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1.
World J Clin Oncol ; 15(2): 317-328, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38455137

RESUMO

BACKGROUND: Limonin is one of the most abundant active ingredients of Tetradium ruticarpum. It exerts antitumor effects on several kinds of cancer cells. However, whether limonin exerts antitumor effects on colorectal cancer (CRC) cells and cancer stem-like cells (CSCs), a subpopulation responsible for a poor prognosis, is unclear. AIM: To evaluate the effects of limonin on CSCs derived from CRC cells. METHODS: CSCs were collected by culturing CRC cells in serum-free medium. The cytotoxicity of limonin against CSCs and parental cells (PCs) was determined by cholecystokinin octapeptide-8 assay. The effects of limonin on stemness were detected by measuring stemness hallmarks and sphere formation ability. RESULTS: As expected, limonin exerted inhibitory effects on CRC cell behaviors, including cell proliferation, migration, invasion, colony formation and tumor formation in soft agar. A relatively low concentration of limonin decreased the expression stemness hallmarks, including Nanog and ß-catenin, the proportion of aldehyde dehydrogenase 1-positive CSCs, and the sphere formation rate, indicating that limonin inhibits stemness without presenting cytotoxicity. Additionally, limonin treatment inhibited invasion and tumor formation in soft agar and in nude mice. Moreover, limonin treatment significantly inhibited the phosphorylation of STAT3 at Y705 but not S727 and did not affect total STAT3 expression. Inhibition of Nanog and ß-catenin expression and sphere formation by limonin was obviously reversed by pretreatment with 2 µmol/L colievlin. CONCLUSION: Taken together, these results indicate that limonin is a promising compound that targets CSCs and could be used to combat CRC recurrence and metastasis.

2.
Artigo em Inglês | MEDLINE | ID: mdl-37610688

RESUMO

OBJECTIVE: Cardiopulmonary bypass (CPB) is a requisite technique for thoracotomy in advanced cardiovascular surgery. However, the consequent myocardial ischemia-reperfusion injury (MIRI) is the primary culprit behind cardiac dysfunction and fatal consequences post-operation. Prior research has posited that myocardial insulin resistance (IR) plays a vital role in exacerbating the progression of MIRI. Nonetheless, the exact mechanisms underlying this phenomenon remain obscure. METHODS: We constructed pyruvate dehydrogenase E1 α subunit (PDHA1) interference and overexpression rats and used ascending aorta occlusion in an in vivo model of CPB-MIRI. We devised an in vivo model of CPB-MIRI by constructing rat models with both pyruvate dehydrogenase E1α subunit (PDHA1) interference and overexpression through ascending aorta occlusion. We analyzed myocardial glucose metabolism and the degree of myocardial injury using functional monitoring, biochemical assays, and histological analysis. RESULTS: We discovered a clear downregulation of glucose transporter 4 (GLUT4) protein content expression in the CPB I/R model. In particular, cardiac-specific PDHA1 interference resulted in exacerbated cardiac dysfunction, significantly increased myocardial infarction area, more pronounced myocardial edema, and markedly increased cardiomyocyte apoptosis. Notably, the opposite effect was observed with PDHA1 overexpression, leading to a mitigated cardiac dysfunction and decreased incidence of myocardial infarction post-global ischemia. Mechanistically, PDHA1 plays a crucial role in regulating the protein content expression of GLUT4 on cardiomyocytes, thereby controlling the uptake and utilization of myocardial glucose, influencing the development of myocardial insulin resistance, and ultimately modulating MIRI. CONCLUSION: Overall, our study sheds new light on the pivotal role of PDHA1 in glucose metabolism and the development of myocardial insulin resistance. Our findings hold promising therapeutic potential for addressing the deleterious effects of MIRI in patients.

