694017

  16. Chronic pancreatitis

    Science.gov (United States)

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... abuse over many years. Repeated episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be ...

  17. Divergent effects of liraglutide, exendin-4, and sitagliptin on beta-cell mass and indicators of pancreatitis in a mouse model of hyperglycaemia.

    Directory of Open Access Journals (Sweden)

    Angeles Mondragon

    Full Text Available Glucagon-like peptide-1 (GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP4 inhibitors improve glucose tolerance by still incompletely understood mechanisms. Each class of antihyperglycemic drugs has also been proposed to increase pancreatitis risk. Here, we compare systematically the effects of two widely-used GLP-1 analogues, liraglutide and exendin-4, and the DPP4 inhibitor, sitagliptin, in the mouse.C57BL6 mice were maintained for 131 days on a normal diet (ND or a diet comprising 60% fat (HFD before measurements of fasting blood glucose and insulin, and intraperitoneal glucose tolerance. Beta- and alpha- cell volume, and Reg3b immunoreactivity, were measured by immunohistochemical analysis of pancreatic slices.Whereas liraglutide (200 µg/kg and exendin-4 (10 µg/kg treatment reduced body weight and/or improved glucose tolerance, sitagliptin (10 mg/kg was without effect on either parameter. Liraglutide caused a sharp reduction in beta-cell mass in both ND and HFD mice, whereas exendin-4 exerted no effect. By contrast, sitagliptin unmasked an action of high fat diet to increase beta-cell mass. Reg3B positive area was augmented by all three agents in normal chow-fed mice, whilst sitagliptin and exendin-4, but not liraglutide, affected this parameter in HFD animals. Correspondingly sitagliptin, but not the GLP-1 analogues, increased circulating amylase levels in ND and HFD mice.Liraglutide improves glucose tolerance in the mouse whilst exerting relatively modest effects on pancreatitis risk. Conversely, exendin-4 and sitagliptin, at doses which exert, respectively, minor or no effects on metabolic parameters, lead to signs of pancreatitis.

  18. cPLA2alpha-evoked formation of arachidonic acid and lysophospholipids is required for exocytosis in mouse pancreatic beta-cells

    DEFF Research Database (Denmark)

    Juhl, Kirstine; Høy, Marianne; Olsen, Hervør L;

    2003-01-01

    Using capacitance measurements, we investigated the effects of intracellularly applied recombinant human cytosolic phospholipase A2 (cPLA2alpha) and its lipolytic products arachidonic acid and lysophosphatidylcholine on Ca2+-dependent exocytosis in single mouse pancreatic beta-cells. cPLA2alpha...... dose dependently (EC50 = 86 nM) stimulated depolarization-evoked exocytosis by 450% without affecting the whole cell Ca2+ current or cytoplasmic Ca2+ levels. The stimulatory effect involved priming of secretory granules as reflected by an increase in the size of the readily releasable pool of granules...

  19. cPLA2a-evoked formation of arachidonic acid and lysophospholipids is required for exocytosis in mouse pancreatic ß-cells

    DEFF Research Database (Denmark)

    Juhl, Kirstine; Høy, Marianne; Olsen, Hervør L.;

    2003-01-01

    Using capacitance measurements, we investigated the effects of intracellularly applied recombinant human cytosolic phospholipase A2 (cPLA2 ) and its lipolytic products arachidonic acid and lysophosphatidylcholine on Ca2+-dependent exocytosis in single mouse pancreatic -cells. cPLA2 dose dependently...... (EC50 = 86 nM) stimulated depolarization-evoked exocytosis by 450% without affecting the whole cell Ca2+ current or cytoplasmic Ca2+ levels. The stimulatory effect involved priming of secretory granules as reflected by an increase in the size of the readily releasable pool of granules from 70...

  20. Preliminary evaluation of 1′-[18F]fluoroethyl-β-D-lactose ([18F]FEL) for detection of pancreatic cancer in nude mouse orthotopic xenografts

    International Nuclear Information System (INIS)

    Introduction: Early detection of pancreatic cancer could save many thousands of lives. Non-invasive diagnostic imaging, including PET with [18F]FDG, has inadequate resolution for detection of small (2–3 mm) pancreatic tumours. We demonstrated the efficacy of PET imaging with an 18F-labelled lactose derivative, [18F]FEDL, that targets HIP/PAP, a biomarker that is overexpressed in the peritumoural pancreas. We developed another analogue, 1-[18F]fluoroethyl lactose ([18F]FEL), which is simpler to synthesise, for the same application. We conducted a preliminary evaluation of the new probe and its efficacy in detecting orthotopic pancreatic carcinoma xenografts in mice. Methods: Xenografts were developed in nude mice by injecting L3.6pl/GL+ pancreatic carcinoma cells into the pancreas of each mouse. Tumour growth was monitored by bioluminescence imaging (BLI); accuracy of BLI tumour size estimates was verified by MRI in two representative mice. When the tumour size reached approximately 2–3 mm, the animals were injected with [18F]FEL (3.7 MBq) and underwent static PET/CT scans. Blood samples were collected at 2, 5, 10, 20 and 60 min after [18F]FEL injection to track blood clearance. Following imaging, animals were sacrificed and their organs and tumours/pancreatic tissue were collected and counted on a gamma counter. Pancreas, including tumour, was frozen, sliced and used for autoradiography and immunohistochemical analysis of HIP/PAP expression. Results: Tumour growth was rapid, as observed by BLI and MRI. Blood clearance of [18F]FEL was bi-exponential, with half-lives of approximately 3.5 min and 40 min. Mean accumulation of [18F]FEL in the peritumoural pancreatic tissue was 1.29 ± 0.295 %ID/g, and that in the normal pancreas of control animals was 0.090 ± 0.101 %ID/g. [18F]FEL was cleared predominantly by the kidneys. Comparative analysis of autoradiographic images and immunostaining results demonstrated a correlation between [18F]FEL binding and HIP

  1. Tat-ATOX1 inhibits streptozotocin-induced cell death in pancreatic RINm5F cells and attenuates diabetes in a mouse model.

    Science.gov (United States)

    Ahn, Eun Hee; Kim, Dae Won; Shin, Min Jea; Ryu, Eun Ji; Yong, Ji In; Chung, Seok Young; Cha, Hyun Ju; Kim, Sang Jin; Choi, Yeon Joo; Kim, Duk-Soo; Cho, Sung-Woo; Lee, Keunwook; Cho, Yoon Shin; Kwon, Hyeok Yil; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

    2016-07-01

    Antioxidant 1 (ATOX1) functions as an antioxidant against hydrogen peroxide and superoxide, and therefore may play a significant role in many human diseases, including diabetes mellitus (DM). In the present study, we examined the protective effects of Tat-ATOX1 protein on streptozotocin (STZ)-exposed pancreatic insulinoma cells (RINm5F) and in a mouse model of STZ-induced diabetes using western blot analysis, immunofluorescence staining and MTT assay, as well as histological and biochemical analysis. Purified Tat-ATOX1 protein was efficiently transduced into RINm5F cells in a dose- and time-dependent manner. Additionally, Tat-ATOX1 protein markedly inhibited reactive oxygen species (ROS) production, DNA damage and the activation of Akt and mitogen activated protein kinases (MAPKs) in STZ-exposed RINm5F cells. In addition, Tat-ATOX1 protein transduced into mice pancreatic tissues and significantly decreased blood glucose and hemoglobin A1c (HbA1c) levels as well as the body weight changes in a model of STZ-induced diabetes. These results indicate that transduced Tat-ATOX1 protein protects pancreatic β-cells by inhibiting STZ-induced cellular toxicity in vitro and in vivo. Based on these findings, we suggest that Tat-ATOX1 protein has potential applications as a therapeutic agent for oxidative stress-induced diseases including DM. PMID:27222268

  2. Inhibition of Human Pancreatic Tumor Growth by Cytokine-Induced Killer Cells in Nude Mouse Xenograft Model

    OpenAIRE

    Kim, Ji Sung; Park, Yun Soo; Kim, Ju Young; Kim, Yong Guk; Kim, Yeon Jin; Lee, Hong Kyung; Kim, Hyung Sook; Hong, Jin Tae; Kim, Youngsoo; Han, Sang-Bae

    2012-01-01

    Pancreatic cancer is the fourth commonest cause of cancer-related deaths in the world. However, no adequate therapy for pancreatic cancer has yet been found. In this study, the antitumor activity of cytokine-induced killer (CIK) cells against the human pancreatic cancer was evaluated in vitro and in vivo. Human peripheral blood mononuclear cells were cultured with IL-2-containing medium in anti-CD3 for 14 days. The resulting populations of CIK cells comprised 94% CD3+, 4% CD3-CD56+, 41% CD3+C...

  3. Chronic Pancreatitis and Systemic Inflammatory Response Syndrome Prevent Impact of Chemotherapy with Gemcitabine in a Genetically Engineered Mouse Model of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Richard F. Knoop

    2014-06-01

    CONCLUSION: We could demonstrate for the first time that an improvement in median overall survival with gemcitabine is significantly abolished by a persistent mild chronic pancreatitis and a systemic inflammatory response syndrome. In particular, the inflammation biomarkers C-reactive protein, IL-6, and IL-1α could indicate the prognostic benefit of gemcitabine chemotherapy and should now be tested in prospective patient-controlled trials.

  4. Ursolic acid inhibits the growth of human pancreatic cancer and enhances the antitumor potential of gemcitabine in an orthotopic mouse model through suppression of the inflammatory microenvironment.

    Science.gov (United States)

    Prasad, Sahdeo; Yadav, Vivek R; Sung, Bokyung; Gupta, Subash C; Tyagi, Amit K; Aggarwal, Bharat B

    2016-03-15

    The development of chemoresistance in human pancreatic cancer is one reason for the poor survival rate for patients with this cancer. Because multiple gene products are linked with chemoresistance, we investigated the ability of ursolic acid (UA) to sensitize pancreatic cancer cells to gemcitabine, a standard drug used for the treatment of pancreatic cancer. These investigations were done in AsPC-1, MIA PaCa-2, and Panc-28 cells and in nude mice orthotopically implanted with Panc-28 cells. In vitro, UA inhibited proliferation, induced apoptosis, suppressed NF-κB activation and its regulated proliferative, metastatic, and angiogenic proteins. UA (20 μM) also enhanced gemcitabine (200 nM)-induced apoptosis and suppressed the expression of NF-κB-regulated proteins. In the nude mouse model, oral administration of UA (250 mg/kg) suppressed tumor growth and enhanced the effect of gemcitabine (25 mg/kg). Furthermore, the combination of UA and gemcitabine suppressed the metastasis of cancer cells to distant organs such as liver and spleen. Immunohistochemical analysis showed that biomarkers of proliferation (Ki-67) and microvessel density (CD31) were suppressed by the combination of UA and gemcitabine. UA inhibited the activation of NF-κB and STAT3 and the expression of tumorigenic proteins regulated by these inflammatory transcription factors in tumor tissue. Furthermore, the combination of two agents decreased the expression of miR-29a, closely linked with tumorigenesis, in the tumor tissue. UA was found to be bioavailable in animal serum and tumor tissue. These results suggest that UA can inhibit the growth of human pancreatic tumors and sensitize them to gemcitabine by suppressing inflammatory biomarkers linked to proliferation, invasion, angiogenesis, and metastasis. PMID:26909608

  5. Ursolic acid inhibits the growth of human pancreatic cancer and enhances the antitumor potential of gemcitabine in an orthotopic mouse model through suppression of the inflammatory microenvironment

    Science.gov (United States)

    Prasad, Sahdeo; Yadav, Vivek R.; Sung, Bokyung; Gupta, Subash C.; Tyagi, Amit K.; Aggarwal, Bharat B.

    2016-01-01

    The development of chemoresistance in human pancreatic cancer is one reason for the poor survival rate for patients with this cancer. Because multiple gene products are linked with chemoresistance, we investigated the ability of ursolic acid (UA) to sensitize pancreatic cancer cells to gemcitabine, a standard drug used for the treatment of pancreatic cancer. These investigations were done in AsPC-1, MIA PaCa-2, and Panc-28 cells and in nude mice orthotopically implanted with Panc-28 cells. In vitro, UA inhibited proliferation, induced apoptosis, suppressed NF-κB activation and its regulated proliferative, metastatic, and angiogenic proteins. UA (20 μM) also enhanced gemcitabine (200 nM)-induced apoptosis and suppressed the expression of NF-κB-regulated proteins. In the nude mouse model, oral administration of UA (250 mg/kg) suppressed tumor growth and enhanced the effect of gemcitabine (25 mg/kg). Furthermore, the combination of UA and gemcitabine suppressed the metastasis of cancer cells to distant organs such as liver and spleen. Immunohistochemical analysis showed that biomarkers of proliferation (Ki-67) and microvessel density (CD31) were suppressed by the combination of UA and gemcitabine. UA inhibited the activation of NF-κB and STAT3 and the expression of tumorigenic proteins regulated by these inflammatory transcription factors in tumor tissue. Furthermore, the combination of two agents decreased the expression of miR-29a, closely linked with tumorigenesis, in the tumor tissue. UA was found to be bioavailable in animal serum and tumor tissue. These results suggest that UA can inhibit the growth of human pancreatic tumors and sensitize them to gemcitabine by suppressing inflammatory biomarkers linked to proliferation, invasion, angiogenesis, and metastasis. PMID:26909608

  6. Extracellular ATP-induced nuclear Ca{sup 2+} transient is mediated by inositol 1,4,5-trisphosphate receptors in mouse pancreatic {beta}-cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zheng; Li, Zhengzheng; Peng, Gong; Chen, Xiaoli; Yin, Wenxuan [National Laboratory of Biomacromolecules, Institute of Biophysics of Chinese Academy of Sciences, 15 Datun Rd., Beijing 100101 (China); Kotlikoff, Michael I. [Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853 (United States); Yuan, Zeng-qiang, E-mail: zqyuan@sun5.ibp.ac.cn [National Laboratory of Biomacromolecules, Institute of Biophysics of Chinese Academy of Sciences, 15 Datun Rd., Beijing 100101 (China); Ji, Guangju, E-mail: gj28@ibp.ac.cn [National Laboratory of Biomacromolecules, Institute of Biophysics of Chinese Academy of Sciences, 15 Datun Rd., Beijing 100101 (China)

    2009-05-01

    Extracellular ATP (eATP) induces an intracellular Ca{sup 2+} transient by activating phospholipase C (PLC)-associated P2X4 purinergic receptors, leading to production of inositol 1,4,5-trisphosphate (IP3) and subsequent Ca{sup 2+} release from intracellular stores in mouse pancreatic {beta}-cells. Using laser scanning confocal microscopy, Ca{sup 2+} indicator fluo-4 AM, and the cell permeable nuclear indicator Hoechst 33342, we examined the properties of eATP-induced Ca{sup 2+} release in pancreatic {beta}-cell nuclei. eATP induced a higher nuclear Ca{sup 2+} transient in pancreatic {beta}-cell nuclei than in the cytosol. After pretreatment with thapsigargin (TG), an inhibitor of sarco-endoplasmic reticulum Ca{sup 2+}-ATPase (SERCA) pumps, the amplitude of eATP-induced Ca{sup 2+} transients in the nucleus was still much higher than those in the cytosol. This effect of eATP was not altered by inhibition of either the plasma membrane Ca{sup 2+}-ATPase (PMCA) or the plasma membrane Na{sup +}/Ca{sup 2+} exchanger (NCX) by LaCl{sub 3} or by replacement of Na{sup +} with N-Methyl-Glucosamine. eATP-induced nuclear Ca{sup 2+} transients were abolished by a cell-permeable IP3R inhibitor, 2-aminoethoxydiphenyl borate (2-APB), but were not blocked by the ryanodine receptor (RyR) antagonist ryanodine. Immunofluorescence studies showed that IP3Rs are expressed on the nuclear envelope of pancreatic {beta}-cells. These results indicate that eATP triggers nuclear Ca{sup 2+} transients by mobilizing a nuclear Ca{sup 2+} store via nuclear IP3Rs.

  7. Atp2c2 Is Transcribed From a Unique Transcriptional Start Site in Mouse Pancreatic Acinar Cells.

    Science.gov (United States)

    Fenech, Melissa A; Sullivan, Caitlin M; Ferreira, Lucimar T; Mehmood, Rashid; MacDonald, William A; Stathopulos, Peter B; Pin, Christopher L

    2016-12-01

    Proper regulation of cytosolic Ca(2+) is critical for pancreatic acinar cell function. Disruptions in normal Ca(2+) concentrations affect numerous cellular functions and are associated with pancreatitis. Membrane pumps and channels regulate cytosolic Ca(2+) homeostasis by promoting rapid Ca(2+) movement. Determining how expression of Ca(2+) modulators is regulated and the cellular alterations that occur upon changes in expression can provide insight into initiating events of pancreatitis. The goal of this study was to delineate the gene structure and regulation of a novel pancreas-specific isoform for Secretory Pathway Ca(2+) ATPase 2 (termed SPCA2C), which is encoded from the Atp2c2 gene. Using Next Generation Sequencing of RNA (RNA-seq), chromatin immunoprecipitation for epigenetic modifications and promoter-reporter assays, a novel transcriptional start site was identified that promotes expression of a transcript containing the last four exons of the Atp2c2 gene (Atp2c2c). This region was enriched for epigenetic marks and pancreatic transcription factors that promote gene activation. Promoter activity for regions upstream of the ATG codon in Atp2c2's 24th exon was observed in vitro but not in in vivo. Translation from this ATG encodes a protein aligned with the carboxy terminal of SPCA2. Functional analysis in HEK 293A cells indicates a unique role for SPCA2C in increasing cytosolic Ca(2+) . RNA analysis indicates that the decreased Atp2c2c expression observed early in experimental pancreatitis reflects a global molecular response of acinar cells to reduce cytosolic Ca(2+) levels. Combined, these results suggest SPCA2C affects Ca(2+) homeostasis in pancreatic acinar cells in a unique fashion relative to other Ca(2+) ATPases. J. Cell. Physiol. 231: 2768-2778, 2016. © 2016 Wiley Periodicals, Inc. PMID:27017909

  8. Cloning of cDNAs that encode human mast cell carboxypeptidase A, and comparison of the protein with mouse mast cell carboxypeptidase A and rat pancreatic carboxypeptidases

    International Nuclear Information System (INIS)

    Human skin and lung mast cells and rodent peritoneal cells contain a carboxypeptidase in their secretory granules. The authors have screened human lung cDNA libraries with a mouse mast cell carboxypeptidase A (MC-CPA) cDNA probe to isolate a near-full-length cDNA that encodes human MC-CPA. The 5' end of the human MC-CPA transcript was defined by direct mRNA sequencing and by isolation and partial sequencing of the human MC-CPA gene. Human MC-CPA is predicted to be translated as a 417 amino acid preproenzyme which includes a 15 amino acid signal peptide and a 94-amino acid activation peptide. The mature human MC-CPA enzyme has a predicted size of 36.1 kDa, a net positive charge of 16 at neutral pH, and 86% amino acid sequence identity with mouse MC-CPA. DNA blot analyses showed that human MC-CPA mRNA is transcribed from a single locus in the human genome. Comparison of the human MC-CPA with mouse MC-CPA and with three rat pancreatic carboxypeptidases shows that these enzymes are encoded by distinct but homologous genes

  9. Donor pre-treatment with tetrahydrobiopterin saves pancreatic isografts from ischemia reperfusion injury in a mouse model

    OpenAIRE

    Maglione, M.; Oberhuber, R.; Cardini, B; Watschinger, K; Hermann, M; Obrist, P; Hengster, P; Mark, W; Schneeberger, S; Werner-Felmayer, G; Pratschke, J; R. Margreiter; Werner, ER; Brandacher, G

    2010-01-01

    Depletion of the nitric oxide synthase cofactor tetrahydrobiopterin (H4B) during ischemia and reperfusion is associated with severe graft pancreatitis. Since clinically feasible approaches to prevent ischemia reperfusion injury (IRI) by H4B-substitution are missing we investigated its therapeutic potential in a murine pancreas transplantation model using different treatment regimens. Grafts were subjected to 16h cold ischemia time (CIT) and different treatment regimens: no treatment, 160μM H4...

  10. Assessment and optimization of electroporation-assisted tumoral nanoparticle uptake in a nude mouse model of pancreatic ductal adenocarcinoma

    OpenAIRE

    West DL; White SB; Zhang Z; Larson AC; Omary RA

    2014-01-01

    Derek Lamont West,1,2 Sarah B White,3 Zhouli Zhang,4 Andrew C Larson,4 Reed A Omary5 1Department of Diagnostic and Interventional Radiology, 2Department of Bioengineering and Nanomedicine, University of Texas Health Sciences Center at Houston, Houston, TX, 3Department of Radiology, Medical College of Wisconsin, Milwaukee, WI; 4Department of Radiology, Northwestern University, Chicago, IL; 5Department of Radiology, Vanderbilt University, Nashville, TN, USA Abstract: Pancreatic ductal adenoca...

  11. Pancreatic Tuberculosis or Autoimmune Pancreatitis

    OpenAIRE

    Ayesha Salahuddin; Muhammad Wasif Saif

    2014-01-01

    Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 relate...

  12. Adoptive immunotherapy of human pancreatic cancer with lymphokine-activated killer cells and interleukin-2 in a nude mouse model

    International Nuclear Information System (INIS)

    A pancreatic cancer cell line was grown in orthotopic and heterotopic positions in young Swiss/NIH nude mice, which were tested with adoptive immunotherapy. Mice were injected with 1 x 10(7) human cancer cells in the subcutaneous tissue and duodenal lobe of the pancreas. The mice were randomly divided into four groups: group IA (LAK + IL-2) (N = 25) received 2 X 10(7) human lymphokine-activated killer (LAK) cells from normal donors by tail vein injection followed by 10,000 units of human recombinant interleukin-2 (IL-2) given intraperitoneally every 12 hours for 28 days; group IB (IL-2) (N = 27) was given the same dose of IL-2 alone; group IC (RPMI-1640) (N = 18) received a placebo consisting of 1 ml of RPMI-1640 intraperitoneally every 12 hours; and group ID (LAK) (N = 14) received 2 X 10(7) LAK cells but no IL-2. Toxicity was significantly higher in group IB, with a mortality rate of 45.5% (10/22 animals) versus a 0% mortality (0/25) in group IA. None of the group IA or IB animals died of pancreatic cancer during the experiment. The animals that did not receive IL-2 died before 28 days in 14.2% of group IC and in 16.7% of group ID. The area under the growth curve of subcutaneous tumors during the course of treatment and the pancreatic tumor weight at the end of treatment were compared in each group. Subcutaneous tumors had a reduced rate of growth in group IA animals compared to all the other treatments. Pancreatic tumor growth was slowed in group IA. The animals treated with IL-2 alone (group IB) showed some slowing of tumor growth that was intermediate between group IA, group IC, and group ID. A similar experiment was done with irradiated (375 rad) mice. Nine nude mice with tumors were treated with LAK + IL-2 (group IIA), eight received IL-2 alone (group IIB), and seven received placebo (group IIC)

  13. Evaluation of Efficacy of Radioimmunotherapy with 90Y-Labeled Fully Human Anti-Transferrin Receptor Monoclonal Antibody in Pancreatic Cancer Mouse Models.

    Directory of Open Access Journals (Sweden)

    Aya Sugyo

    Full Text Available Pancreatic cancer is an aggressive tumor and the prognosis remains poor. Therefore, development of more effective therapy is needed. We previously reported that 89Zr-labeled TSP-A01, an antibody against transferrin receptor (TfR, is highly accumulated in a pancreatic cancer xenograft, but not in major normal organs. In the present study, we evaluated the efficacy of radioimmunotherapy (RIT with 90Y-TSP-A01 in pancreatic cancer mouse models.TfR expression in pancreatic cancer cell lines (AsPC-1, BxPC-3, MIAPaCa-2 was evaluated by immunofluorescence staining. 111In-labeled anti-TfR antibodies (TSP-A01, TSP-A02 were evaluated in vitro by cell binding assay with the three cell lines and by competitive inhibition assay with MIAPaCa-2. In vivo biodistribution was evaluated in mice bearing BxPC-3 and MIAPaCa-2 xenografts. Tumor volumes of BxPC-3 and MIAPaCa-2 were sequentially measured after 90Y-TSP-A01 injection and histological analysis of tumors was conducted.MIAPaCa-2 cells showed the highest TfR expression, followed by AsPC-1 and BxPC-3 cells. 111In-TSP-A01 and 111In-TSP-A02 bound specifically to the three cell lines according to TfR expression. The dissociation constants for TSP-A01, DOTA-TSP-A01, TSP-A02, and DOTA-TSP-A02 were 0.22, 0.28, 0.17, and 0.22 nM, respectively. 111In-TSP-A01 was highly accumulated in tumors, especially in MIAPaCa-2, but this was not true of 111In-TSP-A02. The absorbed dose for 90Y-TSP-A01 was estimated to be 8.3 Gy/MBq to BxPC-3 and 12.4 Gy/MBq to MIAPaCa-2. MIAPaCa-2 tumors treated with 3.7 MBq of 90Y-TSP-A01 had almost completely disappeared around 3 weeks after injection and regrowth was not observed. Growth of BxPC-3 tumors was inhibited by 3.7 MBq of 90Y-TSP-A01, but the tumor size was not reduced.90Y-TSP-A01 treatment achieved an almost complete response in MIAPaCa-2 tumors, whereas it merely inhibited the growth of BxPC-3 tumors. 90Y-TSP-A01 is a promising RIT agent for pancreatic cancer, although further

  14. Pancreatic Cancer

    Science.gov (United States)

    ... hormones that help control blood sugar levels. Pancreatic cancer usually begins in the cells that produce the juices. Some risk factors for developing pancreatic cancer include Smoking Long-term diabetes Chronic pancreatitis Certain ...

  15. Bcl-2 Regulates Reactive Oxygen Species Signaling and a Redox-Sensitive Mitochondrial Proton Leak in Mouse Pancreatic β-Cells.

    Science.gov (United States)

    Aharoni-Simon, Michal; Shumiatcher, Rose; Yeung, Anthony; Shih, Alexis Z L; Dolinsky, Vernon W; Doucette, Christine A; Luciani, Dan S

    2016-06-01

    In pancreatic β-cells, controlling the levels of reactive oxygen species (ROS) is critical to counter oxidative stress, dysfunction and death under nutrient excess. Moreover, the fine-tuning of ROS and redox balance is important in the regulation of normal β-cell physiology. We recently demonstrated that Bcl-2 and Bcl-xL, in addition to promoting survival, suppress β-cell glucose metabolism and insulin secretion. Here, we tested the hypothesis that the nonapoptotic roles of endogenous Bcl-2 extend to the regulation of β-cell ROS and redox balance. We exposed mouse islet cells and MIN6 cells to the Bcl-2/Bcl-xL antagonist Compound 6 and the Bcl-2-specific antagonist ABT-199 and evaluated ROS levels, Ca(2+) responses, respiratory control, superoxide dismutase activity and cell death. Both acute glucose stimulation and the inhibition of endogenous Bcl-2 progressively increased peroxides and stimulated superoxide dismutase activity in mouse islets. Importantly, conditional β-cell knockout of Bcl-2 amplified glucose-induced formation of peroxides. Bcl-2 antagonism also induced a mitochondrial proton leak that was prevented by the antioxidant N-acetyl-L-cysteine and, therefore, secondary to redox changes. We further established that the proton leak was independent of uncoupling protein 2 but partly mediated by the mitochondrial permeability transition pore. Acutely, inhibitor-induced peroxides promoted Ca(2+) influx, whereas under prolonged Bcl inhibition, the elevated ROS was required for induction of β-cell apoptosis. In conclusion, our data reveal that endogenous Bcl-2 modulates moment-to-moment ROS signaling and suppresses a redox-regulated mitochondrial proton leak in β-cells. These noncanonical roles of Bcl-2 may be important for β-cell function and survival under conditions of high metabolic demand. PMID:27070098

  16. Acute pancreatitis

    OpenAIRE

    Bo-Guang Fan; Åke Andrén-Sandberg

    2010-01-01

    Background : Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims : The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods : We reviewed the English-language literature (Medline) addressing pancreatitis. Results : Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingest...

  17. Acute pancreatitis

    OpenAIRE

    Bo-Guang Fan; Åke Andrén-Sandberg

    2010-01-01

    Background: Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims: The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods: We reviewed the English-language literature (Medline) addressing pancreatitis. Results: Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion....

  18. Exendin-4 Improves Glycemic Control, Ameliorates Brain and Pancreatic Pathologies, and Extends Survival in a Mouse Model of Huntington's Disease

    OpenAIRE

    Martin, Bronwen; Golden, Erin; Carlson, Olga D.; Pistell, Paul; Zhou, Jie; Kim, Wook; Frank, Brittany P.; Sam THOMAS; Chadwick, Wayne A.; Greig, Nigel H.; Bates, Gillian P.; Sathasivam, Kirupa; Bernier, Michel; Maudsley, Stuart; Mattson, Mark P.

    2009-01-01

    OBJECTIVE—The aim of this study was to find an effective treatment for the genetic form of diabetes that is present in some Huntington's disease patients and in Huntington's disease mouse models. Huntington's disease is a neurodegenerative disorder caused by a polyglutamine expansion within the huntingtin protein. Huntington's disease patients exhibit neuronal dysfunction/degeneration, chorea, and progressive weight loss. Additionally, they suffer from abnormalities in energy metabolism affec...

  19. Acute Pancreatitis and Pregnancy

    Science.gov (United States)

    ... Acute Pancreatitis > Acute Pancreatitis and Pregnancy test Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is ... of acute pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for ...

  20. COUP-TFII controls mouse pancreatic β-cell mass through GLP-1-β-catenin signaling pathways.

    Directory of Open Access Journals (Sweden)

    Marie Boutant

    Full Text Available BACKGROUND: The control of the functional pancreatic β-cell mass serves the key homeostatic function of releasing the right amount of insulin to keep blood sugar in the normal range. It is not fully understood though how β-cell mass is determined. METHODOLOGY/PRINCIPAL FINDINGS: Conditional chicken ovalbumin upstream promoter transcription factor II (COUP-TFII-deficient mice were generated and crossed with mice expressing Cre under the control of pancreatic duodenal homeobox 1 (pdx1 gene promoter. Ablation of COUP-TFII in pancreas resulted in glucose intolerance. Beta-cell number was reduced at 1 day and 3 weeks postnatal. Together with a reduced number of insulin-containing cells in the ductal epithelium and normal β-cell proliferation and apoptosis, this suggests decreased β-cell differentiation in the neonatal period. By testing islets isolated from these mice and cultured β-cells with loss and gain of COUP-TFII function, we found that COUP-TFII induces the expression of the β-catenin gene and its target genes such as cyclin D1 and axin 2. Moreover, induction of these genes by glucagon-like peptide 1 (GLP-1 via β-catenin was impaired in absence of COUP-TFII. The expression of two other target genes of GLP-1 signaling, GLP-1R and PDX-1 was significantly lower in mutant islets compared to control islets, possibly contributing to reduced β-cell mass. Finally, we demonstrated that COUP-TFII expression was activated by the Wnt signaling-associated transcription factor TCF7L2 (T-cell factor 7-like 2 in human islets and rat β-cells providing a feedback loop. CONCLUSIONS/SIGNIFICANCE: Our findings show that COUP-TFII is a novel component of the GLP-1 signaling cascade that increases β-cell number during the neonatal period. COUP-TFII is required for GLP-1 activation of the β-catenin-dependent pathway and its expression is under the control of TCF7L2.

  1. Acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Bo-Guang Fan

    2010-05-01

    Full Text Available Background: Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims: The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods: We reviewed the English-language literature (Medline addressing pancreatitis. Results: Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions: Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  2. Acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Bo-Guang Fan

    2010-01-01

    Full Text Available Background : Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims : The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods : We reviewed the English-language literature (Medline addressing pancreatitis. Results : Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions : Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  3. [Pancreatic Diseases].

    Science.gov (United States)

    Schöfl, Rainer

    2016-06-22

    The author presents his personal choice of practical relevant papers of pancreatic diseases from 2014 to 2015. Nutritional factors and hypertriglycidemia are discussed as causes of acute pancreatitis. Tools to avoid post-ERCP(endoscopic retrograde cholangiopancreatography) pancreatitis are described and the natural course of fluid collections and pseudocysts is demonstrated. The value of secretin-MRCP(magnetic resonance cholangiopancreatography) for diagnosis of chronic pancreatitis is illustrated. Data help to choose the minimally effective prednisolone dose in autoimmune pancreatitis. The increased prevalence of fractures in patients with chronic pancreatitis highlights the necessity of screening for bone density loss. The association of vitamin D intake with pancreatic cancer is described. The probability of cancer in IPNM is shown and innovative surgical concepts to reduce the loss of pancreatic function are presented. Finally neoadjuvant concepts for the treatment of pancreatic cancer are highlighted. PMID:27329710

  4. Sub-lethal radiation enhances anti-tumor immunotherapy in a transgenic mouse model of pancreatic cancer

    International Nuclear Information System (INIS)

    It is not uncommon to observe circulating tumor antigen-specific T lymphocytes in cancer patients despite a lack of significant infiltration and destruction of their tumors. Thus, an important goal for tumor immunotherapy is to identify ways to modulate in vivo anti-tumor immunity to achieve clinical efficacy. We investigate this proposition in a spontaneous mouse tumor model, Rip1-Tag2. Experimental therapies were carried out in two distinctive trial designs, intended to either intervene in the explosive growth of small tumors, or regress bulky end-stage tumors. Rip1-Tag2 mice received a single transfer of splenocytes from Tag-specific, CD4+ T cell receptor transgenic mice, a single sub-lethal radiation, or a combination therapy in which the lymphocyte transfer was preceded by the sub-lethal radiation. Tumor burden, the extent of lymphocyte infiltration into solid tumors and host survival were used to assess the efficacy of these therapeutic approaches. In either intervention or regression, the transfer of Tag-specific T cells alone did not result in significant lymphocyte infiltration into solid tumors, not did it affect tumor growth or host survival. In contrast, the combination therapy resulted in significant reduction in tumor burden, increase in lymphocyte infiltration into solid tumors, and extension of survival. The results indicate that certain types of solid tumors may be intrinsically resistant to infiltration and destruction by tumor-specific T lymphocytes. Our data suggest that such resistance can be disrupted by sub-lethal radiation. The combinatorial approach presented here merits consideration in the design of clinical trials aimed to achieve T cell-mediated anti-tumor immunity

  5. Pancreatic Tuberculosis or Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Ayesha Salahuddin

    2014-01-01

    Full Text Available Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 related systemic diseases and tuberculosis appear to have some similarities. Case Report. We report a case of a 59-year-old Southeast Asian male who presented with fever, weight loss, and obstructive jaundice. CT scan revealed pancreatic mass and enlarged peripancreatic lymph nodes. Endoscopic ultrasound-guided fine needle aspiration confirmed the presence of mycobacterium tuberculosis. Patient also had high immunoglobulin G4 levels suggestive of autoimmune pancreatitis. He was started on antituberculosis medications and steroids. Clinically, he responded to treatment. Follow-up imaging showed findings suggestive of chronic pancreatitis. Discussion. Pancreatic tuberculosis and autoimmune pancreatitis can mimic pancreatic malignancy. Accurate diagnosis is imperative as unnecessary surgical intervention can be avoided. Endoscopic ultrasound-guided fine needle aspiration seems to be the diagnostic test of choice for pancreatic masses. Long-term follow-up is warranted in cases of chronic pancreatitis.

  6. Complicated Pancreatitis

    NARCIS (Netherlands)

    Bakker, O.J.

    2015-01-01

    Research questions addressed in this thesis: What is the accuracy of serum blood urea nitrogen as early predictor of complicated pancreatitis? ; What is difference in clinical outcome between patients with pancreatic parenchymal necrosis and patients with extrapancreatic necrosis without necrosis

  7. Pancreatic pseudocyst

    Science.gov (United States)

    ... It may also contain tissue from the pancreas, pancreatic enzymes, and blood. ... located behind the stomach. It produces chemicals (called enzymes) ... Pancreatic pseudocysts most often develop after an episode of ...

  8. Hereditary Pancreatitis

    Science.gov (United States)

    ... method of medical management. Patients may be prescribed pancreatic enzyme supplements to treat maldigestion, insulin to treat diabetes, ... in carbohydrates and low in protein and fat. Pancreatic enzymes such as Creon, Pancrease, and Violiase are helpful ...

  9. Complicated Pancreatitis

    OpenAIRE

    Bakker, O.J.

    2015-01-01

    Research questions addressed in this thesis: What is the accuracy of serum blood urea nitrogen as early predictor of complicated pancreatitis? ; What is difference in clinical outcome between patients with pancreatic parenchymal necrosis and patients with extrapancreatic necrosis without necrosis of the pancreatic parenchyma? ; What is the impact of organ failure on mortality in necrotizing pancreatitis? ; Based on individual patient data from randomized trials, does early enteral tube feedin...

  10. Chronic pancreatitis

    OpenAIRE

    Kocher, Hemant M; Froeling, Fieke EM

    2008-01-01

    Chronic pancreatitis is characterised by long-standing inflammation of the pancreas owing to a wide variety of causes, including recurrent acute attacks of pancreatitis. Chronic pancreatitis affects 3–9 people in 100,000; 70% of cases are alcohol-induced.

  11. Chronic pancreatitis

    OpenAIRE

    Kocher, Hemant M; Kadaba, Raghu

    2011-01-01

    Chronic pancreatitis is characterised by long-standing inflammation of the pancreas due to a wide variety of causes, including recurrent acute attacks of pancreatitis. Chronic pancreatitis affects between 3 and 9 people in 100,000; 70% of cases are alcohol-induced.

  12. Near infra-red photoimmunotherapy with anti-CEA-IR700 results in extensive tumor lysis and a significant decrease in tumor burden in orthotopic mouse models of pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Ali A Maawy

    Full Text Available Photoimmunotherapy (PIT of cancer utilizes tumor-specific monoclonal antibodies conjugated to a photosensitizer phthalocyanine dye IR700 which becomes cytotoxic upon irradiation with near infrared light. In this study, we aimed to evaluate the efficacy of PIT on human pancreatic cancer cells in vitro and in vivo in an orthotopic nude mouse model. The binding capacity of anti-CEA antibody to BxPC-3 human pancreatic cancer cells was determined by FACS analysis. An in vitro cytotoxicity assay was used to determine cell death following treatment with PIT. For in vivo determination of PIT efficacy, nude mice were orthotopically implanted with BxPC-3 pancreatic tumors expressing green fluorescent protein (GFP. After tumor engraftment, the mice were divided into two groups: (1 treatment with anti-CEA-IR700 + 690 nm laser and (2 treatment with 690 nm laser only. Anti-CEA-IR700 (100 μg was administered to group (1 via tail vein injection 24 hours prior to therapy. Tumors were then surgically exposed and treated with phototherapy at an intensity of 150 mW/cm2 for 30 minutes. Whole body imaging was done subsequently for 5 weeks using an OV-100 small animal imaging system. Anti-CEA-IR700 antibody bound to the BxPC3 cells to a high degree as shown by FACS analysis. Anti-CEA-IR700 caused extensive cancer cell killing after light activation compared to control cells in cytotoxicity assays. In the orthotopic models of pancreatic cancer, the anti-CEA-IR700 group had significantly smaller tumors than the control after 5 weeks (p<0.001. There was no significant difference in the body weights of mice in the anti-CEA-IR700 and control groups indicating that PIT was well tolerated by the mice.

  13. Two Distinct Pancreatic Amylase Genes Are Active in Ybr Mice

    OpenAIRE

    Strahler, John R.; Meisler, Miriam,

    1982-01-01

    The genetic determinants of pancreatic amylase expression in YBR mice differ in two respects from those of other inbred strains. First, there are two nonallelic amylase isozymes present in YBR pancreas, while most mouse strains express a single pancreatic amylase protein. In addition, the in vivo rate of total pancreatic amylase synthesis is 50% of that in other strains. Both these traits are determined by genetic sites in the region of the Amy-2 locus on mouse chromosome 3. To determine the ...

  14. Autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Bo-Guang Fan

    2009-01-01

    Full Text Available Since the autoimmune pancreatitis was introduced in 1995, it has been recognized as a form of chronic pancreatitis, which is always associated with autoimmune manifestations. As the improvement of technical and instrumental made in ultrasonography, computed tomography and magnetic resonance imaging, the diagnoses of autoimmune pancreatitis is no longer such difficult. Even though the treatment of autoimmune pancreatitis is available with a conservative therapy, there are many points that are still unclearly. These have stimulated widespread interest in this disease from gastroenterologists, endoscopists, pathologists, and prevalent research. The present article provides with our better understanding of the diagnosis and treatment of autoimmune pancreatitis.

  15. Autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Bo-Guang Fan

    2009-09-01

    Full Text Available Since the autoimmune pancreatitis was introduced in 1995, it has been recognized as a form of chronic pancreatitis, which is always associated with autoimmune manifestations. As the improvement of technical and instrumental made in ultrasonography, computed tomography and magnetic resonance imaging, the diagnoses of autoimmune pancreatitis is no longer such difficult. Even though the treatment of autoimmune pancreatitis is available with a conservative therapy, there are many points that are still unclearly. These have stimulated widespread interest in this disease from gastroenterologists, endoscopists, pathologists, and prevalent research. The present article provides with our better understanding of the diagnosis and treatment of autoimmune pancreatitis.

  16. Hereditary pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Richard M Charnley

    2003-01-01

    Hereditary pancreatitis is an autosomal dominant condition,which results in recurrent attacks of acute pancreatitis,progressing to chronic pancreatitis often at a young age.The majority of patients with hereditary pancreatitis expressone of two mutations (R122H or N29I) in the cationictrypsinogen gene (PRSS1 gene). It has been hypothesisedthat one of these mutations, the R122H mutation causespancreatitis by altering a trypsin recognition site sopreventing deactivation of trypsin within the pancreas andprolonging its action, resulting in autodigestion. Families withthese two mutations have been identified in many countriesand there are also other rarer mutations, which have alsobeen linked to hereditary pancreatitis.Patients with hereditary pancreatitis present in the sameway as those with sporadic pancreatitis but at an earlierage. It is common for patients to remain undiagnosed formany years, particularly ifthey present with non-specificsymptoms. Hereditary pancreatitis should always beconsidered in patients who present with recurrent pancreatitiswith a family history of pancreatic disease. If patients withthe 2 common mutations are compared, those with theR122H mutation are more likely to present at a younger ageand are more likely to require surgical intervention than thosewith N29I. Hereditary pancreatitis carries a 40 % lifetimerisk of pancreatic cancer with those patients aged between50 to 70 being most at risk in whom screening tests maybecome important.

  17. Comparison of a chimeric anti-carcinoembryonic antigen antibody conjugated with visible or near-infrared fluorescent dyes for imaging pancreatic cancer in orthotopic nude mouse models

    OpenAIRE

    Maawy, Ali A.; Hiroshima, Yukihiko; Kaushal, Sharmeela; Luiken, George A.; Robert M Hoffman; Bouvet, Michael

    2013-01-01

    Abstract. The aim of this study was to evaluate a set of visible and near-infrared dyes conjugated to a tumor-specific chimeric antibody for high-resolution tumor imaging in orthotopic models of pancreatic cancer. BxPC-3 human pancreatic cancer was orthotopically implanted into pancreata of nude mice. Mice received a single intravenous injection of a chimeric anti-carcinoembryonic antigen antibody conjugated to one of the following fluorophores: 488-nm group (Alexa Fluor 488 or DyLight 488); ...

  18. Autoimmune pancreatitis

    DEFF Research Database (Denmark)

    Detlefsen, Sönke; Drewes, Asbjørn M

    2009-01-01

    bile duct. Obstructive jaundice is a common symptom at presentation, and pancreatic cancer represents an important clinical differential diagnosis. In late stages of the disease, the normal pancreatic parenchyma is often replaced by large amounts of fibrosis. Histologically, there seem to be two...... AIP responds to steroid treatment, also a trial with steroids, can help to differentiate AIP from pancreatic cancer. OUTLOOK AND DISCUSSION: This review presents the pathological, radiologic and laboratory findings of AIP. Moreover, the treatment and pathogenesis are discussed.......BACKGROUND: Autoimmune pancreatitis (AIP) is a relatively newly recognized type of pancreatitis that is characterized by diffuse or focal swelling of the pancreas due to lymphoplasmacytic infiltration and fibrosis of the pancreatic parenchyma. MATERIAL AND METHODS: A PubMed literature search was...

  19. Retraction: "Inactivation of Ink4a/Arf Leads to Deregulated Expression of miRNAs in K-Ras Transgenic Mouse Model of Pancreatic Cancer" by Ali et al.

    Science.gov (United States)

    2016-10-01

    The above article, published online on June 21, 2012 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief, Gary S. Stein, and Wiley Periodicals, Inc. The retraction has been agreed following an investigation from Wayne State University involving the first author and the corresponding author that found Figure 5A to be inappropriately manipulated. Literature Cited Ali S, Banerjee S, Logna F, Bao B, Philip PA, Korc M, Sarkar FH. 2012. Inactivation of Ink4a/Arf leads to deregulated expression of miRNAs in K-Ras transgenic mouse model of pancreatic cancer. J Cell Physiol 227:3373-3380; doi: 10.1002/jcp.24036. PMID:27315161

  20. Glucose triggers protein kinase A-dependent insulin secretion in mouse pancreatic islets through activation of the K+ATP channel-dependent pathway

    DEFF Research Database (Denmark)

    Thams, Peter; Anwar, Mohammad R; Capito, Kirsten

    2005-01-01

    pancreatic islets was determined by radioimmunoassay. RESULTS: In islets cultured at 5.5 mmol/l glucose, and then perifused in physiological Krebs-Ringer medium, the PKA inhibitors, H89 (10 micromol/l) and PKI 6-22 amide (30 micromol/l) did not inhibit glucose (16.7 mmol/l)-induced insulin secretion, but...

  1. Chronic pancreatitis and pancreatic carcinoma.

    OpenAIRE

    Evans, J D; Morton, D. G.; Neoptolemos, J. P.

    1997-01-01

    The differential diagnosis between pancreatic cancer and chronic pancreatitis is very important as the management and prognosis of these two diseases is different. In most patients with pancreatic disease, the diagnosis can be established but there is a subgroup of patients in whom it is difficult to differentiate between these conditions because the clinical presentation is often similar and currently available diagnostic tests may be unable to distinguish between an inflammatory or neoplast...

  2. Pancreatic cancer

    OpenAIRE

    Kocher, Hemant M.; Alrawashdeh, Wasfi

    2010-01-01

    Pancreatic cancer is the fourth most common cause of cancer death in higher-income countries, with 5-year survival only 10% (range 7%–25%), even in people presenting with early-stage cancer. Risk factors include age, smoking, chronic pancreatitis, a family history, and dietary factors. Diabetes mellitus may also increase the risk.

