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

A novel P450 cDNA, designated IVA3, was isolated from a lambda gt11 cDNA library from clofibrate-treated rat liver by screening with the lauric acid omega-hydroxylase, IVA1, cDNA probe. This cDNA encoded a protein with 507 amino acids and a calculated Mr of 58,239. The IVA3 cDNA shared 65% and 97% nucleotide and 72% and 96% DNA-deduced amino acid sequence similarities with IVA1 and IVA2, respectively. The CYP4A gene family, designated the Cyp4a locus, was mapped to mouse chromosome 4 using a panel of mouse-hamster somatic cell hybrids. Levels of the IVA mRNAs were analyzed in rat tissues and cell cultures after treatment with the hypolipidemic drug clofibrate. The IVA1, IVA2, and IVA3 mRNAs were present at very low levels in the livers of untreated rats and markedly induced in rats treated with clofibrate. Dose-response and time-course studies revealed that all three genes were regulated coordinately in liver. In contrast to the coordinate induction in liver, only the CYP4A3 gene was induced in the rat hepatoma cell line McA-RH7777. In the kidney, IVA1 and IVA3 mRNAs were present at low levels and were induced by clofibrate in a manner similar to that in liver. In contrast, the IVA2 mRNA was expressed in the kidney of untreated rats at a level similar to that of the maximally induced IVA2 mRNA in liver. These data indicate that the CYP4A1, CYP4A2, and CYP4A3 genes are regulated coordinately in liver while only CYP4A2 is activated constitutively in kidney.
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PMID:The rat clofibrate-inducible CYP4A subfamily. II. cDNA sequence of IVA3, mapping of the Cyp4a locus to mouse chromosome 4, and coordinate and tissue-specific regulation of the CYP4A genes. 276 33

Total hepatectomy plus liver transplantation was performed on 105 patients considered unsuitable for liver resection. Postoperative 5-year actuarial survivals correlated with the pathologic stage of the tumor: stage I 75%, stage II 68%, stage III 52.1%, and stage IVA 11%. The overall 5-year survival for all patients was 36%. Nodal disease, bilobar tumor, and macroscopic venous invasion were significant poor-prognosis features. In addition, 12 patients with pT4N1M0 lesions (also stage IVA) had hepatectomy plus more extensive en bloc regional resection (Whipple procedure or cluster resection) plus transplantation in an effort to prevent local recurrence. Only 2 of these 12 patients (16.7%) are alive and free of disease after 2 years. Seven patients (58%) have died from tumor recurrence usually originating from distant metastases an average of 10.6 months after transplantation. Successful transplantation for hepatoma depends on screening programs to identify early stage disease. Successful outcome of transplantation for late stage disease, which includes most of the patients in our series, awaits the development of neoadjuvant therapy to control distant microscopic metastases, which are almost certainly present though not apparent at the time of transplantation.
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PMID:Liver transplantation for hepatocellular carcinoma. 774 Aug 11

Between 1980 and 1994, 178 patients were confirmed to have hepatocellular carcinoma (HCC) in our hospital. The 5-year survival rates in patients with HCC of stage I, II and IVA were 38.1%, 31.8% and 3.9%, respectively. No patient in stage III or IVB survived for more than four years. The 5-year survival rates of the patients treated by hepatic resection, ultrasonically guided percutaneous ethanol injection and transcatheter hepatic arterial embolization were 53.7%, 38.7% and 13.5%, respectively. The logrank test showed a significant difference in cumulative survival rates obtained in patients with HCC according to the tumor stage (p < 0.001) or principal treatment procedure (p < 0.001). Twelve patients survived for more than five years. We employed a Cox's proportional hazards model to estimate the factors significantly affecting the survival time. Variables with statistical significance were the clinical stage (p < 0.001), tumor size (maximal tumor diameter) (p < 0.001) and patient's age (p < 0.05). Conclusively, patients in the early stage of HCC associated with mild liver cirrhosis have a significantly better chance for long survival.
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PMID:Hepatocellular carcinoma cases with five-year survival and prognostic factors affecting the survival time. 857 79

We evaluated the therapeutic effect of HVI.CHP in 11 patients with Stage III and IVA multiple hepatocellular carcinoma (group H) in comparison with conventional intraarterial chemotherapy (group S, 12 patients) and transarterial embolization (TAE; group T, 15 patients). The patients in each group had the same background as group H in terms of liver function tests. The Vp3 positive rates in group H (37%) and group S (47%) were significantly higher than group T (0%). One-year survival rates of groups H, S and T were 63. 6%, 8.3% and 46.7%, respectively, and 2-year survival rates were 63.6%, 0% and 20%, respectively. A significant difference was seen between the survival curves of groups H and S (p < 0.01), whereas no significant differences were detected between those of groups H and T. The survival rates for stage IVA patients in groups H, S and T were 55.6%, 10% and 40%, respectively, for 1 year and 55.6%, 0% and 10%, respectively, for 2 years. The difference of survival curves between Stage IVA patients of each group was analogous to those between overall patients of each group. Although 4 patients with Vp3 were included in group H but none in group T, the survival rates of group H were rather higher than in group T at 2 years. These data suggest that HVI.CHP could be the treatment of choice for unresectable multiple hepatocellular carcinoma.
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PMID:[The effect of high-dose intraarterial chemotherapy with percutaneous hepatic venous isolation and charcoal hemoperfusion (HVI.CHP) for unresectable multiple hepatocellular carcinoma--comparison with other therapeutic modalities]. 885 70

