RESUMO
BACKGROUND: Gremlin-1 (GREM1) is a protein closely related to tumor growth, although its function in bladder cancer (BCa) is currently unknown. Our first objective was to study the GREM1 treatment potential in BCa. METHODS: BCa tissue samples were collected for the detection of GREM1 expression using Western blot analysis and Immunofluorescence staining. Association of GREM1 expression with clinicopathology and prognosis as detected by TCGA (The Cancer Genome Atlas) database. The functional investigation was tested by qRT-PCR, western blot analysis, CCK-8, cell apoptosis, wound healing, and transwell assays. The interaction between GREM1 and the downstream PI3K/AKT signaling pathway was assessed by Western blot analysis. RESULTS: GREM1 exhibited high expression in BCa tissues and was linked to poor prognosis. Stable knockdown of GREM1 significantly inhibited BCa cell (T24 and 5637) proliferation, apoptosis, migratory, invasive, as well as epithelial-mesenchymal transition (EMT) abilities. GREM1 promotes the progression in BCa via PI3K/AKT signaling pathway. CONCLUSION: Findings demonstrate that the progression-promoting effect of GREM1 in BCa, providing a novel biomarker for BCa-targeted therapy.
Assuntos
Fosfatidilinositol 3-Quinases , Neoplasias da Bexiga Urinária , Humanos , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt , Prognóstico , Biomarcadores , Neoplasias da Bexiga Urinária/genética , Peptídeos e Proteínas de Sinalização Intercelular/genéticaRESUMO
RATIONALE: Agenesis of the dorsal pancreas (ADP) is a rare congenital anomaly of the pancreas. ADP is associated with some other medical problems such as diabetes mellitus, abdominal pain/bloating, pancreatitis, pancreatic neuroendocrine tumor and so on. In this study, we present a case of ADP with chronic suppurative pancreatitis, summarize the clinical characteristics of the reported cases in China and review the correlative literature. PATIENT CONCERNS: A 51-year-old Chinese man, with a history of impaired fasting glucose, presented with jaundice, pruritus and dark urine. Laboratory analysis showed abnormal liver function and elevated carbohydrate antigen 19-9. DIAGNOSES: Contrast-enhanced computed tomography demonstrated a mass located at the head of pancreas and complete absence of the body and tail of pancreas. Endoscopic retrograde cholangiopancreatography demonstrated an eccentric malignant stricture about 1.6cm of distal common bile duct. INTERVENTIONS: The patient underwent pancreaticoduodenectomy because of the suspicion of pancreatic tumor. The postoperative pathological result was chronic suppurative pancreatitis, with moderate hyperplasia in focal ductal epithelium. OUTCOMES: A long-term follow-up shows that the patient is asymptomatic with well-controlled diabetes mellitus and pancreatic exocrine insufficiency. LESSONS: ADP is a quite rare congenital malformation of the pancreas with poorly-understood pathogenesis. The diagnosis of ADP depends on the imaging examination. The therapeutic strategy varies from person to person due to the different accompanying conditions.
Assuntos
Anormalidades Congênitas , Pâncreas/anormalidades , Pâncreas/diagnóstico por imagem , Pancreatite Crônica/complicações , Colangiopancreatografia Retrógrada Endoscópica , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/cirurgia , Pancreaticoduodenectomia , Pancreatite Crônica/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: To discuss the effect and mechanism of adenovirus-mediated OX40Ig gene transfer in inducing long-term survival of liver allografts in rats. METHODS: Orthotopic liver transplantation was performed from Lewis to Brown Norway (BN) rats through the modified two-cuffed technique, and all rats were randomly divided equally into four groups: control, AdEGFP, AdOX40Ig, and FK506. The survival times of the rats were recorded. The rats' liver function, serum cytokines, hepatocyte pathology, OX40Ig protein level, and mixed lymphocyte reaction (MLR) with or without recombinant interleukin-2 (rIL-2) were evaluated. RESULTS: Compared with the control and AdEGFP groups, the rats in the AdOX40Ig and FK506 groups survived longer (Pâ¯<â¯0.05), experienced less damage to hepatic function (Pâ¯<â¯0.05), and showed milder hepatic cellular rejection and less hepatic cellular apoptosis. Interferon (IFN)-γ and IL-2 content in the serum were lower after operation (Pâ¯<â¯.05) in the AdOX40Ig and FK506 groups. On the contrary, IL-4 and IL-10 content in the serum was higher after operation (Pâ¯<â¯0.05) in the AdOX40Ig and FK506 groups. OX40Ig protein was significantly expressed in the AdOX40Ig group and reached the highest level on the 7th day after operation. With respect to the MLR between BN and Lewis rats, the AdOX40Ig group showed a lighter reaction for the same strain than the control and AdEGFP groups (Pâ¯<â¯0.05), which is different from the MLR between BN and F344 rats. After adding rIL-2 to the MLR system between BN rats in the AdOX40Ig group and Lewis rats, MLR was aggravated. CONCLUSION: Through OX40/OX4OL pathways, OX40Ig created an immunosuppressive effect after liver transplantation in rats. This immunosuppressive effect is associated with reduced IL-2 and can be reversed by adding IL-2 with antigen specificity.
