RESUMEN
Regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs) play important roles in the immune escape of cancer. In this study, we investigated pDCs and pDC-induced inducible costimulator (ICOS)(+) Treg populations in peripheral blood from gastric cancer (GC) patients and healthy donors by flow cytometry. The distribution of these cells in carcinoma tissue, peritumor tissue, and normal gastric mucosa was detected by immunohistochemistry. Plasma and tissue concentration of the cytokines such as interleukin-10 and transforming growth factor-ß1 were also measured. We found that the numbers of pDCs, Tregs, and ICOS(+) Tregs in peripheral blood were increased in GC patients compared with healthy donors. In tissue, Tregs and ICOS(+) Tregs were found distributing mainly in carcinoma tissue, whereas pDCs were mainly found in peritumor tissue. Moreover, the Foxp3(+) ICOS(+) /Foxp3(+) cell ratio in carcinoma and peritumor tissue were higher than that in normal tissue. There were more ICOS(+) Tregs in tumor and peritumor tissue of late-stage GC patients. There was a positive correlation between pDCs and ICOS(+) Tregs in peripheral blood and peritumor tissue from GC patients. In conclusion, pDCs may play a potential role in recruiting ICOS(+) Tregs, and both participate in the immunosuppression microenvironment of GC.
Asunto(s)
Células Dendríticas/inmunología , Proteína Coestimuladora de Linfocitos T Inducibles/inmunología , Neoplasias Gástricas/inmunología , Linfocitos T Reguladores/inmunología , Microambiente Tumoral/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Femenino , Humanos , Tolerancia Inmunológica/inmunología , Interferón-alfa/inmunología , Interleucina-10/inmunología , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/patologíaRESUMEN
Mitofusin-2 (Mfn2) is a mitochondrial outer membrane protein involved in mitochondrial fusion. Its mutation can cause Charcot-Marie-Tooth disease. Recent studies of Mfn2 in cancer research have not included gastric cancer. We confirmed that Mfn2 expression was lower in tumor tissue than in normal gastric mucosal tissue and that it was negatively correlated with tumor size, indicating an anti-tumor role for Mfn2. In vitro experiments showed that Mfn2 overexpression suppressed gastric cancer cell proliferation and colony formation, weakened the invasion and migratory ability of cancer cells by downregulating MMP-2 and MMP-9, halted the cell cycle and induced apoptosis. Western blotting indicated the likely involvement of P21 and PI3K/Akt signaling. Therefore, Mfn2 is a potential anti-tumor gene and a potential therapeutic target for treating gastric cancer. The progress of gastric cancer may be delayed by controlling Mfn2 expression.
Asunto(s)
GTP Fosfohidrolasas , Proteínas Mitocondriales , Enfermedad de Charcot-Marie-Tooth , GTP Fosfohidrolasas/metabolismo , Humanos , Proteínas de la Membrana/metabolismo , Proteínas Mitocondriales/metabolismo , Mutación , Fosfatidilinositol 3-Quinasas/genética , Neoplasias GástricasRESUMEN
BACKGROUND: To conduct a meta-analysis to determine the relative merits of robotic thyroidectomy (RT) and endoscopic thyroidectomy (ET). METHODS: A literature search was performed to identify comparative studies reporting peri-operative outcomes for RT and ET. Pooled odds ratios (ORs) and weighted mean differences (WMDs) with 95% confidence interval (95% CI) were calculated using either a fixed-effects or a random-effects model. RESULTS: Six studies matched the selection criteria, which reported on 2048 subjects, of whom 978 underwent RT and 1070 underwent ET. Comparing the outcomes of RT with ET, this meta-analysis indicated that RT was associated with more complications (WMD = 1.51, 95% CI 1.18 to 1.94) and greater amount of drainage fluid (WMD = 17.10, 95% CI 5.69 to 28.51). Meanwhile, operating time (WMD = 1.50, 95% CI -39.59 to 42.58), conversion (WMD = 0.63, 95% CI 0.07 to 6.17), post-operative hospital stay (WMD = -0.05; 95% CI -0.18 to 0.08), and the number of lymph nodes harvested (WMD = 0.62, 95% CI -0.29 to 1.53) were similar for both procedures. CONCLUSION: The results of this meta-analysis indicated that RT is associated with an increased risk of complications and a greater amount of drainage fluid. Therefore, RT does not appear to have any advantage over ET. Further studies are required to confirm these results.
