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)

Eight patients with liver metastases from adenocarcinoma of the colon or rectum, two with suspected hepatic metastases and one with primary hepatoma were studied with 2-deoxy-2-[18F]-fluro-D-glucose (18F-FDG) using positron emission tomography (PET). In five of the patients with metastatic tumour a second examination was performed four weeks after treatment with recombinant interleukin-2 (rIL2) and fluorouracil (5FU). In all tumours (one primary and eight metastatic) the radioactivity was seen to accumulate in a rim around each tumour with a large central area showing no uptake. In the five cases imaged after treatment with rIL2, the appearance of the tumour uptake was the same as before treatment. In the two cases of suspected but not proven metastases, no abnormal accumulation of 18F-FDG was seen.
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PMID:Pattern of 2-deoxy-2-[18F]-fluro-D-glucose accumulation in liver tumours: primary, metastatic and after chemotherapy. 131 54

For clinical application of adoptive immunotherapy against hepatocellular carcinoma (HCC), it is not easy to prepare tumour specific effector cells such as cytotoxic T lymphocytes (CTL). To induce potent and broad-spectrum effectors, allogeneic cultured hepatoma cell lines (JHH-4 and HuH-6) were used as stimulators of peripheral blood lymphocytes (PBL) instead of autologous HCC cells. Allogeneic tumour- and lymphokine-activated killer cells (ATLAK) were generated by a mixed culture of lymphocytes and allogeneic cultured tumour cells with recombinant interleukin-2 (rIL-2). The tumour-killing activity of ATLAK induced by HuH-6 was confirmed against HuH-6 and other different HCC cell lines (JHH-2, HuH-7 and PLC). These activated lymphocytes were significantly more potent than lymphokine-activated killer cells (LAK) in [51Cr]-releasing assay. The JHH-4 stimulated ATLAK was reactive not only with JHH-4 but also with JHH-2. The lysis of allogeneic targets could be partially inhibited by anti-CD8 and anti-CD3 but not by anti-CD4. Anti-tumour cytotoxicity in these cultures might be mediated by CD3+CD56- and CD3+CD56+ effectors. These results imply that adoptive immunotherapy for HCC with ATLAK may be more feasible than that with LAK.
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PMID:Induction of allogeneic tumour- and lymphokine-activated lymphocytes against hepatocellular carcinoma. 131 67

Treatment of malignant disease with interleukin-2 and lymphokine-activated killer cells activates autoreactive T lymphocytes, stimulates release of cytokines and induces expression of HLA-class II antigens by tumour cells. We studied eight patients with hepatocellular carcinoma treated with a total of 16 courses of recombinant human interleukin-2 and lymphokine-activated killer cells and observed them for features of autoimmune thyroid disease. During the course of treatment there were significant decreases in total serum T4 and T3 and free thyroxine levels, but no change in TSH levels when all patients were analysed as a group. This was due to a number of factors including suppression of thyroid hormone release, haemodilution during interleukin-2 infusion and actual removal of thyroid hormones from the circulation during leukapheresis. Thyroid hormones returned to normal levels during resting period. One patient subsequently developed compensated hypothyroidism (normal total T4, total T3 and free T4 but elevated TSH) and four patients had features of 'sick euthyroid syndrome' (low total T4, total T3 or free T4 but normal TSH). None of the patients studied developed antibodies to thyroglobulin or microsomes. In contrast, no abnormality of thyroid function was seen in any of the nine subjects who received no active treatment. In conclusion, thyroid dysfunction was associated with immunotherapy of malignant disease with interleukin-2 and lymphokine-activated killer cells. This may arise from direct hormonal effects of the cytokines on thyroid hormone production.
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PMID:Thyroid functions in patients treated with interleukin-2 and lymphokine-activated killer cells. 133 2

