Liver Neoplasms
Sort
Pubmeds
(129,298)
Disease
Liver Neoplasms
Description
Tumors or cancer of the LIVER.Read more
Related with
Pubmeds(129329)
Clinical trials(1176)
Pubmed
PARP inhibition and the radiosensitizing effects of the PARP inhibitor ABT-888 in in vitro hepatocellular carcinoma models.
Journal: BMC cancer
April/19/2015
Description

BACKGROUND

Hepatocellular carcinoma is the third cause of cancer related death for which new treatment strategies are needed. Targeting DNA repair pathways to sensitize tumor cells to chemo- or radiotherapy is under investigation for the treatment of several cancers with poly(ADP-ribose) polymerase (PARP) inhibitors showing great potential. The aim of this preclinical study was to evaluate the expression of PARP and PARG genes in a panel of liver cancer cell lines and primary human hepatocytes, their DNA repair capacity and assess the impact on cell survival of PARP inhibitors alone and in combination with radiotherapy.

METHODS

Quantitative PCR was used to measure PARP-1, -2, -3 and PARG mRNA levels and western blotting for PARP-1 protein expression and ADP-ribose polymer formation after exposure of cells to doxorubicin, a topoisomerase II poison. DNA repair capacity was assessed using an in vitro DNA lesion excision/synthesis assay and the effects on cell killing of the PARP inhibitor ABT-888 alone and in combination with ionizing radiation using clonogenic survival.

RESULTS

Although a wide range in expression of the PARPs and PARG was found correlations between PARP-1 and PARP-2 mRNA levels and PARP-1 mRNA and protein levels were noted. However these expression profiles were not predictive of PARP activity in the different cell lines that also showed variability in excision/synthesis repair capacity. 4 of the 7 lines were sensitive to ABT-888 alone and the two lines tested showed enhanced radiosensitivity in the presence of ABT-888.

CONCLUSIONS

PARP inhibitors combined with radiotherapy show potential as a therapeutic option for hepatocellular carcinoma.

Read more
Authors
; ; ; ; ; +2 authors
Related with
Citations(7)
References(31)
Drugs or chemicals(4)
Diseases(2)
Organisms(1)
Processes(4)
Anatomy(2)
Authors(8)
Pubmed
Research progress and prospects of markers for liver cancer stem cells.
Journal: World journal of gastroenterology
October/30/2016
Description

Liver cancer is a common malignancy and surgery is the main treatment strategy. However, the prognosis is still poor because of high frequencies of postoperative recurrence and metastasis. In recent years, cancer stem cell (CSC) theory has evolved with the concept of stem cells, and has been applied to oncological research. According to cancer stem cell theory, liver cancer can be radically cured only by eradication of liver cancer stem cells (LCSCs). This notion has lead to the isolation and identification of LCSCs, which has become a highly researched area. Analysis of LCSC markers is considered to be the primary method for identification of LCSCs. Here, we provide an overview of the current research progress and prospects of surface markers for LCSCs.

Read more
Authors
; ; ; ; ; ;
Related with
Citations(7)
References(60)
Drugs or chemicals(1)
Diseases(1)
Organisms(2)
Processes(1)
Anatomy(2)
Affiliates(1)
Authors(7)
Pubmed
Mechanisms involved in ceramide-induced cell cycle arrest in human hepatocarcinoma cells.
Journal: World journal of gastroenterology
June/5/2007
Description

OBJECTIVE

To investigate the effect of ceramide on the cell cycle in human hepatocarcinoma Bel7402 cells. Possible molecular mechanisms were explored.

METHODS

[3- (4, 5)-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay, plasmid transfection, reporter assay, FACS and Western blotting analyses were employed to investigate the effect and the related molecular mechanisms of C2-ceramide on the cell cycle of Bel7402 cells.

RESULTS

C2-ceramide was found to inhibit the growth of Bel7402 cells by inducing cell cycle arrest. During the process, the expression of p21 protein increased, while that of cyclinD1, phospho-ERK1/2 and c-myc decreased. Furthermore, the level of CDK7 was downregulated, while the transcriptional activity of PPARgamma was upregulated. Addition of GW9662, which is a PPARgamma specific antagonist, could reserve the modulation action on CDK7.