Assuntos
Antígenos de Diferenciação/genética , Rejeição de Enxerto/terapia , Transplante de Fígado , Fígado/patologia , Adenoviridae/genética , Animais , Modelos Animais de Doenças , Técnicas de Transferência de Genes , Terapia Genética , Vetores Genéticos , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/genética , Humanos , Imunossupressores/uso terapêutico , Interferon gama/sangue , Interleucina-2/sangue , Masculino , Ratos , Ratos Endogâmicos Lew , Tacrolimo/uso terapêutico , Transplante HomólogoRESUMO
Cervical cancer is an infectious cancer and the most common gynecologic cancer worldwide. E6/E7, the early genes of the high-risk mucosal human papillomavirus type, play key roles in the carcinogenic process of cervical cancer. However, little was known about its roles in modulating tumor microenvironment, particular extracellular matrix (ECM). In this study, we found that E6/E7 could regulate multiple ECM proteins, especially collagen triple helix repeat containing 1 (CTHRC1). CTHRC1 is highly expressed in cervical cancer tissue and serum and closely correlated with clinicopathological parameters. CTHRC1 promotes cervical cancer cell migration and invasion in vitro and metastasis in vivo. E6/E7 regulates the expression of CTHRC1 in cervical cancer by E6/E7-p53-POU2F1 (POU class 2 homeobox 1) axis. Futhermore, CTHRC1 activates Wnt/PCP signaling pathway. Take together, E6/E7-p53-POU2F1-CTHRC1 axis promotes cervical cancer cell invasion and metastasis and may act as a potential therapeutic target for interventions against cervical cancer invasion and metastasis.
Assuntos
Polaridade Celular , Proteínas da Matriz Extracelular/metabolismo , Fator 1 de Transcrição de Octâmero/metabolismo , Proteínas Oncogênicas Virais/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Via de Sinalização Wnt , Movimento Celular/genética , Proliferação de Células/genética , Proteínas da Matriz Extracelular/sangue , Proteínas da Matriz Extracelular/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Curva ROC , Regulação para Cima/genética , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/genéticaRESUMO
BACKGROUND: ZFAS1 is a newly identified long noncoding RNA (lncRNA) that promotes tumor growth and metastasis. Exosomes mediate cellular communications in cancer by transmitting active molecules. The presence of ZFAS1 in the circulating exosomes and the roles of exosomal ZFAS1 in gastric cancer (GC) remains unknown. The aim of this study was to investigate the potential roles of exosomal ZFAS1 in GC. METHODS: The expression of ZFAS1 was examined in the tumor tissues, serum samples, serum exosomes of GC patients and cell lines using qRT-PCR. The correlation between ZFAS1 expression and the clinicopathological characteristics was analyzed. The characteristics of exosomes were identified using transmission electron microscope (TEM), Nanoparticle Tracking Analysis (NTA), and western blot. The biological roles of ZFAS1 in GC cell growth and mobility were investigated using cell counting, cell colony formation, and transwell migration assay. The potential mechanism of ZFAS1 was demonstrated using flow cytometry, western blot, and qRT-PCR. RESULTS: ZFAS1 expression was elevated in GC cells, tumor tissues, serum and serum exosomes of GC patients. The increased ZFAS1 expression was significantly correlated with lymphatic metastasis and TNM stage. ZFAS1 knockdown inhibited the proliferation and migration of GC cells by suppressing cell cycle progression, inducing apoptosis, and inhibiting epithelial-mesenchymal transition (EMT). On the contrary, ZFAS1 overexpression promoted the proliferation and migration of GC cells. Moreover, ZFAS1 was present in exosomes and could be transmitted by exosomes to enhance GC cell proliferation and migration. CONCLUSION: ZFAS1 could be delivered by exosomes to promote GC progression, which suggests that ZFAS1 may serve as a potential diagnostic and prognostic biomarker for GC.
