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BACKGROUND AND AIM: Studies have verified the protective effect of Hydrogen Sulfide (H2S) on gastric ulcer and ulcerative colitis, but the mechanisms are not fully illustrated. In this study, the possible protective effect of H2S on TNF-α/IFN-γ induced barrier dysfunction was investigated in Caco-2 cell monolayers. METHOD: The barrier function of Caco-2 monolayers was evaluated by measuring trans-epithelial electrical resistance (TEER) and FITC-Dextran 4 kDa (FD-4) trans-membrane flux. ZO-1 and Occludin were chosen as markers of the localization of tight junction (TJ) proteins for immunofluorescence. The expression of MLCK and phosphorylation level of myosin light chain (MLC) were measured by immunoblotting. The activation of NF-kB p65 was analyzed by EMSA and immunofluorescence. RESULTS: NaHS at 500 uM significantly attenuated TNF-α/IFN-γ-indueced Caco-2 monolayer barrier injury. The increased expression of MLCK and increased phosphorylation level of MLC induced by TNF-α/IFN-γ was also inhibited significantly by NaHS. Additionally, NaHS inhibited TNF-α/IFN-γ induced activation and nuclear translocation of NF-kB p65. CONCLUSION: The present study reveals the protective effect of H2S on TNF-α and IFN-γ-induced injury of intestinal epithelial barrier function in Caco-2 monolayers and suggests that the suppression of MLCK-P-MLC signaling mediated by NF-kB P65 might be one of the mechanisms underlying the protective effect of H2S.
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Epitélio/efeitos dos fármacos , Sulfeto de Hidrogênio/farmacologia , Interferon gama/antagonistas & inibidores , Interferon gama/toxicidade , Mucosa Intestinal/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/toxicidade , Biomarcadores/metabolismo , Células CACO-2 , Humanos , Mucosa Intestinal/citologia , Cadeias Leves de Miosina/metabolismo , Quinase de Cadeia Leve de Miosina/metabolismo , Ocludina/metabolismo , Fosforilação , Úlcera Gástrica/patologia , Úlcera Gástrica/prevenção & controle , Proteínas de Junções Íntimas/metabolismo , Fator de Transcrição RelA/metabolismoRESUMO
BACKGROUND: Adenocarcinoma has the highest incidence among malignant tumors of the small intestine (SI). Squamous cell carcinoma (SCC) often occurs in organs covered with squamous epithelium. Primary or metastatic SCC originating from the SI is very rare, with very few cases reported in the literature. CASE SUMMARY: This case report involves a 69-year-old man who developed abdominal pain after lunch. After admission, an abdominal computed tomography scan revealed perforation of the alimentary canal and multiple abnormal low-density lesions in the liver. During laparotomy, an approximately 4 cm × 3 cm-sized solid tumor was found in the jejunum, located 30 cm from the Treitz ligament, with a perforation. An intestinal segment of approximately 15 cm was removed, including the perforated portion. The pathological result was SCC. In combination with liver imaging, a diagnosis of SI SCC with multiple liver metastases was considered. The patient died from hepatic failure 1 mo after the operation. CONCLUSION: SI tumors are very rare compared to those originating in other digestive organs. Due to its insidious onset, the diagnosis of this disease is usually delayed. Clinicians must pay close attention to digestive symptoms such as persistent abdominal pain and melena.
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BACKGROUND: Crohn's disease (CD) causes a range of digestive symptoms including recurrent diarrhea, abdominalgia, and flatulence, and severely impacts the quality of life of patients. Infliximab, a monoclonal antibody against tumor necrosis factor alpha, has recently been promoted as a therapeutic treatment for CD, but its safety margins remain uncertain. We report a case of rapidly progressive colorectal cancer that was diagnosed in a patient with CD who had previously been treated with infliximab. CASE SUMMARY: This case report refers to a 40-year-old male with a 6-year history of CD. The patient underwent transverse colostomy because of inflammatory ileus in 2017. He subsequently received infliximab treatment in 2018. Ten months later, worsening contracture of the transverse colostomy was observed. Imaging tests indicated that the patient may have developed colon cancer with extensive peritoneal implantation. At the same time, colonoscopy revealed a rectal mass and pathological examination indicated well-differentiated adenocarcinoma. Palliative ileostomy was performed to improve defecation in 2019. During the operation, a small nodular mass in the mesentery of the small intestine was identified and pathological examination of the mass revealed advanced adenocarcinoma. The patient was diagnosed with advanced colorectal cancer and administered palliative chemotherapy. He died in June 2020. CONCLUSION: We stress the importance of recognizing the possible occurrence of malignance in patients with CD receiving infliximab.
