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)

We investigated, using rats, the effect of partial hepatectomy (PH) on hepatocellular carcinoma (HCC, KDH-8 and AH-66) cells, and the effect of HCC cells on the regeneration of remaining hepatocytes after PH. Our results showed that PH significantly enhanced the growth of HCC cells in rats. Tumor volume increased more significantly in the partially hepatectomized group (H-group) than in the control group, and the tumor wet weights on the 14th postoperative day were significantly higher in the H-group than in the control group. Such an enhanced growth effect of PH on the injected (s.c.) HCC cells was related to an abrupt increase of tumor volume within 24 hours after operation, which was supported by the mitotic indices (MI) of the KDH-8 cells. These phenomena of the enhanced growth of the HCC cells following PH were not observed at all in rats injected with estrogen receptor (ER)-negative mammary carcinoma (SST-2) or nonepithelial fibrosarcoma (KMT-75) cells. The MIs of the remaining hepatocytes after PH increased abruptly at the 30th postoperative hour and reached a maximum at the 36th postoperative hour, and the MIs were significantly higher in the H-group with the KDH-8 cells than in the H-group without them from the 42th to the 60th postoperative hour. In the control group, the MIs of hepatocytes were not regardless of the presence of KDH-8 cells. From these results, we speculate that some growth factor(s) induced by PH may act on injected (s.c.) HCC cells, and that the other growth factor(s) secreted by HCC cells may act on the regenerating hepatocytes after PH.
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PMID:Kinetic changes of liver regeneration and hepatocellular carcinoma cells after partial hepatectomy in rats. 200 58

The author suspected that the high incidence of early recurrence after macroscopically curative operation in human liver cancers correlated with the production of liver regeneration factor which was induced following partial hepatectomy (PH). The author therefore analyzed whether PH enhanced the growth of liver cancers or not, and the relevant mechanism involved, using rats subcutaneously injected with hepatocellular carcinoma (KDH-8, AH-66) cells. Primarily, it proved that PH significantly enhanced the growth of liver cancers injected in rats. The effect of this enhancement of liver cancer growth appeared as an abrupt increase in tumor volume within 24 hours following PH, which fact was supported by the mitotic indices of the hepatocellular carcinoma (KDH-8) cells. However PH did not affect rats injected with mammary carcinoma (SST-2) cells without estrogen receptor (E2R) or fibrosarcoma (KMT-75) cells. Secondly, based on this result, the author tried to analyze the mechanism of enhanced growth of liver cancers following PH, from the standpoints of; changes in postoperative immunity, expression of cytosol E2R in liver cancer cells or liver regeneration factor, using KDH-8 cells. The changes in postoperative immunity (NK-activity and Blastogenesis) did not correlate with the changes in liver cancer growth. Although serum estradiol (E2) increased significantly after PH, E2R was not detected in the KDH-8 cells used in this experiment. Serum was obtained from healthy rats 24 hours after PH, and 20 mg of serum, as calculated from total protein, was eluted into 50 fractions by high liquid chromatography (column; TSK G3000 SW). When the author examined which fractions stimulated both the growth of primarily cultivated hepatocytes and KDH-8 cells, only the fraction Fr. 30, the molecular weight of which was about 100 Kd, enhanced both. Furthermore, the author performed an in vivo assay to determine the number of days needed for tumor appearance: PHs were carried out 2 months, 5 days and 1 day before, at the same day of, and 1 day and 5 days after KDH-8 cell (500 cells/100 microliters, sc) inoculation. The author also noticed from these in vivo tests that PHs which were performed 1 day before, at the same day of, and 1 day and 5 days after the KDH-8 cell inoculation enhanced significantly the growth of liver cancers.
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PMID:[Experimental analysis of postoperative early recurrence of liver cancer]. 259 75