CONCLUSIONS

Our results support the hypothesis that cell cycle arrest induced by C2-ceramide may be mediated via accumulation of p21 and reduction of cyclinD1 and CDK7, at least partly, through PPARgamma activation. The ERK signaling pathway was involved in this process.

Read more
Authors
; ; ;
Related with
Citations(7)
References(33)
Drugs or chemicals(7)
Diseases(2)
Organisms(1)
Processes(4)
Anatomy(1)
Authors(4)
Pubmed
Usefulness of somatostatin receptor scintigraphy in the management of patients with Zollinger-Ellison syndrome. Groupe de Recherche et d'Etude du Syndrome de Zollinger-Ellison (GRESZE).
Journal: Gut
September/8/1997
Description

BACKGROUND

Management of patients with Zollinger-Ellison syndrome (ZES) depends on the presence of multiple endocrine neoplasia type 1 (MEN 1) or liver metastases, or both. Somatostatin receptor scintigraphy (SRS) detects previously unknown endocrine tumours.

OBJECTIVE

To evaluate SRS findings susceptible to modifying the management of patients with ZES-that is, relevant findings, and the specificity of these findings. The latter were defined according to our current therapeutic strategy in three subgroups of patients (sporadic, MEN 1, and liver metastases).

METHODS

85 consecutive patients without known extra-abdominal metastases were studied between September 1991 and March 1996.

RESULTS

Relevant findings were found in 41% of 49 patients with sporadic disease but without liver metastases, in 22% of 18 patients with MEN 1 but without liver metastases, and in 17% of 18 patients with liver metastases. Follow up was available for 20 (74%) of 27 patients who had 23 relevant findings. Nineteen relevant findings (83%) were confirmed at a median of three (range 0.25-45) months of follow up; four (17%) were not confirmed at 30 (range 12-52) months (p = 0.025). Findings located in the duodenopancreatic area (90%), chest (100%), bone (100%), and liver (60%) were confirmed. Most findings for patients with MEN 1 involved the chest.

CONCLUSIONS

SRS detects many anomalies susceptible to modifying management of patients with ZES, especially in those with sporadic disease. The specificity of hot spots located outside the liver seems very high. By contrast, the specificity of hot spots located in the liver remains to be evaluated when conventional imaging is negative.

Read more
Authors
; ; ; ; ; ;
Related with
Citations(7)
References(22)
Drugs or chemicals(1)
Diseases(3)
Organisms(1)
Authors(7)
Pubmed
Characterization of focal hepatic lesions with SPIO-enhanced MRI.
Journal: World journal of gastroenterology
May/2/2002
Description

OBJECTIVE

To evaluate the value of superparamagnetic iron oxide (SPIO) enhanced MRI in characterizing focal hepatic lesions.

METHODS

Forty-three patients (32 men,11 women, mean age 51 years, age range 25-74 years) with previously identified focal hepatic lesions were enrolled into this study. All the patients underwent plain, Gd-DTPA enhanced MRI and the SPIO enhanced MRI 1-7 d later. The surgico-pathologic diagnosis was aestablished in 31 cases and the diagnosis in other 12 cases was made on the basis of clinical findings and biochemical tests. The signal changes of lesions were analyzed and the CNRs of lesion-to-liver were measured before and after SPIO enhancement. The data were analyzed by paired t test.

RESULTS

Focal hepatic lesions included primary hepatocellular carcinoma (HCC,n=22), hemangioma (n=5), cyst (n=4), metastases (n=5), cirrhotic nodule (n=4), focal nodular hyperplasia (FNH, n=5) and other miscellaneous lesions (n=6). After SPIO enhancement HCC demonstrated iso- or slight hyperintensity on T1WI and moderate hyperintersity on T2WI, hemangioma showed moderate hyperintensity on T1WI and obvious hyperintensity on T2WI, the SI of cyst had no change either on T1WI or on T2WI, cirrhotic nodules revealed iso-intensity on T2WI, and the SI of FNH decreased significantly on T2WI. No specific manifestations were found in the other 6 miscellaneous lesions after SPIO enhancement.