  3. Pancreatic Tuberculosis.

    Science.gov (United States)

    Chaudhary, Poras; Bhadana, Utsav; Arora, Mohinder P

    2015-12-01

    Tuberculosis of the pancreas is extremely rare and in most of the cases mimics pancreatic carcinoma. There are a number of case reports on pancreatic tuberculosis with various different presentations, but only a few case series have been published, and most of our knowledge about this disease comes from individual case reports. Patients of pancreatic tuberculosis may remain asymptomatic initially and manifest as an abscess or a mass involving local lymph nodes and usually present with non-specific features. Pancreatic tuberculosis may present with a wide range of imaging findings. It is difficult to diagnose tuberculosis of pancreas on imaging studies as they may present with masses, cystic lesions or abscesses and mass lesions in most of the cases mimic pancreatic carcinoma. As it is a rare entity, it cannot be recommended but suggested that pancreatic tuberculosis should be considered in cases with a large space occupying lesions associated with necrotic peripancreatic lymph nodes and constitutional symptoms. Ultrasonography/computed tomography/endosonography-guided biopsy is the recommended diagnostic technique. Most patients achieve complete cure with standard antituberculous therapy. The aims of this study are to review clinical presentation, diagnostic studies, and management of pancreatic tuberculosis and to present our experience of 5 cases of pancreatic tuberculosis. PMID:26884661

  4. Pancreatic necrosis

    International Nuclear Information System (INIS)

    Pancreatic necrosis is a possible complication of acute pancreatitis. It is characterized by diffuse inflammation associated with exudation or leakage of pancreatic juice with its proteolytic enzymes into the peripancreatic tissues. Colonic complications of acute pancreatitis are uncommon events. Tha main purpose of our study was to correlate radiological findings of pancreatic necrosis as observed during barium enema to CT patterns. A retrospective study was therefore carried out on 40 patients affected with acute pancreatitis with local and systemic complication. The analysis of the results allowed different patterns to be observed, with the two techniques, in the acute and in the chronich phases. In the acute phase, barium enema of the colon showed inflammatory extrinsic processes involving the wall, with a typical localization related to the spread of pancreatic enzymes along mesenteric pathways, as described by Meyers. CT allowed a thorough evaluation of both the pathologic process and its spatial balance. In the chronic phase, barium enema showed fibrotic trictures and fistulas. CT demonstrated pseudoeystic masses and irregular focal areas of decreased attenuation or irregular pancreatic margins. This correlation shows how an extrinsic inflammatory involvement of the colon with a characteristic tomography may help make a diagnosis and plan therapy

  5. The Adnectin CT-322 is a novel VEGF receptor 2 inhibitor that decreases tumor burden in an orthotopic mouse model of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Miller Andrew F

    2008-11-01

    Full Text Available Abstract Background Pancreatic cancer continues to have a 5-year survival of less than 5%. Therefore, more effective therapies are necessary to improve prognosis in this disease. Angiogenesis is required for tumor growth, and subsequently, mediators of angiogenesis are attractive targets for therapy. Vascular endothelial growth factor (VEGF is a well-characterized mediator of tumor angiogenesis that functions primarily by binding and activating VEGF receptor 2 (VEGFR2. In this study, we evaluate the use of CT-322, a novel biologic (Adnectin. This small protein is based on a human fibronectin domain and has beneficial properties in that it is fully human, stable, and is produced in bacteria. CT-322 binds to and inhibits activation of VEGFR2. Methods The efficacy of CT-322 was evaluated in vivo using two orthotopic pancreatic tumor models. The first model was a human tumor xenograft where MiaPaCa-2 cells were injected into the tail of the pancreas of nude mice. The second model was a syngeneic tumor using Pan02 cells injected into pancreas of C57BL/6J mice. In both models, therapy was initiated once primary tumors were established. Mice bearing MiaPaCa-2 tumors were treated with vehicle or CT-322 alone. Gemcitabine alone or in combination with CT-322 was added to the treatment regimen of mice bearing Pan02 tumors. Therapy was given twice a week for six weeks, after which the animals were sacrificed and evaluated (grossly and histologically for primary and metastatic tumor burden. Primary tumors were also evaluated by immunohistochemistry for the level of apoptosis (TUNEL, microvessel density (MECA-32, and VEGF-activated blood vessels (Gv39M. Results Treatment with CT-322 was effective at preventing pancreatic tumor growth and metastasis in orthotopic xenograft and syngeneic models of pancreatic cancer. Additionally, CT-322 treatment increased apoptosis, reduced microvessel density and reduced the number of VEGF-activated blood vessels in tumors

  6. Harmonic motion imaging for abdominal tumor detection and high-intensity focused ultrasound ablation monitoring: an in vivo feasibility study in a transgenic mouse model of pancreatic cancer.

    Science.gov (United States)

    Chen, Hong; Hou, Gary Y; Han, Yang; Payen, Thomas; Palermo, Carmine F; Olive, Kenneth P; Konofagou, Elisa E

    2015-09-01

    Harmonic motion imaging (HMI) is a radiationforce- based elasticity imaging technique that tracks oscillatory tissue displacements induced by sinusoidal ultrasonic radiation force to assess the resulting oscillatory displacement denoting the underlying tissue stiffness. The objective of this study was to evaluate the feasibility of HMI in pancreatic tumor detection and high-intensity focused ultrasound (HIFU) treatment monitoring. The HMI system consisted of a focused ultrasound transducer, which generated sinusoidal radiation force to induce oscillatory tissue motion at 50 Hz, and a diagnostic ultrasound transducer, which detected the axial tissue displacements based on acquired radio-frequency signals using a 1-D cross-correlation algorithm. For pancreatic tumor detection, HMI images were generated for pancreatic tumors in transgenic mice and normal pancreases in wild-type mice. The obtained HMI images showed a high contrast between normal and malignant pancreases with an average peak-to-peak HMI displacement ratio of 3.2. Histological analysis showed that no tissue damage was associated with HMI when it was used for the sole purpose of elasticity imaging. For pancreatic tumor ablation monitoring, the focused ultrasound transducer was operated at a higher acoustic power and longer pulse length than that used in tumor detection to simultaneously induce HIFU thermal ablation and oscillatory tissue displacements, allowing HMI monitoring without interrupting tumor ablation. HMI monitoring of HIFU ablation found significant decreases in the peak-to-peak HMI displacements before and after HIFU ablation with a reduction rate ranging from 15.8% to 57.0%. The formation of thermal lesions after HIFU exposure was confirmed by histological analysis. This study demonstrated the feasibility of HMI in abdominal tumor detection and HIFU ablation monitoring. PMID:26415128

  7. Imaging of pancreatic diseases

    Energy Technology Data Exchange (ETDEWEB)

    Mihashi, H.; Hirose, J.; Hayasaka, K.; Kamikita, Y.; Asano, A. (Asahikawa Medical College, Hokkaido (Japan))

    1981-11-01

    Diagnosing pancreatic diseases using non invasive methods such as ultrasound and computed tomography was reviewed. Images characteristic to pancreatitis and pancreatic cancer were explained. Pancreatic cancer accompanied with pancreatitis was demonstrated on echograms and scintigrams. The necessity of follow-up observation of pancreatitis was stressed.

  8. Acute pancreatitis

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000287.htm Acute pancreatitis To use the sharing features on this page, ... fatty foods after the attack has improved. Outlook (Prognosis) Most cases go away in a week. However, ...

  9. Acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Al Mofleh Ibrahim

    1997-01-01

    Full Text Available The past few years have witnessed a tremendous progress in our knowledge regarding the pathogenesis, diagnosis, prognostic evaluation and classification of acute pancreatitis. The role of ischemia, lysosomal enzymes, oxygen free radicals, polymorphnuclear cells-byproducts and inflammatory mediators in the pathogenesis of pancreatic necrosis and multiple organ failure has been emphasized. Furthermore, the recent knowledge about agents infecting pancreatic necrosis, routes of infection, bacteriological examination of fine needle aspirate and appropriate antibiotics have changed the concept of acute pancreatitis. New diagnostic tests such as rapid urinary trypsinogen-2 test and inflammatory mediators including polymorphnuclear elastase, C-reactive protein and interleukin-6 contribute to early diagnosis, prognostic evaluation and initiation of an appropriate therapy.

  10. Chronic pancreatitis

    Science.gov (United States)

    ... body Blockage of the tubes (ducts) that drain enzymes from the pancreas Cystic fibrosis High levels of a fat, called ... Limiting caffeine The health care provider may prescribe pancreatic enzymes. You must take these medicines with every meal. ...

  11. Acute pancreatitis

    Science.gov (United States)

    ... rate Lab tests that show the release of pancreatic enzymes will be done. These include: Increased blood amylase level Increased serum blood lipase level Increased urine amylase ... include: Abdominal CT scan Abdominal MRI Abdominal ultrasound

  12. Pancreatic Ductal Adenocarcinoma Associated with Autoimmune Pancreatitis

    OpenAIRE

    Pezzilli, Raffaele; Vecchiarelli, Silvia; Di Marco, Maria Cristina; SERRA, CARLA; Santini, Donatella; Calculli, Lucia; Fabbri, Dario; Rojas Mena, Betzabè; Imbrogno, Andrea

    2011-01-01

    Autoimmune pancreatitis (AIP), in contrast to other benign chronic pancreatic diseases, can be cured with immunosuppressant drugs, thus the differentiation of AIP from pancreatic cancer is of particular interest in clinical practice. There is the possibility that some patients with AIP may develop pancreatic cancer, and this possibility contributes to increasing our difficulties in differentiating AIP from pancreatic cancer. We herein report the case of a 70-year-old man in whom pancreatic ad...

  13. Fusion of cell-penetrating peptides to thermally responsive biopolymer improves tumor accumulation of p21 peptide in a mouse model of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Walker LR

    2014-10-01

    Full Text Available Leslie R Walker,1 Jung Su Ryu,1 Eddie Perkins,2 Lacey R McNally,3 Drazen Raucher1 1Department of Biochemistry, 2Department of Neurosurgery, University of Mississippi Medical Center, Jackson, MS, USA; 3Division of Hematology and Oncology, University of Louisville, Louisville, KY, USAAbstract: Current therapies for the treatment of pancreatic cancer are limited. The limitations of this type of treatment are abundant. The majority of chemotherapeutic agents used in clinics are highly toxic to both tumor cells and normal tissues due to the lack of specificity. Resistance can develop due to overexposure of these agents. To address these issues, these agents must be made more exclusive toward the tumor site. We have developed a macromolecular carrier based on the sequence of the biopolymer elastin-like polypeptide (ELP that is able to aggregate upon reaching the externally heated tumor environment. This carrier is specific to the tumor as it only aggregates at the heated tumor site. ELP is soluble below its transition temperature but will aggregate when the temperature is raised above its transition temperature. ELP was modified by p21, a cell cycle inhibitory peptide, and the addition of Bac, a cell-penetrating peptide with nuclear localization capabilities. In this study, p21-ELP-Bac and its control, ELP-p21, were used in cell proliferation studies using the pancreatic cancer cell lines Panc-1, MiaPaca-2, and S2013. ELP-p21 had little effect on proliferation, while the half maximal inhibitory concentration of p21-ELP-Bac was ~30 µM. As translocation across the plasma membrane is a limiting step for delivery of macromolecules, these polypeptides were utilized in a pancreatic xenograft model to study the plasma clearance, biodistribution, tumor accumulation, and tumor reduction capabilities of the polypeptide with and without a cell-penetrating peptide.Keywords: elastin-like polypeptide, peptide, targeted drug delivery, macromolecule

  14. Acute pancreatitis

    International Nuclear Information System (INIS)

    A prospective study was performed on the relationship of CT findings to the clinical course of 148 patients with acute pancreatitis. The type of pancreatic inflammation seen on CT was classified into six categories based on an overall assessment of size, contour and density of the gland, and peripancreatic abnormalities. The majority (94%) of patients in whom CT showed mild pancreatic changes (grades A, B and C) had two or less positive clinical indicaters of severe pancreatitis (Ranson's signs). In contrast, 92% of patients in whom CT showed more severe changes of pancreatitis (grades D, E or F) had three or more positive signs. The nine patients who died with pancreatitis-related complications were in grades D, E or F. We wish to draw attention to a CT appearance which we have called 'fat islets' (low density intrapancreatic or peripancreatic areas, the contents of which approach fat in attenuation values); there was a strong correlation between this appearance and subsequent infection. (author). 24 refs.; 7 figs.; 4 tabs

  15. Pancreatic Cancer Early Detection Program

    Science.gov (United States)

    2014-07-30

    Pancreatic Cancer; Pancreas Cancer; Pancreatic Adenocarcinoma; Familial Pancreatic Cancer; BRCA 1/2; HNPCC; Lynch Syndrome; Hereditary Pancreatitis; FAMMM; Familial Atypical Multiple Mole Melanoma; Peutz Jeghers Syndrome

  16. GEMMs as preclinical models for testing pancreatic cancer therapies

    OpenAIRE

    Aarthi Gopinathan; Morton, Jennifer P.; Jodrell, Duncan I.; Owen J. Sansom

    2015-01-01

    ABSTRACT Pancreatic ductal adenocarcinoma is the most common form of pancreatic tumour, with a very limited survival rate and currently no available disease-modifying treatments. Despite recent advances in the production of genetically engineered mouse models (GEMMs), the development of new therapies for pancreatic cancer is still hampered by a lack of reliable and predictive preclinical animal models for this disease. Preclinical models are vitally important for assessing therapies in the fi...

  17. Hedgehog/Ras interactions regulate early stages of pancreatic cancer

    OpenAIRE

    Pasca di Magliano, Marina; Sekine, Shigeki; Ermilov, Alexandre; Ferris, Jenny; Dlugosz, Andrzej A.; Hebrok, Matthias

    2006-01-01

    Pancreatic ductal adenocarcinoma (PDA) constitutes a lethal disease that affects >30,000 people annually in the United States. Deregulation of Hedgehog signaling has been implicated in the pathogenesis of PDA. To gain insights into the role of the pathway during the distinct stages of pancreatic carcinogenesis, we established a mouse model in which Hedgehog signaling is activated specifically in the pancreatic epithelium. Transgenic mice survived to adulthood and developed undifferentiated ca...

  18. Spontaneous regression of pancreatic cancer: Real or a misdiagnosis?

    OpenAIRE

    2012-01-01

    Spontaneous tumor regression has been subject of numerous studies and speculations for many years. This phenomenon is exceptional, but well reported, in some types of tumors, but not in pancreatic cancer. Pancreatic cancer has the worst five-year survival rate of any cancer. Despite numerous molecular studies and clinical approaches, using several mouse models, this cancer responds poorly to the existing chemotherapeutic agents and progress on treatment remains elusive. Although pancreatic ca...

  19. Optogenetic Control of Pancreatic Islets.

    Science.gov (United States)

    Reinbothe, Thomas M; Mollet, Inês G

    2016-01-01

    In light of the emerging diabetes epidemic, new experimental approaches in islet research are needed to elucidate the mechanisms behind pancreatic islet dysfunction and to facilitate the development of more effective therapies. Optogenetics has created numerous new experimental tools enabling us to gain insights into processes little was known about before. The spatial and temporal precision that it can achieve is also attractive for studying the cells of the pancreatic islet and we set out to explore the possibilities of this technology for our purposes. We here describe how to use the islets of an "optogenetic beta-cell" mouse line in islet batch incubations and Ca(2+) imaging experiments. This protocol enables light-induced insulin release and provides an all-optical solution to control and measure intracellular Ca(2+) levels in pancreatic beta-cells. The technique is easy to set up and provides a useful tool for controlling the activity of distinct islet cell populations. PMID:26965119

  20. Comparison of a chimeric anti-carcinoembryonic antigen antibody conjugated with visible or near-infrared fluorescent dyes for imaging pancreatic cancer in orthotopic nude mouse models

    Science.gov (United States)

    Maawy, Ali A.; Hiroshima, Yukihiko; Kaushal, Sharmeela; Luiken, George A.; Hoffman, Robert M.; Bouvet, Michael

    2013-12-01

    The aim of this study was to evaluate a set of visible and near-infrared dyes conjugated to a tumor-specific chimeric antibody for high-resolution tumor imaging in orthotopic models of pancreatic cancer. BxPC-3 human pancreatic cancer was orthotopically implanted into pancreata of nude mice. Mice received a single intravenous injection of a chimeric anti-carcinoembryonic antigen antibody conjugated to one of the following fluorophores: 488-nm group (Alexa Fluor 488 or DyLight 488); 550-nm group (Alexa Fluor 555 or DyLight 550); 650-nm group (Alexa Fluor 660 or DyLight 650), or the 750-nm group (Alexa Fluor 750 or DyLight 755). After 24 h, the Olympus OV100 small-animal imaging system was used for noninvasive and intravital fluorescence imaging of mice. Dyes were compared with respect to depth of imaging, resolution, tumor-to-background ratio (TBR), photobleaching, and hemoglobin quenching. The longer wavelength dyes had increased depth of penetration and ability to detect the smallest tumor deposits and provided the highest TBRs, resistance to hemoglobin quenching, and specificity. The shorter wavelength dyes were more photostable. This study showed unique advantages of each dye for specific cancer imaging in a clinically relevant orthotopic model.

  1. Overexpression of monocarboxylate transporter-1 (Slc16a1) in mouse pancreatic ß-cells leads to relative hyperinsulinism during exercise

    DEFF Research Database (Denmark)

    Pullen, Timothy J; Sylow, Lykke; Sun, Gao;

    2012-01-01

    in ß-cells is sufficient to cause EIHI by allowing entry of pyruvate and triggering insulin secretion thus remains unproven. Therefore, we generated a transgenic mouse capable of doxycycline-induced, ß-cell-specific overexpression of MCT1 to test this model directly. MCT1 expression caused isolated...

  2. Genetic ablation of Bcl-x attenuates invasiveness without affecting apoptosis or tumor growth in a mouse model of pancreatic neuroendocrine cancer.

    Directory of Open Access Journals (Sweden)

    Jeffrey H Hager

    Full Text Available Tumor cell death is modulated by an intrinsic cell death pathway controlled by the pro- and anti-apoptotic members of the Bcl-2 family. Up-regulation of anti-apoptotic Bcl-2 family members has been shown to suppress cell death in pre-clinical models of human cancer and is implicated in human tumor progression. Previous gain-of-function studies in the RIP1-Tag2 model of pancreatic islet carcinogenesis, involving uniform or focal/temporal over-expression of Bcl-x(L, demonstrated accelerated tumor formation and growth. To specifically assess the role of endogenous Bcl-x in regulating apoptosis and tumor progression in this model, we engineered a pancreatic beta-cell-specific knockout of both alleles of Bcl-x using the Cre-LoxP system of homologous recombination. Surprisingly, there was no appreciable effect on tumor cell apoptosis rates or on tumor growth in the Bcl-x knockout mice. Other anti-apoptotic Bcl-2 family members were expressed but not substantively altered at the mRNA level in the Bcl-x-null tumors, suggestive of redundancy without compensatory transcriptional up-regulation. Interestingly, the incidence of invasive carcinomas was reduced, and tumor cells lacking Bcl-x were impaired in invasion in a two-chamber trans-well assay under conditions mimicking hypoxia. Thus, while the function of Bcl-x in suppressing apoptosis and thereby promoting tumor growth is evidently redundant, genetic ablation implicates Bcl-x in selectively facilitating invasion, consistent with a recent report documenting a pro-invasive capability of Bcl-x(L upon exogenous over-expression.

  3. Genetic architecture of early pre-inflammatory stage transcription signatures of autoimmune diabetes in the pancreatic lymph nodes of the NOD mouse reveals significant gene enrichment on chromosomes 6 and 7

    Directory of Open Access Journals (Sweden)

    Beatrice Regnault

    2015-12-01

    Full Text Available Autoimmune diseases are characterized by the stimulation of an excessive immune response to self-tissues by inner and/or outer organism factors. Common characteristics in their etiology include a complex genetic predisposition and environmental triggers as well as the implication of the major histocompatibility (MHC locus on human chromosome 6p21. A restraint number of non-MHC susceptibility genes, part of the genetic component of type 1 diabetes have been identified in human and in animal models, while the complete spectrum of genes involved remains unknown. We elaborate herein patterns of chromosomal organization of 162 genes differentially expressed in the pancreatic lymph nodes of Non-Obese Diabetic mice, carefully selected by early sub-phenotypic evaluation (presence or absence of insulin autoantibodies. Chromosomal assignment of these genes revealed a non-random distribution on five chromosomes (47%. Significant gene enrichment was observed in particular for two chromosomes, 6 and 7. While a subset of these genes coding for secreted proteins showed significant enrichment on both chromosomes, the overall pool of genes was significantly enriched on chromosome 7. The significance of this unexpected gene distribution on the mouse genome is discussed in the light of novel findings indicating that genes affecting common diseases map to recombination “hotspot” regions of mammalian genomes. The genetic architecture of transcripts differentially expressed in specific stages of autoimmune diabetes offers novel venues towards our understanding of patterns of inheritance potentially affecting the pathological disease mechanisms.

  4. Specific tumor labeling enhanced by polyethylene glycol linkage of near infrared dyes conjugated to a chimeric anti-carcinoembryonic antigen antibody in a nude mouse model of human pancreatic cancer

    Science.gov (United States)

    Maawy, Ali A.; Hiroshima, Yukihiko; Zhang, Yong; Luiken, George A.; Hoffman, Robert M.; Bouvet, Michael

    2014-10-01

    Labeling of metastatic tumors can aid in their staging and resection of cancer. Near infrared (NIR) dyes have been used in the clinic for tumor labeling. However, there can be a nonspecific uptake of dye by the liver, lungs, and lymph nodes, which hinders detection of metastasis. In order to overcome these problems, we have used two NIR dyes (DyLight 650 and 750) conjugated to a chimeric anti-carcinoembryonic antigen antibody to evaluate how polyethylene glycol linkage (PEGylation) can improve specific tumor labeling in a nude mouse model of human pancreatic cancer. The conjugated PEGylated and non-PEGylated DyLight 650 and 750 dyes were injected intravenously into non-tumor-bearing nude mice. Serum samples were collected at various time points in order to determine serum concentrations and elimination kinetics. Conjugated PEGylated dyes had significantly higher serum dye concentrations than non-PEGylated dyes (p=0.005 for the 650 dyes and ppancreatic tumors subcutaneously implanted into nude mice were labeled with antibody-dye conjugates and serially imaged. Labeling with conjugated PEGylated dyes resulted in significantly brighter tumors compared to the non-PEGylated dyes (p<0.001 for the 650 dyes; p=0.01 for 750 dyes). PEGylation of the NIR dyes also decreased their accumulation in lymph nodes, liver, and lung. These results demonstrate enhanced selective tumor labeling by PEGylation of dyes conjugated to a tumor-specific antibody, suggesting their future clinical use in fluorescence-guided surgery.

  5. Pancreatic cancer.

    Science.gov (United States)

    Kleeff, Jorg; Korc, Murray; Apte, Minoti; La Vecchia, Carlo; Johnson, Colin D; Biankin, Andrew V; Neale, Rachel E; Tempero, Margaret; Tuveson, David A; Hruban, Ralph H; Neoptolemos, John P

    2016-01-01

    Pancreatic cancer is a major cause of cancer-associated mortality, with a dismal overall prognosis that has remained virtually unchanged for many decades. Currently, prevention or early diagnosis at a curable stage is exceedingly difficult; patients rarely exhibit symptoms and tumours do not display sensitive and specific markers to aid detection. Pancreatic cancers also have few prevalent genetic mutations; the most commonly mutated genes are KRAS, CDKN2A (encoding p16), TP53 and SMAD4 - none of which are currently druggable. Indeed, therapeutic options are limited and progress in drug development is impeded because most pancreatic cancers are complex at the genomic, epigenetic and metabolic levels, with multiple activated pathways and crosstalk evident. Furthermore, the multilayered interplay between neoplastic and stromal cells in the tumour microenvironment challenges medical treatment. Fewer than 20% of patients have surgically resectable disease; however, neoadjuvant therapies might shift tumours towards resectability. Although newer drug combinations and multimodal regimens in this setting, as well as the adjuvant setting, appreciably extend survival, ∼80% of patients will relapse after surgery and ultimately die of their disease. Thus, consideration of quality of life and overall survival is important. In this Primer, we summarize the current understanding of the salient pathophysiological, molecular, translational and clinical aspects of this disease. In addition, we present an outline of potential future directions for pancreatic cancer research and patient management. PMID:27158978

  6. Pancreatic pseudocyst

    Institute of Scientific and Technical Information of China (English)

    Samir Habashi; Peter V Draganov

    2009-01-01

    Pancreatic pseudocysts are complications of acute or chronic pancreatitis. Initial diagnosis is accomplished most often by cross-sectional imaging. Endoscopic ultrasound with fine needle aspiration has become the preferred test to help distinguish pseudocyst from other cystic lesions of the pancreas. Most pseudocysts resolve spontaneously with supportive care. The size of the pseudocyst and the length of time the cyst has been present are poor predictors for the potential of pseudocyst resolution or complications, but in general, larger cysts are more likely to be symptomatic or cause complications. The main two indications for some type of invasive drainage procedure are persistent patient symptoms or the presence of complications (infection, gastric outlet or biliary obstruction, bleeding). Three different strategies for pancreatic pseudocysts drainage are available: endoscopic (transpapillary or transmural) drainage, percutaneous catheter drainage, or open surgery. To date, no prospective controlled studies have compared directly these approaches. As a result, the management varies based on local expertise, but in general, endoscopic drainage is becoming the preferred approach because it is less invasive than surgery, avoids the need for external drain, and has a high long-term success rate. A tailored therapeutic approach taking into consideration patient preferences and involving multidisciplinary team of therapeutic endoscopist, interventional radiologist and pancreatic surgeon should be considered in all cases.

  7. Pancreatitis - discharge

    Science.gov (United States)

    ... may ask you to take extra capsules, called pancreatic enzymes. These will help your body absorb fats in ... tell you how many. When you take these enzymes, you may also need to ... stomach. If your pancreas has a lot of damage, you may also ...

  8. Lactoferrin in Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Chun Xiang Jin

    2009-05-01

    Full Text Available The present review is focused on the clinical significance of lactoferrin in pancreatic secretions and stone formation in chronic pancreatitis, and of serum anti-lactoferrin antibody in autoimmune pancreatitis. Lactoferrin secretion is increased in pancreatic secretions in calcified and non-calcified chronic pancreatitis. Lactoferrin, pancreatic stone protein and trypsin are present in pancreatic stones. We cannot conclude which protein is more important for the precipitate and stone formation. The presence of antilactoferrin antibody has been reported in serum in autoimmune diseases, such as autoimmune pancreatitis. The coincidental appearance of autoimmune pancreatitis with extrapancreatic autoimmune diseases strongly suggests a common autoimmune mechanism and lactoferrin is a candidate antigen. Lactoferrin may play an important role as a precipitate protein in pancreatic stone formation in chronic pancreatitis and as an autoantigen in autoimmune pancreatitis. Further studies are required to better understand the role of lactoferin.

  9. Is Pancreatic Cancer Hereditary?

    Science.gov (United States)

    ... Board Patient Education / Basics of Pancreatic Cancer Is pancreatic cancer hereditary? Cancer of the pancreas is a genetic ... found in cigarette smoke. The genetics of hereditary pancreatic cancer is a focus of research at Johns Hopkins. ...

  10. Pancreatic Islet Transplantation

    Science.gov (United States)

    ... Diabetes, Gum Disease, and Other Dental Problems Diabetic Eye Disease Diabetes and Pregnancy Financial Help for Diabetes Care Diabetes Statistics Pancreatic Islet Transplantation What are pancreatic islets? Pancreatic islets, also called ...

  11. Pancreatic tuberculosis masquerading as pancreatic serous cystadenoma

    Institute of Scientific and Technical Information of China (English)

    Seung Goun Hong; Jae Seon Kim; Moon Kyung Joo; Kwang Gyun Lee; Key Hyeon Kim; Cho Rong Oh; Jong-Jae Park; Young-Tae Bak

    2009-01-01

    Solitary pancreatic involvement of tuberculosis is rare,especially in an immunocompetent individual, and it may be misdiagnosed as pancreatic cystic neoplasms.Pancreatic cystic neoplasms are being identified in increasing numbers, probably because of the frequent use of radiology and advances in endoscopic techniques.However, they are composed of a variety of neoplasms with a wide range of malignant potential,and it is often difficult to differentiate pancreatic tuberculosis mimicking cystic neoplasms from benign or malignant pancreatic cystic neoplasms. Non-surgical diagnosis of pancreatic tuberculosis is inconclusive and continues to be a challenge in many cases. If so,then laparotomy should be employed to establish the diagnosis. Therefore, pancreatic tuberculosis should be kept in mind during the differential diagnosis of solitary cystic masses in the pancreas. We report a patient who had solitary pancreatic tuberculosis masquerading as pancreatic serous cystadenoma.

  12. Nonoverlapping roles of PD-1 and FoxP3 in maintaining immune tolerance in a novel autoimmune pancreatitis mouse model.

    Science.gov (United States)

    Zhang, Baihao; Chikuma, Shunsuke; Hori, Shohei; Fagarasan, Sidonia; Honjo, Tasuku

    2016-07-26

    PD-1 (programmed-death 1), an immune-inhibitory receptor required for immune self-tolerance whose deficiency causes autoimmunity with variable severity and tissue specificity depending on other genetic factors, is expressed on activated T cells, including the transcription factor FoxP3(+) Treg cells known to play critical roles in maintaining immune tolerance. However, whether PD-1 expression by the Treg cells is required for their immune regulatory function, especially in autoimmune settings, is still unclear. We found that mice with partial FoxP3 insufficiency developed early-onset lympho-proliferation and lethal autoimmune pancreatitis only when PD-1 is absent. The autoimmune phenotype was rescued by the transfer of FoxP3-sufficient T cells, regardless of whether they were derived from WT or PD-1-deficient mice, indicating that Treg cells dominantly protect against development of spontaneous autoimmunity without intrinsic expression of PD-1. The absence of PD-1 combined with partial FoxP3 insufficiency, however, led to generation of ex-FoxP3 T cells with proinflammatory properties and expansion of effector/memory T cells that contributed to the autoimmune destruction of target tissues. Altogether, the results suggest that PD-1 and FoxP3 work collaboratively in maintaining immune tolerance mostly through nonoverlapping pathways. Thus, PD-1 is modulating the activation threshold and maintaining the balance between regulatory and effector T cells, whereas FoxP3 is sufficient for dominant regulation through maintaining the integrity of the Treg function. We suggest that genetic or environmental factors that even moderately affect the expression of both PD-1 and FoxP3 can cause life-threatening autoimmune diseases by disrupting the T-cell homeostasis. PMID:27410049

  13. 骨形态发生蛋白7对胰岛素分泌的影响及机制研究%Bone morphorgenetic protein 7 improves insulin secretion from mouse pancreatic beta cell line MIN6

    Institute of Scientific and Technical Information of China (English)

    姜友昭; 曾俊; 陈兵

    2012-01-01

    Objective To determine the effect of bone morphorgenetic protein 7 ( BMP7) on insulin secretion in pancreatic beta cells. Methods The expression of three type I receptors of BMP7 , BMPR1 A, BMPR1B and ACVR1A, was detected by Western blotting in mouse pancreatic beta cell line MIN6. Then the MIN6 cells were treated respectively by PBS (control), low-, medium- and high-dose of rhBMP7 (final concentration of rhBMP7 was 10, 50, and 100 ng/ml). Then the insulin level of the culture media was detected by ELISA and the intracellular concentration of calcium was determined by laser confocal microscopy. Results BMPR1A, BMPR1B and ACVR1A were all expressed in the MIN6 cells. The insulin concentration of PBS, low-, medium- and high-dose rhBMP7 treatment was 0.42 ±0. 11, 0.63 ±0.22, 0.82+0.0.19 and 1.24 ±0. 26 ng/(ml ·μxg) , respectively. The insulin concentration of rhBMP7 treatment groups was significantly higher than that of the control (all P 0. 05). Conclusion BMP7 enhances insulin secretion significantly in pancreatic beta cells, which may be due to its regulation of calcium-independent exocytosis.%目的 探讨骨形态发生蛋白7(bone morphorgenetic protein 7,BMP7)对胰岛细胞胰岛素分泌的影响.方法 Westem blot检测小鼠胰岛细胞株MIN6中3种BMP7的Ⅰ型受体BMPR1A、BMPR 1B、ACVR1A的表达情况.将MIN6细胞分为4组:PBS对照组,重组人BMP7( rhBMP7)低、中、高剂量组(rhBMP7终浓度分别为10、50、100 ng/ml),每组设5个复孔.ELISA检测各组细胞培养基中的胰岛素分泌情况.激光共聚焦显微镜检测细胞内钙离子浓度变化.结果 BMPR1A、BMPR1B、ACVR1A均表达于MIN6细胞.PBS对照组及rhBMP7低、中、高剂量组的胰岛素浓度分别为(0.42±0.11)、(0.63±0.22)、(0.82±0.19)、( 1.24 -±0.26) ng/(ml· μg).与对照组相比,rhBMP7低、中、高剂量组的胰岛素分泌均明显增加(P<0.05).PBS对照组及rhBMP7低、中、高剂量组的细胞内钙离子浓度增加分别为(3.5

  14. ERCP in acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Jijo V Cherian; Joye Varghese Selvaraj; Rajesh Natrayan; Jayanthi Venkataraman

    2007-01-01

    BACKGROUND:The role of endoscopic retrograde cholangiopancreatography (ERCP) in the management of acute pancreatitis has evolved over years since its introduction in 1968. Its importance in diagnosing the etiology of pancreatitis has steadily declined with the advent of less invasive diagnostic tools. The therapeutic implications of ERCP in acute pancreatitis are many fold and are directed towards management of known etiological factors or its related complications. This article highlights the current status of ERCP in acute pancreatitis. DATA SOURCES:An English literature search using PubMed database was conducted on ERCP in acute pancreatitis, the etiologies and complications of pancreatitis amenable to endotherapy and other related subjects, which were reviewed. RESULTS: ERCP serves as a primary therapeutic modality for management of biliary pancreatitis in speciifc situations, pancreatitis due to microlithiasis, speciifc types of sphincter of Oddi dysfunction, pancreas divisum, ascariasis and malignancy. In recurrent acute pancreatitis and smoldering pancreatitis it has a deifnite therapeutic utility. Complications of acute pancreatitis including pancreatic-duct disruptions or leaks, benign pancreatic-lfuid collections and pancreatic necrosis can be beneifcially dealt with. Intraductal ultrasound and pancreatoscopy during ERCP are useful in detecting pancreatic malignancy. CONCLUSIONS:The role of ERCP in acute pancreatitis is predominantly therapeutic and occasionally diagnostic. Its role in the management continues to evolve and advanced invasive procedures should be undertaken only in centers dedicated to pancreatic care.

  15. Pancreatic Satellite Cells Derived Galectin-1 Increase the Progression and Less Survival of Pancreatic Ductal Adenocarcinoma

    Science.gov (United States)

    Gao, Jun; Wang, Sen; Ye, Nianyuan; Li, Ping; Gao, Sujun; Miao, Yi; Wang, Daorong; Jiang, Kuirong

    2014-01-01

    Background Galectin-1, a member of carbohydrate-binding proteins with a polyvalent function on tumor progression, was found strongly expressed in pancreatic satellite cells (PSCs), which partner in crime with cancer cells and promote the development of pancreatic ductal adenocarcinoma (PDAC). We evaluated the effects of PSCs derived Galectin-1 on the progression of PDAC, as well as the tumor establishment and development in mouse xenografts. Methods The relationship between immunohistochemistry staining intensity of Galectin-1 and clinicopathologic variables were assessed in 66 PDAC tissues, 18 chronic pancreatitis tissues and 10 normal controls. The roles of PSCs isolated from PDAC and normal pancreas on the proliferative activity, MMP2 and MMP9 expression, and the invasion of CFPAC-1 in the co-cultured system, as well as on the tumor establishment and development in mouse xenografts by mixed implanting with CFPAC-1 subcutaneously were evaluated. Results Galectin-1 expression was gradually increased from normal pancreas (negative), chronic pancreatitis (weak) to PDAC (strong), in which Galectin-1 expression was also increased from well, moderately to poorly differentiated PDAC. Galectin-1 staining intensity of pancreatic cancer tissue was associated with increase in tumor size, lymph node metastasis, perineural invasion and differentiation and UICC stage, and served as the independent prognostic indicator of poor survival of pancreatic cancer. In vitro and in vivo experiments indicated that TGF-β1 upregulated Galectin-1 expression in PSCs, which could further promotes the proliferative activity, MMP2 and MMP9 expression, and invasion of pancreatic cancer cells, as well as the tumor establishment and growth. Conclusion Galectin-1 expression in stromal cells of pancreatic cancer suggests that this protein plays a role in the promotion of cancer cells invasion and metastasis and provides a therapeutic target for the treatment of pancreatic cancer. PMID:24595374

  16. Metformin induced acute pancreatitis

    OpenAIRE

    Alsubaie, Sadeem; Almalki, Mussa H.

    2013-01-01

    Acute pancreatitis frequently presents with abdomen pain but may presents with various skin manifestations as rash and rarely, pancreatic panniculitis. Metformin, one of the most effective and valuable oral hypoglycemic agents in the biguanide class was linked to acute pancreatitis in few cases. Here, we report a case of metformin induce acute pancreatitis in young healthy man with normal renal function.

  17. Ultrasonographic diagnosis of pancreatitis

    International Nuclear Information System (INIS)

    A retrospective analysis of ultrasonograms of 24 patients with acute pancreatitis and 8 patients with chronic pancreatitis was performed. Nine cases were proven by surgery and 23 cases were diagnosed clinically. Generalized pancreatic enlargement with normal or decreased echogenecity was principal findings in acute pancreatitis, while pancreas was normal in size and echogenecity was normal or slightly altered in chronic pancreatitis. Ultrasonography is considered a simple and accurate method in the diagnosis of acute pancreatitis and thus it could be an initial test in patients with suspected acute pancreatitis

  18. PDX-1 Is a Therapeutic Target for Pancreatic Cancer, Insulinoma and Islet Neoplasia Using a Novel RNA Interference Platform

    OpenAIRE

    Liu, Shi-He; Rao, Donald D; Nemunaitis, John; Senzer, Neil; Zhou, Guisheng; Dawson, David; Gingras, Marie-Claude; Wang, Zhaohui; Gibbs, Richard,; Norman, Michael; Nancy S Templeton; DeMayo, Francesco J; O'Malley, Bert; Sanchez, Robbi; Fisher, William E.

    2012-01-01

    Pancreatic and duodenal homeobox-1 (PDX-1) is a transcription factor that regulates insulin expression and islet maintenance in the adult pancreas. Our recent studies demonstrate that PDX-1 is an oncogene for pancreatic cancer and is overexpressed in pancreatic cancer. The purpose of this study was to demonstrate that PDX-1 is a therapeutic target for both hormonal symptoms and tumor volume in mouse models of pancreatic cancer, insulinoma and islet neoplasia. Immunohistochemistry of human pan...

  19. 简便快捷的小鼠胰岛分离纯化方法研究%A Convenient and Efficient Method of Mouse Pancreatic Islet Isolation and Purification

    Institute of Scientific and Technical Information of China (English)

    合湫; 苏恒; 李超; 沈涛; 严新民; 薛元明

    2012-01-01

    目的 探讨小鼠胰岛分离与纯化的方法.方法 采用多点注射灌注胶原酶法消化胰腺,不连续密度梯度离心联合人工挑取的方法分离、纯化胰岛.双硫腙特异性染色后计算胰岛产量及纯度.葡萄糖刺激后测定培养上清液胰岛素水平检测胰岛功能.结果 (1)每只小鼠采用上述分离、纯化法平均得到(114±15)个胰岛,平均纯度为(77.12±3.23)%,胰岛细胞存活率>90%; (2)分离、纯化的胰岛培养上清液中胰岛素水平在无糖、低糖(2.8 mmol/L)和高糖(22.2 mmol/L)刺激下分别为(23.80±3.52) mIU/L、 (67.57 ±4.04) mIU/L和(164.32±10.75) mIU/L,各组间比较,差异有统计学意义(P<0.05).两两比较,低糖组的胰岛素水平为无糖组的2.84倍(P< 0.05),高糖组的胰岛素水平为低糖组的2.43倍(P<0.05),高糖组的胰岛素水平为无糖组的6.90倍(P<0.05).结论 采用多点注射灌注胶原酶法消化胰腺,不连续密度梯度离心联合人工挑取的方法分离、纯化的小鼠胰岛产量及纯度较高,形态完整,不同浓度葡萄糖刺激后胰岛素分泌反应良好,是一种简便、快捷的小鼠胰岛分离方法.%Objective To investigate a convenient and efficient method of mouse pancreatic islets isolation and purification. Methods The isolation of mouse pancreatic islets was carried out by stationary digestion after multi-point injection of collagenase IV solution into the pancreas. A discontinuous Histopaque solution (1119, 1110, 1080 and 1060) was applied for the purification of the islets. Islet cell purity and viability were determined by dithizone ( DTZ) and Trypan blue staining. The islets were cultured overnight and stimulated with different concentration of glucose (0, 2.8 and 22.2mmol/L) for 1 hour. Supernatants were collected for insulin assays by an insulin RIA kit. Results (1) By this optimized islets isolation and purification protocol, each mouse pancreas could yield (114 ± 15) islets, with an

  20. Biomarkers for pancreatic carcinogenesis

    OpenAIRE

    Hustinx, S.R.

    2007-01-01

    Pancreatic cancer is a devastating disease. Most pancreatic cancers (approximately 85%) are diagnosed at a late, incurable stage. The poor prognosis and late presentation of pancreatic cancer patients underscore the importance of early detection, which is the sine qua non for the fight against pancreatic cancer. It is hoped for the future that the understanding of genetic alterations will lead to the rapid discovery of an effective biomarker of pancreatic carcinogenesis. In this thesis we vis...

  1. Complications of pancreatic surgery

    OpenAIRE

    Åke Andrén-Sandberg

    2011-01-01

    Many diseases, including pancreatitis benign tumors and cancer, may require pancreas surgery. Pancreatic resection can lead to a prolonged survival in pancreatic cancer and even a potential chance for cure. However, the pancreatic surgery can result in complications, and high postoperative morbidity rates are still presence. This article reviews the pancreatic abstracts of American Pancreas Club 2011, which involves the more common complications, their prevention and treatment.

  2. Complications of pancreatic surgery

    Directory of Open Access Journals (Sweden)

    Åke Andrén-Sandberg

    2011-01-01

    Full Text Available Many diseases, including pancreatitis benign tumors and cancer, may require pancreas surgery. Pancreatic resection can lead to a prolonged survival in pancreatic cancer and even a potential chance for cure. However, the pancreatic surgery can result in complications, and high postoperative morbidity rates are still presence. This article reviews the pancreatic abstracts of American Pancreas Club 2011, which involves the more common complications, their prevention and treatment.

  3. Pancreatic transplantation

    Directory of Open Access Journals (Sweden)

    Åke Andrén-Sandberg

    2010-01-01

    Full Text Available A pancreas transplant is a surgical procedure to place a healthy pancreas from a donor into a patient whose pancreas no longer functions properly. Exocrine pancreas transplantation remains the standard treatment of choice for patients with diabetes mellitus complicated by end-stage renal disease. The use of pancreas transplantation for type 2 diabetes mellitus is an emerging concept. A pancreas transplant is often done in conjunction with a kidney transplant. Even if pancreas transplantation provides the best glycemic control option for diabetes mellitus, it is associated with significant morbidities related to infectious disease. The present article provides with a review of pancreatic transplantation.

  4. Chronic pancreatitis, pancreatic adenocarcinoma and the black box in-between

    Institute of Scientific and Technical Information of China (English)

    Natalia JURA; Herbert ARCHER; Dafna BAR-SAGI

    2005-01-01

    Pancreatic cancer is a challenging disease for patients, doctors and researchers who for decades have searched for a cure for this deadly malignancy. Although existing mouse models of pancreatic cancer have shed light on the mechanistic basis of the neoplastic conversion of the pancreas, their impact in terms of offering new diagnostics and therapeutic modalities remains limited. Chronic pancreatitis is an inflammatory disease of the pancreas that is associated with a gradual damage of the organ and an increased risk of developing neoplastic lesions. In this review, we propose that detailed studies of chronic inflammatory processes in the pancreas will provide insights into the evolution of pancreatic cancer. This information may prove useful in the design of effective therapeutic strategies to battle the disease.

  5. Pancreatic Cancer (Beyond the Basics)

    Science.gov (United States)

    ... Terms of Use ©2016 UpToDate, Inc. Patient information: Pancreatic cancer (Beyond the Basics) Author David P Ryan, MD ... pancreatic juice to the intestines. This type of pancreatic cancer, called "pancreatic ductal adenocarcinoma," is discussed in this ...

  6. MRI enhancement scanning features and pathology of the orthotropic transplantation nude mouse model with human pancreatic cancer%人胰腺癌原位移植模型MRI增强扫描特征及病理对照研究

    Institute of Scientific and Technical Information of China (English)

    王冬青; 何伟; 罗一烽; 孙维斌; 许云飞; 殷瑞根; 王铮超

    2011-01-01

    Objective To investigate the MRI imaging features, and pathologic basis of the orthotropic transplantation nude mouse model with human pancreatic cancer. Methods Adopting Siemens Magnetom Trio Tim 3.0 Tesla superconductive MRI and breast coil was used to examine 30 orthotropic transplantation nude mouse models of the human pancreatic cancer, these mouse were sampled to acquire TSE-T1 -weighted and T2-weighted transverse axial images. Intraperitoneal injection of Gd DTP A was used to perform continuous dynamic enhancement scanning. Signal intensities of tumors were measured in plain scanning and each phase' s enhancement scanning images, respectively. Intensification rates of tumors were calculated. Pathologic examination of tumors was performed to be compared with the findings of MRI scanning. Results The successful rate of inoculation of 30 nude mice was 100%. The histological findings were comparable with poorly differentiated adenocarcinoma. Compared with signal of adjacent tissues, the MRI findings of the tumors were uniformly slightly hypointensity (90% , 27/30) , or unevenly (10% , 3/30) on TSE-T1WI; uniformly (20% , 6/30) or unevenly (80% , 24/30) hyperintensity with equal or more hyper signal spots on TSE-T2WI. Signal intensities on plain scanning was 228.35 ±11.71, and 1.5,3,6,9, 12 min after enhancement scanning, thesignal intensities were 258.20 ± 11.17, 301.75 ± 17.09, 358.65 ±25.13, 480.05 ± 19.01, 558.35 ± 40.49, which were significantly higher than those in plain scanning (P <0.01). The intensification rate of every phase was 0.13 ±0.04, 0.35 ±0.11, 0.56 ±0.10, 1.10 ±0.10, 1.45 ±0.18, and the difference among these phases was statistically significant (P <0.01). The significantly intensified area was the area where the tumor cells grew actively with rich capillaries; the central area without intensification was the area of necrotic tissue and/or densely packed tumor cells and few capillaries. Conclusions High resolution MRI imaging of

  7. Autoimmune Pancreatitis: A Succinct Overview

    OpenAIRE

    Juan Putra; Xiaoying Liu

    2015-01-01

    Autoimmune pancreatitis is a rare type of chronic pancreatitis with characteristic clinical, radiologic, and histopathologic findings. Diagnosis of autoimmune pancreatitis is often challenging due to its low incidence and nonspecific clinical and radiologic findings. Patients with autoimmune pancreatitis and pancreatic cancer share similar clinical presentations, including obstructive jaundice, abdominal pain and weight loss. Due to these overlapping features, autoimmune pancreatitis patients...

  8. Formation of the tetraploid intermediate is associated with the development of cells with more than four centrioles in the elastase-simian virus 40 tumor antigen transgenic mouse model of pancreatic cancer.

    OpenAIRE

    1991-01-01

    The development of pancreatic cancer in transgenic mice expressing the simian virus 40 tumor antigen placed under controlling regions of the elastase I gene is characterized by the sequential appearance of tetraploid and then multiple aneuploid cell populations. Pancreatic tissues from such transgenic mice were studied between 8 and 32 days of age. Virtually 100% of acinar cell nuclei had immunohistochemically detectable tumor antigen by 18 days. Tetraploid cells were demonstrated by DNA cont...

  9. Pancreatic Pseudocyst Pleural Fistula in Gallstone Pancreatitis

    Directory of Open Access Journals (Sweden)

    Sala Abdalla

    2016-01-01

    Full Text Available Extra-abdominal complications of pancreatitis such as pancreaticopleural fistulae are rare. A pancreaticopleural fistula occurs when inflammation of the pancreas and pancreatic ductal disruption lead to leakage of secretions through a fistulous tract into the thorax. The underlying aetiology in the majority of cases is alcohol-induced chronic pancreatitis. The diagnosis is often delayed given that the majority of patients present with pulmonary symptoms and frequently have large, persistent pleural effusions. The diagnosis is confirmed through imaging and the detection of significantly elevated amylase levels in the pleural exudate. Treatment options include somatostatin analogues, thoracocentesis, endoscopic retrograde cholangiopancreatography (ERCP with pancreatic duct stenting, and surgery. The authors present a case of pancreatic pseudocyst pleural fistula in a woman with gallstone pancreatitis presenting with recurrent pneumonias and bilateral pleural effusions.

  10. PANIC-ATTAC: A Mouse Model for Inducible and Reversible β-Cell Ablation

    OpenAIRE

    Wang, Zhao V.; Mu, James; Schraw, Todd D.; Gautron, Laurent; Elmquist, Joel K.; Zhang, Bei B.; Brownlee, Michael; Scherer, Philipp E

    2008-01-01

    OBJECTIVE—Islet transplantations have been performed clinically, but their practical applications are limited. An extensive effort has been made toward the identification of pancreatic β-cell stem cells that has yielded many insights to date, yet targeted reconstitution of β-cell mass remains elusive. Here, we present a mouse model for inducible and reversible ablation of pancreatic β-cells named the PANIC-ATTAC (pancreatic islet β-cell apoptosis through targeted activation of caspase 8) mous...