AO-90, a methionine-free intravenous amino acid solution (7.43%) showed to potentiate the antitumor effect of 5-fluorouracil (5-FU) when concomitantly used as the nitrogen source in total parenteral nutrition (TPN) in Yoshida sarcoma (YS)-bearing rats. In the present experiment, this potentiation mechanism was studied by determining the serum methionine level and tumor methylenetetrahydrofolate (CH2FH4) content in YS-bearing Donryu rats given AO-90 (nitrogen 0.73g/kg on the 1st day and 1.46g/kg for the remaining 6 days) by TPN for 1 week. The rats were subcutaneously inoculated with 10(4) YS cells in the dorsum 3 days before the start of TPN. Inhibition of thymidylate synthase activity in tumor tissue after dosing of AO-90 (nitrogen 0.68g/kg on the 1st day and 1.36 g/kg for the remaining 6 days) by TPN along with daily intraperitoneal dosing of 5-FU (10 mg/kg) was also evaluated with the inoculation of 10(6) tumor cells. The results were compared with those in tumor-bearing rats given TPN with a commercially available amino acid solution containing methionine. On day 5 of TPN, the tumor-bearing rats given AO-90 showed a significantly lower serum methionine level than the control rats: 101 +/- 11 mumol/l versus 29 +/- 14 mumol/l (p < 0.01); and a higher CH2FH4 content in tumor: 7.0 +/- 2.8 pmol/g protein versus 23.7 +/- 16.6 pmol/g protein (p < 0.05). Thymidylate synthase inhibition was 81.2 +/- 5.1% in the AO-90 group and 30.9 +/- 26.3% in the control group (p < 0.01). The results of the present study suggest that AO-90 potentiate the antitumor effect of 5-FU by biochemical modulation. AO-90 concomitantly given with 5-FU for 7 days was effective not only in the allogeneic tumor model, but also in WKAH and SHR rats previously inoculated with 10(6) of syngeneic KDH-8 hepatoma cells and SST-2 adenocarcinoma cells, respectively. Weight of SST-2 adenocarcinoma in SHR rats after the TPN period was significantly smaller in the AO-90 group than in the control rats given methionine-containing TPN and 5-FU: 2.66 +/- 0.91 versus 5.12 +/- 2.11 (p < 0.05).
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PMID:[The mechanism of potentiation of the antitumor effect of 5-fluorouracil by methionine-free intravenous amino acid solution (AO-90) in rats]. 808 53

The effects of oral administration of cryomilled powder of the soft-shelled turtle (SST powder) on solid and ascites tumor-bearing C3H/He mice were studied. The SST powder was administered orally at a dose of 100 or 500 mg/kg/d for two or four weeks, and then MH134 hepatoma cells were inoculated; oral administration was continued after inoculation. Treatment with the SST powder attenuated the increase in diameter and weight of the tumor and prolonged the survival of mice with solid tumors. However, the same treatment did not show any significant effect in mice with ascites tumor, indicating that the SST powder has no direct killing action on tumor cells. These results suggest that oral administration of the SST powder decreases the growth of solid tumors possibly by activating the host immune system.
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PMID:Anti-tumor effects of orally administered soft-shelled turtle powder in mice. 892 2

ONO-4007 is a new synthetic lipid A derivative with low endotoxic activities. We have examined the therapeutic effects of ONO-4007 on rat hepatocellular carcinoma KDH-8 cells, rat fibrosarcoma KMT-17 cells and rat mammary adenocarcinoma SST-2 cells in vivo. Multiple systemic i.v. administration of ONO-4007 was performed on days 7, 14 and 21 after tumor implantation of KDH-8 and SST-2 cells, and on days 5, 10 and 15 after tumor implantation of KMT-17 cells. ONO-4007 showed significant therapeutic effects on KDH-8 cells; by the administration of ONO-4007 (2.5 mg/kg) 70% of rats were cured and by the administration of ONO-4007 (5 mg/kg) 50% of rats were cured. Furthermore, the ONO-4007 treatment prolonged the mean survival time of KDH-8-bearing rats. However, ONO-4007 had no effect on KMT-17 and SST-2 cells, and it had no direct effect on the growth of KDH-8 cells in vivo. Albeit the stimulation with ONO-4007 induced mRNA expressions of interleukin (IL)-1alpha, IL-6 and tumor necrosis factor (TNF)-a, those of IL-2, IL-4, IL-10 and interferon (IFN)-gamma were not induced. Using a bioassay, we found that the production of TNF-alpha in the tumor tissues was induced by ONO-4007 in a dose-dependent manner. KDH-8 cells were sensitive to human natural TNF-alpha in vitro. However, KMT-17 and SST-2 cells were resistant against TNF-alpha in vitro. These results suggest that ONO-4007 is therapeutically useful for the treatment of TNF-alpha-sensitive tumors.
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PMID:A new synthetic lipid A analog, ONO-4007, stimulates the production of tumor necrosis factor-alpha in tumor tissues, resulting in the rejection of transplanted rat hepatoma cells. 921 14