Asunto(s)
Endoscopía/métodos , Robótica/métodos , Tiroidectomía/métodos , Humanos , Neoplasias de la Tiroides/cirugía , Tiroidectomía/efectos adversosRESUMEN
OBJECTIVE: Gastrointestinal stromal tumors (GISTs) occur rarely in the duodenum. The characteristics of duodenal GIST have not been well clarified. The aim of this study is to clarify the characteristics and surgical prognosis of patients with primary duodenal GIST. METHODS: Data of patients with surgically treated primary duodenal GIST were retrospectively analyzed. Immunohistochemical expressions of p53, p16, and Ki-67 were evaluated to explain the prognosis. RESULTS: Compared with gastric or small intestinal GISTs in historical studies, duodenal GISTs had a relatively smaller size, lower mitotic count, lower Ki-67 LI, lower p16 loss, and similar p53 expression. The 1- and 3-year recurrence-free survival rates of patients with complete resection were 100 and 95.2%. CONCLUSION: Patients with completely resected primary duodenal GIST seem to have a more favorable prognosis. This may be related to the different expressions of some immunohistological makers compared with GISTs of other locations.
Asunto(s)
Neoplasias Duodenales/metabolismo , Neoplasias Duodenales/mortalidad , Tumores del Estroma Gastrointestinal/metabolismo , Tumores del Estroma Gastrointestinal/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Neoplasias Duodenales/patología , Neoplasias Duodenales/cirugía , Femenino , Estudios de Seguimiento , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Inmunohistoquímica , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Recurrencia Local de Neoplasia , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
BACKGROUND: Urinary trypsin inhibitor (UTI) inhibits the inflammatory response and protects against ischemia-reperfusion (I/R) injury. The inflammatory response is mediated by nuclear factor-kappa B (NF-kappaB) and its related target genes and products such as vascular endothelial cell adhesion molecule and CXC chemokines. We aimed to assess the roles of those mediators in a UTI-treated mouse model of hepatic I/R injury. METHODS: Treatment group 1 (UTI given 5 minutes prior to liver ischemia), treatment group 2 (UTI given 5 minutes after the anhepatic phase) and a control group were investigated. Blood and liver samples were obtained and compared at 1, 3, 6 and 24 hours after reperfusion. RESULTS: Attenuation of pathological hepatocellular damage was greater in the treatment groups than in the control group (P<0.05). Compared with the control group, the UTI treatment groups showed significantly lower serum alanine aminotransferase and aspartate aminotransferase levels, decreased myeloperoxidase activity, and reduced NF-kappaB activation. Also downregulated was the expression of tumor necrosis factor-alpha, cytokine-induced neutrophil chemoattractant, and macrophage inflammatory protein-2 at the mRNA level. P-selectin protein and intercellular adhesion molecule-1 protein expression were also downregulated. In addition, the treatment group 1 showed a better protective effect against I/R injury than the treatment group 2. CONCLUSIONS: UTI reduces NF-kappaB activation and downregulates the expression of its related mediators, followed by the inhibition of neutrophil aggregation and infiltration in hepatic I/R injury. The protective role of UTI is more effective in prevention than in treatment.
Asunto(s)
Glicoproteínas/metabolismo , Glicoproteínas/farmacología , Hepatopatías/tratamiento farmacológico , FN-kappa B/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Reacción de Fase Aguda/inmunología , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Quimiocina CXCL2/genética , Quimiocina CXCL2/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/inmunología , Selectina E/genética , Selectina E/metabolismo , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Hepatopatías/inmunología , Hepatopatías/metabolismo , Ratones , Ratones Endogámicos BALB C , Neutrófilos/inmunología , Selectina-P/genética , Selectina-P/metabolismo , Peroxidasa/metabolismo , ARN Mensajero/metabolismo , Daño por Reperfusión/inmunología , Daño por Reperfusión/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
RATIONALE: Adenoid cystic carcinoma (ACC) rarely occurs in the digestive tract, particularly in the gastroesophageal junction. PATIENT CONCERNS: A 44-year-old male vomiting blood was admitted to our hospital. Endoscopic ultrasound showed a 2.2â×â3.0âcm submucosal tumor in the gastroesophageal junction. DIAGNOSIS: According to the histopathological examination, the tumor was composed predominantly of ductal epithelial and myoepithelial cells. Immunohistochemical staining revealed that the tumor expressed cytokeratin, cluster of differentiation 117, p63, and calponin. Based on these findings, ACC was diagnosed. INTERVENTIONS: Endoscopic submucosal dissection (ESD) was performed to remove the tumor. As the margins of the ESD specimen were positive, the patient underwent total gastrectomy with D2 lymphadenectomy. Finally, neither residual tumor nor lymphatic metastasis was detected in the surgical specimens. OUTCOMES: No sign of recurrence has been detected during 36 months of follow-up as of October 2018. LESSONS: ESD may be an alternative treatment for cardial ACC invading the submucosa.