3.
World J Hepatol ; 15(12): 1258-1271, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38223416

RESUMO

Primary liver cancer is a severe and complex disease, leading to 800000 global deaths annually. Emerging evidence suggests that inflammation is one of the critical factors in the development of hepatocellular carcinoma (HCC). Patients with viral hepatitis, alcoholic hepatitis, and steatohepatitis symptoms are at higher risk of developing HCC. However, not all inflammatory factors have a pathogenic function in HCC development. The current study describes the process and mechanism of hepatitis development and its progression to HCC, particularly focusing on viral hepatitis, alcoholic hepatitis, and steatohepatitis. Furthermore, the roles of some essential inflammatory cytokines in HCC progression are described in addition to a summary of future research directions.

4.
World J Gastrointest Oncol ; 14(8): 1600-1603, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36160751

RESUMO

The following letter to the editor highlights the review titled "Inflammatory bowel disease-related colorectal cancer: Past, present and future perspectives" in World J Gastrointest Oncol 2022 March 15; 14(3): 547-567. It is necessary to explore the role of inflammation in promoting tumorigenesis and development of gastrointestinal cancers.

5.
BMC Gastroenterol ; 22(1): 15, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35012467

RESUMO

BACKGROUND: Recent studies have confirmed that combined surgery and anti-TNF therapy could improve outcomes in patients with perianal fistulising Crohn's disease (PFCD). However, the optimal timing for infliximab infusion after surgical intervention is uncertain. We aimed to determine the long-term efficacy of early initiation of infliximab following surgery among PFCD patients. METHODS: We performed a retrospective cohort study of PFCD patients who received combined infliximab and surgical treatment between 2010 and 2018 at a tertiary referral hospital. Patients were grouped according to the time interval between surgery and infliximab infusion, with < 6 weeks into early infliximab induction group and > 6 weeks into delayed infliximab induction group. The primary outcome was to compare surgical re-intervention between early and delayed infliximab induction groups. The secondary outcomes were fistula healing and predictors associated with these outcomes of early infliximab induction approach. RESULTS: One hundred and seventeen patients were included (73 in early infliximab induction, 44 in delayed infliximab induction). The median interval between surgery and infliximab initiation was 9.0 (IQR 5.5-17.0) days in early infliximab induction group and 188.0 (IQR 102.25-455.75) days in delayed infliximab induction group. After followed-up for a median of 36 months, 61.6% of patients in early infliximab induction group and 65.9% in delayed infliximab induction group attained fistula healing (p = 0.643). The cumulative re-intervention rate was 23%, 32%, 34% in early infliximab induction group and 16%, 25%, 25% in delayed infliximab induction group, at 1, 2, and 3 years respectively (p = 0.235). Presence of abscess at baseline (HR = 5.283; 95% CI, 1.61-17.335; p = 0.006) and infliximab maintenance therapy > 3 infusions (HR = 3.691; 95% CI, 1.233-11.051; p = 0.02) were associated with re-intervention in early infliximab induction group. Presence of abscess at baseline also negatively influenced fistula healing (HR = 3.429, 95% CI, 1.216-9.668; p = 0.02). CONCLUSION: Although no clear benefit was shown compared with delayed infliximab induction group, early initiation of infliximab after surgery could achieve promising results for PFCD patients. Before infliximab infusion, durable drainage is required for patients with concomitant abscess or prolonged infliximab maintenance therapy.


Assuntos
Doença de Crohn , Fístula Retal , Doença de Crohn/tratamento farmacológico , Drenagem , Fármacos Gastrointestinais/uso terapêutico , Humanos , Infliximab/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral
6.
World J Clin Cases ; 9(15): 3506-3516, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34046451

RESUMO

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder characterized by recurrent nodules, abscesses, and sinus tracts. Crohn's disease (CD) is characterized by inflammation of the entire digestive tract and belongs to the group of inflammatory bowel diseases, and there are many extraintestinal manifestations, among which hidradenitis suppurativa is one of the rare extraintestinal manifestations. There appears to be a strong association between CD and HS based on clinical and histological similarities (sinus tract development, granulomatous inflammation, and scarring), intersections in pathogenesis (genetic loci, immune dysregulation mechanisms, and microbiome changes), and commonality in treatment. In this review, we summarize recent studies on the association between HS and CD.

