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1.
Biomed Res Int ; 2018: 8719397, 2018.
Article in English | MEDLINE | ID: mdl-29888283

ABSTRACT

Pancreatic cancer is a malignant neoplasm that originates from acinar cells. Acinar cells get reprogrammed to become duct cells, resulting in pancreatic cancer. Pancreatitis is an acinar cell inflammation, leading to "impaired autophagy flux". Pancreatitis promotes acinar-to-ductal transdifferentiation. Expression of amylase gets eliminated during the progression of pancreatic cancer. Amylase is considered as an acinar cell marker; however, its function in cells is not known. Thus, we investigated whether amylase affects the acinar cell autophagy and whether it plays any role in development of pancreatitis. Here, we knocked out ATG12 in a pancreatic cancer cells and acinar cells using CRISPR/Cas9. Autophagy inhibition led to an increase in the expression of duct cell markers and a simultaneous decrease in that of acinar cell markers. It also caused an increase in cell viability and changes in mitochondrial morphology. Next, we knocked out amylase in acinar cells. Amylase deficiency decreased autophagy induced by pancreatitis. Our results suggest that amylase controls pancreatitis-induced autophagy. We found that eliminating amylase expression contributes to pancreatic cancer etiology by decreasing autophagy. Furthermore, our results indicate that amylase plays a role in selective pancreatitis-induced autophagy of pancreatic enzyme vesicles.


Subject(s)
Acinar Cells , Amylases/genetics , Autophagy/genetics , CRISPR-Cas Systems , Gene Knockdown Techniques , Neoplasm Proteins , Pancreatic Neoplasms , Pancreatitis , Acinar Cells/metabolism , Acinar Cells/pathology , Amylases/metabolism , Autophagy-Related Protein 12/genetics , Autophagy-Related Protein 12/metabolism , Cell Line , Humans , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Pancreatitis/genetics , Pancreatitis/metabolism , Pancreatitis/pathology
2.
Intern Med ; 56(22): 2985-2991, 2017 Nov 15.
Article in English | MEDLINE | ID: mdl-28943589

ABSTRACT

Objective The selective arterial secretagogue injection (SASI) test is considered indispensable for the accurate localization of insulinoma. However, the optimum timing of the post-injection evaluation is controversial, as some studies recommend 60 seconds [SASI (60 seconds)] while others support 120 seconds [SASI (120 seconds)]. The aim of this study was to determine the optimum timing for the SASI test evaluation for insulinoma localization. Methods Thirteen patients with surgically proven insulinoma were studied retrospectively. For the SASI test, immunoreactive insulin (IRI) was determined at baseline and at 30, 60, 90, and 120 seconds after calcium gluconate injection. A two-fold or greater increase in IRI over the baseline value was considered positive. The localization abilities of SASI (60 seconds) and SASI (120 seconds) were then compared. Results In 13 patients, a secretagogue was injected into 40 arteries supplying the pancreas. In the SASI (60 seconds) and SASI (120 seconds), the respective findings were as follows: positive predictive value, 72.2% and 68.2%; false positive rate, 25.0% and 35.0%; and rate of positivity in the head and body/tail, 38.5% and 46.2%. When the artery with the largest change was taken as the dominant artery, the localization detection sensitivity was 76.9% for SASI (60 seconds) and 92.3% for SASI (120 seconds). The sensitivity of morphological imaging techniques for localization ranged from 61.5-91.7%. Conclusion Compared with SASI (60 seconds) or morphological imaging, the insulinoma localization ability of SASI (120 seconds) was superior. Given these findings, we believe that the IRI level should be measured at 120 seconds in the SASI test.


Subject(s)
Calcium Gluconate/administration & dosage , Insulinoma/diagnosis , Pancreatic Neoplasms/diagnosis , Adult , Aged , Female , Humans , Injections, Intra-Arterial , Male , Middle Aged , Pancreas/blood supply , Retrospective Studies , Time Factors , Young Adult
3.
J Dig Dis ; 18(5): 302-308, 2017 May.
Article in English | MEDLINE | ID: mdl-28421667