Asunto(s)
Carcinoma Adenoide Quístico/patología , Unión Esofagogástrica/patología , Neoplasias Gástricas/patología , Adulto , Carcinoma Adenoide Quístico/cirugía , Resección Endoscópica de la Mucosa/métodos , Gastrectomía/métodos , Humanos , Masculino , Neoplasias Gástricas/cirugíaRESUMEN
RATIONALE: The efficiency and tolerance of long-term adjuvant imatinib treatment for patient who underwent complete resection of a localized recurrent gastrointestinal stromal tumor (GIST) was unknown. PATIENT CONCERNS: A 45-year-old man underwent complete resection of an intestinal GIST in August 2001. Four years later, a giant (11â×â8â×â6âcm) recurrent GIST located in the retroperitoneum was detected. DIAGNOSIS: The recurrent tumor was positive for CD117 by immunohistochemistry. INTERVENTIONS: The recurrent tumor was completely resected after 4 months of effective imatinib treatment (400âmg/day), and the patient continued imatinib treatment postoperatively. In June 2011, imatinib treatment was stopped for 3 weeks because of hepatitis B infection, and resumed with a reduced dose level of 300âmg/day when liver function recovered. In March 2017, imatinib treatment was interrupted again for 12 days because the patient underwent cholecystectomy. OUTCOMES: In December 2017, a computed tomography scan showed no signs of tumor recurrence. To date, the patient has been under adjuvant imatinib treatment for >12 years without severe side effects. The plasma concentration of imatinib (detected in February 2018) was trough concentration (Cmin) 1015.7âng/mL and peak concentration (Cmax) 1550.5âng/mL. LESSONS: This case report highlights the active role of long-term (>12 years) imatinib treatment after complete resection of localized recurrent GIST.
Asunto(s)
Antineoplásicos/uso terapéutico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/patología , Mesilato de Imatinib/uso terapéutico , Antineoplásicos/administración & dosificación , Quimioterapia Adyuvante , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Mesilato de Imatinib/administración & dosificación , Masculino , Persona de Mediana Edad , Recurrencia Local de NeoplasiaRESUMEN
Background: The leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5) is considered a cancer stem cell marker, and is often overexpressed in tumors. The interaction between Lgr5 and the immune-related tumor microenvironment is not completely understood. The aim of this study was to examine the role of Lgr5 in the microenvironment of gastric cancer (GC), and to explore possible immunological mechanisms influencing Lgr5 expression that are governed by regulatory T cells. Methods: Lgr5 expression was examined in 180 GC tumors by immunohistochemistry, and in 80 pairs of GC tumors for analysis of Th1/Th2 cytokines by ELISA. In addition, SGC7901 cells were co-cultured with patient-derived Tregs, varying concentrations of TGF-ß1, TGF-ß1 neutralizing antibody, or TGF-ß receptor inhibitor SB431542, and Lgr5 and ß-catenin expression were examined by qRT-PCR and western blot. Results: In this study, an immunosuppressive microenvironment was associated with high Lgr5 expression in GC. Furthermore, Lgr5 expression was up-regulated in GC cells co-cultured with Tregs or treated with exogenous TGF-ß1. This up-regulation was partially inhibited by the TGF-ß1 neutralizing antibody, or TGF-ß1 receptor antagonist SB431542. ß-catenin was up-regulated with high Lgr5 expression induced by exogenous TGF-ß1, and this up-regulation was inhibited by SB431542. An increased number of Tregs and high Lgr5 expression in GC tissues were significantly associated with low overall survival. Conclusion: Tregs promoted increased Lgr5 expression in GC cells via TGF-ß1 and TGF-ß1 signaling pathway, which may involve activation of the Wnt signaling pathway. High Lgr5 expression via TGF-ß confer poor prognosis in gastric cancer.
