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1.
Histol Histopathol ; 39(1): 67-77, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37014018

RESUMO

Colorectal cancer is one of the most common cancers with high morbidity and mortality. Effective treatments to improve the prognosis are still lacking. The results of online analysis tools showed that OCT1 and LDHA were highly expressed in colorectal cancer, and the high expression of OCT1 was associated with poor prognosis. Immunofluorescence demonstrated that OCT1 and LDHA co-localized in colorectal cancer cells. In colorectal cancer cells, OCT1 and LDHA were upregulated by OCT1 overexpression, but downregulated by OCT1 knockdown. OCT1 overexpression promoted cell migration. OCT1 or LDHA knockdown inhibited the migration, and the downregulation of LDHA restored the promoting effect of OCT1 overexpression. OCT1 upregulation increased the levels of HK2, GLUT1 and LDHA proteins in colorectal cancer cells. Consequently, OCT1 promoted the migration of colorectal cancer cells by upregulating LDHA.


Assuntos
Neoplasias Colorretais , Humanos , Linhagem Celular Tumoral , Prognóstico , Movimento Celular , Neoplasias Colorretais/genética , Proliferação de Células , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Regulação Neoplásica da Expressão Gênica
2.
World J Gastroenterol ; 28(28): 3706-3719, 2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-36161052

RESUMO

BACKGROUND: Helicobacter pylori (H. pylori) has characteristics of family cluster infection; however, its family-based infection status, related factors, and transmission pattern in central China, a high-risk area for H. pylori infection and gastric cancer, have not been evaluated. We investigated family-based H. pylori infection in healthy households to understand its infection status, related factors, and patterns of transmission for related disease prevention. AIM: To investigate family-based H. pylori infection status, related factors, and patterns of transmission in healthy households for related disease prevention. METHODS: Blood samples and survey questionnaires were collected from 282 families including 772 individuals. The recruited families were from 10 selected communities in the greater Zhengzhou area with different living standards, and the family members' general data, H. pylori infection status, related factors, and transmission pattern were analyzed. H. pylori infection was confirmed primarily by serum H. pylori antibody arrays; if patients previously underwent H. pylori eradication therapy, an additional 13C-urea breath test was performed to obtain their current infection status. Serum gastrin and pepsinogens (PGs) were also analyzed. RESULTS: Among the 772 individuals examined, H. pylori infection rate was 54.27%. These infected individuals were from 246 families, accounting for 87.23% of all 282 families examined, and 34.55% of these families were infected by the same strains. In 27.24% of infected families, all members were infected, and 68.66% of them were infected with type I strains. Among the 244 families that included both husband and wife, spouse co-infection rate was 34.84%, and in only 17.21% of these spouses, none were infected. The infection rate increased with duration of marriage, but annual household income, history of smoking, history of alcohol consumption, dining location, presence of gastrointestinal symptoms, and family history of gastric disease or GC did not affect infection rates; however, individuals who had a higher education level showed lower infection rates. The levels of gastrin-17, PGI, and PGII were significantly higher, and PGI/II ratio was significantly lower in H. pylori-infected groups than in H. pylori-negative groups. CONCLUSION: In our study sample from the general public of central China, H. pylori infection rate was 54.27%, but in 87.23% of healthy households, there was at least 1 H. pylori-infected person; in 27.24% of these infected families, all members were infected. Type I H. pylori was the dominant strain in this area. Individuals with a higher education level showed significantly lower infection rates; no other variables affected infection rates.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Gastrinas , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Humanos , Pepsinogênio A , Pepsinogênios/uso terapêutico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/prevenção & controle , Ureia
3.
Ann Transl Med ; 10(24): 1372, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36660622