  11. Autoimmune pancreatitis can develop into chronic pancreatitis

    OpenAIRE

    Maruyama, Masahiro; Watanabe, Takayuki; Kanai, Keita; Oguchi, Takaya; Asano, Jumpei; Ito, Tetsuya; Ozaki, Yayoi; Muraki, Takashi; Hamano, Hideaki; ARAKURA, Norikazu; Kawa, Shigeyuki

    2014-01-01

    Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into o...

  12. Induction of chronic pancreatitis by pancreatic duct ligation activates BMP2, apelin, and PTHrP expression in mice.

    Science.gov (United States)

    Rastellini, Cristiana; Han, Song; Bhatia, Vandanajay; Cao, Yanna; Liu, Ka; Gao, Xuxia; Ko, Tien C; Greeley, George H; Falzon, Miriam

    2015-10-01

    Chronic pancreatitis (CP) is a devastating disease with no treatments. Experimental models have been developed to reproduce the parenchyma and inflammatory responses typical of human CP. For the present study, one objective was to assess and compare the effects of pancreatic duct ligation (PDL) to those of repetitive cerulein (Cer)-induced CP in mice on pancreatic production of bone morphogenetic protein-2 (BMP2), apelin, and parathyroid hormone-related protein (PTHrP). A second objective was to determine the extent of cross talk among pancreatic BMP2, apelin, and PTHrP signaling systems. We focused on BMP2, apelin, and PTHrP since these factors regulate the inflammation-fibrosis cascade during pancreatitis. Findings showed that PDL- and Cer-induced CP resulted in significant elevations in expression and peptide/protein levels of pancreatic BMP2, apelin, and PTHrP. In vivo mouse and in vitro pancreatic cell culture experiments demonstrated that BMP2 stimulated pancreatic apelin expression whereas apelin expression was inhibited by PTHrP exposure. Apelin or BMP2 exposure inhibited PTHrP expression, and PTHrP stimulated upregulation of gremlin, an endogenous inhibitor of BMP2 activity. Transforming growth factor-β (TGF-β) stimulated PTHrP expression. Together, findings demonstrated that PDL- and Cer-induced CP resulted in increased production of the pancreatic BMP2, apelin, and PTHrP signaling systems and that significant cross talk occurred among pancreatic BMP2, apelin, and PTHrP. These results together with previous findings imply that these factors interact via a pancreatic network to regulate the inflammation-fibrosis cascade during CP. More importantly, this network communicated with TGF-β, a key effector of pancreatic pathophysiology. This novel network may be amenable to pharmacologic manipulations during CP in humans. PMID:26229008

  13. Pancreatic blood flow in experimental acute pancreatitis

    International Nuclear Information System (INIS)

    The etiology and pathogenesis of acute necrotizing hemorrhagic pancreatitis remain controversial. Recent work has suggested that an early fall in pancreatic blood flow, causing ischemia, may be the initiating factor. Using an established rat model of hemorrhagic pancreatitis and the fractional indicator distribution technique with 86RbCl, pancreatic blood flow and tissue perfusion have been measured at various times in the condition. Six groups of ten rats were studied: control sham operation and pancreatitis groups were sacrificed at 1, 6, and 24 hr. Pancreatic blood flow (% of cardiac output) and perfusion (blood flow/g tissue) were measured. Blood flow was increased by a maximum of 53% at 1 hr (P less than 0.001) and remained elevated for 24 hr, and perfusion was increased by a maximum of 70% (P less than 0.001) at 1 hr and remained elevated at 6 hr. Pancreatic perfusion declines after 6 hr due to increasing gland edema. The results demonstrate a significant increase in pancreatic blood flow and perfusion in experimentally induced acute pancreatitis, suggesting a primary inflammatory response, and refute the ischemic etiological theory

  14. Pancreatitis-imaging approach

    Institute of Scientific and Technical Information of China (English)

    Kiran; K; Busireddy; Mamdoh; AlObaidy; Miguel; Ramalho; Janaka; Kalubowila; Liu; Baodong; Ilaria; Santagostino; Richard; C; Semelka

    2014-01-01

    Pancreatitis is defined as the inflammation of the pancreas and considered the most common pancreatic disease in children and adults. Imaging plays a significant role in the diagnosis, severity assessment, recognition of complications and guiding therapeutic interventions. In the setting of pancreatitis, wider availability and good image quality make multi-detector contrastenhanced computed tomography(MD-CECT) the most used imaging technique. However, magnetic resonance imaging(MRI) offers diagnostic capabilities similar to those of CT, with additional intrinsic advantages including lack of ionizing radiation and exquisite soft tissue characterization. This article reviews the proposed definitions of revised Atlanta classification for acute pancreatitis, illustrates a wide range of morphologic pancreatic parenchymal and associated peripancreatic changes for different types of acute pancreatitis. It also describes the spectrum of early and late chronic pancreatitis imaging findings and illustrates some of the less common types of chronic pancreatitis, with special emphasis on the role of CT and MRI.

  15. Pancreatic Cancer Stage 3

    Science.gov (United States)

    ... 3 Description: Stage III pancreatic cancer; drawing shows cancer in the pancreas, common hepatic artery, and portal vein. Also shown ... and superior mesenteric artery. Stage III pancreatic cancer. Cancer ... near the pancreas. These include the superior mesenteric artery, celiac axis, ...

  16. Surgery for pancreatic cancer

    Science.gov (United States)

    ... medlineplus.gov/ency/article/007649.htm Surgery for pancreatic cancer To use the sharing features on this page, ... surgery are used in the surgical treatment of pancreatic cancer. Whipple procedure: This is the most common surgery ...

  17. Acute Pancreatitis in Children

    Science.gov (United States)

    ... a feeding tube or an IV to prevent malnutrition and improve healing. Does my child have to ... intestines. Can my child die from acute pancreatitis? Death from acute pancreatitis is quite rare in children– ...

  18. Diabetes and pancreatic cancer

    OpenAIRE

    MUNIRAJ, T.; Chari, S.T.

    2012-01-01

    The relationship between diabetes and pancreatic cancer is complex. Diabetes or impaired glucose tolerance is present in more than 2/3rd of pancreatic cancer patients. Epidemiological studies have consistently shown a modest increase in the risk of pancreatic cancer in type 2 diabetes, with an inverse relationship to duration of disease. Additionally, recent studies suggest that anti-diabetic medications may modulate the risk of pancreatic cancer in type 2 diabetes. Subjects >50 years of age ...

  19. Biomarkers for pancreatic carcinogenesis

    NARCIS (Netherlands)

    Hustinx, S.R.

    2007-01-01

    Pancreatic cancer is a devastating disease. Most pancreatic cancers (approximately 85%) are diagnosed at a late, incurable stage. The poor prognosis and late presentation of pancreatic cancer patients underscore the importance of early detection, which is the sine qua non for the fight against pancr

  20. Stages of Pancreatic Cancer

    Science.gov (United States)

    ... affect prognosis (chance of recovery) and treatment options. Pancreatic cancer is a disease in which malignant (cancer) cells form in the ... the cancer cells in the liver are actually pancreatic cancer cells. The disease is metastatic pancreatic cancer, not liver cancer. The ...

  1. Pancreatic Cancer Risk Factors

    Science.gov (United States)

    ... factors can affect a person’s chance of getting cancer of the pancreas. Most of these are risk factors for exocrine ... Chronic pancreatitis, a long-term inflammation of the pancreas, is linked with an increased risk of pancreatic cancer (especially in smokers), but most people with pancreatitis ...

  2. Enzymatic Debridement in Necrotizing Pancreatitis

    OpenAIRE

    Cakir, Murat; Tekin, Ahmet; Kucukkartallar, Tevfik; Vatansev, Husamettin; Kartal, Adil

    2015-01-01

    Multiple organ failure and pancreatic necrosis are the factors that determine prognosis in acute pancreatitis attacks. We investigated the effects of collagenase on the debridement of experimental pancreatic necrosis. The study covered 4 groups; each group had 10 rats. Group I was the necrotizing pancreatitis group. Group II was the collagenase group with pancreatic loge by isotonic irrigation following necrotizing pancreatitis. Group III was the collagenase group with pancreatic loge followi...

  3. Spontaneous regression of pancreatic cancer: Real or a misdiagnosis?

    Institute of Scientific and Technical Information of China (English)

    Marta Herreros-Villanueva; Elizabeth Hijona; Angel Cosme; Luis Bujanda

    2012-01-01

    Spontaneous tumor regression has been subject of numerous studies and speculations for many years.This phenomenon is exceptional,but well reported,in some types of tumors,but not in pancreatic cancer.Pancreatic cancer has the worst five-year survival rate of any cancer.Despite numerous molecular studies and clinical approaches,using several mouse models,this cancer responds poorly to the existing chemotherapeutic agents and progress on treatment remains elusive.Although pancreatic cancer tumors seldom undergo spontaneous regression,and some authors take that with skepticism,there are some cases reported in the literature.However,the variability in the description of the reports and technical details could make this process susceptible to misdiagnosis.Distinguishing between different types of pancreatic carcinoma should be taken with caution as they have wide differences in malignant potential.Diseases such as pancreatic benign tumors,insulinomas,or autoimmune pancreatitis could be responsible for this misdiagnosis as a pancreatic cancer.Here we review different cases reported,their clinical characteristics,and possible mechanisms leading to spontaneous regression of pancreatic cancer.We also discuss the possibilities of misdiagnosis.

  4. Primary Pancreatic Choriocarcinoma Presenting as Pancreatitis

    Directory of Open Access Journals (Sweden)

    Biggs Saravanan Ramachandran

    2012-03-01

    Full Text Available Context Pancreatic cancers can present with pancreatitis or its complications. Pancreatic choriocarcinoma is an extremely rare disease to involve pancreas. Case report A 27-year-old married woman presented to our facility with abdominal pain and fullness of 20-day duration. She was clinically diagnosed as acute pancreatitis with pseudocyst as a complication. Serum amylase was elevated with CT scan of abdomen showing a cystic lesion involving the pancreas. We approached the cyst with endoscopic ultrasonography and cyst fluid was aspirated and analyzed. Cyst fluid amylase was elevated and cytology revealed germ cell tumor. Serum beta human chorionic gonadotropin was elevated. She had a swelling over the jaw which also revealed choriocarcinoma in histopathological examination. Patient was started with chemotherapy. Conclusion We report this case of pancreatic choriocarcinoma due to its extreme rarity and the diagnostic dilemma it posed.

  5. Pancreatitis. An update

    International Nuclear Information System (INIS)

    Acute and chronic pancreatitis are becoming increasingly more severe diseases in the western world with far-reaching consequences for the individual patient as well as the socioeconomic situation. This article gives an overview of the contribution of radiological imaging to the diagnostics and therapy of both forms of the disease. Acute pancreatitis can be subdivided into severe (20 %) and mild manifestations. The diagnostics should be performed with computed tomography (CT) or magnetic resonance imaging (MRI) for assessing necrosis or potential infections only in severe forms of pancreatitis. In chronic pancreatitis transabdominal ultrasound should initially be adequate for assessment of the pancreas. For the differential diagnosis between pancreatic carcinoma and chronic pancreatitis, MRI with magnetic resonance cholangiopancreatography (MRCP) followed by an endoscopic ultrasound-guided fine needle aspiration is the method of choice. For the primary diagnosis for acute and chronic pancreatitis ultrasound examination is the modality of first choice followed by radiological CT and MRI with MRCP examinations. (orig.)

  6. Therapy of pancreatic cancer

    International Nuclear Information System (INIS)

    Pancreatic cancer remains one of the most difficult diseases to cure. Japan pancreas society guidelines for management of pancreatic cancer indicate therapeutic algorithm according to the clinical stage. For locally limited pancreatic cancer (cStage I, II, III in Japanese classification system), surgical resection is recommended, however prognosis is still poor. Major randomized controlled trials of resected pancreatic cancer indicates that adjuvant chemotherapy is superior to observation and gemcitabine is superior to 5-fluorouracil (FU). For locally advanced resectable pancreatic cancer (cStage IVa in Japanese classification system (JCS)), we perform neoadjuvant chemoradiotherapy. Phase I study established a recommended dose of 800 mg gemcitabine and radiation dose of 36 Gy. For locally advanced nonresectable pancreatic cancer (cStage IVa in JCS), chemoradiotherapy followed by chemotherapy is recommended. Although pancreatic cancer is chemotherapy resistant tumor, systemic chemotherapy is recommended for metastatic pancreatic cancer (cStage IVb in JCS). Single-agent gemcitabine is the standard first line agent for the treatment of advanced pancreatic cancer. Meta-analysis of chemotherapy showed possibility of survival benefit of gemcitabine combination chemotherapy over gemcitabine alone. We hope gemcitabine combination chemotherapy or molecular targeted therapy will improve prognosis of pancreatic cancer in the future. (author)

  7. Pancreatic Cancer Stage 2A

    Science.gov (United States)

    ... 2A Description: Stage IIA pancreatic cancer; drawing shows cancer in the pancreas and duodenum. The bile duct and pancreatic duct are also shown. Stage IIA pancreatic cancer. Cancer has spread to nearby tissue and organs ...

  8. Pancreatic Cancer Stage 2B

    Science.gov (United States)

    ... 2B Description: Stage IIB pancreatic cancer; drawing shows cancer in the pancreas and in nearby lymph nodes. Also shown are the bile duct, pancreatic duct, and duodenum. Stage IIB pancreatic cancer. Cancer has spread to nearby lymph nodes and ...

  9. Pancreatic Panniculitis: A rare manifestation of Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Ronak Patel

    2015-05-01

    Full Text Available Context Pancreatic panniculitis is a very rare complication associated with pancreatic disease and perhaps even a presage to pancreatic pathology. Case report We present a case of pancreatic panniculitis in a 61 year old patient who was treated for sudden onset of abdominal pain associated with nausea and vomiting secondary to acute pancreatitis of unknown etiology. He subsequently developed skin lesions consistent with pancreatic panniculitis which gradually improved after resolution of his acute condition and treatment with topical steroid cream. Conclusion We discuss and review the literature along with highlighting for the readers the important clinical and histopathologic features of acute pancreatitis associated pancreatic panniculitis.

  10. Hereditary Pancreatic and Hepatobiliary Cancers

    OpenAIRE

    Ashraf Haddad; Kowdley, Gopal C; Timothy M. Pawlik; Cunningham, Steven C.

    2011-01-01

    Hereditary etiologies of pancreatic and hepatobiliary cancers are increasingly recognized. An estimated >10% of pancreatic and increasing number of hepatobiliary cancers are hereditary. The cumulative risk of hereditary pancreatic cancer ranges from measurable but negligible in cystic fibrosis to a sobering 70% in cases of hereditary pancreatitis. Candidates for pancreatic cancer surveillance are those with a risk pancreatic cancer estimated to be >10-fold that of the normal population. Scree...

  11. Pancreatic Enzyme Supplementation in Acute Pancreatitis

    OpenAIRE

    R. V. Patankar; R. Chand; Johnson, C. D.

    1995-01-01

    This study evaluates the effect of oral pancreatic enzyme supplements on pain, analgesic requirement and the incidence of complications in patients with acute pancreatitis. This double blind, prospectively randomised placebo controlled study included 23 patients. Pain was monitored using a visual analogue scale; the analgesic requirement was assessed with a numerical score. No significant differences were noted between the median (range) pain scores of patients who received placebo: 22 (17.1–...

  12. Acute pancreatitis in pregnancy

    OpenAIRE

    Pitchumoni, Capecomorin S; Yegneswaran, Balaji

    2009-01-01

    Acute pancreatitis (AP) is a rare event in pregnancy, occurring in approximately 3 in 10 000 pregnancies. The spectrum of AP in pregnancy ranges from mild pancreatitis to serious pancreatitis associated with necrosis, abscesses, pseudocysts and multiple organ dysfunction syndromes. Pregnancy related hematological and biochemical alterations influence the interpretation of diagnostic tests and assessment of severity of AP. As in any other disease associated with pregnancy, AP is associated wit...

  13. Smoking and Pancreatic Disease

    OpenAIRE

    2013-01-01

    Smoking is a major risk factor for chronic pancreatitis and pancreatic cancer. However, the mechanisms through which it causes the diseases remain unknown. In the present manuscript we reviewed the latest knowledge gained on the effect of cigarette smoke and smoking compounds on cell signaling pathways mediating both diseases. We also reviewed the effect of smoking on the pancreatic cell microenvironment including inflammatory cells and stellate cells.

  14. Laparoscopy in pancreatic tumors

    OpenAIRE

    Shrikhande S; Barreto S; Shukla P.

    2007-01-01

    Recently, increasing number of manuscripts - original articles and case reports have attempted to provide evidence of the forays of minimal access surgery into pancreatic diseases. Many, based on the lack of Level I evidence, still believe that laparoscopy in pancreatic surgery is experimental. This article attempts to look into data exploring the existing use of minimally invasive surgery in pancreatic disease to answer a vital question - what does the evidence say on the current status of l...

  15. Diabetes and Pancreatic Cancer

    OpenAIRE

    Li, Donghui

    2012-01-01

    Type 2 diabetes mellitus is likely the third modifiable risk factor for pancreatic cancer after cigarette smoking and obesity. Epidemiological investigations have found that long-term type 2 diabetes mellitus is associated with a 1.5- to 2.0-fold increase in the risk of pancreatic cancer. A causal relationship between diabetes and pancreatic cancer is also supported by findings from prediagnostic evaluations of glucose and insulin levels in prospective studies. Insulin resistance and associat...

  16. Pancreatic Exocrine Function Testing

    OpenAIRE

    Goff, John S.

    1982-01-01

    It is important to understand which pancreatic function tests are available and how to interpret them when evaluating patients with malabsorption. Available direct tests are the secretin stimulation test, the Lundh test meal, and measurement of serum or fecal enzymes. Indirect tests assess pancreatic exocrine function by measuring the effect of pancreatic secretion on various nutrients. These include triglycerides labeled with carbon 14, cobalamin labeled with cobalt 57 and cobalt 58, and par...

  17. Pancreatic exocrine insufficiency after pancreatic surgery.

    Science.gov (United States)

    Goess, Ruediger; Ceyhan, Güralp O; Friess, Helmut

    2016-06-01

    Pancreatic exocrine insufficiency is an often-underestimated complication following pancreatic surgery. After recent advances in managing acute postoperative complications the focus of current research is now shifting onto the long-term complications following pancreatectomy. Weight loss and steatorrhea as typical symptoms have high influence on the quality of life in the postoperative period. Malnutrition-related symptoms occur late and are often misinterpreted. Enzyme replacement therapy is more or less the only possible treatment option, even though not many controlled trials have been performed in this field. In this review we summarized the pathophysiology, diagnosis, risk factors and treatment options of exocrine insufficiency and focus mainly on patients with pancreaticoduodenectomy (classical Whipple), pylorus-preserving pancreaticoduodenectomy (ppWhipple) or distal pancreatectomy. Incidence of pancreatic exocrine insufficiency after surgery depends mainly on the initial diagnosis, the preoperative exocrine function and is associated with the extent of parenchyma resection. Diagnosing exocrine failure after surgery can be difficult and specific function tests are commonly not routinely performed. Starting and monitoring of enzyme replacement treatment is more based on clinical symptoms, than on objective markers. To improve the performance status of postsurgical patients it is important to consider pancreatic exocrine function as one aspect of quality of life. Further clinical trials should be initiated to gain more specific knowledge about the influence of the different pancreatic resections on pancreatic exocrine function to initialize proper treatment even before major clinical symptoms occur. PMID:27058237

  18. Pancreatic Ductal Adenocarcinoma (PDA) mice lacking Mucin 1 have a profound defect in tumor growth and metastasis

    OpenAIRE

    Besmer, Dahlia M; CURRY, JENNIFER M.; Roy, Lopamudra D.; Tinder, Teresa L; Sahraei, Mahnaz; Schettini, Jorge; Hwang, Sun-Il; Lee, Yong Y.; Gendler, Sandra J.; Mukherjee, Pinku

    2011-01-01

    MUC1 is over expressed and aberrantly glycosolated in >60% of pancreatic ductal adenocarcinomas. The functional role of MUC1 in pancreatic cancer has yet to be fully elucidated due to a dearth of appropriate models. In the present study, we have generated mouse models that spontaneously develop pancreatic ductal adenocarcinoma (KC), which are either Muc1-null (KCKO) or express human MUC1 (KCM). We show that KCKO mice have significantly slower tumor progression and rates of secondary metastasi...

  19. Acute pancreatitis; Pancreatite aigue

    Energy Technology Data Exchange (ETDEWEB)

    Mehdi, M.; Deutsch, J.P.; Arrive, L.; Ayadi, K.; Ladeb, M.F.; Tubiana, J.M. [Centre Hospitalier Universitaire Saint-Antoine, 75 - Paris (France)

    1996-12-31

    The diagnosis of acute pancreatitis is based on clinical examination and basic laboratory tests. The main role of sonography in acute pancreatitis is to evaluate gallstones and small fluid collections. However, sonography is frequently difficult due to intestinal ileus related to pancreatitis. CT is indicated early in the clinical course of acute severe pancreatitis when the diagnosis is uncertain or when complications such as abscess, hemorrhage, or necrosis, are suspected. In addition, CT may be used to assess the prognosis and follow-up of patients. (authors). 20 refs., 12 figs., 4 tabs.

  20. Inactivation of TGFβ receptor II signalling in pancreatic epithelial cells promotes acinar cell proliferation, acinar-to-ductal metaplasia and fibrosis during pancreatitis.

    Science.gov (United States)

    Grabliauskaite, Kamile; Saponara, Enrica; Reding, Theresia; Bombardo, Marta; Seleznik, Gitta M; Malagola, Ermanno; Zabel, Anja; Faso, Carmen; Sonda, Sabrina; Graf, Rolf

    2016-02-01

    Determining signalling pathways that regulate pancreatic regeneration following pancreatitis is critical for implementing therapeutic interventions. In this study we elucidated the molecular mechanisms underlying the effects of transforming growth factor-β (TGFβ) in pancreatic epithelial cells during tissue regeneration. To this end, we conditionally inactivated TGFβ receptor II (TGFβ-RII) using a Cre-LoxP system under the control of pancreas transcription factor 1a (PTF1a) promoter, specific for the pancreatic epithelium, and evaluated the molecular and cellular changes in a mouse model of cerulein-induced pancreatitis. We show that TGFβ-RII signalling does not mediate the initial acinar cell damage observed at the onset of pancreatitis. However, TGFβ-RII signalling not only restricts acinar cell replication during the regenerative phase of the disease but also limits ADM formation in vivo and in vitro in a cell-autonomous manner. Analyses of molecular mechanisms underlying the observed phenotype revealed that TGFβ-RII signalling stimulates the expression of cyclin-dependent kinase inhibitors and intersects with the EGFR signalling axis. Finally, TGFβ-RII ablation in epithelial cells resulted in increased infiltration of inflammatory cells in the early phases of pancreatitis and increased activation of pancreatic stellate cells in the later stages of pancreatitis, thus highlighting a TGFβ-based crosstalk between epithelial and stromal cells regulating the development of pancreatic inflammation and fibrosis. Collectively, our data not only contribute to clarifying the cellular processes governing pancreatic tissue regeneration, but also emphasize the conserved role of TGFβ as a tumour suppressor, both in the regenerative process following pancreatitis and in the initial phases of pancreatic cancer. PMID:26510396

  1. Focal pancreatic enlargement: differentiation between pancreatic adenocarcinoma and focal pancreatitis on CT and ERCP

    International Nuclear Information System (INIS)

    To differentiate the pancreatic adenocarcinoma from focal pancreatitis on CT and ERCP in cases of focal pancreatic enlargement. We analysed CT findings of 66 patients of pancreatic adenocarcinoma (n = 45) or focal pancreatitis (n = 21) with respect to size, density, calcification, pancreatic or biliary duct dilatation, fat plane obliteration around the vessels, direction of retroperitoneal extension, lymphadenopathy, pseudocyst formation and atrophy of pancreas. ERCP available in 48 patients were analysed in respect to morphologic appearance of CBD and pancreatic duct, and distance between the two ducts. The patients in focal pancreatitis were younger with more common history of alcohol drinking. There was no statistical difference in calcifications of the mass (18% in the adenocarcinoma, 33% in the focal pancreatitis), but a tendency of denser, larger number of calcifications was noted in focal pancreatitis. The finding of fat plane obliteration around the vessels were more common in pancreatic adenocarcinoma, and fascial thickenings were more prominent in focal pancreatitis, although not statistically significant. On ERCP, there were no differential points of CBD, pancreatic duct morphology, but distance between the two ducts at the lesion center was more wider in focal pancreatitis. Differentiating focal pancreatitis from pancreatic adenocarcinoma is difficult. However, we should consider the possibility of focal pancreatitis in cases of patients with young age, having alcoholic history in association with CT findings of large numbers of and dense calcifications, and ERCP findings of prominent separation of two duct at the lesion center

  2. Endoscopic pancreatic duct stent placement for inflammatory pancreatic diseases

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The role of endoscopic therapy in the management of pancreatic diseases is continuously evolving; at present most pathological conditions of the pancreas are successfully treated by endoscopic retrograde cholangiopancreatography (ERCP) or endoscopic ultrasound (EUS),or both. Endoscopic placement of stents has played and still plays a major role in the treatment of chronic pancreatitis, pseudocysts, pancreas divisum, main pancreatic duct injuries, pancreatic fistulae, complications of acute pancreatitis, recurrent idiopathic pancreatitis,and in the prevention of post-ERCP pancreatitis. These stents are currently routinely placed to reduce intraductal hypertension, bypass obstructing stones, restore lumen patency in cases with dominant, symptomatic strictures,seal main pancreatic duct disruption, drain pseudocysts or fluid collections, treat symptomatic major or minor papilla sphincter stenosis, and prevent procedure-induced acute pancreatitis. The present review aims at updating and discussing techniques, indications, and results of endoscopic pancreatic duct stent placement in acute and chronic inflammatory diseases of the pancreas.

  3. Imatinib-induced pancreatitis

    Directory of Open Access Journals (Sweden)

    Varma Mahesh

    2010-01-01

    Full Text Available Drug-induced pancreatitis is a rare but serious complication of many drugs, some of which have been well documented. Here we present a case of a middle-aged man with chronic myeloid leukemia who developed acute pancreatitis after being initiated on imatinib mesylate. The case history, the pharmacodynamics, uses, and adverse effects of imatinib mesylate are discussed in detail.

  4. Nutrition, Inflammation, and Acute Pancreatitis

    OpenAIRE

    Max Petrov

    2013-01-01

    Acute pancreatitis is acute inflammatory disease of the pancreas. Nutrition has a number of anti-inflammatory effects that could affect outcomes of patients with pancreatitis. Further, it is the most promising nonspecific treatment modality in acute pancreatitis to date. This paper summarizes the best available evidence regarding the use of nutrition with a view of optimising clinical management of patients with acute pancreatitis.

  5. Pancreatic panniculitis: a cutaneous manifestation of acute pancreatitis

    OpenAIRE

    Laureano, A; Mestre, T; Ricardo, L; Rodrigues, AM; Cardoso, J.

    2014-01-01

    Pancreatic panniculitis is a rare disease in which necrosis of fat in the panniculus and other distant foci occurs in the setting of pancreatic diseases; these diseases include acute and chronic pancreatitis, pancreatic carcinoma, pseudocyst, and other pancreatic diseases. This malady is manifested as tender erythematous nodules on the legs, buttock, or trunk. Histopathologically, it shows the pathognomonic findings of focal subcutaneous fat necrosis and ghost-like anucleated cells with a thi...

  6. Coexistence of Pancreatic Carcinoma and Pancreatic Tuberculosis: Case Report

    OpenAIRE

    Zheng, Zhen-Jiang; Zhang, Hao; Xiang, Guang-Ming; Gong, Jun; Mai, Gang; Liu, Xu-Bao

    2011-01-01

    Pancreatic tuberculosis (TB) is extremely rare and mimics pancreatic carcinoma both clinically and radiologically. This paper discusses the occurrence of 2 heterogeneous masses located in the head and tail of the pancreas in an adult male. In this patient, laparotomy was performed because of the high suspicion of pancreatic carcinoma. Intraoperative fine needle aspiration biopsy revealed the coexistence of pancreatic carcinoma with pancreatic TB, and a combined resection of the distal pancrea...

  7. Fatal Pancreatic Panniculitis Associated with Acute Pancreatitis: A Case Report

    OpenAIRE

    Lee, Woo Sun; Kim, Mi Yeon; Kim, Sang Woo; Paik, Chang Nyol; Kim, Hyung Ok; Park, Young Min

    2007-01-01

    Pancreatic panniculitis is a rare disease in which necrosis of fat in the panniculus and other distant foci occurs in the setting of pancreatic diseases; these diseases include acute and chronic pancreatitis, pancreatic carcinoma, pseudocyst, and other pancreatic diseases. This malady is manifested as tender erythematous nodules on the legs, buttock, or trunk. Histopathologically, it shows the pathognomonic findings of focal subcutaneous fat necrosis and ghost-like anucleated cells with a thi...

  8. Imaging of pancreatitis

    International Nuclear Information System (INIS)

    Full text: Acute pancreatitis (AP) is an acute inflammatory process of the pancreas with variable involvement of peripancreatic tissues or remote organ systems. Mild AP accounts for 75-80% of the cases and it is characterized by interstitial oedema, absent or minimal organ dysfunction, lack of complications and, usually, uneventful recovery. Severe AP is characterized by pancreatic necrosis, protracted clinical course, high incidence of complications, and high mortality rate. The diagnosis of acute pancreatitis (AP) is generally based on clinical and laboratory findings. The role of imaging is to confirm diagnosis, to assess disease severity - especially by detecting pancreatic necrosis-, to reveal complications of the disease and to guide interventions). Contrast- enhanced multidetector CT is the current 'gold standard' imaging modality in the evaluation of patients with AP. The spectrum of findings seen on CT ranges from a normal appearance to diffuse pancreatic enlargement with poorly defined pancreatic contour and heterogeneous attenuation. Stranding of the fat surrounding the pancreas and fluid collections in the anterior pararenal space, the peritoneal cavity or elsewhere, acquiring the form of the anatomic space where they are developed, may also be disclosed. Lack of pancreatic parenchyma enhancement is indicative of the presence of pancreatic necrosis. CT may reveal biliary tract calculi, calcifications in patients with AP combined with chronic pancreatitis- and air in an inflamed pancreas. Pancreatic abscess is usually seen on CT as a focal low attenuation area with a thick wall that may exhibit enhancement following i.v. contrast media administration. Haemorrhage, pseudoaneurysms, renal and splenic parenchyma complications can also be demonstrated by CT. Balthazar et.al have developed CT classification and severity scores based on the presence of fluid collections and pancreatic necrosis. These scores correlate with the incidence of morbidity and

  9. Treatment of acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Al-Mofleh Ibrahim

    1998-01-01

    Full Text Available There is no specific treatment for acute pancreatitis. Majority of patients with acute pancreatitis respond to medical therapy. Supportive measures and close observations represent the cornerstone of the medical therapy. Failure to respond to medical treatment may indicate choledocholithiasis or infected necrosis. Endoscopic papillotomy with stone retrieval is beneficial in patients with severe biliary pancreatitis. Image-guided fine needle aspiration and bacteriological examination of aspirate is reliable in detecting infection and deliniating causative pathogen. Surgical debridement is the method of choice for treatment of infected necrosis. In contrast, in pancreatic abscess, surgery is preserved for those, who do not respond to percutaneous drainage combined with antibiotics. The benefit of antisecretory and antiproteolytic agents is debatable. A combination of antioxidants, calcium channel antagonists and antibiotics may play a major role in the treatment of acute pancreatitis in the future.

  10. Review of idiopathic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Recent advances in understanding of pancreatitis and advances in technology have uncovered the veils of idiopathic pancreatitis to a point where a thorough history and judicious use of diagnostic techniques elucidate the cause in over 80% of cases. This review examines the multitude of etiologies of what were once labeled idiopathic pancreatitis and provides the current evidence on each. This review begins with a background review of the current epidemiology of idiopathic pancreatitis prior to discussion of various etiologies. Etiologies of medications, infections, toxins,autoimmune disorders, vascular causes, and anatomic and functional causes are explored in detail. We conclude with management of true idiopathic pancreatitis and a summary of the various etiologic agents. Throughout this review, areas of controversies are highlighted.

  11. Pancreatic Involvement in Melioidosis

    Directory of Open Access Journals (Sweden)

    Vui Heng Chong

    2010-07-01

    Full Text Available Context Melioidosis is endemic to tropical regions and, despite the common occurrence of intra-abdominal abscesses, pancreatic involvement in melioidosis has not previously been reported. Objective We report our experience with pancreatic melioidosis. Patients All 65 patients treated for melioidosis who had computed tomography (CT scans were identified from prospective databases and were retrospectively reviewed. Main outcome measures A detailed review of cases with pancreas involvement was carried out. Results There were four cases (three males and one female; median age 29.5 years, range: 25-48 years with pancreatic melioidosis, giving a prevalence of 6.2%. All had predisposing conditions (two had poorly controlled diabetes mellitus and two had thalassemia for melioidosis. Fever (100%, anorexia (100%, weight loss (100%, rigor (75% and abdominal pain (75% were the most common symptoms at presentation and the median duration of symptoms before presentation was six weeks (range: 2-8 weeks. All pancreatic abscesses were detected on CT scan. Multiple foci involvement was common (3 to 6 sites: blood (4 patients, liver (3 patients, psoas muscle (2 patients, spleen (2 patients, infected ascites (2 patients and lung (1 patient. Pancreatic involvement ranged from multi-focal micro-abscesses to focal large abscesses and involved all parts of the pancreas (body 100%, head 75% and tail 50%. Associated pancreatic findings included splenic vein thrombosis, peripancreatic inflammation and peripancreatic fat streaking. All the pancreatic abscesses were resolved with antibiotics without requiring pancreatic abscess drainage (including one patient who died from disseminated melioidosis. Conclusion Pancreatic involvement typically occurs as part of multi-organ involvement and commonly manifests as multifoci micro-abscesses. Associated pancreatic abnormalities were also common. All responded to treatment without requiring drainage

  12. Chronic pancreatitis and pancreatic cancer; the clinical aspects and treatment of pancreatic exocrine insufficiency

    NARCIS (Netherlands)

    E.C.M. Sikkens (Edmée)

    2013-01-01

    textabstractIn exocrine pancreatic insufficiency, the pancreas is unable to deliver a sufficient quantity of pancreatic enzymes to the small intestine to digest food. It may occur in several life threatening diseases, including chronic pancreatitis and pancreatic cancer. Due to this lack or absence

  13. Ny klassifikation af pancreatitis acuta

    DEFF Research Database (Denmark)

    Hansen, Benny Østerbye; Schmidt, Palle Nordblad

    2011-01-01

    The course of acute pancreatitis is in the initial phase dominated by a systemic inflammatory response, later by local complications. A new classification defines three specific types of pancreatitis: 1) interstitial oedematous pancreatitis and 2) necrotizing pancreatitis with pancreatic...... parenchymal necrosis, or 3) peripancreatic necrosis alone. The classification also defines four types of collections: 1) Acute peripancreatic fluid collection, 2) pseudocyst, 3) acute post-necrotic collection, and 4) walled-off necrosis. This article summarizes the terminology of the revised Atlanta...

  14. [Etiological factors of acute pancreatitis].

    Science.gov (United States)

    Spicák, J

    2002-09-01

    Acute pancreatitis develops immediately after the causative impulse, while chronic pancreatitis develops after the long-term action of the noxious agent. A typical representative of acute pancreatitis is biliary pancreatitis, chronic pancreatitis develops in alcoholism and has a long latency. As alcoholic pancreatitis is manifested at first as a rule by a potent attack, it is classified in this stage as acute pancreatitis. The most frequent etiological factors in our civilization are thus cholelithiasis and alcoholism (both account for 20-50% in different studies). The assumed pathogenetic principles in acute biliary pancreatitis are the common canal of both efferent ducts above the obturated papilla, duodenopancreatic reflux and intrapancreatic hypertension. A detailed interpretation is however lacking. The pathogenesis of alcoholic pancreatitis is more complicated. Among others some part is played by changes in the calcium concentration and fusion of cellular membranes. Idiopathic pancreatitis occurs in up to 10%, part of the are due to undiagnosed alcoholism and cholelithiasis. Other etiologies are exceptional. Similarly as in cholelithiasis pancreatitis develops also during other pathological processes in the area of the papilla of Vater such as dysfunction of the sphincter of Oddi, ampulloma and juxtapapillary diverticulum, it is however usually mild. The incidence of postoperative pancreatitis is declining. Its lethality is 30% and the diagnosis is difficult. In the pathogenesis changes of the ion concentration are involved, hypoxia and mechanical disorders of the integrity of the gland. Pancreatitis develops in association with other infections--frequently in mumps, rarely in hepatitis, tuberculosis, typhoid and mycoses. Viral pancreatitis is usually mild. In parasitoses pancreatitis develops due to a block of the papilla Vateri. In hyperparathyroidism chronic pancreatitis is more likely to develop, recent data are lacking. As to dyslipoproteinaemias

  15. Antibody Response to Serpin B13 Induces Adaptive Changes in Mouse Pancreatic Islets and Slows Down the Decline in the Residual Beta Cell Function in Children with Recent Onset of Type 1 Diabetes Mellitus.

    Science.gov (United States)

    Kryvalap, Yury; Lo, Chi-Wen; Manuylova, Ekaterina; Baldzizhar, Raman; Jospe, Nicholas; Czyzyk, Jan

    2016-01-01

    Type 1 diabetes mellitus (T1D) is characterized by a heightened antibody (Ab) response to pancreatic islet self-antigens, which is a biomarker of progressive islet pathology. We recently identified a novel antibody to clade B serpin that reduces islet-associated T cell accumulation and is linked to the delayed onset of T1D. As natural immunity to clade B arises early in life, we hypothesized that it may influence islet development during that time. To test this possibility healthy young Balb/c male mice were injected with serpin B13 mAb or IgG control and examined for the number and cellularity of pancreatic islets by immunofluorescence and FACS. Beta cell proliferation was assessed by measuring nucleotide analog 5-ethynyl-2'-deoxyuridine (5-EdU) incorporation into the DNA and islet Reg gene expression was measured by real time PCR. Human studies involved measuring anti-serpin B13 autoantibodies by Luminex. We found that injecting anti-serpin B13 monoclonal Ab enhanced beta cell proliferation and Reg gene expression, induced the generation of ∼80 pancreatic islets per animal, and ultimately led to increase in the beta cell mass. These findings are relevant to human T1D because our analysis of subjects just diagnosed with T1D revealed an association between baseline anti-serpin activity and slower residual beta cell function decline in the first year after the onset of diabetes. Our findings reveal a new role for the anti-serpin immunological response in promoting adaptive changes in the endocrine pancreas and suggests that enhancement of this response could potentially help impede the progression of T1D in humans. PMID:26578518

  16. A natural food sweetener with anti-pancreatic cancer properties.

    Science.gov (United States)

    Liu, C; Dai, L-H; Dou, D-Q; Ma, L-Q; Sun, Y-X

    2016-01-01

    Mogroside V is a triterpenoid isolated from the traditional Chinese medical plant Siraitia grosvenorii. Mogroside V has a high degree of sweetness and a low calorific content. Herein, we found that mogroside V possesses tumor growth inhibitory activity in in vitro and in vivo models of pancreatic cancer by promoting apoptosis and cell cycle arrest of pancreatic cancer cells (PANC-1 cells), which may in part be mediated through regulating the STAT3 signaling pathway. These results were confirmed in vivo in a mouse xenograft model of pancreatic cancer. In xenograft tumors, Ki-67 and PCNA, the most commonly used markers of tumor cell proliferation, were downregulated after intravenous administration of mogroside V. Terminal deoxynucleotidyl transferase dUTP nick end labeling assays showed that mogroside V treatment promoted apoptosis of pancreatic cancer cells in the xenograft tumors. Furthermore, we found that mogroside V treatment significantly reduced the expression of CD31-labeled blood vessels and of the pro-angiogenic factor vascular endothelial growth factor in the xenografts, indicating that mogroside V might limit the growth of pancreatic tumors by inhibiting angiogenesis and reducing vascular density. These results therefore demonstrate that the natural, sweet-tasting compound mogroside V can inhibit proliferation and survival of pancreatic cancer cells via targeting multiple biological targets. PMID:27065453

  17. A natural food sweetener with anti-pancreatic cancer properties

    Science.gov (United States)

    Liu, C; Dai, L-H; Dou, D-Q; Ma, L-Q; Sun, Y-X

    2016-01-01

    Mogroside V is a triterpenoid isolated from the traditional Chinese medical plant Siraitia grosvenorii. Mogroside V has a high degree of sweetness and a low calorific content. Herein, we found that mogroside V possesses tumor growth inhibitory activity in in vitro and in vivo models of pancreatic cancer by promoting apoptosis and cell cycle arrest of pancreatic cancer cells (PANC-1 cells), which may in part be mediated through regulating the STAT3 signaling pathway. These results were confirmed in vivo in a mouse xenograft model of pancreatic cancer. In xenograft tumors, Ki-67 and PCNA, the most commonly used markers of tumor cell proliferation, were downregulated after intravenous administration of mogroside V. Terminal deoxynucleotidyl transferase dUTP nick end labeling assays showed that mogroside V treatment promoted apoptosis of pancreatic cancer cells in the xenograft tumors. Furthermore, we found that mogroside V treatment significantly reduced the expression of CD31-labeled blood vessels and of the pro-angiogenic factor vascular endothelial growth factor in the xenografts, indicating that mogroside V might limit the growth of pancreatic tumors by inhibiting angiogenesis and reducing vascular density. These results therefore demonstrate that the natural, sweet-tasting compound mogroside V can inhibit proliferation and survival of pancreatic cancer cells via targeting multiple biological targets. PMID:27065453

  18. Chronic pancreatitis and pancreatic cancer; the clinical aspects and treatment of pancreatic exocrine insufficiency

    OpenAIRE

    Sikkens, Edmée

    2013-01-01

    textabstractIn exocrine pancreatic insufficiency, the pancreas is unable to deliver a sufficient quantity of pancreatic enzymes to the small intestine to digest food. It may occur in several life threatening diseases, including chronic pancreatitis and pancreatic cancer. Due to this lack or absence of pancreatic enzymes, malabsorption of fat develops, which causes steatorrhea-related symptoms, weight loss, and malnutrition. To reduce morbidity and even mortality, patients should be treated wi...

  19. Can Pancreatic Cancer Be Found Early?

    Science.gov (United States)

    ... Topic Signs and symptoms of pancreatic cancer Can pancreatic cancer be found early? Pancreatic cancer is hard to ... Testing: What You Need to Know . Testing for pancreatic cancer in people at high risk For people in ...

  20. Researchers Identify Early Sign of Pancreatic Cancer

    Science.gov (United States)

    ... of pancreatic cancer Researchers identify early sign of pancreatic cancer September 28, 2014 Tags: PancreaticCancer Brian Wolpin, MD ... discovered a sign of the early development of pancreatic cancer – an upsurge in certain amino acids that occurs ...

  1. Pancreatitis in scrub typhus

    Directory of Open Access Journals (Sweden)

    Alok Bhatt

    2014-01-01

    Full Text Available Scrub typhus is a rickettsial infection prevalent in most parts of India. Acute pancreatitis with pseudocyst formation is a rare complication of this condition. This paper reports acute renal failure, pancreatitis and pseudocyst formation in a 48-year-old female with scrub typhus. Ultrasonography of the abdomen revealed a bulky pancreas with fluid seen along the body of the pancreas in the lesser sac. The infection was successfully treated with doxycycline and supportive treatment. Pancreatitis was managed conservatively. This case report highlights the importance of identifying and managing uncommon complications of a common tropical disease for optimum outcome.

  2. Proghrelin peptides: Desacyl ghrelin is a powerful inhibitor of acylated ghrelin, likely to impair physiological effects of acyl ghrelin but not of obestatin A study of pancreatic polypeptide secretion from mouse islets

    DEFF Research Database (Denmark)

    Kumar, Rajesh; Salehi, Albert; Rehfeld, Jens F;

    2010-01-01

    Proghrelin, produced by the ghrelin (A-like) cells of the gastric mucosa, gives rise to cleavage products, including desacyl ghrelin, acyl ghrelin and obestatin. The products are thought to be secreted concomitantly. In an earlier study we found acyl ghrelin and obestatin, but not desacyl ghrelin......, to suppress the release of hormones from isolated islets of mouse and rat pancreas....

  3. Acute pancreatitis in pregnancy

    Institute of Scientific and Technical Information of China (English)

    Capecomorin S Pitchumoni; Balaji Yegneswaran

    2009-01-01

    Acute pancreatitis (AP) is a rare event in pregnancy,occurring in approximately 3 in 10 000 pregnancies.The spectrum of AP in pregnancy ranges from mild pancreatitis to serious pancreatitis associated with necrosis, abscesses, pseudocysts and multiple organ dysfunction syndromes. Pregnancy related hematological and biochemical alterations influence the interpretation of diagnostic tests and assessment of severity of AP. As in any other disease associated with pregnancy, AP is associated with greater concerns as it deals with two lives rather than just one as in the nonpregnant population. The recent advances in clinical gastroenterology have improved the early diagnosis and effective management of biliary pancreatitis. Diagnostic studies such as endoscopic ultrasound,magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography and therapeutic modalities that include endoscopic sphincterotomy, biliary stenting, common bile duct stone extraction and laparoscopic cholecystectomy are major milestones in gastroenterology. When properly managed AP in pregnancy does not carry a dismal prognosis as in the past.

  4. Familial Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Stephen J. Lanspa

    2010-11-01

    Full Text Available Pancreatic cancer’s high mortality rate equates closely with its incidence, thereby showing the need for development of biomarkers of its increased risk and a better understanding of its genetics, so that high-risk patients can be better targeted for screening and early potential lifesaving diagnosis. Its phenotypic and genotypic heterogeneity is extensive and requires careful scrutiny of its pattern of cancer associations, such as malignant melanoma associated with pancreatic cancer, in the familial atypical multiple mole melanoma syndrome, due to the CDKN2A germline mutation. This review is designed to depict several of the hereditary pancreatic cancer syndromes with particular attention given to the clinical application of this knowledge into improved control of pancreatic cancer.

  5. Perspectives in Pancreatic Pain

    Directory of Open Access Journals (Sweden)

    A. S. Salim

    1997-01-01

    Full Text Available This review describes some of the mechanisms which are thought to be important in the causation of pain in chronic pancreatitis. Both medical and surgical techniques for treating this pain are described.

  6. Pancreatic islet cell tumor

    Science.gov (United States)

    ... may include: Fasting glucose level Gastrin level Glucose tolerance test Secretin stimulation test for pancreas Blood glucagon ... PhD, and the A.D.A.M. Editorial team. Related MedlinePlus Health Topics Pancreatic Cancer Browse the ...

  7. What Is Pancreatic Cancer?

    Science.gov (United States)

    ... very important to distinguish between exocrine and endocrine cancers of the pancreas. They have distinct risk factors and causes, have ... are by far the most common type of pancreas cancer. If you are told you have pancreatic cancer, ...

  8. Pancreatic exocrine function testing

    International Nuclear Information System (INIS)

    It is important to understand which pancreatic function tests are available and how to interpret them when evaluating patients with malabsorption. Available direct tests are the secretin stimulation test, the Lundh test meal, and measurement of serum or fecal enzymes. Indirect tests assess pancreatic exocrine function by measuring the effect of pancreatic secretion on various nutrients. These include triglycerides labeled with carbon 14, cobalamin labeled with cobalt 57 and cobalt 58, and para-aminobenzoic acid bound to a dipeptide. Of all these tests the secretin stimulation test is the most accurate and reliable if done by experienced personnel. However, the indirect tests are simpler to do and appear to be comparable to the secretin test at detecting pancreatic exocrine insufficiency. These indirect tests are becoming clinically available and clinicians should familiarize themselves with the strengths and weaknesses of each

  9. Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis

    OpenAIRE

    Tian, Hua; Callahan, Christopher A.; DuPree, Kelly J.; Darbonne, Walter C; Ahn, Christina P.; Scales, Suzie J.; de Sauvage, Frederic J.

    2009-01-01

    The Hedgehog (Hh) pathway has been implicated in pancreatic cancer but its role remains controversial. To delineate the cell populations able to respond to Hh ligand stimulation, we expressed an oncogenic allele of Smoothened (SmoM2) to cell autonomously activate Hh signaling in the mouse pancreas. Surprisingly, we found that expression of SmoM2 in epithelial cells was not able to activate the pathway and had no impact on pancreatic development or neoplasia. In contrast, activation of Smo in ...