Asunto(s)
Regulación Neoplásica de la Expresión Génica/inmunología , Proteínas de Neoplasias/inmunología , Receptores Acoplados a Proteínas G/inmunología , Neoplasias Gástricas , Linfocitos T Reguladores/inmunología , Factor de Crecimiento Transformador beta1/inmunología , Línea Celular Tumoral , Supervivencia sin Enfermedad , Femenino , Humanos , Tolerancia Inmunológica , Masculino , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de Supervivencia , Linfocitos T Reguladores/patología , Microambiente Tumoral/inmunología , Vía de Señalización Wnt/inmunologíaRESUMEN
OBJECTIVE: To investigate the specific anti-breast cancer immune response induced by dendritic cells (DC) loaded with trastuzumab and apoptotic Her-2+ breast cancer cells. METHODS: DCs were generated from healthy peripheral blood mononuclear cells (PBMCs) in the presence of recombinant cytokines GM-CSF, IL-4 and TNF-alpha. Mature DCs were harvested after 7 days' co-culture of PBMCs and trastuzumab-treated apoptotic SKBr3 cells. The morphologic characteristics and ultrastructure of the DC were observed under the inverted phase-contrast microscope and transmission electron microscope (TEM), respectively. Flow cytometry (FCM) was used to check the expression of several DC specific markers: CD14, CD1a, CD64, CD80, CD83, CD86, HLA-ABC and HLA-DR. DC-cytokine induced killer (DC-CIK) cells were prepared by co-culture of DCs and peripheral blood lymphocytes in the presence of anti-CD3 antibodies and human IL-2 at an appropriate concentration. The number of antigen-specific T cells was analyzed by human interferon gamma enzyme linked immunospot (ELISPOT) assay. MTT assay was employed to assess the lysis of breast cancer cell line induced by DC-CIK cells. RESULTS: 5 minutes after the adding of DCs to SKBr3 cells pretreated with trastuzumab, the apoptotic SKBr3 cells were found to be circled by DCs. 48 hours later, many membrane-wrapped organelles of the apoptotic target cells in the cytoplasm of DCs were found by TEM. The majority of the organelles were degraded. Fewer organelles from the apoptotic cells were found in DCs without Herceptin. More than 60% in every group of DCs expressed a high-affinity receptor for IgG (FcgammaRI or CD64). CD14 expression on the mature DCs were comparatively lower, and HLA-DR and HLA-ABC expressions were higher in the trastuzumab group. The expression of CD1a, CD80, CD83 and CD86 in trastuzumab group were higher than those in immature DCs group (P < 0.05). ELISPOT assay suggests that the spot number of antigen-specific T cells were higher in trastuzumab group than that in the antigen unloaded DCs group (P < 0.05). The lysis of SKBr3 cells induced by the SKBr3 antigen loaded DC-CIK cells were 1.7 times higher than that of CIK. CONCLUSION: The lysis of SKBr3 cells induced by DC-CIK was increased after that DCs were combined with trastuzumab to capture antigen from SKBr3 cells. These findings support further investigation into the use of combination immunotherapy of the humanized monoclonal antibody, DC vaccines and immunological effector cells.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Células Asesinas Inducidas por Citocinas/inmunología , Citocinas/metabolismo , Citotoxicidad Inmunológica/inmunología , Células Dendríticas/inmunología , Anticuerpos Monoclonales Humanizados , Apoptosis , Línea Celular Tumoral , Técnicas de Cocultivo , Células Dendríticas/citología , Células Dendríticas/metabolismo , Células Dendríticas/ultraestructura , Humanos , Receptor ErbB-2/metabolismo , Receptores de IgG/metabolismo , TrastuzumabRESUMEN
OBJECTIVE: To evaluate the effectiveness and safety of the combination chemotherapy of capecitabine (X) with fractionated administration of cisplatin (C) in Chinese patients with advanced gastric cancer (AGC). METHODS: 141 patients with AGC were enrolled between July 2002 and August 2004. All patients had measurable tumor according to the criteria of RECIST, Karnofsky performance status > or = 60, adequate bone marrow, renal and hepatic functions. Prior radiotherapy or adjuvant chemotherapy was not permitted. Patients received oral administration of capecitabine at a dose of 1000 mg/m(2) twice a day on D1-D14, and intravenous infusion of fractionated cisplatin at a dose of 20 mg/m(2)/day on D1-D5. The regimen was repeated every 3 weeks, totally for 6 cycles. RESULTS: Of the 141 evaluable patients, there were 104 men and 37 women, with a median age of 54 years (range, 23 - 80 years). Metastases before chemotherapy were detected in lymph nodes (46.8%), liver (40.4%), lung (5.7%) and other area (10.6%). The median treatment duration was 6 cycles (range, 3 - 6 cycles). The objective response rate (RR) was 36.2% (51/141). The median follow-up period was 17.5 months. The median time to progress (TTP) was 9.0 months, and the median overall survival (OS) was 12.0 months. The most common treatment-related adverse events (grade 3/4) were: hand-foot syndrome (HFS) (2.1%), leucopenia (0.7%), abnormal alanine transaminase elevation (2.8%). There was no treatment-related death. CONCLUSION: Capecitabine combined with fractionated cisplatin is highly effective and well tolerated as a first-line treatment for advanced gastric cancer, with comparable results to 5-Fu plus cisplatin combination therapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/análogos & derivados , Estudios de Seguimiento , Dermatosis del Pie/inducido químicamente , Dermatosis de la Mano/inducido químicamente , Humanos , Leucopenia/inducido químicamente , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Inducción de Remisión , Neoplasias Gástricas/patología , Tasa de Supervivencia , Vómitos/inducido químicamente , Adulto JovenRESUMEN
