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)

In a Phase II clinical trial, 14 patients with histologically proven primary hepatocellular carcinoma were treated with adriamycin administered intravenously at a dose of 75 mg/m2 every 3 weeks. All 11 evaluable patients responded with 3 exhibiting complete tumor regression after two, three, and five courses of adriamycin respectively. The remission durations for these 3 were 3, 6, and 7 months, and their survivals were 8, 9, and 13 months, respectively. The median survival of the evaluable patients is 8 months (range 1-13 months). The side effects encountered included myelosuppression, anorexia, nausea, vomiting, and alopecia. Adriamycin seems to be an effective agent in hepatocellular carcinoma. Further trials are underway to test its true efficacy both singly and in combination with other drugs in the management of this tumor.
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PMID:Treatment of hepatocellular carcinoma with adriamycin. Preliminary communication. 16 83

Authors report a case of intraventricular hemorrhage with hepatic insufficiency. A 36-year-old man was admitted following the sudden onset of coma. For 10 years before admission he had suffered general fatigue and jaundice, which were treated with medication as acute hepatitis. On the day of admission he began to suffer from a severe headache. Within one hour he was comatose and began to have vomiting, followed by seizures characterized by tonic movement of the right extremities. Lumbar puncture showed an initial pressure over 400 mmH2O, with grossly bloody spinal fluid. Numerous hemorrhages were noted in both optic fundi. Bilateral carotid angiography demonstrated slight enlargement of left lateral ventricle. Computerized tomography revealed that the lareral, third and fourth ventricles were dilated. There were discrete areas of increased absorption coefficient with values measuring between 30 to 35 in the Hounsfield scale in all ventricles. Two burr holes in both frontal areas were performed. About 50ml of blood clot at left ventricle and 30 ml of blood clot with liquor at right ventricle were removed. The patient died 7 days after operation. Autopsy revealed clotted blood in the whole ventricular system, mainly in right anterior horn of lateral ventricle, and a markedly cirrhotic liver with hepatoma. In our review of the literature, the relationship between intraventricular hemorrhage and bleeding tendency caused by hepatic insufficiency was discussed.
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PMID:[Intraventricular hemorrhage with hepatic insufficiency--report of a case (author's transl)]. 23 Dec 14

Bajiaolian (Dysosma pleianthum), one species in the Mayapple family, has been widely used as a general remedy and for the treatment of snake bite, weakness, condyloma accuminata, lymphadenopathy and tumours in China for thousands of years. However, the textbooks of traditional Chinese medicine mention little about the toxicity of Bajiaolian. Within 1 year, the authors saw five people who manifested nausea, vomiting, diarrhoea, abdominal pain, thrombocytopenia, leucopenia, abnormal liver function tests, sensory ataxia, altered consciousness and persistant peripheral tingling or numbness after drinking infusions made with Bajiaolian. The herb was recommended by either traditional Chinese medical doctors or herbal pharmacies for postpartum recovery and treatment of a neck mass, hepatoma, lumbago and dysmenorrhoea. Podophyllotoxin is one of the main ingredients of the Bajiaolian root. The clinical manifestations observed in our patients were consistent with podophyllum intoxication. Podophyllotoxin intoxication usually results from the accidental ingestion or topical application of podophyllum resin. However, these cases of Bajiaolian intoxication were iatrogenic and results from 'therapeutic doses' of Bajiaolian cited in the textbooks of traditional Chinese medicine.
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PMID:Podophyllotoxin intoxication: toxic effect of Bajiaolian in herbal therapeutics. 136 Nov 36

A phase I study of YM-881 (zinostatin stimalamer), neocarzinostatin combined with butylesterified styrene maleate, suspended in iodized poppy oil ethyl ester, was conducted in patients with hepatocellular carcinoma by giving single intra-arterial infusions via catheters inserted by Seldinger's method. Four dose levels, 2, 4, 6, and 8 mg, were tested. Major adverse reactions were fever, anorexia, nausea, vomiting, and abnormal hepatic function. Both the incidence and severity of adverse reactions tended to increase with the 8 mg dose. Tumor regression of 50% or more occurred in one receiving 2 mg and one receiving 4 mg. The results of the study suggest that doses of 6 mg or less may be appropriate for the phase II studies.
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PMID:[Phase I study of YM881 (zinostatin stimalamer) suspension by hepatic arterial infusion. Research Group for Intra-arterial Infusion Therapy with YM881]. 165 86

