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)

Antibody-dependent cellular cytotoxicity (ADCC) increased with the development of tumors in C3H/He mice bearing spontaneous breast cancer or the syngeneic hepatoma MH-134 and in C57BL/6 mice bearing the syngeneic Lewis lung carcinoma 3LL. This cytotoxicity decreased after treatment with guinea pig, monoclonal IgM anti-Thy 1.2 serum and complement to the non-cancer level thus indicating that the increased ADCC in mice with cancer seems mainly attributable to cells with the Thy 1 antigen. On the other hand, NK activity decreased greatly when mice had tumors. Treatment with monoclonal IgM anti-Thy 1.2 serum and complement showed no significant influence on the natural killer (NK) activity of spleen cells of mice bearing MH-134 cancer, but in the 3LL-bearing mice the activity decreased significantly.
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PMID:Dissociation of natural killer activity and antibody-dependent cellular cytotoxicity in spleen cells of tumor bearing mice. 660 26

The present study suggests that newly synthesized histamine is involved in the development of some animal tumors (e.g., Lewis lung carcinoma in mice and Morris hepatoma in rats). A marked induction of histidine decarboxylase (HDC) and an increase in the histamine concentration were observed in the tumors approximately 1 week after inoculation, and there were parallel increases in ornithine decarboxylase activity and the concentrations of polyamines. The H2 receptor antagonist, cimetidine, significantly reduced tumor growth in the animal models while the H1 receptor antagonist, dexchlorpheniramine, had no effect, suggesting that histamine could act via H2 receptor sites. Extensive depletion of tumor histamine induced by local injection of Compound 48/80 did not result in a significant cytostatic effect. Monofluoromethylhistidine (MFMH), an enzyme-activated irreversible inhibitor of HDC, retarded the growth of hepatoma tissue culture cells grown in culture, and when infused s.c. at 60 mg/kg/day it greatly inhibited the development of tumors induced i.m. by hepatoma tissue culture cells in Buffalo rats. MFMH also had pronounced antitumoral effects on EMT6 sarcomas and Lewis lung carcinomas in mice, which were associated with inhibition of HDC and depletion of the histamine content of the tumors. These cytostatic effects were clearly enhanced when MFMH was combined in therapy with the specific ornithine decarboxylase inhibitor, DL-alpha-difluoromethylornithine. The antitumoral effects of the combination were associated with marked decreases in the tumor histamine and putrescine contents. It is proposed that nascent histamine, like newly synthesized putrescine and spermidine, plays a role in the rapid proliferation of animal tumors. Inhibition of HDC by essentially nontoxic drugs such as MFMH could represent a novel approach to the control of neoplastic growth.
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PMID:Involvement of histamine in growth of mouse and rat tumors: antitumoral properties of monofluoromethylhistidine, an enzyme-activated irreversible inhibitor of histidine decarboxylase. 669 68

The behavior of phosphoribosylformylglycinamidine ( FGAM ) synthetase (EC 6.3.5.3) activity was elucidated in normal and proliferating tissues and in murine and human neoplasms. Enzymic activity was measured in the 100,000 X g crude supernatant fluid prepared from tissue homogenates. The assay was based on coupling FGAM produced to diazotizable aminoimidazole ribonucleotide. In the crude extracts of normal rat liver and hepatoma 3924A, the apparent KmS of FGAM synthetase for formylglycinamide ribonucleotide, adenosine triphosphate and L-glutamine were 0.06, 1.5, and 0.03 mM, respectively. The liver and hepatoma 3924A FGAM synthetases were saturated at formylglycinamide ribonucleotide, adenosine triphosphate, and L-glutamine concentrations of 0.1, 7.0, and 0.5 mM, respectively; both enzymes had a pH optimum of 7.4. In the liver of normal adult rats, the FGAM synthetase activity was 7.2 to 10.7 nmol/hr/mg protein. The synthetase specific activity in hepatomas of slow and medium growth rates increased 1.2- to 2.2-fold, and in rapidly growing hepatomas it was elevated 3.2- to 5-fold over the values of the respective control normal livers. There was a positive correlation between the increase in synthetase activity and hepatoma proliferation rate. In rat tissues of high cell renewal activity, thymus, spleen, and testis, synthetase specific activity was 7.0-, 3.9-, and 3.3-fold higher than that of normal liver. In the 24- and 48-hr regenerating liver, FGAM synthetase specific activity was increased by 1.2- and 1.5-fold, respectively. In 5-day-old differentiating liver, specific activity was 202% of the adult value; when data were expressed per average cell, the activity was 55% of that of the adult liver. The markedly increased activity in the rapidly proliferating hepatomas appears to be more characteristic of neoplastic growth than of normal liver proliferation. FGAM synthetase activity was also increased in human renal cell carcinoma and hepatocellular and colon carcinomas to 1.4-, 2.7-, and 3.8-fold of the activity of the respective homologous normal and host tissues. The synthetase activity in the rapidly proliferating murine Lewis lung carcinoma was 9.6-fold that of the normal lung. The increased activity of FGAM synthetase should confer selective advantages to the cancer cells and marks this glutamine-utilizing enzyme as a potentially important target in the design of chemotherapy.
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PMID:Proliferation-linked increase in phosphoribosylformylglycinamidine synthetase activity (EC 6.3.5.3). 672 84

