在结果中搜索
成果类型 (Type)
收录类型 (Indexed By)
- 已选条件:
The anti-hepatocellular carcinoma activity of Mel-P15 is mediated by natural killer cells
Xu, T;Cui, TX;Peng, LP;Kong, S;Zou, JQ;Tian, XS
ONCOLOGY LETTERS 2017年 14卷6期 页码:6901-6906
ANTIMICROBIAL ACTIVITY; INTERFERON-GAMMA; IN-VIVO; MELITTIN; PEPTIDE; CANCER; RECOGNITION; APOPTOSIS; BACTERIA; INNATE
Mel-P15 is a peptide derived from melittin, the main toxic component in the venom of the European honeybee Apis mellifera. In the present study, the antitumor effects of Mel-P15 and the underlying molecular mechanisms of these effects in vivo were investigated. Mel-P15 directly stimulated natural killer (NK) cell cytotoxicity in vitro, which was increased to 55.45% at a 4 mu g/ml dose of Mel-P15. In the mouse liver cancer (H22) xenograft mice model, Mel-P15 suppressed tumor growth in vivo; the tumor inhibitory rate was 61.15% following treatment with 2 mg/kg Mel-P15. In addition, the immune response was activated following Mel-P15 treatment. Mel-P15 treatment increased the spleen and thymus indices, promoted splenocyte proliferation, stimulated NK cytotoxicity and upregulated the secretion of cytokines, including interleukin-2, interferon-gamma and tumor necrosis factor-a. In addition, the tumor inhibitory effect of Mel-P15 on BEL-7402-bearing nude mice was abrogated by the selective depletion of NK cells via the intraperitoneal injection of an anti-asialo GM-1 antibody. The results suggest that Mel-P15 inhibits tumor growth in vivo by promoting NK cell cytotoxicity. Mel-P15 may therefore be a potential immunotherapy candidate for the treatment of hepatocellular carcinoma.
Novel crosstalk between KLF4 and ZEB1 regulates gemcitabine resistance in pancreatic ductal adenocarcinoma
Wang, ZY;Chen, Y;Lin, YL;Wang, XX;Cui, XP;Zhang, ZH;Xian, GZ;Qin, CK
INTERNATIONAL JOURNAL OF ONCOLOGY 2017年 51卷4期 页码:1239-1248
EPITHELIAL-MESENCHYMAL TRANSITION; SIGNALING PATHWAY; CANCER-CELLS; LUNG ADENOCARCINOMA; TUMOR-SUPPRESSOR; DOWN-REGULATION; UP-REGULATION; METASTASIS; PROGRESSION; INHIBITION
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with broad resistance to chemotherapeutic drugs. Kruppel-like factor 4 (KLF4) is a candidate tumor suppressor in PDAC. However, the precise role of KLF4 in gemcitabine resistance of PDAC remains largely unclear. In this study, we demonstrated that gemcitabine inhibited KLF4 expression. Moreover, gemcitabine also reduced the levels of miR-200b and miR-183, but promoted ZEB1 expression in PDAC cells. KLF4 knockdown blocked the expression of miR-200b and miR-183, and inversely, KLF4 overexpression promoted the expression of miR-200b and miR-183, suggesting that KLF4 positively regulated the expression of miR-200b and miR-183. Moreover, KLF4 knockdown enhanced ZEB1 expression and gemcitabine resistance while KLF4 overexpression induced the opposite effect. ChIP assays verified that KLF4 positively regulated the expression of miR-200b and miR-183 by directly binding to their promoters. Then, miR-200b and miR-183 directly inhibited ZEB1 expression by targeting its 3'UTR region. ZEB1 knockdown attenuated gemcitabine resistance in PDAC cells. KLF4 overexpression promoted gemcitabine sensitivity of PDAC in vivo by negatively regulating ZEB1 expression. Our results revealed that novel crosstalk between KLF4 and ZEB1 regulated gemcitabine resistance in PDAC.