7.
Am J Cancer Res ; 10(11): 3920-3934, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33294277

RESUMO

Colorectal cancers (CRC) with microsatellite instability (MSI) or mismatch repair-deficiency (dMMR), but without detectable MMR germline mutations are termed Lynch-like syndrome (LLS). We assess the clinicopathologic and molecular characteristics of LLS tumors and the proportion in LLS, which remain poorly investigated in China. We enrolled 404 CRC patients with surgery in our institution from 2014 to 2018. LLS tumors were detected by a molecular stratification based on MMR protein expression, MLH1 methylation and MMR gene mutation. LLS tumors were profiled for germline mutations in 425 cancer-relevant genes. Among 42 MMR-deficient tumors, 7 (16.7%) were attributable to MLH1 methylation and 7 (16.7%) to germline mutations, leaving 28 LLS cases (66.6%). LLS tumors were diagnosed at a mean age of 60.7 years, had an almost equivalent ratio among rectum, left colon and right colon, and had high rates of lymph node metastases (50%, 4/28 N2). Most MMR gene mutations (88.2%, 15/17) in LLS tumors were variants of unknown significance (VUS). Two novel frameshift mutations were detected in ATM and ARID1A, which are emerging as candidate responsible genes for LLS. In this study, 28 (66.6%) MMRd tumors were classified as LLS, which were significantly higher than reports of western countries. LLS tumors were more likely to carry lymph node metastases. However, it's hard to differentiated LLS tumors from LS through family history, tumor location, histological type of tumors, immunohistochemistry (IHC) for MMR proteins and MSI analysis.

8.
World J Gastroenterol ; 26(14): 1554-1563, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32327905

RESUMO

Infliximab (IFX), as a drug of first-line therapy, can alter the natural progression of Crohn's disease (CD), promote mucosal healing and reduce complications, hospitalizations, and the incidence of surgery. Perianal fistulas are responsible for the refractoriness of CD and represent a more aggressive disease. IFX has been demonstrated as the most effective drug for the treatment of perianal fistulizing CD. Unfortunately, a significant proportion of patients only partially respond to IFX, and optimization of the therapeutic strategy may increase clinical remission. There is a significant association between serum drug concentrations and the rates of fistula healing. Higher IFX levels during induction are associated with a complete fistula response in these patients. Given the apparent relapse of perianal fistulizing CD, maintenance therapy with IFX over a longer period seems to be more beneficial. It appears that patients without deep remission are at an increased risk of relapse after stopping anti-tumor necrosis factor agents. Thus, only patients in prolonged clinical remission should be considered for withdrawal of IFX treatment when biomarker and endoscopic remission is demonstrated, especially when the hyperintense signals of fistulas on T2-weighed images have disappeared on magnetic resonance imaging. Fundamentally, the optimal timing of IFX use is highly individualized and should be determined by a multidisciplinary team.


Assuntos
Doença de Crohn/tratamento farmacológico , Infliximab/administração & dosagem , Fístula Retal/tratamento farmacológico , Indução de Remissão/métodos , Prevenção Secundária/métodos , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Esquema de Medicação , Humanos , Imageamento por Ressonância Magnética , Proctoscopia , Fístula Retal/diagnóstico , Fístula Retal/etiologia , Recidiva , Fatores de Tempo , Resultado do Tratamento , Cicatrização/efeitos dos fármacos
9.
Aging (Albany NY) ; 11(16): 6053-6068, 2019 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-31469661

