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)

The effect of radiation on chemical hepatocarcinogenesis was examined in 3 groups of male ACI/N rats. In Group I, 21 rats received dietary administration of N-2-fluorenylacetamide (FAA) (0.02%) for 16 weeks. Six of the rats were killed at the cessation of FAA exposure. The remaining rats were then given the basal diet until termination (32 weeks). In Group II, 16 rats were given FAA for 16 weeks. The animals were then given radiation (whole body; 3 Gy) and kept on the diet for the subsequent 16 weeks. Thirteen rats of Group III were kept on the basal diet throughout the experiment. They received radiation for 16 weeks after the start of the experiment. Liver tumors were obtained in Groups I and II. The multiplicity of the neoplastic nodules or hepatocellular carcinomas of Group II (6.5 +/- 2.5 or 1.4 +/- 0.9) was significantly greater than that of Group I (2.9 +/- 1.7 or 0.3 +/- 0.4, respectively) (P less than 0.001). Furthermore, the incidence of hepatocellular carcinoma of Group II (13/16) was also significantly higher than that of Group I (4/15) (P less than 0.003). The results clearly indicate a synergistic effect of radiation with FAA on the hepatocarcinogenesis. The effect of radiation in this rat model appeared to be on the early progression of the carcinogenesis.
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PMID:Synergistic effect of radiation on N-2-fluorenylacetamide-induced hepatocarcinogenesis in male ACI/N rats. 212 84

Differential effects of total parenteral nutrition (TPN) on host nutrition and growth of cancer are unclear. Growth of adult ACI-N rats bearing transplanted Morris hepatocarcinoma no. 3924A given TPN with or without fat was studied in comparison with Purina Chow-fed, fasting, and semifasting (either amino acid or dextrose alone) rats over 5 days. The isocaloric, isonitrogenous TPN regimens with or without fat maintained body weight and nitrogen balance of cancer-bearing rats equally well. When compared with Chow-fed rats, the volume of the cancer, its weight, doubling time, protein content, and incorporation of thymidine into DNA were similar in rats given TPN either with or without fat. Although the volume of the cancer decreased in fasting and semifasting rats, the nutritional status of the host was also impaired. Administration of TPN to cancer-bearing rats was associated with an abnormal increase in serum lactic acid level, which was not ameliorated by the use of fat to reduce the carbohydrate load. Although TPN with and without fat maintains the nutritional status, hepatomegaly and hepatic steatosis limit the administration of carbohydrate and fat as energy substrates in this system.
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PMID:Total parenteral nutrition with and without fat as substrate for growth of rats and transplanted hepatocarcinoma. 241 57

A cDNA clone bearing the mRNA sequence for rat alpha X protein (alpha X) was isolated from a cDNA library constructed from rat liver mRNA. The nucleotide sequence of alpha X protein cDNA showed 97% homology with that of the 3'-proximal domain of alpha 1-inhibitor III cDNA. The amino acid sequence deduced from that of alpha X cDNA also exhibited high homology with the primary sequences of alpha 1-inhibitor III and alpha 2-macroglobulin. K231 ascites hepatoma cells were transplanted into male ACI rats, and the level of alpha X mRNA in the liver of the tumor-bearing rats was determined by RNA blot hybridization with the cDNA probe. The serum concentration of alpha X decreased to about 30% of the control value with time after transplantation. The amount of alpha X mRNA in the liver of tumor-bearing rats was proportional to the serum concentration of alpha X. The serum concentrations of transferrin and albumin in the tumor-bearing rats also decreased to about 30 and 60% of the normal levels, respectively. However, the amounts of mRNAs for transferrin and albumin in the liver of tumor-bearing rats did not decrease. These findings indicate that the mechanisms of tumor-associated decrease in the concentrations of different serum proteins in tumor-bearing rats may differ.
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PMID:Tumor-associated expression of a serum protein, termed aX protein (alpha 1-inhibitor III), and its mRNA in rat liver. 251 Nov 84

The number of silver-stained nucleolar proteins (AgNOR) was counted in preneoplastic and neoplastic rat liver lesions induced by N-2-fluorenylacetamide (FAA) and was compared with that of bromodeoxyuridine (BrdU)-incorporating cells detected immunohistochemically using monoclonal antibody against BrdU. Male ACI/N rats were given diet containing 200 ppm FAA for 12, 16 or 20 weeks to induce hepatocellular foci and tumors. The mean numbers of AgNOR stained by a one-step silver colloid method and BrdU-labeling indices in various liver cell lesions were as follows: nontreated liver (n = 20), 1.20 and 0.08; nonlesional areas (n = 20), 1.33 and 0.13; altered liver cell foci (n = 80), 2.04 and 4.05 [eosinophilic cell type (n = 20), 1.78 and 1.82; clear cell type (n = 20), 1.45 and 1.77; basophilic cell type (n = 20), 1.99 and 4.58; hyperbasophilic cell type (n = 20), 2.94 and 8.02]; neoplastic nodules (n = 10), 3.11 and 2.99; hepatocellular carcinomas (n = 10), 7.22 and 8.29. Thus, the mean number of AgNOR and the value of BrdU-labeling index were well correlated and both values showed a stepwise increase from normal liver cells to liver cell carcinoma, although some scatter was present. These data suggest that mean number of AgNOR may reflect the cellular kinetics in rat hepatocarcinogenesis, and the one-step silver colloid method for demonstration of AgNOR may therefore be a simple and useful staining to examine the proliferative nature of cells.
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PMID:Nucleolar organizer regions in hepatocarcinogenesis induced by N-2-fluorenylacetamide in rats: comparison with bromodeoxyuridine immunohistochemistry. 251 66