RESUMO

Background: Apatinib is approved in China for the treatment of advanced gastric adenocarcinoma that had progressed or relapsed after standard systemic chemotherapy treatments. However, the effectiveness of Apatinib under real-world condition has not been evaluated and the drug performance under ideal and controlled circumstances has not been validated. In fact, genetic factors, poor healthcare access, social economic status, comorbidities compliance and other factors play significant role in drug performance under "real-world" conditions. Real-world experience can help validate the safety and efficacy of apatinib. Methods: In this observational, prospective study we evaluated the safety and efficacy of Apatinib in patient treated in China. Between March 2018 and March 2019, a total of 943 patients with gastric cancer treated with Apatinib were enrolled. Response Evaluation Criteria in Solid Tumors, version 1.1 and Common Terminology Criteria for Adverse Events, version 4.0 were used to evaluate efficacy and adverse effects. Results: The median progression-free survival (PFS) was 5.65 months (5.22-6.05 months), and the median overall survival (OS) was 11.47 months (10.41-12.52 months). Apatinib in combination with more than two agents was superior to single agent apatinib in overall response rate (ORR) [18.18% vs. 9.43%, 95% confidence interval (CI): 1.03-5.90] and disease control rate (DCR) (82.82% vs. 77.87%, 95% CI: 1.21-2.59). Apatinib in combination with single agent chemotherapy was also superior to apatinib alone with DCR (86.29% vs. 77.87%, 95% CI: 1.47-2.99) irrespective of the dose (250 or 500 mg). In the patient cohort who received a starting dose of 250 mg, the DCRs of the combined treatment and monotherapy groups were 86.22% vs. 80.00% (95% CI: 1.18-3.09), respectively. The most common treatment-emergent adverse events were anemia, anorexia and thrombocytopenia (66.28%, 37.75%, 36.06%, respectively). Conclusions: Efficacy of Apatinib in this observational study is promising and toxicities are manageable. Combination of Apatinib with chemotherapy agents has a higher response rate and better disease control at the expense of increased serious adverse events. Better OS can be achieved by receiving apatinib treatment earlier. As a supplement and further validation of explanatory randomized controlled trials, the real-world study reflects the real efficacy of apatinib in practical application.

4.
Cancer Cell Int ; 21(1): 661, 2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34895232

RESUMO

BACKGROUND: Gastric cancer is a highly aggressive malignant tumor with heterogeneity and is still a global health problem. The present study aimed to investigate the role of Cyclin I-like (CCNI2) in the regulation of phenotype and tumorigenesis, as well as its underlying mechanisms. METHOD: The expression profile of CCNI2 in gastric cancer was determined based on The Cancer Genome Atlas (TCGA) database and immunohistochemical staining. The effects of altered CCNI2 expression on the biological phenotypes such as proliferation, clone formation, apoptosis and migration of gastric cancer cell lines BGC-823 and SGC-7901 were investigated. Mice xenograft models were established to reveal the role of CCNI2 knockdown on tumorigenesis. The potential mechanism of CCNI2 regulating gastric cancer was preliminarily determined by RNA sequencing. RESULT: CCNI2 was abundantly expressed in gastric cancer and was positively correlated with pathological stage. Knockdown of CCNI2 slowed down the malignant progression of gastric cancer by inhibiting tumor cell proliferation, increasing the susceptibility to apoptosis and suppressing migration. Moreover, downregulation of CCNI2 attenuated the ability of gastric cancer cells to form tumors in mice. Additionally, there was an interaction between CCNI2 and transcription factor hepatoma-derived growth factor (HDGF) in SGC-7901 cells. Knockdown of CCNI2 alleviated the promoting effects of HDGF overexpression in gastric cancer cells. CONCLUSIONS: CCNI2 promoted the progression of human gastric cancer through HDGF, which drew further interest regarding its clinical application as a potential therapeutic target.

5.
Signal Transduct Target Ther ; 6(1): 414, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34873151

RESUMO

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 µM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.


Assuntos
Antivirais/administração & dosagem , Azidas/administração & dosagem , Tratamento Farmacológico da COVID-19 , Desoxicitidina/análogos & derivados , SARS-CoV-2/metabolismo , Timo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Coronavirus Humano OC43/metabolismo , Desoxicitidina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Timo/metabolismo , Timo/virologia
6.
Front Oncol ; 11: 757307, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778073

