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BACKGROUND: Post-pancreaticoduodenectomy pancreatic fistula associated hemorrhage (PPFH) is one of the leading lethal complications. Our study was to analyze the risk factors and managements of hemorrhage associated with pancreatic fistula after pancreaticoduodenectomy, and to evaluate treatment options. METHOD: We analyzed 445 patients who underwent pancreaticoduodenectomy or pylorus-preserving pancreaticoduodenectomy and evaluated the relevance between clinical data and PPFH. RESULTS: The incidence of postoperative pancreatic fistula (POPF) was 27.42% (122/445), and the incidence of PPFH was 4.49% (20/445). Among the 20 patients with PPFH, 7 died and 13 were cured. Interventional angiographic therapy was performed for 10 patients and 5 were successfully treated. Relaparotomy was performed for 5 patients and 2 were successfully cured. Univariate logistic regression analysis indicated that several risk factors were related to PPFH: the nature of tumor (carcinoid/low-grade or high-grade malignancy), preoperative day 1 serum prealbumin, preoperative day 1 total bilirubin (TBIL), operative time, blood loss in the operation, operative method (vascular resection and revascularization), postoperative day 3 TBIL, biliary fistula, and the grade of POPF. The multivariate stepwise logistic regression analysis demonstrated that the nature of tumor and the grade of POPF were independently risk factors of PPFH. Receiver operating characteristic curve indicated that preoperative day 1 serum prealbumin level <173 mg/L and postoperative day 3 TBIL level ≥168 µmol/L were the risk factors of PPFH. CONCLUSIONS: The risk of PPFH was found to be increased with high potential malignancy and high grade of POPF. Angiography-embolization is one of the major and effective therapies for PPFH. Extraluminal-intraluminal PPFH is more serious and needs more aggressive treatments.
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Hemorragia/etiologia , Fístula Pancreática/complicações , Pancreaticoduodenectomia/efeitos adversos , Adulto , Idoso , Embolização Terapêutica , Feminino , Hemorragia/terapia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Pré-Albumina/análise , Fatores de RiscoRESUMO
BACKGROUND: Apoptosis-stimulating of p53 protein 2 (ASPP2) is one of the ASPP family members and it has been reported to be associated with human cancer. However, the role of it in pancreatic cancer is still not clear. METHODS: We analyzed the expression level of ASPP2 in cancer tissue samples with RT-qPCR, Western Blotting assay and immunohistochemistry staining. We studied the biological function of ASPP2 and its mechanism with gene overexpression and gene silencing technologies. We determined the sensitivity of pancreatic cells with differential ASPP2 level to gemcitabine and whether autophagy inhibition affected the gemcitabine resistance, both in vitro and in vivo. RESULTS: Expression of ASPP2 was downregulated in cancerous tissues in comparison with para-cancerous tissues. ASPP2 expression was linked to clinical outcomes in patients and down-regulation of ASPP2 increased cell proliferation, autophagic flux, the activity of AMP Kinase of pancreatic cancer cells and vice versa. Knockdown of ASPP2 results in increased resistance to gemcitabine, which was attributed to the enhanced autophagy. CONCLUSIONS: ASSP2 expression is lower in cancerous tissues and decreased ASPP2 lead to higher cancer cells proliferation and autophagic flux, which contribute to the gemcitabine resistance.