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OBJECTIVE: To study the expression of coagulation factor VII(FVII)/tissue factor(TF)complex in colorectal carcinoma (CRC)and its correlation with clinicopathologic factor. METHODS: The expression of coagulation factor VII protein was studied by immunohistochemistry and Western blot.The expression of tissue factor and coagulation factor VII at the mRNA levels were evaluated by quantitative realtime RT-PCR in 45 cases of CRC. RESULTS: (1) FVII overexpression was ectopicly detected in CRC specimens at protein level by immunohistochemistry and Western blot, but not in adjacent non-cancerous mucosa of colorectum;(2)FVII protein mainly localized in the cytoplasm of colon cancer cells.The positive ratios of FVII protein expression in stages I, II, III and IV by immunohistochemistry assay were 33.3%, 40.0%, 64.7% and 80.0% respectively(P=0.001); (3)The expression of FVII mRNA in CRC with hepatic metastasis was significantly higher than that in CRC without hepatic metastasis.The relative expression was 5.33+/-2.88 and 1.47+/-0.51 respectively(P=0.03). Overexpression FVII gene was unrelated with tumor size, differentiation, depth of invasion, lymph node metastasis and TNM staging.There existed some relation between the gene and protein level by Spearman correlation, r=0.58, P=0.003;(4)The expression of TF mRNA in CRC significantly correlated with lymph node metastasis, hepatic metastasis and TNM staging.The expression of tissue factor was a critical factor to predict liver metastasis by logistic regression analysis(P=0.001). CONCLUSION: Colorectal cancer can ectopicly synthesize coagulation factor VII.Tissue factor expression may play a role in the process of developing hepatic metastasis.The microenvironment of high dose FVII protein may promote tumor metastasis.
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Neoplasias Colorretais/metabolismo , Fator VII/metabolismo , Neoplasias Hepáticas/secundário , Tromboplastina/metabolismo , Adulto , Idoso , Neoplasias Colorretais/patologia , Fator VII/genética , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/metabolismo , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tromboplastina/genéticaRESUMO
OBJECTIVE: To evaluate the prognostic value of lateral pelvic lymph node metastasis on low rectal cancer. METHODS: One hundred and seventy-six patients with low rectal cancer who underwent radical resection combined with lateral pelvic lymph node dissection between 1994 and 2005 were reviewed. The data of the cases was investigated to define the prognostic value of lateral pelvic lymph node metastasis on the patients. RESULTS: Lateral node metastasis occurred in 33 patients (18.8%), and 51.5% of the metastasis occurred in internal iliac nodes or nodes at middle rectal roots and 39.4% in obturator nodes. Age < or =40 years, infiltrative cancer, T34 tumor, upward lymph node metastasis were risk factors for lateral node metastasis in low rectal cancer (P < 0.05). The overall 5-year survival rate was 64.1%, and it was 94.1%, 79.1%, 42.1% for patients with TNM stage I, II, III cancer, respectively. Tumor size, depth of infiltration, upward lymph node metastasis, lateral node metastasis was correlated significantly with prognosis (P < 0.05). The 5-year survival rate of the patients without lateral metastasis was 73.6%, which was significant higher than that of patients with lateral metastasis (21.4%, P < 0.05). CONCLUSION: Lateral pelvic lymph node metastasis is an important prognostic factor for low rectal cancer.