Previous studies on continuous hepatic artery infusions of recombinant interleukin-2 (IL-2) have shown that in a nontumor-bearing animal a continuous infusion given in a circadian "day cycled" pattern was much less toxic and could be given with 10 times higher doses of IL-2 than if the constant pattern of infusion was used. In the present study, circadian-patterned continuous hepatic artery infusions of IL-2 were used in hepatoma-bearing rats. Doses of 10 mg/m2/day could be tolerated when IL-2 was given in a "day cycle" rhythm. Control animals were given 1 mg/m2/day of constant infusion IL-2, which was the highest hepatic artery infusion dose tolerated at a constant rate without mortality in nontumor-bearing animals. Animals treated with the constant infusions of IL-2 had a 37.5% mortality rate and a 25% objective response rate in measurable tumor size. Animals receiving the "day cycle" had no mortality and a 100% objective response rate. The conclusion was that "day cycled" circadian-patterned continuous hepatic artery infusions of IL-2 could be given with much lower toxicity and much improved tumor response rates than constant continuous infusions.
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PMID:Improving responses in hepatomas with circadian-patterned hepatic artery infusions of recombinant interleukin-2. 147 73

Interleukin-2 was entrapped in liposomes (Lip-IL-2) and injected into rats. The intraperitoneal injection of Lip-IL-2 into rats bearing an ascites-forming rat hepatoma (AH-66) significantly increased the survival time when compared with rats administered free IL-2 or saline-containing liposomes. The number of peritoneal exudate cells (PEC) increased markedly after intraperitoneal injection of Lip-IL-2 and consisted mainly of macrophages. The level of tumor necrosis factor alpha (TNF-alpha) and the intensity of free radicals increased in the ascites at 48 hrs after Lip-IL-2 administration, whereas TNF-alpha was not detected and the intensity of free radicals did not increase after free IL-2 administration. Our findings suggested that entrapment of IL-2 into liposomes enhanced its potential for cancer therapy, presumably by activating macrophages to produce TNF-alpha and free radicals.
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PMID:Effect of liposomal interleukin-2 on ascites-forming rat hepatoma. 151 92

We tried a infusion of interleukin-2 (IL-2) of a relatively low dose via an intrasplenic arterial catheter connected to a chronometric infusion (IS-IL-2). Eighteen patients of colorectal cancer with metastases to the liver or lung or of unresectable hepatoma received a 24 hour continuous infusion with low dose recombinant of IL-2 (mainly 8 x 10(5) JRU/day) for 25-40 days. All patients tolerated this protocol of the therapy and the main toxic effects were fever and general fatigue. Such serious toxicity as previously reported by high dose IL-2 therapy was not observed. Data of hepatic and renal functions were normal. IS-IL-2 therapy induced a high incidence of eosinophilia (12/18) and thrombocythemia (12/18). Peripheral natural killer (NK) and LAK activities were augmented in all patients and total white blood cell counts were increased during IS-IL-2 therapy. An increase in IL-2 receptor expression of peripheral blood mononuclear cells and significant rises in numbers of Leu11 (CD16)+, OKM1(CD11)+ and OKIa1(HLA-DR)+ were observed. Of 18 patients 12 were evaluable for their response to therapy. Partial response (PR) was observed in one unresectable hepatoma and 11 demonstrated no change (NC) or progressive disease (PD). Six patients were not evaluable because of additional therapy (3 cases) or decreasing tumor cell markers having no measurable lesions (3 cases). Three patients of colorectal cancer from an unresectable group were presumed to have micrometastases to the liver as suggested by an elevated serum CEA level. After receiving IS-IL-2 therapy they demonstrated a decrease in the serum CEA level for more than 3 years after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical trials of intrasplenic arterial infusion of interleukin-2 (IS-IL-2) to patients with advanced cancer. 162 39

Recombinant interleukin-2 (rIL-2) and adriamycin were administered systemically to treat nine patients (age 15.5-68 years, mean 48.9 years) with far advanced primary hepatocellular carcinoma. Three patients were newly diagnosed, and the remaining patients had received surgery, transcatheter arterial embolization, chemotherapy and other treatments but without improvement. RIL-2 was given at a dose of 10,000 to 30,000 units/kg every 8 hours for consecutive 9 days, and on the fifth day, a single dose of adriamycin 30 to 60 mg/M2 was administered. Four patients interrupted the immunotherapy because of severe intolerable side effects, 4 patients completed one course and the remaining one received 2 courses of treatment. Various adverse reactions were encountered, however, they subsided promptly after stop of therapy. All patients failed to respond to the regimen. Primary hepatic tumors continued to enlarge in 8 patients and remained unchanged in one, and pulmonary metastases also increased in size and number in 4 patients. Transient decrease in serum alpha-fetoprotein was found in 6 patients. These results suggests that systemic IL-2 immunotherapy, even in combination with chemotherapy, is not effective for the treatment of far advanced hepatocellular carcinoma. However, in viewing of its immune amplifying effect, rIL-2 in combination with other treatment modalities may still be worth trying in early stages of hepatocellular carcinoma.
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PMID:Immunochemotherapy with recombinant interleukin-2 and adriamycin in primary hepatocellular carcinoma. 164 35