A study evaluating the efficacy of high-intensity therapeutic ultrasound (HITU) as a treatment modality in experimental hepatoma is reported. Morris hepatoma (3924) 1 x 10(6) cells were transferred subcutaneously into 40 male ACI rats (weight, 150 to 200 g). Animals were divided into four experimental groups: group 1 (n = 10) consisted of untreated controls; group 2 (n = 10) received intraperitoneal cyclophosphamide 50 mg/kg as a single dose; group 3 (n = 10) underwent HITU only; and group 4 (n = 10) received both chemotherapy (as in group 2) and HITU (as in group 3). HITU was administered with a 5.5-cm diameter 4-MHz quartz transducer creating a continuous wave with 400 W/cm2 focal intensity. The entire tumor was irradiated in 1-mm increments (horizontal and vertical) using treatment cycles of 4 seconds on and 11 seconds off. Total body weight and tumor volume were measured on the day of treatment, and 4 weeks later. At 4 weeks, the animals were killed, the tumor was excised and weighed, and tumor volume was determined. Tumor volume in all treated animals (groups 2, 3 and 4) was significantly smaller than in controls (P less than .001) at 4 weeks, and tumor volume for animals in group 4 was significantly smaller than for those in groups 2 and 3 (P less than .01). These data indicate that HITU significantly reduces tumor size when compared with control rats with Morris hepatoma. A synergistic effect of chemotherapy and HITU was observed and resulted in an enhanced tumor response and reduction of tumor size.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of high-intensity therapeutic ultrasound irradiation in the treatment of experimental hepatoma. 272 89

The hepatocarcinogenic potencies of three newly identified hydroxymethyl derivatives of 4-(N,N-dimethylamino)azobenzene [(DAB) CAS: 60-11-7], i.e., 2'-CH2OH-DAB, 3'-CH2OH-DAB, and 4'-CH2OH-DAB, were strictly evaluated in a long-term test (400 days) and compared to the potency of 3'-CH3-DAB. ACI/N rats, known to be less sensitive to azo dye carcinogenesis, were given one of these compounds in their diets for 120 days. The incidence of hepatocellular carcinoma in group 2 (20/20), which was given 3'-CH2OH-DAB, was much higher than that in any of the other groups: group 1 (2'-CH2OH-DAB; 4/19), group 3 (4'-CH2OH-DAB; 1/25), or group 4 (3'-CH3-DAB; 3/24). These data suggest that 3'-CH2OH-DAB is the most potent hepatocarcinogen in the series of azo dyes. Possible reasons for the potency of the chemical are discussed.
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PMID:Hepatocarcinogenic activities of hydroxymethyl derivatives of 4-(N,N-dimethylamino)azobenzene in ACI/N rats. 311 9

Hypoxia, leading to cells in resting or slow replication phases may be a cause of chemotherapy and radiation therapy resistance in some tumors. Perfluorochemicals (PFC) may potentiate response to these therapies by increasing oxygen delivery to the tumor, forcing cells into more therapy-responsive replicating phases. To assess the effects of PFC on tumor growth and chemotherapy response, 91 ACI rats bearing 1 cc flank Morris hepatoma tumors were divided into groups: Group I, control; Group II, Adriamycin (ADR) 10 mg/kg intraperitoneally (IP); Group III, Cytoxan (CTX) 100 mg/kg IP; Group IV, PFC 20 mL/kg IV; Group V, ADR and PFC; Group VI, CTX and PFC. Animals were kept in 0.5 FiO2 for 24 hours after treatment, and mortality and tumor volumes determined 2 weeks later. Tumor DNA turnover was measured using opposing pathways assay of 14C-thymidine uptake and degradation. In a separate group, tumor tissue pO2 was measured polarographically with an oxygen microelectrode before and after injection of PFC (20 mL/kg). The survival was significantly reduced in group IV (4%) compared with group I, control (73%). Both ADR and CTX slowed the growth of the tumor, while PFC alone significantly accelerated tumor growth. The tumor response to ADR was potentiated by the addition of PFC. These results were confirmed by DNA synthesis evaluation. The mean pO2 level prior to injection was 6.6 +/- 1.96 mmHg compared with 18.92 +/- 1.00 mmHg after PFC injection (P less than or equal to .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of perfluorochemicals on tumor growth and chemotherapy response. 344 Sep 9

