Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to investigate the relationship between the VEGF level and the counts of dendritic cells (DCs) in peripheral blood of patients with hepatocellular carcinoma (HCC) before and after transcatheter arterial chemoembolization (TACE), the peripheral blood was obtained from 37 patients with HCC who treated by TACE. The blood was obtained on the day before TACE, the first day, the 7th day and the 15th day after TACE respectively. The counts of DCs were quantified by flow cytometry. The plasma VEGF level was measured by ELESA kit. It was shown after TACE, the counts of DCs in peripheral blood were decreased significantly (P<0.05), and the VEGF level in peripheral blood was increased significantly (P<0.05). The counts of DCs in peripheral blood had an inverse correlation with the plasma VEGF level (r=-0.57, P<0.05) after TACE. It was concluded that in patients with HCC after TACE, the increased plasma VEGF level appeared to have the effect to suppress the maturation of DCs, which may contribute to reduction of the body's anti-tumor immunity effect, with a consequence of recur and metastasis of tumor.
 ...
PMID:Relationship between the changes of VEGF level and dendritic cells in peripheral blood of patients with hepatocellular carcinoma after transcatheter arterial chemoembolization. 1739 11

The objective of this study was to explore whether a specific inhibitor of PI3K, wortmannin, could potentiate the antitumor effect of radiation in vivo, particularly on radioresistant murine tumors. C3H/HeJ mice bearing syngeneic hepatocarcinoma (HCa-I) were treated with 25 Gy radiation, wortmannin, or both. Wortmannin was administered intraperitoneally (1 mg/kg) once daily for 14 days. Tumor response to treatment was determined by a tumor growth delay assay. Possible mechanisms of action were explored by examining the level of apoptosis and regulating molecules. The expression of regulating molecules was analyzed by Western blot for p53 and p21(WAF1/CIP1), and immunohistochemical staining for p21(WAF1/CIP1), CD31 and VEGF. In the tumor growth delay assay, wortmannin increased the effect of tumor radioresponse with an enhancement factor (EF) of 2.00. The level of apoptosis achieved by the combined treatments was shown to be no more than an additive effect; peak apoptotic index was 11% in radiation alone, 13% in wortmannin alone, and 19% in the combination group. Markedly increased areas of necrosis at 24 h in the combination group were noted. Western blotting showed upregulation of p21(WAF1/CIP1) in the combination treatment group, which correlated with low levels of VEGF. Microvascular density was evidently also reduced, based on low expression of CD31. In murine hepatocarcinoma, the antitumor effect of radiation was potentiated by wortmannin. The mechanism seems to involve not only the increase of induced apoptosis but also enhanced vascular injury. Wortmannin, in combination with radiation therapy, may have potential benefits in cancer treatment.
 ...
PMID:Enhancement of tumor radioresponse by wortmannin in C3H/HeJ hepatocarcinoma. 1743 77

Effect of kallikrein-binding protein (KBP), an endogenous angiogenic inhibitor, on the growth of hepatocellular carcinoma and the possible mechanism were investigated. KBP inhibited proliferation and induced apoptosis of endothelial cells, but had no effect on the proliferation and apoptosis of hepatocarcinoma cell line HepG2. Intraperitoneal injection of KBP significantly suppressed the tumor growth and inhibited intratumoral neovascularization both in grafted hepatocarcinoma mice and xenografted hepatocarcinoma athymic mice. Moreover, KBP reduced expression of VEGF and HIF-1alpha nuclear translocation in HepG2 cells and xenografts. Down-regulation of VEGF in tumor cells through inhibiting HIF-1alpha may represent a novel mechanism for the anti-angiogenic and anti-tumor activity of KBP.
 ...
PMID:Kallikrein-binding protein suppresses growth of hepatocellular carcinoma by anti-angiogenic activity. 1771 61