More than 10(11) killer cells are needed for adoptive immunotherapy, but it is difficult to obtain so many from patients. Peripheral blood lymphocytes (PBL) treated with lectin and then with recombinant interleukin-2 (rIL-2) give many lectin-induced lymphokine-activated killer (LILAK) cells, studied here for proliferation, cytotoxicity, IL-2 receptors (IL-2R) and subsets. PBL obtained from hepatoma patients or healthy adults were incubated with phytohaemagglutinin (PHA) or concanavalin A (ConA) for 3 days and with rIL-2 for 4 days. Then the medium was replaced with fresh medium containing rIL-2 every 3 or 4 days, with the volume increased as cells proliferated. Cytotoxicity was expressed as the percentage lysis of target cells by 4 h 51Cr release. LILAK cells from healthy adults increased 120-fold in 2 weeks when incubated with ConA; the lymphokine-activated killer (LAK) cells increased 7-fold. The percentage of IL-2R+ cells increased more with ConA than with rIL-2 alone. ConA induced more suppressor T cells than PHA. LILAK cells obtained from patients by PHA treatment increased 180-fold in 2 weeks. Their cytotoxicity to Daudi cells was 1% before culture and 91% in 2 weeks; that of LAK cells was 60%. LILAK cells were cytotoxic to the tumour target cells, but not to allogeneic PBL. Adoptive immunotherapy may become more practical if many LILAK cells can be obtained at once by large-scale culture, such as by a hollow-fibre system.
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PMID:Proliferation and cytotoxicity of lectin-induced lymphokine-activated killer (LILAK) cells. 165 42

The changes in the tumour-binding potential of human peripheral blood lymphocytes (PBL) after activation by interleukin-2 (IL-2) was investigated by directly counting the number of lymphocytes bound to lined hepatoma cell monolayers. A significant increase in the tumour-binding potential of PBL was found after activation by more than 100 U/ml of IL-2. Maximal tumour-binding potential was achieved at 1000 U/ml of activation, and an overdose of IL-2 activation slightly decreased this potential. These changes were almost exactly the same as the changes in anti-tumour cytotoxicity as measured by a 4-hr 51Cr-release assay. In addition, the kinetics of tumour binding by lymphokine-activated killer (LAK) cells was shown to be almost identical to that of tumour cell lysis. These results thus provide evidence that induction and regulation of LAK activity are mediated by changes in tumour-binding potential of lymphocytes after activation by IL-2.
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PMID:Evidence that induction and regulation of lymphokine-activated killer (LAK) activity are mediated by changes in tumour-binding potential of lymphocytes after activation by interleukin-2 (IL-2). 165 65

Recombinant interleukin-2 (rIL-2) and adriamycin were administered systemically to treat nine patients (age 15.5-68 years, mean 48.9 +/- 15.5 years) with far advanced primary hepatocellular carcinoma. Three patients were newly diagnosed, and the remaining patients had received surgery, transcatheter arterial embolization, chemotherapy and other treatments but without improvement. rIL-2 was given at a dose of 10,000 to 30,000 units/kg every 8 hours for consecutive 9 days, and on the fifth day, a single dose of adriamycin 30 to 60 mg/m2 was administered. Four patients interrupted the immunotherapy because of severe intolerable side effects, 4 patients completed one course and the remaining one received 2 courses of treatment. Various adverse reactions were encountered, however, they subsided promptly after stopping therapy. All patients failed to respond to the regimen. Primary hepatic tumors continued to enlarge in 8 patients and remained unchanged in one, and pulmonary metastasis also increased in size and number in 4 patients. Transient decrease in serum alpha-fetoprotein was found in 6 patients. These results suggest that systemic IL-2 immunotherapy, even in combination with chemotherapy, is not effective for the treatment of far advanced hepatocellular carcinoma. However, in view of its immune amplifying effect, rIL-2 in combination with other treatment modalities may still be worth trying in early stages of hepatocellular carcinoma.
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PMID:Immunochemotherapy with recombinant interleukin-2 and adriamycin in primary hepatocellular carcinoma. 166 52


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