CONCLUSIONS

SPIO enhanced-MRI can improve the characterization confidence for diagnosis of focal hepatic lesions.

Read more
Authors
; ; ; ; ;
Related with
Citations(7)
References(30)
Drugs or chemicals(6)
Diseases(8)
Organisms(1)
Anatomy(1)
Authors(6)
Pubmed
Dichloroacetate enhances adriamycin-induced hepatoma cell toxicity in vitro and in vivo by increasing reactive oxygen species levels.
Journal: PloS one
December/30/2014
Description

A unique bioenergetic feature of cancer, aerobic glycolysis is considered an attractive therapeutic target for cancer therapy. Recently, dichloroacetate (DCA), a small-molecule metabolic modulator, was shown to reverse the glycolytic phenotype, induce reactive oxygen species (ROS) generation, and trigger apoptosis in various tumor cells. In this work, the capacity of DCA to enhance Adriamycin (ADM) efficacy in hepatoma cells by modulating glucose metabolism and redox status was evaluated. Two human hepatoma (HCC-LM3 and SMMC-7721) and a normal liver (LO2) cell lines were treated with DCA or ADM alone, or in combination. Exposure of hepatoma cells to DCA/ADM combination resulted in significantly decreased cell viability and increased percentage of apoptotic cells as well as intracellular ROS levels, in comparison with treatment with DCA or ADM alone. However, simultaneous treatment with the thiol antioxidant N-acetylcysteine (NAC, 10 mmol/L) reduced the elevated ROS levels and protected hepatoma cells from the cytotoxic effects of DCA/ADM combination. L-buthionine-[S,R]-sulfoximine, an inhibitor of glutathione synthesis, enhanced hepatoma cell sensitivity to DCA/ADM combination. Interestingly, treatment with DCA/ADM combination did not significantly increase cytotoxicity in normal hepatocytes in comparison with the drugs administered individually. Finally, DCA reduced tumor growth and enhanced ADM efficacy on HCC-LM3 hepatoma in mice. Overall, our data suggest that DCA enhances ADM cytotoxicity in hepatoma cells by increasing intracellular ROS levels and provide a strong biochemical rationale for the use of DCA in combination with ADM for treatment of hepatoma.

Read more
Authors
; ; ; ; ; ;
Related with
Citations(7)
References(39)
Drugs or chemicals(4)
Diseases(2)
Organisms(3)
Processes(2)
Anatomy(1)
Affiliates(2)
Authors(7)
Pubmed
Challenges of advanced hepatocellular carcinoma.
Journal: World journal of gastroenterology
May/16/2017
Description

Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials.

Read more
Authors
; ; ; ; ;
Related with
Citations(7)
References(120)
Drugs or chemicals(3)
Diseases(4)
Organisms(1)
Anatomy(2)
Affiliates(1)
Authors(6)
Pubmed
Ruptured hepatoblastoma with massive internal bleeding in an adult.
Journal: World journal of gastroenterology
February/26/2006
Description

Hepatoblastoma is the most common primary hepatic tumor of children. However, only a very few cases have been reported in adults. Most studies support treatment with chemotherapy followed by surgical resection. We present the first reported case of adult hepatoblastoma in Taiwan. A 52-year-old female suffered from sudden onset of abdominal pain and general weakness for days. Internal bleeding with hemorrhagic shock was suspected and two massive lesions in both lobes of the liver with hemoperitoneum were noted from imaging studies. Surgical resection of the larger left lobe tumor and radio-frequency ablation of the right smaller one were performed. The histopathology diagnosis was of a hepatoblastoma.