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Proteínas Reguladoras de Apoptose/metabolismo , Autofagia/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desoxicitidina/farmacologia , Regulação para Baixo , Feminino , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Neoplasias Pancreáticas/metabolismo , RNA Interferente Pequeno , Reação em Cadeia da Polimerase em Tempo Real , GencitabinaRESUMO
Introduction: Central pancreatectomy (CP) is a standard surgical procedure for benign and low-grade malignant pancreatic neoplasms in the body and neck of the pancreas. Higher incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) after CP than after pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) has been reported, but no nomogram for prediction of CR-POPF after open CP has been previously established. Methods: Patients undergoing open CP for benign or low-grade malignant pancreatic neoplasms in the department of Hepatobiliary and Pancreatic (HBP) surgery of Shanghai Changhai Hospital affiliated to Naval Medical University between January 01, 2009 and December 31,2020 were enrolled. Pre-, intra- and post-operative parameters were analyzed retrospectively. Results: A total of 194 patients, including 60 men and 134 women, were enrolled with median age of 52 years (21~85 years). 84 patients (43.3%) were overweight (BMI>23.0 Kg/m2) and 14 (7.2%) were obese (BMI>28.0 Kg/m2). Pathological diagnoses ranged from serous cystic neoplasm (32.5%), solid pseudopapillary neoplasm (22.2%), pancreatic neuroendocrine tumor (20.1%), intraductal papillary mucinous neoplasm (18.0%) to mucinous cystic neoplasm (5.2%). All patients had soft pancreatic texture. Main pancreatic duct diameters were ≤0.3cm for 158 patients (81.4%) and were ≥0.5cm in only 12 patients (6.2%). A stapler (57.7%) or hand-sewn closure (42.3%) were used to close the pancreatic remnant. The pancreatic anastomosis techniques used were duct to mucosa pancreaticojejunostomy (PJ)-interrupted suture (47.4%), duct to mucosa PJ-continuous suture (43.3%), duct to mucosa "HO" half-purse binding PJ (5.2%) and invaginating pancreaticogastrostomy (4.1%). Post-surgical incidences of CR-POPF of 45.9%, surgical site infection of 28.9%, postpancreatectomy hemorrhage of 7.7% and delayed gastric emptying of 2.1% were found. Obesity and pancreatic anastomosis technique were independent risk factors of CR-POPF, with a concordance index of 0.675 and an Area Under the Curve of 0.678. Discussion: This novel nomogram constructed according to obesity and pancreatic anastomosis technique showed moderate predictive performance of CR-POPF after open CP.
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Objectives: This study aimed to examine the incidence of bifid pancreatic duct (BPD) in pancreaticoduodenectomy (PD) and clarify its impact on clinically relevant postoperative pancreatic fistula (CR-POPF). Background: Until now, all the literature about BPD during PD are published as case reports, and the incidence of BPD in PD and its impact on CR-POPF remain unknown. Results: A total of 438 consecutive PDs were divided into two groups: the former year group and the latter year group. The former year group included 215 consecutive PDs, while the latter year group included 223. In the latter year group, we found 16 BPDs during PD (O-BPD); the incidence of O-BPD is 7.17%. Of them, there were eight patients who had BPD in the preoperative imaging (I-BPD). All the I-BPDs are O-BPDs; which means that 50% of O-BPDs were a single pancreatic duct in the preoperative imaging (I-SPD). There were 17 I-BPDs in the 438 consecutive PDs; the incidence of I-BPD is 3.88%. In the former year group, the rate of severe complications of I-BPD and I-SPD is 77.78% and 27.18%, respectively (p = 0.003); the rate of CR-POPF of I-BPD is higher than I-SPD, 55.56% vs. 27.18%, but there were no statistically significant differences. In the latter year group, the rate of severe complications of O-BPD and O-SPD is 50% and 18.36%, and the rate of CR-POPF of O-BPD and O-SPD is 37.5% and 22.22%, respectively; both of them have statistically significant differences, and the p-value is 0.003 and 0.006, respectively. In the subgroup analysis, both the rate of severe complications and the rate of CR-POPF of I-BPD were higher than O-BPD, 77.78% vs. 50%, and 55.56% vs. 37.5%, but there were no statistically significant differences in both of them; the p-value is 0.174 and 0.434, respectively. Univariate and multivariate analyses showed that BPD was an independent risk factor of CR-POPF. Conclusions: The incidence of O-BPD in PD is 7.17%, 50% of O-BPDs were I-SPD, and the incidence of I-BPD is 3.88%. BPD is an independent risk factor of CR-POPF. The suture closure method may be a simple, safe, and effective method in dealing with BPD in PD.
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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.