  10. Autoimmune pancreatitis results from loss of TGFβ signalling in S100A4-positive dendritic cells

    OpenAIRE

    Boomershine, C S; Chamberlain, A; Kendall, P.; Afshar-Sharif, A-R; Huang, H; Washington, M.K.; Lawson, W.E.; Thomas, J. W.; Blackwell, T S; Bhowmick, N A

    2009-01-01

    Background and aims: Autoimmune pancreatitis (AIP) is a poorly understood human disease affecting the exocrine pancreas. The goal of the present study was to elucidate the pathogenic mechanisms underlying pancreatic autoimmunity in a murine disease model. Methods: A transgenic mouse with an S100A4/fibroblast-specific protein 1 (FSP1) Cre-mediated conditional knockout of the transforming growth factor β (TGFβ) type II receptor, termed Tgfbr2 fspKO , was used to determine the direct role of TGF...

  11. Cathepsin L inactivates human trypsinogen whereas cathepsin L deletion reduces the severity of pancreatitis in mice

    Science.gov (United States)

    Wartmann, Thomas; Mayerle, Julia; Kähne, Thilo; Sahin-Tóth, Miklós; Ruthenbürger, Manuel; Matthias, Rainer; Kruse, Anne; Reinheckel, Thomas; Peters, Christoph; Weiss, F. Ulrich; Sendler, Matthias; Hans-Lippert; Schulz, Hans-Ulrich; Aghdassi, Ali; Dummer, Annegret; Teller, Steffen; Halangk, Walter; Lerch, Markus M.

    2010-01-01

    Background & Aims Acute pancreatitis is characterized by an activation cascade of digestive enzymes in the pancreas. The first of these, trypsinogen, can be converted to active trypsin by the peptidase cathepsin B (CTSB). We investigated whether cathepsin L (CTSL), the second most abundant lysosomal cysteine proteinase, can also process trypsinogen to active trypsin and has a role in pancreatitis. Methods In CTSL-deficient (Ctsl−/−) mice, pancreatitis was induced by injection of cerulein or infusion of taurocholate into the pancreatic duct. Human tissue, pancreatic juice, mouse pancreatitis specimens, and recombinant enzymes were studied by enzyme assay, immunoblot, N-terminal sequencing, immunocytochemistry, and electron microscopy analyses. Isolated acini from Ctsl−/− and Ctsb−/− mice were studied. Results CTSL was expressed in human and mouse pancreas, where it colocalized with trypsinogen in secretory vesicles and lysosomes and was secreted into pancreatic juice. Severity of pancreatitis was reduced in Ctsl−/− mice, compared with wild-type controls, whereas apoptosis and intrapancreatic trypsin activity were increased in Ctsl−/− mice. CTSL induced cleavage of trypsinogen occurred 3 amino acids toward the C terminus from the CTSB activation site and resulted in a truncated, inactive form of trypsin and an elongated propeptide (TAP). This elongated TAP was not detected by ELISA but was effectively converted to an immunoreactive form by CTSB. Levels of TAP thus generated by CTSB were not associated with disease severity, although this is what the TAP-ELISA is used to determine in the clinic. Conclusions CTSL inactivates trypsinogen and counteracts the ability of CTSB to form active trypsin. In mouse models of pancreatitis, absence of CTSL induces apoptosis and reduces disease severity. PMID:19900452

  12. Cyclopamine disrupts tumor extracellular matrix and improves the distribution and efficacy of nanotherapeutics in pancreatic cancer.

    Science.gov (United States)

    Zhang, Bo; Jiang, Ting; Shen, Shun; She, Xiaojian; Tuo, Yanyan; Hu, Yu; Pang, Zhiqing; Jiang, Xinguo

    2016-10-01

    The dense extracellular matrix in pancreatic ductal adenocarcinoma dramatically reduces the penetration and efficacy of nanotherapeutics. Disruption of the tumor extracellular matrix may help improve the distribution and efficacy of nanotherapeutics in pancreatic cancer. In this study, we tested whether cyclopamine, a special inhibitor of the hedgehog signaling pathway with powerful anti-fibrotic activity, could promote the penetration and efficacy of nanotherapeutics in pancreatic cancer. It was shown that cyclopamine disrupted tumor extracellular fibronectins, decompressed tumor blood vessels, and improved tumor perfusion. Furthermore, cyclopamine improved the accumulation and intratumoral distribution of i.v.-administered fluorescence indicator-labeled nanoparticles. Finally, cyclopamine also significantly improved the tumor growth inhibition effect of i.v.-injected nanotherapeutics in pancreatic tumor xenograft mouse models. Thus, cyclopamine may have great potential to improve the therapeutic effects of nanomedicine in patients with pancreatic cancer. PMID:27376555

  13. Imaging of acute pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Merkle, Elmar M.; Goerich, Johannes [Department of Radiology, University Hospitals of Ulm, Steinhoevel Strasse 9, 89075 Ulm (Germany)

    2002-08-01

    Acute pancreatitis is defined as an acute inflammatory process of the pancreas with variable involvement of peripancreatic tissues or remote organ systems. This article reports the current classification, definition and terminology, epidemiology and etiology, pathogenesis and pathological findings, clinical and laboratory findings, and finally imaging findings of acute pancreatitis with emphasis on cross-sectional imaging modalities such as ultrasound, computed tomography, and magnetic resonance imaging. (orig.)

  14. Mucins and Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Isabelle Van Seuningen

    2010-10-01

    Full Text Available Pancreatic cancer is characterized by an often dramatic outcome (five year survival < 5% related to a late diagnosis and a lack of efficient therapy. Therefore, clinicians desperately need new biomarkers and new therapeutic tools to develop new efficient therapies. Mucins belong to an ever increasing family of O-glycoproteins. Secreted mucins are the main component of mucus protecting the epithelia whereas membrane-bound mucins are thought to play important biological roles in cell-cell and cell-matrix interactions, in cell signaling and in modulating biological properties of cancer cells. In this review, we will focus on the altered expression pattern of mucins in pancreatic cancer, from the early neoplastic lesion Pancreatic Intraepithelial Neoplasia (PanIN to invasive pancreatic carcinomas, and the molecular mechanisms (including genetic and epigenetic regulation and signaling pathways known to control their expression. Moreover, we will discuss the recent advances about the biology of both secreted and membrane-bound mucins and their key roles in pancreatic carcinogenesis and resistance to therapy. Finally, we will discuss exciting opportunities that mucins offer as potential therapeutic targets in pancreatic cancer.

  15. Common activation of canonical Wnt signaling in pancreatic adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Marina Pasca di Magliano

    Full Text Available Pancreatic ductal adenocarcinoma (PDA is an extremely aggressive malignancy, which carries a dismal prognosis. Activating mutations of the Kras gene are common to the vast majority of human PDA. In addition, recent studies have demonstrated that embryonic signaling pathway such as Hedgehog and Notch are inappropriately upregulated in this disease. The role of another embryonic signaling pathway, namely the canonical Wnt cascade, is still controversial. Here, we use gene array analysis as a platform to demonstrate general activation of the canonical arm of the Wnt pathway in human PDA. Furthermore, we provide evidence for Wnt activation in mouse models of pancreatic cancer. Our results also indicate that Wnt signaling might be activated downstream of Hedgehog signaling, which is an early event in PDA evolution. Wnt inhibition blocked proliferation and induced apoptosis of cultured adenocarcinoma cells, thereby providing evidence to support the development of novel therapeutical strategies for Wnt inhibition in pancreatic adenocarcinoma.

  16. Pancreatic encephalopathy- a rare complication of severe acute biliary pancreatitis

    OpenAIRE

    Vlad Denis Constantin; Alexandru Carȃp; Bogdan Socea; Simona Bobic

    2014-01-01

    Background. Pancreatic encephalopathy is a rare complication of severe acute pancreatitis, with high mortality, being difficult to diagnose and treat, thus requiring continuous research regarding its management. Materials and Methods. Of 20 patients diagnosed with severe acute pancreatitis on admission at Department of Emergency and Admission (DEA), from January 1st 2010 to March 31st 2014, 5 cases complicated by pancreatic encephalopathy were analyzed using a descriptive observational...

  17. Pancreatic tissue fluid pressure during drainage operations for chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N; Borly, L; Madsen, P; Matzen, Peter

    1990-01-01

    Pancreatic tissue fluid pressure was measured in 10 patients undergoing drainage operations for painful chronic pancreatitis. The pressure was measured by the needle technique in the three anatomic regions of the pancreas before and at different stages of the drainage procedure, and the results...... a decrease in pancreatic tissue fluid pressure during drainage operations for pain in chronic pancreatitis. Regional pressure decrease were apparently unrelated to ERCP findings....

  18. Endoscopic pancreatic duct stent placement for inflammatory pancreatic diseases

    OpenAIRE

    Testoni, Pier Alberto

    2007-01-01

    The role of endoscopic therapy in the management of pancreatic diseases is continuously evolving; at present most pathological conditions of the pancreas are successfully treated by endoscopic retrograde cholangio-pancreatography (ERCP) or endoscopic ultrasound (EUS), or both. Endoscopic placement of stents has played and still plays a major role in the treatment of chronic pancreatitis, pseudocysts, pancreas divisum, main pancreatic duct injuries, pancreatic fistulae, complications of acute ...

  19. Influence of treatment with pancreatic extracts on pancreatic enzyme secretion.

    OpenAIRE

    Mössner, J.; Wresky, H P; Kestel, W; Zeeh, J; Regner, U; Fischbach, W

    1989-01-01

    We have evaluated the effects of porcine pancreatic extracts on human pancreatic secretion. Ten male volunteers were intubated with a 4-lumen jejunal tube to collect gastric and duodenal secretions separately via the first and third tube, to infuse PEG 4000 distal the pylorus via the second tube and to apply porcine pancreatic extracts via the fourth tube distal the ligament of Treitz. Pancreatic extracts were given four times at 40 minute intervals; the first two as active enzymes and subseq...

  20. SEL1L deficiency impairs growth and differentiation of pancreatic epithelial cells

    Directory of Open Access Journals (Sweden)

    Schimenti John C

    2010-02-01

    Full Text Available Abstract Background The vertebrate pancreas contains islet, acinar and ductal cells. These cells derive from a transient pool of multipotent pancreatic progenitors during embryonic development. Insight into the genetic determinants regulating pancreatic organogenesis will help the development of cell-based therapies for the treatment of diabetes mellitus. Suppressor enhancer lin12/Notch 1 like (Sel1l encodes a cytoplasmic protein that is highly expressed in the developing mouse pancreas. However, the morphological and molecular events regulated by Sel1l remain elusive. Results We have characterized the pancreatic phenotype of mice carrying a gene trap mutation in Sel1l. We show that Sel1l expression in the developing pancreas coincides with differentiation of the endocrine and exocrine lineages. Mice homozygous for the gene trap mutation die prenatally and display an impaired pancreatic epithelial morphology and cell differentiation. The pancreatic epithelial cells of Sel1l mutant embryos are confined to the progenitor cell state throughout the secondary transition. Pharmacological inhibition of Notch signaling partially rescues the pancreatic phenotype of Sel1l mutant embryos. Conclusions Together, these data suggest that Sel1l is essential for the growth and differentiation of endoderm-derived pancreatic epithelial cells during mouse embryonic development.

  1. Type 1 autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Zen Yoh

    2011-12-01

    Full Text Available Abstract Before the concept of autoimmune pancreatitis (AIP was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of

  2. Loperamide-Induced Acute Pancreatitis

    OpenAIRE

    Halla Vidarsdottir; Hanna Vidarsdottir; Pall Helgi Moller; Einar Stefan Bjornsson

    2013-01-01

    Acute pancreatitis is a common disease leading to hospitalizations, most often caused by gallstones or alcohol. We present a case of a patient diagnosed with acute pancreatitis considered to be due to loperamide treatment for diarrhea.

  3. Metabolic pancreatitis: Etiopathogenesis and management

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Kota

    2013-01-01

    Full Text Available Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis. Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson′s disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis.

  4. Genetics Home Reference: hereditary pancreatitis

    Science.gov (United States)

    ... National Cancer Institute: Pancreatic Cancer National Institute of Diabetes and Digestive and Kidney Diseases Educational Resources (9 links) Boston Children's Hospital Cleveland Clinic: Cancer of the Pancreas Cleveland Clinic: Pancreatitis Disease InfoSearch: ...

  5. Drugs Approved for Pancreatic Cancer

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Pancreatic Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Pancreatic Cancer Abraxane (Paclitaxel Albumin-stabilized Nanoparticle Formulation) Afinitor (Everolimus) ...

  6. Drug-induced acute pancreatitis

    OpenAIRE

    Eland, I.A.

    2008-01-01

    textabstractAcute pancreatitis is an inflammatory disease of the pancreas with sudden onset. The severity of acute pancreatitis may vary from mild to life threatening. There are many risk factors for acute pancreatitis, among which gallstones and alcohol abuse are most widely known. Drugs are considered as potential risk factors for acute pancreatitis, but have received relatively little attention in the medical literature. In this thesis, several epidemiological studies were performed to ass...

  7. Folate Deficiency in Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Gopalakrishna Rajesh

    2010-07-01

    Full Text Available Dear Sir, While there has been a spurt of interest in genetic alterations associated with pancreatitis in the past few years, interest in the role of environmental factors has largely focused on alcoholism and smoking with insufficient attention being paid to the contributions of nutritional deficiency, and the role of environmental toxins in the pathogenesis of pancreatitis. Braganza and Dormandy [1] argue convincingly about the role played by cytochrome P450 monooxygenases (especially CYP1A enzyme induction by xenobiotics and the resultant oxidative stress, as also the now increasingly recognized reductive stress posed by the metabolites in initiating pancreatic injury. Their article underlines the important part played by the deficiency of methyl and thiol molecules in different stages of the progression of pancreatic damage. Furthermore, they attempt to establish a link between environmental and genetic factors and bring in a holistic view on the etiopathogenesis of chronic pancreatitis. We have recently demonstrated lower plasma methionine levels in two cohorts of chronic pancreatitis patients; one of tropical chronic pancreatitis and the other, of alcoholic chronic pancreatitis as compared to healthy controls [2] which suggests that deficiency of methyl groups may be a factor in various forms of pancreatitis. Similarly, we have shown lower red cell glutathione levels in chronic pancreatitis patients with tropical chronic pancreatitis and alcoholic chronic pancreatitis, indicating deficiency of thiol molecules. In addition, we have demonstrated significantly higher levels of plasma total homocysteine in chronic pancreatitis patients than in healthy controls. Moreover, our study has shown that there is a deficiency of red cell folate in the majority of chronic pancreatitis patients, more so in tropical chronic pancreatitis; and that folate deficiency appeared to be the key factor in hyperhomocysteinemia in chronic pancreatitis patients

  8. Uncommon pancreatic tumors and pseudotumors.

    Science.gov (United States)

    Lalwani, Neeraj; Mannelli, Lorenzo; Ganeshan, Dhakshina Moorthy; Shanbhogue, Alampady K; Dighe, Manjiri K; Tiwari, Hina Arif; Maximin, Suresh; Monti, Serena; Ragucci, Monica; Prasad, Srinivasa R

    2015-01-01

    A heterogeneous group of uncommon neoplastic and non-neoplastic pancreatic pathologies exists that can mimic pancreatic adenocarcinoma. These "imitators" are unique and may demonstrate characteristic clinical and imaging features. Imaging characteristics of some of these diverse lesions are not well described in the literature, and erroneous diagnoses of these entities as pancreatic carcinoma may be responsible for unnecessary surgeries. Knowledge of these selected pancreatic pathologies is essential to facilitate optimal patient management. PMID:25063236

  9. Brain Metastasis in Pancreatic Cancer

    OpenAIRE

    Marko Kornmann; Doris Henne-Bruns; Jan Scheele; Christian Rainer Wirtz; Thomas Kapapa; Johannes Lemke

    2013-01-01

    Pancreatic cancer is a fatal disease with a 5-year survival rate below 5%. Most patients are diagnosed at an advanced tumor stage and existence of distant metastases. However, involvement of the central nervous system is rare in pancreatic cancer. We retrospectively analyzed all cases of brain metastases in pancreatic cancer reported to date focusing on patient characteristics, clinical appearance, therapy and survival. Including our own, 12 cases of brain metastases originating from pancreat...

  10. Diabetes and Pancreatic Cancer-2014

    OpenAIRE

    Andre Luiz De Souza; Muhammad Wasif Saif

    2014-01-01

    Context Pancreatic cancer is the fourth leading cause of cancer mortality in the United States. Most of the patients are diagnosed in the metastatic staging. Consolidated risk factors include chronic pancreatitis, smoking and family history. Although controversial, diabetes mellitus has been increasingly associated with pancreatic cancer as a risk factor as opposed to just a manifestation of the disease. Biomarkers for early diagnosis of pancreatic cancer among diabetic patients and metformin...

  11. Concurrent Lymphoma and Pancreatic Adenocarcinoma

    OpenAIRE

    Jiun Miin Lai; Mehrdad Nikfarjam; Peter Crowley

    2011-01-01

    Context Retroperitoneal lymph node enlargement in patients with pancreatic cancer is sometimes treated as incurable disease. Nonmetastatic causes of lymphadenopathy should however be considered. Case reports Two cases of significant retroperitoneal lymphadenopathy in the setting of pancreatic cancer, treated by pancreaticoduodenectomy and lymph node dissection are described. Both cases had a final diagnosis of concurrent pancreatic cancer and lymphoma with no evidence of pancreatic lymph node...

  12. Obstructive Jaundice in Chronic Pancreatitis

    OpenAIRE

    Hollands, M. J.; Little, J. M.

    1989-01-01

    Significant obstructive jaundice in chronic pancreatitis is generally considered to be rare. Eleven of 57 consecutive patients with proven chronic pancreatitis have developed significant obstructive jaundice of more than transient duration. Eight presented as jaundice complicating known pancreatitis and three as jaundice of unknown cause. Life table analysis showed a steady rise in the risk of developing jaundice up to the end of 10 years from the onset of chronic pancreatitis. Jaundice was f...

  13. Drug-induced acute pancreatitis

    NARCIS (Netherlands)

    I.A. Eland

    2003-01-01

    textabstractAcute pancreatitis is an inflammatory disease of the pancreas with sudden onset. The severity of acute pancreatitis may vary from mild to life threatening. There are many risk factors for acute pancreatitis, among which gallstones and alcohol abuse are most widely known. Drugs are consid

  14. Acute pancreatitis and Cushing's syndrome.

    OpenAIRE

    Clague, H W; B. Warren; Krasner, N.

    1984-01-01

    A case of acute necrotizing pancreatitis in a 53-year-old man with an ectopic adrenocorticotrophin (ACTH) producing bronchial carcinoma is described. The aetiology of acute pancreatitis in relation to steroid therapy and malignancy is discussed and it is suggested that excess endogenous steroid production may also cause acute pancreatitis.

  15. Treatment Option Overview (Pancreatic Cancer)

    Science.gov (United States)

    ... affect prognosis (chance of recovery) and treatment options. Pancreatic cancer is a disease in which malignant (cancer) cells form in the ... the cancer cells in the liver are actually pancreatic cancer cells. The disease is metastatic pancreatic cancer, not liver cancer. The ...

  16. General Information about Pancreatic Cancer

    Science.gov (United States)

    ... affect prognosis (chance of recovery) and treatment options. Pancreatic cancer is a disease in which malignant (cancer) cells form in the ... the cancer cells in the liver are actually pancreatic cancer cells. The disease is metastatic pancreatic cancer, not liver cancer. The ...

  17. Gadolinium induced recurrent acute pancreatitis.

    Science.gov (United States)

    Blasco-Perrin, H; Glaser, B; Pienkowski, M; Peron, J M; Payen, J L

    2013-01-01

    Acute pancreatitis is a sudden swelling and inflammation of the pancreas. The two most common causes are alcohol use and biliary stones. Drug-induced acute pancreatitis are rare (1.4-2%). In this present study, we present a case of recurrent acute pancreatitis induced by a specific magnetic-resonance-imaging (MRI) contrast agent called gadobenate dimeglumine. PMID:23395575

  18. Pancreatic ascariasis with periampullary carcinoma

    OpenAIRE

    Arulprakash, S; Sahu, Manoj Kumar; Dutta, Amit Kumar; Joseph, A; Chandy, George M.

    2015-01-01

    Ascarias lumbricoides infestation is endemic in tropical countries. Most infections are asymptomatic, but it can produce a wide spectrum of manifestations including hepatobiliary and pancreatic complications. There are reports of association of biliary ascariasis with bilary malignancies in the past, but same is not known for pancreatic ascariasis. We report a case of association of periampullary malignancy with pancreatic ascariasis.

  19. Prognostic Factors in Pancreatic Cancer

    OpenAIRE

    Åke Andrén-Sandberg

    2012-01-01

    Prognostic factors in pancreatic cancer have been a hot topic for the clinical pancreatology, and many studies have been involved in the field. The author reviewed the pancreatic abstracts of American Pancreas Club 2011, and sumarized "highlight" of all the abstracts in prognostic factors in pancreatic cancer.

  20. Familial pancreatic cancer: genetic advances

    OpenAIRE

    Rustgi, Anil K.

    2014-01-01

    This review by Rustgi elaborates on the known genetic syndromes that underlie familial pancreatic cancer. It aims to delineate the subtypes of syndromic hereditary pancreatic cancer in which germline genetic mutations have been identified and nonsyndromic familial pancreatic cancer in which genetic information is emerging.

  1. Hypocalcemia in acute pancreatitis revisited

    Directory of Open Access Journals (Sweden)

    Armin Ahmed

    2016-01-01

    Full Text Available Hypocalcemia is a frequent finding in acute pancreatitis. Severe hypocalcemia can present with neurological as well as cardiovascular manifestations. Correction of hypocalcemia by parenteral calcium infusion remains a controversial topic as intracellular calcium overload is the central mechanism of acinar cell injury in pancreatitis. The current article deals with the art and science of calcium correction in pancreatitis patients.

  2. Tests of pancreatic exocrine function - clinical significance in pancreatic and non-pancreatic disorders.

    Science.gov (United States)

    Keller, Jutta; Aghdassi, Ali Alexander; Lerch, Markus M; Mayerle, Julia V; Layer, Peter

    2009-01-01

    The pancreas functions as the main factory for digestive enzymes and therefore enables food utilisation. Pancreatic exocrine insufficiency, partial or complete loss of digestive enzyme synthesis, occurs primarily in disorders directly affecting pancreatic tissue integrity. However, other disorders of the gastrointestinal tract, such as coeliac disease, inflammatory bowel disease, Zollinger-Ellison syndrome or gastric resection can either mimic or cause pancreatic exocrine insufficiency. The overt clinical symptoms of pancreatic exocrine insufficiency are steatorrhoea and maldigestion, which frequently become apparent in advanced stages. Several direct and indirect function tests are available for assessment of pancreatic function but until today diagnosis of excretory insufficiency is difficult as in mild impairment clinically available function tests show limitations of diagnostic accuracy. This review focuses on diagnosis of pancreatic exocrine insufficiency in pancreatic and non-pancreatic disorders. PMID:19505669

  3. Diagnosis and treatment of pancreatic exocrine insufficiency

    OpenAIRE

    2013-01-01

    Pancreatic exocrine insufficiency is an important cause of maldigestion and a major complication in chronic pancreatitis. Normal digestion requires adequate stimulation of pancreatic secretion, sufficient production of digestive enzymes by pancreatic acinar cells, a pancreatic duct system without significant outflow obstruction and adequate mixing of the pancreatic juice with ingested food. Failure in any of these steps may result in pancreatic exocrine insufficiency, which leads to steatorrh...

  4. GEMMs as preclinical models for testing pancreatic cancer therapies.

    Science.gov (United States)

    Gopinathan, Aarthi; Morton, Jennifer P; Jodrell, Duncan I; Sansom, Owen J

    2015-10-01

    Pancreatic ductal adenocarcinoma is the most common form of pancreatic tumour, with a very limited survival rate and currently no available disease-modifying treatments. Despite recent advances in the production of genetically engineered mouse models (GEMMs), the development of new therapies for pancreatic cancer is still hampered by a lack of reliable and predictive preclinical animal models for this disease. Preclinical models are vitally important for assessing therapies in the first stages of the drug development pipeline, prior to their transition to the clinical arena. GEMMs carry mutations in genes that are associated with specific human diseases and they can thus accurately mimic the genetic, phenotypic and physiological aspects of human pathologies. Here, we discuss different GEMMs of human pancreatic cancer, with a focus on the Lox-Stop-Lox (LSL)-Kras(G12D); LSL-Trp53(R172H); Pdx1-cre (KPC) model, one of the most widely used preclinical models for this disease. We describe its application in preclinical research, highlighting its advantages and disadvantages, its potential for predicting clinical outcomes in humans and the factors that can affect such outcomes, and, finally, future developments that could advance the discovery of new therapies for pancreatic cancer. PMID:26438692

  5. GEMMs as preclinical models for testing pancreatic cancer therapies

    Directory of Open Access Journals (Sweden)

    Aarthi Gopinathan

    2015-10-01

    Full Text Available Pancreatic ductal adenocarcinoma is the most common form of pancreatic tumour, with a very limited survival rate and currently no available disease-modifying treatments. Despite recent advances in the production of genetically engineered mouse models (GEMMs, the development of new therapies for pancreatic cancer is still hampered by a lack of reliable and predictive preclinical animal models for this disease. Preclinical models are vitally important for assessing therapies in the first stages of the drug development pipeline, prior to their transition to the clinical arena. GEMMs carry mutations in genes that are associated with specific human diseases and they can thus accurately mimic the genetic, phenotypic and physiological aspects of human pathologies. Here, we discuss different GEMMs of human pancreatic cancer, with a focus on the Lox-Stop-Lox (LSL-KrasG12D; LSL-Trp53R172H; Pdx1-cre (KPC model, one of the most widely used preclinical models for this disease. We describe its application in preclinical research, highlighting its advantages and disadvantages, its potential for predicting clinical outcomes in humans and the factors that can affect such outcomes, and, finally, future developments that could advance the discovery of new therapies for pancreatic cancer.

  6. Somatostatin receptor-1 induces cell cycle arrest and inhibits tumor growth in pancreatic cancer.

    Science.gov (United States)

    Li, Min; Wang, Xiaochi; Li, Wei; Li, Fei; Yang, Hui; Wang, Hao; Brunicardi, F Charles; Chen, Changyi; Yao, Qizhi; Fisher, William E

    2008-11-01

    Functional somatostatin receptors (SSTR) are lost in human pancreatic cancer. Transfection of SSTR-1 inhibited pancreatic cancer cell proliferation in vitro. We hypothesize that stable transfection of SSTR-1 may inhibit pancreatic cancer growth in vivo possibly through cell cycle arrest. In this study, we examined the expression of SSTR-1 mRNA in human pancreatic cancer tissue specimens, and investigated the effect of SSTR-1 overexpression on cell proliferation, cell cycle, and tumor growth in a subcutaneous nude mouse model. We found that SSTR-1 mRNA was downregulated in the majority of pancreatic cancer tissue specimens. Transfection of SSTR-1 caused cell cycle arrest at the G(0)/G(1) growth phase, with a corresponding decline of cells in the S (mitotic) phase. The overexpression of SSTR-1 significantly inhibited subcutaneous tumor size by 71% and 43% (n = 5, P < 0.05, Student's t-test), and inhibited tumor weight by 69% and 47% (n = 5, P < 0.05, Student's t-test), in Panc-SSTR-1 and MIA-SSTR-1 groups, respectively, indicating the potent inhibitory effect of SSTR-1 on pancreatic cancer growth. Our data demonstrate that overexpression of SSTR-1 significantly inhibits pancreatic cancer growth possibly through cell cycle arrest. This study suggests that gene therapy with SSTR-1 may be a potential adjuvant treatment for pancreatic cancer. PMID:18823376

  7. Slc26a6敲除对小鼠胰腺导管上皮细胞Slc26a3和CFTR表达水平的影响%Effect of Slc26a6 Knock-Out on Slc26a3 and CFTR Expression in Mouse Pancreatic Ducts

    Institute of Scientific and Technical Information of China (English)

    宋莹; 赵岳; 刘伯纯; 石黑洋; 金春香

    2011-01-01

    wild-type (0 .08± 0 .003) and Slc26a6 knock-out mice (0 .05±0 .003) .Conclusion Slc26a6 knock-out has no effects on the expression of Slc26a3 and CFTR in the mouse pancreatic ducts .The activation of CFTR by SLC26A6 does not depend on the increasing of CFTR expression . Slc26a3 maybe involved in the secretion of HCO3- on the mouse pancreatic duct cells ,but the relationship between SLC26A6 and SLC26A3 is not clear in details .

  8. The clinical assessment of intraductal ultrasonography in the differential diagnosis of pancreatic carcinoma and chronic pancreatitis.

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To assess and compare the clinical value of intraductal ultrasonography (IDUS) in the differential diagnosis of pancreatic carcinoma and chronic pancreatitis with conventional imaging methods. Methods: IDUS was carried out in eighteen patients with pancreatic carcinoma and chronic pancreatitis

  9. Controlled clinical study on pancreatic stenting in the relief of pain of advanced pancreatic cancer with dilated pancreatic duct

    Institute of Scientific and Technical Information of China (English)

    高飞

    2014-01-01

    Objective To explore the efficacy of pancreatic stenting in the relief of abdominal pain of advanced pancreatic cancer with dilated pancreatic duct.Methods A tolal of 61 patients with advanced pancreatic carcinoma companied with dilated pancreatic duct were divided into two groups.Twenty-eight cases(two cases were excluded because of stent loss)in stent group treated with

  10. Small-Molecule Inhibition of GCNT3 Disrupts Mucin Biosynthesis and Malignant Cellular Behaviors in Pancreatic Cancer.

    Science.gov (United States)

    Rao, Chinthalapally V; Janakiram, Naveena B; Madka, Venkateshwar; Kumar, Gaurav; Scott, Edgar J; Pathuri, Gopal; Bryant, Taylor; Kutche, Hannah; Zhang, Yuting; Biddick, Laura; Gali, Hariprasad; Zhao, Yan D; Lightfoot, Stan; Mohammed, Altaf

    2016-04-01

    Pancreatic cancer is an aggressive neoplasm with almost uniform lethality and a 5-year survival rate of 7%. Several overexpressed mucins that impede drug delivery to pancreatic tumors have been therapeutically targeted, but enzymes involved in mucin biosynthesis have yet to be preclinically evaluated as potential targets. We used survival data from human patients with pancreatic cancer, next-generation sequencing of genetically engineered Kras-driven mouse pancreatic tumors and human pancreatic cancer cells to identify the novel core mucin-synthesizing enzyme GCNT3 (core 2 β-1,6 N-acetylglucosaminyltransferase). In mouse pancreatic cancer tumors, GCNT3 upregulation (103-fold; P pancreatic cancer cells reduced proliferation and spheroid formation. Using in silico small molecular docking simulation approaches, we identified talniflumate as a novel inhibitor that selectively binds to GCNT3. In particular, docking predictions suggested that three notable hydrogen bonds between talniflumate and GCNT3 contribute to a docking affinity of -8.3 kcal/mol. Furthermore, talniflumate alone and in combination with low-dose gefitinib reduced GCNT3 expression, leading to the disrupted production of mucins in vivo and in vitro Collectively, our findings suggest that targeting mucin biosynthesis through GCNT3 may improve drug responsiveness, warranting further development and investigation in preclinical models of pancreatic tumorigenesis. Cancer Res; 76(7); 1965-74. ©2016 AACR. PMID:26880801

  11. Atorvastatin-induced pancreatitis

    Directory of Open Access Journals (Sweden)

    Prajapati Samir

    2010-01-01

    Full Text Available Drugs account for 1-2% of all cases of pancreatitis. A 58-year-old man was prescribed atorvastatin 10 mg for 6 months for hyperlipidemia. He developed acute abdominal pain and vomiting with epigastric tenderness. Serum lipase and CT scan of the patient suggested the presence of acute pancreatitis. The patient was hospitalized; atorvastatin was stopped and treated symptomatically. He recovered completely within 10 days of drug withdrawal. The causality of the adverse drug reaction according to Naranjo and WHO-UMC Scale was probable. The exact mechanism of pancreatitis due to atorvastatin is not known. It may be a class effect of HMG CoA reductase inhibitors as it had been reported with other statins too. The definite causal relationship is difficult to establish, as rechallenge with the suspected drug was not done due to ethical consideration.

  12. Drug-induced pancreatitis.

    Science.gov (United States)

    Nitsche, Claudia; Maertin, Sandrina; Scheiber, Jonas; Ritter, Christoph A; Lerch, Markus M; Mayerle, Julia

    2012-04-01

    Drugs are thought to be a rare cause for acute pancreatitis; however 525 different drugs are listed in the World Health Organization (WHO) database suspected to cause acute pancreatitis as a side effect. Many of them are widely used to treat highly prevalent diseases. The true incidence is not entirely clear since only few systematic population based studies exist. The majority of the available data are derived from case reports or case control studies. Furthermore, the causality for many of these drugs remains elusive and for only 31 of these 525 dugs a definite causality was established. Definite proof for causality is defined by the WHO classification if symptoms reoccur upon rechallenge.In the actual algorithm the diagnosis is confirmed if no other cause of acute pancreatitis can be detected, and the patient is taking one of the suspected drugs. PMID:22314811

  13. Primary Pancreatic Lymphomas

    Directory of Open Access Journals (Sweden)

    Muhammad Wasif Saif

    2006-05-01

    Full Text Available Extranodal non-Hodgkin’s lymphomas (NHLs represent up to 30-40% of all NHL cases. The gastrointestinal tract is the most commonly involved extranodal site; accounting for about half of such cases [1]. Stomach and the small intestine constitute the most common gastrointestinal sites. Secondary invasion of the pancreas from contiguous, retroperitoneal lymph node disease is the prevalent mode of involvement. Secondary involvement of the pancreas from the duodenum or adjacent peripancreatic lymphadenopathy is well-known. Primary pancreatic lymphoma (PPL is an extremely rare disease [2]. PPL can present as an isolated mass mimicking pancreatic carcinoma. However, unlike carcinomas, PPL are potentially treatable [3].

  14. Congenital pancreatic cysts

    Directory of Open Access Journals (Sweden)

    Seddighy A

    1998-07-01

    Full Text Available Congenital cyst of the pancreas is an uncommon problem in the pediatric patient. The common symptoms at the time of diagnosis have been abdominal mass and pain or fullness, nausea and vomiting. Despite of various paraclinic methods for diagnosis, ultrasound is now recognized as the most effective and best noninvasive method for diagnosis of pancreatic cyts. Surgical intervention is the best mode of therapy. Upper abdominal cystic mass are seen in the fetus and newborn infants. In Amirkabir Hospital, during 12 years from 1981 to 1993, 8 pancreatic cysts have been operated on and only in this case it was congenital.

  15. Chemoradiotherapy in pancreatic carcinoma

    Directory of Open Access Journals (Sweden)

    Pathy Sushmita

    2009-01-01

    Full Text Available Pancreatic cancer patients present late in their course and surgical resection as a modality of treatment is of limited value. Majority develop loco-regional failure and distant metastasis, therefore, adjuvant therapy comprising of radiotherapy and chemotherapy are useful treatment options to achieve higher loco-regional control. Specialized irradiation techniques like intra-operative radiotherapy that help to increase the total tumor dose have been used, however, controvertible survival benefit was observed. Various studies have shown improved median and overall survival with chemoradiotherapy for advanced unresectable pancreatic carcinoma. The role of new agents such as topoisomerase I inhibitors also needs further clinical investigations.

  16. Unusual complications of pancreatitis

    International Nuclear Information System (INIS)

    The computed tomography (CT) appearances of varying grades of severity of acute pancreatitis, and its complications, have been described. Body-wall ecchymosis in the periumbilical region (Cullen's sign) and loins (Grey Turner's sign), though rare, are frequently mentioned in the clinical literature. Massive, exclusively retroperitoneal, involvement is also exceedingly rare. Computed tomography depiction of these signs is sparsely documented. The CT documentation, with clinico-surgical correlation, of two cases of severe acute pancreatitis with these unusual complications, is presented. 9 refs., 3 figs

  17. Post-partum pancreatitis.

    Directory of Open Access Journals (Sweden)

    Pai P

    1993-04-01

    Full Text Available Acute pancreatitis in pregnancy and post-partum period, rarely encountered in surgical practice, can have a lethal effect on the mother and the foetus. We report here a case of a 35 year old tertigravida who presented with high grade fever, abdominal pain with distension, tachycardia and tachypnoea. Chest examination and X-rays were suggestive of pneumonia. The abdomen was tense and tender. Peristalsis was absent. Ultrasound revealed presence of fluid in the abdominal cavity which on paracentesis was found to contain Gram positive cocci. Fluid amylase levels were high. On exploratory laparotomy, haemorrhagic oedematous pancreatitis was noticed. The patient expired on the 2nd post operative day.

  18. MR imaging of pancreatic diseases

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Katsuyoshi E-mail: itokatsu@po.cc.yamaguchi-u.ac.jp; Koike, Shinji; Matsunaga, Naofumi

    2001-05-01

    This article presents current MR imaging techniques for the pancreas, and review a spectrum of MR imaging features of various pancreatic diseases. These include: 1) congenital anomalies such as anomalous union of pancreatobiliary ducts, divisum, and annular pancreas, 2) inflammatory diseases, including acute or chronic pancreatitis with complications, groove pancreatitis, and autoimmune pancreatitis, tumor-forming pancreatitis, 3) pancreatic neoplasms, including adenocarcinoma, islet cell tumors, and cystic neoplasms (microcystic adenoma, mucinous cystic neoplasms, and intraductal mucin-producing pancreatic tumor). Particular attention is paid to technical advances in MR imaging of the pancreas such as fat-suppression, MR pancreatography (single- or multi-slice HASTE), and thin-section 3D multiphasic contrast-enhanced dynamic sequences. Imaging characteristics that may lead to a specific diagnosis or narrow the differential diagnosis are also discussed.

  19. Isoniazid-Induced Recurrent Pancreatitis

    Directory of Open Access Journals (Sweden)

    Sarah Mattioni

    2012-05-01

    Full Text Available Context Drug induced pancreatitis are rare but potentially serious. Thus, drug withdrawal is warranted. Case report A 79-year-old woman who was treated with antituberculosis therapy for 5 weeks was admitted to our unit for pancreatitis. Usual etiologies of pancreatitis were eliminated. Because of vomiting, antituberculosis therapy was withdrawn and symptoms disappeared. Eight days later, the same treatment was reintroduced and the patient presented recurrent pancreatitis; thus, treatment was withheld again followed by disappearance of clinical and biological abnormalities. Two days later, a treatment without isoniazid was reintroduced and no recurrence of symptoms was observed. Conclusions We have experienced a case of isoniazid induced pancreatitis. This is a rare cause of pancreatitis but potentially fatal thus recognition of drug induced pancreatitis and definitive withdrawal of the drug is required.

  20. Neoadjuvant Therapy in Pancreatic Cancer: Review Article

    OpenAIRE

    Moritz Pross; Wellner, Ulrich F.; Kim C Honselmann; Carlo Jung; Steffen Deichmann; Tobias Keck; Dirk Bausch

    2015-01-01

    We performed a literature review for neoadjuvant therapy in pancreatic cancer. We divided the results into resectable disease and local advanced pancreatic cancer. Results Neoadjuvant therapy in pancreatic cancer is safe. But currently no standard guidelines exist in neoadjuvant approaches on pancreatic cancer. For local advanced pancreatic cancer the available data tends to show a positive effect on survival rates for neoadjuvant approaches.

  1. Environmental risk factors for chronic pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Nitsche, Claudia; Simon, Peter; Weiss, F Ulrich; Fluhr, Gabriele; Weber, Eckhard; Gärtner, Simone; Behn, Claas O; Kraft, Matthias; Ringel, Jörg; Aghdassi, Ali; Mayerle, Julia; Lerch, Markus M

    2011-01-01

    Chronic pancreatitis has long been thought to be mainly associated with immoderate alcohol consumption. The observation that only ∼10% of heavy drinkers develop chronic pancreatitis not only suggests that other environmental factors, such as tobacco smoke, are potent additional risk factors, but also that the genetic component of pancreatitis is more common than previously presumed. Either disease-causing or protective traits have been indentified for mutations in different trypsinogen genes, the gene for the trypsin inhibitor SPINK1, chymotrypsinogen C, and the cystic fibrosis transmembane conductance regulator (CFTR). Other factors that have been proposed to contribute to pancreatitis are obesity, diets high in animal protein and fat, as well as antioxidant deficiencies. For the development of pancreatic cancer, preexisting chronic pancreatitis, more prominently hereditary pancreatitis, is a risk factor. The data on environmental risk factors for pancreatic cancer are, with the notable exception of tobacco smoke, either sparse, unconfirmed or controversial. Obesity appears to increase the risk of pancreatic cancer in the West but not in Japan. Diets high in processed or red meat, diets low in fruits and vegetables, phytochemicals such as lycopene and flavonols, have been proposed and refuted as risk or protective factors in different trials. The best established and single most important risk factor for cancer as well as pancreatitis and the one to clearly avoid is tobacco smoke. PMID:21734390

  2. 胰腺导管上皮细胞转分化为胰岛样细胞%Transdifferentiation of mouse pancreatic ductal epithelial cells into islet-like cells

    Institute of Scientific and Technical Information of China (English)

    赵艳艳; 余勤; 李志臻; 秦贵军

    2010-01-01

    BACKGROUND: Islet transplantation is an effective method for the treatment of type 1 diabetes mellitus and parts of type 2 diabetes mellitus. However, its application is hindered by insufficient sources and immunologic rejection. Though transdifferentiation of pancreatic stem cells is at the starting step, it is thought to be the hopeful source for islet cell transplantation.OBJECTIVE: To look for a suitable cells-transplantation source for the treatment of diabetes mellitus. METHODS: The pancreatic ductal epithelial cells were separated from Kunming mice and cultured in DMEM/F12 medium supplemented with keratinocyte growth factor, hepatocyte growth factor and nicotinamide, etc. Samples were taken at different time points for light microscopy and electron microscope. The changes of CK-19 and PDX-1 were detected by immunocytochemistry at 1 and 16 days. The expressions of insulin and glucagon gene were detected by RT-PCR at 1 and 16 days. The physiologic function of these islet-like clusters was determined by dithizone staining and glucose stimulation at 21 days. RESULTS AND CONCLUSION: A large number of epitheliod cells were CK-19 immunoreactive positive and few of them were PDX-1 positive at 1 day after isolation, then CK-19 positive cells proliferated quickly and formed substantial plaques of epithelial cells in cobblestone pattern. At 16 days later, these cells begin to form islet-like clusters gradually, while most of them were PDX-1 immunoreactive positive. The analysis of mRNA by RT-PCR showed very low levels of insulin and glucagon mRNA in the starting materials but increase was found as the process of transdifferentiation. At 21 day differentiated islet-like clusters were stained red by dithizone. In those samples exposed to a stimulatory 15 mmol/L glucose, there was a 1.6-fold increase in insulin compared with to 5.6 mmol/L glucose (P < 0.05). Pancreatic ductal cells of adult Kunming mice could proliferate quickly and have the potency of

  3. Design and synthesis of an in vivo-efficacious PIM3 kinase inhibitor as a candidate anti-pancreatic cancer agent.

    Science.gov (United States)

    Nakano, Hirofumi; Hasegawa, Tsukasa; Saito, Nae; Furukawa, Kaoru; Mukaida, Naofumi; Kojima, Hirotatsu; Okabe, Takayoshi; Nagano, Tetsuo

    2015-12-15

    Serine/threonine kinase PIM3 is a potential therapeutic target for pancreatic cancer. Here, we describe the evolution of our previous PIM1 inhibitor 1 into PIM3 inhibitor 11 guided by use of the crystal structure of PIM1 as a surrogate to provide a basis for rational modification. Compound 11 potently inhibits PIM3 kinase activity, as well as growth of several pancreatic cancer cell lines. In a mouse xenograft model, 11 inhibited growth of human pancreatic cancer cell line PCI66 with negligible body weight loss. Thus, 11 appears to be a promising lead compound for further optimization to develop new anti-pancreatic cancer agents. PMID:26547690

  4. Proinflammatory Cytokines Induce Endocrine Differentiation in Pancreatic Ductal Cells via STAT3-Dependent NGN3 Activation

    Directory of Open Access Journals (Sweden)

    Ivan Achel Valdez

    2016-04-01

    Full Text Available A major goal of diabetes research is to develop strategies that replenish pancreatic insulin-producing beta cells. One emerging strategy is to harness pancreatic plasticity—the ability of pancreatic cells to undergo cellular interconversions—a phenomenon implicated in physiological stress and pancreatic injury. Here, we investigate the effects of inflammatory cytokine stress on the differentiation potential of ductal cells in a human cell line, in mouse ductal cells by pancreatic intraductal injection, and during the progression of autoimmune diabetes in the non-obese diabetic (NOD mouse model. We find that inflammatory cytokine insults stimulate epithelial-to-mesenchymal transition (EMT as well as the endocrine program in human pancreatic ductal cells via STAT3-dependent NGN3 activation. Furthermore, we show that inflammatory cytokines activate ductal-to-endocrine cell reprogramming in vivo independent of hyperglycemic stress. Together, our findings provide evidence that inflammatory cytokines direct ductal-to-endocrine cell differentiation, with implications for beta cell regeneration.

  5. Proinflammatory Cytokines Induce Endocrine Differentiation in Pancreatic Ductal Cells via STAT3-Dependent NGN3 Activation.

    Science.gov (United States)

    Valdez, Ivan Achel; Dirice, Ercument; Gupta, Manoj K; Shirakawa, Jun; Teo, Adrian Kee Keong; Kulkarni, Rohit N

    2016-04-19

    A major goal of diabetes research is to develop strategies that replenish pancreatic insulin-producing beta cells. One emerging strategy is to harness pancreatic plasticity-the ability of pancreatic cells to undergo cellular interconversions-a phenomenon implicated in physiological stress and pancreatic injury. Here, we investigate the effects of inflammatory cytokine stress on the differentiation potential of ductal cells in a human cell line, in mouse ductal cells by pancreatic intraductal injection, and during the progression of autoimmune diabetes in the non-obese diabetic (NOD) mouse model. We find that inflammatory cytokine insults stimulate epithelial-to-mesenchymal transition (EMT) as well as the endocrine program in human pancreatic ductal cells via STAT3-dependent NGN3 activation. Furthermore, we show that inflammatory cytokines activate ductal-to-endocrine cell reprogramming in vivo independent of hyperglycemic stress. Together, our findings provide evidence that inflammatory cytokines direct ductal-to-endocrine cell differentiation, with implications for beta cell regeneration. PMID:27068459

  6. Pancreatic and hepatobiliary cancers.

    Science.gov (United States)

    Buck, Andreas K; Herrmann, Ken; Eckel, Florian; Beer, Ambros J

    2011-01-01

    Morphology-based imaging modalities have replaced classical conventional nuclear medicine modalities for detection of liver or pancreatic lesions. With positron emission tomography and the glucose analog F-18 fluorodeoxyglucose (FDG), a sensitive and specific modality for the detection of hepatic metastases and extrahepatic tumor deposits from hepatocellular or pancreatic cancer is available. F-18 FDG PET can increase the accuracy of staging primary tumors of the liver or the pancreas, and can be used for response monitoring. Radiopharmaceuticals such as Ga-68 DOTATOC and F-18 DOPA allow the specific detection of neuroendocrine pancreatic tumors and their metastatic deposits. Hybrid scanners such as PET-CT integrate morphologic and metabolic information, and allow to increase the sensitivity and specificity of noninvasive imaging in many tumor entities. The development of specific radiopharmaceuticals and technical innovations such as SPECT-CT has increased the reliability of conventional scintigraphic imaging. This chapter focuses on the use of PET-CT in hepatobiliary and pancreatic cancers. PMID:21331938

  7. Radioimmunoassay of pancreatic glucagon

    International Nuclear Information System (INIS)

    The author presents some of the problems and concepts related to the development of a radioimmunoassay of pancreatic glucagon. A specific derivatization of glucagon for raising specific anti-glucagon antisera is introduced, and special procedures for diminishing the non-specific effect are outlined. (G.T.H.)

  8. Chronic Pancreatitis in Children

    Science.gov (United States)

    ... fewer than 10 grams of fat. About 20 potato chips contain 10 grams of fat, so it takes discipline to make sure to stay within this range. Patients who have lost the ability to digest food will be prescribed pills containing pancreatic enzymes to help with digestion. They may also be ...

  9. Pancreatic Cancer Stage 4

    Science.gov (United States)

    ... lung, liver, and peritoneal cavity. An inset shows cancer cells spreading from the pancreas, through the blood and lymph system, to another ... abdomen that contains the intestines, stomach, and liver). Cancer may also have spread to ... pancreas or to lymph nodes. Stage IV pancreatic cancer. ...