RESUMO

BACKGROUND: Much importance is attached to the clinical application value of circulating tumor cells (CTCs), meanwhile tumor-proximal CTCs detection has interested researchers for its unique advantage. This research mainly discusses the correlation of portal venous (PoV) CTCs counts in different epithelial-mesenchymal transition status with clinicopathologic parameters and postoperative prognosis in resectable pancreatic ductal adenocarcinoma patients (PDAC). METHODS: PDAC patients (n=60) who received radical resection were enrolled in this research. PoV samples from all patients and peripheral venous (PV) samples from 32 patients among them were collected to verify spatial heterogeneity of CTCs distribution, and explore their correlation with clinicopathologic parameters and clinical prognosis. RESULTS: CTCs detectable rate and each phenotype count of PoV were higher than those of PV. Patients with recurrence had higher PV and PoV epithelial CTCs (E-CTCs) counts than recurrence-free patients (P<0.05). Some unfavourable clinicopathologic parameters were closely related to higher PoV CTCs counts. Multivariate regression analysis demonstrated that PoV mesenchymal CTC (M-CTC)s≥1/5 ml was an independent risk factor for metastasis free survival (MFS) (P=0.003) and overall survival (OS) (P=0.043). CONCLUSIONS: Our research demonstrated that portal venous was a preferable vessel for CTC test, and patients with PoV M-CTC≥1/5 ml had shorter MFS and OS time in resectable PDAC patients. PoV CTC phenotype detection has the potential to be a reliable and accurate tool to identify resectable PDAC patients with high tendency of postoperative metastasis for better stratified management.

7.
Carcinogenesis ; 42(9): 1179-1188, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34111280

RESUMO

Gastric cancer (GC) is one of the most prevalent cancers and severely endangers human health. Due to the low rate of diagnosis, most patients with GC are diagnosed as advanced. CDC42 effector protein 3 (CDC42EP3) has been revealed to be involved in several types of human cancers' development and progression. However, the function of CDC42EP3 in GC is not yet clear. CDC42EP3 expression was detected by immunohistochemistry, quantitative real-time PCR and Western blot assay in tumor tissues and cell lines of GC. CDC42EP3 knockdown cell models were constructed by lentivirus transfection. Cell proliferation was evaluated by the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The wound-healing assay and the transwell assay were utilized to assess the cell migration. Also, the cell apoptosis and the cell cycle were evaluated by flow cytometry. Moreover, the mechanism was investigated by Human Apoptosis Antibody Array. The in vivo experiments were conducted to verify the effects of CDC42EP3 knockdown on the tumor growth of GC. The expression level of CDC42EP3 was up-regulated in tumor tissues. High CDC42EP3 expression was positively related to more advanced tumor grade. CDC42EP3 knockdown inhibited cell proliferation and migration, promoted cell apoptosis and suppressed the tumor growth. On the other hand, it was also found that the silencing of CDC42EP3 inhibited HSP27 and IGF-1sR expression as well as promoted Caspase3, p53, TNF-α, TNF-ß, TRAILR-1 and TRAILR-2 expression. CDC42EP3 was revealed to work as a tumor promoter in the development and progression of GC, which could be a promising therapeutic target for the therapy of GC.


Assuntos
Reguladores de Proteínas de Ligação ao GTP/metabolismo , Neoplasias Gástricas , Idoso , Animais , Apoptose , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Reguladores de Proteínas de Ligação ao GTP/genética , Técnicas de Silenciamento de Genes , Inativação Gênica , Xenoenxertos , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Regulação para Cima
8.
J Cancer ; 12(6): 1678-1686, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613755

RESUMO

Circular RNAs (circRNAs) are associated with various diseases, including cancers. However, their roles in colorectal cancer (CRC) have not been established. Hsa_circ_0000847 (circ_SMAD2) is a novel circRNA that was found to be elevated in CRC cell lines and tissues. High circ_SMAD2 levels were positively correlated with CRC clinicopathological features. Functional assays revealed that circ_SMAD2 enhanced CRC cell invasion, proliferation, and tumor growth. Mechanistically, circ_SMAD2 elevated Ribophorin II (RPN2) levels by inhibiting miR-1258. Therefore, circ_SMAD2 is a potential indicator for CRC progression.

9.
Int J Surg Case Rep ; 80: 105525, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33592425

RESUMO

INTRODUCTION AND IMPORTANCE: Hemoclips have been used to protect leakage after endoscopic resection of large colorectal polyps or early-staged rectal cancer, or for perforation of the sigmoid colon during colonoscopy. However, endoscopic clips were seldom used to manage anastomotic leakage after low anterior resection of rectal cancer. CASE PRESENTATION: A patient with postoperative anastomotic leakage after low anterior resection for rectal cancer was successfully treated by endoscopic hemoclips under colonoscopic vision after failure of conservative treatment. Postoperative course was uncomplicated and the patient was discharged from the hospital seven days later. CLINICAL DISCUSSION AND CONCLUSION: Endoscopic hemoclips should be considered as an alternative option for the treatment of an anastomotic leakage in cases where conservative treatment has failed. As they are safe and effective for closure, however good bowel preparation and strict inclusion criteria are required.

