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)

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

Liposome-entrapped doxorubicin (Lip-Dox) was evaluated in two phase I clinical trials in patients with hepatic malignancy. Patients with metastases from primary gastric or colonic tumours and patients with hepatoma were eligible. Lip-Dox was extremely well tolerated and acute toxicities such as nausea and vomiting were totally eliminated; no antiemetics were used even at doses of 80 mg/m2. Toxicities such as alopecia and myelosuppression were also ameliorated. There were tumor regressions and reductions in hepatomegaly in patients treated on both the weekly and 21-day studies. The maximum tolerated dose (MTD) in the weekly study was 22.5 mg/m2/week and in the 21-day trial the MTD was 70 mg/m2.
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PMID:A phase I clinical evaluation of liposome-entrapped doxorubicin (Lip-Dox) in patients with primary and metastatic hepatic malignancy. 152 87

The in vivo tissue distribution of adriamycin (ADM) entrapped in liposomes conjugated with anti-human alpha-fetoprotein (AFP) monoclonal antibody (Lip-ADM = Ab) and the therapeutic effects of the conjugates on the AFP producing human hepatoma xenograft, Li-7, transplanted in BALB/c nu/nu murine liver were studied. The tissue distribution studies of Lip-ADM = Ab revealed that ADM levels were augmented in tumors, when Lip-ADM = Ab was administered intravenously as compared with free ADM or ADM entrapped in liposomes (Lip-ADM) alone. In addition, cardiac distribution of ADM was decreased in mice using ADM entrapped in liposomes. The therapeutic effects of Lip-ADM = Ab were tested in vivo on the experimentally transplanted Li-7 in liver. The anti-tumor effects of Lip-ADM = Ab were greater than those of Lip-ADM or free ADM as assessed by tumor weight. This experiment also indicated that the toxicity of ADM was reduced when the drug was injected using liposomes entrapped form by the body-weight losses and spleen weights.
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PMID:[Experimental studies on targeting chemotherapy using adriamycin entrapped in liposomes conjugated with anti-human alpha-fetoprotein monoclonal antibody]. 171 Nov 47

We investigated experimentally the effect of adriamycin (ADM) conjugated with anti alpha-fetoprotein (AFP) monoclonal antibodies and entrapped in liposomes (Lip-ADM = AbAFP) in vitro or in vivo. In the present study, we examined the importance of the conjugated antibody for the induction of selective therapeutic effect of Lip-ADM = AbAFP against AFP producing tumors. As the target tumors, AFP producing human hepatoma strain, Li-7, and AFP non-producing human breast cancer strain, MX-1 maintained in BALB/c nu/nu male mice were used. In order to evaluate the importance of the conjugated antibody, we prepared also ADM conjugated with normal mouse IgG, and entrapped in liposomes Lip-ADM = NIgG, of which therapeutic effects were compared with that of Lip-ADM = AbAFP. Judging from the tumor growth curve and the tumor weight, the therapeutic effect of Lip-ADM = AbAFP was greater against Li-7 than that of Lip-ADM = NIgG. On the other hand, both conjugates showed similar effects against MX-1. As the results it is suggested that the antibody which recognizes the antigen expressed on the target tumor cells can solely increase the therapeutic effect of ADM entrapped in liposomes (Lip-ADM) and that the main factors which contribute to the efficient therapeutic effect of the conjugate were the sensitibility to ADM, the affinity of the tumor cells to liposomes and the superiority of the conjugated antibody.
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PMID:[Importance of the conjugated antibody for the induction of selective effect of adriamycin conjugated with anti AFP monoclonal antibody and entrapped in liposomes against AFP producing tumors]. 247 19

