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BACKGROUND: Pancreatic cancer (PC) can be considered a representative cancer type of the human body. As demonstrated by some studies, microRNA (miR)-499 is dysregulated in various cancer types including PC, for which chemotherapy involving 5-fluorouracil (5-FU) has long been considered the first-line therapy. However, there are complex and comprehensive mechanisms related to 5-FU, which have not been fully elucidated. This study thus aimed to examine the molecular mechanisms of 5-FU resistance through miR-499a-5p in PC. METHODS: The expression of miR-499a-5p in PC was measured using quantitative polymerase chain reaction (PCR). MiR-499a-5p was examined in-vivo for its effects on the malignant phenotypes of PC cells. RESULTS: The results of the present study demonstrated miR-499a-5p to be upregulated in PC and 5-FU resistant PC tissues. According to in vitro assays in PC cells (PANC1/FR), miR-499a-5p was found to affect adenosine triphosphate (ATP) binding cassette subfamily B member 1 (P-gp), ATP binding cassette subfamily C member 1 (MRP1), and ATP binding cassette subfamily G member 2 (BCRP), thereby facilitating 5-FU resistance in PC cells. Functions assays indicated that suppressed miR-499a-5p expression inhibited the proliferation and migration of cells but facilitated apoptosis in the PC cell line; by contrast, miR-499a-5p overexpression triggered the inverse phenotypic changes of cells. Concerning the mechanisms involved, miR-499a-5p increased PI3K/Akt signaling by targeting phosphatase and tensin homolog (PTEN). CONCLUSIONS: Taken together, these findings demonstrate that miR-499a-5p can be potentially applied to PC therapy.

Objective To extract and identify the chemical constituents in the leaf and stem of Ervatamia officinalis.Methods The solvent extraction approach and silica column chromatography were used to separate the chemical constituents,and their structures were identified by physicochemical properties and spectra analysis.Results Ten compounds were isolated and their structures were identified as α-amyrin(1),α-amyrin acetate(2),palmitic acid(3),tetratriacontanol(4),stigmasterol(5),β-daucosterol(6),lupeol(7),calycosin(8),luteolin(9),and glaucocalyxin A(10).Conclusion Compound 1,3~10 have been isolated from this plant for the first time,and compound 7,9 and 10 have been isolated from Ervatamia genus for the first time.

S100 proteins are a calcium-binding protein family containing two EF-hand domains exclusively expressed in vertebrates and play roles in many cellular activities. Human S100P gene was first cloned as a 439 bp cDNA in placenta and it was found to be associated with human prostate cancer. Here we describe the cloning of the 1297 bp full-length cDNA, and the characterization of the tissue-specific expression of the human S100P gene. It is abundantly expressed in many tissues including placenta by Northern blot and RT-PCR analysis, unlike the expression pattern of other S100 family genes.

Menin, encoded by the MEN1 gene, was initially identified as a tumor suppressor for endocrine neoplasia. Our previous report showed that Menin enhances PPARα transactivity preventing triglyceride accumulation in the liver. Here, we further explore the role of Menin in liver steatosis. Transient transfection assays demonstrate that Menin inhibits the transcriptional activity of nuclear receptor liver X receptor α (LXRα). Accordingly, Menin overexpression results in reduced expression of LXRα target genes, such as lipogenic enzymes including SREBP-1c, FASN and SCD-1. Co-immunoprecipitation assays revealed physical interaction between Menin and LXRα. Collectively, our data suggest that Menin acts as a novel corepressor of LXRα and functions as a negative regulator of hepatic lipogenesis.

