Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early diagnosis of HCC is possible because certain risk factors for this tumor are known and because sensitive and relatively inexpensive diagnostic tools are available. Early diagnosis of HCC is also possible because of the long phase of asymptomatic tumor growth and the tumor's tendency to grow as a solitary mass in many patients. In two consensus development conferences held in Anchorage, Alaska and in Milan, Italy, chronic carriers of HBsAg, patients with cirrhosis, patients with rare metabolic liver diseases, and individuals with family histories of HCC were identified as patients at high risk for HCC and therefore as candidates for periodic screening. At the Anchorage conference, it was recommended that healthy carriers have at least yearly determinations of serum AFP and that carriers with additional risk factors (e.g., cirrhosis) be screened every 6 months by abdominal US scans and determination of serum AFP levels. No specific recommendations were released for HBsAg-negative patients with chronic liver disease. At the Milan conference, it was recommend that patients with cirrhosis or with certain congenital metabolic conditions known to be at risk for HCC should be screened by AFP determination and US scan twice a year. It was also recommended that HBsAg carriers older than 35 years or with family histories of HCC should be screened for HCC by determinations of serum AFP levels and aminotransferase levels once a year.
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PMID:Screening for cancer in viral hepatitis. 1121 10

Forty years after its discovery, estimation of serum AFP remains a useful test for clinicians involved in management of patients with HCC or chronic liver disease. The test, when used with the conventional cut-off point of 500 ng/mL, has a sensitivity of about 50% and a specificity of more than 90% in detecting the presence of HCC in a patient with coexisting liver disease. New tests that can significantly increase the specificity at lower levels (i.e., between 10 and 500 ng/mL) are available but have, to date, been too complex to be widely applied in clinical practice. Serum AFP estimation may also be useful in monitoring response to therapy, particularly as more effective systemic regimens are becoming available. Indeed, there is preliminary evidence that changes in serum AFP may be a more accurate and sensitive way of determining the degree of response to treatment than conventional imaging procedures that rely on physical determination of tumor size. It may, perhaps, be time to add changes in serum AFP to the conventional imaging criteria for assessing response in clinical trials.
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PMID:The role of serum alpha-fetoprotein estimation in the diagnosis and management of hepatocellular carcinoma. 1121 12

Gene therapy using replication-competent adenovirus that selectively propagates in tumor cells may be an effective treatment for cancer. We developed an adenovirus that would be replication specific for hepatocellular carcinoma (HCC). Based on our finding that the E1B55k-deficient adenovirus was able to replicate in human primary hepatocytes, we therefore designed an adenovirus carrying E1A and attenuated E1B gene driven by the alpha-fetoprotein promoter (Adv-AFP-E1AdB), thus restricting the replication specificity in AFP-producing HCC. Replication of Adv-AFP-E1AdB in primary hepatocytes was practically negligible 4 days after infection. Although Adv-AFP-E1AdB replicated slowly in AFP-producing HCC, it efficiently destroyed HCC cells independent of their p53 status. Experiments were conducted in vivo using systemic administration of Adv-AFP-E1AdB and we observed tumor size reduction in nude mice having liver cancer. The use of replication-competent adenovirus deficient of the E1B gene coupled to an AFP-targeting strategy may be a safe and efficacious treatment for HCC.
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PMID:Target gene therapy for alpha-fetoprotein-producing hepatocellular carcinoma by E1B55k-attenuated adenovirus. 1140 92