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Linfonodos/patologia , Metástase Linfática/patologia , Neoplasias Retais/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Modelos Logísticos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pelve/patologia , Prognóstico , Neoplasias Retais/patologia , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To assess the expression of Promatrilysin in LoVo colon cancer cell by FVIIa stimulation,and to investigate the effect of MAPKs signal transduction pathway on up-regulation of Promatrilysin. METHODS: (1) The expression of ProMMP-7 was detected by Western blot at different time points (0,2,4,6,9,12 and 24 h) and with different doses of (0,0.1,1,5,10,25 and 100 nmol/L) FVIIa stimulation. The change of ProMMP-7 expression was observed with 5 mg/L tissue factor (TF) antibody prior to 100 nmol/L FVIIa. (2) The activation of MAPKs (ERK, p38, JNK) signaling pathways were assessed at different time points after being stimulated with 100 nmol/L FVIIa and the changes of ProMMP-7 expression were detected after the special signal pathway inhibitors (PD98059,SB203580,SP600125) were applied,respectively. RESULTS: (1) The expression of ProMMP-7 in LoVo cells was up-regulated by FVII a in a time-effect dependent and dose-effect dependent manner,and markedly reached the peak level at h12, 5.5 folds that of the control group (P=0.006).The up-regulation of ProMMP-7 was completely inhibited by blockade with TF antibody. (2) A time-dependent phosphorylation of ERK1/2 and P38 in LoVo cells was induced with FVIIa incubation,reached the peak at min10,2.2 folds and 3.9 folds those of the control groups respectively, but not JNK. (3) The upregulation effect of ProMMP-7 was partially blocked after incubation of ERK1/2 inhibitors PD98059 and P38 inhibitors SB203580 prior to FVIIa, The expression of ProMMP-7 decreased by 32%+/-5% and 61%+/-10% respectively (P<0.05).whereas JNK inhibitors SP600125 did not have the effect. CONCLUSION: FVIIa induces tissue factor-dependent up-regulation of ProMMP-7 in LoVo cells. ERK1/2 and p38 signal pathways are not only involved in TF/FVIIa mediated signaling,but also related to the upregulation of MMP-7 in LoVo cells.
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Neoplasias do Colo/metabolismo , Precursores Enzimáticos/metabolismo , Fator VII/farmacologia , Metaloendopeptidases/metabolismo , Tromboplastina/farmacologia , Antracenos/farmacologia , Linhagem Celular Tumoral , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Humanos , Imidazóis/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinase 7 da Matriz/metabolismo , Piridinas/farmacologiaRESUMO
OBJECTIVE: To evaluate the therapeutic effects of transabdominal radical total gastrectomy on cardiac cancer and analyze the factors influencing the prognosis. METHODS: The clinicopathologic data of 56 cardiac cancer patients, 42 males and 14 females, aged 59 (27 - 81), who underwent transabdominal radical total gastrectomy from April 1993 to March 2003 were analyzed retrospectively. RESULTS: The total lymph node metastatic incidence of the 56 patients was 71.4% (40/56). In 19 patients who underwent para-aortic lymphadenectomy, the metastatic rate of lymph node group 16 was 31.6% (6/19). The important factors influencing lymph node metastasis included the depth of tumor invasion, Borrmann type of the tumor, tumor size, and esophageal infiltration. The postoperative morbidity rate was 21.4% (12/56) and the postoperative complication rate was 3.6% (2/56). The overall 1-, 3-, and 5-year postoperative survival rates for the entire patient cohort were 77.6%, 47.7%, and 37.1% respectively. Univariate analysis showed that lymph node metastases, tumor size, histopathological type of the tumor, Borrmann type of the tumor, depth of tumor invasion, and esophageal infiltration significantly influenced the postoperative survival. The 5-year survival rate of the patients without lymph node metastasis was 63.3%, significantly higher than that of the patients with lymph node metastasis (25.4%, P = 0.011). Multivariate analysis by Cox regression showed that lymph node metastasis was an independent prognostic factor (P = 0.042). CONCLUSION: Transabdominal radical total gastrectomy is an effective and safe procedure for treatment of Siewert type II and type III cardiac cancer. Lymph node metastasis is an important prognostic factor of these tumors.