Unresectable hepatocellular carcinoma is related to a poor prognosis. Encouraging response rates and survival have been reported with intra-arterial (i.a.) chemotherapy and chemo-embolisation, but limited data are available on the association of the two treatment modalities. We therefore started a new programme combining i.a. chemotherapy with chemo-embolisation. The treatment regimen consisted of L-leucovorin (100 mg/m2 i.v.), 5-fluorouracil (800 mg/m2 i.a.), and carboplatin (250 mg/m2 i.a.). Chemo-embolisation with mitoxantrone (10 mg/m2) plus ethiodized oil followed immediately. The same treatment plus gelatin sponge was given after 28 days. 26 patients entered the study and were evaluable for response and side-effects. Main patient characteristics were: males 21, females 5: median age 68 years (range 42-76 years); stage TNM II-III 17, IVA 9; Child's A 12, Child's B 14; elevated baseline alpha-fetoprotein 17; cirrhosis 25. 14 patients had a partial response (54%; 95% confidence interval 33-73%), 3 had stabilisation and 9 had progressive disease. Median survival was 11 months (range 2-20+). 16 patients had grade I-II pain and 15 grade I-II fever. Our results indicate that the regimen is safe, well tolerated and capable of inducing objective remissions in a high percentage of patients with hepatocellular carcinoma.
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PMID:Intra-arterial chemotherapy followed by chemo-embolisation in unresectable hepatocellular carcinoma. 907

Tumoral recurrence rate and survival of patients with hepatocellular carcinoma (HCC) treated by orthotopic liver transplantation (OLT) depend on tumor stage. Thereby, from the beginning of our program, we selected only patients with solitary tumors < or = 5 cm without vascular invasion, thus avoiding the use of the tumor-node-metastasis (TNM) staging system as a selection tool. The present study reports the results obtained in 58 consecutive patients (52 +/- 8 years, 47 males) with HCC (7 incidentals) transplanted between 1989 and 1995. Transplantation was indicated because of tumor diagnosis in 40 cases and advanced liver failure in 18. Mean tumor size at staging was 28.2 +/- 12.1 mm. No adjuvant treatment was applied during the waiting period (58.9 +/- 45.1 days). The pathological tumor-node-metastasis (pTNM) classification allocated 15 patients to stage I, 19 to stage II, 11 to stage IIIA, and 13 to stage IVA showing preoperative understaging in 43% of the cases with known tumor. After a median follow up of 31 months, only two patients have shown tumor recurrence and fifteen have died, the 1-, 3-, and 5-year survival being 84%, 74%, and 74%. All HCV+ patients remain infected and 94% showed significant liver disease (6 cirrhosis). Six patients have had a second transplant. In conclusion, the application of restrictive criteria not following the TNM staging system prompts excellent results for liver transplantation in patients with HCC, both in terms of survival and disease recurrence, even without applying adjuvant treatment; however, the survival data should be tempered by the appearance of complications that may worsen the long-term prognosis.
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PMID:Liver transplantation for small hepatocellular carcinoma: the tumor-node-metastasis classification does not have prognostic power. 962 Mar 29

Vascular endothelial growth factor (VEGF) is closely related to angiogenesis in various human cancers. However, little is known of its circulating levels in hepatocellular carcinoma (HCC). We examined circulating VEGF levels in chronic liver disease to assess their clinical significance. Plasma VEGF concentrations were determined, by enzyme immunoassay, in patients with chronic hepatitis (CH; n = 36), liver cirrhosis (LC; n = 77), and HCC (n = 86) for a cross-sectional study. Plasma VEGF levels in healthy controls (n = 20) and CH, LC, and HCC patients were 17.7 +/- 5.4 (mean +/- SD), 30.6 +/- 22.8, 34.4 +/- 27.0, and 51.1 +/- 71.9 pg/ml, respectively. The levels were significantly elevated in the HCC group, compared with the control, CH, and LC groups. Plasma VEGF levels in stage I, II, III, IVA, and IVB HCC patients were 27.6 +/- 16.1, 26.5 +/- 13.7, 35.8 +/- 15.3, 45.4 +/- 39.4, and 103.1 +/- 123.2 pg/ml, respectively. The stage IVB patients with remote metastasis showed significantly marked elevation compared with the patients at the other stages. Platelet numbers were weakly correlated with plasma VEGF levels in the HCC group. Plasma VEGF level was highly elevated in patients with HCC, particularly those with metastatic disease. We consider that plasma VEGF is a possible tumor marker for metastasis of HCC. Circulating VEGF may be derived mainly from the large burden of tumor cells, and partly from platelets activated by the vascular invasion of HCC cells.
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PMID:Circulating vascular endothelial growth factor (VEGF) is a possible tumor marker for metastasis in human hepatocellular carcinoma. 965 17