The doubling time (Td) for hepatoma 3924A in ACI rats is relatively constant between different treatments when growth resumes after treatment with either chemotherapy or radiotherapy. Advantage was taken of this to estimate the fraction of surviving cells (SF) from in vivo growth delay (GD) data using the expression SF = 1/2GD/Td. Survival curves were constructed for several recently published treatment schedules which employed alternating radiotherapy and chemotherapy, and for both daily and multiple fractions per day (MFD) radiation schedules. A doubling time of 5.2 days was assumed, in the range observed for control and regrowing treated tumors, which yields one surviving cell at the TCD37 (3650 cGy single dose). The single fraction, multi-target, single hit model, SF = 1 - (1 - e-D/D0)n with D0 = 406 cGy and n = 1.63 is a reasonable representation of the data over the dose range 375-2250 cGy. The D0 of 406 cGy should be considered as a relative, not absolute value which is dependent on the radiosensitivity of the tumor cells and the accuracy of the doubling time, but is useful in relating the single dose data to more complex radiation schedules. Using D0 = 406 cGy, n = 1.63, and f = number of fractions, the multi-fraction, multi-target, single hit model SF = (1 - [1 - e-D/D0]n)f closely fits our data for 30 daily fractions given at 100 to 375 cGy/day for total radiation doses of 3000 to 11,250 cGy. The fraction of surviving cells for daily radiation alternated with three courses of cyclophosphamide (CP) was in good agreement with an additive effect of the two modalities at radiation doses of 3000 to 5640 cGy. Multiple fractions per day radiation given as 250 cGy fractions was more effective than predicted by the model both when given alone or alternately with cyclophosphamide.
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PMID:Solid tumor models for the assessment of different treatment modalities: XXVI. Estimates of cell survival from tumor growth delay after alternating radiotherapy and chemotherapy. 381 88

The localization of 111In activity in the tumor and draining lymph nodes of the H-4-II-E ACI rat hepatoma was investigated following the injection of 111In-chloride. In this tumor model, the tumors metastasize to the regional lymph nodes in male rats only. The following experiments were performed: (a) biodistribution of 111In; (b) correlation of 111In uptake with [3H]thymidine; (c) gamma camera imaging; (d) autoradiography; (e) iron competition and (f) binding of 131I-transferrin to H-4-II-E cells. Tumor-to-muscle ratios of 111In in males were 4.9:1 in the primary tumor and 9.1:1 in the metastatic lymph nodes 24 h post injection. In the lymph node metastases in the males, a significant correlation between 111In uptake and [3H]thymidine was observed (r = 0.737) suggesting that 111In uptake in the metastases is related to cellular proliferation. No such correlation was observed in either primary tumors (both male and female) or in the draining lymph nodes of the females. Metastatic lymph nodes in males could be detected in gamma camera images while draining nodes in females could not be delineated. Injection of ferric citrate prior to 111In administration resulted in a significant reduction of 111In uptake in the liver, spleen and tumor and increased the amount of activity recovered from the kidney. Measurements of the binding of 131I-labeled rat transferrin to H-4-II-E cells in vitro suggest that these cells display transferrin receptors.
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PMID:Distribution and mechanism of uptake of 111InCl3 in a tumor model for lymph node metastases. 404 44

The concentration of L-glutamine was determined in freeze-clamped samples of normal liver of adult male fed rats (5.7-6.1 mumol/g) and in transplantable hepatomas of vastly different proliferative rates. The L-glutamine concentration in the slowly growing hepatomas was in the range of the normal liver and it decreased in relation to the increase of hepatoma growth rate, in the most rapidly growing tumors amounting to 12% of that of normal liver. In 24-hour regenerating liver, the glutamine content was slightly reduced (by 17%). In normal rat organs of high cell renewal, such as testis, intestinal mucosa, spleen, and thymus, the L-glutamine concentration was 18 to 46% of that of normal rat liver. The L-glutamine content was similar in rat brain and liver, but it was 1.6-fold higher in the heart, and low in the blood. Glutamine synthetase (EC 6.3. 1.3) activity in normal adult liver of ACI/N strain rats was 1,000 nmol per hr per mg protein; the activity increased in the very slowly growing hepatoma 20, but decreased markedly in all the other hepatomas. Thus, glutamine synthetase activity was essentially transformation-linked. The negative correlation of glutamine content with growth rate in transplanted hepatomas appears to be more closely linked with the activities of enzymes that utilize glutamine. The low L-glutamine concentration in the rapidly growing hepatomas provides a potential marker for anti-glutamine chemotherapy selectively targeted against the glutamine-utilizing enzymes.
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PMID:Negative correlation of L-glutamine concentration with proliferation rate in rat hepatomas. 614 11


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