RESUMO
High mobility group box 1 protein (HMGB1), a nuclear non-histone DNA-binding protein, is secreted extracellularly during inflammation and is a late mediator of inflammatory responses. The pro-inflammatory activity of recombinant HMGB1 proteins is dependent upon the formation of complexes with other mediators, such as lipopolysaccharide (LPS). This study investigated the influence of heparin on LPS+HMGB1-mediated inflammatory responses in cultured macrophages and a murine sepsis model. HMGB1 promoted the phosphorylation of p38 and ERK1/2. HMGB1 enhanced the induction of the pro-inflammatory cytokine, TNF-α, by LPS in macrophages. Heparin blocked the binding of HMGB1 to the surface of macrophages, and suppressed the phosphorylation of p38 and ERK1/2, but not JNK; TNF-α secretion was also decreased. However, heparin alone did not affect LPS-induced production of TNF-α. Heparin reduced lethality in mice exposed to LPS+HMGB1. To conclude, heparin inhibited LPS-induced HMGB1-amplified inflammatory responses by blocking HMGB1 binding to macrophage surfaces. Heparin could be used therapeutically as an effective inhibitor of HMGB1-associated inflammation.
Assuntos
Proteína HMGB1/metabolismo , Heparina/farmacologia , Macrófagos/efeitos dos fármacos , Sepse/tratamento farmacológico , Animais , Linhagem Celular , Modelos Animais de Doenças , Ativação Enzimática , Inflamação/imunologia , Lipopolissacarídeos/imunologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Sepse/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The main treatment strategies for chronic pancreatitis in young patients include therapeutic endoscopic retrograde cholangio-pancreatography (ERCP) intervention and surgical intervention. Therapeutic ERCP intervention is performed much more extensively for its minimally invasive nature, but a part of patients are referred to surgery at last. Historical and follow-up data of 21 young patients with chronic pancreatitis undergoing duodenum-preserving total pancreatic head resection were analyzed to evaluate the outcomes of therapeutic ERCP intervention and surgical intervention in this study. The surgical complications of repeated therapeutic ERCP intervention and surgical intervention were 38% and 19% respectively. During the first therapeutic ERCP intervention to surgical intervention, 2 patients developed diabetes, 5 patients developed steatorrhea, and 5 patients developed pancreatic type B pain. During the follow-up of surgical intervention, 1 new case of diabetes occurred, 1 case of steatorrhea recovered, and 4 cases of pancreatic type B pain were completely relieved. In a part of young patients with chronic pancreatitis, surgical intervention was more effective than therapeutic ERCP intervention on delaying the progression of the disease and relieving the symptoms.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica/métodos , Pancreatectomia/métodos , Pancreatite Crônica/cirurgia , Adolescente , Adulto , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Diabetes Mellitus/etiologia , Feminino , Seguimentos , Humanos , Masculino , Dor Pós-Operatória/etiologia , Pancreatectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Esteatorreia/etiologia , Resultado do Tratamento , Adulto JovemRESUMO
Pancreatic fistula (PF) remains the most frequent complication after pancreaticoduodenectomy (PD). This study was undertaken to explore the risk factors of postoperative PF following PD and discuss the management of PF in our center. A single-center respective study, involving 241 patients who underwent PD between September 2015 and June 2018, was conducted. Differences in the demographic data, preoperative, intraoperative and postoperative variables between the group with PF [International Study Group on Pancreatic Surgery (ISGPS) grade B/C] and the group without PF (no PF and ISGPS grade BL) were evaluated. The diagnosis and grading of PF were in strict accordance with ISGPS. Risk factors were analyzed by univariate analysis and multivariate logistic regression analysis. The results showed that postoperative PF occurred in 50 (20.7%) of the patients; 25 (10.4%) patients had a PF type BL, 46 (19.1%) patients developed a PF type B and 4 (1.6%) had a PF type C. Univariate analysis showed that fasting blood glucose (P=0.02), pancreatic texture (P< 0.001) and pancreatic duct diameter (P=0.01) were correlated with PF. Multivariate logistic regression analysis identified one independent risk factor for postoperative PF: soft pancreatic texture (OR=3.251, P=0.002). Among the cases, there were three postoperative deaths, giving a 60-day hospital mortality rate of 1.2% (3/241), and the mortality related to PF was 4.0% (2/50). One of the patients died from multiple organ failure caused by postoperative abdominal hemorrhage. In conclusion, soft pancreatic texture is an independent risk factor for PF. Surgeons should be well aware of this risk factor when performing a PD.