To investigate the frequency of HER-2 oncogene amplification in primary hepatocellular carcinoma (HCCs) and its relationships with clinicopathological parameters and prognosis, 42 surgical samples from patients with primary HCCs were detected for their HER-2 oncogene amplification by dual FISH technique, and then the correlations between HER-2 amplification and clinicopathological characteristics and prognosis were analyzed statistically. HER-2 oncogene amplification was detected in 9 of 42 (21.4%) primary HCCs, including 4 (9.5%) cases with high copy (HC) and 5 (11.9%) ones with low copy (LC). HER-2 amplification was associated significantly with postoperative survival time of HCC patients examined (P = 0.046) and the presence of HER-2 gene amplification showed a trend toward a correlation with tumor size (P = 0.085), but wasn't relative to sex, age, AFP level, HBV infection, postoperative relapse and clinical staging of HCC patients tested (P > 0.05). On the other hand, gain of the HER-2 oncogene copy was examined in 31 of 42(73.8%) primary HCCs, consisting of 9 (21.4%) cases with HER-2 amplification and 22(52.4%) ones with aneusomy 17/polysomy 17. There weren't significant relationships between gain of HER-2 oncogene copy and, HCC patient's sex, tumor size, clinical staging, postoperative relapse and survival time (P > 0.05), but gain of HER-2 oncogene copy correlated significantly to patients' age, AFP level and HBV infection (P < 0.05). The study indicated that there were a lower frequency of HER-2 oncogene amplification and a higher frequency of aneusomy 17/polysomy 17 in primary HCCs and that HER-2 oncogene amplification activation might be involved in the development and progression of a subset of HCCs, and seemed to be a valuably independent prognosis factor predicting postoperative poorer survival for patients with HCC.
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PMID:[Quantitative detection of HER-2 oncogene amplification in primary hepatocellular carcinoma using dual FISH technique and its clinical significance]. 1158 36

AIM:To offer a more simple method with a high sensitivity and specificity for detection of hepatoma cells in peripheral blood of the patients with HCC.METHODS:Improved nested RT-PCR method was used to detect the expression of AFP mRNA in nuclear cells separated from peripheral venous blood.RESULTS:AFP mRNA contained in tenhepatoma cells was detected from 2mL peripheral blood.CONCLUSION:The improved nested RT-PCR assay for AFP mRNA expressed in cancer cells in peripheral blood might be a valuable method for clinical diagnosis of HCC.
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PMID:Detection of hepatoma cells in peripheral blood of HCC patients by nested RT-PCR. 1181 49

AIM:To clone and identify the whole cDNA of MXR7 gene and to find out its expression in human HCC, and normal tissues.METHODS:The DNA primers were designed and synthesized according to the whole cDNA sequence of MXR7 gene. The cDNA of human HCC was taken as the template while the cDNA of MXR7 gene was synthesized by polymerase chain reaction (PCR). Recombinant DNA conforming to reading frame was constructed by connecting purified PCR product of the cDNA of MXR7 gene with expression vector pGEX-5X-1 of fusion protein. The plasmid MXR7/pGEX-5X-1 was identified by sequencing. Using (32)P labeled MXR7 cDNA as probe, MXR7 mRNA expression was detected by Northern blot analysis in 12 different human normal tissues, 7 preoperatively untreated non-liver tumor tissues, 30 preoperatively untreated HCC, the paracancerous liver tissues and 12 normal liver tissues samples.RESULTS:Restriction enzyme and sequence analysis confirmed that the insertion sequence in vector pGEX-5X-1 was the same as the cDNA sequence of MXR7 gene. Northern blot analysis showed no expression of MXR7 mRNA in 12 kinds of normal human tissues including liver, 7 tumor tissues in other sites and 12 normal liver tissues, the frequencies of MXR7 mRNA expression in HCC and paracancerous liver tissues were 76.6% and 13.3%, respectively. The frequency of MXR7 mRNA expression in HCC without elevation of serum AFP and in HCC <5cm was 90% (9/10) and 83.3% (5/6), respectively.CONCLUSION:MXR7 mRNA is highly expressed in human HCC, which is specific and occurs at an early stage of HCC, suggesting MXR7 mRNA can be a tumor biomarker for HCC. The detection of MXR7 mRNA expression in the biopsied liver tissue is helpful in discovering early subclinical liver cancer in those with negative serum AFP.
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PMID:Cloning and expression of MXR7 gene in human HCC tissue. 1181 23