ABSTRACT

OBJECTIVES: To evaluate the utility of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA + -M2BP) level as a marker for chronic pancreatitis (CP). METHODS: We measured the serum WFA+ -M2BP level of 74 patients with CP who had undergone endoscopic retrograde cholangiopancreatography and 30 normal controls (NC) using a glycan sugar chain-based immunoassay and investigated the relationship between serum WFA+ -M2BP levels and the Cambridge classification of CP. RESULTS: Serum WFA+ -M2BP level was significantly higher in patients with CP than in NC (0.64 ± 0.28 vs 0.34 ± 0.25, P < 0.001). The levels (expressed as cut-off index) of WFA+ -M2BP for the classification of mild, moderate and marked CP were 0.44, 0.63 and 0.87, respectively. Thus, serum WFA+ -M2BP levels increased with increasing CP severity. With a cut-off value of 0.34, 0.59 and 0.61, the area under the receiver operating characteristic curve, sensitivity and specificity were 0.829, 91.9% and 63.3% for mild CP; 0.891, 81.8% and 85.0% for moderate CP; and 0.888, 92.0% and 74.7% for marked CP, respectively. Multivariate analysis revealed that elevated serum WFA+ -M2BP was independently associated with moderate and marked CP, respectively. CONCLUSION: Serum WFA+ -M2BP level is a useful marker for grading CP severity.


Subject(s)
Antigens, Neoplasm/blood , Membrane Glycoproteins/blood , Pancreatitis, Chronic/diagnosis , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Case-Control Studies , Cholangiopancreatography, Endoscopic Retrograde , Female , Humans , Male , Middle Aged , Plant Lectins , ROC Curve , Receptors, N-Acetylglucosamine , Sensitivity and Specificity , Severity of Illness Index
4.
Jpn J Clin Oncol ; 47(6): 520-528, 2017 Jun 01.
Article in English | MEDLINE | ID: mdl-28334992

ABSTRACT

OBJECTIVE: Currently, serum chromogranin A is a well-established biomarker for pancreatic neuroendocrine tumors; however, other pancreatic diseases, oral use of a proton pump inhibitor and renal impairment can affect chromogranin A. Meanwhile, chromogranin B, belonging to the same granin family as chromogranin A, is not fully examined in these conditions. The present study aimed to evaluate the utility of chromogranin B as a pancreatic neuroendocrine tumor biomarker. METHODS: Serum chromogranin B levels were determined by radioimmunoassay and serum chromogranin A levels by enzyme-linked immunosorbent assay in pancreatic neuroendocrine tumor (n = 91) and other pancreatic conditions, and in healthy people (n = 104), to assess the relationships with clinical features. RESULTS: The diagnostic ability of chromogranin B was as good as chromogranin A. The area under the curve was 0.79 for chromogranin B (sensitivity/specificity: 72%/77%), and 0.78 for chromogranin A (sensitivity/specificity: 79%/64%). Chromogranin B was not affected by proton pump inhibitor use and age, which affected chromogranin A. The number of cases without liver metastases was larger in pancreatic neuroendocrine tumor patients with positive chromogranin B and negative chromogranin A. Though chromogranin A significantly elevated cases with proton pump inhibitor treatment and had positive correlation with age, chromogranin B did not have the tendencies. However, both chromogranin B and chromogranin A elevated in the case with renal impairment. In addition, the logistic regression analysis showed that chromogranin B was superior to chromogranin A in differentiation of pancreatic neuroendocrine tumor from other pancreatic diseases. CONCLUSIONS: Compared with chromogranin A, chromogranin B may be more useful during proton pump inhibitor treatment and can detect tumors without liver metastases. In addition, chromogranin B may be an excellent biomarker when differentiation of pancreatic neuroendocrine tumor from other pancreatic diseases is required.


Subject(s)
Biomarkers, Tumor/blood , Chromogranin A/blood , Chromogranin B/blood , Neuroendocrine Tumors/blood , Pancreatic Neoplasms/blood , Adult , Age Factors , Aged , Aged, 80 and over , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Gastrins/blood , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Neuroendocrine Tumors/drug therapy , Pancreatic Neoplasms/drug therapy , Proton Pump Inhibitors/therapeutic use , ROC Curve , Young Adult
6.
J Hepatobiliary Pancreat Sci ; 24(2): 95-102, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27926987

ABSTRACT

BACKGROUND: Although everolimus has become a key therapeutic agent in patients with advanced pancreatic neuroendocrine neoplasms (PNEN), its efficacy and safety in clinical practice remains unclear. METHODS: Forty-seven patients with advanced PNEN treated with everolimus were reviewed retrospectively. To evaluate the safety of everolimus as a long-term treatment, the patients were divided into two groups according to treatment duration: group A, ≤1 year (n = 21); group B, >1 year (n = 26). RESULTS: Among 42 patients with pancreatic neuroendocrine tumors (PNET), the median progression-free survival, overall survival, and objective response rate were 27.5 months, 60.8 months, and 19.0%, respectively. Two patients with pancreatic neuroendocrine carcinomas (PNEC) with lower Ki-67 index and well-differentiated tumors showed favorable responses. More patients in group A discontinued everolimus owing to adverse drug reactions (ADRs) than in group B. The median relative dose intensity was significantly lower in group B than group A (P = 0.045), whereas the drug interruption rate was significantly higher in group B than group A (P < 0.001). CONCLUSIONS: Everolimus showed significant clinical benefit in Japanese patients with advanced PNEN. Prevention of severe ADRs by appropriate dose reduction and interruption is necessary for a long-term continuation of everolimus.