Assuntos
Fístula Pancreática/epidemiologia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fístula Pancreática/etiologia , Fístula Pancreática/mortalidade , Complicações Pós-Operatórias/mortalidade , Medição de Risco , Análise de SobrevidaRESUMO
Pancreatic progenitor cells represent both a potential source of transplantable islets for the treatment of diabetes and a valuable instrument for the investigation of the tumorigenesis of pancreatic carcinoma. It has been reported that pancreatic ductal cells of adults have the characteristics of pancreatic progenitors, but whether these cells can generate endocrine cells requires verification. Here, the differentiation of daughter cells of CD24(-) pancreatic ductal cells into insulin-secreting cells in vitro is reported. Crude pancreatic ductal cells were first obtained from adult mice by gradient centrifugation, and then the CD24(-) cells were isolated with a fluorescence-activated cell sorter. The isolated cells were cultured in serum-containing medium at clonal density to form epithelial colonies (ECs). The ECs were then stimulated with basic fibroblast growth factor (bFGF). After 72 h, insulin-secreting cells were observed in the ECs. These results indicate that the daughter cells of CD24(-) pancreatic ductal cells can differentiate into insulin-secreting cells in vitro when stimulated with exogenous bFGF. Therefore, CD24(-) pancreatic ductal cells have the potential to be pancreatic progenitor cells.
Assuntos
Antígeno CD24/metabolismo , Diferenciação Celular/fisiologia , Células Secretoras de Insulina/citologia , Ductos Pancreáticos/citologia , Células-Tronco Adultas/citologia , Células-Tronco Adultas/metabolismo , Animais , Separação Celular , Células Cultivadas , Células Clonais , Feminino , Citometria de Fluxo , Células Secretoras de Insulina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Ductos Pancreáticos/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismoRESUMO
AIM: To investigate the effect of delayed ethyl pyruvate (EP) delivery on distant organ injury, survival time and serum high mobility group box 1 (HMGB1) levels in rats with experimental severe acute pancreatitis (SAP). METHODS: A SAP model was induced by retrograde injection of artificial bile into the pancreatic ducts of rats. Animals were divided randomly into three groups (n = 32 in each group): sham group, SAP group and delayed EP treatment group. The rats in the delayed EP treatment group received EP (30 mg/kg) at 12 h, 18 h and 30 h after induction of SAP. Animals were sacrificed, and samples were obtained at 24 h and 48 h after induction of SAP. Serum HMGB1, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr) levels were measured. Lung wet-to-dry-weight (W/D) ratios and histological scores were calculated to evaluate lung injury. Additional experiments were performed between SAP and delayed EP treatment groups to study the influence of EP on survival times of SAP rats. RESULTS: Delayed EP treatment significantly reduced serum HMGB1 levels, and protected against liver, renal and lung injury with reduced lung W/D ratios (8.22 +/- 0.42 vs 9.76 +/- 0.45, P < 0.01), pulmonary histological scores (7.1 +/- 0.7 vs 8.4 +/- 1.1, P < 0.01), serum AST (667 +/- 103 vs 1 368 +/- 271, P < 0.01), ALT (446 +/- 91 vs 653 +/- 98, P < 0.01) and Cr (1.2 +/- 0.3 vs 1.8 +/- 0.3, P < 0.01) levels. SAP rats had a median survival time of 44 h. Delayed EP treatment significantly prolonged median survival time to 72 h (P < 0.01). CONCLUSION: Delayed EP therapy protects against distant organ injury and prolongs survival time via reduced serum HMGB1levels in rats with experimental SAP. EP may potentially serve as an effective new therapeutic option against the inflammatory response and multiple organ dysfunction syndrome (MODS) in SAP patients.