RESUMO

BACKGROUND: Dysregulation of numerous lncRNAs has been recently confirmed in glioma; however, the majority of their roles and mechanisms involved in this notorious disease remain largely unclear. This study aims to explore the roles and molecular mechanisms of LINC01198 implicated in the proliferation and chemoresistance in glioma. RESULTS: LINC01198 was elevated in glioma, and this predicted a poorer prognosis for patients with glioma. LINC01198 knockdown inhibited, while LINC01198 overexpression promoted, glioma cell proliferation and resistance to temozolomide. Mechanistically, NEDD4-1 (neural precursor cell expressed, developmentally downregulated 4, E3 ubiquitin protein ligase) and phosphatase and tensin homolog (PTEN) were recruited by LINC01198, which functioned as a scaffold. Moreover, we showed that LINC01198 exerted its oncogenic activities by enhancing the NEDD4-1-dependent repression of PTEN. CONCLUSIONS: Our study elucidated the role of oncogenic LINC01198 in glioma proliferation and temozolomide resistance, and this role may serve as a promising target for glioma therapy. METHODS: LINC01198 expression in glioma tissues and that in paired normal tissues were measured by qRT-PCR. The functional roles of LINC01198 in glioma were demonstrated by a series of in vitro experiments. CCK-8 assay, RNA pulldown, RNA immunoprecipitation and western blotting were used to demonstrate the potential mechanisms of LINC01198.


Assuntos
Neoplasias Encefálicas/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Glioma/metabolismo , Ubiquitina-Proteína Ligases Nedd4/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , RNA Longo não Codificante/metabolismo , Temozolomida/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica , Glioma/tratamento farmacológico , Glioma/genética , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Longo não Codificante/genética , Temozolomida/uso terapêutico
10.
Arq Bras Cir Dig ; 32(1): e1420, 2019 Feb 07.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30758468

RESUMO

BACKGROUND: Clinical characteristics are keys to improve identification and treatment of Crohn´s disease (CD) so that large sample analysis is of great value. AIM: To explore the clinical characteristics of perianal fistulising CD. METHODS: Analysis of 139 cases focused on their clinical data. RESULTS: The proportion of males and females is 3.3:1; the mean age is 28.2 years; 47.5% of patients had anal fistula before CD diagnosis. Patients with prior perianal surgery and medication accounted for 64.7% and 74.1% respectively. The L3 type of lesion was present in 49.6% and the B1 and B2 types for 51.8% and 48.2% respectively; complex anal fistula was diagnosed in 90.6%. Symptoms of diarrhea were found in 46% and perianal lesions alone in 29.5% of patients. Abnormal BMI values was present in 44.6%; active CD activity index in 64.7%; and 94.2% had active perianal disease activity index. A proportion of patients manifest abnormal C-reactive protein, erythrocyte sedimentation rate, platelet, hemoglobin and albumin. CONCLUSION: We suggest that patients with anal fistula associated to these clinical features should alert the medical team to the possibility of CD, which should be further investigated through endoscopy and imaging examination of alimentary tract to avoid the damage of anal function by routine anal fistula surgery.


Assuntos
Doença de Crohn/complicações , Fístula Retal/etiologia , Adulto , Doença de Crohn/diagnóstico , Feminino , Humanos , Masculino , Períneo
11.
ABCD (São Paulo, Impr.) ; 32(1): e1420, 2019. tab
Artigo em Inglês | LILACS | ID: biblio-983669

