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)

Interferon alpha is the only available therapy for patients with chronic hepatitis B. With interferon alpha 3-15 MU thrice weekly or 5 MU daily during 3-6 months one-third of the patients achieve seroconversion of HBeAg and HBV-DNA together with normalization of aminotransferases and slight improvement of histology. Loss of HBsAg is reported in a minority of responders during treatment, but increases during follow-up. Patients with baseline alanine aminotransferase of at least twice the upper limit of normal and low HBV-DNA concentration achieve the best response rates. HIV-positive patients with low CD4 counts and Asians are poor responders. As side-effects influenza-like symptoms are experienced by almost all patients. Mild leukopenia, thrombocytopenia and decreased hairgrowth are frequently reported. Severe depression, depersonalization and psychosis are reported in a small number of patients but tend to be poorly recognized in some studies. The decision whether dose reduction is indicated seems strongly related to the opinion of the investigator. Although long-term effects on the occurrence of cirrhosis and the development of hepatocellular carcinoma are not available yet, the achieved results are promising.
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PMID:Current status of interferon alpha in the treatment of chronic hepatitis B. 143 94

Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) secreted by a hepatoma cell line, HA22T/GVH, was purified and assessed for its effects in vivo on blood leukocytes and bone marrow granulocyte-macrophage progenitor cells (CFU-GM) in ICR mice pretreated with a sublethal dose of cyclophosphamide (cytoxan). The hGM-CSF preparations were natural and had no detectable endotoxin. Five days after the administration of 300 mg/kg cytoxan, severe leukopenia with marked myelopoietic suppression was induced. The cytoxan-treated mice were then injected intraperitoneally with 10,000 units of purified hGM-CSF/mouse daily for three days. Leukopenia was totally abrogated and the leukocyte number greatly increased to a level 2- to 3-fold higher than in GM-CSF-uninjected mice. Differential white cell count showed that the subpopulations of leukocytes responsive to hGM-CSF stimulation were mainly of neutrophils and monocytes, while the lymphocytes remained unaffected. Meanwhile, in the bone marrow, hGM-CSF administration induced an apparent (3-fold) increase in the number of myeloid progenitor cells, CFU-GM. However, the effect in vivo of a single hGM-CSF injection could only maintain for 48 hrs. In addition, the loss in body weight caused by cytoxan was less in the mice with subsequent hGM-CSF than those without CSF. These results suggest that injection of GM-CSF can effectively reconstitute the cytotoxic drug-damaged myelopoiesis without apparent in vivo toxic reaction.
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PMID:In vivo stimulation of myelopoiesis in cyclophosphamide-treated mice by purified human GM-CSF. 165 33

A clinical trial of transarterial chemoembolization for hepatocellular carcinoma using pirarubicin (4'-0-tetrahydropyranyladriamycin, THP) was performed. Although adriamycin has been widely utilized for chemoembolization on the hepatocellular carcinoma, myocardial toxicity has been occasionally observed as its serious side effect. THP has an advantage that myocardial and gastrointestinal complications are less frequent than adriamycin. Ten patients with hepatocellular carcinoma were included in this study. Emulsion of 30-60 mg of THP and lipiodol was administered through a catheter inserted into the right or left hepatic artery, and thereafter, transarterial embolization was performed. PR was observed in seven of the ten patients and MR in two. Only one patient showed NC. Serum alpha-fetoprotein levels decreased in nine of the ten patients, and PIVKA II in the peripheral blood disappeared in all five patients that had been positive before the chemo-embolization four weeks after the treatment. Side effects included nausea in two patients just after administration of THP, but leukopenia below 2,000/cmm, was not observed in any of the patients. No other serious side effect was observed. From these results, THP was suggested to be a useful chemotherapeutic agent for hepatocellular carcinoma.
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PMID:[A clinical trial of transarterial chemoembolization for hepatocellular carcinoma using 4'-0-tetrahydropyranyladriamycin]. 169 81