10.
Cancer Manag Res ; 11: 6625-6635, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31406476

RESUMO

Background: HOXA10 has been reported to be deregulated in many kinds of cancers including gastric cancer. But its role in gastric cancer progression is controversial. Therefore, the current study was performed to explore the role and mechanism of HOXA10 in gastric cancer. Materials and methods: IHC and Western blotting assays were used to assess HOXA10 expression in gastric cancer tissues and cells. Lentivirus infection was used to alter HOXA10, STAT3 and JAK1 expression in gastric cancer NCI-N87 and MKN28 cells. MTT, cloning formation, flow cytometry and in vivo xenotransplantation experiments were carried out to assess cell proliferation, cloning formation, apoptosis and tumorigenesis. Results: HOXA10 expression was obviously increased in gastric cancer tissues and cells when compared with the normal gastric tissue samples and cells. Upregulation of HOXA10 significantly enhanced cell proliferation, cloning formation and tumorigenesis abilities and reduced cell apoptosis in gastric cancer, and promoted the activation of JAK1/STAT3 signaling. In addition, we showed that the effects of HOXA10 on the promotion of cell viability and tumorigenesis and cell apoptosis repression were all weakened when JAK1 or STAT3 was downregulated. Conclusion: This study demonstrates that HOXA10 functions as an oncogene in gastric cancer through activating JAK1/STAT3 signaling.

11.
Int J Biol Macromol ; 108: 1120-1127, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29274428

RESUMO

A complicated sulfated fucoidan, SHPPB2, was purified from Sargassum henslowianum by DEAE-cellulose 52 and Sephacryl S-300 column chromatography. Via chemical and spectral method, SHPPB2 was found to contain mannose, glucuronic acid, galactose, xylose, and fucose, in a ratio of 17.4: 13.5: 10.5: 16.8: 41.8, as well as 21.4% of sulfate. The methylation analysis demonstrated terminal, 3-, 4-, 2, 3-, and 3, 4- linked fucose, 2-, 2, 3-, 2, 4-, and 2, 4, 6- linked mannose, terminal, 4-, 6-, 2, 4-, 3, 4-, and 3, 6- linked galactose, terminal and 4- linked xylose, and 4- linked glucuronic acid. In addition, the sulfate groups were substituted on the C-2, C-3 or C-4 of 3- and 4- linked fucose, on the C-4 or C-6 of 2- linked mannose, and on C-2 or C-3 of 4- and 6- linked galactose. With the treatment of SHPPB2 in the N-methyl-N'-nitro-nitrosoguanidine (MNNG) induced gastric cancer rats, it was observed with an increased body weight, and improved immune organ indices. Furthermore, SHPPB2 could significantly promote splenocyte proliferation induced by ConA or LPS in gastric cancer rats, and improve anti-inflammatory cytokines (IL-2, IL-4, and IL-10) secretion, but reduce pro-inflammatory cytokines (IL-6 and TNF-α). Taken together, it suggested that SHPPB2 could improve immune function in gastric cancer rats. Thus, it could be explored as a potential immuno-therapy for gastric cancer treatment.


Assuntos
Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Sargassum/química , Neoplasias Gástricas/imunologia , Animais , Peso Corporal/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citocinas/sangue , Masculino , Ratos , Ratos Wistar , Baço/imunologia , Neoplasias Gástricas/sangue
12.
Zhonghua Wei Chang Wai Ke Za Zhi ; 20(12): 1417-1421, 2017 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-29280128

RESUMO

OBJECTIVE: To evaluate the efficacy of sacral nerve stimulation (SNS) therapy for fecal incontinence. METHODS: Clinical researches which evaluated the efficacy of SNS and were published between 1946 and 2016 were systematically searched from electronic databases, including PubMed, Ovid Medline, Web of Science, Wanfang database and Chinese Journal Full-text Database. Grey area literatures were also searched. Influence of SNS therapy on fecal incontinence episodes (FIE) or Wexner incontinence score (WIS) was systematically evaluated. The statistical analysis was performed by RevMan5.2. RESULTS: A total of 6 studies including 270 patients (147 patients in SNS group and 123 patients in control group) with fecal incontinence were enrolled in this systematic review. SNS therapy was associated with a significant reduction in FIE (SMD=-0.69, 95%CI: -0.97 to -0.41, P<0.001) and a significant reduction in WIS (SMD=-5.05, 95%CI: -8.73 to -1.36, P=0.007). Sensitivity analysis showed that the results of this study were stable and the direction and significance of results were not changed (P=0.000 for both). Publication bias was not found by funnel picture in this study. CONCLUSION: SNS significantly improves the outcome of patients with fecal incontinence.