RESUMO

ABSTRACT Background: Clinical characteristics are keys to improve identification and treatment of Crohn´s disease (CD) so that large sample analysis is of great value. Aim: To explore the clinical characteristics of perianal fistulising CD. Methods: Analysis of 139 cases focused on their clinical data. Results: The proportion of males and females is 3.3:1; the mean age is 28.2 years; 47.5% of patients had anal fistula before CD diagnosis. Patients with prior perianal surgery and medication accounted for 64.7% and 74.1% respectively. The L3 type of lesion was present in 49.6% and the B1 and B2 types for 51.8% and 48.2% respectively; complex anal fistula was diagnosed in 90.6%. Symptoms of diarrhea were found in 46% and perianal lesions alone in 29.5% of patients. Abnormal BMI values was present in 44.6%; active CD activity index in 64.7%; and 94.2% had active perianal disease activity index. A proportion of patients manifest abnormal C-reactive protein, erythrocyte sedimentation rate, platelet, hemoglobin and albumin. Conclusion: We suggest that patients with anal fistula associated to these clinical features should alert the medical team to the possibility of CD, which should be further investigated through endoscopy and imaging examination of alimentary tract to avoid the damage of anal function by routine anal fistula surgery.


RESUMO Racional: As características clínicas são fundamentais para melhorar a identificação e o tratamento da doença de Crohn (DC), de modo que a análise da amostra seja de grande valor. Objetivo: Explorar as características clínicas da DC fistulizante perianal. Métodos: Análise de 139 casos focados em seus dados clínicos. Resultados: A proporção de homens e mulheres foi de 3,3: 1; a média de idade de 28,2 anos; 47,5% dos pacientes tiveram fístula anal antes do diagnóstico de DC. Pacientes com cirurgia perianal prévia e medicação representaram 64,7% e 74,1%, respectivamente. O tipo de lesão L3 estava presente em 49,6% e os tipos B1 e B2, em 51,8% e 48,2%, respectivamente; fístula anal complexa foi diagnosticada em 90,6%. Sintomas de diarréia foram encontrados em 46% e lesões perianais isoladas em 29,5% dos pacientes. Valores anormais de IMC estavam presentes em 44,6%; índice de atividade DC ativa em 64,7%; e 94,2% tinham índice de atividade de doença perianal ativo. Proporção significativa de pacientes tinha proteína-C reativa, taxa de sedimenta do eritrócito, plaquetas hemoglobina e albumina anormais. Conclusão: Sugere-se que pacientes com fístula anal associada às essas características clínicas alertem a equipe médica para a possibilidade de DC, que deve ser investigada por endoscopia e exame de imagem do trato digestivo para evitar dano na função anal pela operação que rotineiramente é realizada no tratamento da fístula anal.


Assuntos
Humanos , Masculino , Feminino , Adulto , Doença de Crohn/complicações , Fístula Retal/etiologia , Períneo , Doença de Crohn/diagnóstico
12.
World J Gastroenterol ; 24(30): 3414-3425, 2018 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-30122880

RESUMO

AIM: To explore the role and mechanism of total flavone of Abelmoschus manihot (TFA) on epithelial-mesenchymal transition (EMT) progress of Crohn's disease (CD) intestinal fibrosis. METHODS: First, CCK-8 assay was performed to assess TFA on the viability of intestinal epithelial (IEC-6) cells and select the optimal concentrations of TFA for our further studies. Then cell morphology, wound healing and transwell assays were performed to examine the effect of TFA on morphology, migration and invasion of IEC-6 cells treated with TGF-ß1. In addition, immunofluorescence, real-time PCR analysis (qRT-PCR) and western blotting assays were carried out to detect the impact of TFA on EMT progress. Moreover, western blotting assay was performed to evaluate the function of TFA on the Smad and MAPK signaling pathways. Further, the role of co-treatment of TFA and si-Smad or MAPK inhibitors has been examined by qRT-PCR, western blotting, morphology, wound healing and transwell assays. RESULTS: In this study, TFA promoted transforming growth factor-ß1 (TGF-ß1)-induced (IEC-6) morphological change, migration and invasion, and increased the expression of epithelial markers and reduced the levels of mesenchymal markers, along with the inactivation of Smad and MAPK signaling pathways. Moreover, we revealed that si-Smad and MAPK inhibitors effectively attenuated TGF-ß1-induced EMT in IEC-6 cells. Importantly, co-treatment of TFA and si-Smad or MAPK inhibitors had better inhibitory effects on TGF-ß1-induced EMT in IEC-6 cells than either one of them. CONCLUSION: These findings could provide new insight into the molecular mechanisms of TFA on TGF-ß1-induced EMT in IEC-6 cells and TFA is expected to advance as a new therapy to treat CD intestinal fibrosis.