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OBJECTIVE: To improve the prognosis and safety of extended pancreaticoduodenectomy for patients with pancreatic cancer in the uncinate process of pancreas. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Artéria Mesentérica Superior/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
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 microg/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 stage I E 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.
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Linfoma/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adolescente , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Linfoma/patologia , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Prognóstico , Estudos RetrospectivosRESUMO
Menin, the product of the Men1 gene, which is frequently mutated in pancreatic neuroendocrine tumors, acts as a chromatin-remodeling factor to modulate the transcription of cell cycle regulators by interacting with histone modification factors. However, the function of menin and its underlying mechanisms in pancreatic ductal adenocarcinoma remain unknown. Here, we found that menin inhibited pancreatic cancer cell growth in vitro and in vivo and that its expression was gradually lost during pancreatic carcinogenesis. Menin overexpression significantly activated the expression of the cyclin-dependent kinase (CDK) inhibitors p18 and p27, accompanied with a decrease in DNA methylation levels of p18 and p27 promoters. Mechanistically, we found that interaction of menin with DNA methyltransferase 1 (Dnmt1) competitively pulled down Dnmt1 from p18 and p27 promoters, leading to the downregulation of DNA methylation levels. Moreover, menin expression was suppressed by Dnmt1 downstream of the Hedgehog signaling pathway, and menin overexpression strongly antagonized the promotion effect of hedgehog signaling on pancreatic cancer cell proliferation. Taken together, the interaction between menin and Dnmt1 reversibly regulates pancreatic cancer cell growth downstream of Hedgehog pathways with complex mutual modulation networks, suggesting that the Hedgehog/Dnmt1/menin axis is a potential molecular target for pancreatic cancer therapy.
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DNA (Citosina-5-)-Metiltransferases/fisiologia , Proteínas Hedgehog/fisiologia , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas/fisiologia , Transdução de Sinais/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p18/genética , Inibidor de Quinase Dependente de Ciclina p27/genética , Cicloexilaminas/farmacologia , DNA (Citosina-5-)-Metiltransferase 1 , Metilação de DNA , Feminino , Proteínas Hedgehog/agonistas , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Tiofenos/farmacologiaRESUMO
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.
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Adenocarcinoma/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Neoplasias Pancreáticas/genética , Idoso , Feminino , Perfilação da Expressão Gênica/normas , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos/normas , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To clarify the clinicopathological significance of lymphatic vessel density (LVD) and distribution in pancreatic cancer. METHODS: We measured LVD in 43 pancreatic cancer specimens by immunostaining with specific lymphatic endothelium marker, and examined their relationship with well-defined clinicopathological variables. RESULTS: Intratumoral LVD (9.4 +/- 10.0) was significantly lower than periturmoral (16.0 +/- 9.7) (P < 0.001) and nontumoral LVD (13.5 +/- 6.0) (P < 0.01). Increased peritumoral LVD correlated significantly with tumor staging (P < 0.05) and lymph node involvement (P < 0.05). CONCLUSION: The lymphatic vessels distribution in pancreatic cancer samples and peritumoral lymphangiogenesis may promote the malignant progression and lymph node metastasis of pancreatic cancer.
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Adenocarcinoma/patologia , Linfonodos/patologia , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Vasos Linfáticos/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To determine the clinicopathologic characteristics and the relationship between related gene expression and pathobiologic behavior of pancreatic mucinous noncystic adenocarcinoma. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Adenocarcinoma Mucinoso/patologia , Neoplasias Pancreáticas/patologia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/secundário , Idoso , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Neoplasias Duodenais/patologia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/secundário , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Pancreáticas/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/metabolismoRESUMO
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.