The human recombinant interleukin 2 (IL-2) was entrapped in liposomes, and the therapeutic effects of the liposomes containing IL-2 (Lip-IL-2) were experimentally studied using the rat hepatoma strain, AH-66, maintained in donryu rats and challenged subcutaneously in the inguinal region. The peri-tumor injections of Lip-IL-2 (15 X 10(4)/kg units for the IL-2 dose) significantly inhibited the tumor growth as determined from the relative mean tumor weight, although no therapeutic effects were observed when the unentrapped IL-2 or liposomes containing saline was administered rats in the same way as the injections of Lip-IL-2. They also prolonged the survival time of rats. The studies of serum IL-2 values after i.v. or s.c. injections of Lip-IL-2 revealed that IL-2 was released gradually from the liposomes containing IL-2 into the circulation. As the result of the tumor tissue staining of the immunoperoxidase 18 hrs after the peri-tumor injection of IL-2, it was shown that a number of macrophages infiltrated into the tumor tissue and degenerated tumor cells were observed adjacent to those macrophages. It is suggested that Lip-IL-2 is useful as an antineoplastic agent in the immunotherapy and that the therapeutic effects of Lip-IL-2 would be related to both the slow release of IL-2 and the cytotoxicity on the tumor cells mediated by the macrophages.
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PMID:[Antitumor effect of IL-2 entrapped in liposomes on rat hepatoma, AH-66]. 278 45

We presented two patients with post-Lip-TAE biloma resulting in portal occlusion, and reviewed 20 previous studies including our cases to investigate their clinical characteristics. Case 1. A 31-year-old woman suffered from an HCC located at the S8 segment, and had a superselective embolization of feeding arteries using 3 ml of Lip, 300 mg of CBDCA, and 40 mg of Epi-Adriamycin (Epi-ADM). Eleven weeks later, CT showed multiple cystic lesions, and the percutaneous transhepatic drainages of the lesions were established. At 21 weeks after Lip-TAE, we found occlusion of the right branch of portal vein on CT, but she recovered from this condition, and was discharged 1 year later. Case 2. A 62-year-old man was diagnosed as HCC located at S7-6 segments, and was infused with 3 ml of Lip, 150 mg of CBDCA, and 30 mg of Epi-ADM through a right hepatic artery. Ten weeks later, CT showed a cystic lesion in the S7-8 segments, occlusion of the right anterior segmental branch of the portal vein, and the same drainage was also established. Unfortunately, he died of liver failure 18 weeks later. In the literature, biloma after Lip-TAE occurred at 71.2 mean days, ranging from 7 to 180 days, a with remarkable increase in biliary tree-associated enzymes. Seven (35%) of 20 patients died of liver failure or sepsis during 3 weeks and 1 year, and 3 (60%) of 5 patients accompanied by occlusion of a certain portal branch frequently died. We consider that these patients need intensive care and should be under long follow-up.
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PMID:[Two hepatocellular carcinoma patients with biloma after transarterial embolization with lipiodol (Lip-TAE) leading to occlusion of portal vein]. 757 88

We compared the segmental SMANCS/Lip-TAI and the segmental SMANCS/Lip-TAE and studied the effectiveness of both treatments and the influence and/or the side effects on liver function. In resected cases, we studied histopathologic examination. The response rate of the group treated by TAI was 28.6%, and that of the group treated by TAE was 76.5%. In the group treated by TAE, the therapeutic effects were good in nodular type HCC, using small doses of SMANCS. In both groups, the incidence and degree of side effects showed no significant difference. Hepatic insufficiency occurred in a few cases of the group treated by TAI. In resected cases, viable areas remained below the tumor capsule. In conclusion, segmental SMANCS/Lip-TAE seemed to be an effective treatment without any serious complications.
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PMID:[Efficiency of segmental SMANCS/Lip-TAE for hepatocellular carcinoma--comparative studies in the efficacy of segmental SMANCS/Lip-TAI]. 902 Sep 43