Read more
Authors
; ; ; ; ; +3 authors
Related with
Citations(7)
References(22)
Diseases(4)
Organisms(1)
Affiliates(1)
Authors(9)
Pubmed
Correlation between the expression of divalent metal transporter 1 and the content of hypoxia-inducible factor-1 in hypoxic HepG2 cells.
Journal: Journal of cellular and molecular medicine
September/7/2008
Description

Transferrin and transferrin receptor are two key proteins of iron metabolism that have been identified to be hypoxia-inducible genes. Divalent metal transporter 1 (DMT1) is also a key transporter of iron under physiological conditions. In addition, in the 5' regulatory region of human DMT1 (between -412 and -570), there are two motifs (CCAAAGTGCTGGG) that are similar to hypoxia-inducible factor-1 (HIF-1) binding sites. It was therefore speculated that DMT1 might also be a hypoxia-inducible gene. We investigated the effects of hypoxia and hypoxia/re-oxygenation on the expression of DMT1 and the content of HIF-1alpha in HepG2 cells. As we expected, a very similar tendency in the responses of the expression of HIF-1alpha, DMT1+IRE (iron response element) and DMT1-IRE proteins to chemical (CoCl(2)) or physical hypoxia was observed. A highly significant correlation was found between the expression of DMT1 proteins and the contents of HIF-1 in hypoxic cells. After the cells were exposed to hypoxia and subsequent normoxia, no HIF-1alpha could be detected and a significant decrease in DMT1+IRE expression (P<0.05), but not in DMT1-IRE protein (versus the hypoxia group), was observed. The findings implied that the HIF-1 pathway might have a role in the regulation of DMT1+IRE expression during hypoxia.

Read more
Authors
; ; ; ; ; ;
Related with
Citations(7)
References(40)
Genes(2)
Drugs or chemicals(5)
Diseases(2)
Organisms(1)
Processes(4)
Anatomy(3)
Affiliates(1)
Authors(7)
Pubmed
Preparation and activity of conjugate of monoclonal antibody HAb18 against hepatoma F(ab')(2) fragment and staphylococcal enterotoxin A.
Journal: World journal of gastroenterology
April/17/2002
Description

OBJECTIVE

To prepare the conjugate of staphylococcal enterotoxin A (SEA) protein which is a bacterial SAg and the F(ab')(2) fragment of mAb HAb18 against human hepatocellular carcinoma (HCC), and identify its activity in order to use SAg in the targeting therapy of HCC.

METHODS

MAb HAb18 was extracted from the abdominal dropsy of Balb/c mice, and was purified through chromatography column SP 40HR with Fast protein liquid chromatography (FPLC) system. The F(ab')(2) fragment of mAb HAb18 was prepared by papainic digestion method. The conjugate of mAb HAb18 F(ab')(2) fragment and SEA was prepared with chemical conjugating reagent N succinimidyl 3 (2-pyridyldithio) propionate (SPDP) and purified through chromatography column Superose 12 with FPLC system. The molecular mass and purity of each collected peak were identified with SDS-PAGE assay. The protein content was assayed by Lowry's method. The antibody activity of HAb18 F(ab')(2) against HCC in the conjugate was identified by indirect immunocytochemical ABC method, and the activity of SEA in the conjugate to activate peripheral blood mononuclear cells (PBMC) was identified with MTT assay.

RESULTS

The IgG mAb HAb18 was extracted, and purified successfully. Immunocytochemical staining demonstrated that it reacted with most of HHCC cells of human HCC cell line. There were two peaks in the process of purification of the prepared HAb18 F(ab')(2) SEA conjugate. SDS-PAGE assay demonstrated that the molecular mass of the first peak was about 130 ku, and the second peak was the mixture of about 45 ku and a little 100 ku proteins. The immunocytochemical staining was similar in HAb18 F(ab') (2) SEA conjugate and HAb18 F(ab') (2), i.e.the cytoplasm and/or cell membranes of most HHCC cells were positively stained. The MTT assay showed that the optical absorbance (A) value at 490 nm of HAb18 F(ab') (2) SEA conjugate was 0.182 +/- 0.012, that of negative control was 0.033 +/- 0.009, and there was significant difference between them (P < 0.05).

CONCLUSIONS

SPDP is a good protein conjugating reagent and can be used in preparing protein conjugate. The conjugate of mAb HAb18 F(ab') (2) fragment and SEA protein was prepared successfully in present study and can be used in the experimental study of HCC targeting therapy with the conjugate of SAg and anti HCC mAbs or their fragments.

Read more
Authors
; ;
Related with
Citations(7)
References(40)
Drugs or chemicals(5)
Diseases(2)
Organisms(4)
Anatomy(1)
Affiliates(1)
Authors(3)
load more...