We conducted these experiments to investigate the differences between continuous portal and one shot portal infusion of 5-fluorouracil (5-FU) using male Donryu rats. Continuous portal infusion of 5-FU (20 mg/kg/day x 5 days) revealed no remarkable side effects on the rats with significant decrease in the number of liver metastases generated by intraportal inoculation of ascites hepatoma AH60C. Consecutive 5-day administration of 5-FU (20 mg/kg x 5) by one shot method via spleen resulted in no metastases but caused death in 75% of rats because of severe leukopenia and dehydration. The rats receiving one shot infusion of 5-FU (33.3 mg/kg x 3, day 1, 3, 5) via spleen showed a significant decrease in the number of metastases without lethal side effects. Continuous portal infusion of 5-FU would be a safe and effective therapy to prevent liver metastases, whereas one shot portal infusion of 5-FU may give rise to severe side effects while preventing liver metastases.
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PMID:[An experimental study on portal infusion of 5-fluorouracil]. 187 31

We have previously demonstrated that individualized dosing of etoposide (VP16) by 72-hour infusion is feasible and that the extent of leukopenia is a function of plasma concentration, pretreatment WBC (WBCp), albumin (ALB), performance status (PS), and bone marrow function (based on transfusion requirements). In the current study, 45 patients were randomized between a fixed dose of VP16 (125 mg/m2/d) versus individualized dosing to a target WBC nadir (WBCN) of 1,700/microL. The total dose was increased by an average of 22% in the latter patients (459 +/- 130 mg/m2 v 375 mg/m2, P = .002). This was associated with a decrease in both the mean WBCN (1,510 +/- 950 v 2,500 +/- 1,420/microL, P = .013) and in the variability of the WBCN (P = .039). The VP16 clearance (mL/min) was not correlated with body surface area. Partial responses were observed in one patient each with hepatoma and non-Hodgkin's lymphoma. We conclude that pharmacologically based dosing may be a means of increasing dose intensity without increasing the incidence of life-threatening toxicity due to a decrease in variability around a target WBC.
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PMID:Pharmacologically based dosing of etoposide: a means of safely increasing dose intensity. 207 47

A phase 1 study of etoposide for hepatocellular carcinoma and cholangiocarcinoma was undertaken by single arterial infusion (9 cases; range of doses levels; step 1: 50 mg/m2, step 2: 75 mg/m2, step 3: 120 mg/m2). Mild leukopenia (2500/mm3 in step 2 and 2400/mm3 in step 3) was observed in 2 cases. Thrombocytopenia or anemia was not observed in these doses. Hypotension was experienced 2 hrs. after infusion in one case of step 2. The post-infusion plasma decay of etoposide was biphasic with t1/2 alpha ranging from 0.59 approximately 0.63 h and t1/2 beta ranging from 5.40 approximately 6.57 h. AUC0-24 increased in association with the increase of the doses. Hepatic artery infusion of etoposide was performed without serious complication and the dose limiting toxicity was leukopenia.
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PMID:[Hepatic arterial infusion of etoposide in the treatment of primary liver neoplasms]. 215 86

Radiation tolerance of the partially irradiated liver was studied in eight patients with primary hepatoma treated by a multimodal approach. Seven patients were treated by transarterial embolization therapy (TAE) with Lipiodol-MMC, and two patients were treated by operation, combined with radiotherapy. Six patients had liver cirrhosis and the other one had renal dysfunction. Respiration-gated irradiation was employed to reduce a treatment volume for seven patients. Radiation portals were carefully tailored using the embolized Lipiodol or a metal clip inserted into the tumor as references. Two or three portals were used for each patient. The treatment volume ranged from 64 to 1400 cm3. The target dose ranged from 50.4 Gy to 81.0 Gy, from 73.5 to 108.6 in TDF. Liver function tests (GOT, GPT, LDH, ALP, ChE and total Bilirubin) were examined for 30 weeks after initiation of irradiation. Three patients showed abnormal value in more than 5 tests. Of these three patients, the hepatic hilum was included in the treatment volume in two, and the tumor progressed during the observation period in two. Leukopenia and thrombopenia were observed, but these values were not below 2000 and 40000/mm3, respectively, although the thrombocyte count before irradiation was below 100000/mm3 in 7 patients. AFP titers decreased after the treatment in six out of seven patients with abnormally elevated pretreatment titer. The survival period after staring irradiation was 6.5 to 25 months. "The volume dose" did not correlate well with the degree of the liver function aggravation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Radiation tolerance of partially irradiated liver in a multidisciplinary treatment for hepatoma]. 216 20