Gilvocarcin V, isolated rom a Streptomyces culture showed activity against experimental tumors such as sarcoma 180, Ehrlich carcinoma, Meth 1 fibrosarcoma, MH134 hepatoma and lymphocytic leukemia P388. In particular, 40% of treated mice survived for 60 days, after intraperitoneal administration of gilvocarcin V to mice bearing Ehrlich ascites carcinoma. But it was marginally active against B16 melanoma and did not produce prolongation of lifespan of mice bearing Lewis lung carcinoma.
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PMID:Gilvocarcins, new antitumor antibiotics. 3. Antitumor activity. 679 76

1. All available evidence for and against the concept of ectopic hyperparathyroidism, including 307 case reports of tumor hypercalcemia, was collated. 2. Of 104 combined cases of tumors of the kidney, lung, liver, head, neck and esophagus, 91 (88%) were in men. 3. The parathyroid glands were examined in 170 of 307 cases and parathyroid hyperplasia or adenoma were described in 34 cases. This high frequency may reflect higher likelihood of reporting such association. 4. Analysis of the histological pattern of tumors associated with humoral hypercalcemia revealed a marked association with certain histological types in different organs, such as clear-cell carcinoma of the kidney and ovary, hepatocarcinoma and cholangiocarcinoma, pheochromocytoma, and squamous-cell carcinoma of the lung, head, neck, esophagus, and urogenital tract. This histological correlation is not compatible with the "random derepression" hypothesis. 5. The existence of tumor humoral hypercalcemia is well documented, as 61 of 74 operated patients sustained remission of hypercalcemia following tumor removal. 6. The evidence for ectopic PTH being produced by tumor is not well documented and is based on conflicting radioimmunoassay results. We have found no case in the literature which fulfilled unequivocally criteria of ectopic production of biologically active PTH. There has been a lack of studies of tumors for the presence of biologically active hypercalcemic factors because only relatively insensitive bioassays are available at present. More information is also required on microscopic bone changes in tumor hypercalcemia as x-ray studies alone are inadequate. 7. On the basis of the present evidence, causes and mechanisms of tumor hypercalcemia are likely to be multiple.
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PMID:Tumor hypercalcemia and "ectopic hyperparathyroidism". 699 43

The epipodophyllotoxin derivatives VM 26 and VP 16-213 are currently entering phase III studies. The mechanism of their action is incompletely understood, but the greatest lethal effect is experienced in the late S and G2 phases. In transplanted tumors both drugs have shown marked schedule dependency and human studies also support this. As a single agent VP 16-213 is among the most active drugs in small-cell carcinoma of the lung. Significant clinical activity (> 20% response frequency) has been observed for both drugs in Hodgkin's disease, non-Hodgkin lymphomas and possibly in other more rare tumors (monocytic leukemia, hepatoma and teratoma). Although further clinical studies of both drugs would be ideal, it seems possible at present to justify a discontinuation of VM-26 in order to concentrate the efforts on VP 16-213. Further studies are needed to define optimal dose and schedule and place in combination chemotherapy.
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PMID:The epipodophyllotoxin derivatives VM-26 and VP-16-213, 1976-1979, a review. 700 63