The aim of the study was to determine the occurrence and the risk factors of diabetes mellitus (DM) in Chinese patients with chronic pancreatitis (CP), with particular emphasis on those with endoscopic or surgical therapy for CP.Four hundred forty-five contacted CP patients in our hospital between January 1, 1997, and July 31, 2007, were followed up. Risk factors for DM were determined in a multivariate analysis after exclusion of 58 patients.The cumulative rate of DM was 51.5% (SD, 8%) at 20 years after the onset of CP and 27.8% (SD, 6%) at 10 years after endotherapy or surgery, without significant difference between the 2 therapies (P = 0.243). The age at the onset of CP (hazard ratio, 1.032; 95% confidential interval, 1.012-1.052), smoking (2.859, 1.448-5.645), chronic pain (0.412, 0.180-0.945), and pancreatic calcifications (2.326, 1.203-4.496) were identified as independent risk factors for developing DM in the patients before any invasive therapy. Smoking (2.203, 1.153-4.209) and distal pancreatectomy (5.412, 2.506-11.690) were the independent risk factors for DM development in patients after invasive therapy.The risk of DM seems to be mainly caused by progression of CP because it increased with older age, absence of chronic pain, and pancreatic calcifications, whereas this risk is influenced by smoking and distal pancreatectomy.

To improve the prognosis and safety of extended pancreaticoduodenectomy for patients with pancreatic cancer in the uncinate process of pancreas.From January 2004 to March 2008, 26 extended pancreaticoduodenectomies with full length superior mesenteric artery (SMA) isolation and mesentery root resection were performed for the ductal adenocarcinomas in the uncinate process of pancreas. There were 16 males and 10 females aging from 30 to 75 years old [medium age (55.0 +/- 13.0) years old]. Eleven of 26 patients were combined with portal vein-superior mesenteric vein resection. The effect and safety of this procedure were analyzed retrospectively.There was no operative mortality in all patients. The pathological examination showed that all the incisal margins were negative. After a follow-up of 7 to 45 months, the pain relief was occurred in all patients. The 1-year, 2-year accumulated survival rates were 72.2%, and 48.1%, respectively.Full length SMA isolation and the mesentery resection in extended pancreaticoduodenectomy are safe and effective. The procedure is also benefit for the patients in improving the survival rate and quality of life.

AIM: To study the pathogenetic processes and the role of gene expression by microarray analyses in expediting our understanding of the molecular pathophysiology of pancreatic adenocarcinoma, and to identify the novel cancer-associated genes. METHODS: Nine histologically defined pancreatic head adenocarcinoma specimens associated with clinical data were studied. Total RNA and mRNA were isolated and labeled by reverse transcription reaction with Cy5 and Cy3 for cDNA probe. The cDNA microarrays that represent a set of 4 096 human genes were hybridized with labeled cDNA probe and screened for molecular profiling analyses. RESULTS: Using this methodology, 184 genes were screened out for differences in gene expression level after nine couples of hybridizations. Of the 184 genes, 87 were upregulated and 97 downregulated, including 11 novel human genes. In pancreatic adenocarcinoma tissue, several invasion and metastasis related genes showed their high expression levels, suggesting that poor prognosis of pancreatic adenocarcinoma might have a solid molecular biological basis. CONCLUSION: The application of cDNA microarray technique for analysis of gene expression patterns is a powerful strategy to identify novel cancer-associated genes, and to rapidly explore their role in clinical pancreatic adenocarcinoma. Microarray profiles provide us new insights into the carcinogenesis and invasive process of pancreatic adenocarcinoma. Our results suggest that a highly organized and structured process of tumor invasion exists in the pancreas.

To determine the clinicopathologic characteristics and the relationship between related gene expression and pathobiologic behavior of pancreatic mucinous noncystic adenocarcinoma.Among the 249 pancreatic carcinoma cases from the department files, 6 tumors were identified to meet the pathologic criteria of colloid carcinoma. Envision immunohistochemical staining technique was used to detect expression of p21(ras), p21(WAF1), p16, p33(ING1), p53, ATM, MDM2, PCNA, Cyclins (D1, D3, A, B and E). Intra- and extra- cellular mucin production were determined by AB-PAS staining. Clinically, all of 6 cases were followed to June, 2003.In all 6 cases, the tumors were located in the head of the pancreas and all displayed similar microscopic findings. Duodenal invasion was seen in 4 cases and perineural invasion was seen in 1 case. Tumor metastasis in the liver was seen in 2 cases and in the regional lymph nodes in 2 cases. Positive immunostaining was seen in 5 cases with p21(ras), 3 cases with p21(WAF1), 1 case with p16, 4 cases with p33(ING1), 2 cases with p53, 3 cases with ATM, 3 cases with MDM2, 6 cases with PCNA, 3 cases with cyclinA, 3 cases with cyclinD1, 4 cases with cyclinD3, 4 cases with cyclinB and 6 cases with cyclinE. Both extracellular and intracellular mucin was strongly positive for AB-PAS staining. Clinical follow-up found that 2 patients died of their tumors at 14 and 20 months. Three patients were alive after 28, 49 and 87 months of follow-up. One case were lost contact.Pancreatic mucinous noncystic adenocarcinoma has distinct morphologic features and biologic behavior. Multiple gene products including many cyclins may be involved in the pathogenesis of pancreatic colloid carcinoma. The tumor has an aggressive behavior with a high frequency of invasion and metastases, though the prognosis could be better than that of ordinary ductal adenocarcinoma of pancreas.