AIM:To investigate the predictors for recurrence or metastasis of HCC, and to evaluate the effect of antiangiogenic therapy on the growth of transplantable human HCC in nude mice.METHODS:RT-PCR was used to measure the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in 56 pairs of nontumorous liver and tumor samples. Sixty blood samples from human HCC were examined by nested RT-PCR to find out AFP mRNA. Recombinant human endostatin and polyclonal antibody against VEGF were administered to treat human HCC transplanted in nude mice.RESULTS:Thirty of 56 HCC samples showed stronger expression of MMP9 in tumorous tissues than in nontumorous tissues. Fifteen of the 26 patients with relative expression level of MMP-9 more than 0.34 developed tumor recurrence or metastasis, whereas only 7 of 30 patients with relative expression level less than 0.34 developed tumor recurrence (P < 0.05). There was no significant difference in the relative expression level of VEGF between patients with postoperative recurrence or metastasis and those without recurrence. AFP mRNA was detectable in 53.3% of patients with HCC. The sensitivity and specificity of AFP mRNA as a marker to detect hematogenous dissemination of HCC cells was 81.8% and 84.4%, respectively. Recombinant human endostatin and polyclonal antibody against VEGF inhibited the growth of transplantable HCC in nude mice by 52.2% and 45.7%, respectively.CONCLUSION: MMP-9 expression in HCC correlates with the postoperative recurrence or metastasis of HCC. Patients with high level of MMP-9 expression in HCC are susceptible to metastasis.AFP mRNA could serve as an indicator of hematogenous spreading of HCC cells in circulation and a predictor of recurrence or metastasis of HCC. Antiangiogenesis may be an adjuvant therapy for HCC.
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PMID:Recurrence or metastasis of HCC:predictors, early detection and experimental antiangiogenic therapy. 1181 24

Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient-like metastatic model of human HCC in nude mice (LCI-D20) and a low metastatic model of human HCC in nude mice (LCI-D35) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding. Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-1 increased gradually following tumor progression in LCI-D20 model, and correlated with tumor size and AFP level. Phasic expression of tissue intercellular adhesion molecule-1 in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including anti-angiogenesis,antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vitro and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.
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PMID:Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential. 1181 39

A 69-year-old female with unresectable hepatocellular carcinoma was treated with continuous arterial infusion of low-dose cisplatin (10 mg/body/day) and 5-fluorouracil (250 mg/body/day). The regimen was continued for 5 days then discontinued for 2 days, and repeated for 4 weeks. The portal tumor thrombus almost disappeared and HCC was smaller than before chemotherapy. Tumor marker (AFP and PIVKA-II) decreased remarkably. As tumor markers increased again 2 months later, the same regimen chemotherapy was performed once more. The patient was treated with arterial chemotherapy as an outpatient. The present case of hepatocellular carcinoma with portal tumor thrombus was effectively treated by arterial infusion chemotherapy with low dose cisplatin and 5-fluorouracil.
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PMID:[A case of hepatocellular carcinoma with portal tumor thrombus effectively treated by arterial infusion chemotherapy with low-dose cisplatin and 5-fluorouracil]. 1197 46

Two chimerical regulation sequences for gene expression, one (called ATrPS) harboring an enhancer of human alpha1-antitrypsin gene (AT) and a promoter and silencer(rPS)of rat afp gene, and another (called rAFP) consisting of enhancer III of rat afp gene and its rPS, were constructed, respectively. Then, two CAT expression vectors, rAFP-pCAT and ATrPS-pCAT, were constructed in which the cat reporter gene was put under the control of these elements, respectively. CAT activities could were detected in the AFP positive liver cancer cells and also in those liver cancer cells, liver cells or non-liver cells whose AFP were negative. Results showed that for both constructs, the CAT activities could be found in all AFP positive hepatoma cells, however, while this activity can not be detected in all AFP negative cells. Similar results were observed in primary cell cultures. The results showed that our regulation elements of gene expression really possessed cell-type specificity for AFP positive cells. The cell-type specificity remains when the length of rAFP was cut short as to 0.67 kb; and the activity seemed higher. These regulatory sequences of gene expression may be used in gene therapy for primary liver cancer.
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PMID:Construction of Two AFP-positive Hepatoma Cell-specific Gene Regulatory Sequences. 1216 38


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