HCRP1 downregulation promotes hepatocellular carcinoma cell migration and invasion through the induction of EGFR activation and epithelial-mesenchymal transition
Xu, JW;Zhang, X;Wang, HL;Ge, SJ;Gao, TH;Song, L;Wang, XX;Li, H;Qin, YJ;Zhang, ZH
BIOMEDICINE & PHARMACOTHERAPY 2017年 88卷 页码:421-429
CANCER-CELLS; EXPRESSION; METASTASIS; GROWTH; PROLIFERATION; PROGNOSIS; RNA; EMT
Hepatocellular carcinoma related protein 1 (HCRP1), which is essential for internalization and degradation of ubiquitinated membrane receptors, is downregulated in several tumors and strongly affects the outcomes of cancer patients. It is reported the expression of HCRP1 is inversely related to epidermal growth factor receptor (EGFR) in breast cancer and lead to resistance to cetuximab in ovarian cancer. However, its exact mechanism in the progression of Hepatocellular carcinoma (HCC) remains unknown. Herein, HCRP1 expression and its clinical significance were examined in 101 HCC patients using immunohistochemistry. Cell proliferation, migration and invasion assays were conducted in HCC cell lines. EGFR activation and degradation were then observed after EGF inducing in HCRP1 knockdown HepG2 cells. In addition, we also detected whether epithelial-to-mesenchymal transition (EMT) was involved in the malignancy promoted by HCRP1. The results showed that 59 of the 101 HCC cases exhibited downregulation of HCRP1 expression (P < 0.01) as compared to 30 benign liver lesions and 20 normal liver tissues, all of which showed a high level of HCRP1. HCRP1 expression was significantly related to age (P = 0.017), pathological grade (P = 0.003), tumor encapsulation (P = 0.037), recurrence (P = 0.039) and death (P = 0.015), but unrelated to cirrhosis (P = 0.216), tumor size (P = 0.273), and distant metastasis (P = 0.554). Lower HCRP1 expression was correlated with shorter RFS and OS (P < 0.001), and decreased HCRP1 level is an independent prognostic marker in HCC patients (P < 0.05). Overexpression of HCRP1 decreased and knockdown increased HCC cell proliferation, migration and invasion. HCRP1 depletion increased EGFR activation and inhibited EGFR degradation. EMT phenotype was promoted after HCRP1 downregulation via increase of Snail and Twist1 and activation of Akt phosphorylation in HepG2 cells. Conversely, upregulation of HCRP1 in SMMC-7721 cells led to the opposite effect. In conclusion, our study indicated that downregulation of HCRP1 is a valuable prognostic factor involved in EGFR regulation and acquisition of the mesenchymal phenotype of HCC cells. (C) 2017 Elsevier Masson SAS. All rights reserved.
Metformin potentiates the anticancer activities of gemcitabine and cisplatin against cholangiocarcinoma cells in vitro and in vivo
Zhu, HQ;Ma, JB;Song, X;Gao, HJ;Ma, CQ;Chang, H;Li, HG;Liu, FF;Lu, J;Zhou, X
ONCOLOGY REPORTS 2016年 36卷6期 页码:3488-3496
ANTIDIABETIC DRUG METFORMIN; HEPATOCELLULAR-CARCINOMA CELLS; INTRAHEPATIC CHOLANGIOCARCINOMA; GASTRIC-CANCER; BREAST-CANCER; STEM-CELLS; OLD DRUG; THERAPY; PATHWAY; PROLIFERATION
Metformin, an oral biguanide drug used to treat type 2 diabetes, has displayed anticancer activities in several types of cancer cells. The combination of gemcitabine and cisplatin is the standard chemotherapy regimen for cholangiocarcinoma, but its benefit is limited. The present study aimed to investigate whether metformin could enhance the activities of gemcitabine and cisplatin against cholangiocarcinoma, and the underlying mechanisms. Metformin inhibited the proliferation of human cholangiocarcinoma RBE and HCCC-9810 cells and induced cell cycle arrest at the G0/G1 phase by increasing the activation of AMP-activated protein kinase (AMPK) pathways. Metformin upregulated the expression of p21(waf1) and p27(kip1), and downregulated the expression of cyclin D1, a key protein required for cell cycle progression. The combination of gemcitabine and cisplatin inhibited the proliferation and induced the apoptosis of human cholangiocarcinoma cells by inducing the phosphorylation of AMPK, downregulating cyclin D1, and activating caspase-3. Administration of metformin enhanced the efficacy of gemcitabine and cisplatin to suppress the growth of cholangiocarcinoma tumors established in experimental models by inhibiting cell proliferation and inducing cell apoptosis through their effects on AMPK, cyclin D1 and caspase-3. Given that metformin has been used to treat type 2 diabetes patients for over half a century due to its superior safety profile, the results presented here indicate that metformin may be a potent agent for enhancing the efficacy of gemcitabine and cisplatin in the treatment of cholangiocarcinoma.