Subject(s)
Antineoplastic Agents/therapeutic use , Everolimus/therapeutic use , Neuroendocrine Tumors/drug therapy , Pancreatic Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Japan , Male , Middle Aged , Retrospective Studies , Treatment Outcome
7.
J Gastroenterol ; 51(2): 85-92, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26725837

ABSTRACT

Chronic pancreatitis is considered to be an irreversible progressive chronic inflammatory disease. The etiology and pathology of chronic pancreatitis are complex; therefore, it is important to correctly understand the stage and pathology and provide appropriate treatment accordingly. The newly revised Clinical Practice Guidelines of Chronic Pancreatitis 2015 consist of four chapters, i.e., diagnosis, staging, treatment, and prognosis, and includes a total of 65 clinical questions. These guidelines have aimed at providing certain directions and clinically practical contents for the management of chronic pancreatitis, preferentially adopting clinically useful articles. These revised guidelines also refer to early chronic pancreatitis based on the Criteria for the Diagnosis of Chronic Pancreatitis 2009. They include such items as health insurance coverage of high-titer lipase preparations and extracorporeal shock wave lithotripsy, new antidiabetic drugs, and the definition of and treatment approach to pancreatic pseudocyst. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the publication of the first edition.


Subject(s)
Pancreatitis, Chronic/diagnosis , Pancreatitis, Chronic/therapy , Practice Guidelines as Topic , Evidence-Based Medicine/methods , Humans , Japan , Pain Management/methods , Pancreatitis, Chronic/pathology , Prognosis , Severity of Illness Index
8.
Nihon Shokakibyo Gakkai Zasshi ; 110(8): 1487-94, 2013 Aug.
Article in Japanese | MEDLINE | ID: mdl-23912009

ABSTRACT

A 51-year-old man presenting with fever, weight loss and general fatigue was diagnosed with jaundice and liver tumors and admitted to our hospital for further investigation and treatment. We diagnosed multiple pyogenic liver abscesses, obstructive jaundice, and silent syphilis. The patient was successfully treated with endoscopic biliary stenting, endoscopic nasobiliary drainage, percutaneous transhepatic abscess drainage, and, most effectively, transcatheter regional hepatic arterial infusion with antibiotics. We speculated that the decline in neutrophil phagocytic function may concern to occur the pyogenic liver abscess.


Subject(s)
Liver Abscess, Pyogenic/complications , Neutrophils/physiology , Phagocytosis/physiology , Anti-Bacterial Agents/administration & dosage , Humans , Infusions, Intra-Arterial , Jaundice, Obstructive/complications , Liver Abscess, Pyogenic/drug therapy , Male , Middle Aged , Syphilis/complications
9.
Nihon Shokakibyo Gakkai Zasshi ; 109(10): 1770-5, 2012 Oct.
Article in Japanese | MEDLINE | ID: mdl-23047635

ABSTRACT

Case reports of protein-losing gastroenteropathy (PLGE) associated with not only mixed connective tissue disease (MCTD) but also Sjögren syndrome (SjS) are very rare. We report a first case of PLGE in a patient with both MCTD and SjS. A 58-year-old Japanese woman was referred and admitted to our hospital because of abdominal fullness and lower leg edema. Her past medical history revealed SjS at age 40. Physical examination demonstrated lower leg edema and Raynaud's phenomenon. Blood chemistry data showed severe hypoproteinemia. Anti RNP antibody was positive. MCTD was diagnosed. The alpha-1 antitrypsin clearance level was high. The (99m)Tc-DTPA human serum albumin scintigraphy demonstrated abnormal accumulation in the intestine. PLGE associated with both MCTD and SjS was diagnosed, but she was successfully treated by prednisolone.


Subject(s)
Mixed Connective Tissue Disease/complications , Protein-Losing Enteropathies/complications , Sjogren's Syndrome/complications , Female , Humans , Middle Aged
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