Assuntos
Exossomos/fisiologia , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Exossomos/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Transporte de RNA/fisiologia , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Células Tumorais CultivadasRESUMO
BACKGROUND: Gastric cardia adenocarcinoma (GCA) is a common malignant tumor of the digestive tract with a high incidence in China. Genetic factors such as single nucleotide polymorphisms (SNPs) may contribute to the carcinogenesis of GCA. METHODS: We conducted a hospital-based case-control study to evaluate the genetic association of functional SNPs with susceptibility to GCA development. A total of 330 GCA cases and 608 controls were recruited for this study. The SNPs OPG rs3102735 T>C and rs2073618 G>C, RANK rs1805034 T>C, and RANKL rs9533156 T>C and rs2277438 A>G were determined using the ligation detection reaction method. RESULTS: Our findings suggest that RANK rs1805034 T>C is associated with susceptibility to GCA, which is more evident among male patients, elderly patients (≥ 60 years), smokers, and patients who do not consume alcohol. CONCLUSION: Based on our findings, the functional SNP RANK rs1805034 T>C may be an indicator for individual susceptibility to GCA. However, further larger studies with other ethnic populations and tissue-specific biological characterization are required to confirm the current findings.
Assuntos
Adenocarcinoma/epidemiologia , Adenocarcinoma/genética , Receptor Ativador de Fator Nuclear kappa-B/genética , Fumar/epidemiologia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Marcadores Genéticos/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Distribuição por SexoRESUMO
UNLABELLED: High risk human papillomavirus (HPV) infection is the major cause of cervical cancer. Bacterial vaginosis (BV) is considered as the most prevalent vaginal imbalance affecting women of reproductive age. However, the relationship between HPV and BV infection is unclear. This study aimed to assess the prevalence of human papillomavirus (HPV) infection combined with bacterial vaginosis (BV) infection in Shanghai suburbs and evaluate associations between bacterial vaginosis with HPV infection, cervical intraepithelial neoplasia (CIN) and cervical cancer. METHODS: From October 1, 2009 to October 31, 2013, a total number of 3502 women who visited Fengxian Hospital, Southern Medical University were enrolled in this study. All participants gave informed consent and agreed to HPV, BV, chlamydia, mycoplasma and thinprepcytologic test (TCT). In addition, all women took histopathologic examination under colposcopy. Statistical analyses were done using SPSS 17.0 for windows (IBM). In present study the overall BV-positive rate was 9.25%. The top three high risk HPV types were listed as follows (in descending order): HPV16, 52, 58. Moreover, our data showed BV infection tended to occur in the HPV positive women, HPV infection also tended to occur in the BV positive women. Most of the women who present HPV with BV infection were younger than 30 years old. We also found that CIN and cervical cancer occurred mainly in HPV/BV positive and HPV with BV positive group. BV infection and HPV infection may haveconsistency or synergies. HPV with BV infection may increase the incidence of CIN and cervical cancer.
RESUMO
AIM: To identify the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and gastric cancer (GC) susceptibility. METHODS: Systematic searches were performed on the electronic databases PubMed, ISI, Web of knowledge, CNKI and Wanfang, as well as manual searching of the references of the identified articles. A total of 26 papers were included in this meta-analysis. Overall and subgroup analyses were performed. Odds ratio (OR) and 95%CI were used to evaluate the associations between MTHFR polymorphisms and GC risk. The I (2) statistics were used to evaluate between-study heterogeneity. Sensitivity analysis was also performed. RESULTS: Increased risk was found for the MTHFR C677T polymorphism under four genetic models (TT + CT vs CC: OR = 1.23, P = 0.002; T vs C: OR = 1.15, P = 0.001; TT vs CC: OR = 1.37, P = 0.0005; TT vs CT + CC: OR = 1.17, P = 0.0008). Subgroup analysis by ethnicity suggested that C677T polymorphism conferred a risk of GC in eastern but not in western populations. Stratification by tumor site showed an association between the C677T polymorphism and gastric cardia cancer and non-cardia GC in the worldwide population and in eastern populations. Regardless of comparisons with controls or diffuse-type GC, a positive association was found for the C677T polymorphism and an increased risk of intestinal-type GC in the whole population and in western populations. With regard to the A1298C polymorphism, we found that genotype CC was significantly decreased and conferred protection against GC in eastern populations (CC vs AA: OR = 0.44, P = 0.03; CC vs AC + AA: OR = 0.46, P = 0.04). CONCLUSION: MTHFR C677T polymorphism is a risk factor for GC, and the A1298C polymorphism may be a protective factor against GC in eastern populations.
Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Neoplasias Gástricas/genética , Frequência do Gene , Predisposição Genética para Doença , Humanos , Razão de Chances , Fenótipo , Fatores de Proteção , Medição de Risco , Fatores de Risco , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/etnologia , Neoplasias Gástricas/patologiaRESUMO
AIM: To assess the clinicopathological and biological significance of cripto in human colorectal cancer. METHODS: Real-time reverse-transcription polymerase chain reaction (PCR) was used to examine cripto mRNA levels in primary colon cancer and normal colon tissues as well as normal and metastatic lymph nodes from colon cancers. Human colon cancer LS-174T cells were transfected with cripto small interfering RNA (siRNA), and mRNA and protein levels were evaluated using real-time PCR and western blot analysis, respectively. The growth of cancer cells was evaluated using the MTT assay and colony formation in soft agar. Invasion was examined using a Transwell assay, and the expressions of matrix metalloproteinase (MMP)-7 and MMP-9 were determined using western blot assay. RESULTS: Cripto was significantly overexpressed in primary colon cancer and metastatic lymph nodes. Silencing cripto gene expression with cripto siRNA resulted in a significant decrease in colony formation in soft agar in the colon cancer cell line LS-174T. Cripto siRNA treatment decreased the migration and invasion capabilities of the colon cancer cell line LS-174T in vitro. Furthermore, cripto siRNA treatment inhibited the expression of matrix MMP-7 and MMP-9. CONCLUSION: The results provide evidence that cripto siRNA could be an effective approach for the inhibition of cancer cell invasion and migration and thus has potential for use in devising novel preventive and therapeutic strategies for colon cancer metastasis.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Proteínas Ligadas por GPI/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Neoplasias/metabolismo , Idoso , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Proteínas Ligadas por GPI/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Metaloproteinase 7 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Interferência de RNA , RNA Mensageiro/metabolismo , Fatores de Tempo , Transfecção , Regulação para CimaRESUMO
BACKGROUND: Anastomotic leakage is the most significant complication after low anterior resection (LAR) for rectal carcinoma, and it is the major cause of postoperative mortality and morbidity. The objective of the present study was to investigate whether the use of a transanal tube as an alternative endoluminal diversion technique for rectal carcinoma can reduce the 30-day leakage rate after LAR. METHODS: From June 2003 to December 2009, a total of 398 patients were randomized to a transanal tube or not after LAR. Inclusion criteria for randomization were biopsy-proven carcinoma of the rectum located ≤15 cm above the anal verge, measured with a rigid rectoscope; age≥18 years; informed consent; ability to understand the study information; estimated survival of >6 months; anterior resection for the lesion; final negative air leakage test; intact anastomotic stapler rings; and the absence of major intraoperative adverse events. RESULTS: Patient demographics, tumor size and location, Duke's stage, preoperative co-morbidity, and operative details were comparable between the two groups in general analysis and subgroup analysis (double-staple technique and handsewn technique). The overall rate of symptomatic leakage was 6.78% (27 of 398 patients). Patients randomized to a transanal tube (n=200) had leakage in 4.0% (8 of 200 patients) and those without a tube (n=198) in 9.6% (19 of 198 patients) (p=0.026). With regard to the double-staple technique subgroup, 3.7% (7 of 188) patients with a tube presented with a symptomatic anastomotic leakage, compared with 9.3% (17 of 182) of those without a tube (p=0.028). Of the patients with anastomotic leakage in the double-staple technique subgroup, the need for urgent abdominal reoperation was 28.6% (two of seven patients) in those randomized to a transanal tube and 82.4% (14 of 17) in those without (p=0.021). The 30-day mortality after LAR was nil. In the double-staple technique subgroup, a quicker resumption of gastrointestinal motility manifested by a smaller ratio of patients with flatus>postoperative day (POD) 3 (p=0.019) and a smaller ratio of poor gastrointestinal electromyogram on POD 3 (p<0.001) was associated with use of a transanal tube. Additionally, patients with a tube appeared to have a lower rectal resting pressure by POD 3 (4.0±2.2 vs. 5.0±2.2 kPa; p<0.001) or POD 5 (4.3±2.3 vs. 5.6±2.3 kPa; p<0.001), compared to the resting pressures patients without the device, respectively. A shorter length of hospital stay was associated with use of a transanal tube both in the double-staple technique subgroup (p<0.001) and the handsewn technique subgroup (p=0.011). Multivariate logistic regression analysis revealed that body mass index>25 kg/m2 and a poor gastrointestinal electromyogram on POD 3 were found to be independent risk factors for anastomotic leakage in the low anastomosis subgroup. CONCLUSIONS: The presence of a transanal tube is effective and safe in decreasing the rate of clinically significant anastomotic leaks and in mitigating the clinical consequences of leakage after anterior resection for rectal cancer with the technique of total mesorectal excision and double-staple anastomosis. The potential benefits of transanal tube placement are multifactorial, including drainage, reduction of endoluminal pressure, and promotion of gastrointestinal motility. Obesity and poor gastrointestinal electromyogram on POD 3 are independent risk factors for anastomotic leakage in patients with low anastomosis.