ONO-4007 is a new synthetic lipid A derivative with low endotoxic activities. ONO-4007 was effective against KDH-8, a tumor necrosis factor (TNF)-sensitive rat hepatoma cell line, but neither effective against KMT-17, a TNF-resistant rat fibrosarcoma cell line, nor SST-2, a TNF-resistant rat mammary adenocarcinoma cell line. We have established two sublines from KDH-8 to further examine the therapeutic mechanisms of ONO-4007 in vivo: TNF-sensitive KDH-8/YK and TNF-resistant cKDH-8/11. The two sublines equally proliferated in vitro. Multiple systemic i.v. administration of ONO-4007 was performed on days 7, 14 and 21 after tumor implantation. Although treatment with ONO-4007 had no effect on the growth of cKDH-8/11 in WKAH rats in vivo, 60% of KDH-8/YK-bearing rats treated with ONO-4007 survived. The administration of ONO-4007 brought about significant therapeutic effects on KDH-8/YK-bearing rats but not on cKDH-8/11-bearing rats. These results suggest that ONO-4007 is therapeutically useful for the treatment of TNF-alpha-sensitive tumors.
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PMID:Therapeutic effects of a new synthetic lipid A analog, ONO-4007, on rat hepatoma KDH-8 depend on tumor necrosis factor-sensitivity of the tumor cells. 940 18

Targeting of G-protein coupled receptors (GPCRs) like somatostatin-14 (SST-14) could have a potential interest in delivery of anti-cancer agents to tumor cells. Attachment of SST to different nano-carriers e.g. polymeric nanoparticles is limited due to the difficulty of interaction between SST itself and those nano-carriers. Furthermore, the instability problems associated with the final formulation. Attaching of SST to gold nanoparticles (AuNPs) using the positive and negative charge of SST and citrate-AuNPs could be considered a new technique to get stable non-aggregated AuNPs coated with SST. Different analyses techniques have been performed to proof the principle of coating between AuNPs and SST. Furthermore, cellular uptake studies on HCC-1806, HELA and U-87 cell lines has been investigated to show the ability of AuNPs coated SST to enter the cells via SST receptors. Dynamic light scattering (DLS) indicated a successful coating of SST on the MUA-AuNPs surface. Furthermore, all the performed analysis including DLS, SDS-PAGE and UV-VIS absorption spectra indicated a successful coating of AuNPs with SST. Cellular uptake studies on HCC-1806, HELA and U-87 cell lines showed that the number of AuNPs-SST per cell is signiflcantly higher compared to citrate-AuNPs when quantified using inductively coupled plasma spectroscopy. Moreover, the binding of AuNPs-SST to cells can be suppressed by addition of antagonist, indicating that the binding of AuNPs-SST to cells is due to receptor-specific binding. In conclusion, AuNPs could be attached to SST via adsorption to get stable AuNPs coated SST. This new formulation has a potential to target SST receptors localized in many normal and tumor cells.
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PMID:Novel gold nanoparticles coated with somatostatin as a potential delivery system for targeting somatostatin receptors. 2703 9