To analyse the clinical features of uncinate process carcinoma of the pancreas and the diagnosis and treatment of this malignancy.Fifty-nine patients with pancreas uncinate process carcinoma treated from January 1998 to September 2002 at our hospital were analysed retrospectively.Major symptoms of these patients were upper abdominal pain accompanied with lumbar pain, body weight loss and jaundice. Thirty-seven patients received regional pancreaticoduodenectomy (RP), 16 partial resection of the superior mesenteric vein-portal vein (SMV-PV) or superior mesenteric artery (SMA) and reconstruction, 1 anhydrous alcohol injection in the celiac nerve plexus, regional chemotherapy via a chemotherapy pump, and liver biopsy, and 5 no operation. The survival of the patients after operation was 2-46 months (median 12.1 months). Eleven patients are still alive with a longest survival of 46 months. The 1- and 3-year survival rates were 37.7% and 5.6%.Pancreas uncinate process carcinoma invading the adjacent SMV/SMA-PV causes difficulty in early diagnosis and poor prognosis, which are related to its location, not tumor's aggressive nature. This carcinoma has a high resection rate of 89.8%.

To prospectively evaluate the long-term effect of pancreaticoduodenectomy with regional lymphadenectomy.One hundred and twenty-one patients with ductal adenocarcinoma in the pancreatic head treated from 1996 to 2001 were studied prospectively. The enrollment of the patients was dependent on 7 criteria. The patients were divided into two groups: regional lymphadenectomy (group A, n = 50) and routine Whipple procedure (group B, n = 71). Their pre- and postoperative conditions, clinicopathological data, survival rates were studied.It was comparable between the 2 groups in age, sex, preoperative risk factors, operative management, and postoperative complication. Clinicopathological results showed no difference in tumor size and plexus invasion; but the frequency of lymph node involvement and the amount of resected lymph node in group A were significantly higher than those in group B. The rate of local recurrence was significantly higher in group A than in group B. The survival rates of 1-, 3-, 5-year in group A were 70.8%, 31.4%, 20.9%, respectively, which were higher than those in group B. No direct relations were observed between nodal involvement and survival rate.Lymphadenectomy in radical pancreaticoduodenectomy could remove lymph nodes effectively and sufficiently, and reduce the rate of local recurrence so as to improve the long-term survival rate.

AIM: To identify new diagnostic markers and drug targets, the gene expression profiles of pancreatic cancer were compared with that of adjacent normal tissues utilizing cDNA microarray analysis. METHODS: cDNA probes were prepared by labeling mRNA from samples of six pancreatic carcinoma tissues with Cy5-dUTP and mRNA from adjacent normal tissues with Cy3-dUTP respectively through reverse transcription. The mixed probes of each sample were then hybridized with 12800 cDNA arrays (12648 unique human cDNA sequences), and the fluorescent signals were scanned by ScanArray 3000 scanner (General Scanning, Inc.). The values of Cy5-dUTP and Cy3-dUTP on each spot were analyzed and calculated by ImaGene 3.0 software (BioDiscovery, Inc.). Differentially expressed genes were screened according to the criterion that the absolute value of natural logarithm of the ratio of Cy5-dUTP to Cy3-dUTP was greater-than 0.69. RESULTS: Among 6 samples investigated, 301 genes, which accounted for 2.38% of genes on the microarry slides, exhibited differentially expression at least in 5. There were 166 over-expressed genes including 136 having been registered in Genebank, and 135 under-expressed genes including 79 in Genebank in cancerous tissues. CONCLUSION: Microarray analysis may provide invaluable information on disease pathology, progression, resistance to treatment, and response to cellular microenvironments of pancreatic carcinoma and ultimately may lead to improving early diagnosis and discovering innovative therapeutic approaches for cancer.