Assuntos
Proteína HMGB1/sangue , Pancreatite/sangue , Pancreatite/tratamento farmacológico , Piruvatos/uso terapêutico , Doença Aguda , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Creatinina/sangue , Modelos Animais de Doenças , Estimativa de Kaplan-Meier , Rim/fisiopatologia , Fígado/fisiopatologia , Pulmão/fisiopatologia , Masculino , Pancreatite/induzido quimicamente , Ratos , Ratos Wistar , Traumatismo por Reperfusão/prevenção & controle , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangueRESUMO
AIM: To investigate the persistence of side population (SP) cells in pancreatic cancer and their role and mechanism in the drug resistance. METHODS: The presentation of side population cells in pancreatic cancer cell line PANC-1 and its proportion change when cultured with Gemcitabine, was detected by Hoechst 33342 staining and FACS analysis. The expression of ABCB1 and ABCG2 was detected by real-time PCR in either SP cells or non-SP cells. RESULTS: SP cells do exist in PANC-1, with a median of 3.3% and a range of 2.1-8.7%. After cultured with Gemcitabine for 3 d, the proportion of SP cells increased significantly (3.8% +/- 1.9%, 10.7% +/- 3.7%, t = 4.616, P = 0.001 < 0.05). ABCB1 and ABCG2 expressed at higher concentrations in SP as compared with non-SP cells (ABCB1: 1.15 +/- 0.72, 5.82 +/- 1.16, t = 10.839, P = 0.000 < 0.05; ABCG2: 1.16 +/- 0.75, 5.48 +/- 0.94, t = 11.305, P = 0.000 < 0.05), which may contribute to the efflux of fluorescent staining and drug resistance. CONCLUSION: SP cells with inherently high resistance to chemotherapeutic agents do exist in pancreatic cancers, which may be candidate cancer stem cells contributing to the relapse of the tumor.
Assuntos
Resistencia a Medicamentos Antineoplásicos , Células-Tronco Neoplásicas/fisiologia , Neoplasias Pancreáticas , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Antimetabólitos Antineoplásicos/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Forma Celular , Desoxicitidina/análogos & derivados , Desoxicitidina/metabolismo , Humanos , Células-Tronco Neoplásicas/citologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , GencitabinaRESUMO
OBJECTIVE: To isolate and identify the side population (SP) cells in pancreatic cancer and investigate the role of phosphatidylinositol 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway in the survival and proliferation of them. METHODS: Pancreatic cancer cell of the lines PANC-1, BXPC-3, ASPC-1, PC-3, and SW-1990 were cultured. Hoechst 33432 staining and fluorescence-activated cell sorter (FACS) were used to sort the SP cells. Verapamil, inhibitor of ATP binding cassette (ABC) transporter, was added before the Hoechst 33342 inoculation to observe its influence on the SP proportion. Media with LY294002, specific inhibitor of P13K, or rapamycin, specific inhibitor of mammalian target of rapamycin (mTOR), were used to culture PANC-1 cells to observe the survival of cells. Twenty-one NOD-SCID mice were randomly divided into 7 equal groups. Four groups were inoculated subcutaneously with SP cells of the concentrations of 5x10(5), 5x10(4), 5x10(3), or 1x10(3) at the right axillary fossa and with non-SP cells at the left then Hoechst 33342 staining, flow cytometric sorting were used to detect the content of SP cells at the left axillary fossa. The other 3 groups were injected subcutaneously with non-Hoechst 33342 treated cells of the concentrations of 5x10(5), 5x10(4), 5x10(3), or 1x10(3) at the right axillary fossa and PBS at the left axillary fossa. Ten weeks later the mice were killed to undergo pathological examination. RESULTS: All cell lines were found to exhibit verapamil-sensitive SP cells except BXPC-3 cells. The SP cell proportion of the PANC-1 cells was 7.84%. No SP cell was found in the cells treated with verapamil. The colony-formation ability of the SP cells was (43.7+/-3.1)%, significantly higher than those of the non-SP cells and cells without Hoechst 33342 cells [(8.3+/-1.6)% and (10.2+/-1.9)% respectively, both P=0.000]. The tumorigenic ability of the SP cells was 100 times as those of the non-SP cells and Hoechst 33342 un-treated cells. After addition of LY294002 and rapamycin the fractions of the SP cells in the in PANC-1 cells decreased from (7.60+/-0.27)% to (1.90+/-0.22)% and (1.14+/-0.20)% respectively, both P=0.000, and they preferentially inhibited the SP cells rather than non-SP cells. CONCLUSION: SP cells are enriched in pancreatic cancer stem-like cells. PI3K/mTOR pathway is critical for pancreatic SP cells maintenance that can be selected as a new target for inhibiting cancer stem-like cells.