  10. Hyperamylasaemia: pathognomonic to pancreatitis?

    OpenAIRE

    Burden, Sam; Poon, Anna Sau Kuk; Masood, Kausar; Didi, Mohamed

    2013-01-01

    An 82-year-old woman, presented with a history of vomiting, abdominal mass and a significantly raised amylase, but no clinical evidence of pancreatitis. Abdominal ultrasound and CT scans showed an ovarian tumour, and no evidence of pancreatitis—as is often associated with a raised amylase. The patient underwent bilateral ovariectomy and hysterectomy and made a good recovery.

  11. Focal autoimmune pancreatitis

    OpenAIRE

    Maren, N Vander; Everarts, Ph; Nicaise, G.

    2014-01-01

    A 70-year-old man was referred for evaluation of mild epigastric discomfort with tiredness. He had no particular medical history and admitted drinking two glasses of wine a day. Biology showed a small increase in CRP and pancreatic enzymes (lipases and amylases).

  12. Autoantibodies in chronic pancreatitis

    DEFF Research Database (Denmark)

    Rumessen, J J; Marner, B; Pedersen, N T;

    1985-01-01

    In 60 consecutive patients clinically suspected of having chronic pancreatitis the serum concentration of the immunoglobulins (IgA, IgG, IgM), the IgG- and IgA-type non-organ-specific autoantibodies against nuclear material (ANA), smooth and striated muscle, mitochondria, basal membrane, and...

  13. Pancreatic Cancer: A Review.

    Science.gov (United States)

    Yabar, Cinthya S; Winter, Jordan M

    2016-09-01

    Pancreatic cancer is now the third leading cause of cancer related deaths in the United States, yet advances in treatment options have been minimal over the past decade. In this review, we summarize the evaluation and treatments for this disease. We highlight molecular advances that hopefully will soon translate into improved outcomes. PMID:27546841

  14. Study on chronic pancreatitis and pancreatic cancer using MRS and pancreatic juice samples

    Institute of Scientific and Technical Information of China (English)

    Jian Wang; Chao Ma; Zhuan Liao; Bing Tian; Jian-Ping Lu

    2011-01-01

    AIM: To investigate the markers of pancreatic diseases and provide basic data and experimental methods for the diagnosis of pancreatic diseases. METHODS: There were 15 patients in the present study, among whom 10 had pancreatic cancer and 5, chronic pancreatitis. In all patients, pancreatic cancer or chronic pancreatitis was located on the head of the p-a-ncreas. Pathology data of all pa tients was confirmed by biopsy and surgery. Among the 10 patients with pancreatic cancer, 3 people had a medical history of longterm alcohol consumption. Of 5 patients with chronic pancreatitis, 4 men suffered from alcoholic chronic pancreatitis. Pancreatic juice samples were obtained from patients by endoscopic retrograde cholangiopancreatography. Magnetic resonance spectroscopyn was performed on an 11.7-T scanner (Bruker DRX-500) using Call-Purcell-Meiboom-Gill pulse sequences. The parameters were as follows: spectral width, 15 KHz; time domain, 64 K; number of scans, 512; and acquisition time, 2.128 s. RESULTS: The main component of pancreatic juice included leucine, iso-leucine, valine, lactate, alanine, acetate, aspartate, lysine, glycine, threonine, tyrosine, histidine, tryptophan, and phenylalanine. On performing 1D 1H and 2D total correlation spectroscopy, we found a triplet peak at the chemical shift of 1.19 ppm, which only appeared in the spectra of pancreatic juice obtained from patients with alcoholic chronic pancreatitis. This triplet peak was considered the resonance of the methyl of ethoxy group, which may be associated with the metabolism of alcohol in the pancreas. CONCLUSION: The triplet peak, at the chemical shift of 1.19 ppm is likely to be the characteristic metabolite of alcoholic chronic pancreatitis.

  15. Characterisation of a transgenic mouse expressing R122H human cationic trypsinogen

    Directory of Open Access Journals (Sweden)

    Mössner Joachim

    2006-10-01

    Full Text Available Abstract Background The R122H mutation of the cationic trypsinogen was found in patients with hereditary pancreatitis. A transgenic animal carrying this mutation could be useful as a genetic model system of pancreatitis. Methods Mice transgenic for the human R122H cationic trypsinogen were generated using the -205 fragment of the rat elastase promoter. The presence of the transgene was assayed in the DNA, in pancreatic mRNA and in zymogen granule lysates. Serum levels of amylase, lipase and cytokines (MCP-1, IL-6 were monitored and the histological appearance of the tissue was investigated. Pancreatitis was induced by 7 hourly injections of 50 μg/kg cerulein. The procedure was repeated twice weekly for 10 consecutive weeks. The animals were sacrificed 24 (n = 8 and 48 hours (n = 8 after the first injection and at the end of the whole treatment (n = 7. Results The transgene was detected at the genomic level and in pancreatic mRNA. The corresponding protein was found in low amounts in zymogen granule lysates. R122H mice showed elevated pancreatic lipase, but there was no spontaneous development of pancreatitis within 18 months. After induction of pancreatitis, levels of lipase (after 24 hours and amylase (after 48 hours were higher in R122H mice compared to controls. Repeated treatment with cerulein resulted in a slightly more severe pancreatitis in R122H animals. Amylase, lipase, and the cytokine levels were similar to controls. Conclusion The R122H transgenic mouse failed to develop a spontaneous pancreatitis but a repeatedly provoked cerulein-induced pancreatitis led to a slightly more severe pancreatitis. The rather small difference in comparison to controls could be due to the low expression of the transgene in the mouse pancreas.

  16. CT-Guided Pancreatic Percutaneous Fine-Needle Biopsy in Differential Diagnosis between Pancreatic Cancer and Chronic Pancreatitis

    OpenAIRE

    Michele Carlucci; Alessandro Zerbi; Danilo Parolini; Sandro Sironi; Angelo Vanzulli; Carlo Staudacher; Agostino Faravelli; Paola Garancini; Alessandro del Maschio; Valerio di Carlo

    1989-01-01

    Differential diagnosis between pancreatic cancer and chronic pancreatitis is still difficult to establish. In 63 patients with suspected pancreatic neoplasm we performed: serum CA 19-9 assessment, abdominal ultrasound, CT scan and CT-guided pancreatic percutaneous fine-needle biopsy. The conclusive diagnosis was pancreatic cancer in 40 patients and chronic pancreatitis in 23 patients. With regard to the differential diagnosis, sensitivity and specificity were respectively 80% and ...

  17. Acute pancreatitis: Etiology and common pathogenesis

    Institute of Scientific and Technical Information of China (English)

    Guo-Jun Wang; Chun-Fang Gao; Dong Wei; Cun Wang; Si-Qin Ding

    2009-01-01

    Acute pancreatitis is an inflammatory disease of the pancreas. The etiology and pathogenesis of acute pancreatitis have been intensively investigated for centuries worldwide. Many causes of acute pancreatitis have been discovered, but the pathogenetic theories are controversial. The most common cause of acute pancreatitis is gallstone impacting the distal common bile-pancreatic duct. The majority of investigators accept that the main factors for acute billiary pancreatitis are pancreatic hyperstimulation and bile-pancreatic duct obstruction which increase pancreatic duct pressure and active trypsin reflux. Acute pancreatitis occurs when intracellular protective mechanisms to prevent trypsinogen activation or reduce trypsin activity are overwhelmed. However, little is known about the other acute pancreatitis. We hypothesize that acute biliary pancreatitis and other causes of acute pancreatitis possess a common pathogenesis. Pancreatic hyperstimulation and pancreatic duct obstruction increase pancreatic duct pressure, active trypsin reflux, and subsequent unregulated activation of trypsin within pancreatic acinar cells. Enzyme activation within the pancreas leads to auto-digestion of the gland and local inflammation. Once the hypothesis is confirmed, traditional therapeutic strategies against acute pancreatitis may be improved. Decompression of pancreatic duct pressure should be advocated in the treatment of acute pancreatitits which may greatly improve its outcome.

  18. 多时间节点荷人胰腺癌SW1990细胞裸鼠模型的建立及其MRI表现%Establishment of the nude mouse model bearing human pancreatic adenocarcinoma in multiple timepoints and its 3.0T MRI findings

    Institute of Scientific and Technical Information of China (English)

    潘璜; 邵成伟; 田建明

    2012-01-01

    Objective To establish nude mouse tumor models bearing human pancreatic adenocarcinoma SW1990 cells in multiple sites at different time-points and investigate the feasibiilty of multiple tumor-bearing in these models; then the findings and detection rate of 3.0T magnetic resonance image (MRI) in subcutaneous transplanted tumors was analyzed. Methods A total of 6 BALB/C nude mice were randomized into 3 groups (2 mice per group ).At the 1st,8th,15th day,the mice were injected subcutaneously with the suspension of SW1990 cells at left axilla and right axilla and right groin in sequence.Three weeks later,all the bearing-tumor mice were performed with MRI non-contrast enhanced scanning plus Gd-DTPA enhanced scan and the subcutaneous masses were subjected to pathological analysis.Results All the 6 nude mice were alive during the study and obvious mass was observed in every injected site.The tumor size was positively associated with the grwing time.There were 9 tumors which could be de.ted by noncontrast enhanced MRI scanning and one more tumor was detected by contrast enhanced scanning.2 tumors were not detected,the 2 tumors were located at subcutaneous of right groin,with the shortest growing time,and the major axis of the 2 un-detected tumors was less than 5mm.Despite the MRI findings of the transplanted masses similar to that of human pancreatic adenocarcinoma with bleeding,necrosis,they presented the characteristics of a clear rim,with "pseudocapeule" sign.All the 12 masses were similar with human pancreatic adenocarcinoma under light microscope.Conclusions It is feasible to transplant human pancreatic adenocarcinoma cell at three different subcutaneous sites (injected at three different points of time) in the nude mouse,with a minimal survival time of three weeks.However,routine 3.0T MRI cannot detect the early tumors (growing time within 1 week,major axis <5 mm).%目的 研究裸鼠荷载多时间节点人胰腺癌细胞的能力,分析其MRI表现及

  19. Diabetes and Pancreatic Cancer-2014

    Directory of Open Access Journals (Sweden)

    Andre Luiz De Souza

    2014-03-01

    Full Text Available Context Pancreatic cancer is the fourth leading cause of cancer mortality in the United States. Most of the patients are diagnosed in the metastatic staging. Consolidated risk factors include chronic pancreatitis, smoking and family history. Although controversial, diabetes mellitus has been increasingly associated with pancreatic cancer as a risk factor as opposed to just a manifestation of the disease. Biomarkers for early diagnosis of pancreatic cancer among diabetic patients and metformin as a biologic therapy for pancreatic cancer are herein discussed. Methods Review of the literature and evaluation of two Abstracts (#180 and #253 from the 2014 ASCO Gastrointestinal Cancers Symposium focusing on pancreatic adenocarcinoma and diabetes diagnosis and therapeutics. Results Abstract #180 discusses the role of metabolic biomarkers in the early diagnosis of pancreatic cancer among diabetic patients, especially recently diagnosed. Abstract #253 debates metformin as a candidate radiosensitizer for pancreatic cancer, although it fails to reject its null hypothesis. Conclusion Search for methods that can identify pancreatic cancer patients among new-onset diabetic patients could result in early diagnosis of this lethal disease. Metformin is a target therapy that increases median overall survival but is not a radiation sensitizer in patients with pancreatic cancer who present with diabetes.

  20. Acute pancreatitis: clinical vs. CT findings

    International Nuclear Information System (INIS)

    In a prospective study of 91 patients with acute pancreatitis, computed tomographic (CT) findings were correlated with the clinical type of acute pancreatitis. In acute edematous pancreatitis (63 patients; 16 with repeat CT), CT was normal (28%) or showed inflammation limited to the pancreas (61%). Phlegmonous changes were present in 11%, including one patient with focal pancreatic hemorrhage, indicating that clinically unsuspected hemorrhagic pancreatitis can occur. In acute necrotizing (hemorrhagic, suppurative) pancreatitis (nine patients; eight with repeat CT), no patient had a normal CT scan and 89% had phlegmonous changes. One patient had hemorrhagic pancreatitis and three had abscesses. In acute exacerbation of chronic pancreatitis (10 patients; three with repeat CT), there were pancreatic calcifications (70%), a focal mass (40%), and pancreatic ductal dilation (30%). On follow-up CT, the findings of acute pancreatitis did not always disappear with resolution of the clinical symptons. This was especialy true of phlegmonous pancreatitis, where the CT findings could persist for months

  1. Acute Pancreatitis: Surgery, Pathophysiology and Probiotic Prophylaxis

    NARCIS (Netherlands)

    Minnen, L.P. van

    2006-01-01

    Acute pancreatitis is a challenging disease with a clinical course that is often difficult to predict. In severe acute pancreatitis, mortality increases significantly if intestinal bacteria translocate from the intestine and infect pancreatic necrosis. Surgical and prophylactic treatment strategies

  2. Exocrine pancreatic enzyme and calcium secretion in health and pancreatitis.

    OpenAIRE

    Clain, J E; Barbezat, G O; Marks, I N

    1981-01-01

    Calcium, enzyme, and total protein secretion were measured in secretin stimulated pancreatic juice in health, "early" chronic pancreatitis, and in chronic calcific pancreatitis. Increased concentrations of trypsin, total protein, and calcium, and increased outputs of calcium and protein were shown to be present in the "early" stages of the disease, indicating that an environment conducive to the formation of protein plugs and possibly later calcification already exists.

  3. Groove Pancreatitis: A Rare form of Chronic Pancreatitis

    OpenAIRE

    Bharivi Jani; Fadi Rzouq; Shreyas Saligram; Atta Nawabi; Marian Nicola; Katie Dennis; Carly Ernst; Ali Abbaszadeh; John Bonino; Mojtaba Olyaee

    2015-01-01

    Context: Groove pancreatitis is a rare form of chronic pancreatitis affecting the "groove" of the pancreas among the pancreatic head, duodenum, and common bile duct. The exact cause is unknown, although there are associations with long-term alcohol abuse, smoking, peptic ulcer disease, heterotopic pancreas, gastric resection, biliary disease, and anatomical or functional obstruction of the minor papilla. The diagnosis can be challenging. Endoscopic ultrasound (EUS) and magnetic resonance chol...

  4. Role of pancreatic stellate cells in chemoresistance in pancreatic cancer

    OpenAIRE

    McCarroll, Joshua A.; Naim, Stephanie; Sharbeen, George; Russia, Nelson; Lee, Julia; Kavallaris, Maria; Goldstein, David; Phillips, Phoebe A.

    2014-01-01

    Pancreatic cancer is highly chemoresistant. A major contributing factor is the characteristic extensive stromal or fibrotic reaction, which comprises up to 90% of the tumor volume. Over the last decade there has been intensive research into the role of the pro-fibrogenic pancreatic stellate cells (PSCs) and their interaction with pancreatic cancer cells. As a result of the significant alterations in the tumor microenvironment following activation of PSCs, tumor progression, and chemoresistanc...

  5. Design of a nanoplatform for treating pancreatic cancer

    Science.gov (United States)

    Manawadu, Harshi Chathurangi

    Pancreatic cancer is the fourth leading cause of cancer-related deaths in the USA. Asymptomatic early cancer stages and late diagnosis leads to very low survival rates of pancreatic cancers, compared to other cancers. Treatment options for advanced pancreatic cancer are limited to chemotherapy and/or radiation therapy, as surgical removal of the cancerous tissue becomes impossible at later stages. Therefore, there's a critical need for innovative and improved chemotherapeutic treatment of (late) pancreatic cancers. It is mandatory for successful treatment strategies to overcome the drug resistance associated with pancreatic cancers. Nanotechnology based drug formulations have been providing promising alternatives in cancer treatment due to their selective targeting and accumulation in tumor vasculature, which can be used for efficient delivery of chemotherapeutic agents to tumors and metastases. The research of my thesis is following the principle approach to high therapeutic efficacy that has been first described by Dr. Helmut Ringsdorf in 1975. However, I have extended the use of the Ringsdorf model from polymeric to nanoparticle-based drug carriers by exploring an iron / iron oxide nanoparticle based drug delivery system. A series of drug delivery systems have been synthesized by varying the total numbers and the ratio of the tumor homing peptide sequence CGKRK and the chemotherapeutic drug doxorubicin at the surfaces of Fe/Fe3O 4-nanoparticles. The cytotoxicity of these nanoformulations was tested against murine pancreatic cancer cell lines (Pan02) to assess their therapeutic capabilities for effective treatments of pancreatic cancers. Healthy mouse fibroblast cells (STO) were also tested for comparison, because an effective chemotherapeutic drug has to be selective towards cancer cells. Optimal Experimental Design methodology was applied to identify the nanoformulation with the highest therapeutic activity. A statistical analysis method known as response

  6. Magnetic resonance imaging for acute pancreatitis

    OpenAIRE

    Xiao, Bo; Zhang, Xiao-Ming

    2010-01-01

    Acute pancreatitis is characterized by acute chemical injury of the pancreatic parenchyma and peripancreatic tissue. The increased frequency of death in acute pancreatitis is directly correlated with the degree and progress of pancreatic necrosis. Moreover, the occurrence of some local complications in acute pancreatitis, such as pancreatic hemorrhage, peripancreatic abscess or large pseudocyst, and pseudoaneurysm, could influence the choice of treatment for these patients. Magnetic resonance...

  7. Contemporary Management of Acute Biliary Pancreatitis

    OpenAIRE

    Orhan Ozkan

    2014-01-01

    Acute biliary pancreatitis is one of the major causes of acute pancreatitis.Gallstones, biliary sludge and microlithiasis, especially in pancreatitis without detectable reason, can be the cause of acute pancreatitis. Acute biliary pancreatitis has many controversions in the literature, and its classification and guidelines are being updated very frequently. Atlanta classifications which determine the definitions and guidelines about acute pancreatitis were renewed and published in 2013. It ha...

  8. CEBPA exerts a specific and biologically important proapoptotic role in pancreatic β cells through its downstream network targets

    DEFF Research Database (Denmark)

    Barbagallo, Davide; Condorelli, Angelo Giuseppe; Piro, Salvatore;

    2014-01-01

    Transcription factor CEBPA has been widely studied for its involvement in hematopoietic cell differentiation and causal role in hematological malignancies. We demonstrate here that it also performs a causal role in cytokine-induced apoptosis of pancreas β cells. Treatment of two mouse pancreatic ...... regulator within the apoptotic network activated in pancreatic β cells during insulitis, and Arl6ip5, Tnfrsf10b, Traf2, and Ubc are key executioners of this program....

  9. Prospectively Isolated NGN3-Expressing Progenitors From Human Embryonic Stem Cells Give Rise to Pancreatic Endocrine Cells

    OpenAIRE

    Cai, Qing; Bonfanti, Paola; Sambathkumar, Rangarajan; Vanuytsel, Kim; Vanhove, Jolien; Gysemans, Conny; Debiec-Rychter, Maria; Raitano, Susanna; Heimberg, Harry; Ordovas, Laura; Verfaillie, Catherine

    2014-01-01

    Pancreatic endocrine progenitors obtained from human embryonic stem cells (hESCs) represent a promising source to develop cell-based therapies for diabetes. Although endocrine pancreas progenitor cells have been isolated from mouse pancreata on the basis of Ngn3 expression, human endocrine progenitors have not been isolated yet. As substantial differences exist between human and murine pancreas biology, we investigated whether it is possible to isolate pancreatic endocrine progenitors from di...

  10. Ascl1b and Neurod1, instead of Neurog3, control pancreatic endocrine cell fate in zebrafish

    OpenAIRE

    Flasse, Lydie; Pirson, Justine; Stern, David,; Von Berg, Virginie; Manfroid, Isabelle; Peers, Bernard; Voz, Marianne

    2013-01-01

    Background NEUROG3 is a key regulator of pancreatic endocrine cell differentiation in mouse, essential for the generation of all mature hormone producing cells. It is repressed by Notch signaling that prevents pancreatic cell differentiation by maintaining precursors in an undifferentiated state. Results We show that, in zebrafish, neurog3 is not expressed in the pancreas and null neurog3 mutant embryos do not display any apparent endocrine defects. The control of endocrine cell fate is inste...

  11. Groove pancreatitis and pancreatic heterotopia in the minor duodenal papilla.

    Science.gov (United States)

    Chatelain, Denis; Vibert, Eric; Yzet, Thierry; Geslin, Guillaume; Bartoli, Eric; Manaouil, David; Delcenserie, Richard; Brevet, Marie; Dupas, Jean-Louis; Regimbeau, Jean-Marc

    2005-05-01

    Groove pancreatitis is a rare form of segmental chronic pancreatitis that involves the anatomic space between the head of the pancreas, the duodenum, and the common bile duct. We report 2 cases of groove pancreatitis with pancreatic heterotopia in the minor papilla. Patients were a 44-year-old woman and a 47-year-old man. Both had a past history of alcohol consumption and presented with abdominal pain, vomiting, and weight loss caused by duodenal stenosis. Abdominal computed tomography revealed thickening of the duodenal wall and enlargement of the pancreatic head in both patients. In 1 patient, ultrasound endoscopy showed a dilated duct in the head of the pancreas. Pancreaticoduodenectomy was performed to rule out pancreatic adenocarcinoma and because of the severity of the symptoms. In both cases, gross and microscopic examinations showed fibrous scar of the groove area. The Santorini duct was dilated and contained protein plugs in both patients, with abscesses in 1 of them. In both cases, there were microscopic foci of heterotopic pancreas with mild fibrosis in the wall of the minor papilla. Groove pancreatitis is often diagnosed in middle-aged alcoholic men presenting with clinical symptoms caused by duodenal stenosis. The pathogenesis of this rare entity could be because of disturbance of the pancreatic secretion through the minor papilla. Pancreatitis in heterotopic pancreas located in the minor papilla and chronic consumption of alcohol seem to be important pathogenic factors. PMID:15841034

  12. Pancreatic encephalopathy- a rare complication of severe acute biliary pancreatitis

    Directory of Open Access Journals (Sweden)

    Vlad Denis Constantin

    2014-10-01

    Full Text Available Background. Pancreatic encephalopathy is a rare complication of severe acute pancreatitis, with high mortality, being difficult to diagnose and treat, thus requiring continuous research regarding its management. Materials and Methods. Of 20 patients diagnosed with severe acute pancreatitis on admission at Department of Emergency and Admission (DEA, from January 1st 2010 to March 31st 2014, 5 cases complicated by pancreatic encephalopathy were analyzed using a descriptive observational, retrospective, single-center study. Results. The study shows different types of diagnostic algorithm and therapeutical approaches, in correlation with morbidity and mortality rates. Conclusions. Our study highlighted the fact that speed is critical, early management being the key to outcome.

  13. Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets.

    Science.gov (United States)

    Lumelsky, N; Blondel, O; Laeng, P; Velasco, I; Ravin, R; McKay, R

    2001-05-18

    Although the source of embryonic stem (ES) cells presents ethical concerns, their use may lead to many clinical benefits if differentiated cell types can be derived from them and used to assemble functional organs. In pancreas, insulin is produced and secreted by specialized structures, islets of Langerhans. Diabetes, which affects 16 million people in the United States, results from abnormal function of pancreatic islets. We have generated cells expressing insulin and other pancreatic endocrine hormones from mouse ES cells. The cells self-assemble to form three-dimensional clusters similar in topology to normal pancreatic islets where pancreatic cell types are in close association with neurons. Glucose triggers insulin release from these cell clusters by mechanisms similar to those employed in vivo. When injected into diabetic mice, the insulin-producing cells undergo rapid vascularization and maintain a clustered, islet-like organization. PMID:11326082

  14. Follicular pancreatitis: a distinct form of chronic pancreatitis-an additional mimic of pancreatic neoplasms.

    Science.gov (United States)

    Gupta, Rajib K; Xie, Bill H; Patton, Kurt T; Lisovsky, Mikhail; Burks, Eric; Behrman, Stephen W; Klimstra, David; Deshpande, Vikram

    2016-02-01

    Follicular pancreatitis is a recently described variant of chronic pancreatitis characterized clinically by the formation of a discrete pancreatic mass and histologically by the presence of florid lymphoid aggregates with reactive germinal centers. Our aim was to study the clinical and histologic features of follicular pancreatitis, as well as to critically examine potential overlap with autoimmune pancreatitis. Immunohistochemistry for Bcl-2, CD21, κ and λ light chains as well as IgG4 and IgG were performed. We found a total of 6 patients (male-female ratio, 2:1; mean age, 57 years) who fulfilled the diagnosis of follicular pancreatitis in our institutions. Four had an incidental diagnosis, while two presented with abdominal pain, fatigue, and elevated liver enzymes. On imaging, 3 patients had a discrete solid mass, whereas 2 cases showed a dilated main pancreatic duct, mimicking an intraductal pancreatic mucinous neoplasm on imaging. One patient had a lesion in the intra-pancreatic portion of the common bile duct. On histopathology, all cases showed numerous lymphoid follicles with Bcl-2-negative germinal centers either in a periductal or in a more diffuse (periductal and intra-parenchymal) fashion, but without attendant storiform fibrosis, obliterative phlebitis, or granulocytic epithelial lesions. IgG4-to-IgG ratio was <40% in 5 cases. A comparison cohort revealed germinal centers in 25% of type 1 autoimmune pancreatitis and 2% of type 2 autoimmune pancreatitis cases, but none were periductal in location. In conclusion, follicular pancreatitis, an under-recognized mimic of pancreatic neoplasms is characterized by intrapancreatic lymphoid follicles with reactive germinal centers. PMID:26563969

  15. Computed tomography of pancreatic trauma

    Energy Technology Data Exchange (ETDEWEB)

    Jeffrey, R.B. Jr.; Federle, M.P.; Crass, R.A.

    1983-05-01

    In a review of over 300 CT scans of abdominal trauma, we encountered 13 patients with surgically proved pancreatic injuries. CT correctly diagnosed pancreatic fractures, contusions, or posttraumatic pseudocysts in 11 of these patients. There were two false positive and two false negative diagnoses. The CT diagnosis of pancreatic trauma may be difficult in selected patients who are scanned soon after injury. Acutely, the actual plane of a pancreatic fracture may be difficult to identify with CT, and the peripancreatic soft-tissue changes of traumatic pancreatitis are often subtle. Eight of 11 correctly diagnosed pancreatic injuries showed thickening of the left anterior renal fascia on CT scans. This sign should prompt a critical evaluation of the pancreas of the traumatized patient.

  16. Biliary scintigraphy in acute pancreatitis

    International Nuclear Information System (INIS)

    A prospective study was carried out in 60 patients to determine the efficacy of 99/sup m/Tc-PIPIDA scintigraphy in differentiating biliary pancreatitis from nonbiliary pancreatitis. Forty patients were classified as having biliary pancreatitis and 20 patients as having the nonbiliary type. Scintigraphic scans were divided into five main types according to the time to visualization of the gallbladder and the time to excretion of 99/sup m/Tc-PIPIDA into the intestinal tract. Normal scans were obtained in 95% of patients (19/20) with nonbiliary pancreatitis; 22.5% of patients (9/40) with biliary pancreatitis had normal scans. It is concluded that elevated amylase levels together with an abnormal biliary scan, as defined by the criteria presented here, indicate biliary pancreatitis, while a normal scan largely excludes such diagnosis

  17. Biliary scintigraphy in acute pancreatitis

    International Nuclear Information System (INIS)

    A prospective study was carried out in 60 patients to determine the efficacy of /sup 99m/Tc-PIPIDA scintigraphy in differentiating biliary pancreatitis from nonbiliary pancreatitis. Forty patients were classified as having biliary pancreatitis and 20 patients as having the nonbiliary type. Scintigraphic scans were divided into five main types according to the time to visualization of the gallbladder and the time to excretion of /sup 99m/Tc-PIPIDA into the intestinal tract. Normal scans were obtained on 95% of patients (19/20) with nonbiliary pancreatitis; 22.5% of patients (9/40) with biliary pancreatitis had normal scans. It is concluded that elevated amylase levels together with an abnormal biliary scan, as defined by the criteria presented here, indicate biliary pancreatitis, while a normal scan largely excludes such diagnosis

  18. Carbofuran-Induced Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Rizos E

    2004-01-01

    Full Text Available CONTEXT: Carbamate insecticides are widely used in commercial agriculture and home gardening. A serious side effect of organophosphate and carbamate intoxication is the development of acute pancreatitis. CASE REPORT: A 36-year-old Caucasian woman was admitted to our hospital with cholinergic crisis and pancreatitis soon after the ingestion of a carbamate insecticide (carbofuran. An abdominal CT scan disclosed pancreatic necrosis with intrapancreatic fluid collection, consistent with the development of a pancreatic pseudocyst in a subsequent CT scan. No predisposing factor for pancreatitis was evident. Pseudocholinesterase levels returned to normal 7 days later and the patient was discharged in good physical condition one month after admission. DISCUSSION: Although acute pancreatitis is not infrequent after organophosphate intoxication, it is quite rare after carbamate ingestion and has not been previously reported after carbofuran intoxication.

  19. Rapid Evolution from the First Episode of Acute Pancreatitis to Chronic Pancreatitis in Human Subjects

    OpenAIRE

    Elie Aoun; Adam Slivka; Papachristou, Dionysios J.; David C. Whitcomb; Ferga C. Gleeson; Georgios I Papachristou

    2007-01-01

    Context Growing evidence suggests that recurrent acute pancreatitis leads to chronic pancreatitis, but this sequence is seldom reported in human subjects. The sentinel acute pancreatitis event hypothesis suggests that an initial episode of acute pancreatitis is the first step in a complicated series of events ultimately leading to chronic pancreatitis. Objective To identify patients who evolved from recurrent acute pancreatitis to chronic pancreatitis. Setting The Severity of Acute Pancreatit...

  20. Acute pancreatitis following paracetamol overdose

    OpenAIRE

    Fernandes, Roland

    2009-01-01

    A 17-year-old woman presented with acute abdominal pain and vomiting 3 h after she attempted to commit suicide by ingesting 30×500 mg paracetamol tablets. The woman was found to have a raised amylase level, and a CT scan confirmed the diagnosis of acute pancreatitis. According to the Naranjo adverse drug reaction probability scale, it is likely that the pancreatitis was induced by the paracetamol ingestion. A literature search reported 36 cases of pancreatitis following excessive doses of par...

  1. Approaches Towards Endogenous Pancreatic Regeneration

    OpenAIRE

    Banerjee, Meenal; Kanitkar, Meghana; Bhonde, Ramesh R.

    2005-01-01

    The phenomenon of pancreatic regeneration in mammals has been well documented. It has been shown that pancreatic tissue is able to regenerate in several species of mammal after surgical insult. This tissue is also known to have the potential to maintain or increase its β-cell mass in response to metabolic demands during pregnancy and obesity. Since deficiency in β-cell mass is the hallmark of most forms of diabetes, it is worthwhile understanding pancreatic regeneration in the context of this...

  2. Acute pancreatitis complicating severe dengue

    OpenAIRE

    Vishakha Jain; O P Gupta; Tarun Rao; Siddharth Rao

    2014-01-01

    Dengue is an arthropod borne viral infection endemic in tropical and subtropical continent. Severe dengue is life threatening. Various atypical presentations of dengue have been documented. But we present a rare and fatal complication of severe dengue in form of acute pancreatitis. A 27-year-old male had presented with severe dengue in decompensated shock and with pain in abdomen due to pancreatitis. The pathogenesis of acute pancreatitis in dengue is not clearly understood, but various mecha...

  3. Helicobacter pylori and pancreatic diseases

    OpenAIRE

    Bulajic, Milutin; Panic, Nikola; Löhr, Johannes Matthias

    2014-01-01

    A possible role for Helicobacter pylori (H. pylori) infection in pancreatic diseases remains controversial. H. pylori infection with antral predomination leading to an increase in pancreatic bicarbonate output and inducing ductal epithelial cell proliferation could contribute to the development of pancreatic cancer via complex interactions with the ABO genotype, dietary and smoking habits and N-nitrosamine exposure of the host. Although the individual study data available so far is inconsiste...

  4. Lung Injury in Acute Pancreatitis

    OpenAIRE

    Raffaele Pezzilli; Lara Bellacosa; Cristina Felicani

    2009-01-01

    Most knowledge has been accumulated on the mechanisms involved in the development of distant organ injuries during the course of severe acute pancreatitis. Among the various distant organ dysfunctions, both the development of acute lung injury and acute respiratory distress syndrome represent serious complications. In the following paragraphs the pathophysiological mechanisms capable of determining lung injury during the course of acute pancreatitis will be reviewed. Pancreatic Enzymes and...

  5. Nutrition Support in Acute Pancreatitis

    OpenAIRE

    Orestis Ioannidis; Athina Lavrentieva; Dimitrios Botsios

    2008-01-01

    The management of acute pancreatitis differs according to its severity. Approximately 75% of patients with acute pancreatitis have mild disease with a mortality rate below 1%. Mortality increases up to 20% if the disease progresses to its severe necrotizing form and, in the most severe cases, mortality can increase to 30-40%. Severe acute pancreatitis is usually accompanied by systemic inflammatory response syndrome (SIRS) which results in hypermetabolism with prominent protein catabolism. Ac...

  6. Genetic Susceptibility to Pancreatic Cancer

    OpenAIRE

    Klein, Alison P

    2012-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States. However, it has the poorest prognosis of any major tumor type, with a 5-yr survival rate of approximately 5%. Cigarette smoking, increased body mass index, heavy alcohol consumption, and a diagnosis of diabetes mellitus have all been demonstrated to increase risk of pancreatic cancer. A family history of pancreatic cancer has also been associated with increased risk suggesting inherited g...

  7. Pancreatic scintiphotography in diabetes mellitus

    International Nuclear Information System (INIS)

    Pancreatic scintiphotography was performed in 108 cases of patients with diabetes mellitus. Scintiphotos were taken at 30 min. after intravenous injection of approximately 200μCi of 75Se-selenomethionine using a Toshiba gamma camera. The relationship between the degree of pancreatic uptake of 75Se-selenomethionine and the types and duration of diabetes, vascular complications and the average range of fasting blood sugar levels were studied. In some cases, pancreatic scintiphotos were taken at 10, 30 and 50 min. after injection of 75Se-selenomethionine, and the degrees of the pancreatic uptake were compared on each time course. Only two out of 24 cases of insulin-dependent diabetics showed normal pancreatic scintiphotos. On the other hand, two out of 47 cases of mild diabetics treated with diet alone showed no uptake in pancreatic scintiphotos. There was a tendency toward abnormal pancreatic scintiphotos in chronic diabetics. Especially, of the 15 cases who had diabetes for more than eleven years, only one case showed a normal pancreatic scintiphoto. Abnormal pancreatic scintiphotos were found more frequently in the group of poorly controlled diabetics than in the group of well controlled diabetics. In cases showing normal pancreatic scintiphotos, diabetic retinopathy was less frequently found. Out of 36 cases which had sequential pancreatic scintiphotos, hypertension and/or arteriosclerosis were found more frequently in the 20 cases which showed a delay in reaching a plateau of the activity. However, the uptake in sequential pancreatic scintiphotos showed no definite correlation between diabetic retinopathy and other diabetic conditions. (auth.)

  8. Repeated Gene Transfection Impairs the Engraftment of Transplanted Porcine Neonatal Pancreatic Cells

    Directory of Open Access Journals (Sweden)

    Min Koo Seo

    2011-02-01

    Full Text Available BackgroundPreviously, we reported that neonatal porcine pancreatic cells transfected with hepatocyte growth factor (HGF gene in an Epstein-Barr virus (EBV-based plasmid (pEBVHGF showed improved proliferation and differentiation compared to those of the control. In this study, we examined if pancreatic cells transfected repeatedly with pEBVHGF can be successfully grafted to control blood glucose in a diabetes mouse model.MethodsNeonatal porcine pancreatic cells were cultured as a monolayer and were transfected with pEBVHGF every other day for a total of three transfections. The transfected pancreatic cells were re-aggregated and transplanted into kidney capsules of diabetic nude mice or normal nude mice. Blood glucose level and body weight were measured every other day after transplantation. The engraftment of the transplanted cells and differentiation into beta cells were assessed using immunohistochemistry.ResultsRe-aggregation of the pancreatic cells before transplantation improved engraftment of the cells and facilitated neovascularization of the graft. Right before transplantation, pancreatic cells that were transfected with pEBVHGF and then re-aggregated showed ductal cell marker expression. However, ductal cells disappeared and the cells underwent fibrosis in a diabetes mouse model two to five weeks after transplantation; these mice also did not show controlled blood glucose levels. Furthermore, pancreatic cells transplanted into nude mice with normal blood glucose showed poor graft survival regardless of the type of transfected plasmid (pCEP4, pHGF, or pEBVHGF.ConclusionFor clinical application of transfected neonatal porcine pancreatic cells, further studies are required to develop methods of overcoming the damage for the cells caused by repeated transfection and to re-aggregate them into islet-like structures.

  9. [Latest advances in acute pancreatitis].

    Science.gov (United States)

    de-Madaria, Enrique

    2015-09-01

    The present article analyses the main presentations on acute pancreatitis at Digestive Disease Week 2015. Arterial pseudoaneurysm is an uncommon complication of acute pancreatitis (incidence 0.7%) and mortality from this cause is currently anecdotal. Diabetes mellitus has little impact on the clinical course of acute pancreatitis, unlike cirrhosis, which doubles the risk of mortality. Intake of unsaturated fat could be associated with an increased severity of acute pancreatitis and is a confounding factor in studies evaluating the relationship between obesity and morbidity and mortality. PET-CT (positron emission tomography-computed tomography) could be a non-invasive tool to detect infection of collections in acute pancreatitis. Peripancreatic fat necrosis is less frequent than pancreatic fat necrosis and is associated with a better clinical course. If the clinical course is poor, increasing the calibre of the percutaneous drains used in the treatment of infected necrosis can avoid surgery in 20% of patients. The use of low molecular-weight heparin in moderate or severe pancreatitis could be associated with a better clinical course, specifically with a lower incidence of necrosis. In acute recurrent pancreatitis, simvastatin is a promising drug for prophylaxis of new episodes of acute pancreatitis. Nutritional support through a nasogastric tube does not improve clinical course compared with oral nutrition. PMID:26520203

  10. Helicobacter pylori and pancreatic diseases

    Institute of Scientific and Technical Information of China (English)

    Milutin; Bulajic; Nikola; Panic; Johannes; Matthias; L?hr

    2014-01-01

    A possible role for Helicobacter pylori(H. pylori) infec-tion in pancreatic diseases remains controversial. H. pylori infection with antral predomination leading to an increase in pancreatic bicarbonate output and induc-ing ductal epithelial cell proliferation could contribute to the development of pancreatic cancer via complex interactions with the ABO genotype, dietary and smok-ing habits and N-nitrosamine exposure of the host. Although the individual study data available so far is inconsistent, several meta-analyses have reported an increased risk for pancreatic cancer among H. pylori seropositive individuals. It has been suggested that H. pylori causes autoimmune pancreatitis due to molecu-lar mimicry between H. pylori a-carbonic anhydrase(a-CA) and human CA type Ⅱ, and between H. pylori plasminogen-binding protein and human ubiquitin-protein ligase E3 component n-recognin 2, enzymes that are highly expressed in the pancreatic ductal andacinar cells, respectively. Future studies involving large numbers of cases are needed in order to examine the role of H. pylori in autoimmune pancreatitis more fully. Considering the worldwide pancreatic cancer burden, as well as the association between autoimmune pan-creatitis and other autoimmune conditions, a complete elucidation of the role played by H. pylori in the gen-esis of such conditions could have a substantial impact on healthcare.

  11. Dynamic Proteomic Analysis of Pancreatic Mesenchyme Reveals Novel Factors That Enhance Human Embryonic Stem Cell to Pancreatic Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Holger A. Russ

    2016-01-01

    Full Text Available Current approaches in human embryonic stem cell (hESC to pancreatic beta cell differentiation have largely been based on knowledge gained from developmental studies of the epithelial pancreas, while the potential roles of other supporting tissue compartments have not been fully explored. One such tissue is the pancreatic mesenchyme that supports epithelial organogenesis throughout embryogenesis. We hypothesized that detailed characterization of the pancreatic mesenchyme might result in the identification of novel factors not used in current differentiation protocols. Supplementing existing hESC differentiation conditions with such factors might create a more comprehensive simulation of normal development in cell culture. To validate our hypothesis, we took advantage of a novel transgenic mouse model to isolate the pancreatic mesenchyme at distinct embryonic and postnatal stages for subsequent proteomic analysis. Refined sample preparation and analysis conditions across four embryonic and prenatal time points resulted in the identification of 21,498 peptides with high-confidence mapping to 1,502 proteins. Expression analysis of pancreata confirmed the presence of three potentially important factors in cell differentiation: Galectin-1 (LGALS1, Neuroplastin (NPTN, and the Laminin α-2 subunit (LAMA2. Two of the three factors (LGALS1 and LAMA2 increased expression of pancreatic progenitor transcript levels in a published hESC to beta cell differentiation protocol. In addition, LAMA2 partially blocks cell culture induced beta cell dedifferentiation. Summarily, we provide evidence that proteomic analysis of supporting tissues such as the pancreatic mesenchyme allows for the identification of potentially important factors guiding hESC to pancreas differentiation.

  12. Dynamic Proteomic Analysis of Pancreatic Mesenchyme Reveals Novel Factors That Enhance Human Embryonic Stem Cell to Pancreatic Cell Differentiation.

    Science.gov (United States)

    Russ, Holger A; Landsman, Limor; Moss, Christopher L; Higdon, Roger; Greer, Renee L; Kaihara, Kelly; Salamon, Randy; Kolker, Eugene; Hebrok, Matthias

    2016-01-01

    Current approaches in human embryonic stem cell (hESC) to pancreatic beta cell differentiation have largely been based on knowledge gained from developmental studies of the epithelial pancreas, while the potential roles of other supporting tissue compartments have not been fully explored. One such tissue is the pancreatic mesenchyme that supports epithelial organogenesis throughout embryogenesis. We hypothesized that detailed characterization of the pancreatic mesenchyme might result in the identification of novel factors not used in current differentiation protocols. Supplementing existing hESC differentiation conditions with such factors might create a more comprehensive simulation of normal development in cell culture. To validate our hypothesis, we took advantage of a novel transgenic mouse model to isolate the pancreatic mesenchyme at distinct embryonic and postnatal stages for subsequent proteomic analysis. Refined sample preparation and analysis conditions across four embryonic and prenatal time points resulted in the identification of 21,498 peptides with high-confidence mapping to 1,502 proteins. Expression analysis of pancreata confirmed the presence of three potentially important factors in cell differentiation: Galectin-1 (LGALS1), Neuroplastin (NPTN), and the Laminin α-2 subunit (LAMA2). Two of the three factors (LGALS1 and LAMA2) increased expression of pancreatic progenitor transcript levels in a published hESC to beta cell differentiation protocol. In addition, LAMA2 partially blocks cell culture induced beta cell dedifferentiation. Summarily, we provide evidence that proteomic analysis of supporting tissues such as the pancreatic mesenchyme allows for the identification of potentially important factors guiding hESC to pancreas differentiation. PMID:26681951

  13. Pancreatic and hepatobiliary cancer

    International Nuclear Information System (INIS)

    Although radical operations can cure resectable cancer of the pancreas or biliary tract, few patients present with resectable disease. Most patients with pancreatic cancer present with lesions in the head of the pancreas that have either spread beyond the local area by hematogenous or peritoneal routes or are technically unresectable because of the local extent of disease. For the latter group the main surgical options are palliative biliary bypass alone or in combination with elective gastroenterostomy. Carcinoma of the biliary tract (gallbladder or bile duct) is uncommon compared to other gastrointestinal malignancies and has a wide range of natural history. Until recently surgery was the only therapy considered in most patients even though most lesions were unresectable and only palliative procedures could be performed. If gains are to be made with the locally unresectable pancreatic or biliary tract lesions, they will have to come through treatment with radiation, chemotherapy, or a combination of both

  14. A conserved rule for pancreatic islet organization.

    Directory of Open Access Journals (Sweden)

    Danh-Tai Hoang

    Full Text Available Morphogenesis, spontaneous formation of organism structure, is essential for life. In the pancreas, endocrine α, β, and δ cells are clustered to form islets of Langerhans, the critical micro-organ for glucose homeostasis. The spatial organization of endocrine cells in islets looks different between species. Based on the three-dimensional positions of individual cells in islets, we computationally inferred the relative attractions between cell types, and found that the attractions between homotypic cells were slightly, but significantly, stronger than the attractions between heterotypic cells commonly in mouse, pig, and human islets. The difference between α-β cell attraction and β-β cell attraction was minimal in human islets, maximizing the plasticity of islet structures. Our result suggests that although the cellular composition and attractions of pancreatic endocrine cells are quantitatively different between species, the physical mechanism of islet morphogenesis may be evolutionarily conserved.

  15. Pancreatic Cancer in 2014

    Directory of Open Access Journals (Sweden)

    Serafim Kaltsas

    2014-03-01

    Full Text Available 5-FU/LV: 5-fluorouracil and leucovorin; FOLFIRINOX: 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin; FOLFOX: 5-flouorouracil, leucovorin and oxaliplatin; HA: hyaluronic acid; JAK: Janus kinase; MM-398: irinotecan sucrosofate; MPACT: Metastatic Pancreatic Adenocarcinoma Clinical Trial; PARP: poly (ADP-ribose polymerase; PEGPH: pegylated recombinant human hyaluronidase; PSCA: prostate stem cell antigen; SN-38: active metabolite of irinotecan; SPARC: secreted protein acidic and rich in cysteine

  16. Sensory nerves and pancreatitis

    OpenAIRE

    Li, Qingfu; PENG, JIE

    2014-01-01

    Sensory nerves are a kind of nerve that conduct afferent impulses from the periphery receptors to the central nervous system (CNS) and are able to release neuromediators from the activated peripheral endings. Sensory nerves are particularly important for microcirculatory response, and stimulation of pancreatic sensory nerves releases a variety of neuropeptides such as substance P (SP), calcitonin gene-related peptide (CGRP), etc., leading to neurogenic inflammation characterized as the local ...

  17. Inhibitors of pancreatic lipase

    OpenAIRE

    Lunagariya, Nitin A.; Patel, Neeraj K.; Jagtap, Sneha C.; Bhutani, Kamlesh K.

    2014-01-01

    Obesity is a disorder of lipid metabolism and continues to be a global problem, ranking fifth for deaths worldwide. It also leads to diabetes, cardiovascular disorders, musculoskeletal disorders and some types of cancer. Obesity is regarded as the output of a long-term imbalance between energy intake and energy expenditure. Digestion and absorption of dietary lipids by pancreatic lipase, a major source of excess calorie intake, can be targeted for development of anti-obesity agents. Being the...

  18. Post-partum pancreatitis.

    OpenAIRE

    Pai P; Shah H; Samsi A

    1993-01-01

    Acute pancreatitis in pregnancy and post-partum period, rarely encountered in surgical practice, can have a lethal effect on the mother and the foetus. We report here a case of a 35 year old tertigravida who presented with high grade fever, abdominal pain with distension, tachycardia and tachypnoea. Chest examination and X-rays were suggestive of pneumonia. The abdomen was tense and tender. Peristalsis was absent. Ultrasound revealed presence of fluid in the abdominal cavity which on paracent...

  19. Activation of cannabinoid receptor 2 reduces inflammation in acute experimental pancreatitis via intra-acinar activation of p38 and MK2-dependent mechanisms.

    Science.gov (United States)

    Michler, Thomas; Storr, Martin; Kramer, Johannes; Ochs, Stefanie; Malo, Antje; Reu, Simone; Göke, Burkhard; Schäfer, Claus

    2013-01-15

    The endocannabinoid system has been shown to mediate beneficial effects on gastrointestinal inflammation via cannabinoid receptors 1 (CB(1)) and 2 (CB(2)). These receptors have also been reported to activate the MAP kinases p38 and c-Jun NH(2)-terminal kinase (JNK), which are involved in early acinar events leading to acute pancreatitis and induction of proinflammatory cytokines. Our aim was to examine the role of cannabinoid receptor activation in an experimental model of acute pancreatitis and the potential involvement of MAP kinases. Cerulein pancreatitis was induced in wild-type, CB(1)-/-, and MK2-/- mice pretreated with selective cannabinoid receptor agonists or antagonists. Severity of pancreatitis was determined by serum amylase and IL-6 levels, intracellular activation of pancreatic trypsinogen, lung myeloperoxidase activity, pancreatic edema, and histological examinations. Pancreatic lysates were investigated by Western blotting using phospho-specific antibodies against p38 and JNK. Quantitative PCR data, Western blotting experiments, and immunohistochemistry clearly show that CB(1) and CB(2) are expressed in mouse pancreatic acini. During acute pancreatitis, an upregulation especially of CB(2) on apoptotic cells occurred. The unselective CB(1)/CB(2) agonist HU210 ameliorated pancreatitis in wild-type and CB(1)-/- mice, indicating that this effect is mediated by CB(2). Furthermore, blockade of CB(2), not CB(1), with selective antagonists engraved pathology. Stimulation with a selective CB(2) agonist attenuated acute pancreatitis and an increased activation of p38 was observed in the acini. With use of MK2-/- mice, it could be demonstrated that this attenuation is dependent on MK2. Hence, using the MK2-/- mouse model we reveal a novel CB(2)-activated and MAP kinase-dependent pathway that modulates cytokine expression and reduces pancreatic injury and affiliated complications. PMID:23139224

  20. [Acute pancreatitis and pregnancy].