We have established a cell co-culture system for assessing potential cytotoxic effects of drugs and their metabolites in vitro. Human hepatoma cells (HepG2) were cultured for 7 days in modified Earle's medium in order to induce their drug metabolising (primarily mixed function oxidase) enzymes. K562 human erythroleukemic cells in Transwells, were used as indicator cells for the cytotoxic effects of cyclophosphamide (CYP) and Ondansetron (OND) and/or their metabolites, produced by induced HepG2 cells in the co-cultures. CYP was found to be approximately 1000 times more toxic to K562 cells when cultured in the presence of induced HepG2 cells. OND, a selective 5-HT3 receptor antagonist which is used as an anti-emetic during chemotherapy, was not found to be cytotoxic in the co-cultures at concentrations as high as 100 microM. Since OND has been particularly useful in relieving vomiting induced by cisplatin (cisPt) chemotherapy, we also examined the effect of cisPt on K562 cells in the presence and absence of OND, and found no evidence that OND significantly enhances the cytotoxic effect of cisPt on these cells alone or in co-cultures with induced HepG2 cells. The induced HepG2 co-culture system uses cells of human origin and clearly has considerable potential for examining the effects of drugs and their metabolites on indicator cells derived from a tissue of choice. This system may be particularly useful in the assessment of metabolism and toxicity of new drugs intended for human use.
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PMID:Development of a co-culture system with induced HepG2 cells and K562 cells for examining drug metabolism in vitro. Studies with cyclophosphamide, ondansetron and cisplatin. 165 50

Sixty-three patients with unresectable hepatocellular carcinoma (HCC) were treated with cisplatin-phosphatidyl-choline-Lipiodol (CPL) suspension. Partial response (PR) and minor response (MR) were obtained in 3 of 14 cases (21.4%) by one shot therapy, and in 13 of 43 cases (30.2%) by TAE therapy. AFP decreased in 11 of 15 patients (73.3%) by one shot therapy, and in 32 of 33 patients (97%) by TAE therapy. PIVKA II also decreased. The one-year survival rate was 74% in TAE therapy, and 52% in one shot therapy. The two-year survival rate was 53% in TAE therapy, and 28% in one shot therapy. Nausea, vomiting and fever were noted in most cases as adverse effects, but they were slight. The concentration of free-CDDP in the peripheral venous blood was lower and continued longer than that of CDDP on the market. These results suggest that CPL was useful as an anticancer agent for arterial chemotherapy or TAE therapy for unresectable HCC.
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PMID:[Assessment of therapeutic effects of cisplatin-phosphatidyl-choline-lipiodol (CPL) suspension for hepatocellular carcinoma]. 165 24

A phase II study of YM 881 (zinostatin stimalamer) to determine the response and safety was conducted in patients with hepatocellular carcinoma by injecting a suspension of the drug into the hepatic artery. Repeated doses of 4 to 6 mg of the drug were given every 4 weeks so that the tumor tissues were filled with the suspension. Of the 195 registered patients, 15 were ineligible for the study, 8 dropped out, and data were missing for 5. A total of 167 patients completed the study. Response was assessed in the 167 patients who completed the study. CR was found in one, PR in 59, MR in 25, NC in 67, and PD in 15, with a response rate of 35.9. The safety of the drug was assessed in 177, excluding ineligible patients and 3 who dropped out because of the concurrent use of other drugs. Adverse reactions were found in 93.2% of the patients, and abnormal values in clinical laboratory tests in 60.5%. Major unwanted symptoms included fever, nausea, vomiting, and anorexia. Major abnormal changes in laboratory tests were elevated total bilirubin and LDH and abnormal hepatic function. About half the patients had malaise and pain related to the intra-arterial infusion therapy. The one year survival rate was 56.9%, and the duration of survival of 50% of the patients was 407 days.
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PMID:[Phase II study of YM881 (zinostatin stimalamer) suspension injected into the hepatic artery. Research Group for Intra-arterial Injection Therapy with YM881]. 171 7