Assuntos
Células-Tronco Neoplásicas/citologia , Neoplasias Pancreáticas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Quinases/metabolismo , Transdução de Sinais , Animais , Benzimidazóis/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Serina-Treonina Quinases TOR , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
AIM: To observe whether pancreatic and duodenal homeobox factor-1 enhances the differentiation of pancreatic ductal epithelial cells into insulin-producing cells in vitro. METHODS: Rat pancreatic tissue was submitted to digestion by collegenase, ductal epithelial cells were separated by density gradient centrifugation and then cultured in RPMI1640 medium with 10% fetal bovine serum. After 3-5 passages, the cells were incubated in a six-well plate for 24 h before transfection of recombination plasmid XlHbox8VP16. Lightcycler quantitative real-time RT-PCR was used to detect the expression of PDX-1 and insulin mRNA in pancreatic epithelial cells. The expression of PDX-1 and insulin protein was analyzed by Western blotting. Insulin secretion was detected by radioimmunoassay. Insulin-producing cells were detected by dithizone-staining. RESULTS: XlHbox8 mRNA was expressed in pancreatic ductal epithelial cells. PDX-1 and insulin mRNA as well as PDX-1 and insulin protein were significantly increased in the transfected group. The production and insulin secretion of insulin-producing cells differentiated from pancreatic ductal epithelial cells were higher than those of the untransfected cells in vitro with a significant difference (1.32 +/- 0.43 vs 3.48 +/- 0.81, P < 0.01 at 5.6 mmol/L; 4.86 +/- 1.15 vs 10.25 +/- 1.32, P < 0.01 at 16.7 mmol/L). CONCLUSION: PDX-1 can differentiate rat pancreatic ductal epithelial cells into insulin-producing cells in vitro. In vitro PDX-1 transfection is a valuable strategy for increasing the source of insulin-producing cells.
Assuntos
Células Epiteliais/metabolismo , Proteínas de Homeodomínio/metabolismo , Insulina/metabolismo , Ductos Pancreáticos/metabolismo , Transativadores/metabolismo , Animais , Diferenciação Celular , Células Cultivadas , Células Epiteliais/citologia , Proteínas de Homeodomínio/genética , Masculino , Ductos Pancreáticos/citologia , Plasmídeos , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Transativadores/genética , TransfecçãoRESUMO
AIM: To study the correlations of Pancreas duodenal homeobox-1 with pancreatic cancer characteristics, including pathological grading, TNM grading, tumor metastasis and tumor cell proliferation. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect PDX-1 mRNA expression in pancreatic cancer tissue and normal pancreatic tissue. The expression of PDX-1 protein was measured by Western blot and immunohistochemistry. Immunohistochemistry was also used to detect proliferative cell nuclear antigen (PCNA). Correlations of PDX-1 with pancreatic cancer characteristics, including pathological grading, TNM grading, tumor metastasis and tumor cell proliferation, were analyzed by using c2 test. RESULTS: Immunohistochemistry showed that 41.1% of pancreatic cancers were positive for PDX-1 expression, but normal pancreatic tissue except islets showed no staining for PDX-1. In consistent with the result of imunohistochemistry, Western blot showed that 37.5% of pancreatic cancers were positive for PDX-1. RT-PCR showed that PDX-1 expression was significantly higher in pancreatic cancer tissues than normal pancreatic tissues (2(-3.56 +/- 0.35) vs 2(-8.76 +/- 0.14), P < 0.01). Lymph node metastasis (P < 0.01), TNM grading (P < 0.05), pathological grading (P < 0.05) and tumor cell proliferation (P < 0.01) were significantly correlated with PDX-1 expression levels. CONCLUSION: PDX-1 is re-expressed in pancreatic cancer, and PDX-1-positive pancreatic cancer cells show more malignant potential compared to PDX-1-negative cells. Therefore, PDX-1-positive cells may be tumor stem cells and PDX-1 may act as alternate surface marker of pancreatic cancer stem cells.
Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Homeodomínio/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Transativadores/metabolismo , Idoso , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologiaRESUMO
BACKGROUND: The pancreas has a strong regeneration potential in mammals. Previous studies suggested that pancreas regeneration is correlated with proliferation and differentiation of pancreatic stem cells, but the field of pancreatic stem cells is still in its infancy. This study was undertaken to detect the expression of pancreas/duodenal homeobox-1 (PDX-1) and proliferation of pancreatic duct epithelial cells in remnant pancreas during regeneration after partial pancreatectomy in rats, and characterize the source of pancreatic stem cells. METHODS: Partial pancreatectomy (90%) was performed on four- to five-week-old Sprague-Dawley rats, and duct epithelial cells and acinar cells were detected by immunohistochemical staining and scored using the 5-bromo-2-deoxyuridine (BrdU) labelling index at various time points. Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to assess the expression of PDX-1 protein and mRNA, respectively. RESULTS: At 24 hours after partial pancreatectomy, proliferation started in the main, large and small duct cells, and persisted in small duct cells to day 5. The experimental and control groups were significantly different (P<0.001). BrdU-positive acinar cells were greatly increased and reached a peak on day 5. PDX-1 protein was only faintly detectable in pancreatic ductal cells on day 1 after partial pancreatectomy. On days 2 and 3, a 2-3 fold increase in PDX-1 protein was observed, corresponding to the characteristic 42 kD protein in Western blotting. The operated and sham-operated groups also differed significantly (P<0.05). PDX-1 protein expression on days 5 and 7 after operation did not differ from that of the control group. RT-PCR revealed that PDX-1 mRNA expression did not significantly differ between the operated group and the sham-operated group at various time points. CONCLUSIONS: Pancreatic stem cells in pancreatic ductal epithelial cells are involved in the regeneration of remnant pancreas and the expression of PDX-1 in ductal cells is due to posttranscriptional regulation.
Assuntos
Proliferação de Células , Células Epiteliais/metabolismo , Proteínas de Homeodomínio/biossíntese , Pâncreas/patologia , Pâncreas/cirurgia , Ductos Pancreáticos/patologia , Células-Tronco/citologia , Transativadores/biossíntese , Animais , Bromodesoxiuridina/farmacologia , Imuno-Histoquímica , Transplante das Ilhotas Pancreáticas/métodos , Pancreatectomia , Ductos Pancreáticos/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVE: To analyze the indication and choice of operation technique for duodenum-preserving resection of pancreatic head. METHODS: The Clinical material of the 22 patients who received duodenum-preserving resection of pancreatic head (DPPHR) from January 2001 to January 2006 was analyzed. Of the 22 cases, 8 cases presented with mucinous cystadenoma, 2 cases with mucinous cystadenocarcinoma, 4 cases with solid-pseudopapillary tumors, 2 cases with pancreatic endocrine tumors, 4 cases with chronic pancreatitis, 1 case with lymph epidermis cyst, 1 case with serous cystadenoma. The indication, choice of operation technique of DPPHR and the prevention and management of the post-operative complications were investigated. RESULTS: No patient died of the operation. Three cases (13.6%) developed pancreatic fistula after the operation, 1 case (4.5%) developed biliary fistula, 1 case (4.5%) developed abdominal infection and 2 cases of duodenal fistula occurred (9.1%). CONCLUSIONS: DPPHR retains the continuity of stomach, duodenum and biliary ducts. The operation is safe and it reduces wounds and excision scope. This procedure can be used in benign and low malignant lesions in the head and neck of the pancreas.
Assuntos
Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Pancreatite/cirurgia , Adulto , Idoso , Duodeno/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Resultado do TratamentoRESUMO
This study aimed to examine the clinical efficacy of minimally invasive percutaneous catheter drainage (PCD) versus open laparotomy with temporary closure in the treatment of abdominal compartment syndrome (ACS) in patients with early-stage severe acute pancreatitis (SAP). Clinical data of 212 patients who underwent PCD and 61 patients who were given open laparotomy with temporary closure in our hospital over the last 10-year period were retrospectively analyzed, and outcomes were compared, including total and post-decompression intensive care unit (ICU) and hospital stays, physiological data, organ dysfunction, complications, and mortality. The results showed that the organ dysfunction scores were similar between the PCD and open laparotomy groups 72 h after decompression. In the PCD group, 134 of 212 (63.2%) patients required postoperative ICU support versus 60 of 61 (98.4%) in the open laparotomy group (P<0.001). Additionally, 87 (41.0%) PCD patients experienced complications as compared to 49 of 61 (80.3%) in the open laparotomy group (P<0.001). There were 40 (18.9%) and 32 (52.5%) deaths, respectively, in the PCD and open laparotomy groups (P<0.001). In conclusion, minimally invasive PCD is superior to open laparotomy with temporary closure, with fewer complications and deaths occurring in PCD group.