We studied the long-term outcome of percutaneous isolated hepatic perfusion (PIHP) for patients with hepatocellular carcinoma. This study included 31 patients with Stage IVA and 5 with IVB disease treated by PIHP until December, 1997. The mean age and tumor diameter were 55 and 7.7 cm, respectively. Twenty-two had portal vein invasion, 13 had hepatic vein invasion, and all patients had multiple intrahepatic metastases of more than 5 tumor foci. The PIHP with adriamycin or cisplatin was undertaken in a total of 50 treatments in these 36 patients. CR was observed in 6 and PR in 13 with an overall response rate of 59%, excluding 4 patients who were not evaluable. Five of 6 patients with CR remain free of disease at 7 to 54 months after the first treatment. The overall survival rate was 67% at 1 year and 32% at 5 years. The survival rates of Stage IVA patients (1-year = 71%, 5-year = 36%) were higher than Stage IVB patients (1-year = 20%, 5-year = 0%). The 5-year survival rates of patients with vascular invasion (Vp1-3 = 23%, Vv1-3 = 8%) were lower than those without it (Vp0 = 47%, Vv0 = 51%). These results indicated that PIHP achieved a 5-year survival rate of approximately 40% in patients with multiple advanced hepatocellular carcinoma in the absence of distant organ metastases and marked vascular invasion, and yielded complete long-term remission in some of these patients.
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PMID:[The long-term results of percutaneous isolated hepatic perfusion for patients with advanced hepatocellular carcinoma]. 970 4

Primary hepatocellular carcinoma (HCC) is a common malignancy with a dismal prognosis; new modalities of treatment as alternatives to surgery have been developed for unresectable patients. The authors obtain baseline data for the natural history of HCC so that the efficacy of new treatments may be evaluated. A retrospective study of 157 untreated patients with tissue-proven or serodiagnosed HCC was conducted. Clinical characteristics including laboratory investigation, treatment received, survival from the time of diagnosis, and prognostic factors were evaluated. There were 129 men and 28 women (ratio, 4.6:1). Median age was 50.9 years (range, 14.1-85.3 years). The most common symptoms and signs were weight loss (68.2%), abdominal fullness (62.5%), abdominal pain (51.6%), hepatomegaly (73.7%), ascites (45.2%), and jaundice (40.6%). Eighteen percent had extrahepatic metastases of which the lungs were the most common site. Seventy percent were hepatitis B virus related. Overall median survival was 8.7 weeks after the time of diagnosis. Survivals by stages were: TNM II, 16.6 weeks; TNM III, 7.3 weeks; TNM IVA, 9.7 weeks; TNM IVB, 7.6 weeks; Okuda II, 10.7 weeks; and Okuda III, 7.3 weeks. Multivariate analysis revealed serum total bilirubin and albumin as independent prognostic factors of survival. Common causes of death were upper gastrointestinal hemorrhage (34.1%), cancer-related causes (cachexia, HCC rupture, metastatic disease, 31.8%), and hepatic failure (25.0%). Patients with HCC were diagnosed at late stages of their disease and the advanced nature of the tumor precluded effective therapy. Earlier tumor detection at a time when patients are better candidates for treatment may be aided by an active surveillance program of high risk groups.
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PMID:Natural history of untreated primary hepatocellular carcinoma: a retrospective study of 157 patients. 970 39

The authors report 3 cases of liver transplantations in children between 4 and 10 years of age, complicated with malignant hepatic tumors after biliary atresia. The preoperative abdominal computed tomography (CT) scans of all 3 cases showed hepatic masses. The serum alpha-fetoprotein levels were elevated highly in 2 cases. After living-related liver transplantation (LRLT), the pathologic findings of the masses in the resected livers showed hepatocellular carcinoma in 2 cases and hepatoblastoma in the other. All cases were associated with biliary cirrhosis. The stage of the liver tumor in the 3 cases using the TNM system was IVA (T4, N0, M0), II (T2, N0, M0) and IVA (T4, N0, M0). Chemotherapy was used in all cases after liver transplantation, and all patients survived with no recurrence. The results suggest that even though malignant liver tumors rarely are complicated with biliary atresia in childhood, one should be alert to the occurrence of hepatic malignancy and perform routine screening of alpha-fetoprotein levels, abdominal CT scans, and magnetic resonance imagings.
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PMID:Liver transplantation for biliary atresia associated with malignant hepatic tumors. 1122 90


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