Assuntos
Terapia por Estimulação Elétrica , Incontinência Fecal/terapia , Bases de Dados Factuais , Humanos , Plexo Lombossacral , Qualidade de Vida , Resultado do Tratamento
13.
Mol Med Rep ; 16(5): 6916-6919, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28901504

RESUMO

Angiogenesis serves a role in the growth, metastasis and prognosis of tumors. The aim of the present study was to evaluate the angiogenic ability and clinical significance of the immune biomarker soluble interleukin­2 receptor (sIL­2R) in gastric cancer (GC) patients. Serum levels of sIL­2R were measured in 35 GC patients with different stages of disease and 32 healthy individuals, and it was investigated whether the levels were associated with angiogenesis factors, including vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)­ß1. Human umbilical vein endothelial cells (HUVECs) were pretreated with or without recombinant human (rh)sIL­2R, VEGF and TGF­ß1 for 24 h, and then the HUVECSs were harvested to determine the degree of angiogenesis. The supernatants were also collected for VEGF and TGF­ß1 testing. Serum levels of sIL­2R were higher in GC patients than in healthy individuals, as were the levels of VEGF and TGF­ß1. In addition, serum levels of sIL­2R were positively associated with the levels of VEGF and TGF­ß1. Angiogenesis of HUVECs was also increased by rhsIL­2R pretreatment. VEGF and TGF­ß1 secretion were also incre-ased in supernatants that were pretreated with rhsIL­2R. The results of the present study suggested that serum levels of sIL­2R contributes to the pathophysiology of GC progression and may be used as a prognostic biomarker for GC.


Assuntos
Receptores de Interleucina-2/metabolismo , Neoplasias Gástricas/diagnóstico , Idoso , Biomarcadores/sangue , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Fisiológica/efeitos dos fármacos , Prognóstico , Receptores de Interleucina-2/sangue , Receptores de Interleucina-2/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/farmacologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Fator de Crescimento Transformador beta1/sangue , Fator de Crescimento Transformador beta1/metabolismo , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/metabolismo
14.
Am J Cancer Res ; 7(5): 1136-1150, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28560062

RESUMO

MiRNA have been found to play a role in a plethora of cellular processes of cancer cells such as cell apoptosis, cell proliferation, invasion, migration metabolism and stem cell differentiation. Dysregulation of miR-146b-5p has been documented in a variety of human malignancies. However, the biological functions and molecular mechanisms of miR-146b-5p in ovarian cancer remain unknown. In this study, our results show that miR-146b-5p was unregulated in colorectal cancer (CRC) tissues compared with the adjacent non-cancerous tissues. Ectopic overexpression of miR-146b-5p in CRC promoted cell growth, invasion and glycolysis, while knockdown of miR-146b-5p inhibited the growth, invasion and glycolysis of CRC cells. The oncogenic effect of miR-146b-5p is also confirmed in vivo. Mechanically, miR-146b-5p targets the 3'-UTR of pyruvate dehydrogenase B (PDHB) and exerts oncogenic effect. Overexpression of PDHB abolished the oncogenic effects of miR-146b-5p on the growth, invasion and glycolysis of CRC cells. Taken together, our results show that miR-146b-5p is an oncogenic miRNA in CRC which exerts its effect by directly targeting PDHB.