Assuntos
Cateterismo/efeitos adversos , Descompressão Cirúrgica/efeitos adversos , Drenagem/efeitos adversos , Hipertensão Intra-Abdominal/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Pancreatite/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateterismo/métodos , Descompressão Cirúrgica/métodos , Drenagem/métodos , Feminino , Humanos , Hipertensão Intra-Abdominal/complicações , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Pancreatite/complicações , Complicações Pós-OperatóriasRESUMO
Over the past decades, cancer has become one of the toughest challenges for health professionals. The epidemiologists are increasingly directing their research efforts on various malignant tumor worldwide. Of note, incidence of cancers is on the rise more quickly in developed countries. Indeed, great endeavors have to be made in the control of the life-threatening disease. As we know it, pancreatic cancer (PC) is a malignant disease with the worst prognosis. While little is known about the etiology of the PC and measures to prevent the condition, so far, a number of risk factors have been identified. Genetic factors, pre-malignant lesions, predisposing diseases and exogenous factors have been found to be linked to PC. Genetic susceptibility was observed in 10% of PC cases, including inherited PC syndromes and familial PC. However, in the remaining 90%, their PC might be caused by genetic factors in combination with environmental factors. Nonetheless, the exact mechanism of the two kinds of factors, endogenous and exogenous, working together to cause PC remains poorly understood. The fact that most pancreatic neoplasms are diagnosed at an incurable stage of the disease highlights the need to identify risk factors and to understand their contribution to carcinogenesis. This article reviews the high risk factors contributing to the development of PC, to provide information for clinicians and epidemiologists.
Assuntos
Interação Gene-Ambiente , Predisposição Genética para Doença , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Sistema ABO de Grupos Sanguíneos/genética , Consumo de Bebidas Alcoólicas/fisiopatologia , Diabetes Mellitus/genética , Diabetes Mellitus/patologia , Humanos , Incidência , Obesidade/genética , Obesidade/patologia , Pâncreas/metabolismo , Pâncreas/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Pancreatite Crônica/genética , Pancreatite Crônica/patologia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Prognóstico , Fatores de Risco , Fumar/fisiopatologia , Análise de Sobrevida , Neoplasias PancreáticasRESUMO
OBJECTIVE: To explore the expression and clinical significance of MUC4 mRNA in peripheral blood mononuclear cells of pancreatic cancer patients. METHODS: The expression of MUC4 mRNA in peripheral blood mononuclear cells of pancreatic cancer patients were detected with reverse transcription realtime PCR. RESULTS: Expression of MUC4 mRNA was not detected in the peripheral blood mononuclear cells of chronic pancreatitis patients and normal healthy people, but was observed in those of pancreatic cancer patients. The positive expression rate of MUC4 mRNA in pancreatic cancer patients was 60%, which was significantly higher than those of chronic pancreatitis patients and normal healthy people (P < 0.01). The positive expression rate of MUC4 mRNA increased with the development of clinical stage, and the positive expression rate in stage of II - IV (TNM system) was 76.92%, which was significantly higher than that of I - II stage (P < 0.01). CONCLUSIONS: Expression of MUC4 mRNA is highly correlated with the clinical stage in pancreatic cancer patients. Detecting the expression of MUC4 mRNA in peripheral blood mononuclear cells of pancreatic cancer patients may be helpful for the early diagnosis and differential diagnosis.