miR-1299 suppresses cell proliferation of hepatocellular carcinoma (HCC) by targeting CDK6
Zhu, HQ;Wang, GC;Zhou, X;Song, X;Gao, HJ;Ma, CQ;Chang, H;Li, HG;Liu, FF;Lu, J;Ma, JB
BIOMEDICINE & PHARMACOTHERAPY 2016年 83卷 页码:792-797
CANCER CELLS; TRANSITION; APOPTOSIS
microRNA (miRNA) plays critical role in HCC initiation and development, many miRNAs have been reported to regulate HCC progression. In this study, we studied the role of miR-1299 in cell proliferation of HCC. We found miR-1299 was significantly downregulated in HCC cells and tissues. miR-1299 overexpression inhibited cell proliferation and arrested cell cycle in G0/G1 phase analyzed by MTT assay, soft agar assay, BrdU cell proliferation assay and cell cycle assay, while miR-1299 knockdown promoted cell proliferation and accelerated G1/S transition. Further analysis suggested the key regulator of G1/S transition, cyclin-dependent kinase 6 (CDK6) was the target of miR-1299, miR-1299 inhibited CDK6 expression and bound to the 3'UTR of CDK6. When double knockdown of miR-1299 and CDK6 promoted cell proliferation copied the phenotype caused by miR-1299 overexpression, suggesting miR-1299 inhibits cell proliferation by targeting CDK6. In summary, our data revealed miR-1299 inhibits cell proliferation, and might be a target for HCC therapy. (C) 2016 Published by Elsevier Masson SAS.
Effects of sphincter of Oddi motility on the formation of cholesterol gallstones
Rong, ZH;Chen, HY;Wang, XX;Wang, ZY;Xian, GZ;Ma, BZ;Qin, CK;Zhang, ZH
WORLD JOURNAL OF GASTROENTEROLOGY 2016年 22卷24期 页码:5540-5547
RABBIT SPHINCTER; DISEASE; CHOLECYSTOKININ; HYPERCHOLESTEROLEMIA; CHOLELITHIASIS; GALLBLADDER; OCTAPEPTIDE; ROLES; CELLS; MICE
AIM: To investigate the mechanisms and effects of sphincter of Oddi (SO) motility on cholesterol gallbladder stone formation in guinea pigs.;-;METHODS: Thirty-four adult male Hartley guinea pigs were divided randomly into two groups, the control group (n = 10) and the cholesterol gallstone group (n = 24), which was sequentially divided into four subgroups with six guinea pigs each according to time of sacrifice. The guinea pigs in the cholesterol gallstone group were fed a cholesterol lithogenic diet and sacrificed after 3, 6, 9, and 12 wk. SO manometry and recording of myoelectric activity were obtained by a multifunctional physiograph at each stage. Cholecystokinin-A receptor (CCKAR) expression levels in SO smooth muscle were detected by quantitative real-time PCR (qRT-PCR) and serum vasoactive intestinal peptide (VIP), gastrin, and cholecystokinin octapeptide (CCK-8) were detected by enzyme-linked immunosorbent assay at each stage in the process of cholesterol gallstone formation.;-;RESULTS: The gallstone formation rate was 0%, 0%, 16.7%, and 83.3% in the 3, 6, 9, and 12 wk groups, respectively. The frequency of myoelectric activity in the 9 wk group, the amplitude of myoelectric activity in the 9 and 12 wk groups, and the amplitude and the frequency of SO in the 9 wk group were all significantly decreased compared to the control group. The SO basal pressure and common bile duct pressure increased markedly in the 12 wk group, and the CCKAR expression levels increased in the 6 and 12 wk groups compared to the control group. Serum VIP was elevated significantly in the 9 and 12 wk groups and gastrin decreased significantly in the 3 and 9 wk groups. There was no difference in serum CCK-8 between the groups.;-;CONCLUSION: A cholesterol gallstone-causing diet can induce SO dysfunction. The increasing tension of the SO along with its decreasing activity may play an important role in cholesterol gallstone formation. Expression changes of CCKAR in SO smooth muscle and serum VIP and CCK-8 may be important causes of SO dysfunction.