OBJECTIVE: To investigate the effects of immunologic effector cells to enhance apoptosis induced by adriamycin (ADR) in multi-drug resistant human breast cancer cell line MCF7/ADR. METHODS: The immunologic effector cells were induced and expanded by IFN-gamma, McAb CD3, IL-1 and IL-2. The expression of P-glycoprotein (P-gp) and its relation to apoptosis in target cells were detected by TUNEL technique and immunohistochemical staining. Flow cytometry (FCM) was carried out to determine the expression level of human breast cancer related P185 antigen and the positive rate of Annexin V-FITC/PI expression. The subcellular distribution of ADR and Annexin V expression in the target cells were detected by fluorescence microscopy. RESULTS: The immunologic effector cells down-regulated the expression of P185 and P-gp in MCF7/ADR cells. The accumulation and subcellular distribution of ADR in MCF7/ADR cells were increased after co-culture with the immunologic effector cells. After treatment with the immunologic effector cells in combination with ADR, apoptosis rate of the target cells was 10 times higher than that induced by ADR alone, and 13 times higher than that induced by the immunologic effector cells alone. CONCLUSION: Immunologic effector cells can simultaneously down-regulate the expression of P185 and P-gp in MCF7/ADR cell line, and increase the apoptosis rate of MCF7/ADR cells in combination with ADR.
Asunto(s)
Antibióticos Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Doxorrubicina/farmacología , Resistencia a Antineoplásicos , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Regulación hacia Abajo , Resistencia a Múltiples Medicamentos , Femenino , Humanos , Células Asesinas Activadas por Linfocinas/inmunología , Receptor ErbB-2/metabolismoRESUMEN
This study aimed to evaluate the efficacy of FOLFOX6, SOX and XELOX as neoadjuvant chemotherapy for advanced gastric cancer. The study retrospectively assessed clinicopathological data of patients who received a radical D2 gastrectomy for gastric cancer from January 2010 to January 2013.The patients were either not administered neoadjuvant chemotherapy (control) or were given FOLFOX6, SOX and XELOX prior to surgery. The metastatic rate was also higher for the control group compared with the three chemotherapy regimens in N2 station lymph nodes (P < 0.001). The SOX group had significantly lower metastatic total and N2 station lymph nodes than FOLFOX6 and XELOX (P < 0.01). The frequency of metastatic lymph nodes relative to total lymph nodes examined was 9.9, 6.6, 3.9 and 5.3% for control, FOLFOX6, SOX and XELOX groups, respectively. In conclusion, SOX may be the most effective of these treatments as preoperative chemotherapy for Chinese patients with advanced gastric cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Gastrectomía , Terapia Neoadyuvante , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Estudios de Casos y Controles , Quimioterapia Adyuvante , China/epidemiología , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/secundario , Neoplasias Gástricas/cirugía , Tasa de SupervivenciaRESUMEN
AIM: To investigate the expression of cyclooxygenase-2 (COX-2) in gastric cancer and its relation with the liver metastasis and prognosis. METHODS: Expression of COX-2 mRNA and protein was examined in gastric cancer and its paired substantial normal tissue by semi-quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. The relation between COX-2 expression and prognosis was investigated in 195 cases. RESULTS: The expression of COX-2 mRNA in gastric cancer tissue was significantly higher than that in normal tissue in 47 cases (w = 792, P<0.01). The COX-2 mRNA in pT3-4 tissue expressed higher than that in pT1-2 tissue (w = 204, P<0.05). The positive expression rate of COX-2 protein was 57.9% (113/195). The COX-2 expression was significantly related to histological type, lymphnode metastasis, venous invasion and liver metastasis (P<0.05). No relation was found between COX-2 expression and invasion depth, peritoneal metastasis and International Union against Cancer TNM stage. The multiple regression analysis showed that the COX-2 expression and venous invasion were obviously associated with liver metastasis (P<0.05). However, there was no significant correlation between COX-2 immunoreactivity and prognosis. CONCLUSION: COX-2 may play an important role in the development of gastric cancer, and the over-expression of COX-2 protein may be a high risk factor for liver metastasis.