Assuntos
Adenocarcinoma/metabolismo , Biomarcadores Tumorais/biossíntese , Monócitos/metabolismo , Mucinas/biossíntese , Neoplasias Pancreáticas/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Biomarcadores Tumorais/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucinas/genética , Estadiamento de Neoplasias , Neoplasias Pancreáticas/patologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The purpose of this study was to investigate the etiology, pathological characteristics, management and prognosis of chronic pancreatitis in the Chinese population. The clinical data of 142 patients with chronic pancreatitis were retrospectively studied. All patients were of Chinese nationality and hospitalized from January 2008 to December 2011. Their ages ranged from 14 to 76 years, with a mean of 43 years. Of 142 patients, there were 72 cases of obstructive chronic pancreatitis (50.70%), 19 cases of alcoholic chronic pancreatitis (13.38%), 14 cases of autoimmune pancreatitis (9.86%) and 37 cases of undetermined etiology (26.06%). Pathologically, the average inflammatory mass diameter was 3.8 ± 3.3 cm, biliary obstruction occurred in 36 cases, gall stones in 70 cases, calcification in 88 cases, ductal dilatation in 61 cases, side branch dilatation in 32 cases, ductal irregularity in 10 cases, lymphocytic inflammation in 23 cases, obliterative phlebitis in 14 cases, extra pancreatic lesion in 19 cases and fibrosis in 142 cases. Location of pancreatic lesion in the region of head (n=97), neck (n=16), body (n=12), tail (n=15) and whole pancreas (n=2) influenced the choice of surgical procedures. Ninety-four patients (66.20%) received surgical treatment and 33.80% received other treatments. After operation, 80.85% of 94 patients experienced decreased pain, and 8.51% of 94 showed recovery of endocrine function but with a complication rate of 12.77%. All the operations were performed successfully. According to the pain scale of European Organization for Research and Treatment of Cancer (QLQ-C30) a decrease from 76 ± 22 to 14 ± 18 was observed. Etiology, pathological characteristics, management and prognosis of chronic pancreatitis in the Chinese population vary from others.
Assuntos
Doenças Autoimunes/epidemiologia , Colestase/epidemiologia , Pancreatite Alcoólica/epidemiologia , Pancreatite Crônica/patologia , Pancreatite Crônica/terapia , Adolescente , Adulto , Idoso , Doenças Autoimunes/terapia , China/epidemiologia , Colestase/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite Alcoólica/terapia , Pancreatite Crônica/etiologia , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
AIM: To investigate the effect of nutritional support therapy on severe acute pancreatitis (SAP). METHODS: A total of 96 patients with severe acute pancreatitis were divided randomly into control and treatment groups. The former group received total parenteral nutrition (TPN) via central venous infusion, while parenteral nutrition (PN) and enteral nutrition (EN) therapies were applied in different phases for the latter group. The nutrition status, acute phase responses, pancreas lesions, enteric mucosa penetrability and immune functions were monitored. RESULTS: Body weight and prealbumin concentration were increased in treatment group, compared to those in the control group, but albumin concentration did not change significantly. Acute physiology and chronic health evaluation II (APACHE II) scores decreased after 7 d of treatment, whereas the scores of the control group decreased on the 11(th) day. Concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukine-6 (IL-6) and serum C reactive protein (CRP) dropped earlier in the treatment group (on the 4(th) day) than that in the control group (on the 7(th) day). No difference was observed in pancreatic lesions between the control and treatment groups. Concentration of endotoxin and lactulose/manicol (L:M) ratio of urine did not change in treatment group, but those in the control group were elevated markedly. Compared with the treatment group, CD4:CD8 T cells ratio and immunoglobulin G (IgG) concentration in the control group decreased significantly. CONCLUSION: Compared to TPN, the combined therapy of EN and PN could improve the nutrition status and moderate the acute phase response obviously. Moreover, the integrity of enteric mucosa and immune function were protected more effectively in treatment group than in the control one. On the other hand, EN did not simulate the excretion of pancreas and avoid exaggerating the inflammation of pancreas. Thus, appropriate application of PN and EN appears to be more effective for patients with SAP.