We have studied the induction of a granulocyte-associated leukocytosis (leukemoid reaction) in C3HA, C57B1/6, and DBA/2 mice by a number of transplantable tumors of different origin. Leukemia L1210, Hepatoma 22, a transplantable mammary carcinoma of spontaneous C3HA origin, and a L929 culture fibroblasts-derived rhabdomyosarcoma, all induced a leukemoid reaction in their specific mouse strain. Melanoma B16 and Lewis lung carcinoma gave no reaction; Adenocarcinoma 755 and Harding-Passey melanoma evoked a leukocytosis but not due to an increase in neutrophils. Some extratumoral factors can influence the hematological response; the intensity of final leukemoid reaction was higher in female mice than in males bearing the same tumor. On the other hand, Ehrlich ascites tumor transplanted in all three inbred mouse strains rendered different levels of leukemoid reaction; response was higher in DBA/2, intermediate in C3HA and lower in C57B1/6.
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PMID:Leukemoid reaction induced by different transplantable tumors in three inbred mouse strains. 707 May 57

Tetrocarcin A, isolated from a Micromonospora culture showed activity against experimental i.p. inoculated tumors such as Ehrlich carcinoma, MH134 hepatoma, B16 melanoma. But it was not active against solid tumors such as sarcoma 180 and Ehrlich carcinoma. It was marginally active against the growth of solid Lewis lung carcinoma without prolonging the life span of the tumor-bearing mice. It was active against P388 leukemia (i.v.-i.v. system). It did not show myelosuppression and nephrotoxicity in mice. DNA and protein synthesis of P388 cells in culture were more significantly suppressed than RNA synthesis by tetrocarcin A.
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PMID:Tetrocarcins, new antitumor antibiotics. 3. Antitumor activity of tetrocarcin A. 714 4

The antitumor effect of human fibroblast interferon (HuIFN-beta) was examined using a nude mouse-human tumor xenograft group. Eight subcutaneously transplanted tumors--one line each of ovarian carcinoma, laryngeal carcinoma, carcinoma of the nasopharynx and hepatoma, and two lines each of lung carcinoma and melanoma--were used. HuIFN-beta at 1 X 10(5) IU/mouse was injected subcutaneously around the tumor or into the tumor itself. In the former case, statistically significant growth-suppressive effects were observed in one lung carcinoma (PC-12) and both melanomas (AM-1 and SK-14), but no effect was seen on the other five tumors. Further studies were made to ascertain the effects of intratumoral injections. Increased growth inhibition was observed in both melanomas (AM-1 and SK-14), but not in lung cancer (PC-12). Complete regression was seen in 3 of 8 mice carrying SK-14. The sensitivity of tumors to HuIFN-beta was correlated to the inhibitory effect of HuIFN-beta on cell division detected by histological observation.
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PMID:Effects of human fibroblast interferon on human tumors transplanted into nude mice: sensitivity of human tumors to interferon. 716 May 83

Changes in the growth kinetics of the intestinal epithelium were observed in mice bearing the Lewis lung carcinoma and the T1699 mammary adenocarcinoma and in rats bearing the H-4-II-E2 hepatoma. Proliferative activity in the jejunal tissue was markedly depressed with increasing tumour burden. Simultaneously, a significant reduction in total crypt cellularity occurred, followed by a reduction in villus height. While the total number of proliferative cells per crypt decreased, the relative proliferative compartment within the shrinking crypt increased. The rate of mucosal DNA synthesis remained constant during the initial cytokinetic changes, falling only after proliferative activity of the intestine was reduced to less than 50% of control levels. No general correlation could be drawn from the three tumour models studied between the level of gastrointestinal proliferation and tumour size, tumour growth rate or loss of weight by the tumour-bearing animals. However, intestinal proliferation was reduced by 50% when the tumour burden for each of the three tumours reached 6--8% of the host animal weight.
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PMID:Alterations in gastrointestinal steady-state kinetics associated with the growth of experimental tumours. 723 13


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