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Cárdia , Gastrectomia/métodos , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Gastrectomia/estatística & dados numéricos , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Análise de Regressão , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de SobrevidaRESUMO
Long non-coding RNA-imprinted maternally expressed transcript (non-protein coding) (H19) has been previously identified to be involved in the development of a number of types of cancer. However, the function of H19 in the pathogenesis of colorectal cancer remains unclear. The expression level of H19 in colorectal tumor tissues, and the association between H19 expression and clinicopathological variables and prognosis was investigated in the present study. In addition, the effect of H19 overexpression on viability, migration and epithelial-mesenchymal transition (EMT) of colon cancer cells was investigated in HCT-116 and SW-480 cells. The results of the present study suggest that overexpression of H19 is associated with decreased recurrence-free survival and overall survival rates in patients with colorectal cancer, and increased viability and migration in colon cancer cells. The induction of the EMT process may be an underlying molecular mechanism associated with the H19-induced increased metastasis potential of colon cancer cells.
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The human cervical cancer oncogene (HCCR) has been found to be overexpressed in a variety of human cancers. However, the level of expression of HCCR and its biological function in gastric cancer are largely unknown. In this study, we evaluated HCCR expression in several gastric cancer cell lines and in one normal gastric mucosal cell line. We established a 5-FU-resistant gastric cancer cell subline, and we evaluated its HCCR expression. HCCR expression levels were high in gastric cancer lines, and expression was significantly increased in the 5-FU-resistant cancer cell subline. HCCR expression affected cell growth by regulating apoptosis in the cancer cells, and it had a positive correlation with p-STAT3 expression. Western blot and luciferase reporter assays showed that the activation of STAT3 upregulated HCCR expression in a positive feedback loop model. In vivo and in vitro studies showed that HCCR plays an important role in the apoptosis induced by 5-FU. Our data demonstrate that HCCR is probably involved in apoptosis and cancer growth and that it functions as a p-STAT3 stimulator in a positive feedback loop model. In gastric cancer cells, HCCR confers a more aggressive phenotype and resistance to 5-FU-based chemotherapy.
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Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas/genética , Fator de Transcrição STAT3/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Animais , Antimetabólitos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Western Blotting , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Regulação para Baixo/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Camundongos Nus , Microscopia Confocal , Proteínas Proto-Oncogênicas/metabolismo , Interferência de RNA , Terapêutica com RNAi/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Recently, long noncoding RNA (lncRNA) H19 has been reported to be related with VDR signaling and the development of inflammatory diseases including osteoarthritis. The aim of this study was to investigate the correlation between the expression level of H19 and VDR in ulcerative colitis (UC) tissues and to investigate the effect of H19 overexpression on intestinal epithelial barrier function. METHODS: The expression level of H19, miR-675-5p, and VDR in UC tissues and paired normal tissues collected from 12 patients with UC was investigated by quantitative real-time polymerase chain reaction. Caco-2 monolayers were used to test the effect of H19 and miR-675-5p overexpression on the intestinal epithelial barrier function and the status of tight junction proteins and VDR. Luciferase assay was used to validate the target site of miR-675-5p in the 3'UTR of VDR mRNA. RESULTS: The expression of H19 was found to be negatively correlated with the expression of VDR in UC tissues (r = 0.5369, P < 0.05). The expression of miR-675-5p was also found to be negatively correlated with the expression of VDR in UC tissues (r = 0.5233, P < 0.01). H19 overexpression increased Caco-2 monolayer permeability and decreased the expression of tight junction proteins and VDR, which was significantly attenuated by cotransfection with miR-675-5p inhibitors. The 3'UTR of VDR mRNA was validated to be one of the direct targets of miR-675-5p. CONCLUSIONS: This study reveals the destructive effect of H19 overexpression on intestinal epithelial barrier function and suggests a potential role of H19 in the development of UC. In addition, H19 overexpression may be one of the mechanisms underlying the decreased expression of VDR in UC tissues and the interaction between H19 and VDR signaling may provide potential therapeutic targets for UC.