    Science.gov (United States)

    Scollo, P; Licitra, G

    1993-12-01

    Aetiologic factors (gallstones, hyperlipidemia I-IV, hypertriglyceridaemia) make their occurrence, mainly, in the third trimester of gestation. Two cases of acute pancreatitis in pregnancy are described; in both cases patients referred healthy diet, no habit to smoke and no previous episode of pancreatitis. An obstructive pathology of biliary tract was the aetiologic factor. Vomiting, upper abdominal pain are aspecific symptoms that impose a differential diagnosis with acute appendicitis, cholecystitis and obstructive intestinal pathology. Laboratory data (elevated serum amylase and lipase levels) and ultrasonography carry out an accurate diagnosis. The management of acute pancreatitis is based on the use of symptomatic drugs, a low fat diet alternated to the parenteral nutrition when triglycerides levels are more than 28 mmol/L. Surgical therapy, used only in case of obstructive pathology of biliary tract, is optimally collected in the third trimester or immediately after postpartum. Our patients, treated only medically, delivered respectively at 38th and 40th week of gestation. Tempestivity of diagnosis and appropriate therapy permit to improve prognosis of a pathology that, although really associated with pregnancy, presents high maternal mortality (37%) cause of complications (shock, coagulopathy, acute respiratory insufficiency) and fetal (37.9%) by occurrence of preterm delivery. PMID:8139793

  1. Pancreatic and peri-pancreatic lesions mimic pancreatic islet cell tumor in multidetector computed tomography

    Institute of Scientific and Technical Information of China (English)

    XUE Hua-dan; LIU Wei; XIAO Yu; SUN Hao; WANG Xuan; LEI Jing; JIN Zheng-yu

    2011-01-01

    Objective This pictorial review aimed to summarize the most possible differential diagnosis of pancreatic islet cell tumor (PICT).Data sources Data used in this review were mainly from Medline and Pubmed in English. And all clinical images in this review were from Department of Radiology, Peking Union Medical College Hospital, Beijing, China.Study selection Cases of pancreatic cystadenoma, solid pseudo-papillary tumor of the pancreas, pancreatic metastasis, pancreatic adenocarcinoma, para-pancreatic neuroendocrine tumors, Castleman disease, gastrointestinal stromal tumor, splenic artery aneurysm and accessory spleen were selected in this pictorial review for differential diagnosis of PICT.Results Careful analysis of imaging features and correlation with the clinical manifestations may allow a more specific diagnosis. It is also important that the radiologist is familiar with the anatomic variants and disease entities which mimic pancreatic islet cell tumor in order to avoid an improper treatment protocol.Conclusions Many congenital anatomic variants or other pancreatic and peri-pancreatic diseases may mimic MDCT appearance of pancreatic islet cell tumor. Radiological, clinical and pathological characteristics should be considered for the final diagnosis.

  2. Diagnosis and treatment of pancreatic pseudocysts in chronic pancreatitis.

    Science.gov (United States)

    Aghdassi, Ali; Mayerle, Julia; Kraft, Matthias; Sielenkämper, Andreas W; Heidecke, Claus-Dieter; Lerch, Markus M

    2008-03-01

    Pancreatic pseudocysts are a well-known complication of acute or chronic pancreatitis, with a higher incidence in the latter. Diagnosis is accomplished most often by computed tomographic scanning, by endoscopic retrograde cholangiopancreatography, or by ultrasound, and a rapid progress in the improvement of diagnostic tools enables detection with high sensitivity and specificity. Different strategies contribute to the treatment of pancreatic pseudocysts: endoscopic transpapillary or transmural drainage, percutaneous catheter drainage, or open surgery. The feasibility of endoscopic drainage is highly dependent on the anatomy and topography of the pseudocyst, but provides high success and low complication rates. Percutaneous drainage is used for infected pseudocysts. However, its usefulness in chronic pancreatitis-associated pseudocysts is questionable. Internal drainage and pseudocyst resection are frequently used as surgical approaches with a good overall outcome, but a somewhat higher morbidity and mortality compared with endoscopic intervention. We therefore conclude that pseudocyst treatment in chronic pancreatitis can be effectively achieved by both endoscopic and surgical means. This review entails publications referring to the classification of pancreatic pseudocysts, epidemiology, diagnostic tools, and therapeutic options for pancreatic pseudocysts. Only full articles were considered for the review. Based on a search in PubMed, the MeSH terms "pancreatic pseudocysts and classification," "diagnosis," and "endoscopic, percutaneous, and surgical treatment" were used either alone or in combination. PMID:18376299

  3. Mouse adhalin

    DEFF Research Database (Denmark)

    Liu, L; Vachon, P H; Kuang, W;

    1997-01-01

    analyze the biological roles of adhalin, we cloned the mouse adhalin cDNA, raised peptide-specific antibodies to its cytoplasmic domain, and examined its expression and localization in vivo and in vitro. The mouse adhalin sequence was 80% identical to that of human, rabbit, and hamster. Adhalin was...... specifically expressed in striated muscle cells and their immediate precursors, and absent in many other cell types. Adhalin expression in embryonic mouse muscle was coincident with primary myogenesis. Its expression was found to be up-regulated at mRNA and protein levels during myogenic differentiation in...

  4. Pancreatic polypepetide inhibits pancreatic enzyme secretion via a cholinergic pathway

    International Nuclear Information System (INIS)

    In rat pancreatic slices, rat pancreatic polypeptide (PP) or C-terminal hexapeptide of PP [PP-(31-36)] inhibited potassium-stimulated amylase release in a dose-dependent manner. The inhibition was unaffected by addition of hexamethonium but blocked by atropine. In contrast, PP-(31-36) did not have any effect on acetylcholine- or cholecystokinin octapeptide-stimulated amylase release. In addition, when pancreatic slices were incubated with [3H]choline, PP-(31-36) inhibited the potassium-evoked release of synthesized [3H]acetylcholine in a dose-dependent manner. The inhibitory action of PP was unaffected by adrenergic, dopaminergic, or opioid receptor antagonists. Thus PP inhibits pancreatic enzyme secretion via presynaptic modulation of acetylcholine release. This newly identified pathway provides a novel mechanism for hormonal inhibition of pancreatic enzyme secretion via modulation of the classic neurotransmitter function

  5. Meandering Main Pancreatic Duct in a Case of Recurrent Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Mahesh Prakash

    2016-03-01

    Full Text Available Meandering main pancreatic duct is an anatomical variant of main pancreatic duct, characterized by abnormal configuration of the duct in pancreatic head region. Meandering pancreatic duct can be underlying cause for recurrent pancreatitis. This less common variant can be easily diagnosed on imaging, particularly magnetic resonance cholangiopancreatography.

  6. Possible Involvement of Pancreatic Fatty Infiltration in Pancreatic Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Mika Hori

    2016-03-01

    Full Text Available Pancreatic cancer is difficult to diagnose in its early stage and is one of the most lethal human cancers. Thus, it is important to clarify its major risk factors, predictive factors and etiology. Here, we focus on fatty infiltration of the pancreas and suggest that it could be a risk factor for pancreatic cancer. Fatty infiltration of the pancreas is observed as ectopic adipocytes infiltrating the pancreatic tissue and is positively correlated with obesity and the prevalence of diabetes mellitus, which are risk factors for pancreatic cancer. However, whether fatty infiltration is a major risk factor for pancreatic cancer has not been established. Recent clinical studies show there is a positive correlation between fatty infiltration of the pancreas and pancreatic precancerous lesions or ductal adenocarcinomas. Animal experimental studies also show an association between fatty infiltration of the pancreas and pancreatic precancerous lesions or ductal adenocarcinomas development. Syrian golden hamsters, which are sensitive to chemical carcinogens in the pancreas, develop fatty infiltration of the pancreas with age. The combination of a high-fat diet and a chemical carcinogen that induces a K-ras mutation increases the severity of fatty infiltration of the pancreas. Thus, fatty infiltration of the pancreas is suggested to promote pancreatic carcinogenesis via a K-ras activating mutation. It is assumed that increased expression of adipokines and of inflammatory and proliferation-associated factors elicited by fatty infiltration of the pancreas may contribute to pancreatic precancerous lesions or ductal adenocarcinomas development. Accumulating evidence suggests that in addition to suppression of Ras activation, methods to modulate fatty infiltration in the pancreas can be considered as a strategy for preventing pancreatic cancer.

  7. Groove pancreatitis: A rare form of chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Bharivi Jani

    2015-01-01

    Full Text Available Context: Groove pancreatitis is a rare form of chronic pancreatitis affecting the "groove" of the pancreas among the pancreatic head, duodenum, and common bile duct. The exact cause is unknown, although there are associations with long-term alcohol abuse, smoking, peptic ulcer disease, heterotopic pancreas, gastric resection, biliary disease, and anatomical or functional obstruction of the minor papilla. The diagnosis can be challenging. Endoscopic ultrasound (EUS and magnetic resonance cholangiopancreatography are the preferred imaging modalities. The treatment of choice is conservative although surgical intervention can sometimes be required. Case Report: A 57-year-old male with a history of human immunodeficiency virus and hepatitis B presented with 4 days of epigastric pain. Abdominal exam revealed absent bowel sounds and epigastric tenderness. He had a creatinine of 1.72 mg/dL, potassium of 2.9 mmol/L, and a normal lipase level of 86 U/L. Liver enzymes and total bilirubin were normal. Computed tomography abdomen showed high-grade obstruction of the second portion of the duodenum without any obvious mass. An esophagogastroduodenoscopy showed a mass at the duodenal bulb causing luminal narrowing, with biopsies negative for malignancy. Magnetic resonance imaging revealed a mass in the region of the pancreatic head and descending duodenum. EUS revealed a 3 cm mass in the region of pancreatic head with irregular borders and no vascular invasion. Fine needle aspiration (FNA was nondiagnostic. The patient then underwent a Whipple′s procedure. Pathology of these specimens was negative for malignancy but was consistent with para-duodenal or groove pancreatitis. Conclusion: The low incidence of groove pancreatitis is partly due to lack of familiarity with the disease. Groove pancreatitis should be considered in the differential for patients presenting with pancreatic head lesions and no cholestatic jaundice, especially when a duodenal obstruction

  8. Beer and its Non-Alcoholic Compounds: Role in Pancreatic Exocrine Secretion, Alcoholic Pancreatitis and Pancreatic Carcinoma

    Directory of Open Access Journals (Sweden)

    Peter Feick

    2010-03-01

    Full Text Available : In this article we provide an overview of the newest data concerning the effect of non-alcoholic constituents of alcoholic beverages, especially of beer, on pancreatic secretion, and their possible role in alcoholic pancreatitis and pancreatic carcinoma. The data indicate that non-alcoholic constituents of beer stimulate pancreatic enzyme secretion in humans and rats, at least in part, by direct action on pancreatic acinar cells. Some non-alcoholic compounds of beer, such as quercetin, resveratrol, ellagic acid or catechins, have been shown to be protective against experimentally induced pancreatitis by inhibiting pancreatic secretion, stellate cell activation or by reducing oxidative stress. Quercetin, ellagic acid and resveratrol also show anti-carcinogenic potential in vitro and in vivo. However, beer contains many more non-alcoholic ingredients. Their relevance in beer-induced functional alterations of pancreatic cells leading to pancreatitis and pancreatic cancer in humans needs to be further evaluated.

  9. Acute necrotizing pancreatitis in rats

    NARCIS (Netherlands)

    B. van Ooijen (Baan)

    1988-01-01

    textabstractThe specific aim of the present study was to investigate whether eicosanoids play a role in acute necrotizing pancreatitis. Because of the limited number of patients with acute pancreatitis admitted to the hospital each year, as well as the practical difficulties encountered in studying

  10. Pharmacological approach to acute pancreatitis

    DEFF Research Database (Denmark)

    Bang, Ulrich-Christian; Semb, Synne; Nojgaard, Camilla;

    2008-01-01

    The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may....... Evidence based pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted....

  11. Diet and Pancreatic Cancer Prevention

    Directory of Open Access Journals (Sweden)

    Ilaria Casari

    2015-11-01

    Full Text Available Pancreatic cancer is without any doubt the malignancy with the poorest prognosis and the lowest survival rate. This highly aggressive disease is rarely diagnosed at an early stage and difficult to treat due to its resistance to radiotherapy and chemotherapy. Therefore, there is an urgent need to clarify the causes responsible for pancreatic cancer and to identify preventive strategies to reduce its incidence in the population. Some circumstances, such as smoking habits, being overweight and diabetes, have been identified as potentially predisposing factors to pancreatic cancer, suggesting that diet might play a role. A diet low in fat and sugars, together with a healthy lifestyle, regular exercise, weight reduction and not smoking, may contribute to prevent pancreatic cancer and many other cancer types. In addition, increasing evidence suggests that some food may have chemo preventive properties. Indeed, a high dietary intake of fresh fruit and vegetables has been shown to reduce the risk of developing pancreatic cancer, and recent epidemiological studies have associated nut consumption with a protective effect against it. Therefore, diet could have an impact on the development of pancreatic cancer and further investigations are needed to assess the potential chemo preventive role of specific foods against this disease. This review summarizes the key evidence for the role of dietary habits and their effect on pancreatic cancer and focuses on possible mechanisms for the association between diet and risk of pancreatic cancer.

  12. Surgery for pancreatic cancer -- discharge

    Science.gov (United States)

    ... enable JavaScript. Pancreatic surgery is done to treat cancer of the pancreas gland. When You Are in the Hospital All ... Claudius C, Lillemoe KD. Palliative Therapy for Pancreatic Cancer. In: Cameron ... Vickers SM. Exocrine Pancreas. In: Townsend CM Jr, Beauchamp RD, Evers BM, ...

  13. Whipple Procedure for Pancreatic Cancer

    Medline Plus

    Full Text Available WHIPPLE PROCEDURE FOR PANCREATIC CANCER UNIVERSITY OF MARYLAND MEDICAL CENTER BALTIMORE, MD January 7, 2008 00:00:11 ANNOUNCER: This year, an estimated 37,000 new cases of pancreatic cancer will be diagnosed in this country. Since there ...

  14. Pancreatic adenocarcinoma pathology : changing "landscape"

    NARCIS (Netherlands)

    Brosens, Lodewijk A A; Hackeng, Wenzel M; Offerhaus, G Johan; Hruban, Ralph H; Wood, Laura D

    2015-01-01

    Pancreatic cancer is a devastating disease. At time of diagnosis the disease is usually advanced and only a minority of patients are eligible for surgical resection. The overall 5-year survival is 6%. However, survival of patients with early stage pancreatic cancer is significantly better. To improv

  15. Acute pancreatitis after a course of clarithromycin.

    NARCIS (Netherlands)

    Schouwenberg, B.J.J.W.; Deinum, J.

    2003-01-01

    We present a case of acute pancreatitis after a course of clarithromycin. An 84-year-old woman died of suspected pneumonia and cardiac failure. Autopsy surprisingly revealed acute pancreatitis. Except for the use of clarithromycin no other cause for her acute pancreatitis was obvious. Pancreatitis i

  16. Enteral feeding without pancreatic stimulation

    DEFF Research Database (Denmark)

    Kaushik, Neeraj; Pietraszewski, Marie; Holst, Jens Juul;

    2005-01-01

    OBJECTIVE: All forms of commonly practiced enteral feeding techniques stimulate pancreatic secretion, and only intravenous feeding avoids it. In this study, we explored the possibility of more distal enteral infusions of tube feeds to see whether activation of the ileal brake mechanism can result...... in enteral feeding without pancreatic stimulation, with particular reference to trypsin, because the avoidance of trypsin stimulation may optimize enteral feeding in acute pancreatitis. METHODS: The pancreatic secretory responses to feeding were studied in 36 healthy volunteers by standard double...... plasma glucagon-like peptide-1 and peptide YY concentrations. CONCLUSIONS: Our results suggest that enteral feeding can be given without stimulating pancreatic trypsin secretion provided it is delivered into the mid-distal jejunum. The mechanism may involve activation of the ileal brake mechanism....

  17. [Prolonged acute pancreatitis after bone marrow transplantation].

    Science.gov (United States)

    De Singly, B; Simon, M; Bennani, J; Wittnebel, S; Zagadanski, A-M; Pacault, V; Gornet, J-M; Allez, M; Lémann, M

    2008-04-01

    Acute pancreatitis is not infrequent after allogenic marrow transplantation. Several causes can predispose to pancreatitis, including Graft-Versus-Host Disease (GVHD), a condition which is probably underestimated. In the literature, few description of pancreatic GVHD can be found. Pancreatic GVHD diagnosis can be difficult if pancreatic involvement occurs without other typical manifestations of GVHD. We report the case of a woman, 54 years old, suffering from prolonged, painful pancreatitis two months after allogenic bone marrow transplantation for acute myeloid leucemia. Pancreatic GVHD diagnosis was performed after five weeks on duodenal biopsies despite the absence of diarrheoa. The patient dramatically improved within few days on corticosteroids. PMID:18378104

  18. Endoscopic transpapillary drainage of infected pancreatic pseudocyst complicating pancreatitis,a report of 18 cases

    Directory of Open Access Journals (Sweden)

    Zhi-feng ZHAO

    2011-07-01

    Full Text Available Objective To evaluate the effectiveness of endoscopic transpapillary drainage in the treatment of infected pancreatic pseudocyst complicating pancreatitis.Methods The data of 18 cases of pancreatitis with infected pancreatic pseudocyst having undergone endoscopic transpapillary drainage from Jan.2004 to Jun.2006 were retrospectively analyzed.All patients were diagnosed and then checked postoperatively by endoscopic retrograde cholangiopancreatography(ERCP and CT.All patients were treated by endoscopic sphincterectomy(EST,endoscopic pancreatic sphincterectomy(EPS,or endoscopic nose-pancreatic pseudocysts drainage(ENPPD.Extraction of pancreatic duct stones and dilatation of pancreatic duct stricture were performed selectively.Results During the treatment,removal of pancreatic stones was performed in 6 cases.Pancreatic duct dilatation was performed in 9 cases with pancreatic duct narrowing,and 8 cases received pancreatic stents drainage.Postoperatively,clinical symptoms were evidently alleviated in 18 patients,and with a large amount of purulent pancreatic fluid drained.Symptom of infection,including abdominal pain and fever,were within 48 hours after drainage,and were controlled within 1 week.Pancreatic pseudocysts disappeared in 16 cases,and conspicuously shrank in 2 patients.Pancreatic function recovered gradually following endoscopic transpapillary nose-pancreatic pseudocyst drainage.Conclusions In the treatment of pancreatitis with infected pancreatic pseudocyst,endoscopic transpapillary nose-pancreatic pseudocysts drainage is a preferred method for its safety,less trauma,lower expenditure,convenient and conspicuous curative effect.

  19. Dexamethasone mediates protection against acute pancreatitis via upregulation of pancreatitis-associated proteins

    OpenAIRE

    Kandil, Emad; Lin, Yin-yao; Bluth, Martin H; Zhang, Hong; Levi, Gabriel; Zenilman, Michael E

    2006-01-01

    AIM: To examine the influence of dexamethasone on pancreatitis-associated protein (PAP) gene expression using both in vitro and in vivo models of acute pancreatitis and to study how PAP gene expression correlates with severity of pancreatitis.

  20. Alteration of chaperonin60 and pancreatic enzyme in pancreatic acinar cell under pathological condition

    OpenAIRE

    Li, Yong-Yu; Bendayan, Moise

    2005-01-01

    AIM: To investigate the changes of chaperonin60 (Cpn60) and pancreatic enzymes in pancreatic acinar cells, and to explore their roles in the development of experimental diabetes and acute pancreatitis (AP).

  1. Evaluation of pancreatic scintigram in the diagnosis of pancreatic diseases

    International Nuclear Information System (INIS)

    The classification of accumulative patterns with the pancreatic scintigram findings of chronic pancreatitis and carcinoma of the pancreas were compared with endoscopic retrograde pancreatography (ERP) findings and Pancreozymin-Secretin test (P-S test). I) The frequency of pancreatic cancer was 93%, whilst, the chronic pancreatitis was 88% in the abnormal pancreatic scintigram. II) In the scintigram the type II (localyzed defect shadows) of pancreatic cancer was comparatively high and it is proportional to evidence. derived from ERP. Localized diagnostic certainty is helpful, although the two tests are related. The P-S test is only restricted to the carcinoma of head, whilst, scintigram is more useful to detect the carcinoma of the body and tail of the pancreas. III) As for the chronic pancreatitis, there are various accumulative patterns. This is resemblance to that of ERP findings, but in the P-S normal test, it showed discrepancy in part of the result. Particularly, in the type I (slightly generalized low uptake with density silhouette) and type II. Therefore in order to obtain an accurate diagnosis, it is essential to have both the P-S test and scintigram. (author)

  2. Pancreatic microcirculatory impairment in experimental acute pancreatitis in rats

    Institute of Scientific and Technical Information of China (English)

    Zong-Guang Zhou; You-Dai Chen; Wei Sun; Zhong Chen

    2002-01-01

    AIM: To study the feature of pancreatic microcirculatoryimpairment, especially the initial changes, in caerulein-induced experimental acute pancreatitis (AP).METHODS: The pancreatic microcirculation of caerulein-induced AP model was studied by intravital fluorescencemicroscopy with FITC-labeled erythrocytes (FITC-RBC),scanning electron microscopy of vascular corrosion casts,and light microscopy of Chinese ink-injected/cleared tissues.RESULTS: Animals in caerulein-treated group showedhyperamylemia (× 2), pancreatic oedema, infiltration ofinflammatory cells in pancreas. Constrictions of intralobulararteriolar sphincters, presence of vacuoles in all layers ofsphincter, and gross irregularity in capillary network of aciniwere found in the AP specimens. The decrease of pancreaticcapillary blood flow (0.34±0.10 nl @ min-1 vs0.910.06 nl @rain-1 of control, P<0.001), reduction of functional capillarydensity(277± 13 cm-1 vs349±8 cm-1 of control, P<0.001),and irregular intermittent perfusion were observed incaerulein-induced groups.CONCLUSION: Impairment and constriction of pancreaticintralobular arteriolar sphincter are the initial microcirculatorylesions in the early phase of acute pancreatitis, and play akey role in the pancreatic ischaemia and pancreaticmicrovascular failure in acute pancreatitis.

  3. Contrast-enhanced sonography in pancreatic diseases

    Energy Technology Data Exchange (ETDEWEB)

    Rickes, Steffen [Department of Internal Medicine, AMEOS Hospital GmbH, Halberstadt (Germany); Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University, Magdeburg (Germany)], E-mail: rickes@medkl.salvator-kh.de; Rauh, Peter; Uhle, Christine; Ensberg, Daniel [Department of Internal Medicine, AMEOS Hospital GmbH, Halberstadt (Germany); Moenkemueller, Klaus; Malfertheiner, Peter [Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University, Magdeburg (Germany)

    2007-11-15

    Contrast-enhanced sonography is a widely available imaging modality for the diagnosis of pancreatic diseases. With this procedure, pancreatic tumours can be differentiated better. Furthermore, contrast-enhanced sonography produces good results in the staging of acute pancreatitis severity, especially in the detection of pancreatic necrosis. In this review article the value of contrast-enhanced sonography in the diagnosis of pancreatic diseases will be described and discussed.

  4. Is acute recurrent pancreatitis a chronic disease?

    OpenAIRE

    Mariani, Alberto; Testoni, Pier Alberto

    2008-01-01

    Whether acute recurrent pancreatitis is a chronic disease is still debated and a consensus is not still reached as demonstrated by differences in the classification of acute recurrent pancreatitis. There is major evidence for considering alcoholic pancreatitis as a chronic disease ab initio while chronic pancreatitis lesions detectable in biliary acute recurrent pancreatitis (ARP) seem a casual association. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation, hereditary a...

  5. Cancer Stem Cells in Pancreatic Cancer

    International Nuclear Information System (INIS)

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer

  6. Alcoholic pancreatitis:Lessons from the liver

    Institute of Scientific and Technical Information of China (English)

    Dahn; L; Clemens; Katrina; J; Mahan

    2010-01-01

    The association between alcohol consumption and pancreatitis has been recognized for over 100 years. Despite the fact that this association is well recognized, the mechanisms by which alcohol abuse leads to pancreatic tissue damage are not entirely clear. Alcohol abuse is the major factor associated with pancreatitis in the Western world. Interestingly, although most cases of chronic pancreatitis and many cases of acute pancreatitis are associated with alcohol abuse, only a small percentage of individuals w...

  7. Pancreas Divisum and Acute or Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Raffaele Pezzilli

    2012-01-01

    Full Text Available The role of pancreas divisum as a pancreatic ductal anomaly able to induce acute or chronic pancreatitis is still under debate; some authors consider the pancreas as a variant of the pancreatic ductal system able to induce acute or chronic pancreatitis as a result of relative outflow obstruction [1, 2, 3], whereas others consider this finding a simple morphological anomaly of the pancreatic ductal system without any clinical consequence [4, 5, 6].

  8. Imaging in the diagnosis of chronic pancreatitis

    OpenAIRE

    Vasile D. Balaban; Andrei M. Lungu; Dragoș Cuzino; Săndica Bucurică; Bogdan Macadon; Mihăiță Pătrășescu; Raluca S. Costache; Petruț Nuță; Constantin Ştefani; Florentina Ioniță-Radu; Mariana Jinga

    2014-01-01

    Chronic pancreatitis is characterised by progressive and irreversible damage of the pancreatic parenchyma and ductal system, which leads to chronic pain, loss of endocrine and exocrine functions. Clinically, pancreatic exocrine insufficiency becomes apparent only after 90% of the parenchima has been lost. Despite the simple definition, diagnosing chronic pancreatitis remains a challenge, especially for early stage disease. Because pancreatic function tests can be normal until l...

  9. Diabetes, pancreatic cancer, and metformin therapy

    OpenAIRE

    Gong, Jun; Robbins, Lori A.; Lugea, Aurelia; Waldron, Richard T.; Jeon, Christie Y.; Pandol, Stephen J

    2014-01-01

    Pancreatic cancer carries a poor prognosis as most patients present with advanced disease and preferred chemotherapy regimens offer only modest effects on survival. Risk factors include smoking, obesity, heavy alcohol, and chronic pancreatitis. Pancreatic cancer has a complex relationship with diabetes, as diabetes can be both a risk factor for pancreatic cancer and a result of pancreatic cancer. Insulin, insulin-like growth factor-1 (IGF-1), and certain hormones play an important role in pro...

  10. Detecting Early Pancreatic Cancer- Problems and Prospects

    OpenAIRE

    Chari, Suresh T.

    2007-01-01

    Pancreatic cancer has a poor prognosis. Improving survival will require diagnosis of early pancreatic cancer which can be defined based on resectability, size or curability. Pancreatic cancer progresses from non-invasive precursor lesions to invasive cancer over a variable time period. Retrospective review of CT scans done prior to diagnosis suggests that pancreatic cancer resectability may be significantly improved if detected as few as 6 months before clinical diagnosis. Since pancreatic ca...

  11. Clinical Impact of the KL-6 Concentration of Pancreatic Juice for Diagnosing Pancreatic Masses

    OpenAIRE

    Kazuya Matsumoto; Yohei Takeda; Kenichi Harada; Takumi Onoyama; Soichiro Kawata; Yasushi Horie; Teruhisa Sakamoto; Masaru Ueki; Norimasa Miura; Yoshikazu Murawaki

    2015-01-01

    Background and Aim. Pancreatic juice cytology (PJC) is considered optimal for differentially diagnosing pancreatic masses, but the accuracy of PJC ranges from 46.7% to 93.0%. The aim of this study was to evaluate the clinical impact of measuring the KL-6 concentration of pancreatic juice for diagnosing pancreatic masses. Methods. PJC and the KL-6 concentration measurements of pancreatic juice were performed for 70 consecutive patients with pancreatic masses (39 malignancies and 31 benign). Re...

  12. Is Zinc Concentration in Pancreatic Fluid a Marker for Pancreatic Diseases?

    OpenAIRE

    Surakit Pungpapong; James S Scolapio; Timothy A. Woodward; Wallace, Michael B.; Massimo Raimondo

    2005-01-01

    Objectives An imbalance of free radicals and scavenging processes has been implicated in the pathogenesis of pancreatic tissue injury. Gradual decreases in antioxidant enzyme expression in pancreatic cells from normal pancreas to chronic pancreatitis to pancreatic cancer have been reported. Zinc is one of the components of antioxidant enzymes and may play a role in the pathogenesis of pancreatic diseases. A recent report showed a significant decrease in pancreatic zinc output in patients with...

  13. Activation of Pancreatic Stellate Cells in Human and Experimental Pancreatic Fibrosis

    OpenAIRE

    Haber, Paul S; Keogh, Gregory W.; Apte, Minoti V.; Moran, Corey S.; Stewart, Nancy L.; Crawford, Darrell H.G.; Pirola, Romano C.; McCaughan, Geoffrey W.; Ramm, Grant A; Wilson, Jeremy S.

    1999-01-01

    The mechanisms of pancreatic fibrosis are poorly understood. In the liver, stellate cells play an important role in fibrogenesis. Similar cells have recently been isolated from the pancreas and are termed pancreatic stellate cells. The aim of this study was to determine whether pancreatic stellate cell activation occurs during experimental and human pancreatic fibrosis. Pancreatic fibrosis was induced in rats (n = 24) by infusion of trinitrobenzene sulfonic acid (TNBS) into the pancreatic duc...

  14. Update on Endoscopic Management of Main Pancreatic Duct Stones in Chronic Calcific Pancreatitis

    OpenAIRE

    Choi, Eun Kwang; Lehman, Glen A.

    2012-01-01

    Pancreatic duct stones are a common complication during the natural course of chronic pancreatitis and often contribute to additional pain and pancreatitis. Abdominal pain, one of the major symptoms of chronic pancreatitis, is believed to be caused in part by obstruction of the pancreatic duct system (by stones or strictures) resulting in increasing intraductal pressure and parenchymal ischemia. Pancreatic stones can be managed by surgery, endoscopy, or extracorporeal shock wave lithotripsy. ...

  15. 14.2.Pancreatitis

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930325 A clinical study on a lipid—based sys-tem of parenteral nutrition in acute pancreati-tis.ZHU Jiangfan (朱江帆),et al.Dept Hepato-bill Surg,lst Teach Hosp,3rd Milit Med Coll.Chin J Digest 1992;12(4):195—197.A controlled prospective study on a lipid-based system of parenteral nutrition has beencarried out in patients with acute pancreatitis.The results show that the patients’ positive ni-trogen balance can be obtained and the visceralproteins can be maintained within normal range

  16. Pancreatic islet transplantation

    Directory of Open Access Journals (Sweden)

    Corrêa-Giannella Maria

    2009-09-01

    Full Text Available Abstract Background No formulation of exogenous insulin available to date has yet been able to mimic the physiological nictemeral rhythms of this hormone, and despite all engineering advancements, the theoretical proposal of developing a mechanical replacement for pancreatic β cell still has not been reached. Thus, the replacement of β cells through pancreas and pancreatic islet transplantation are the only concrete alternatives for re-establishing the endogenous insulin secretion in type 1 diabetic patients. Since only 1 to 1.5% of the pancreatic mass corresponds to endocrine tissue, pancreatic islets transplantation arises as a natural alternative. Data from the International Islet Transplant Registry (ITR from 1983 to December 2000 document a total of 493 transplants performed around the world, with progressively worse rates of post-transplant insulin independence. In 2000, the "Edmonton Protocol" introduced several modifications to the transplantation procedure, such as the use of a steroid-free immunosuppression regimen and transplantation of a mean islet mass of 11,000 islet equivalents per kilogram, which significantly improved 1-year outcomes. Although the results of a 5-year follow-up in 65 patients demonstrated improvement in glycemic instability in a significant portion of them, only 7.5% of the patients have reached insulin independence, indicating the need of further advances in the preservation of the function of transplanted islet. In addition to the scarcity of organs available for transplantation, islets transplantation still faces major challenges, specially those related to cell loss during the process of islet isolation and the losses related to the graft site, apoptosis, allorejection, autoimmunity, and immunosuppression. The main strategies to optimize islet transplantation aim at improving all these aspects. Conclusion Human islet transplantation should be regarded as an intervention that can decrease the frequency of

  17. Metronidazole-induced pancreatitis.

    LENUS (Irish Health Repository)

    O'Halloran, E

    2010-01-01

    A 25-year-old caucasian lady presented to the Accident & Emergency department complaining of acute onset severe epigastric pain radiating through to the back with associated nausea and vomiting. A diagnosis of acute pancreatitis was made. Symptoms commenced after the third dose of Metronidazole therapy prescribed for a recurrent periodontal abscess. The patient described a similar episode 10 months previously. On neither occasion were any other medications being taken, there was no history of alcohol abuse and no other gastro-intestinal aetiology could be identified on imaging. Symptoms resolved quickly upon discontinuation of the antibiotic agent. We conclude therefore that Metronidazole can reasonably be identified as the only potential causative agent.

  18. Remodelling sympathetic innervation in rat pancreatic islets ontogeny

    Directory of Open Access Journals (Sweden)

    Hiriart Marcia

    2009-06-01

    Full Text Available Abstract Background Pancreatic islets are not fully developed at birth and it is not clear how they are vascularised and innervated. Nerve Growth Factor (NGF is required to guide sympathetic neurons that innervate peripheral organs and also in cardiovascular system and ovary angiogenesis. Pancreatic beta cells of a transgenic mouse that over-expressed NGF in attracts sympathetic hyper-innervation towards them. Moreover, we have previously demonstrated that adult beta cells synthesize and secrete NGF; however, we do not know how is NGF secreted during development, nor if it might be trophic for sympathetic innervation and survival in the pancreas. We analyzed sympathetic innervation and vasculature development in rat pancreatic islets at different developmental stages; foetal (F19, early postnatal (P1, weaning period (P20 and adults. We temporarily correlated these events to NGF secretion by islet cells. Results Sympathetic fibres reached pancreatic islets in the early postnatal period, apparently following blood vessels. The maximal number of sympathetic fibres (TH immunopositive in the periphery of the islets was observed at P20, and then fibres entered the islets and reached the core where beta cells are mainly located. The number of fibres decreased from that stage to adulthood. At all stages studied, islet cells secreted NGF and also expressed the high affinity receptor TrkA. Foetal and neonatal isolated islet cells secreted more NGF than adults. TrkA receptors were expressed at all stages in pancreatic sympathetic fibres and blood vessels. These last structures were NGF–immunoreactive only at early stages (foetal and P0. Conclusion The results suggest that NGF signalling play an important role in the guidance of blood vessels and sympathetic fibres toward the islets during foetal and neonatal stages and could also preserve innervation at later stages of life.

  19. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Nandy, Debashis; Mukhopadhyay, Debabrata, E-mail: mukhopadhyay.debabrata@mayo.edu [Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, 200 First Street SW, Guggenheim 1321C, Rochester, MN 55905 (United States)

    2011-02-24

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed.

  20. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    International Nuclear Information System (INIS)

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed

  1. Segmental pancreatic autotransplantation for chronic pancreatitis. A preliminary report

    International Nuclear Information System (INIS)

    A patient who underwent 95% pancreatectomy with autotransplantation of the body and tail of the gland to the femoral area for chronic pancreatitis is presented. The pain resolved, and the patient's blood glucose level remained within normal limits. High levels of insulin were found in the iliac vein on the transplanted side. Patency of the graft was demonstrated by technetium scan and arteriography and followed by a color-coded Doppler imaging system. Segmental pancreatic autotransplantation offers a method of relieving pain with preservation of endocrine function in selected patients with chronic pancreatitis

  2. Chronic Pancreatitis, Type 3c Diabetes, and Pancreatic Cancer Risk

    OpenAIRE

    Whitcomb, David C

    2014-01-01

    About half of all patients with chronic pancreatitis (CP) develop diabetes mellitus (DM) due to the loss of islet cell mass, not just beta cells as in Type 1 DM (T1DM), or due to insulin resistance, as in Type 2 DM (T2DM). Patients with DM from loss of islets due to pancreatic disease or resection are diagnosed with pancreatogenic or Type 3c DM (T3cDM). Patients with T3cDM also lose counter-regulatory hormones, such as glucagon and pancreatic polypeptide, and experience maldigestion associate...

  3. Stanniocalcin 2 alters PERK signalling and reduces cellular injury during cerulein induced pancreatitis in mice

    Directory of Open Access Journals (Sweden)

    DiMattia Gabriel E

    2011-05-01

    Full Text Available Abstract Background Stanniocalcin 2 (STC2 is a secreted protein activated by (PKR-like Endoplasmic Reticulum Kinase (PERK signalling under conditions of ER stress in vitro. Over-expression of STC2 in mice leads to a growth-restricted phenotype; however, the physiological function for STC2 has remained elusive. Given the relationship of STC2 to PERK signalling, the objective of this study was to examine the role of STC2 in PERK signalling in vivo. Results Since PERK signalling has both physiological and pathological roles in the pancreas, STC2 expression was assessed in mouse pancreata before and after induction of injury using a cerulein-induced pancreatitis (CIP model. Increased Stc2 expression was identified within four hours of initiating pancreatic injury and correlated to increased activation of PERK signalling. To determine the effect of STC2 over-expression on PERK, mice systemically expressing human STC2 (STC2Tg were examined. STC2Tg pancreatic tissue exhibited normal pancreatic morphology, but altered activation of PERK signalling, including increases in Activating Transcription Factor (ATF 4 accumulation and autophagy. Upon induction of pancreatic injury, STC2Tg mice exhibited limited increases in circulating amylase levels and increased maintenance of cellular junctions. Conclusions This study links STC2 to the pathological activation of PERK in vivo, and suggests involvement of STC2 in responding to pancreatic acinar cell injury.

  4. Genes and Proteins Differentially Expressed during In Vitro Malignant Transformation of Bovine Pancreatic Duct Cells

    Directory of Open Access Journals (Sweden)

    R. Jesnowski

    2007-02-01

    Full Text Available Pancreatic carcinoma has an extremely bad prognosis due to lack of early diagnostic markers and lack of effective therapeutic strategies. Recently, we have established an in vitro model recapitulating the first steps in the carcinogenesis of the pancreas. SV40 large T antigen-immortalized bovine pancreatic duct cells formed intrapancreatic adenocarcinoma tumors on k-rasmut transfection after orthotopic injection in the nude mouse pancreas. Here we identified genes and proteins differentially expressed in the course of malignant transformation using reciprocal suppression subtractive hybridization and 2D gel electrophoresis and mass spectrometry, respectively. We identified 34 differentially expressed genes, expressed sequence tags, and 15 unique proteins. Differential expression was verified for some of the genes or proteins in samples from pancreatic carcinoma. Among these genes and proteins, the majority had already been described either to be influenced by a mutated ras or to be differentially expressed in pancreatic adenocarcinoma, thus proving the feasibility of our model. Other genes and proteins (e.g., BBC1, GLTSCR2, and rhoGDlα, up to now, have not been implicated in pancreatic tumor development. Thus, we were able to establish an in vitro model of pancreatic carcinogenesis, which enabled us to identify genes and proteins differentially expressed during the early steps of malignant transformation.

  5. Pancreatic panniculitis associated with acute pancreatitis and hemorrhagic pseudocysts: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Yong Suk; Kim, Mi Sung; Park, Chan Sub; Park, Ji Yeon; Park, Noh Hyuck [Kwandong Univ., Myongji Hospital, Goyang (Korea, Republic of)

    2012-10-15

    Pancreatic panniculitis is an inflammation and necrosis of fat at distant foci in patients with pancreatic disorders, most frequently, pancreatitis and pancreatic carcinoma. Clinically, pancreatic panniculitis is manifested by painless or painful subcutaneous nodules on the legs, buttocks, or trunk. The usual sites are the distal parts of the lower extremities. To the best of our knowledge, there have not been many reports for the radiologic findings of pancreatic panniculitis. In this article, we report a case of pancreatic panniculitis, including radiologic findings of CT and ultrasonography. The patient was presented with painful subcutaneous nodules on the trunk, and had underlying acute pancreatitis and hemorrhagic pseudocysts.

  6. Groove Pancreatitis: Spiral CT Findings

    International Nuclear Information System (INIS)

    To describe the spiral CT findings of groove pancreatitis, a little known entity, and to review its differential diagnosis. We present 8 cases of groove pancreatitis. or pancreatitis affecting the groove between pancreatic head, duodenum and common bile duct, all studied with spiral CT. For two cases, in which were performed cephalic duodenopancreatectomies, anatomopathological correlations were available. In the other 6 cases, radiological follow-ups of anywhere between 5 and 36 months were utilized. In all eight cases, spiral CT showed expansion and increasing density of lipids within the groove with poor contrast enhancement indicative of the fibrous nature of this pathology, and associated with cystic areas in its interior and/or the duodenal wall. the pancreatic head was unaffected in pure forms of groove pancreatitis, and hypodense areas were observed in zones of cephalic segmental enhancement. Knowledge of this little known form of chronic pancreatitis, and the radiological findings that permit its diagnosis are important for the radiologist since its differential diagnosis includes neoplasia of the peri-ampullary region. (Author) 6 refs

  7. Pharmacological challenges in chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Anne Estrup Olesen

    2013-01-01

    Full Text Available Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion. Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes. Many patients limit their food intake because of the pain caused by eating and in some cases food intake is more or less substituted with alcohol, tobacco and coffee. Alcohol and drug interaction are known to influence the pharmacokinetics by altering either drug absorption or by affecting liver metabolism. Since patients suffering from chronic pancreatitis experience severe pain, opioids are often prescribed as pain treatment. Opioids have intrinsic effects on gastrointestinal motility and hence can modify the absorption of other drugs taken at the same time. Furthermore, the increased fluid absorption caused by opioids will decrease water available for drug dissolution and may hereby affect absorption of the drug. As stated above many factors can influence drug absorption and metabolism in patients with chronic pancreatitis. The factors may not have clinical relevance, but may explain inter-individual variations in responses to a given drug, in patients with chronic pancreatitis.

  8. Molecular biology of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Miroslav Zavoral; Petra Minarikova; Filip Zavada; Cyril Salek; Marek Minarik

    2011-01-01

    In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancreatic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations (somatic point mutations and allelic losses) affect oncogenes and tumor-suppressor genes within RAS, AKT and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53). Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.

  9. Liraglutide-induced acute pancreatitis.

    Science.gov (United States)

    Jeyaraj, Santhosh; Shetty, Ananth Samith; Kumar, Champat Raj Roopesh; Nanditha, Arun; Krishnamoorthy, Satheesh; Raghavan, Arun; Raghavan, K; Ramachandran, Ambady

    2014-01-01

    An obese lady of 51 year with Type 2 Diabetes Mellitus for 13 years was prescribed Liraglutide, a glucagon like peptide (GLP-1) analogue (Victoza) for glycaemic control and reduction of weight. She was on gliclazide and Insulin prior to initiation of Liraglutide. Eight weeks after initiation of GLP -1 analogue, she developed severe abdominal pain, nausea and vomiting. She was admitted to a private hospital and evaluated. Biochemical tests and CT scan revealed presence of pancreatitis and she was treated for acute pancreatitis. Liraglutide was withdrawn and symptoms subsided. Subsequent follow-up showed that pancreatic enzyme levels were normal. PMID:25327099

  10. Radiological evaluation following pancreatic transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Marincek, B.; Schulthess, G.K. von; Schlumpf, R.; Decurtins, M.; Largiader, F.

    1988-12-01

    Technical complications are relatively common after pancreatic transplantation, and most require radiological evaluation. Ultra sonography and computed tomography are helpful in the identification of peripancreatic and intra-abdominal fluid collections. Sterile fluid collections can be effectively treated by percutaneous catheter drainage, whereas most intra-abdominal infections require surgical intervention. Angiography is performed primarily for diagnosis of vascular thrombosis. Recent results suggest that magnetic resonance may be a useful non-invasive method for the detection of pancreatic transplant rejection. Further imaging studies are needed to better define the development of progressive fibrotic atrophy in long-term functioning pancreatic transplants.

  11. Severe Acute Pancreatitis in Pregnancy

    Directory of Open Access Journals (Sweden)

    Bahiyah Abdullah

    2015-01-01

    Full Text Available This is a case of a pregnant lady at 8 weeks of gestation, who presented with acute abdomen. She was initially diagnosed with ruptured ectopic pregnancy and ruptured corpus luteal cyst as the differential diagnosis. However she then, was finally diagnosed as acute hemorrhagic pancreatitis with spontaneous complete miscarriage. This is followed by review of literature on this topic. Acute pancreatitis in pregnancy is not uncommon. The emphasis on high index of suspicion of acute pancreatitis in women who presented with acute abdomen in pregnancy is highlighted. Early diagnosis and good supportive care by multidisciplinary team are crucial to ensure good maternal and fetal outcomes.

  12. Acute pancreatitis caused by bortezomib.

    Science.gov (United States)

    Solakoglu, Tevfik; Akyol, Pinar; Guney, Tekin; Dilek, Imdat; Atalay, Roni; Koseoglu, Huseyin; Akin, Ebru; Demirezer Bolat, Aylin; Buyukasik, Naciye Semnur; Ersoy, Osman

    2013-01-01

    Drug-induced pancreatitis has been reported rarely. Bortezomib is a selective and reversible proteasome inhibitor used for the treatment of patients with multiple myeloma (MM). Recently, one case report about acute pancreatitis (AP) caused by bortezomib was published in the international literature. Herein we report a case of AP in a 67-year-old male on bortezomib therapy. On the fourth day after the first administration of bortezomib, the patient admitted to the hospital with symptoms of AP. The common etiological factors for AP were all excluded. Than the patient was diagnosed as bortezomib-induced pancreatitis. PMID:23561979

  13. Proteomics in Pancreatic Cancer Research

    Science.gov (United States)

    Geng, Ruihui; Li, Zhaoshen; Li, Shude; Gao, Jun

    2011-01-01

    Pancreatic cancer is a highly aggressive malignancy with a poor prognosis and deeply affects the life of people. Therefore, the earlier diagnosis and better treatments are urgently needed. In recent years, the proteomic technologies are well established and growing rapidly and have been widely applied in clinical applications, especially in pancreatic cancer research. In this paper, we attempt to discuss the development of current proteomic technologies and the application of proteomics to the field of pancreatic cancer research. This will explore the potential perspective in revealing pathogenesis, making the diagnosis earlier and treatment. PMID:22084685

  14. Vitamin D and pancreatic cancer

    OpenAIRE

    Stolzenberg-Solomon, Rachael Z.

    2008-01-01

    Sun exposure has been associated with lower death rates for pancreatic cancer in ecological studies. Skin exposure to solar ultra-violet B radiation induces cutaneous production of precursors to 25-hydroxy (OH) vitamin D (D) and is considered the primary contributor to vitamin D status in most populations. Pancreatic islet and duct cells express 25-(OH) D3-1α-hydroxylase that generates the biologically active 1,25-dihydroxy(OH)2 D form. Thus, 25(OH)D concentrations could affect pancreatic fun...

  15. Pancreatic tissue fluid pressure and pain in chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N

    1992-01-01

    A casual relation between pancreatic pressure and pain has been searched for decades but lack of appropriate methods for pressure measurements has hindered progress. During the 1980's the needle method has been used for direct intraoperative pancreatic tissue fluid pressure measurements and later...... for percutaneous sonographically-guided pressure measurements. Clinical and experimental evaluation of the method showed comparable results at intraoperative and percutaneous measurements and little week-to-week variation. Furthermore, comparable pressures in duct and adjacent pancreatic tissue were...... found, i.e. the needle pressure mirrors the intraductal pressure. Comparisons of pain registrations, morphological and functional parameters with pancreatic tissue fluid pressure measurements have revealed a relation between pressure and pain which probably is causal. In patients with pain the high...