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Adipogenia/genética , Hepatócitos/metabolismo , Receptores Nucleares Órfãos/genética , Proteínas Proto-Oncogênicas/genética , Animais , Western Blotting , Células Cultivadas , Expressão Gênica , Células HEK293 , Células Hep G2 , Humanos , Imunoprecipitação , Lipogênese/genética , Fígado/citologia , Fígado/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Receptores X do Fígado , Camundongos Endogâmicos C57BL , Receptores Nucleares Órfãos/metabolismo , Cultura Primária de Células , Ligação Proteica , Proteínas Proto-Oncogênicas/metabolismo , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
During chemotherapy, drug resistance caused by autophagy remains a major challenge to successful treatment of cancer patients. The purpose of this study is to show that ulinastatin (UTI), a trypsin inhibitor, could reduce the resistance of liver cancer cells to chemotherapeutic agent epirubicin (EPI). We achieved this conclusion by analyzing the effect of EPI alone or UTI plus EPI on SMMC-7721 and MHCC-LM3 liver cancer cells. We also generated an EPI-resistant liver cancer cell line (MHCC-LM3er cells), and found that UTI could sensitize the LM3er cells to EPI. Autophagy usually functions to protect cancer cells during chemotherapy. Our study showed that UTI inhibited the autophagy induced by EPI in liver cancer cells, which promoted apoptosis, and therefore, reduced the resistance of the cancer cells to EPI. Further studies showed that the UTI-mediated inhibition on autophagy was achieved by inhibiting transcriptional factor nuclear factor-κB (NF-κB) signaling pathway. To verify our results in vivo, we injected MHCC-LM3 liver cancer cells or EPI-resistant LM3er cells into mice, and found that EPI could only effectively inhibit the growth of tumor in MHCC-LM3 cell-injected mice, but not in LM3er cell-injected mice. However, when UTI was also administered, the growth of tumor was inhibited in the MHCC-LM3er cell-injected mice as well. Our results suggest that UTI may be used in combination with anti-cancer drugs, such as EPI, to improve the outcome of cancer therapy.
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Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Epirubicina/farmacologia , Glicoproteínas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Animais , Antibióticos Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Western Blotting , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Nus , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Inibidores da Tripsina/farmacologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
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 12 800 cDNA arrays (12 648 unique human cDNA sequences), and the fluorescent signals were scanned by ScanArray 3 000 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.
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Perfilação da Expressão Gênica , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Pancreáticas/genética , Biomarcadores Tumorais/análise , Enzimas/genética , Regulação Neoplásica da Expressão Gênica , Marcadores Genéticos , Humanos , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/genética , RNA Neoplásico/genética , RNA Neoplásico/isolamento & purificaçãoRESUMO
OBJECTIVE: To analyse the clinical features of uncinate process carcinoma of the pancreas and the diagnosis and treatment of this malignancy. METHOD: Fifty-nine patients with pancreas uncinate process carcinoma treated from January 1998 to September 2002 at our hospital were analysed retrospectively. RESULTS: 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%. CONCLUSIONS: 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%.
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Carcinoma/patologia , Carcinoma/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Carcinoma/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pancreatectomia/métodos , Neoplasias Pancreáticas/mortalidade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: To prospectively evaluate the long-term effect of pancreaticoduodenectomy with regional lymphadenectomy. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Excisão de Linfonodo , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Pancreáticas/patologia , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
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.
Assuntos
Fígado Gorduroso/metabolismo , PPAR alfa/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Animais , Regulação para Baixo/genética , Fígado Gorduroso/genética , Fígado Gorduroso/prevenção & controle , Técnicas de Silenciamento de Genes , Fígado/metabolismo , Masculino , Camundongos , Especificidade de Órgãos , Proteínas Proto-Oncogênicas/deficiência , Proteínas Proto-Oncogênicas/genética , RNA Interferente Pequeno/genéticaRESUMO
OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Assuntos
Povo Asiático/estatística & dados numéricos , Diabetes Mellitus/etnologia , Pancreatite Crônica/etnologia , Adulto , Idade de Início , Calcinose/etnologia , Distribuição de Qui-Quadrado , China/epidemiologia , Endoscopia/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Dor/etnologia , Pancreatectomia/efeitos adversos , Pancreatite Crônica/cirurgia , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Fumar/etnologia , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
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.