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Colite Ulcerativa/genética , Mucosa Intestinal/fisiologia , RNA Longo não Codificante/metabolismo , Receptores de Calcitriol/metabolismo , Transdução de Sinais/genética , Colite Ulcerativa/fisiopatologia , Humanos , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
OBJECTIVE: To investigate the role of tissue factor expression in the invasive ability of human colon carcinoma cells and to analyze the correlation between tissue factor and MMP-2 and MMP-9. METHODS: HT-29 cells with sense-TFcDNA transfection and LoVo cells with antisense-TFcDNA transfection were implanted subcutaneously into nude mice as well as controls. The expressions of MMP-9 and MMP-2 at the protein and mRNA levels were detected by Western blot and RT-PCR respectively; Gelatin zymography was used for assay of the MMP-9 and MMP-2 activities in the supernatant cultured media of LoVo cells with antisense-TFcDNA transfection and controls. RESULTS: The expressions of MMP-9 and MMP-2 at the protein and mRNA levels in the group of HT-29 cells with sense-TFcDNA were significantly increased with untransfected HT-29 cells. The expression in the group of LoVo cells with antisense-TFcDNA had a significant decrease than that of the controls. The MMP-9 and MMP-2 activities of LoVo cells with antisense-TFcDNA were weakened because of the lower expression of tissue factor by gelatin zymography. The expression of MMP-9 and MMP-2 were closely correlated to the expression of tissue factor. CONCLUSION: Tissue factor can increase the invasive ability of human colon carcinoma cells. The partial mechanism is that TF can upregulate the expressions of MMP-9 and MMP-2. Tissue factor may be an inner agonist in the secretion of MMPs in colon carcinoma cells.
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Neoplasias do Colo/metabolismo , Metaloproteinases da Matriz/biossíntese , Tromboplastina/biossíntese , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/patologia , Humanos , Masculino , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/genética , Metaloproteinases da Matriz/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Transplante de Neoplasias , Tromboplastina/genética , TransfecçãoRESUMO
OBJECTIVE: To investigate the role of tissue factor (TF) in the invasion and hematogenous metastasis of human colorectal carcinoma cells. METHODS: The eukaryotic expression vectors pcDNA3.1/Zeo bearing either sense or antisense TFcDNA were transfected into HT-29 and LoVo cells by the way of lipofactamine 2000. TF proteins in transfected cells were detected by Western Blot. Then the transfected and un-transfected tumor cells were implanted into nude mice (Balb/c Nu/Nu) to produce primary tumor, lung metastasis and liver metastasis respectively. RESULTS: HT-29 and LoVo cells with sense-TFcDNA transfection showed increased TF expression compared with the cells without transfection, but the cells with antisense-TFcDNA transfection got the contrary change. The primary tumor growth and invasive range, lung metastasis and live metastasis all increased in sense transfectants but reduced in antisense transfectants. CONCLUSIONS: TF can increase the invasion and hematogenous metastatic ability of human colorectal carcinoma cells.
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Neoplasias Colorretais/patologia , Células Neoplásicas Circulantes/patologia , Tromboplastina/fisiologia , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , DNA Antissenso/genética , DNA Complementar/genética , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Camundongos Nus , Invasividade Neoplásica , Tromboplastina/biossíntese , Tromboplastina/genética , TransfecçãoRESUMO
Lipopolysaccharide was found to be elevated in the plasma of necrotizing enterocolitis (NEC) and inflammatory bowel disease (IBD) patients and may play an important role in the pathogenesis and propagation of these intestinal diseases. To illustrate the destructive effect of lipopolysaccharide (LPS) and to test the protective effect of 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) on LPS-induced barrier injury, an in vitro intestinal epithelia barrier model was established with Caco-2 monolayers and treated with clinically relevant concentrations (1-10 ng/ml) of LPS with or without 1,25(OH)2D3. Transepithelial electrical resistance (TEER) and FITC-Dextran 40kda (FD-40) flux were measured to reflect monolayer permeability. We found that LPS at clinically relevant concentrations increased intestinal permeability by downregulating and redistributing tight junction (TJ) proteins. 1,25(OH)2D3 added at baseline or at day 4 abrogated the destructive effect of LPS on monolayer permeability by restoring the expression and localization of TJ proteins. LPS, at clinically relevant concentrations, also downregulated the expression of vitamin D receptor (VDR); 1,25 (OH)2D3, however, could restore the expression of VDR. Our findings illustrate the mechanism underlying the destructive effect of clinically relevant concentrations of LPS on intestinal TJ barrier and provide evidence for the clinical application of vitamin D in LPS-related intestinal barrier dysfunction.