15.
Gene ; 575(2 Pt 1): 270-5, 2016 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-26343796

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, and its prevalence is rapidly increasing in Han Chinese individuals. Several studies have demonstrated that polymorphisms of the PARVB gene may play crucial roles in the development of NAFLD. Therefore, the present study was designed to investigate the association of rs5764455 and rs6006473 polymorphisms in PARVB with the Han Chinese population's susceptibility to NAFLD. METHODS: A total of 384 cases of NAFLD patients and 384 healthy controls were enrolled in this study. Their clinical information and serum biochemical indexes were analyzed. A sample (5 ml) of fasting venous blood was taken from each subject for DNA extraction, after which SNP probes were customized, and real-time PCR was used to detect SNP in the PARVB gene. RESULTS: Patients with genotype AA of rs5764455 SNP locus in PARVB gene had a higher incidence of NAFLD than patients with genotypes AG and GG (62.1% vs. 50.3% and 46.9%, respectively, p-values=0.034). Patients with genotype TT of rs6006473 SNP had a higher incidence of NAFLD than patients with genotypes CT and CC (56.9% vs. 49.9% and 42.0%, respectively, p-values=0.017). The ORs of the A allele and AA genotype of rs5764455 for NAFLD were 1.30 and 1.62, respectively; those of the T allele and TT genotype of rs6006473 for NAFLD were 1.34 and 1.35, respectively. Further analysis revealed that patients with genotype AA of rs5764455 and genotype TT of rs6006473 had higher levels of plasma triglyceride, LDL-C, ALT and AST (p-values<0.05). Likewise, patients with genotype AA of rs5764455 had a higher incidence of moderate to severe NAFLD than patients with genotypes AG and GG (62.7% vs. 44.3% and 43.0%, respectively, p-values=0.026). Patients with genotype TT of rs6006473 had a higher incidence of moderate to severe NAFLD than patients with genotypes CT and CC (59.6% vs. 46.6% and 30.9%, respectively, p-values=0.001). CONCLUSIONS: Our study found polymorphisms of rs5764455 and rs6006473 in PARVB gene in the Han Chinese population, and these polymorphisms were associated with the occurrence and progression of NAFLD.


Assuntos
Actinina/genética , Alelos , Genótipo , Hepatopatia Gordurosa não Alcoólica/genética , Polimorfismo de Nucleotídeo Único , Actinina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , China/epidemiologia , Feminino , Humanos , Fígado/metabolismo , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia
16.
Int J Clin Exp Med ; 8(1): 1370-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25785139

RESUMO

TP53 and KRAS mutations are commonly found in colorectal tumors. The rates of mutation of these two genes in colorectal carcinoma were compared to better understand their contribution to the disease. Here, colorectal tissue samples were obtained from 49 patients with colorectal adenoma, 90 patients with single primary colorectal carcinoma, 32 patients with multiple primary colorectal carcinoma, and 50 healthy individuals. Real-time PCR was used to amplify exons 5-8 of TP53 and codons 12-13 (exon 1) of KRAS from each sample. Clinical and pathological features of tumor samples were recorded, and these features were compared against mutation status using multivariate logistic regression. The proportions of samples with mutations of KRAS and/or TP53 were significantly different between control individuals and those with colorectal lesions (P < 0.05). Indeed, more than 80% of carcinoma samples were positive for either a KRAS or TP53 mutation. Further, mutations in KRAS and/or TP53 were significantly more common among the two groups with confirmed carcinoma than in individuals with colorectal adenoma (P < 0.05). Interestingly, TP53 mutations were significantly more frequent than KRAS mutations in the colorectal adenoma group (P < 0.01). However, no associations were observed for the frequency of KRAS or TP53 mutations between well-differentiated and poorly-differentiated tumors, different tumor stages, or other clinical and pathological features like age, sex, family history, tumor location, and stage and grade of differentiation. In conclusion, KRAS and TP53 mutations are important contributors to colorectal cancer, and TP53 mutation appears to occur earlier than KRAS mutation.

17.
Int J Clin Exp Med ; 8(11): 21629-34, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26885116

RESUMO

AIMS: To investigate the association of phosphatase and tensin homologue deleted on chromosome ten (PTEN) gene rs3830675, and additional interaction with drinking and smoking on colorectal cancer (CRC), based on a hospital based Chinese case-control study. METHODS: A total of 850 subjects (413 males and 437 females) were studied, including 422 colorectal cancer cases and 428 controls. Rs3830675 was selected for genotyping in the case-control study. Logistic regression model was used to examine the association between rs3830675 and colorectal cancer, and additional interaction with alcohol consumption and smoking. RESULTS: The frequencies for rs3830675 (-) alleles was higher in cases than that in controls, (-) allele of rs3830675 was 24.4% in controls and 29.4% in CRC subjects (p=0.005). Logistic analysis showed that the carriers of (-) allele of rs3830675 revealed increased CRC risk than those with (+/+) genotype, adjusted OR (95% CI) was 1.35(1.12-1.98). We found a significant interaction between alcohol consumption and rs3830675, drinkers with (-/-) or (-/+) of rs3830675 genotype have highest colorectal cancer risk, compared to never drinking subjects with (+/+) genotype, OR (95% CI) was 2.57 (1.66-3.33), after covariates adjustment. In addition, we also found that smokers with (-/-) or (-/+) of rs3830675 genotype have highest colorectal cancer risk, compared to never smokers with (+/+) genotype, OR (95% CI) was 3.01 (1.58-6.05). CONCLUSIONS: The (-) allele of rs3830675 was positively with colorectal cancer risk. There was a significant role of interaction of rs3830675 with alcohol consumption and smoking on colorectal cancer.