We compared the effectiveness of treatments and the influence of side effects on liver function and clinical symptoms between segmental SMANCS/ Lip TAI and segmental SMANCS/Lip-TAE. The early tumor response rate of the group treated by TAI was 23.6%, and that of the group treated by TAE was 80.0%. In the group treated by TAE, the therapeutic effects were better in the nodular type than in the diffuse type of HCC, and we were also able to obtain a good tumor response rate on the multiple HCC and large HCC. However, there was no difference in the response period between the groups treated by TAI and TAE. In both groups, there were no significant differences in the appearance rate and degree of side effects. In conclusion, segmental SMANCS/Lip-TAE seemed to be an effective treatment for HCC without any serious complications.
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PMID:[Comparative studies on the antitumor activities and side effects of segmental SMANCS/Lip-TAE with segmental SMANCS/Lip-TAI for hepatocellular carcinoma]. 951 92

Adriamycin (ADM) was encapsulated in a galactose-conjugated hepatotropic liposome (hLip-ADM) and its ability to enhance the antitumor effect while reducing toxicity was compared with that of free ADM and a control Lip-ADM (cLip-ADM), in two in vitro animal models. Liver metastases were induced in rats by an intravenous injection of 8 x 10(6) AH-130 rat hepatoma tumor cells. All forms of the ADM completely inhibited liver metastasis when given at a dose of 5 mg/kg on day 14 after tumor implantation, whereas liver metastatic foci were observed in six of ten rats in the control group. The reduction in ADM toxicity by liposomalization was remarkable, as significant body weight loss was observed only in the free ADM group, in which four of ten rats died. Additional experiments utilized a human colon cancer xenograft (TK-4) to induce the growth of the liver metastases in mice by orthotopic implantation. The hLip-ADM completely inhibited liver metastasis in rats (0/11), whereas liver metastases developed in 10 of 12 mice in the control group and in 5 of 12 mice given cLip-ADM. Interestingly, liposomal ADM did not have a significant inhibitory effect on transplanted tumor growth assessed 6 weeks after transplantation. These findings indicate that hLip-ADM may be an effective strategy for inhibiting liver metastases from human colon cancer.
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PMID:Antimetastatic effect of hepatotropic liposomal adriamycin on human metastatic liver tumors. 1138 5

The high rate of recurrence after surgical resection of hepatocellular carcinoma (HCC) is a major therapeutic challenge. Postoperative injection of 131-iodine-labeled lipiodol (131I-Lip) into the hepatic artery has been proposed as adjuvant treatment (Lau et al.). We analyzed 2 retrospective series of matched patients treated in our unit before and after addition of 131I-Lip adjuvant therapy to our standard surgical strategy. Thirty-eight patients who had undergone surgical resection of HCC after January 1999 were given adjuvant intra-arterial injection of 131I-Lip after surgery. These patients were matched with 38 other patients who had undergone surgical resection only between January 1997 and January 1999. The frequency of recurrences, disease-free rates, and overall survival rates were compared. The 2 groups were similar for clinical, biologic, or histologic parameters studied and Cancer Liver Italian Program scores. There were 15 recurrences in the group without adjuvant treatment and 9 in the group with 131I-Lip adjuvant treatment. The 1-, 2-, and 3-year disease-free survival rates (+/-95% confidence interval) were different (P <.02): 94.7% +/- 3.6%, 83.7% +/- 6.1%, and 68.4% +/- 9.7%, respectively, in the 131I-Lip group versus 73.7% +/- 7.1%, 54.3% +/- 8.2%, and 41.5% +/- 10.5% in the surgery group. The 1-, 2-, and 3-year survival rates (+/-95% confidence interval) also were different (P <.02): 94.7% +/- 3.6%, 91.7% +/- 4.6%, and 91.7% +/- 4.6%, respectively, in the 131I-Lip group versus 94.7% +/- 3.6%, 71.3% +/- 7.8%, and 49.9% +/- 10% in the surgery group. In conclusion, this retrospective analysis supports the promising contribution of postoperative injection of 131I-Lip after resection of HCC. A randomized study including more patients would be necessary to confirm its contribution to therapeutic management.
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PMID:Adjuvant intra-arterial injection of iodine-131-labeled lipiodol after resection of hepatocellular carcinoma. 1583 34


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