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Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Lipopolissacarídeos/toxicidade , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Vitamina D/análogos & derivados , Células CACO-2 , Humanos , Substâncias Protetoras/farmacologia , Vitamina D/farmacologiaRESUMO
Studies have suggested the role of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in protecting intestinal barrier function from injuries induced by multiple reagents. Vitamin D deficiency was reported to be associated with poor prognosis in patients with alcoholic liver disease (ALD). This study is designed to investigate the effect of 1,25(OH)2D3 on ethanol-induced intestinal barrier dysfunction and the underlying mechanisms utilizing Caco-2 cell monolayers and a mouse model with acute ethanol injury. In Caco-2 monolayers, ethanol significantly increased monolayer permeability, disrupted TJ distribution, increased phosphorylation level of MLC, and induced generation of ROS compared with controls. However, pre-treatment with 1,25(OH)2D3 greatly ameliorated the ethanol-induced barrier dysfunction, TJ disruption, phosphorylation level of MLC, and generation of ROS compared with ethanol-exposed monolayers. Mice fed with vitamin d-sufficient diet had a higher plasma level of 25(OH)D3 and were more resistant to ethanol-induced acute intestinal barrier injury compared with the vitamin d-deficient group. These results suggest that the suppression of generation of ROS and increased phosphorylation level of MLC might be one of the mechanisms underlying the protective effect of 1,25(OH)2D3 on ethanol-induced intestinal barrier injury and provide evidence for the application of vitamin D as therapeutic factors against ethanol-induced gut leakiness.
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Calcitriol/farmacologia , Etanol/toxicidade , Mucosa Intestinal/efeitos dos fármacos , Animais , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Impedância Elétrica , Feminino , Humanos , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Cadeias Leves de Miosina/metabolismo , Permeabilidade , Fosforilação , Substâncias Protetoras/farmacologia , Proteína da Zônula de Oclusão-1/análiseRESUMO
OBJECTIVE: To evaluate the effect of combined resection for the treatment of T(4) gastric cancer and to refine the indication for en bloc dissection. METHODS: Clinical data of 69 cases receiving combined resection were analyzed retrospectively, and compared with those of 45 cases undergoing palliative gastrectomy. RESULTS: Of 69 cases, 54 patients underwent curative combined resection, 15 patients underwent palliative combined resection, including 24 with transverse colectomy, 22 with pancreatico-splenectomy, 8 with left lateral lobectomy of liver, 6 with pancreatico-splenectomy and transverse colectomy, 5 with pancreaticoduodenectomy, 2 with cholecystectomy, 1 with splenectomy, 1 with phrenectomy. The total rate of lymph node metastasis was 88.4%; the operative mortality rate was 4.3%; the morbidity rate was 14.5%. The postoperatively 1-, 3-, 5-year survival rates of CR group and NCR group were 66.9%, 39.1%, 26.8% and 33.4%, 7.4%, 0% respectively (P < 0.01). The five year survival rate of curative resection group was 34.1%. CONCLUSIONS: An en bloc combined resection can cure some T(4) patients, and improve the five-year survival rate.