Sixteen children, aged 16 days to 13 years with hepatoblastoma (HB) (13 patients) or hepatocellular carcinoma (HCC) (3 patients), were given a total of 89 courses of cisplatin and doxorubicin (PLADO) as IV continuous infusion. All tumors were confined to the liver except for 1 hepatoblastoma patient with pulmonary metastases at presentation. Tumor response to PLADO was evaluable in 10 children (8 HB, 2 HCC) treated with preoperative chemotherapy and in another 2 HB patients treated when they developed pulmonary metastases after initial treatment with surgery alone. There were 2 complete responses (2 HB with pulmonary recurrences), 7 very good partial responses (6 HB and 1 HCC), 2 partial responses (1 HB, 1 HCC), and 1 stable disease (HB). The last patient underwent orthotopic liver transplantation whereas all the other patients had their tumor completely excised at delayed surgery. Documented toxicity was BM depression (16 patients), infection (11), vomiting (11), mucositis (3), hearing loss (1), and cardiotoxicity (1). These data indicate that PLADO in continuous infusion is effective in the treatment of malignant epithelial liver tumors with acceptable toxicity.
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PMID:Effectiveness and toxicity of cisplatin and doxorubicin (PLADO) in childhood hepatoblastoma and hepatocellular carcinoma: a SIOP pilot study. 185 Aug 17

Hereditary tyrosinemia results from an inborn error in the final step of tyrosine metabolism. The disease is known to cause acute and chronic liver failure, renal Fanconi's syndrome, and hepatocellular carcinoma. Neurologic manifestations have been reported but not emphasized as a common problem. In this paper, we describe neurologic crises that occurred among children identified as having tyrosinemia on neonatal screening since 1970. Of the 48 children with tyrosinemia, 20 (42 percent) had neurologic crises that began at a mean age of one year and led to 104 hospital admissions. These abrupt episodes of peripheral neuropathy were characterized by severe pain with extensor hypertonia (in 75 percent), vomiting or paralytic ileus (69 percent), muscle weakness (29 percent), and self-mutilation (8 percent). Eight children required mechanical ventilation because of paralysis, and 14 of the 20 children have died. Between crises, most survivors regained normal function. We found no reliable biochemical marker for the crises (those we evaluated included blood levels of tyrosine, succinylacetone, and hepatic aminotransferases). Urinary excretion of delta-aminolevulinic acid, a neurotoxic intermediate of porphyrin biosynthesis, was elevated during crises but also during the asymptomatic periods. Electrophysiologic studies in seven patients and neuromuscular biopsies in three patients showed axonal degeneration and secondary demyelination. We conclude that episodes of acute, severe peripheral neuropathy are common in hereditary tyrosinemia and resemble the crises of the neuropathic porphyrias.
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PMID:Neurologic crises in hereditary tyrosinemia. 215 31

Intratumor injection of OK-432, a biological response modifier, in the treatment of small HCC was studied in 7 inoperable patients. After evaluation with ultrasound (US), computed tomography (CT), angiography and US-guided biopsy, implantation of a steel coil in the tumor, intratumor injection was performed under US guidance. After completion of the treatment, liver biopsy and image studies were again done to evaluate the extent of tumor necrosis. One patient was alive and well without recurrence 19 months after treatment. Four had recurrent tumors at different site of the liver 4 months, 9 months, 9 months and 8 months later. Two died of progressive malignancy 3 months and 8 months later. In the 6 patients with elevated serum alpha-fetoprotein (AFP) levels, 4 had decreased AFP after treatment, and the 2 mortalities had steadily increased AFP. The most common side effects are fever and chills. Transient abdominal pain with elevated transaminase activities, cough with hemoptysis, and vomiting were seen in 1 case each. After treatment, the biopsy specimens showed total necrosis of HCC. Although the T4/T8 ratio of peripheral blood was increased as compared with that before treatment in 4 cases, peritumoral cytotoxic T lymphocyte and monocyte infiltration were seen in one specimen only, and another 7 examined specimens showed negative staining with monoclonal antibodies of T cells. We conclude that intratumor injection of OK-432 is an alternative treatment for small HCC in inoperable cases. The effectiveness may be due to the direct tumoricidal mechanism of OK-432.
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PMID:Intratumor injection of OK-432 for the treatment of small hepatocellular carcinoma. 217 23


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