18.
Tumour Biol ; 35(5): 4113-22, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24425105

RESUMO

Although the association between hypoxia-inducible factor-1α (HIF-1α) C1772T polymorphism and risk of malignancy has been widely studied, results from published studies remained controversial. Therefore, the relationship between them was further assessed in this meta-analysis. The databases of PubMed, Embase, and Wanfang were searched, and odds ratio with 95% confidence interval (OR and 95% CI) were used to assess the strength of the association. A total of 38 case-control studies with 23,876 participants were included. Overall, the T allele of HIF-1α C1772T was significantly associated with increased risk of malignancy development (OR and 95% CI 1.18 (1.00-1.38), P = 0.048 for T carriers vs. CC; 1.22 (1.05-1.41), P = 0.010 for T carriers vs. C carriers). When subgroup analyses were conducted, T allele was further found to be associated with increased risk of malignancy development for Asians rather than Caucasians (OR and 95% CI 1.36 (1.10-1.67), P = 0.004 for Asians) and for population-based studies (OR and 95% CI 1.19 (1.01-1.41), P = 0.040). Between-study heterogeneity existed in genetic comparison models, and meta-regression indicated that the participants' ethnicities and types of malignancy might be the sources of heterogeneity. No publication bias was found. In conclusion, this study indicated that HIF-1α C1772T polymorphism was significantly associated with increased risk of malignancy development for Asians. More studies were further required to focus on the relationship between HIF-1α C1772T polymorphism and risk of a specific type of tumor.


Assuntos
Predisposição Genética para Doença , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias/genética , Polimorfismo Genético , Estudos de Casos e Controles , Humanos , Neoplasias/etiologia , Risco
19.
Int J Clin Oncol ; 18(3): 478-86, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22527847

RESUMO

BACKGROUND: Our aims were to detect circulating cell-free human telomerase reverse transcriptase (hTERT) mRNA in the plasma of gastric cancer patients and evaluate its potential diagnostic and prognostic value. METHODS: Real-time quantitative reverse transcription-polymerase chain reaction was employed to detect circulating cell-free hTERT mRNA from 118 gastric cancer patients, 40 chronic atrophic gastritis (CAG) patients, and 58 healthy controls. RESULTS: Circulating cell-free hTERT mRNA was detected in all gastric cancer patients, 39 (97.5 %) CAG patients and 56 (96.6 %) healthy control individuals, respectively. However, it was higher in gastric cancer than in CAG and healthy controls (all at P < 0.05). Moreover, its high level was significantly correlated with clinical stages (P < 0.001) and lymph nodes metastasis (P < 0.001). There was no difference between circulating cell-free mRNA and other parameters. The area under the receiver operating characteristic (ROC) curve was 0.891, and the optimal cut-off point was 0.18, providing a sensitivity of 66 % and a specificity of 87 %. The ROC analysis showed that the diagnosis capability of circulating cell-free mRNA was statistically significantly higher than that of carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA19-9), alone [CEA (0.656); CA19-9 (0.722)] or in combination (0.756). Kaplan-Meier analysis demonstrated a correlation between increased circulating cell-free hTERT mRNA and reduced disease-free survival (P < 0.001) and overall survival (P < 0.001). Cox analysis indicated that it was an independent prognostic factor for disease-free survival and overall survival. CONCLUSIONS: We concluded that circulating cell-free hTERT mRNA might serve as a potential and useful noninvasive tumor marker for gastric cancer.


Assuntos
RNA Mensageiro/sangue , Neoplasias Gástricas/sangue , Neoplasias Gástricas/diagnóstico , Telomerase/sangue , Adulto , Idoso , Biomarcadores Tumorais/sangue , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Células Neoplásicas Circulantes/metabolismo , Prognóstico , Neoplasias Gástricas/patologia
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