To maintain a tumour vasculature in proportion of the tumour growth, the endothelial cells proliferate and up-regulate the expression of the VEGF receptor 2 (VEGFR-2), whose expression is restricted to this cell type. This specificity implies that one therapeutically target the tumour endothelium. We investigated the use of immunoliposomes (IL), containing conjugated Fab' fragments of the monoclonal rat anti-VEGFR-2 antibody DC101 (DC101-IL) to cargo doxorubicin to the tumour endothelium. In vitro, fluorescein-labelled IL displayed a 7 fold better binding to VEGFR-2-positive 293T cells in comparison to unspecific liposomes. Balb/C mice were injected subcutaneously with syngeneic hepatocellular carcinoma cells. One set of animals was treated with DC101-IL filled with doxorubicin when the tumours were bigger than 400 mm3. A specific delivery of doxorubicin to endothelial cells of the tumour vessels could be demonstrated by the red fluorescence of doxorubicin with laser scanning microscopy, but neither a delay of tumour growth nor a shrinking of the tumour mass was observed. Yet necrosis in the tumours treated with doxorubicin containing vehicles was larger than in the tumours of the control groups. A second set of animals was treated with DC101-IL filled with doxorubicin when the tumours were smaller than 1 mm3. DC101-IL filled with doxorubicin led to a significant delay in tumour growth up to 7 weeks compared to empty DC101-IL, free doxorubicin, and HEPES/Glucose (HEPES/Glucose vs. DOX-DC101-IL, p = 0.001; unpaired, two-tailed Student's t-test) and to a higher amount of necrotic areas in the tumours (p = 0.053; 1 way ANOVA with 4 groups). These findings suggest that IL designed to bind specifically to VEGFR-2 can be used to deliver doxorubicin to the tumour endothelium and may impair the "angiogenic switch" of the tumours.
 ...
PMID:Effects on hepatocellular carcinoma of doxorubicin-loaded immunoliposomes designed to target the VEGFR-2. 1796 16

Hepatocellular carcinoma (HCC) is a highly invasive tumor characterized by vigorous neovascularization. The purpose of this study is to examine the expression of Twist, a highly conserved bHLH transcription factor that is known to promote EMT, and evaluate its effect on tumor angiogenesis and metastasis of HCC. The mRNA expression of Twist, VEGF, E-cadherin, and N-cadherin was determined by Real-Time RT-PCR in 30 pairs of hepatocellular carcinomas and matched non-cancerous tissues. Immunohistochemistry was carried out to analyze the protein expression of Twist, VEGF, E-cadherin, and N-cadherin in 40 hepatocellular carcinoma cases. The staining of endothelial cells for CD34 was used to evaluate the MVD. We found that Twist mRNA and protein were both increased in HCC as compared to non-cancerous tissues. The HCC specimens showing positive Twist expression had a higher microvessel density than those without Twist expression. And up-regulated Twist protein was significantly associated with intrahepatic and extrahepatic metastasis (p=0.048 and P=0.039 respectively). In addition, patients with Twist expression had poor prognosis. We also found that the expression of Twist positively correlated with up-regulation of VEGF and N-cadherin (P=0.002 and p=0.016 respectively), but not with downregulation of E-cadherin in HCC. Our results demonstrate that Twist may play an important role in the angiogenesis and metastasis of HCC. Twist expression may become a potential novel prognostic factor for the disease survival of HCC.
 ...
PMID:Up-regulation of Twist induces angiogenesis and correlates with metastasis in hepatocellular carcinoma. 1798 1

Hepatocellular carcinoma (HCC) is characterized as a highly chemoresistant cancer with no effective systemic therapy. Despite surgical or locoregional therapies, prognosis remains poor because of high tumor recurrence or tumor progression, and currently there are no well-established effective adjuvant therapies. The molecular biology of carcinogenesis and tumor progression of HCC has been increasingly understood with intense research in recent years. Several important intracellular signaling pathways such as the Ras/Raf/Mek/Erk pathway and PI3k/Akt/mTOR pathway have been recognized, and the role of several growth factors and angiogenic factors such as EGF and VEGF has been confirmed. Effective agents targeting these molecular abnormalities have been developed and widely tested in preclinical studies of HCC cell lines or xenograft models. Several agents have entered clinical trials in HCC patients, and recent data indicated that a multikinase inhibitor targeting Ras kinase and VEGFR-2, sorafenib, is effective in prolonging survival of patients with advanced HCC. The management of advanced HCC is entering the era of molecular targeting therapy, which is of particular significance for HCC in view of the lack of existing effective systemic therapy for this cancer.
 ...
PMID:From molecular biology to targeted therapies for hepatocellular carcinoma: the future is now. 1808 80