Assuntos
Abelmoschus/química , Doença de Crohn/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Flavonas/farmacologia , Extratos Vegetais/farmacologia , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Doença de Crohn/patologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Fibrose , Flavonas/uso terapêutico , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Proteínas Smad/genética , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
13.
World J Gastroenterol ; 21(8): 2475-82, 2015 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-25741157

RESUMO

AIM: To evaluate the efficacy and long-term outcome of infliximab combined with surgery to treat perianal fistulizing Crohn's disease (CD). METHODS: The work was performed as a prospective study. All patients received infliximab combined with surgery to treat perianal fistulizing CD, which was followed by an immunosuppressive agent as maintenance therapy. RESULTS: A total of 28 patients with perianal fistulizing CD were included. At week 30, 89.3% (25/28) of the patients were clinically cured with an average healing time of 31.4 d. The CD activity index decreased to 70.07±77.54 from 205.47±111.13 (P<0.01) after infliximab treatment. The perianal CD activity index was decreased to 0.93±2.08 from 8.54±4.89 (P<0.01). C-reactive protein, erythrocyte sedimentation rate, platelets, and neutrophils all decreased significantly compared with the pretreatment levels (P<0.01). Magnetic resonance imaging results for 16 patients after therapy showed that one patient had a persistent presacral-rectal fistula and another still had a cavity without clinical symptoms at follow-up. After a median follow-up of 26.4 mo (range: 14-41 mo), 96.4% (27/28) of the patients had a clinical cure. CONCLUSION: Infliximab combined with surgery is effective and safe in the treatment of perianal fistulizing CD, and this treatment was associated with better long-term outcomes.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Doença de Crohn/tratamento farmacológico , Imunossupressores/uso terapêutico , Fístula Retal/cirurgia , Adolescente , Adulto , China , Terapia Combinada , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Feminino , Humanos , Infliximab , Imageamento por Ressonância Magnética , Masculino , Estudos Prospectivos , Fístula Retal/diagnóstico , Fístula Retal/etiologia , Centros de Atenção Terciária , Fatores de Tempo , Resultado do Tratamento , Cicatrização/efeitos dos fármacos , Adulto Jovem
14.
Zhonghua Wei Chang Wai Ke Za Zhi ; 16(4): 323-7, 2013 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-23608791

RESUMO

OBJECTIVE: To evaluate the efficacy of infliximab combined with surgery in the treatment of perianal fistulizing Crohn disease (CD). METHODS: Clinical data of 15 patients with perianal fistulizing CD receiving infliximab combined with surgery in the Affiliated Hospital of Nanjing University of Chinese Medicine from March 2010 to June 2011 were analyzed retrospectively. One week after operation, all the patients received infliximab infusion thrice at weeks 0, 2, and 6. Crohn disease activity index (CDAI), perianal Crohn disease activity index (PDAI), body mass index (BMI), routine blood test and endoscopy were evaluated at week 0, 14. Adverse reactions and healing time were recorded. RESULTS: At week 14, the response rate was 100% with 86.7% (13/15) complete responders. One patient had local improvement and one developed recurrent fistula. The mean healing time was 32.5 (20-45) d. Anorectal stenosis in 4 patients was significantly improved. At week 14, CDAI decreased to 114.0±90.3 from 230.5±97.5 after IFX treatment. PCDAI decreased to 2.8±3.2 from 9.9±3.4, and BMI increased to (21.5±3.0)kg/m(2) from (19.1±3.1)kg/m(2). C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelet and neutrophil were significantly decreased from baseline (all P<0.01). Intestinal mucosa healed completely in one patient. There were no serious adverse events except hypokalemia in one patient and severe infusion reaction in another. CONCLUSION: Infliximab combined with surgery is effective and safe for perianal fistulizing CD.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/cirurgia , Fístula Retal/tratamento farmacológico , Fístula Retal/cirurgia , Adolescente , Adulto , Terapia Combinada , Doença de Crohn/complicações , Feminino , Seguimentos , Humanos , Infliximab , Masculino , Fístula Retal/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
15.
Int J Colorectal Dis ; 28(4): 547-53, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22914965