Assuntos
Nutrição Enteral , Pancreatite/fisiopatologia , Pancreatite/terapia , Nutrição Parenteral Total , Nutrição Parenteral , Doença Aguda , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/complicações , Índice de Gravidade de DoençaRESUMO
Membrane-type 2 matrix metalloproteinase (MT2-MMP) has been identified as a powerful modulator of the pericellular environment that promotes tumor invasion and metastasis. In this study, we investigated the association of MT2-MMP and hypoxia-inducible factor-1α (HIF-1α) expression in pancreatic cancer with regard to their clinical prognostic significance. Of the tissue specimens obtained from the 78 patients included in this study, 46 (59%) were found to be positive for MT2-MMP immunostaining and MT2-MMP expression was colocalized with HIF-1α in pancreatic cancer. Using the Spearman's rank analysis, the protein and mRNA expression level of MT2-MMP was found to be significantly correlated with HIF-1α and CD34-microvascular density in pancreatic cancer. Furthermore, the expression of MT2-MMP in response to hypoxia was increased in a time-dependent manner and the promoter luciferase reporter revealed upregulation of MT2-MMP expression induced by HIF-1α in pancreatic cancer cells. Moreover, the Cox regression model indicated that MT2-MMP was an independent prognostic factor in patients with pancreatic cancer. Our results demonstrated that the overexpression of MT2-MMP was induced by HIF-1α in response to hypoxia and was an independent prognostic factor for pancreatic cancer progression.
RESUMO
BACKGROUND & OBJECTIVE: Sonic hedgehog (SHH) signaling pathway is important for modulating cellular interaction in the development of mammalian embryo. Epidermal growth factor receptor (EGFR) has been involved in the regulation of cell proliferation and differentiation. Proliferating cell nuclear antigen (PCNA) is an indicator of cell proliferation. This study was to investigate the expression of SHH, EGFR and PCNA in pancreatic cancer, and explore their correlations to cell proliferation. METHODS: The expression of SHH, EGFR, and PCNA in 49 specimens of pancreatic cancer and 49 specimens of normal pancreatic tissues adjacent to cancer was detected by immunohistochemistry. Their interrelations were analyzed. RESULTS: The positive rates of SHH and EGFR were significantly higher in pancreatic cancer than in normal tissue adjacent to cancer (79.6% vs.14.3%, 73.5% vs.16.3%, P<0.05). The expression of SHH and EGFR in pancreatic cancer had no correlation to patientsoage, tumor size, pathologic type, and tumor site (P>0.05), but were correlated to lymph node metastasis and TNM stage (P<0.05). The strong positive rate of PCNA was significantly higher in pancreatic cancer than in normal tissues (83.7% vs. 20.4%, P<0.05). SHH expression was positively correlated to EGFR expression (r1=0.232, P<0.05). SHH and EGFR expression were positively correlated to PCNA expression(r2=0.412, P<0.05û r3=0.186, P<0.05). CONCLUSION: SHH and EGFR signal pathways are active in pancreatic carcinoma, and are closely correlated to cancer cell proliferation.
Assuntos
Proliferação de Células , Receptores ErbB/metabolismo , Proteínas Hedgehog/metabolismo , Neoplasias Pancreáticas/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Adulto , Idoso , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/patologia , Transdução de SinaisRESUMO
AIM: To investigate the expression of sonic hedgehog (SHH) and epidermal growth factor receptor (EGFR) signal molecules in pancreatic cancer cells, and to assess the inhibitory effects through the blockade of the SHH and EGFR signaling pathways by cyclopamine and Iressa, respectively. METHODS: The expression of SHH and EGFR in pancreatic cancer cell lines (PANC-1, SUIT-2, and ASPC-1) was detected by RT-PCR and Western blot analysis. After treatment with different concentrations of cyclopamine, alone or in combination with Iressa, the antiproliferative effect on pancreatic cancer cells was analyzed by methyl thiazolyl tetrazolium assays. A flow cytometry analysis was used to detect the cellular cycle distribution and apoptosis of pancreatic cancer cells. RESULTS: All of the 3 pancreatic cancer cell lines expressed SHH, Smoothened (SMO), and EGFR. Cyclopamine could downregulate the expression of EGFR in all cell lines. Cyclopamine or Iressa could induce a growth inhibitory effect in a dose-dependent manner. Moreover, the combined use of 2.5 micromol/L cyclopamine and 1 micromol/L Iressa induced an enhanced inhibitory effect and a greater apoptosis rate than any agent alone. The percentage of the cell population of the G0/G1 and sub-G1 phases was significantly increased along with the increasing dose of cyclopamine and/or Iressa. CONCLUSION: The blockade of the sonic hedgehog signal pathway enhances the antiproliferative effect of the EGFR inhibitor through the downregulation of its expression in pancreatic cancer cells. The simultaneous blockade of SHH and EGFR signaling represents possible targets of new treatment strategies for pancreatic carcinoma.