Asunto(s)
Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/secundario , Prostaglandina-Endoperóxido Sintasas/genética , Neoplasias Gástricas/enzimología , Neoplasias Gástricas/genética , Secuencia de Bases , Ciclooxigenasa 2 , Cartilla de ADN , Humanos , Neoplasias Hepáticas/enzimología , Neoplasias Hepáticas/genética , Proteínas de la Membrana , Metástasis de la Neoplasia , Pronóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Gástricas/patologíaRESUMEN
AIM: Ischemia/reperfusion (I/R) injury is one of the major obstacles for intestinal transplantation (ITx). Urinary trypsin inhibitor (Ulinastatin, UTI) suppresses proteases and stabilizes lysosomal membranes. We supposed that Ulinastatin would diminish I/R injury of intestinal graft. METHODS: UTI- treated group and untreated control group were investigated by histological assessment at 1.5, 4, 24, and 72 h after ITx. Myeloperoxidase (MPO) activity was used as the activity of neutrophils, and malondialdehyde (MDA) was used as an index of lipid peroxidation. TNFalpha and i-NOS mRNA expression in graft tissue were measured by semi-quantitative RT-PCR. CD11b+Gr1+ cells in graft lamina propria were analyzed by flow cytometry. RESULTS: Histological scores of the graft showed that the tissue injury was markedly attenuated by UTI treatment at different time points after ITx, with reduced MPO and MDA value in the grafts. The expression of TNFalpha and i-NOS mRNA was profoundly inhibited, while the infiltration of CD11b+ Gr1+ cells into the intestinal graft was decreased in UTI group. CONCLUSION: Urinary trypsin inhibitor attenuates I/R injury in mouse intestinal transplantation by reducing monocytes infiltration and down-regulation of TNFalpha and i-NOS mRNA expression.
Asunto(s)
Glicoproteínas/farmacología , Intestinos/trasplante , Daño por Reperfusión/tratamiento farmacológico , Inhibidores de Tripsina/farmacología , Animales , Antígeno CD11b/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/patología , Malondialdehído/metabolismo , Ratones , Ratones Endogámicos BALB C , Monocitos/metabolismo , Monocitos/patología , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa de Tipo II , Peroxidasa/metabolismo , ARN Mensajero/análisis , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
BACKGROUND: Annular pancreas in adults is a rare embryologic abnormality detected after development of complications. Embryology, diagnosis and treatment strategies for symptomatic adult annular pancreas remain controversial. In this paper we reevaluated these problems in view of the technological and theoretical advances. METHODS: In 2 patients with annular pancreas, one(36-year-old male patient) presenting with duodenal obstruction and duodenal ulcer associated with duodenocolic fistula underwent Billroth II gastrectomy and fistula ectomy and the other(17-year-old male patient) presenting with duodenal obstruction and duodenal ulcer underwent Billroth II gastrectomy. English language literature about annular pancreas etiology, diagnosis and treatment was reviewed. RESULTS: Both of the patients had uneventfully recovered. Abdominal computed tomography, endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography showed typical images of annular pancreas. Duodenal bypass procedure, choledochojejunostomy, endoscopic sphincterotomy or biliary stenting, and pancreatic resection were alternative to treat this sort of anomaly. CONCLUSIONS: Annular pancreas in adults is a rare congenital abnormality, while newer imaging modalities and an index of suspicion may assist in finding more cases. The management of this congenital anomaly should be individualized according to the associated complications.