  16. Targeted Alpha Therapy Approach to the Management of Pancreatic Cancer

    International Nuclear Information System (INIS)

    Evidence for the efficacy of targeted alpha therapy for the control of pancreatic cancer in preclinical models is reviewed. Results are given for in vitro pancreatic cancer cells and clusters and micro-metastatic cancer lesions in vivo. Two complementary targeting vectors are examined. These are the C595 monoclonal antibody that targets the MUC1 antigen and the PAI2 ligand that targets the uPA receptor. The expression of the tumor-associated antigen MUC-1 and the uPA receptor on three pancreatic cancer cell lines is reported for cell clusters, human mouse xenografts and lymph node metastases, as well as for human pancreatic cancer tissues, using immuno-histochemistry, confocal microscopy and flow cytometry. The targeting vectors C595 and PAI2 were labeled with the alpha emitting radioisotope 213Bi using the chelators cDTPA and CHX-A″ to form the alpha-conjugates (AC). Cell clusters were incubated with the AC and examined at 48 hours. Apoptosis was documented using the TUNEL assay. In vivo, the anti-proliferative effect for tumors was tested at two days post-subcutaneous cell inoculation. Mice were injected with different concentrations of AC by local or systemic administration. Changes in tumor progression were assessed by tumor size. MUC-1 and uPA are strongly expressed on CFPAC-1, PANC-1 and moderate expression was found CAPAN-1 cell clusters and tumor xenografts. The ACs can target pancreatic cells and regress cell clusters (∼100 μm diameter), causing apoptosis in some 70–90 % of cells. At two days post-cell inoculation in mice, a single local injection of 74 MBq/kg of AC causes complete inhibition of tumor growth. Systemic injections of 111, 222 and 333 MBq/kg of alpha-conjugate caused significant tumor growth delay in a dose dependent manner after 16 weeks, compared with the non-specific control at 333 MBq/kg. Cytotoxicity was assessed by the MTS and TUNEL assays. The C595 and PAI2-alpha conjugates are indicated for the treatment of micro

  17. The role of diagnostic radiology in pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Elmas, Nevra E-mail: elmas@med.ege.edu.tr

    2001-05-01

    Acute pancreatitis is a frequent inflammatory and necrotic process of pancreas and peripancreatic field. To detect the presence of infected or sterile necrotic components and hemorrhage of the pancreatic paranchyma is important for therapeutic approach. Chronic pancreatitis is characterized by irreversible exocrine dysfunction, progressive loss of pancreatic tissue and morphological changes of the pancreatic canal. Imaging modalities play a primary role in the management of both acute and chronic pancreatitis. CT and MR imaging confirm the diagnosis and detect the severity of disease. In chronic pancreatitis, MRCP after Secretin administration, Spiral CT and endoscopic US seems to replace diagnostic ERCP. However differentiation of pseudotumor of chronic pancreatitis from the pancreatic carcinoma is difficult with either imaging modalities.

  18. Magnetic resonance imaging of pancreatitis: an update.

    Science.gov (United States)

    Manikkavasakar, Sriluxayini; AlObaidy, Mamdoh; Busireddy, Kiran K; Ramalho, Miguel; Nilmini, Viragi; Alagiyawanna, Madhavi; Semelka, Richard C

    2014-10-28

    Magnetic resonance (MR) imaging plays an important role in the diagnosis and staging of acute and chronic pancreatitis and may represent the best imaging technique in the setting of pancreatitis due to its unmatched soft tissue contrast resolution as well as non-ionizing nature and higher safety profile of intravascular contrast media, making it particularly valuable in radiosensitive populations such as pregnant patients, and patients with recurrent pancreatitis requiring multiple follow-up examinations. Additional advantages include the ability to detect early forms of chronic pancreatitis and to better differentiate adenocarcinoma from focal chronic pancreatitis. This review addresses new trends in clinical pancreatic MR imaging emphasizing its role in imaging all types of acute and chronic pancreatitis, pancreatitis complications and other important differential diagnoses that mimic pancreatitis. PMID:25356038

  19. The role of diagnostic radiology in pancreatitis

    International Nuclear Information System (INIS)

    Acute pancreatitis is a frequent inflammatory and necrotic process of pancreas and peripancreatic field. To detect the presence of infected or sterile necrotic components and hemorrhage of the pancreatic paranchyma is important for therapeutic approach. Chronic pancreatitis is characterized by irreversible exocrine dysfunction, progressive loss of pancreatic tissue and morphological changes of the pancreatic canal. Imaging modalities play a primary role in the management of both acute and chronic pancreatitis. CT and MR imaging confirm the diagnosis and detect the severity of disease. In chronic pancreatitis, MRCP after Secretin administration, Spiral CT and endoscopic US seems to replace diagnostic ERCP. However differentiation of pseudotumor of chronic pancreatitis from the pancreatic carcinoma is difficult with either imaging modalities

  20. Computerized tomography in acute and chronic pancreatitis

    International Nuclear Information System (INIS)

    Modern imaging techniques have revolutionized the diagnostic evaluation of pancreatitis, primarily demonstrating its complications. Computerized tomography (CT) is a more sensitive method than ultrasonography and pancreatic ductography. A chart review revealed 214 patients at our hospital with a discharge diagnosis of pancreatitis. Sixty patients had CT for evaluation of possible complications. Only five scans were normal. Of 37 cases of acute pancreatitis, 92% demonstrated localized or diffuse enlargement, and 65% showed loss of pancreatic outline. Other frequent findings included thickening of perirenal fascia (49%), ileus (43%), edema of mesentery (35%), and inflammatory exudate (32%). Abscess and pseudocyst were each detected in 8% of cases. In chronic pancreatitis 65% of patients showed localized or diffuse pancreatic enlargement. Atrophy of the gland (30%), calcification (30%), pseudocyst (26%), and dilated pancreatic ducts (17%) were also seen. CT is effective in evaluating pancreatitis and its complications. 14 references, 5 figures, 2 tables

  1. Is acute recurrent pancreatitis a chronic disease?

    Institute of Scientific and Technical Information of China (English)

    Alberto Mariani; Pier Alberto Testoni

    2008-01-01

    Whether acute recurrent pancreaUtis is a chronic disease is still debated and a consensus is not still reached as demonstrated by differences in the classification of acute recurrent pancreatitis.There is major evidence for considering alcoholic pancreatitis as a chronic disease ab initio while chronic pancreatitis lesions detectable in biliary acute recurrent pancreatitis (ARP) seem a casual association.Cystic fibrosis transmembrane con ductance regulator (CFTR) gene mutation,hereditary and obstructive pancreatitis seem an acute disease that progress to chronic pancreatitis,likely as a consequence of the activation and proliferation of pancreatic stellate cells that produce and activate collagen and therefore fibrosis.From the diagnostic point of view,in patients with acute recurrent pancreatitis Endoscopic ultrasound (EUS) seems the more reliable technique for an accurate evaluation and follow-up of some ductal and parenchymal abnormalities suspected for early chronic pancreatitis.

  2. Diagnosis of acute necrotizing pancreatitis and acute hemorrhagic pancreatitis in 5 severe acute pancreatitis by plain computed tomography

    International Nuclear Information System (INIS)

    The diagnosis of acute pancreatitis is still mainly based on the clinical signs and symptoms of patients. In a prospective study of 64 patients with acute pancreatitis, computed tomography (CT) findings were correlated with the clinical types of acute pancreatitis. We were able to correctly diagnose 3 acute necrotizing pancreatitis with autopsy and 2 acute hemorrhagic pancreatitis by plain CT about 48 hours after onset. At present, CT about 48 hours after onset seems to be the most accurate method for the early detection of necrotizing, hemorrhagic and edematous forms of acute pancreatitis. (author)

  3. Role of Neurogenic Inflammation in Pancreatitis and Pancreatic Pain

    OpenAIRE

    Vera-Portocarrero, Louis; Karin N Westlund

    2005-01-01

    Pain arising from pancreatic diseases can become chronic and difficult to treat. There is a paucity of knowledge regarding the mechanisms that sensitize neural pathways that transmit noxious information from visceral organs. In this review, neurogenic inflammation is presented as a possible amplifier of the noxious signal from peripheral organs including the pancreas. The nerve pathways that transmit pancreatic pain are also reviewed as a conduit of the amplified signals. It is likely that co...

  4. CT of the superior mesenteric artery root in pancreatitis and pancreatic carcinoma

    International Nuclear Information System (INIS)

    Previous reports suggested that pancreatitis does not produce CT changes in the region of the root of the superior mesenteric artery (SMA) while pancreatic carcinoma does. The authors have reviewed 103 CT studies from patients with proved pancreatitis (n = 61) or pancreatic carcinoma (n = 42). Masked CT studies (obscuring all regions except the root of the SMA) were evaluated for infiltration of the fat around the SMA, adjacent lymph nodes, focal mass abutting the SMA, and mass circumferentially encasing the SMA. Streaky infiltration around the SMA was seen in patient with pancreatitis (58%) and pancreatic carcinoma (52%). Lymph nodes were seen in both pancreatitis (28%) and carcinoma (17%). Focal mass abutting the SMA was seen in pancreatitis (7%) and carcinoma (26%). Encasement of the SMA was seen only in carcinoma (17%). Both pancreatitis and pancreatic carcinoma can produce CT findings in the region of the root of the SMA. Encasement of the SMA was the only finding specific to patients with pancreatic carcinoma

  5. A non-invasive method of quantifying pancreatic volume in mice using micro-MRI.

    Directory of Open Access Journals (Sweden)

    Jose L Paredes

    Full Text Available In experimental models of pancreatic growth and recovery, changes in pancreatic size are assessed by euthanizing a large cohort of animals at varying time points and measuring organ mass. However, to ascertain this information in clinical practice, patients with pancreatic disorders routinely undergo non-invasive cross-sectional imaging of the pancreas using magnetic resonance imaging (MRI or computed tomography (CT. The aim of the current study was to develop a thin-sliced, optimized sequence protocol using a high field MRI to accurately calculate pancreatic volumes in the most common experimental animal, the mouse. Using a 7 Telsa Bruker micro-MRI system, we performed abdominal imaging in whole-fixed mice in three standard planes: axial, sagittal, and coronal. The contour of the pancreas was traced using Vitrea software and then transformed into a 3-dimensional (3D reconstruction, from which volumetric measurements were calculated. Images were optimized using heart perfusion-fixation, T1 sequence analysis, and 0.2 to 0.4 mm thick slices. As proof of principle, increases in pancreatic volume among mice of different ages correlated tightly with increasing body weight. In summary, this is the first study to measure pancreatic volumes in mice, using a high field 7 Tesla micro-MRI and a thin-sliced, optimized sequence protocol. We anticipate that micro-MRI will improve the ability to non-invasively quantify changes in pancreatic size and will dramatically reduce the number of animals required to serially assess pancreatic growth and recovery.

  6. A Novel Ras Inhibitor (MDC-1016 Reduces Human Pancreatic Tumor Growth in Mice

    Directory of Open Access Journals (Sweden)

    Gerardo G Mackenzie

    2013-10-01

    Full Text Available Pancreatic cancer has one of the poorest prognoses among all cancers partly because of its persistent resistance to chemotherapy. The currently limited treatment options for pancreatic cancer underscore the need for more efficient agents. Because activating Kras mutations initiate and maintain pancreatic cancer, inhibition of this pathway should have a major therapeutic impact. We synthesized phospho-farnesylthiosalicylic acid (PFTS; MDC-1016 and evaluated its efficacy, safety, and metabolism in preclinical models of pancreatic cancer. PFTS inhibited the growth of human pancreatic cancer cells in culture in a concentration- and time-dependent manner. In an MIA PaCa-2 xenograft mouse model, PFTS at a dose of 50 and 100 mg/kg significantly reduced tumor growth by 62% and 65% (P < .05 vs vehicle control. Furthermore, PFTS prevented pancreatitis-accelerated acinar-to-ductal metaplasia in mice with activated Kras. PFTS appeared to be safe, with the animals showing no signs of toxicity during treatment. Following oral administration, PFTS was rapidly absorbed, metabolized to FTS and FTS glucuronide, and distributed through the blood to body organs. Mechanistically, PFTS inhibited Ras-GTP, the active form of Ras, both in vitro and in vivo, leading to the inhibition of downstream effector pathways c-RAF/mitogen-activated protein-extracellular signal-regulated kinase (ERK kinase (MEK/ERK1/2 kinase and phosphatidylinositol 3-kinase/AKT. In addition, PFTS proved to be a strong combination partner with phospho-valproic acid, a novel signal transducer and activator of transcription 3 (STAT3 inhibitor, displaying synergy in the inhibition of pancreatic cancer growth. In conclusion, PFTS, a direct Ras inhibitor, is an efficacious agent for the treatment of pancreatic cancer in preclinical models, deserving further evaluation.

  7. Whipple Procedure for Pancreatic Cancer

    Medline Plus

    Full Text Available ... painless jaundice. He underwent a series of diagnostic studies which indicated that he had a pancreatic head ... a cancer of the head of pancreas. Subsequent studies performed showed that he did not have any ...

  8. Primary pancreatic neoplasms in children

    International Nuclear Information System (INIS)

    Pancreatic tumors are infrequent in children. We are reporting the imaging diagnostic findings observed in a 9 patient series managed during the 1989-2000 with different types of pancreatic neoplasms (insulinoma n=2, pancreatoblastoma n=1, solid papillary-cystic carcinoma n=4, and adenocarcinoma n=2). Imaging exams included: ultrasonography, computed tomography, angiography and magnetic resonance. Imaging studies were useful to demonstrate the tumoral mass in 8/9 cases (89%), with only one false negative case (insulinoma). In this patient (6 years old), US, CT and angiography were negative for pancreatic tumor; final diagnosis was achieved by venous insulin dosimetry and intraoperative US. Pancreatic localization was determined in 7/9 cases (77%), excluding an undetected insulinoma and a huge pancreatoblastoma (14 x 10 cm). However, the imaging diagnosis was useful for staging and planning an adequate surgical approach. (author)

  9. Whipple Procedure for Pancreatic Cancer

    Medline Plus

    Full Text Available ... MD January 7, 2008 00:00:11 ANNOUNCER: This year, an estimated 37,000 new cases of pancreatic cancer will be diagnosed in this country. Since there is no screening test for ...

  10. Whipple Procedure for Pancreatic Cancer

    Medline Plus

    Full Text Available ... January 7, 2008 00:00:11 ANNOUNCER: This year, an estimated 37,000 new cases of pancreatic ... surgical resident, Dr. Didi Prostein, and a fourth- year medical student, Sarah Matthew. Also today I have ...

  11. Whipple Procedure for Pancreatic Cancer

    Medline Plus

    Full Text Available ... that little tissue right there. If those digestive juices leak into the abdominal cavity, they can cause ... out. Just saw a little rush of pancreatic juice there from the center of the pancreas. Almost ...

  12. Whipple Procedure for Pancreatic Cancer

    Medline Plus

    Full Text Available WHIPPLE PROCEDURE FOR PANCREATIC CANCER UNIVERSITY OF MARYLAND MEDICAL CENTER BALTIMORE, MD January 7, 2008 00:00: ... pancreas, a pancreaticoduodenectomy, more commonly known as a Whipple, could be an option. 00:00:57 H. ...

  13. Dynamic CT of pancreatic tumors

    Energy Technology Data Exchange (ETDEWEB)

    Hosoki, T.

    1983-05-01

    Dynamic computed tomography was performed on 19 patients with clinically diagnosed pancreatic and peripancreatic tumors. There were 10 patients with pancreatic cancer, three with inflammatory pancreatic masses, two with cystadenoma, one with insuloma, and three with peripancreatic tumors. Computed tomography was performed with a Varian-V-360-3 scanner; scanning was for 30 consecutive sec at 3 sec intervals after the bolus injection of 50 ml of contrast medium into the antecubital vein. Dynamic computed tomography (CT) may be more useful than conventional contrast CT because it facilitates: (1) correct evaluation of tumor vascularity allowing a differential diagnosis; (2) location of the boundary between tumor and a nontumor tissue; (3) detection of small tumors; and (4) visualization of pancreatic invasion by peripancreatic tumors. In addition, contrast enhancement and the degree of vascular proliferation can be quantitatively assessed by analyzing time-density curves.

  14. Dynamic CT of pancreatic tumors

    International Nuclear Information System (INIS)

    Dynamic computed tomography was performed on 19 patients with clinically diagnosed pancreatic and peripancreatic tumors. There were 10 patients with pancreatic cancer, three with inflammatory pancreatic masses, two with cystadenoma, one with insuloma, and three with peripancreatic tumors. Computed tomography was performed with a Varian-V-360-3 scanner; scanning was for 30 consecutive sec at 3 sec intervals after the bolus injection of 50 ml of contrast medium into the antecubital vein. Dynamic computed tomography (CT) may be more useful than conventional contrast CT because it facilitates: (1) correct evaluation of tumor vascularity allowing a differential diagnosis; (2) location of the boundary between tumor and a nontumor tissue; (3) detection of small tumors; and (4) visualization of pancreatic invasion by peripancreatic tumors. In addition, contrast enhancement and the degree of vascular proliferation can be quantitatively assessed by analyzing time-density curves

  15. Pancreatic cyst in the mediastinum

    International Nuclear Information System (INIS)

    On concrete example it is shown that diagnosis of pancreatic cyst localized in thoracic and peritoneal cavities is difficult. The diagnosis may be corrected only after histological analysis and dynamic observation

  16. PANCREATIC CARCINOMA: REVIEW OF LITERATURE

    Directory of Open Access Journals (Sweden)

    Veena Kumari

    2015-05-01

    Full Text Available It is well known that the prognosis of pancreatic cancer is extremely poor, even when treated with radical surgery. The overall 5 year survival rate following surgical intervention is around 10%.With the increasing use of CT scans for other reasons not related to pancreas, a variety of neoplastic and non - neoplastic lesions are increasingly encountered in clinical practice. The distinction of these lesions has significant therapeutic and prognostic implications. Regarding ductal carcinoma, key distinguishing features from chronic pancreatitis and a discussion of the concept of pancreatic intraepithelial neoplasia ( PanIN are included. Precursors, mo lecular carcinogenesis, risk factors and different morphological patterns of tumors arising from exocrine pancreas are discussed. Research on early detection is ongoing. Screening of people with a family history of hereditary pancreatitis plays an importan t role in the early detection of ductal carcinoma of pancreas.

  17. Whipple Procedure for Pancreatic Cancer

    Medline Plus

    Full Text Available ... 11 ANNOUNCER: This year, an estimated 37,000 new cases of pancreatic cancer will be diagnosed in ... or should not be rushed along. Now, with new technologies - - let me put my hand in there ...

  18. Genetic alterations in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Muhammad Wasif Saif; Lena Karapanagiotou; Kostas Syrigos

    2007-01-01

    The diagnosis of pancreatic cancer is devastating for patients and their relatives as the incidence rate is approximately the same as mortality rate. Only a small percentage, which ranges from 0.4% to 4% of patients who have been given this diagnosis, will be alive at five years. At the time of diagnosis, 80% of pancreatic cancer patients have unresectable or metastatic disease.Moreover, the therapeutic alternatives offered by chemotherapy or radiotherapy are few, if not zero. For all these reasons, there is an imperative need of analyzing and understanding the primitive lesions that lead to invasive pancreatic adenocarcinoma. Molecular pathology of these lesions is the key of our understanding of the mechanisms underlying the development of this cancer and will probably help us in earlier diagnosis and better therapeutic results. This review focuses on medical research on pancreatic cancer models and the underlying genetic alterations.

  19. Whipple Procedure for Pancreatic Cancer

    Medline Plus

    Full Text Available WHIPPLE PROCEDURE FOR PANCREATIC CANCER UNIVERSITY OF MARYLAND MEDICAL CENTER BALTIMORE, MD January 7, 2008 00:00: ... During this webcast from the University of Maryland Medical Center, you'll be able to watch the ...

  20. Nutrition Support in Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Orestis Ioannidis

    2008-07-01

    Full Text Available The management of acute pancreatitis differs according to its severity. Approximately 75% of patients with acute pancreatitis have mild disease with a mortality rate below 1%. Mortality increases up to 20% if the disease progresses to its severe necrotizing form and, in the most severe cases, mortality can increase to 30-40%. Severe acute pancreatitis is usually accompanied by systemic inflammatory response syndrome (SIRS which results in hypermetabolism with prominent protein catabolism. Acute malnutrition, commonly observed in patients with acute pancreatitis, is associated with immunological disturbances, septic complications and delayed healing of surgical wounds, and may lead to multiorgan dysfunction or failure syndrome (MODS or MOFS and increased morbidity and mortality [1].

  1. Whipple Procedure for Pancreatic Cancer

    Medline Plus

    Full Text Available ... say I'm very, very circumspect about any injury to the vein under these circumstances because this ... here. I don't want to have any injury to the pancreatic tissues. Okay. Good. Can I ...

  2. Surgical treatment of acute pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Klose, K.J.; Neher, M.; Kuhn, F.P.; Kuemmerle, F.; Thelen, M.

    1983-03-31

    The diagnosis of acute pancreatitis is based on anamnestic, clinical and chemical data. Ultrasound and computed tomography permit direct visualisation of the pancreas and establish the diagnosis. In cases of haemorrhagic-necrotising pancreatitis they demonstrate the extent of morphological changes and permit exclusion of other causes of an acute abdomen. The imaging methods support indications for operation in cases of subtotal or total parenchymatous necrosis and in pancreatic abscesses. Conservative expectant approaches in patients with severe clinical course and slight morphological changes as well as in agreement of clinical and morphological findings are facilitated. Complete demonstration of parenchymatous and peripancreatic necroses furnishes useful additional information for total extirpation. Gallstone disease can be demonstrated or excluded preoperatively. Since introduction of ultrasound and computed tomography for the diagnosis of acute pancreatitis a marked diminution of early surgical intervention and delayed operation has been achieved.

  3. Pharmacological challenges in chronic pancreatitis

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Brokjaer, Anne; Fischer, Iben Wendelboe Deleuran;

    2014-01-01

    . Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes. Many patients limit their food intake because of the pain caused by eating and in some cases......Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion...... often prescribed as pain treatment. Opioids have intrinsic effects on gastrointestinal motility and hence can modify the absorption of other drugs taken at the same time. Furthermore, the increased fluid absorption caused by opioids will decrease water available for drug dissolution and may hereby...

  4. Autoimmune pancreatitis. An update

    International Nuclear Information System (INIS)

    Autoimmune pancreatitis (AIP) is a rare disease, the pathophysiological understanding of which has been greatly improved over the last years. The most common form, type 1 AIP belongs to the IgG4-related diseases and must be distinguished from type 2 AIP, which is a much rarer entity associated with chronic inflammatory bowel disease. Clinically, there is an overlap with pancreatic cancer. Imaging and further criteria, such as serological and histological parameters are utilized for a differentiation between both entities in order to select the appropriate therapy and to avoid the small but ultimately unnecessary number of pancreatectomies. The diagnostics of AIP are complex, whereby the consensus criteria of the International Association of Pancreatology have become accepted as the parameters for discrimination. These encompass five cardinal criteria and one therapeutic criterion. By applying these criteria AIP can be diagnosed with a sensitivity of 84.9 %, a specificity of 100 % and an accuracy of 93.8 %. The diagnosis of AIP is accomplished by applying several parameters of which two relate to imaging. As for the routine diagnostics of the pancreas these are ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). Important for the differential diagnosis is the exclusion of signs of local and remote tumor spread for which CT and MRI are established. The essential diagnostic parameter of histology necessitates sufficient sample material, which cannot usually be acquired by a fine needle biopsy. CT or MRI are the reference standard methods for identification of the optimal puncture site and imaging-assisted (TruCut) biopsy. In patients presenting with unspecific upper abdominal pain, painless jaundice combined with the suspicion of a pancreatic malignancy in imaging but a mismatch of secondary signs of malignancy, AIP should also be considered as a differential diagnosis. As the diagnosis of AIP only partially relies on imaging radiologists also

  5. Acute biliary pancreatitis: Diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Hazem Zakaria

    2009-01-01

    Full Text Available Gallstones are the commonest cause of acute pancreatitis (AP, a potentially life-threatening condition, worldwide. The pathogenesis of acute pancreatitis has not been fully understood. Laboratory and radiological investigations are critical for diagnosis as well prognosis prediction. Scoring systems based on radiological findings and serologic inflammatory markers have been proposed as better predictors of disease severity. Early endoscopic retrograde cholangiopancreatography (ERCP is beneficial in a group of patients with gallstone pancreatitis. Laparoscopic cholecystectomy with preoperative endoscopic common bile duct clearance is recommended as a treatment of choice for acute biliary pancreatitis. The timing of cholecystectomy, following ERCP, for biliary pancreatitis can vary markedly depending on the severity of pancreatitis

  6. On obesity in acute pancreatitis

    OpenAIRE

    Segersvärd, Ralf

    2005-01-01

    Over-nutrition is one of today s most visible public health problems. Currently over 40% of the Swedish population is either overweight or obese. Acute pancreatitis (AP) is an acute inflammatory process of the pancreas with variable involvement of regional tissues and/or remote organ systems. The morbidity and mortality associated with acute pancreatitis is largely determined by the involvement of distant organs such as the liver and lung and by the development of organ fail...

  7. Antimetabolite Treatment for Pancreatic Cancer

    OpenAIRE

    Valenzuela, Malyn May Asuncion; Neidigh, Jonathan W.; Wall, Nathan R.

    2014-01-01

    Pancreatic cancer is a deadly and aggressive disease. Less than 1% of diagnosed patients survive 5 years with an average survival time of only 4–8 months. The only option for metastatic pancreatic cancer is chemotherapy where only the antimetabolites gemcitabine and 5-fluorouracil are used clinically. Unfortunately, efforts to improve chemotherapy regimens by combining, 5-fluorouracil or gemcitabine with other drugs, such as cisplatin or oxaliplatin, have not increased cell killing or improve...

  8. Genetic abnormalities in pancreatic cancer

    OpenAIRE

    Zamboni Giuseppe; Beghelli Stefania; Moore Patrick S; Scarpa Aldo

    2003-01-01

    Abstract The incidence and mortality of pancreatic adenocarcinoma are nearly coincident having a five-year survival of less than 5%. Enormous advances have been made in our knowledge of the molecular alterations commonly present in ductal cancer and other pancreatic malignancies. One significant outcome of these studies is the recognition that common ductal cancers have a distinct molecular fingerprint compared to other nonductal or endocrine tumors. Ductal carcinomas typically show alteratio...

  9. Diet and Pancreatic Cancer Prevention

    OpenAIRE

    Ilaria Casari; Marco Falasca

    2015-01-01

    Pancreatic cancer is without any doubt the malignancy with the poorest prognosis and the lowest survival rate. This highly aggressive disease is rarely diagnosed at an early stage and difficult to treat due to its resistance to radiotherapy and chemotherapy. Therefore, there is an urgent need to clarify the causes responsible for pancreatic cancer and to identify preventive strategies to reduce its incidence in the population. Some circumstances, such as smoking habits, being overweight and d...

  10. Cystic Lesions in Autoimmune Pancreatitis

    OpenAIRE

    Gompertz, Macarena; Morales, Claudia; Aldana, Hernán; Castillo, Jaime; Berger, Zoltán

    2015-01-01

    Autoimmune pancreatitis (AIP) can be chronic or recurrent, but frequently completely reversible after steroid treatment. A cystic lesion in AIP is a rare finding, and it can mimic a pancreatic cystic neoplasm. Difficulties in an exact diagnosis interfere with treatment, and surgery cannot be avoided in some cases. We report the history of a 63-year-old male presenting with jaundice and pruritus. AIP was confirmed by imaging and elevated IgG4 blood levels, and the patient completely recovered ...

  11. Surgical management of chronic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Stavros Gourgiotis; Stylianos Germanos; Marco Pericoli Ridolifni

    2007-01-01

    BACKGROUND:Treatment of chronic pancreatitis (CP) is a challenging condition for surgeons. During the last decades, increasing knowledge about pathophysiology of CP, improved results of major pancreatic resections, and integration of sophisticated diagnostic methods in clinical practice have resulted in signiifcant changes in surgery for CP. DATA SOURCES:To detail the indications for CP surgery, the surgical procedures, and outcome, a Pubmed database search was performed. The abstracts of searched articles about surgical management of CP were reviewed. The articles could be identiifed and further scrutinized. Further references were extracted by cross-referencing. RESULTS: Main indications of CP for surgery are intractable pain, suspicion of malignancy, and involvement of adjacent organs. The goal of surgical treatment is to improve the quality of life of patients. The surgical approach to CP should be individualized according to pancreatic anatomy, pain characteristics, baseline exocrine and endocrine function, and medical co-morbidity. The approach usually involves pancreatic duct drainage and resection including longitudinal pancreatojejunostomy, pancreatoduodenectomy (Whipple's procedure), pylorus-preserving pancreatoduodenectomy, distal pancreatectomy, total pancreatectomy, duodenum-preserving pancreatic head resection (Beger's procedure), and local resection of the pancreatic head with longitudinal pancreatojejunostomy (Frey's procedure). Non-pancreatic and endoscopic management of pain has also been advocated. CONCLUSIONS:Surgical procedures provide long-term pain relief, a good postoperative quality of life with preservation of endocrine and exocrine pancreatic function, and are associated with low early and late mortality and morbidity. In addition to available results from randomized controlled trials, new studies are needed to determine which procedure is the most effective for the management of patients with CP.

  12. Anorexia nervosa and pancreatic ascites.

    OpenAIRE

    Isaacs, P.; Saunders, A J; Rosen, B. K.; Sladen, G E

    1986-01-01

    Acute alcoholic pancreatitis was undiagnosed in a patient with anorexia nervosa who subsequently developed pancreatic ascites and oedema, wrongly attributed to protein malnutrition alone. She became hyperphagic in an attempt to reverse the malnutrition and hence the abdominal swelling, indicating that the goal of attaining a thin shape was the major determinant of the eating disorder in this patient. Measurement of ascitic fluid amylase concentration should be carried out in all patients with...

  13. How grim is pancreatic cancer?

    OpenAIRE

    Elroy Patrick Weledji; George Enoworock; Martin Mokake; Motaze Sinju

    2016-01-01

    Pancreatic ductal carcinoma continues to be the most lethal malignancy with rising incidence. It is the fourth most common cause of cancer death in the western world due to its low treatment success rate. In addition, because of its rapid growth and silent course, diagnosis is often only established in the advanced stages. As one of the most aggressive malignancies, the treatment of this disease is a great challenge to clinicians. This paper reviewed the natural history of pancreatic cancer, ...

  14. Delineation of glutamate pathways and secretory responses in pancreatic islets with β-cell-specific abrogation of the glutamate dehydrogenase

    DEFF Research Database (Denmark)

    Vetterli, Laurène; Carobbio, Stefania; Pournourmohammadi, Shirin; Martin-Del-Rio, Rafael; Skytt, Dorte M; Waagepetersen, Helle S.; Tamarit-Rodriguez, Jorge; Maechler, Pierre

    2012-01-01

    In pancreatic β-cells, glutamate dehydrogenase (GDH) modulates insulin secretion, although its function regarding specific secretagogues is unclear. This study investigated the role of GDH using a β-cell-specific GDH knockout mouse model, called βGlud1(-/-). The absence of GDH in islets isolated ...

  15. [Surgical management of pancreatic cancer].

    Science.gov (United States)

    Kim, Song Cheol

    2008-02-01

    Pancreatic cancer is a major problematic concern among all forms of gastrointestinal malignancies because of its poor prognosis. Although significant progress has been made in the surgical treatment in terms of increased resection rate and decreased treatment-related morbidity and mortality, the true survival rate still remains below 5% today. Surgical options for pancreatic cancer are based on the its unique anatomy and physiology, catastrophic tumor biology, experience of surgeon, and status of patients. Four main options exist for the surgical treatment of pancreatic cancer. These include standard "Whipple" pancreaticoduodenectomy (PD), pylorus preserving PD (PPPD), distal pancreatectomy (left-side pancreatectomy), and total pancreatectomy according to the location of tumor. Portal vein involvement by tumor is regarded as an anatomical extension of disease, and en bloc resection of portal vein with tumor is recommended if technically feasible, which is stated in 2002 AJCC tumor staging for pancreatic cancer. In comparison of the survival rates between standard and extended resection of pancreatic head cancer, no significant survival benefit was demonstrated from the prospective reports. PPPD may be superior to standard PD in respect to nutrition and quality of life without any deleterious effect upon long term survival or tumor recurrence. New surgical treatment modalities including modified extended pancreatectomy, neoadjuvant chemotherapy, and radical antegrade modular distal pancreatectomy have been tried to improve the patients' survival. However, early diagnosis and treatment remain as key factors for the cure of pancreatic cancer irrespective of various surgical trials. PMID:18349571

  16. Genetic abnormalities in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Zamboni Giuseppe

    2003-01-01

    Full Text Available Abstract The incidence and mortality of pancreatic adenocarcinoma are nearly coincident having a five-year survival of less than 5%. Enormous advances have been made in our knowledge of the molecular alterations commonly present in ductal cancer and other pancreatic malignancies. One significant outcome of these studies is the recognition that common ductal cancers have a distinct molecular fingerprint compared to other nonductal or endocrine tumors. Ductal carcinomas typically show alteration of K-ras, p53, p16INK4, DPC4 and FHIT, while other pancreatic tumor types show different aberrations. Among those tumors arising from the exocrine pancreas, only ampullary cancers have a molecular fingerprint that may involve some of the same genes most frequently altered in common ductal cancers. Significant molecular heterogeneity also exists among pancreatic endocrine tumors. Nonfunctioning pancreatic endocrine tumors have frequent mutations in MEN-1 and may be further subdivided into two clinically relevant subgroups based on the amount of chromosomal alterations. The present review will provide a brief overview of the genetic alterations that have been identified in the various subgroups of pancreatic tumors. These results have important implications for the development of genetic screening tests, early diagnosis, and prognostic genetic markers.

  17. Radiologic evaluation of pancreatic pseudocyst

    International Nuclear Information System (INIS)

    Pancreatic pseudocyst is a collection of necrotic tissue, old blood and secretions that escaped from the pancreas damaged by pancreatitis, trauma and chronic alcoholism. There is no epithelial cell lining the cystic wall. With the advent of ultrasound and CT more accurate diagnosis can be made. Our study was carried out to analyse the radiological and clinical findings of 32 cases of pancreatic pseudocysts confirmed at Wonju College of Medicine Yonsei University from Jan. 1979 to Aug. 1986. The results are as follows: 1. Male to female ratio was 4.3:1 Incidence was the most common in 4th decades. 2. The most frequent symptom was epigastric pain (100%). 3. In a total of 32 cases, 15 cases had a underlying cause of pancreatitis, 9 cases abdominal trauma. 4. In laboratory findings, serum amylase level was elevated in 23 cases, leucocytosis in 10 cases. 5. On chest films, the lungs were mostly normal. Soft tissue mass density in 12 cases was the most common finding on abdomen films. 6. UGI series were helpful in directing attention by pancreatic pseudocysts' location and size. 7. Ultrasonogram using primary procedure for the detection of pseudocyst (23 cases) disclosed anechoic lesion in 8 cases, mixed echo lesion in 15 cases. Mixed echo patterns, in terms of internal echo patters, were echogenic spots (8 cases), septation and echogenic spots (3 cases), fluid-fluid level (3 cases), etc. 8. CT scanning is the best imaging procedure, providing detailed morphologic information about the pancreatic pseudocyst and surrounding tissue.

  18. Pancreatic multicenter ultrasound study (PAMUS)

    International Nuclear Information System (INIS)

    Aim: To describe the typical CEUS pattern of pancreatic lesions and to evaluate the diagnostic accuracy of Contrast-enhanced ultrasound (CEUS) in their characterization. Materials and methods: All US and CEUS examinations of focal pancreatic masses performed in six centers during a period of five years were reviewed. Inclusion criteria were: focal pancreatic mass pathologically proved, visible at ultrasound (US) and studied with CEUS. All lesions were then evaluated for size, aspect and enhancement pattern. Sensitivity, specificity, positive and negative predictive values with 95% CIs were calculated to define diagnostic accuracy of CEUS in respect to pathology. Diagnostic confidence of US and CEUS, discerning between benign and malignant lesions, were represented by using ROC (receiver operating characteristics) curves. Agreement was evaluated by means of k statistics. Results: 1439 pancreatic lesions were included. At CEUS the lesions were divided into solid (89%) and cystic (12%) masses and classified into six and eight categories, respectively. Among the solid lesions, adenocarcinomas were characterized with an accuracy of 87.8%. Among the cystic lesions, cystic tumors were diagnosed with an accuracy of 97.1%. ROC curve area increased from 0.637 for US to 0.877 for CEUS (p < 0.0001). Inter-observer agreement was slightly higher for solid (k = 0.78) than cystic (k = 0.62) lesions. In none of the centers side effects were reported. Conclusion: CEUS is accurate in the characterization of pancreatic lesions. CEUS should be considered as a complementary imaging method for pancreatic lesions characterization.

  19. Radiologic evaluation of pancreatic pseudocyst

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, T. H.; Kim, Y. J.; Hong, I. S.; Kim, M. S.; Sung, K. J. [Yeonsei University Wonju College of Medicine, Wonju (Korea, Republic of)

    1986-12-15

    Pancreatic pseudocyst is a collection of necrotic tissue, old blood and secretions that escaped from the pancreas damaged by pancreatitis, trauma and chronic alcoholism. There is no epithelial cell lining the cystic wall. With the advent of ultrasound and CT more accurate diagnosis can be made. Our study was carried out to analyse the radiological and clinical findings of 32 cases of pancreatic pseudocysts confirmed at Wonju College of Medicine Yonsei University from Jan. 1979 to Aug. 1986. The results are as follows: 1. Male to female ratio was 4.3:1 Incidence was the most common in 4th decades. 2. The most frequent symptom was epigastric pain (100%). 3. In a total of 32 cases, 15 cases had a underlying cause of pancreatitis, 9 cases abdominal trauma. 4. In laboratory findings, serum amylase level was elevated in 23 cases, leucocytosis in 10 cases. 5. On chest films, the lungs were mostly normal. Soft tissue mass density in 12 cases was the most common finding on abdomen films. 6. UGI series were helpful in directing attention by pancreatic pseudocysts' location and size. 7. Ultrasonogram using primary procedure for the detection of pseudocyst (23 cases) disclosed anechoic lesion in 8 cases, mixed echo lesion in 15 cases. Mixed echo patterns, in terms of internal echo patters, were echogenic spots (8 cases), septation and echogenic spots (3 cases), fluid-fluid level (3 cases), etc. 8. CT scanning is the best imaging procedure, providing detailed morphologic information about the pancreatic pseudocyst and surrounding tissue.

  20. Pancreatic Involvement in Salmonella Infection

    Directory of Open Access Journals (Sweden)

    Pezzilli R

    2003-11-01

    Full Text Available CONTEXT: Salmonella has been identified as a causative agent of acute pancreatitis. OBJECTIVE: We prospectively evaluated the frequency of acute pancreatitis, pancreatic enzyme elevation and morphological pancreatic abnormalities in patients with Salmonella infection. SUBJECTS: Thirty consecutive patients with salmonellosis (Salmonella enterica serovar Enteritidis: n=25; Salmonella enterica serovar Typhimurium: n=5 and 30 sex- and age-matched healthy subjects were studied. MAIN OUTCOME MEASURES: All subjects underwent serum amylase and lipase determination and ultrasonography. RESULTS: None of the subjects developed acute pancreatitis. Two patients (6.7% and two controls showed serum amylase activity above the upper reference limit whereas, in five patients (16.7% and one control subject (3.3%, the serum lipase activity appeared above the upper reference limit. Salmonella infection significantly increased serum activity of lipase (P less than 0.001 while it did not significantly affect serum amylase levels (P=0.204. Serum lipase activity was significantly higher in patients infected by Salmonella enterica serovar Typhimurium than in those infected by Salmonella enterica serovar Enteritidis (P=0.012. Ultrasonography did not show pancreatic abnormalities in any of the subjects. CONCLUSIONS: Our data demonstrated an elevation of serum lipase activity in gastroenteritis due to Salmonella infection, but this elevation does not seem to have clinical significance. The elevation of serum lipase seems to be particularly related to infection from Salmonella enterica serovar Typhimurium.

  1. Early Developmental Perturbations in a Human Stem Cell Model of MODY5/HNF1B Pancreatic Hypoplasia

    Directory of Open Access Journals (Sweden)

    Adrian Kee Keong Teo

    2016-03-01

    Full Text Available Patients with an HNF1BS148L/+ mutation (MODY5 typically exhibit pancreatic hypoplasia. However, the molecular mechanisms are unknown due to inaccessibility of patient material and because mouse models do not fully recapitulate MODY5. Here, we differentiated MODY5 human-induced pluripotent stem cells (hiPSCs into pancreatic progenitors, and show that the HNF1BS148L/+ mutation causes a compensatory increase in several pancreatic transcription factors, and surprisingly, a decrease in PAX6 pancreatic gene expression. The lack of suppression of PDX1, PTF1A, GATA4, and GATA6 indicates that MODY5-mediated pancreatic hypoplasia is mechanistically independent. Overexpression studies demonstrate that a compensatory increase in PDX1 gene expression is due to mutant HNF1BS148L/+ but not wild-type HNF1B or HNF1A. Furthermore, HNF1B does not appear to directly regulate PAX6 gene expression necessary for glucose tolerance. Our results demonstrate compensatory mechanisms in the pancreatic transcription factor network due to mutant HNF1BS148L/+ protein. Thus, patients typically develop MODY5 but not neonatal diabetes despite exhibiting pancreatic hypoplasia.

  2. Radiotherapy in pancreatic cancer

    International Nuclear Information System (INIS)

    Purpose and approach: to summarize the current knowledge on the role of radiotherapy in the treatment of pancreatic ductal adenocarcinoma (PDAC). The results of meta-analyses, phase III-studies, and phase II-studies using chemoradiation (CRT) and chemotherapy for resectable and non-resectable PDAC are reviewed. Results and conclusion: the role of CRT is undefined in the adjuvant setting but there may be a role as additive treatment after R1 resection. Locally advanced borderline resectable tumors may shrink down and be subject to potentially curative resections. In locally advanced clearly unresectable cancers the effect of CRT as well as chemotherapy is poorly defined and the sequence of chemotherapy and CRT should be re-evaluated. Patients with PDAC should always be treated within studies to identify optimal treatment results. (orig.)

  3. Simultaneous characterization of pancreatic stellate cells and other pancreatic components within three-dimensional tissue environment during chronic pancreatitis

    Science.gov (United States)

    Hu, Wenyan; Fu, Ling

    2013-05-01

    Pancreatic stellate cells (PSCs) and other pancreatic components that play a critical role in exocrine pancreatic diseases are generally identified separately by conventional studies, which provide indirect links between these components. Here, nonlinear optical microscopy was evaluated for simultaneous characterization of these components within a three-dimensional (3-D) tissue environment, primarily based on multichannel detection of intrinsic optical emissions and cell morphology. Fresh rat pancreatic tissues harvested at 1 day, 7 days, and 28 days after induction of chronic pancreatitis were imaged, respectively. PSCs, inflammatory cells, blood vessels, and collagen fibers were identified simultaneously. The PSCs at day 1 of chronic pancreatitis showed significant enlargement compared with those in normal pancreas (ppancreatic components coincidently within 3-D pancreatic tissues. It is a prospect for intravital observation of dynamic events under natural physiological conditions, and might help uncover the key mechanisms of exocrine pancreatic diseases, leading to more effective treatments.

  4. Diagnosis of pancreatitis in dogs and cats.

    Science.gov (United States)

    Xenoulis, P G

    2015-01-01

    Pancreatitis is the most common disorder of the exocrine pancreas in both dogs and cats. Ante-mortem diagnosis of canine and feline pancreatitis can be challenging. The clinical picture of dogs and cats with pancreatitis varies greatly (from very mild to severe or even fatal) and is characterised by non-specific findings. Complete blood count, serum biochemistry profile and urinalysis should always be performed in dogs and cats suspected of having pancreatitis, although findings are not-specific for pancreatitis. Serum amylase and lipase activities and trypsin-like immunoreactivity (TLI) concentrations have no or only limited clinical value for the diagnosis of pancreatitis in either dogs or cats. Conversely, serum pancreatic lipase immunoreactivity (PLI) concentration is currently considered to be the clinicopathological test of choice for the diagnosis of canine and feline pancreatitis. Abdominal radiography is a useful diagnostic tool for the exclusion of other diseases that may cause similar clinical signs to those of pancreatitis. Abdominal ultrasonography can be very useful for the diagnosis of pancreatitis, but this depends largely on the clinician's experience. Histopathological examination of the pancreas is considered the gold standard for the diagnosis and classification of pancreatitis, but it is not without limitations. In clinical practice, a combination of careful evaluation of the animal's history, serum PLI concentration and abdominal ultrasonography, together with pancreatic cytology or histopathology when indicated or possible, is considered to be the most practical and reliable means for an accurate diagnosis or exclusion of pancreatitis compared with other diagnostic modalities. PMID:25586803

  5. Walled-off pancreatic necrosis and other current concepts in the radiological assessment of acute pancreatitis*

    OpenAIRE

    Cunha, Elen Freitas de Cerqueira; Rocha, Manoel de Souza; Pereira, Fábio Payão; Blasbalg, Roberto; Baroni, Ronaldo Hueb

    2014-01-01

    Acute pancreatitis is an inflammatory condition caused by intracellular activation and extravasation of inappropriate proteolytic enzymes determining destruction of pancreatic parenchyma and peripancreatic tissues. This is a fairly common clinical condition with two main presentations, namely, endematous pancreatitis - a less severe presentation -, and necrotizing pancreatitis - the most severe presentation that affects a significant part of patients. The radiological evaluation, particularly...

  6. Inflammation, Autophagy, and Obesity: Common Features in the Pathogenesis of Pancreatitis and Pancreatic Cancer

    OpenAIRE

    Gukovsky, Ilya; Ning LI; Todoric, Jelena; Gukovskaya, Anna; Karin, Michael

    2013-01-01

    Inflammation and autophagy are cellular defense mechanisms. When these processes are deregulated (deficient or overactivated) they produce pathologic effects, such as oxidative stress, metabolic impairments, and cell death. Unresolved inflammation and disrupted regulation of autophagy are common features of pancreatitis and pancreatic cancer. Furthermore, obesity, a risk factor for pancreatitis and pancreatic cancer, promotes inflammation and inhibits or deregulates autophagy, creating an env...