Upregulation of Leucine Zipper Protein mRNA in Hepatocellular Carcinoma Associated With Poor Prognosis
Li, GB;Yuan, L;Liu, DJ;Liu, J
TECHNOLOGY IN CANCER RESEARCH & TREATMENT 2016年 15卷3期 页码:517-522
HEPATITIS-B-VIRUS; CANCER CELLS; MOTIF; CARCINOGENESIS; EXPRESSION; MUTATIONS; MIGRATION; LEVEL; JAPAN; STAGE
Background: Leucine zipper protein (LUZP) plays key roles in development. Overexpression of LUZP was documented in several types of solid tumors. In this study, expression of LUZP messenger RNA (LUZP mRNA) in human hepatocellular carcinoma (HCC) was examined, and the correlations of LUZP mRNA level with patients' characteristics and prognosis were also investigated. Methods: Total RNA was extracted from HCC and paired noncancerous liver tissues of 77 patients. Expression of LUZP mRNA in the tissues was determined by real-time quantitative reverse transcriptase polymerase chain reaction. Using average LUZP mRNA level in noncancerous liver tissues as the cutoff, patients with HCC were categorized into high-expression group and low-expression group. Correlations of LUZP mRNA with clinical parameters were analyzed. Overall survival of the patients in the 2 groups was analyzed by Kaplan-Meier method. Results: The LUZP mRNA level was significantly higher in HCC samples than in the noncancerous liver tissues (1.87 + 0.11 vs 0.58 + 0.05, P <.01). Significant differences were found between the 2 groups in terms of portal vein invasion, Tumor Lymph Node Metastasis (TNM) stage, and recurrence of HCC. The current study failed to find significant differences between the 2 groups in clinical characteristics such as age, gender, lymph node metastasis, hepatitis B virus infection, family HCC history, and alcohol intake. Overall survival in high-expression group was 12 months while that in the low-expression group was 34 months (P =.03). Conclusion: The LUZP mRNA is a prognostic indicator in HCC, and overexpression is associated with poor prognosis in patients with HCC.
Clinical Outcomes of Patients with Severe Hepatic Hereditary Hemorrhagic Telangiectasia After Banding of the Hepatic Artery and Banding/Ligation of Branches of the Hepatic Artery
Liu, ZC;Lu, XF;Yang, H;Liu, HD;Song, X;Ning, SL;Xu, YF;Chen, YX
EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY 2016年 51卷4期 页码:594-601
WEBER-RENDU DISEASE; QUALITY-OF-LIFE; ROW HELICAL CT; VASCULAR MALFORMATIONS; LIVER-TRANSPLANTATION; ARTERIOVENOUS-FISTULAS; VARICEAL HEMORRHAGE; OSLER-DISEASE; INVOLVEMENT; EMBOLIZATION
Objective/background: To evaluate the effectiveness of double banding/ligation of hepatic arteries in treating patients with hepatic hereditary hemorrhagic telangiectasia (HHHT).;-;Methods: From January 2004 to December 2013, 35 patients were diagnosed with HHHT, among whom 11 woman and two men with a mean +/- SD age of 44 +/- 9 years were treated by double hepatic artery banding/ligation for cardiac insufficiency and/or portal hypertension. The outcomes were evaluated prospectively by measuring clinical manifestations, imaging features, liver and cardiac function, pulmonary arterial systolic pressure, and post-operative complications. Quality of life was evaluated with the Short Form Health Survey questionnaire.;-;Results: For each patient, the common hepatic artery and one branch of the left and/or right hepatic artery were banded, and other significantly dilated hepatic artery branches were ligated. No patient died after surgery. Clinical symptoms were improved in all patients, although ischemic cholangitis was observed in two patients and treated conservatively. Cardiac function, classified per the New York Heart Association (NYHA) cardiac functional grading, improved (NYHA III-IV vs. NYHA I-II); pulmonary arterial systolic pressure significantly decreased in all patients (48 +/- 8 mmHg vs. 24 +/- 4 mmHg; P < .001) and remained in the normal range (26 +/- 3 mmHg) at the end of follow up. The levels of gamma-glutamyl transpeptidase and alkaline phosphatase decreased in 11 patients (144 +/- 94 U/L vs. 71 +/- 34 U/L; P = .003) and 10 patients (207 +/- 71 U/L vs. 105 +/- 32 U/L; P = .001), respectively. Patients were followed up for 50 +/- 28 months (range 6-113 months); one death resulted from causes unrelated to surgery and all dimensions of quality of life improved in all surviving patients.;-;Conclusions: This study helps to establish double hepatic artery banding/ligation as an effective therapy for selected patients with HHHT. (C) 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