RESUMO

OBJECTIVE: The aim of this article is to study the inhibitory effects of baicalin on the growth and metastasis of orthotopic xenografts consisting of human HCT-116 colorectal cancer cells that are deficient in the mismatch repair gene hMLH1 in nude mice. METHODS: A fluorescent orthotopic transplantation model of HCT-116 cells was established. The treatment groups were administered baicalin 50 mg/kg (G2), 100 mg/kg (G3), and 200 mg/kg (G4), and the negative control group (G1) was administered 5 % NaHCO3. The volume and vascular density of the primary tumors, body weights, survival conditions, and death rates of the mice were analyzed. RESULTS: On the 14th, 21st, and 28th days, tumor volume in the treatment groups was significantly smaller than that in the control group, and the differences were statistically significant. At the end of the experiment, the survival rate of the experimental animals in the G3 was significantly higher than that in the G1 and G4 (P < 0.05). There were no significant differences in both the weights and surface vascular densities of the primary tumor and the metastatic tumor among all groups. CONCLUSION: Baicalin had a significant inhibitory effect on the growth of nude mouse orthotopic xenografts consisting of human HCT-116 colorectal tumor cells that are deficient in the mismatch repair gene hMLH1.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/deficiência , Neoplasias Colorretais/tratamento farmacológico , Reparo de Erro de Pareamento de DNA/genética , Flavonoides/uso terapêutico , Proteínas Nucleares/deficiência , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Neoplasias Colorretais/irrigação sanguínea , Neoplasias Colorretais/patologia , Fluorescência , Proteínas de Fluorescência Verde/metabolismo , Células HCT116 , Humanos , Camundongos , Camundongos Nus , Proteína 1 Homóloga a MutL , Metástase Neoplásica , Proteínas Nucleares/genética , Análise de Sobrevida , Resultado do Tratamento , Carga Tumoral
16.
Zhonghua Wai Ke Za Zhi ; 50(9): 843-7, 2012 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-23157964

RESUMO

OBJECTIVE: To study the anticancer effects of Baicalin on an orthotopic transplantation mouse model of mismatch repair gene deficient colorectal cancer. METHODS: Sixty orthotopic transplantation mice model of human colon cancer cell line HCT-116 expressing eGFP were established, which were divided randomly into negative controlled group (5% NaHCO3) and 50, 100, 200 mg/kg Baicalin groups. The nude mice were treated with intragastric infusion twice a day. Nude mice growth state, average weigh, inhibition rate of transplanted tumor, tumor metastasis and survival state were observed. RESULTS: At 14, 21 and 28 days after treatment with different dose of Baicalin, tumor growth velocity was significantly slower in the treatment groups, and tumor volume was significantly smaller than the controlled group (there were (832 ± 637), (2012 ± 1566) and (2494 ± 1557) mm(3) respectively in 14, 21 and 28 days) (F = 4.433, P < 0.05). At the end point of study, survival state of 100 mg/kg group (13/15) was superior to controlled group (8/15) and 200 mg/kg group (8/15) (χ(2) = 4.665 and 3.980, P < 0.05).However, there were no significant differences in tumor metastasis and tumor surface vessel density. CONCLUSIONS: Baicalin has statistically significant effects in inhibiting tumor growth in an orthotopic transplantation mouse model of mismatch repair gene deficient colorectal cancer, and 100 mg/kg may be an ideal treatment dose.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Colorretais/tratamento farmacológico , Flavonoides/uso terapêutico , Proteínas Nucleares/genética , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Flavonoides/administração & dosagem , Deleção de Genes , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína 1 Homóloga a MutL , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Asian Pac J Cancer Prev ; 13(9): 4263-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23167325