  7. Autophagy Inhibition Dysregulates TBK1 Signaling and Promotes Pancreatic Inflammation.

    Science.gov (United States)

    Yang, Shenghong; Imamura, Yu; Jenkins, Russell W; Cañadas, Israel; Kitajima, Shunsuke; Aref, Amir; Brannon, Arthur; Oki, Eiji; Castoreno, Adam; Zhu, Zehua; Thai, Tran; Reibel, Jacob; Qian, Zhirong; Ogino, Shuji; Wong, Kwok K; Baba, Hideo; Kimmelman, Alec C; Pasca Di Magliano, Marina; Barbie, David A

    2016-06-01

    Autophagy promotes tumor progression downstream of oncogenic KRAS, yet also restrains inflammation and dysplasia through mechanisms that remain incompletely characterized. Understanding the basis of this paradox has important implications for the optimal targeting of autophagy in cancer. Using a mouse model of cerulein-induced pancreatitis, we found that loss of autophagy by deletion of Atg5 enhanced activation of the IκB kinase (IKK)-related kinase TBK1 in vivo, associated with increased neutrophil and T-cell infiltration and PD-L1 upregulation. Consistent with this observation, pharmacologic or genetic inhibition of autophagy in pancreatic ductal adenocarcinoma cells, including suppression of the autophagy receptors NDP52 or p62, prolonged TBK1 activation and increased expression of CCL5, IL6, and several other T-cell and neutrophil chemotactic cytokines in vitro Defective autophagy also promoted PD-L1 upregulation, which is particularly pronounced downstream of IFNγ signaling and involves JAK pathway activation. Treatment with the TBK1/IKKε/JAK inhibitor CYT387 (also known as momelotinib) not only inhibits autophagy, but also suppresses this feedback inflammation and reduces PD-L1 expression, limiting KRAS-driven pancreatic dysplasia. These findings could contribute to the dual role of autophagy in oncogenesis and have important consequences for its therapeutic targeting. Cancer Immunol Res; 4(6); 520-30. ©2016 AACR. PMID:27068336

  8. The City Mouse and the Country Mouse

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Once two mice (老鼠) were good friends. One lived in the city, the other lived in the country (乡村). After many years, the city mouse came to see the country mouse. The country mouse took him to his house in a field. He gave him the nicest food that he could find. The city mouse said,

  9. Loss of Periostin Results in Impaired Regeneration and Pancreatic Atrophy after Cerulein-Induced Pancreatitis.

    Science.gov (United States)

    Hausmann, Simone; Regel, Ivonne; Steiger, Katja; Wagner, Nadine; Thorwirth, Manja; Schlitter, Anna M; Esposito, Irene; Michalski, Christoph W; Friess, Helmut; Kleeff, Jörg; Erkan, Mert

    2016-01-01

    The extracellular matrix molecule periostin (POSTN, encoded by POSTN), which is secreted by activated pancreatic stellate cells, has important functions in chronic pancreatitis and pancreatic cancer. However, the role of POSTN in acute pancreatitis and subsequent regeneration processes has not been addressed so far. We analyzed the function of POSTN in pancreatic exocrine regeneration after the induction of a severe acute pancreatitis. Postn-deficient mice and wild-type control animals received repetitive cerulein injections, and a detailed histologic analysis of pancreatic tissues was performed. Although there was no difference in pancreatitis severity in the acute inflammatory phase, the recovery of the exocrine pancreas was massively impaired in Postn-deficient mice. Loss of Postn expression was accompanied by strong pancreatic atrophy and acinar-to-adipocyte differentiation, which was also reflected in gene expression patterns. Our data suggest that POSTN is a crucial factor for proper exocrine lineage-specific regeneration after severe acute pancreatitis. PMID:26632158

  10. Mouse lymphotoxin.

    Science.gov (United States)

    Trivers, G; Braungart, D; Leonard, E J

    1976-07-01

    The addition of PHA to C3H mouse spleen cells in tissue culture led to the production of lymphotoxin (LT). Cytotoxicity was assayed by addition of the culture fluids to syngeneic target cells labeled with tritiated thymidine; after an incubation period of 72 hr the amount of radioactivity released into the supernatant was measured. The LT activity in unfractionated culture fluids survived lyophilization, remained unchanged for many weeks at 4 degrees C, and progressively decreased on heating at 56 degrees C for periods from 1 to 9 hr. Based on the G-200 Sephadex distribution coefficients for several preparations, the m.w. of mouse lymphotoxin was about 41,000 daltons. Lymphotoxin from three different spleen cell production runs was recovered from isoelectric focusing columns in sharply focused peaks, the pH of which ranged from 4.4 to 4.8. PMID:1084362

  11. Endoscopic ultrasound features of chronic pancreatitis

    DEFF Research Database (Denmark)

    Rana, Surinder Singh; Vilmann, Peter

    2015-01-01

    As endoscopic ultrasound (EUS) is the most sensitive imaging modality for diagnosing pancreatic disorders, it can demonstrate subtle alterations in the pancreatic parenchymal and ductal structure even before traditional imaging and functional testing demonstrate any abnormality. In spite of this...

  12. Angiographic diagnosis and differentiation of pancreatic tumours

    International Nuclear Information System (INIS)

    In an 8-year period (1971-1978) 92 patients were examined because of suspected pancreatic tumour and the following symptoms were found: in 13 cases (14.1%) inoperable pancreatic carcinoma, in 2 cases insuloma, in 5 patients pancreatic cyst, in 5 cases pancreatitis, in one patient pancreatic abscess and in 12 cases alterations in the environing organs. The observed angiographic symptoms are described in detail. Except the richly vascularized tumour grown together with the stomach all pancreatic carcinomas were poor in vessels and they caused tumourous invasions in the greater arteries. The obliteration of the lienal vein, as well as the development of mesenteric venous collateral circulation signify an inoperable stage. The signs of the differential diagnosis of the pancreatitis and the carcinoma are dealt with in detail. In case of secondary pancreatic tumours - not even detectable by post-mortem examination - the angiographic signs are to be taken into consideration. (author)

  13. Somatostatin receptor expression and biological functions in endocrine pancreatic cells: review based on a doctoral thesis.

    Science.gov (United States)

    Ludvigsen, Eva

    2007-01-01

    Type 1 diabetes is resulting from the selective destruction of insulin-producing betacells within the pancreatic islets. Somatostatin acts as an inhibitor of hormone secretion through specific receptors (sst1-5). All ssts were expressed in normal rat and mouse pancreatic islets, although the expression intensity and the co-expression pattern varied between ssts as well as between species. This may reflect a difference in response to somatostatin in islet cells of the two species. The Non-Obese Diabetic (NOD) mouse model is an experimental model of type 1 diabetes, with insulitis accompanied by spontaneous hyperglycaemia. Pancreatic specimens from NOD mice at different age and stage of disease were stained for ssts. The islet cells of diabetic NOD mice showed increased islet expression of sst2-5 compared to normoglycemic NOD mice. The increase in sst2-5 expression in the islets cells may suggest either a contributing factor in the process leading to diabetes, or a defense response against ongoing beta-cell destruction. Somatostatin analogues were tested on a human endocrine pancreatic tumour cell line and cultured pancreatic islets. Somatostatin analogues had an effect on cAMP accumulation, chromogranin A secretion and MAP kinase activity in the cell line. Treatment of rat pancreatic islets with somatostatin analogues with selective receptor affinity was not sufficient to induce an inhibition of insulin and glucagon secretion. However, a combination of selective analogues or non-selective analogues via costimulation of receptors can cause inhibition of hormone production. For insulin and glucagon, combinations of sst2 + sst5 and sst1 + sst2, respectively, showed a biological effect. In summary, knowledge of islet cell ssts expression and the effect of somatostatin analogues with high affinity to ssts may be valuable in the future attempts to influence beta-cell function in type 1 diabetes mellitus, since down-regulation of beta-cell function may promote survival of

  14. Case of severe acute pancreatitis with near total pancreatic necrosis diagnosed by dynamic CT scanning

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Kazunori; Kakugawa, Yoichiro; Amikura, Katsumi; Miyagawa, Kikuo; Matsuno, Seiki; Sato, Toshio

    1987-09-01

    A 42 year-old woman with severe acute pancreatitis had drainage of the pancreatic bed, cholecystostomy and jejunostomy on admission, but symptoms were not improved. Fourteen days after admission, clinical sepsis and septisemia were recognized. Dynamic CT scanning of the pancreas showed near total pancreatic necrosis. Symptoms were improved after necrosectomy of the pancreas and debridement of the peripancreatic necrotic tissue were performed. Our experience suggests the usefulness of dynamic CT scanning for detection of pancreatic necrosis in severe acute pancreatitis.

  15. Isolated Pancreatic Tuberculosis Mimicking Focal Pancreatitis and Causing Segmental Portal Hypertension

    OpenAIRE

    Rana, Surinder S.; Deepak K Bhasin; Chalapathi Rao; Kartar Singh

    2010-01-01

    Context Isolated pancreatic tuberculosis is a common mimicker of pancreatic malignancy and a common presentation is abdominal pain. However, segmental portal hypertension is very uncommon. Case report A case of isolated pancreatic tuberculosis mimicking focal pancreatitis and causing segmental portal hypertension is presented. Conclusion A histological or microbiological diagnosis of the presence of pancreatic masses is necessary to detect potentially treatable diseases, such as tuberculosis,...

  16. A Case of Pancreatic Cancer in the Setting of Autoimmune Pancreatitis with Nondiagnostic Serum Markers

    OpenAIRE

    Chandrasegaram, Manju D; Chiam, Su C.; Nguyen, Nam Q; Andrew Ruszkiewicz; Adrian Chung; Neo, Eu L; Chen, John W; Worthley, Christopher S.; Brooke-Smith, Mark E.

    2013-01-01

    Background. Autoimmune pancreatitis (AIP) often mimics pancreatic cancer. The diagnosis of both conditions is difficult preoperatively let alone when they coexist. Several reports have been published describing pancreatic cancer in the setting of AIP. Case Report. The case of a 53-year-old man who presented with abdominal pain, jaundice, and radiological features of autoimmune pancreatitis, with a “sausage-shaped” pancreas and bulky pancreatic head with portal vein impingement, is presented. ...

  17. CLINICAL STUDY ON ACUTE PANCREATITIS

    Directory of Open Access Journals (Sweden)

    Suhaib Rehaman

    2015-07-01

    Full Text Available INTRODUCTION : Early diagnosis and severity evaluation on patients with acute pancreatitis are very important due to its potential morbidity and mortality. Given the wide spectrum of disease seen, the care of patients with pancreatitis must be highly individualized. Sev eral clinical, laboratory and radiologic factors and many scoring systems have been proposed for outcome prediction. AIMS AND OBJECTIVES: To study the symptomatology, clinical presentation and management in pancreatitis . To study the severity of acute panc reatitis according to Glasgow Scale . METHODS: Present study includes consecutive 38 patients hospitalized in CSI Holdsworth Memorial Hospital over the period of 2 years. All patients were thoroughly investigated and were stratified according to the Glasgow criteria. Data was collected on complications, investigations and interventions undertaken, outcome, duration of stay in hospital and ICU. STATISTICAL ANALYSIS USED: Descriptive, Chi square tests, Crosstabs (Contingency coefficient analysis . RESULTS : Mean age of presentation in our study was 43.1 years. There was a male predominance accounting for 68.4% compared to 31.6% females. Alcohol was the main etiological factor in about 50% of the patients. Sensitivity to S. amylase was about 100%. Accuracy of USG abdomen in diagnosing pancreatitis was about 88.5%. Ascitis was the commonest complication seen in 13.2%. Mean duration of hospital stay was 6.2 days. The patient were stratified according to Glasgow scoring system into mild (0 - 3 and severe (>3 panc reatitis. In our study 32 people were graded with mild pancreatitis, all improved and in 6 people who were graded with severe pancreatitis, 83.3 % improved and 2.6% expired because of complications. Test statistics showed Contingency coefficient 0.355 and P 0.019 (NS. CONCLUSION : Glasgow scoring system remains a valid predicting system for the outcome in patients with acute pancreatitis. It is simple easy to apply with

  18. Endoscopic diagnostic of chronic pancreatitis.

    Science.gov (United States)

    Cubranić, Aleksandar; Dintinjana, Renata Dobrila; Vanis, Nenad

    2014-12-01

    Chronic pancreatitis is defined as a continuous inflammatory pancreatic disease, one characterized by irreversible morphological changes, often associates with pain and sometimes with the loss of endocrine and exocrine function. As a histological confirmation of chronic pancreatitis is often unavailable, the diagnosis is traditionally based on imaging methods such as computerized tomography (CT) or endoscopic retrograde cholangiopancreatography (ERCP), and recently magnetic resonance cholangiopancreatography (MRCP) as a noninvasive alternative to ERCP. Developments in the classification system of CP include the Marseille classification of 1963 which offered histopathologic criteria for CP, the Cambridge classification of 1984 which introduced imaging features of computed tomography (CT), transabdominal ultrasound (TUS) and endoscopic retrograde cholangiopancreatography (ERCP) for classification of CP as well as Rosemont classification system of 2007 which presented the endoscopic ultrasonography diagnosis of CP. Endoscopic ultra-sonography (EUS) was first introduced as a diagnostic method for evaluation of pancreatic disease in 1986. It has experienced significant improvements since then and allowed for an alternative approach in diagnosing patients with pancreatic diseases. In patients with suspected pancreatic masses EUS-guided fine needle aspiration (EUS-FNA) is the best method for obtaining tissue diagnosis and differentiating CP from pancreatic carcinoma. The recent studies indicate that EUS is the method of choice when compared with other imaging methods such as ERCP because it frequently provides more accurate diagnostics. The aim of this review is to discuss the findings in endoscopic diagnostics up to the present moment and to indicate advantages, limitations and possible complications along with the current recommendations in CP diagnostics. PMID:25842773

  19. Lessons Learnt in Management of Acute Pancreatitis

    OpenAIRE

    Deshpande Aparna; Velhal Rishikesh; Thanky Harsh; Soman Sundeep; Shah Ritesh

    2008-01-01

    Objective Acute Pancreatitis continues to be a confounding clinical problem and can pose a formidable challenge in its management. This invited review discusses the various clinical studies done while managing cases of acute pancreatitis and the possible avenues for further studies. Method Clinical studies done on various aspects of pancreatitis viz. severity prediction using bedside index of severity in acute pancreatitis score and its validation in Indian patients, current status of interve...

  20. Prevention and Intervention Strategies in Acute Pancreatitis

    OpenAIRE

    Besselink, M.G.H.

    2008-01-01

    Acute pancreatitis is a common, costly, potentially lethal, and poorly understood disease, mostly caused by gallstones. In the past decade the incidence of acute pancreatitis in the Netherlands increased by 50% to over 3400 admissions in 2006, most likely due to an increase of gallstone disease. About 20% of patients will develop severe acute pancreatitis, a disease characterized by organ failure and/or pancreatic necrosis, resulting in a high mortality rate. Because the incidence of acute pa...

  1. Acute pancreatitis - severity classification, complications and outcome

    OpenAIRE

    Andersson, Bodil

    2010-01-01

    Acute pancreatitis, with an annual incidence of approximately 35 per 100 000 inhabitants in Sweden, is in most cases mild and self-limiting. Severe acute pancreatitis, affecting 10-15% of the cases is, however, associated with severe complications and even death. The optimal management of acute pancreatitis includes accurate early prediction of the disease severity. The aims of this thesis were to investigate early severity classification, complications and outcome in acute pancreatitis patie...

  2. Diet and risk of acute pancreatitis

    OpenAIRE

    Oskarsson, Viktor

    2016-01-01

    Acute pancreatitis is a sudden inflammation of the pancreas. It has a broad spectrum of clinical outcomes, ranging from mild and self-limiting to severe and potentially fatal, and is often followed by recurrent attacks and/or progression to a chronic disease state (so-called chronic pancreatitis); especially if it is classified as non-gallstone-related acute pancreatitis. Alcohol abuse is considered to be the most important risk factor for non-gallstone-related acute pancreatitis. Even though...

  3. Acute Pancreatitis: Surgery, Pathophysiology and Probiotic Prophylaxis

    OpenAIRE

    van Minnen, L. P.

    2006-01-01

    Acute pancreatitis is a challenging disease with a clinical course that is often difficult to predict. In severe acute pancreatitis, mortality increases significantly if intestinal bacteria translocate from the intestine and infect pancreatic necrosis. Surgical and prophylactic treatment strategies are challenged by complex pathophysiology of the disease. This thesis addresses some key aspects of acute pancreatitis: surgical management, pathophysiology and probiotic prophylaxis. Outcome in pa...

  4. Minimally invasive treatment of infected pancreatic necrosis

    OpenAIRE

    Wroński, Marek; Cebulski, Włodzimierz; Słodkowski, Maciej; Krasnodębski, Ireneusz W.

    2014-01-01

    Infected pancreatic necrosis is a challenging complication that worsens prognosis in acute pancreatitis. For years, open necrosectomy has been the mainstay treatment option in infected pancreatic necrosis, although surgical debridement still results in high morbidity and mortality rates. Recently, many reports on minimally invasive treatment in infected pancreatic necrosis have been published. This paper presents a review of minimally invasive techniques and attempts to define their role in t...

  5. Acute pancreatitis in children and adolescents

    OpenAIRE

    SUZUKI, Mitsuyoshi; Sai, Jin Kan; Shimizu, Toshiaki

    2014-01-01

    In this Topic Highlight, the causes, diagnosis, and treatment of acute pancreatitis in children are discussed. Acute pancreatitis should be considered during the differential diagnosis of abdominal pain in children and requires prompt treatment because it may become life-threatening. The etiology, clinical manifestations, and course of acute pancreatitis in children are often different than in adults. Therefore, the specific features of acute pancreatitis in children must be considered. The e...

  6. The outcome of management of acute pancreatitis

    OpenAIRE

    T. R. Nagarjuna; Prasad H. L.

    2016-01-01

    Background: Acute pancreatitis is a potentially life threatening disease. The initial management of patients with pancreatitis focuses on establishing the diagnosis, estimating its severity, addressing the major symptoms (i.e., pain, nausea, vomiting, and hypovolemia), and limiting its progression. Therefore, the present study has been undertaken to record the outcome of management of acute pancreatitis. Methods: The study population consisted of 40 cases of acute pancreatitis that fulfill...

  7. Animal models for investigating chronic pancreatitis

    OpenAIRE

    Aghdassi Alexander A; Mayerle Julia; Christochowitz Sandra; Weiss Frank U; Sendler Matthias; Lerch Markus M

    2011-01-01

    Abstract Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in t...

  8. Pathophysiology of alcoholic pancreatitis: An overview

    Institute of Scientific and Technical Information of China (English)

    Parimal Chowdhury; Priya Gupta

    2006-01-01

    Use of alcohol is a worldwide habit regardless of socioeconomic background. Heavy alcohol consumption is a potential risk factor for induction of pancreatitis. The current review cites the updated literature on the alcohol metabolism, its effects on gastrointestinal and pancreatic function and in causing pancreatic injury, genetic predisposition of alcohol induced pancreatitis. Reports describing prospective mechanisms of action of alcohol activating the signal transduction pathways, induction of oxidative stress parameters through the development of animal models are being presented.

  9. Transgastric Pancreatic Necrosectomy: How I Do It.

    Science.gov (United States)

    Zyromski, Nicholas J; Nakeeb, Attila; House, Michael G; Jester, Andrea L

    2016-02-01

    Necrotizing pancreatitis is a serious medical problem that often requires intervention to debride necrotic pancreatic and peripancreatic tissue. Recently, minimally invasive approaches have been applied to pancreatic necrosectomy. The purpose of this report is to review the history of transgastric pancreatic debridement, identify appropriate patient selection criteria, and highlight technical "pearls." We present this subject matter in the context of our own clinical experience, with a primary focus on a "How I Do It" type of technical description. PMID:26691148

  10. Venous Complications of Pancreatitis: A Review

    OpenAIRE

    Yashant Aswani; Priya Hira

    2015-01-01

    Pancreatitis is notorious to cause vascular complications. While arterial complications include pseudoaneurysm formation with a propensity to bleed, venous complications can be quite myriad. Venous involvement in pancreatitis often presents with thrombosis. From time to time case reports and series of unusual venous complications associated with pancreatitis have, however, been described. In this article, we review multitudinous venous complications in the setting of pancreatitis and propose ...

  11. Drug induced acute pancreatitis: Does it exist?

    OpenAIRE

    Tenner, Scott

    2014-01-01

    As the incidence of acute pancreatitis continues to rise, establishing the etiology in order to prevent recurrence is important. Although the etiology of acute pancreatitis is not difficult in the majority of patients, almost a quarter of patients are initially labeled as having idiopathic acute pancreatitis. When confronted with a patient with acute pancreatitis and no clear etiology defined as an absence alcoholism, gallstones (ultrasound and/or MRI), a normal triglyceride level, and absenc...

  12. STUDY ANALYSIS OF ACUTE PANCREATITIS BY CT

    OpenAIRE

    Bulabai; Hemhnath

    2015-01-01

    AIM: Study analysis of pancreatitis by computed tomography in terms of morphology of pancreas in acute pancreatitis, complications of pancreatitis and duration of hospital stay by grading the severity of disease using Modified CT severity index. MATERIAL AND METHOD: This prospective study of 100 patients suspected of pancreatitis was evaluated with multidetector spiral CT scanner, somatom, (Spirit) Siemens at Tertiary care center, for period of one year. The series consists of pat...

  13. Eosinophilic Pancreatitis Diagnosed With Endoscopic Ultrasound

    OpenAIRE

    Kakodkar, Samir; Omar, Hina; Cabrera, Julio; Chi, Kenneth

    2015-01-01

    Eosinophilic pancreatitis (EP) is a rare clinical entity, and few cases have been reported. It usually presents on imaging as a pancreatic mass leading to common bile duct obstruction and jaundice. Since it can mimic a malignancy, eosinophilic pancreatitis is often diagnosed after “false positive” pancreatic resections. To our knowledge, we report the only known case of EP in which the diagnosis was made by fine needle aspiration and core biopsy of the pancreas during EUS, sparing the patient...

  14. Exocrine pancreatic function in diabetes mellitus.

    OpenAIRE

    Dandona, P; Freedman, D B; Foo, Y.; Perkins, J.; Katrak, A; Mikhailidis, D P; Rosalki, S B; Beckett, A. G.

    1984-01-01

    An investigation of serum immunoreactive trypsin concentration and pancreatic isoamylase activity in patients with diabetes mellitus has shown that exocrine pancreatic deficit is maximal in insulin dependent diabetics, intermediate in those controlled with sulphonylureas, and absent in patients controlled with biguanides or diet or both. A significant correlation between the serum concentrations of both these pancreatic enzymes and C peptide was found. Serum pancreatic enzyme concentrations w...

  15. Molecular regulation of pancreatic stellate cell function

    OpenAIRE

    Jaster Robert

    2004-01-01

    Abstract Until now, no specific therapies are available to inhibit pancreatic fibrosis, a constant pathological feature of chronic pancreatitis and pancreatic cancer. One major reason is the incomplete knowledge of the molecular principles underlying fibrogenesis in the pancreas. In the past few years, evidence has been accumulated that activated pancreatic stellate cells (PSCs) are the predominant source of extracellular matrix (ECM) proteins in the diseased organ. PSCs are vitamin A-storing...

  16. Pancreatic Involvement in Critically ill Patients

    OpenAIRE

    Abhinav Agrawal; Sayee Sundar Alagusundarmoorthy; Sarfaraz Jasdanwala

    2015-01-01

    Elevation of pancreatic enzymes is often observed in patients admitted to intensive care units in the United States. Elevated pancreatic enzymes can occur due to acute pancreatitis or numerous non-specific reasons. Non-specific enzyme elevation can be seen in patients with head injury, acute renal failure, diabetic ketoacidosis or patients on hemodialysis. Patients with severe acute pancreatitis can be admitted to the intensive care units for intensive care or patients admitted to the intensi...

  17. Pancreatic Hyperenzymemia: Clinical Significance and Diagnostic Approach

    OpenAIRE

    Luca Frulloni; Franca Patrizi; Laura Bernardoni; Giorgio Cavallini

    2005-01-01

    An increase in the serum concentration of pancreatic enzymes (amylase and lipase) is commonly an expression of inflammatory or neoplastic pancreatic disease. However, an elevation of pancreatic enzymes, generally mild, may be a non-specific phenomenon without any clinical implication. The large spreading of the serum pancreatic enzymes dosage in clinical practice, particularly in emergency rooms, results in a large number of patients with elevated amylase and/or lipase serum levels without...

  18. Cancer Stem Cells in Pancreatic Cancer

    OpenAIRE

    Karl-Walter Jauch; Hendrik Seeliger; Hanno Niess; Qi Bao; Andrea Renner; Yue Zhao; Bruns, Christiane J.

    2010-01-01

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC t...

  19. Papillocystic Variant of Acinar Cell Pancreatic Carcinoma

    Directory of Open Access Journals (Sweden)

    Jasim Radhi

    2010-01-01

    Full Text Available Acinar cell pancreatic carcinoma is a rare solid malignant neoplasm. Recent review of the literature showed occasional cases with papillary or papillocystic growth patterns, ranging from 2 to 5 cm in diameter. We report a large 10 cm pancreatic tumor with papillocystic pathology features involving the pancreatic head. The growth pattern of these tumors could be mistaken for intraductal papillary mucinous tumors or other pancreatic cystic neoplasms.

  20. Serum pancreatic lipase activity in cystic fibrosis.

    OpenAIRE

    Junglee, D; Penketh, A; Katrak, A; Hodson, M.E.; Batten, J C; Dandona, P

    1983-01-01

    Patients with cystic fibrosis have been found to have abnormal serum concentrations of immunoreactive trypsin and abnormal activities of pancreatic isoamylase. A study was undertaken to discover whether activity of pancreatic lipase is also altered in cystic fibrosis. Serum from 23 patients with cystic fibrosis was assayed for immunoreactive trypsin and pancreatic lipase. Median serum pancreatic lipase activity was significantly lower in patients with cystic fibrosis than in controls, as was ...

  1. 六味地黄丸对自发性2型糖尿病模型小鼠胰岛素表达水平的影响%Effects of Liuweidihuang pill on insulin levels in sera and pancreatic islets from spontaneous mouse models of human type 2 diabetes administrated with different doses

    Institute of Scientific and Technical Information of China (English)

    吕璐; 郑源强; 张精彩; 李斯琦; 王晓东; 尹星; 徐佳; 韩新荣; 石艳春

    2016-01-01

    目的:探讨不同剂量六味地黄丸对自发性2型糖尿病模型小鼠血清和胰岛内胰岛素表达水平的影响。方法:将6~8周龄自发性2型糖尿病模型小鼠( KK-Ay小鼠)随机分3组(无药对照组、低剂量组、高剂量组), C57 BL/6 J小鼠作为遗传对照组,各组小鼠分别给予蒸馏水或六味地黄丸灌胃15周。每周测定空腹血糖、体质量、摄食量;给药15周后,ELISA法测定小鼠外周血血清胰岛素含量,免疫荧光法和免疫组织化学法检测胰岛中胰岛素表达水平,比较各组检测结果。结果:六味地黄丸给药后,KK-Ay小鼠空腹血糖降低,体质量和摄食量得到控制;给药组小鼠血清胰岛素含量和胰岛内胰岛素表达水平明显降低,且低剂量组的降低程度比高剂量组更明显。结论:六味地黄丸对自发性2型糖尿病模型小鼠高血糖、肥胖、胰岛素抵抗具有一定的治疗作用,且低剂量组降低血清和胰岛内胰岛素水平的效果优于高剂量组。%Objective:To investigate the effects of Liuweidihuang pill on the insulin levels in sera and pancreatic islets from spontaneous mouse models of human type 2 diabetes administrated with different doses .Methods:The 6-8 week-old KK-Ay mice were randomly divided into three groups including no drug control group ,low-dose group and high-dose group,in addition C57BL/6J mice were used as a genetic control group .All the animals were given with different dose Liuweidihuang pill solutions or sterile distilled water by intragastrical administration for fifteen weeks .The fasting blood glucose ,body mass and food consumption were measured weekly .The serum insulin levels were surveyed by ELISA .And the insulin levels in the pancreas islets were detected by immunofluorescence and immunohistochemistry .Results:Decreased fasting blood glucose ,controlled body mass and food consumption ,and lower levels of insulin in the sera and

  2. Blunt pancreatic trauma: A persistent diagnostic conundrum?

    Science.gov (United States)

    Kumar, Atin; Panda, Ananya; Gamanagatti, Shivanand

    2016-02-28

    Blunt pancreatic trauma is an uncommon injury but has high morbidity and mortality. In modern era of trauma care, pancreatic trauma remains a persistent challenge to radiologists and surgeons alike. Early detection of pancreatic trauma is essential to prevent subsequent complications. However early pancreatic injury is often subtle on computed tomography (CT) and can be missed unless specifically looked for. Signs of pancreatic injury on CT include laceration, transection, bulky pancreas, heterogeneous enhancement, peripancreatic fluid and signs of pancreatitis. Pan-creatic ductal injury is a vital decision-making parameter as ductal injury is an indication for laparotomy. While lacerations involving more than half of pancreatic parenchyma are suggestive of ductal injury on CT, ductal injuries can be directly assessed on magnetic resonance imaging (MRI) or encoscopic retrograde cholangio-pancreatography. Pancreatic trauma also shows temporal evolution with increase in extent of injury with time. Hence early CT scans may underestimate the extent of injures and sequential imaging with CT or MRI is important in pancreatic trauma. Sequential imaging is also needed for successful non-operative management of pancreatic injury. Accurate early detection on initial CT and adopting a multimodality and sequential imaging strategy can improve outcome in pancreatic trauma. PMID:26981225

  3. SEVERE PANCREATITIS AFTER ENDOSCOPIC SPHYNCTEROTOMY - CLINICAL REPORT

    Directory of Open Access Journals (Sweden)

    R. Neagoe

    2010-02-01

    Full Text Available Pancreatitis remains the major complication of endoscopic retrograde cholangiopancreatography (ERCP, and hyperenzynemia after ERCP is common. Severe post-ERCP pancreatitis is rare but it demands hospitalization and sometimes interventions (percutaneous drainage or surgery due to complications. We present a case of severe post-ERCP pancreatitis wich required surgical approach, with good postoperative outcome.

  4. Treatment Options by Stage (Pancreatic Cancer)

    Science.gov (United States)

    ... affect prognosis (chance of recovery) and treatment options. Pancreatic cancer is a disease in which malignant (cancer) cells form in the ... the cancer cells in the liver are actually pancreatic cancer cells. The disease is metastatic pancreatic cancer, not liver cancer. The ...

  5. The relationship between diabetes and pancreatic cancer

    OpenAIRE

    Larsson Jörgen; Herrington Margery; Wang Feng; Permert Johan

    2003-01-01

    Abstract About 80% of pancreatic cancer patients have glucose intolerance or frank diabetes. This observation has led to the following two hypotheses: i. pancreatic cancer causes the associated diabetes and ii. the conditions associated with diabetes promote the development of pancreatic cancer. Evidence supporting both hypotheses has been accumulated in previous studies. This article reviews these studies, especially those that have been conducted recently.

  6. Retinoid signaling in pancreatic cancer, injury and regeneration.

    Directory of Open Access Journals (Sweden)

    Emily K Colvin

    Full Text Available BACKGROUND: Activation of embryonic signaling pathways quiescent in the adult pancreas is a feature of pancreatic cancer (PC. These discoveries have led to the development of novel inhibitors of pathways such as Notch and Hedgehog signaling that are currently in early phase clinical trials in the treatment of several cancer types. Retinoid signaling is also essential for pancreatic development, and retinoid therapy is used successfully in other malignancies such as leukemia, but little is known concerning retinoid signaling in PC. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the role of retinoid signaling in vitro and in vivo in normal pancreas, pancreatic injury, regeneration and cancer. Retinoid signaling is active in occasional cells in the adult pancreas but is markedly augmented throughout the parenchyma during injury and regeneration. Both chemically induced and genetically engineered mouse models of PC exhibit a lack of retinoid signaling activity compared to normal pancreas. As a consequence, we investigated Cellular Retinoid Binding Protein 1 (CRBP1, a key regulator of retinoid signaling known to play a role in breast cancer development, as a potential therapeutic target. Loss, or significant downregulation of CRBP1 was present in 70% of human PC, and was evident in the very earliest precursor lesions (PanIN-1A. However, in vitro gain and loss of function studies and CRBP1 knockout mice suggested that loss of CRBP1 expression alone was not sufficient to induce carcinogenesis or to alter PC sensitivity to retinoid based therapies. CONCLUSIONS/SIGNIFICANCE: In conclusion, retinoid signalling appears to play a role in pancreatic regeneration and carcinogenesis, but unlike breast cancer, it is not mediated directly by CRBP1.

  7. Computed tomography and the dilated pancreatic duct: An ominous sign

    Energy Technology Data Exchange (ETDEWEB)

    Palmer Gold, R.; Seaman, W.B.

    1981-01-15

    The main pancreatic duct has been visualized with both ultrasound and computed tomography. A normal pancreatic duct has been reported using CT, and controversy persists over whether a normal duct can be routinely imaged with ultrasound. The dilated pancreatic duct has always been associated with disease - usually pancreatitis or a proximal obstructing pancreatic carcinoma. In the patient with no clinical history or laboratory data suggesting pancreatitis, a dilated pancreatic duct implies a proximal tumor.

  8. Pancreatic Lesion: Malignancy or Abscess?

    Science.gov (United States)

    Shulik, Oleg; Cavanagh, Yana; Grossman, Matthew

    2016-01-01

    BACKGROUND Pancreatic abscesses are rare. They may be seen in patients with pancreatic inflammation or pancreatitis. Patients with pancreatic abscesses may have abdominal pain, fever, chills, and nausea/vomiting or an inability to eat. Presentation with alternate symptomatology is extremely unusual. CASE REPORT A 67-year-old Asian male presented with painless, afebrile obstructive jaundice and a CA 19-9 of 1732 IU. He was found to have a 3.1×2.4 cm low-density lesion in the head of the pancreas and the right lobe of the liver, suggesting malignancy. Surgical management was considered, however additional diagnostic workup, including an endoscopic retrograde cholangiopancreatography (ERCP), was performed to complete staging of the presumed mass. A smooth, 3-cm-long, tapering stricture was found it the common bile duct. It was stented from the common hepatic duct to the duodenum. Subsequent endoscopic ultrasound (EUS) evaluation of the pancreatic head lesion revealed a drainable fluid collection that was aspirated and found to contain pyogenic material on pathology. The patient's symptoms resolved, and he was subsequently managed conservatively. A repeat ERCP confirmed complete resolution of the previously visualized cystic lesion. Interestingly, laboratory values showed concomitant normalization of CA 19-9 to 40 IU. CONCLUSIONS EUS-guided biopsy is not widely regarded as a required step before surgery, in the management of patients with pancreatic masses. It is generally reserved for determination of resectability or staging, and only utilized when clinically indicated. However, this practice may be associated with an inherently significant risk of misdiagnosis and subsequent unnecessary surgery, as illustrated by this case. Malignancy was initially suspected in our patient and surgical resection was recommended. Endoscopic measures were only pursued to complete staging. We propose that EUS-guided biopsy may be a crucial diagnostic step in the management algorithm

  9. Lung Cancer Signatures in Plasma Based on Proteome Profiling of Mouse Tumor Models

    OpenAIRE

    Taguchi, Ayumu; Politi, Katerina; Pitteri, Sharon J.; Lockwood, William W; Faça, Vitor M.; Kelly-Spratt, Karen; Wong, Chee-Hong; Zhang, Qing; Chin, Alice; Park, Kwon-Sik; Goodman, Gary; Gazdar, Adi F.; Sage, Julien; Dinulescu, Daniela M.; Kucherlapati, Raju

    2011-01-01

    We investigated the potential of in-depth quantitative proteomics to reveal plasma protein signatures that reflect lung tumor biology. We compared plasma protein profiles of four mouse models of lung cancer with profiles of models of pancreatic, ovarian, colon, prostate, and breast cancer and two models of inflammation. A protein signature for Titf1/Nkx2-1, a known lineage-survival oncogene in lung cancer, was found in plasmas of mouse models of lung adenocarcinoma. An EGFR signature was foun...

  10. CHANGING TRENDS IN CHRONIC PANCREATITIS

    Directory of Open Access Journals (Sweden)

    Sreenidhi

    2014-02-01

    Full Text Available BACKGROUND: AIMS : To determine the demographic profile , to evaluate risk factors of chronic pancreatitis , frequency of complications and therapeutic modalities for management of chronic pancreatitis . METHODS : Data analyzed retrospectively from 177 patients of chronic pancreatitis admitted in the Department of Surgery in our institute between Jan 2003 & Decembe r 2012 . RESULTS : Male predominance , mean age of presentation is 32yrs , 66% with Alcohol consumption was the main risk factor , with associated diabetes and gall stones. Pain abdomen was the commonest mode of presentation , and USG sensitivity rate was 55%. P arenchymal calcification , Ductal calculi , pseudocyst were the commonest complications. Medical line of management was the initial therapy and surgical intervention was done as indicated. Number of readmissions noted. CONCLUSIONS : Although Kerala is known for highest prevalence of chronic pancreatitis in our country , it is a noted di sease & is on the rise in the state of Karnataka. Mean age of onset is older as compared to two decades ago and also a shift of etiology from tropical t o a lcoholic pancreatitis has been noted.

  11. Laparoscopic Drainage of Pancreatic Pseudocysts

    Directory of Open Access Journals (Sweden)

    Filip Eugen Târcoveanu

    2015-09-01

    Full Text Available Pancreatic pseudocyst is a complication of acute or chronic pancreatitis. The invasive treatment (surgical or endoscopic is recommended if the pseudocyst persisted for more than 6 weeks after the diagnosis and if the size is larger than 6 cm and is symptomatic. The laparoscopic techniques have been developed to provide the patient with the benefits of a minimal access alternative. The aim of this article is to analyze the postoperative results of the pancreatic pseudocyst laparoscopic surgery. We have accomplished a restrospective study using clinical and para-clinical test results and postoperative results from the patients who have been treated with laparoscopic drainage. We reported a case of a large symptomatic pseudocyst after an attack of gallstone pancreatitis. Laparoscopic cholecystectomy and extern drainage have been performed at the same time with good postoperative results. Starting with year 2000 until year 2015, 85 patients, diagnosed with pancreatic pseudocyst, have been treated in the First Surgical Clinic, University Hospital Saint Spiridon Iasi. From which only 8 have been treated with laparoscopic drainage, encountering no mortality and morbidity. Postoperative hospital stay was 9,41 days. The postoperative drainage duration was between 5 and 21 days with a mean of 7 days. Late postoperative results were good in 6 patients and mediocre in the 2 patients. Conclusion: The laparoscopic technique has all the benefits of the minimal invasive approach. Better postoperative results were seen in cysto-digestive anastomosis using a Endo GIA stapler.

  12. Radiological aspect of pancreatic pseudocysts

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Tae Sub; Lim, Sue Jin; Yoo, Hyung Sik; Suh, Jung Ho; Park, Chang Yun [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1982-06-15

    Pancreatic pseudocyst occurs as a complication of pancreatitis or trauma, which results in the escape of pancreatitis enzymes from the parenchyma or ductal system of pancreas. At that time, serum amylase may have retuned to normal level, and the patient may be subjectively asymptomatic. In this phase, the radiologic findings are relatively greater significance than laboratory data. In the conventional radiologic study, pancreatic pseudocyst have been frequently confused with other retroperitoneal mass, but recently with clinical application of ultrasound and CT scan, more accurate diagnosis can be obtained. The brief results are as follows: 1. Male to female ratio was 3 : 2 in 15 patients. Incidence was more common in young adult age. Most frequent symptom was epigastric pain, and which was noted in 11 cases of patients. 7 cases of patients had past history of abdominal trauma and past history of pancreatitis was only in 1 case. Most common laboratory findings was leukocytosis in 8 cases of patients and elevated serum amylase was also noted in 7 cases. 2. In each 5 cases of patients, plain chest roentgenologic evidence of left side pleural effusion and hemidiaphragm elevation were observed. 3. On flat abdomen film, soft mass shadow was visualized in 8 cases of patients. On UGI series, evidence of retrogastric space widening was observed in 11 cases of patients. 4. The location of pseudocyst is mainly in body and tail of pancrease in 11 cases of patients. 5. More accureable diagnosis can be obtained through application of ultrasound and CT scan.

  13. Radiological aspect of pancreatic pseudocysts

    International Nuclear Information System (INIS)

    Pancreatic pseudocyst occurs as a complication of pancreatitis or trauma, which results in the escape of pancreatitis enzymes from the parenchyma or ductal system of pancreas. At that time, serum amylase may have retuned to normal level, and the patient may be subjectively asymptomatic. In this phase, the radiologic findings are relatively greater significance than laboratory data. In the conventional radiologic study, pancreatic pseudocyst have been frequently confused with other retroperitoneal mass, but recently with clinical application of ultrasound and CT scan, more accurate diagnosis can be obtained. The brief results are as follows: 1. Male to female ratio was 3 : 2 in 15 patients. Incidence was more common in young adult age. Most frequent symptom was epigastric pain, and which was noted in 11 cases of patients. 7 cases of patients had past history of abdominal trauma and past history of pancreatitis was only in 1 case. Most common laboratory findings was leukocytosis in 8 cases of patients and elevated serum amylase was also noted in 7 cases. 2. In each 5 cases of patients, plain chest roentgenologic evidence of left side pleural effusion and hemidiaphragm elevation were observed. 3. On flat abdomen film, soft mass shadow was visualized in 8 cases of patients. On UGI series, evidence of retrogastric space widening was observed in 11 cases of patients. 4. The location of pseudocyst is mainly in body and tail of pancrease in 11 cases of patients. 5. More accureable diagnosis can be obtained through application of ultrasound and CT scan

  14. PCMdb: Pancreatic Cancer Methylation Database

    Science.gov (United States)

    Nagpal, Gandharva; Sharma, Minakshi; Kumar, Shailesh; Chaudhary, Kumardeep; Gupta, Sudheer; Gautam, Ankur; Raghava, Gajendra P. S.

    2014-02-01

    Pancreatic cancer is the fifth most aggressive malignancy and urgently requires new biomarkers to facilitate early detection. For providing impetus to the biomarker discovery, we have developed Pancreatic Cancer Methylation Database (PCMDB, http://crdd.osdd.net/raghava/pcmdb/), a comprehensive resource dedicated to methylation of genes in pancreatic cancer. Data was collected and compiled manually from published literature. PCMdb has 65907 entries for methylation status of 4342 unique genes. In PCMdb, data was compiled for both cancer cell lines (53565 entries for 88 cell lines) and cancer tissues (12342 entries for 3078 tissue samples). Among these entries, 47.22% entries reported a high level of methylation for the corresponding genes while 10.87% entries reported low level of methylation. PCMdb covers five major subtypes of pancreatic cancer; however, most of the entries were compiled for adenocarcinomas (88.38%) and mucinous neoplasms (5.76%). A user-friendly interface has been developed for data browsing, searching and analysis. We anticipate that PCMdb will be helpful for pancreatic cancer biomarker discovery.

  15. SGLT2 Deletion Improves Glucose Homeostasis and Preserves Pancreatic β-Cell Function

    OpenAIRE

    Jurczak, Michael J.; Lee, Hui-Young; Birkenfeld, Andreas L; Jornayvaz, Francois R.; Frederick, David W.; Pongratz, Rebecca L.; Zhao, Xiaoxian; Moeckel, Gilbert W.; Samuel, Varman T.; Whaley, Jean M.; Shulman, Gerald I.; Kibbey, Richard G

    2011-01-01

    OBJECTIVE Inhibition of the Na+-glucose cotransporter type 2 (SGLT2) is currently being pursued as an insulin-independent treatment for diabetes; however, the behavioral and metabolic consequences of SGLT2 deletion are unknown. Here, we used a SGLT2 knockout mouse to investigate the effect of increased renal glucose excretion on glucose homeostasis, insulin sensitivity, and pancreatic β-cell function. RESEARCH DESIGN AND METHODS SGLT2 knockout mice were fed regular chow or a high-fat diet (HF...

  16. Molecular Biology of Pancreatic Ductal Adenocarcinoma Progression: Aberrant Activation of Developmental Pathways

    OpenAIRE

    Rhim, Andrew D.; Stanger, Ben Z.

    2010-01-01

    Embryonic development marks a period of peak tissue growth and morphogenesis in the mammalian lifecycle. Many of the pathways that underlie cell proliferation and movement are relatively quiescent in adult animals but become reactivated during carcinogenesis. This phenomenon has been particularly well documented in pancreatic cancer, where detailed genetic studies and a robust mouse model have permitted investigators to test the role of various developmental signals in cancer progression. In ...

  17. Inhibition of renalase expression and signaling has antitumor activity in pancreatic cancer.

    Science.gov (United States)

    Guo, Xiaojia; Hollander, Lindsay; MacPherson, Douglas; Wang, Ling; Velazquez, Heino; Chang, John; Safirstein, Robert; Cha, Charles; Gorelick, Fred; Desir, Gary V

    2016-01-01

    An essential feature of cancer is dysregulation of cell senescence and death. Renalase, a recently discovered secreted flavoprotein, provides cytoprotection against ischemic and toxic cellular injury by signaling through the PI3K-AKT and MAPK pathways. Here we show that renalase expression is increased in pancreatic cancer tissue and that it functions as a growth factor. In a cohort of patients with pancreatic ductal adenocarcinoma, overall survival was inversely correlated with renalase expression in the tumor mass, suggesting a pathogenic role for renalase. Inhibition of renalase signaling using siRNA or inhibitory anti-renalase antibodies decreased the viability of cultured pancreatic ductal adenocarcinoma cells. In two xenograft mouse models, either the renalase monoclonal antibody m28-RNLS or shRNA knockdown of renalase inhibited pancreatic ductal adenocarcinoma growth. Inhibition of renalase caused tumor cell apoptosis and cell cycle arrest. These results reveal a previously unrecognized role for the renalase in cancer: its expression may serve as a prognostic maker and its inhibition may provide an attractive therapeutic target in pancreatic cancer. PMID:26972355

  18. Role of Parathyroid Hormone-Related Protein Signaling in Chronic Pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Falzon, Miriam, E-mail: mfalzon@utmb.edu; Bhatia, Vandanajay [Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555 (United States)

    2015-06-18

    Chronic pancreatitis (CP), a progressive inflammatory disease where acini are destroyed and replaced by fibrous tissue, increases the risk for pancreatic cancer. Risk factors include alcohol, smoking, and obesity. The effects of these risk factors are exacerbated in patients with mutations in genes that predispose to CP. The different environmental and genetic factors produce the same clinical phenotype; once CP develops, disease course is the same regardless of etiology. Critical questions still need to be answered to understand what modifies predisposition to develop CP in persons exposed to risk factors. We postulate that risk factors modulate endogenous pathways, with parathyroid hormone-related protein (PTHrP) signaling being one such pathway. In support, PTHrP levels are elevated in mice treated with alcohol, and in mouse models of cerulein- and pancreatic duct ligation-induced CP. Disrupting the Pthrp gene in acinar cells exerts protective effects (decreased edema, histological damage, amylase and cytokine release, and fibrosis) in these CP models. PTHrP levels are elevated in human CP. Currently, CP care lacks specific pharmacological interventions. Targeting PTHrP signaling may present a novel therapeutic strategy that inhibits pancreatic inflammation and fibrosis, especially since the risk of developing pancreatic cancer is strongly associated with duration of chronic inflammation.

  19. Differentiation of autoimmune pancreatitis from suspected pancreatic cancer by fluorine-18 fluorodeoxyglucose positron emission tomography

    International Nuclear Information System (INIS)

    Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been widely used for the diagnosis of pancreatic cancer. Because autoimmune pancreatitis is easily misdiagnosed as pancreatic cancer and can be tested for by FDG-PET analysis based on the presence of suspected pancreatic cancer, we attempted to clarify the differences in FDG-PET findings between the two conditions. We compared FDG-PET findings between 15 patients with autoimmune pancreatitis and 26 patients with pancreatic cancer. The findings were evaluated visually or semiquantitatively using the maximum standardized uptake value and the accumulation pattern of FDG. FDG uptake was found in all 15 patients with autoimmune pancreatitis, whereas it was found in 19 of 26 patients (73.1%) with pancreatic cancer. An accumulation pattern characterized by nodular shapes was significantly more frequent in pancreatic cancer, whereas a longitudinal shape indicated autoimmune pancreatitis. Heterogeneous accumulation was found in almost all cases of autoimmune pancreatitis, whereas homogeneous accumulation was found in pancreatic cancer. Significantly more cases of pancreatic cancer showed solitary localization, whereas multiple localization in the pancreas favored the presence of autoimmune pancreatitis. FDG uptake by the hilar lymph node was significantly more frequent in autoimmune pancreatitis than in pancreatic cancer, and uptake by the lachrymal gland, salivary gland, biliary duct, retroperitoneal space, and prostate were seen only in autoimmune pancreatitis. FDG-PET is a useful tool for differentiating autoimmune pancreatitis from suspected pancreatic cancer, if the accumulation pattern and extrapancreatic involvement are considered. IgG4 measurement and other current image tests can further confirm the diagnosis. (author)

  20. Epithelial mesenchymal transition and pancreatic tumor initiating CD44+/EpCAM+ cells are inhibited by γ-secretase inhibitor IX.

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    Vindhya Palagani

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is an aggressive disease with a high rate of metastasis. Recent studies have indicated that the Notch signalling pathway is important in PDAC initiation and maintenance, although the specific cell biological roles of the pathway remain to be established. Here we sought to examine this question in established pancreatic cancer cell lines using the γ-secretase inhibitor IX (GSI IX to inactivate Notch. Based on the known roles of Notch in development and stem cell biology, we focused on effects on epithelial mesenchymal transition (EMT and on pancreatic tumor initiating CD44+/EpCAM+ cells. We analyzed the effect of the GSI IX on growth and epithelial plasticity of human pancreatic cancer cell lines, and on the tumorigenicity of pancreatic tumor initiating CD44+/EpCAM+ cells. Notably, apoptosis was induced after GSI IX treatment and EMT markers were selectively targeted. Furthermore, under GSI IX treatment, decline in the growth of pancreatic tumor initiating CD44+/EpCAM+ cells was observed in vitro and in a xenograft mouse model. This study demonstrates a central role of Notch signalling pathway in pancreatic cancer pathogenesis and identifies an effective approach to inhibit selectively EMT and suppress tumorigenesis by eliminating pancreatic tumor initiating CD44+/EpCAM+ cells.