A prospective study was conducted to assess the safety and efficacy of the addition of oral verapamil to intravenous Adriamycin (doxorubicin) for the management of patients with unresectable hepatocellular carcinoma (HCC). All 28 patients studied had histologically verified disease, and cirrhosis was present in 20 of the 21 patients with adequate tissue sampling. The overall median survival was 57 days. Chemotherapy was terminated in seven patients after one course of treatment. Partial response and complete response were noted in four patients (19%) and one patient (4.8%), respectively, among the 21 patients evaluated. Side effects related to the chemotherapy were present in all patients studied. Death from fulminating sepsis occurred in three of the 13 patients with leukopenia. Symptomatic myocardial dysfunction developed in one patient. The addition of verapamil apparently did not potentiate the tumoricidal effect of systemic Adriamycin on HCC but probably did increase its complications.
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PMID:Doxorubicin for unresectable hepatocellular carcinoma. A prospective study on the addition of verapamil. 216 94

Immunotherapy with interleukin (IL)-2 possesses great potential in the treatment of immune-mediated diseases and cancers. However, only a few reports on a small number of children have appeared in the literature. From March 1988 to March 1989, 11 children and adolescents were treated with IL-2. They included 1 patient with hepatocellular carcinoma, 1 with hepatoblastoma, 6 with childhood atopic dermatitis, and 3 with juvenile rheumatoid arthritis. The dosages ranged from 10,000 to 50,000 U/kg every 8 hours by intravenous drip. The following side effects were observed: anorexia, fever, and chillness (100%), general malaise (82%), irritability (64%), diarrhea (100%), nausea and vomiting (73%), weight gain (82%), edema (82%), abdominal distension (73%), oliguria (82%), cough (91%), dyspnea (27%), pleural effusion (40%), hypotension (82%), skin eruption (82%), oral ulcer (18%), enlarged liver (73%) liver function abnormalities (82%), renal function impairment (36%), electrolyte imbalance (73%), anemia (91%), thrombocytopenia (54%), leukopenia (18%), and eosinophilia (73%). Immunologically, numbers of natural killer cells were increased and natural killer and lymphokine-activated killer cell activities were augmented after IL-2 treatment. There was a tendency for serum levels of IL-2 and receptor IL-2 to decrease, especially in patients with atopic eczema. Ten patients (91%) completed one course (9 to 12 days) of therapy, and the remaining patient interrupted the treatment because of intolerable adverse effects. Clinically, complete remission for 3 months was obtained in 1 juvenile rheumatoid arthritis patient, transient improvement (2 to 6 weeks) in all atopic dermatitis patients, minor response in the hepatoblastoma patient, and no response in the patient with hepatocellular carcinoma.
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PMID:Interleukin-2 immunotherapy in children. 217 36

A total of 20 patients with histologically proven primary hepatocellular carcinoma (PHC) received mitoxantrone IV at a dose of 10-16 mg/m2 every 3 weeks. All patients had previous hepatitis B infection. None underwent remission after treatment; 2 had stable disease and 18 progressive disease. The median overall survival was 13 weeks (range, 1-59 weeks). There was no evidence of significant antitumor activity for mitoxantrone in our patients with PHC. Hematotoxicity occurred in 100% of the patients with grades 2-4 leukopenia, 89% of those with grades 1-4 anemia, and 26% of those with grades 2-3 thrombocytopenia. Cardiotoxicity occurred in 20% of the patients after 14-30 mg/m2 mitoxantrone; these included complete heart block with fatal outcome in one case, decreased ventricular ejection fraction in one, and sinus tachycardia in two. Nausea, vomiting, fever, diarrhea, and alopecia were mild and occurred in 15%-45% of the patients Therefore, patients with PHC following hepatitis B infection may be less tolerant to mitoxantrone, resulting in the apparent increase in toxicities.
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PMID:Phase II study of mitoxantrone in unresectable primary hepatocellular carcinoma following hepatitis B infection. 253 94


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