In this study the small interfering RNA(siRNA) targeting human VEGF effectively inhibited the expression of VEGF in human hepatoma cell line, SMMC7721, and could dramatically decrease the tumorigenicity of SMMC7721 s.c. xenograft tumor. Chemically synthesized siRNA targeting VEGF was transiently transfected into SMMC7721 cells by lipofectamine, RT-PCR and Elisa analysis suggested that the expression of VEGF mRNA and secreted protein in SMMC7721 cells with VEGF siRNA transfection were suppressed with inhibition rates of 76.16% and 96.28% respectively compared with negative control, but the growth rate of SMMC 7721 cells with VEGF siRNA transfection was the same as the control cells. In vivo test, siRNA was injected directly into implanted tumors and the tumors volume were calculated at different time interval. Result showed that VEGF siRNA greatly inhibited the growth of tumors tissues, which was consistent with decrease of VEGF mRNA and protein compared with control. In addition, the VEGF siRNA-treated group exhibited obvious signs of necrosis compared with control.
 ...
PMID:[Reduction of tumorigenicity of SMMC7721 hepatoma cell line by VEGF siRNA]. 1825 31

Technical advancements in imaging, in radiation therapy (RT) planning and RT delivery, have facilitated the safe delivery of conformal radiation therapy to patients with unresectable hepatocellular carcinoma (HCC). Although experience in liver cancer RT is limited, the RT technologies and tools to deliver RT safely are being disseminated rapidly. A variety of doses and RT fractionations have been used to treat HCC, and RT has been used in combination with other therapies including transarterial hepatic chemoembolization (TACE). Outcomes following RT alone or RT and TACE appear better than outcomes following similar historical controls of TACE alone, however, randomized trials of RT are needed. The first site of recurrence following RT is most often within the liver, away from the high dose volume, providing rationale for combining RT with regional or systemic therapies. Given the vascular properties of HCC, the combination of RT with anti-VEGF targeted agents may improve outcomes further.
 ...
PMID:The evolving role of radiation therapy in hepatocellular carcinoma. 1828 10

Technical advancements in radiation therapy (RT) have facilitated the safe delivery of conformal, dose-escalated radiation to a wide spectrum of hepatocellular carcinoma (HCC) patients. A variety of doses and RT fractionation schemes have been used, and RT has been used in combination with transarterial chemoembolization (TACE). Compared to untreated historical controls or those treated with TACE alone, outcomes following RT alone or TACE and RT are better. Despite advances in RT delivery, liver toxicity following RT remains a dose-limiting factor, and investigations to better understand the pathophysiology of RT-induced liver toxicity are warranted. For most tumors, RT can provide sustained local control. However, HCC tends to recur within the liver away from the irradiated volume, providing rationale for combining RT with systemic or regional therapies. There is a particular interest in combining RT with anti-VEGF-targeted agents for their independent activity in HCC as well as their radiation sensitization properties. Randomized trials of RT are warranted.
 ...
PMID:Conformal radiotherapy for hepatocellular carcinoma. 1830 83

Although transcatheter arterial chemoembolization (TACE) is considered to be an effective treatment for advanced hepatocellular carcinoma (HCC), it is difficult to achieve complete necrosis by TACE alone due to incomplete embolization and tumor angiogenesis. Recent studies have shown that tegafur/uracil (UFT) inhibits tumor angiogenesis in several cancer types. Therefore, this study was conducted to test the efficacy and toxicity of the UFT administration after TACE in advanced HCC. Thirty patients with HCC who had been treated with TACE alone more than three times and had a recurrence within 6 months were enrolled. All of the patients were treated with TACE and 28 patients were randomly assigned to the UFT (UFT 300 mg/day, three days after TACE, n=14) and control groups (n=14). The primary end point was the time to treatment failure (TTF) and the secondary end points were mainly the response rate and toxicity. Administration and observation were continued up to 6 months after TACE unless local recurrence was detected or serious adverse events developed. The median TTF in the control group was 87 days, whereas in the UFT group it was 127 days, thus significantly prolonged as compared to the control group (P=0.0016). Moreover, the overall response rate (35.7%) in the UFT group was significantly higher than that in the control group (0%). As for toxicity, only 4 patients in the UFT group developed grade 1-2 toxicities such as ascites. Serious complications by TACE were not observed in either group. Notably, there were no increases in the serum VEGF levels in the UFT group whereas those in the control group increased significantly. In conclusion, UFT administration after TACE was an effective treatment and showed no severe adverse events. This regimen may have an adjuvant role and antiangiogenic function in advanced HCC.
 ...
PMID:Adjuvant chemotherapy with tegafur/uracil administration after transcatheter arterial chemoembolization for advanced hepatocellular carcinoma. 1842 98


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>