RESUMO

Colorectal cancer has become a major disease threatening human health. To establish animal models that exhibit the characteristics of human colorectal cancer will not only help to study the mechanisms underlying the genesis and development effectively, but also provide ideal carriers for the screening of medicines and examining their therapeutic effects. In this study, we established a stable, colon cancer nude mouse model highly expressing green fluorescent protein (GFP) for spontaneous metastasis after surgical orthotopic implantation (SOI). GFP- labeled colon cancer models for metastasis after SOI were successfully established in all of 15 nude mice and there were no surgery-related complications or deaths. In week 3, primary tumors expressing GFP were observed in all model animals under fluoroscopy and two metastatic tumors were monitored by fluorescent imaging at the same time. The tumor volumes progressively increased with time. Seven out of 15 tumor transplanted mice died and the major causes of death were intestinal obstruction and cachexia resulting from malignant tumor growth. Eight model animals survived at the end of the experiment, 6 of which had metastases (6 cases to mesenteric lymph nodes, 4 hepatic, 2 pancreatic and 1 mediastinal lymph node). Our results indicate that our GFP-labeled colon cancer orthotopic transplantation model is useful with a high success rate; the transplanted tumors exhibit similar biological properties to human colorectal cancer, and can be used for real-time, in vivo, non-invasive and dynamic observation and analysis of the growth and metastasis of tumor cells.


Assuntos
Adenocarcinoma/secundário , Neoplasias do Colo/metabolismo , Modelos Animais de Doenças , Proteínas de Fluorescência Verde/metabolismo , Neoplasias Hepáticas/secundário , Adenocarcinoma/irrigação sanguínea , Adenocarcinoma/metabolismo , Animais , Caquexia/etiologia , Neoplasias do Colo/irrigação sanguínea , Neoplasias do Colo/patologia , Humanos , Neoplasias Hepáticas/metabolismo , Metástase Linfática , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microvasos/patologia , Transplante de Neoplasias , Neovascularização Patológica/patologia , Imagem Óptica , Redução de Peso
18.
World J Gastroenterol ; 16(46): 5822-9, 2010 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-21155003

RESUMO

AIM: To retrospectively evaluate the magnetic resonance imaging (MRI) features of adult retrorectal tumors and compare with histopathologic findings. METHODS: MRI features of 21 patients with preoperative suspicion of retrorectal tumors were analyzed based on the histopathological and clinical data. RESULTS: Fourteen benign cystic lesions appeared hypointense on T1-weighted images, and hyperintense on T2-weighted images with regular peripheral rim. Epidermoid or dermoid cysts were unilocular, and tailgut cysts were multilocular. Presence of intracystic intermediate signal intensity was observed in one case of tailgut cyst with a component of adenocarcinoma. Six solid tumors were malignant lesions and showed heterogeneous intensity on MRI. Mucinous adenocarcinomas showed high signal intensity on T2-weighted and mesh-like enhancing areas on fat-suppressed T2-weighted images. There was a fistula between the mass and anus with an internal opening in mucinous adenocarcinomas arising from anal fistula. Gastrointestinal stromal tumors displayed low signal intensity on T1-weighted images, and intermediate to high signal intensity on T2-weighted images. Central necrosis could be seen as a high signal on T2-weighted images. CONCLUSION: MRI is a helpful technique to define the extent of the retrorectal tumor and its relationship to the surrounding structures, and also to demonstrate possible complications so as to choose the best surgical approach.


Assuntos
Imageamento por Ressonância Magnética/métodos , Neoplasias Retais/patologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Adulto Jovem
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