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Gastrectomia/métodos , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Pancreatectomia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the clinical diagnosis, treatment and immunohistochemical characteristics of rectal stromal tumors. METHODS: Immunohistochemical expression of CD117 was retrieved in 20 cases of mesenchymal tumors of the rectum. And we analyzed the immunohistochemical characteristics, clinical data of rectal stromal tumors, and the results retrospectively. RESULTS: Sixteen cases of rectal stromal tumors, 3 cases of leiomyosarcomas and 1 case of schwannoma were diagnosed. Histologically, 2 cases of GISTs were classified as benign, 1 as borderline and 13 as malignant. All of rectal stromal tumors (100%) were strongly positive for CD117, and 14 cases (88%) positive for CD34. The demographic profile of rectal stromal tumors showed a male predominance with average age of 60 years old. The main symptoms were urinary retention, constipation and abdominal pain. 14 cases were positive in digital rectal examination. The recurrence rate of local and radical resection in malignant stromal tumors was 4/4 and 3/6. 1, 3, 5-year survival rates were 89%, 64%, 48%, respectively. After operation mean survival time of was 47 months. CONCLUSIONS: The specific GIST constituted the majority of mesenchymal tumors in rectum. It usually showed malignant biological behavior. Invasion and recurrence were common. Earlier diagnosis and radical resection had better prognosis. Periodically following up can help to detect the recurrence timely.
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Tumores do Estroma Gastrointestinal , Neoplasias Retais , Adulto , Idoso , Feminino , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/diagnóstico , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the role of tissue factor (TF) expression in the invasive and metastatic ability of colorectal carcinoma and explore the influence of TF on the invasive ability of HT-29 cells. METHODS: TF expression of specimens from 85 colorectal carcinomas and 6 colorectal adenomas was observed by immunohistochemistry. The role of TF expression in prognosis and tumor invasion and metastasis was analyzed. The plasmids pcDNA3.1/Zeo bearing either sense or antisense-TFcDNA were transfected into HT-29 cells by the way of Lipofectamine 2000. TF proteins in transfected and untransfected HT-29cells were detected by Western blot. In vitro Matrigel invasion assays were performed to show the invasive ability of those cells. RESULTS: TF expression was positive in 40 (47.1%) of 85 colorectal carcinoma specimens, but negative in normal mucosa and adenoma specimens. TF expression showed significant correlation with tumor invasive depth (r = 0.895, P < 0.01). TF expression showed significant correlation with synchronous and metachronous hepatic metastasis (r = 0.974, P < 0.01 and r = 0.963, P < 0.01 respectively). TF expression was a significant risk factor for hepatic metastasis (P < 0.01) and prognosis (P < 0.01). TF expression in HT-29 cells with sense/antisense-TFcDNA transfection was more/less than that of the cells without transfection. The invasive ability of HT-29 cells with sense-TFcDNA transfection was increased in vitro compared with the untransfected cells, but HT-29 cells with antisense-TFcDNA transfection got the contrary change. CONCLUSIONS: TF may take part in the invasive and metastatic process of primary colorectal carcinoma, and TF expression may be an indicator of hepatic metastasis and prognosis for colorectal carcinoma patients. TF expression may increase the invasive ability of HT-29 cell in vitro.
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Neoplasias Colorretais/patologia , Tromboplastina/análise , Western Blotting , Movimento Celular , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Células HT29 , Humanos , Imuno-Histoquímica , Modelos Logísticos , Análise Multivariada , Tromboplastina/genéticaRESUMO
OBJECTIVE: To evaluate risk factors associated with morbidity and mortality in patients undergoing surgery for obstructing colorectal cancer. METHODS: One hundred and eleven patients who underwent emergency surgery for obstructing colorectal cancer from January 2001 to December 2009 were retrospectively reviewed. RESULTS: Forty-nine patients had obstruction proximal to the splenic flexure and 62 patients at or distal to the splenic flexure. The morbidity and mortality rates of the emergency surgery for malignant obstruction were 21.6% and 5.4%, respectively. Twenty-three patients received resection with primary anastomosis with intraoperative lavage for left-sided lesions. There was no difference in morbidity between right-sided cancer and left-sided cancer(P>0.05). Univariable analysis showed that complications rate was higher in patients with higher ASA score (3-4) and in those aged over 60 years. Multivariate logistic regression analysis revealed that ASA score(3-4) was an independent risk factor. CONCLUSIONS: Emergency surgery for obstructing colorectal cancer is associated with high rates of morbidity and mortality. Selection of the proper operation and intensive treatment after surgery are recommended in high risk patients.