Protective Effect of Edaravone on Glutamate-Induced Neurotoxicity in Spiral Ganglion Neurons
Bai, XH;Zhang, C;Chen, AP;Liu, WW;Li, JF;Sun, Q;Wang, HB
NEURAL PLASTICITY 2016年
FREE-RADICAL SCAVENGER; DEVELOPING RAT COCHLEA; GUINEA-PIG; REPERFUSION INJURY; INDUCED OTOTOXICITY; IN-VIVO; ISCHEMIA; INFARCTION; APOPTOSIS; TRAUMA
"excitotoxicity" and lead to neuronal death. As bipolar neurons, spiral ganglion neurons (SGNs) function as a "bridge" in transmitting auditory information from the ear to the brain and can be damaged by excessive glutamate which results in sensorineural hearing loss. In this study, edaravone, a free radical scavenger, elicited both preventative and therapeutic effects on SGNs against glutamate-induced cell damage that was tested by MTT assay and trypan blue staining. Ho. 33342 and PI double staining revealed that apoptosis as well as necrosis took place during glutamate treatment, and apoptosis was the main type of cell death. Oxidative stress played an important role in glutamate-induced cell damage but pretreatment with edaravone alleviated cell death. Results of western blot demonstrated that mechanisms underlying the toxicity of glutamate and the protection of edaravone were related to the PI3K pathway and Bcl-2 protein family.
Utility of an immunostaining panel for diagnosis of hepatocellular carcinoma in fine needle-aspiration biopsies of the liver
Xu, JW;Sun, YH;Chu, CQ;Ge, SJ;Wang, XX;Wang, QX;Zhang, ZH
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2016年 9卷8期 页码:7878-7888
IMMUNOHISTOCHEMICAL-MARKER; ALPHA-FETOPROTEIN; GLYPICAN-3; ARGINASE-1; CANCER; DIFFERENTIATION; BIOMARKER; HEPPAR-1; PROTEIN; HSP70
Background: Histological identification of liver nodules between hepatocellular carcinoma (HCC) and other lesions can be full of challenges sometimes, especially in fine-needle aspiration (FNA) biopsies. Our aim was to investigate the efficacy of combined use of Arginase-1, Glypican-3 (GPC-3), heat shock protein 70 (HSP70) and cytokeratin 7 (CK7) in differentiating these lesions in FNA biopsies. Methods: Immunohistochemistry for these four markers was done in 45 HCCs, 22 metastatic carcinoma, 15 intrahepatic cholangiocarcinoma, 12 hepatocellular adenoma, 8 focal nodular hyperplasia, 12 large regenerative nodules arising in cirrhotic livers, and 10 specimens of normal liver tissues. Results: Arginase-1 reactivity was present in 43 of 45 HCCs (96.0%) and all of the benign liver lesions recruited in this study but not in any of MCs and ICCs (P < 0.001). GPC-3 stained 37 of 45 HCCs (82%) and only 1 of 22 MCs (5%), however, all cases of ICCs and the other benign lesions were negative for GPC-3 expression (P < 0.05). HSP70 showed markedly immunoreactivity in progressive tumors, 38 of 45 HCCs (84%), 18 of 22 MCs (82%), and 11 of 15 ICCs (73%), but was negative for all of the benign cases (P < 0.001). All ICCs showed diffused and strong immunostaining for CK7, but only 3 of 45 HCCs (7%) were detected to react with CK7. The combination of the four immunostaining markers for the diagnosis of HCC could raise the sensitivity and specificity to 98% and 100%, respectively. Conclusion: This study demonstrates that Arginase-1 is an extremely effective and specific immunohistochemistry marker for confirming hepaticorigin, while GPC-3 and HSP70 is typically positive in malignant lesions. Our results indicated the accuracy of diagnosis can be enhanced by their combination of these four markers.
每页: 条
- <<
- <
- >
- >>