Asunto(s)
Páncreas/anomalías , Adolescente , Adulto , Bario , Obstrucción Duodenal/etiología , Obstrucción Duodenal/cirugía , Humanos , Masculino , Páncreas/diagnóstico por imagen , Páncreas/patología , Páncreas/cirugía , Radiografía Abdominal , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To investigate hyperthermia enhanced expression of heat shock protein70 (HSP70) in breast cancer drug sensitive cell line MCF7 and multi-drug resistant (MDR) cell line MCF7/ADR, so as to increase cytotoxic activity of immunologic effector cells against the target cells, and to provide an experimental basis for cell immunotherapy based on hyperthermia. METHODS: The immunological effector cells were induced and expanded by cytokines. Breast cancer cell lines MCF7 and MCF7/ADR were treated at 42 degrees C for an hour. Then after being incubated for additional 4 hours, 24 hours and 48 hours, the cells were digested. Flow cytometry (FCM) was used to detect the expression of HSP70 on the target cells. MTT assay was employed to evaluate cell proliferation and the cytotoxic activity of immunologic effector cells against target cells. RESULTS: The expressions of HSP70 in both the target cells had significant difference. The expression of HSP70 in MCF7/ADR cells was higher than in MCF7 cells before hyperthermia. After hyperthermia the expression of HSP70 increased by 6 folds in MCF7/ADR cells, and 22 folds in MCF7 cells and was higher than in MCF7/ADR cells at hour 4. The proliferation inhibition fraction of hyperthermia against MCF7 was significantly lower than that of MCF7/ADR. The cytotoxic activity of immunologic effector cells against MCF7 cells was lower than against MCF7/ADR cells before hyperthermia. After hyperthermia the cytotoxic activity of immunologic effector cells against MCF7 cells rose by 86.23%, and was higher than against MCF7/ADR cells (rose by 30.32%). CONCLUSION: The expression of HSP70 in breast cancer drug sensitive cell line MCF7 and MDR cell line MCF7/ADR were enhanced significantly by hyperthermia. Cytotoxic activity of immunologic effector cells against both the target cells were increased by hyperthermia. The differential expressions of HSP70 in breast cancer drug sensitive cell line MCF7 and MDR cell line MCF7/ADR affect the cytotoxic activity of immunologic effector cells.
Asunto(s)
Neoplasias de la Mama/patología , Fiebre , Proteínas HSP70 de Choque Térmico/biosíntesis , Células Asesinas Activadas por Linfocinas/inmunología , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Proliferación Celular , Resistencia a Antineoplásicos/genética , Femenino , Proteínas HSP70 de Choque Térmico/genética , HumanosRESUMEN
A 67-year-old female presented with a primary hepatic gastrointestinal stromal tumor that was detected by computed tomography and diagnosed based on histopathological and genetic analyses. The tumor was microscopically composed of spindle cells and epithelioid cells, and immunohistochemistry results showed positive staining for CD117 and CD34 expression. A genetic analysis revealed a heterozygous point mutation and deletion in exon 11 of c-KIT. After an R0 resection, imatinib mesylate was administered for 1 year until its use was discontinued due to severe side effects. Two years after the original operation, the tumor recurred in the residual liver and was completely resected again. Imatinib mesylate was administered for 2 years until it was replaced by sunitinib malate because of disease progression. The patient has survived for 53 mo after undergoing a sequential therapy consisting of surgical excision, imatinib and sunitinib.
Asunto(s)
Antineoplásicos/administración & dosificación , Benzamidas/administración & dosificación , Tumores del Estroma Gastrointestinal/terapia , Hepatectomía , Indoles/administración & dosificación , Neoplasias Hepáticas/terapia , Piperazinas/administración & dosificación , Inhibidores de Proteínas Quinasas/administración & dosificación , Pirimidinas/administración & dosificación , Pirroles/administración & dosificación , Anciano , Antineoplásicos/efectos adversos , Benzamidas/efectos adversos , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Biopsia , Quimioterapia Adyuvante , Análisis Mutacional de ADN , Sustitución de Medicamentos , Femenino , Tumores del Estroma Gastrointestinal/química , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/patología , Humanos , Mesilato de Imatinib , Inmunohistoquímica , Neoplasias Hepáticas/química , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Mutación , Piperazinas/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas/efectos adversos , Sunitinib , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
PURPOSE: The tetraspanin CD151 acts as a promoter of metastasis and invasion in several tumors. However, the role of CD151 in human gastric cancer (HGC) remains unclear. METHODS: Twenty HGC specimens and matched nontumor samples, human gastric epithelial cells (HGEC), and four gastric cancer cell lines were used to analyze CD151 expression. Short hairpin RNA-mediated downregulation of CD151 expression in HGC cells was performed to examine the role of CD151 in the proliferation and metastasis/invasion of HGC cells in vivo and in vitro. The relationship of CD151 with integrin α3 in HGC cells was investigated by silencing integrin α3 followed by co-immunoprecipitation and immunofluorescence staining. Finally, the prognostic value of CD151 and integrin α3 was evaluated by immunohistochemistry in tissue microarrays of 76 HGC patients. RESULTS: CD151 was expressed at higher levels in HGC tissues and HGC cells than in nontumor tissues and HGEC cells. Down-regulation of CD151 by vshRNA-CD151 impaired metastasis and invasion of HGC-27 cells, but did not affect cell proliferation. CD151 formed a complex with integrin α3 in HGC cells. CD151-cDNA transfection rescued the metastatic potential and invasiveness of HGC-27-vshCD151 cells, but not those of HGC-27-vshintegrin α3 cells in vitro. Clinically, CD151 overexpression was significantly correlated with high TNM stage, depth of invasion and positive lymph node involvement (p<0.05), and high levels of integrin α3 were associated with large tumor size, high TNM stage, depth of invasion and lymph node involvement (p<0.05). Importantly, the postoperative 5-year overall survival of patients with CD151(low) and/or integrin α3(low) was higher than that of patients with CD151(high) and/or integrin α3(high). CONCLUSION: CD151 is positively associated with the invasiveness of HGC, and CD151 or the combination of CD151 and integrin α3 is a novel marker for predicting the prognosis of HGC patients and may be potential therapeutic targets.