Isolated metastatic melanoma of the pancreas is very rare. Currently, there is very limited experience with surgical resection of pancreatic metastasis. The potential benefit of metastasectomy can improve the quality of life and survival time of patients. We present a case of a 39-year-old Chinese male with a solitary pancreatic tumor which was considered a cystic benign lesion for years. Pathology and immunohistochemistry showed that the tumor in pancreatic tail was a metastasis from a malignant melanoma of the eyeball. No other metastastic foci were found in abdomen. The tumor was completely resected with combined distal pancreatectomy and splenectomy. The patient has survived 25 mo without any signs of local recurrence or other metastatic lesions after operation, indicating that complete surgical resection of a solitary metastatic melanoma of the pancreas can prolong the survival time of patients.

AIM: To heighten recognition of primary pancreatic lymphoma (PPL) in clinical practice. METHODS: A retrospective review of the clinical presentation, imaging characteristics and pathological features of PPL patients were presented, as well as their diagnosis and treatment, in combination with literature review. RESULTS: Histological diagnosis was made in four patients by surgery and in two patients by EUS-FNA. The six PPL patients (5 males and 1 female; age range, 16-65 years; mean age, 46 years) had the duration of symptoms for two weeks to three months. The primary presenting symptoms, though not characteristic, were abdominal pain, abdominal masses, weight loss, jaundice, nausea and vomiting. One of the patients developed acute pancreatitis. In one patient, the level of serum CA19-9 was 76.3 μg/L. Abdominal CT scan showed that three of the six tumors were located in the head of pancreas, two in the body and tail, and one throughout the pancreas. Diameter of the tumors in the pancreas in four cases was more than 6 cm, with homogeneous density and unclear borders. Enhanced CT scan showed that only the tumor edges were slightly enhanced. The pancreatic duct was irregularly narrowed in two cases whose tumors were located in the pancreatic head and body, in which endoscopic retrograde cholangiopancreatography (ERCP) showed that the proximal segment was slightly dilated. Two patients underwent Whipple operation, one patient underwent pancreatectomy, and another patient underwent operative biliary decompression. PPL was in stageIE in 2 patients and in stage II E in 4 patients according to the Ann Arbor classification system. The diagnosis of B-cell non-Hodgkin’s lymphoma was made in all patients histopathologically. All six patients underwent systemic chemotherapy, one of whom was also treated with gamma radiometry. One patient died two weeks after diagnosis, two patients lost follow-up, two patients who received chemotherapy survived 49 and 37 mo, and the remaining patient is still alive 21 mo, after diagnosis and treatment. CONCLUSION: PPL is a rare form of extranodal lymphoma originating from the pancreatic parenchyma. Clinical and imaging findings are otherwise not specific in the differentiation of pancreatic lymphoma and pancreatic cancer, which deserves attention. EUS-guided fine-needle aspiration (EUS-FNA) of the pancreas requires experienced cytopathologists as well as advanced immunohistochemical assays to obtain a final diagnosis on a small amount of tissue. Surgery and adjuvant chemotherapy or radiotherapy can produce fairly good outcomes.

Fatty liver is strongly associated with metabolic syndrome. Here, we show that the impaired hepatic expression of menin, the product of the MEN1 (multiple endocrine neoplasia type 1) tumor suppressor gene, represents a common feature of several fatty liver mouse models. The liver specific ablation of MEN1 gene expression in healthy mice induced hepatic steatosis under high-fat dietary conditions. Moreover, overexpression of menin in livers of steatotic db/db mice reduced liver triglyceride accumulation. At the molecular level, we found that menin acts synergistically with the nuclear receptor PPARα to control gene expression of fatty acid oxidation. Collectively, these data suggest a crucial role for menin as an integrator of the complex transcriptional network controlling hepatic steatosis.Structured summary of protein interactionsMenin physically interacts with PPAR alpha by anti tag coimmunoprecipitation (View Interaction: 1, 2).