Asunto(s)
Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Tetraspanina 24/metabolismo , Anciano , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Immunoblotting , Inmunoprecipitación , Técnicas In Vitro , Integrina alfa3/genética , Integrina alfa3/metabolismo , Masculino , Persona de Mediana Edad , Pronóstico , Unión Proteica , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Gástricas/genética , Tetraspanina 24/genéticaRESUMEN
AIM: To study the therapeutic efficacy of a new transnasal ileus tube advanced endoscopically for adhesive small bowel obstruction. METHODS: A total of 186 patients with adhesive small bowel obstruction treated from September 2007 to February 2011 were enrolled into this prospective randomized controlled study. The endoscopically advanced new ileus tube was used for gastrointestinal decompression in 96 patients and ordinary nasogastric tube (NGT) was used in 90 patients. The therapeutic efficacy was compared between the two groups. RESULTS: Compared with the NGT group, the ileus tube group experienced significantly shorter time for relief of clinical symptoms and improvement in the findings of abdominal radiograph (4.1 ± 2.3 d vs 8.5 ± 5.0 d) and laboratory tests (P < 0.01). The overall effectiveness rate was up to 89.6% in the ileus tube group and 46.7% in the NGT group (P < 0.01). And 10.4% of the patients in the ileus tube group and 53.3% of the NGT group underwent surgery. For recurrent adhesive bowel obstruction, ileus tube was also significantly more effective than NGT (95.8% vs 31.6%). In the ileus tube group, the drainage output on the first day and the length of hospital stay were significantly different depending on the treatment success or failure (P < 0.05). The abdominal radiographic improvement was correlated with whether or not the patient underwent surgery. CONCLUSION: Ileus tube can be used for adhesive small bowel obstruction. Endoscopic placement of the ileus tube is convenient and worthy to be promoted despite the potential risks.
Asunto(s)
Descompresión Quirúrgica , Obstrucción Intestinal/cirugía , Intubación Gastrointestinal/instrumentación , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adherencias TisularesRESUMEN
AIM: To conduct a meta-analysis to determine the relative merits of robotic surgery (RS) and laparoscopic surgery (LS) for rectal cancer. METHODS: A literature search was performed to identify comparative studies reporting perioperative outcomes for RS and LS for rectal cancer. Pooled odds ratios and weighted mean differences (WMDs) with 95% confidence intervals (95% CIs) were calculated using either the fixed effects model or random effects model. RESULTS: Eight studies matched the selection criteria and reported on 661 subjects, of whom 268 underwent RS and 393 underwent LS for rectal cancer. Compared the perioperative outcomes of RS with LS, reports of RS indicated favorable outcomes considering conversion (WMD: 0.25; 95% CI: 0.11-0.58; P = 0.001). Meanwhile, operative time (WMD: 27.92, 95% CI: -13.43 to 69.27; P = 0.19); blood loss (WMD: -32.35, 95% CI: -86.19 to 21.50; P = 0.24); days to passing flatus (WMD: -0.18, 95% CI: -0.96 to 0.60; P = 0.65); length of stay (WMD: -0.04; 95% CI: -2.28 to 2.20; P = 0.97); complications (WMD: 1.05; 95% CI: 0.71-1.55; P = 0.82) and pathological details, including lymph nodes harvested (WMD: 0.41, 95% CI: -0.67 to 1.50; P = 0.46), distal resection margin (WMD: -0.35, 95% CI: -1.27 to 0.58; P = 0.46), and positive circumferential resection margin (WMD: 0.54, 95% CI: 0.12-2.39; P = 0.42) were similar between RS and LS. CONCLUSION: RS for rectal cancer is superior to LS in terms of conversion. RS may be an alternative treatment for rectal cancer. Further studies are required.