UMLS:C0345904 - FACTA Search

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Query: UMLS:C0345904 (liver cancer)
15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied a selective enhancement of the mitomycin C (MMC)-induced antitumor effect focusing on the intracellular metabolism by NAD(P)H:quinone oxidoreductase (DT-diaphorase, DTD). The level of cellular DTD activity related well to the degree of MMC-induced DNA total cross links and cell growth inhibition in human cancer cell lines, KB, PH101, SH101 and K562. A DTD inhibitor, dicoumarol (DIC) or flavin adenine dinucleotide (FAD), inhibited the MMC-induced DNA damage and cytotoxicity at a non-toxic concentration. The DTD-mediated MMC activation was pH-dependent, and highest at pH 6 and lowest at pH 8. Although an inverse relationship appeared to exist between DTD activity and MMC efficacy in human xenografts implanted into nude mice and 9 fresh human tumor specimens, the investigation in 3 culture cells, HEC-46, HCC-48 and HCC-50, established from those xenografts, showed that DTD activated MMC in a pH-dependent manner as well as the other cell lines. Significant tumor pH reduction from 7.1 to 6.7 by continuous glucose infusion also increased the MMC-induced tumor growth inhibition in the human tumor xenografts. Thus, we conclude that bioreductive activation by DTD in a pH-dependent manner may be of key importance in the MMC-induced antitumor effect and that an increased MMC efficacy at a reduced pH caused by hyperglycemia may be applied to clinical use as a new manipulation for a biochemical modulation of MMC.
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PMID:DT-diaphorase as a target enzyme for biochemical modulation of mitomycin C. 856 14

Irsogladine used clinically as an anti-gastric ulcer agent, at 10(-6)-10(-4)M, inhibited cell proliferation and tubular morphogenesis of vascular endothelial cells, but the proliferation of human epidermoid cancer or glioma cells was not inhibited by this drug, even at 10(-4)M. In vivo studies demonstrated that p.o. administration of irsogladine significantly inhibited tumor growth of human glioma cells in mice, and histological analysis showed a dramatic decrease of the neovascularization in the tumors. In mice transplanted with chambers containing human glioma cells or hepatic cancer cells, irsogladine also inhibited angiogenesis. These in vivo and in vitro assays demonstrate that irsogladine may be a unique and potent inhibitor of tumor angiogenesis.
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PMID:Inhibition of tumor growth and neovascularization by an anti-gastric ulcer agent, irsogladine. 860 95

Effects of a newly developed angiogenesis inhibitor, TNP-470 (AGM-1470) alone and in combination with cisplatinum on tumor-bearing rats were investigated. Wistar-King A male rats were subcutaneously inoculated with 10(7) cultured syngeneic liver cancer cells that had been induced by oral intake of 3'-methyl-4-dimethylaminoazobenzen, and were used as tumor-bearing rats. Tumor sizes and changes in serum copper levels were measured after administration of TNP-470. Administration of TNP-470 (5, 10, 20 or 30mg/kg, s.c., daily for 7 days) inhibited tumor growth in a dose-dependent manner. The suppressive effects were the same in the rats which were administered TNP-470 (20mg/kg, s.c., daily for 7 days) and cisplatinum (0.5 mg/kg, s.c., daily for 7 days) simultaneously, and rats administered cisplatinum (0.5mg/kg, s.c., daily for 7 days) following TNP-470 (20mg/kg, s.c., daily for 7 days). These inhibitory effects were almost the same as that of cisplatinum (0.5mg/kg, s.c., daily for 7 days) alone. While, administration of TNP-470 (20mg/kg, s.c., daily for 7 days) following cisplatinum treatment (0.5 mg/kg, s.c., daily) showed markedly higher anti-tumor effects, compared with these groups. Administration of TNP-470 caused elevation of serum copper levels in normal rats as well as tumor-bearing rats with the same degree. Serum copper levels remained normal after discontinuation of TNP-470 in normal rats, while in tumor-bearing rats, it decreased during the first week and re-elevated in 2 to 3 weeks after discontinuation of TNP-470. This re-elevation of serum copper levels was related to rapid tumor growth after discontinuation of TNP-470. Furthermore, there was also a positive correlation between serum copper levels and capillary density in the tumor. In conclusion, TNP-470 had anti-tumor effect in a dose-dependent manner against a rat liver cancer, with markedly higher effects when it was administered following cisplatinum. Serum copper levels after discontinuation of TNP-470 treatment might indicate re-proliferation of the capillaries in the tumor tissue.
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PMID:[Anti-tumor effects of an angiogenesis inhibitor, TNP-470 (AGM-1470) alone and in combination with cisplatinum, and changes in serum copper levels in liver cancer bearing rats]. 872 76

Zymosan, a non-specific macrophage-stimulating agent, modifies favourably tumour growth in the liver but has minor effect on renal tumours. The mechanism accounting for variation is still to be clarified. The effect of zymosan on liver cancer may be mediated by the macrophage-monocyte system. Kupffer cells are in vitro cytotoxic against colon cancer cell lines. The kidney is sparse in macrophage elements. The prostaglandin synthesis inhibitor, indomethacin, inhibits tumor growth. In Wistar-FU rats inoculated in the liver and the kidney with an adenocarcinoma cell suspension, pretreatment with zymosan (3 mg x 100 g[-1]) significantly reduced both tumour take and liver volume. This effect was attenuated by concomitant administration of indomethacin (0.2 mg x 100 g[-1]). After 2 weeks there was still reduced liver tumour volume. No significant effects on tumour take or growth were observed when the cells were inoculated into the kidney. There was no significant effect of zymosan on an hepatoma in Lister-Hooded rats. Pretreatment with indomethacin had no effect on tumor take or initial growth.
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PMID:The influence of zymosan and indomethacin on liver and kidney tumor growth. An experimental study in rats. 938 96

The therapeutic results of liver transplantation for primary liver cancer have not been satisfactory. The high rate of recurrence appears to be due to the inadequate care taken in selecting the most appropriate candidates for orthotopic liver transplantation (OLT), the presence of circulating hepatocellular carcinoma (HCC) cells and micrometastases at the time of liver transplantation, and the tumor growth-promoting effects of immunosuppressive agents. We believe that HCC patients must be carefully staged in order to identify those most suitable for OLT. We therefore induced HCC in pure-strain rats by the oral administration of diethylnitrosamine (DEN) and studied the outcomes of liver transplantation at various time points (70, 120, and 134 days) after the initiation of carcinogenesis. The mean survival time (MST +/- SD) of the non-OLT control group (N = 14) was 18.2 +/- 5 days after Day 120. The survival time of the four rats in the OLT Day 120 group was 81.3 +/- 20.6 days after transplantation. One rat showing full weight recovery soon after transplantation survived for 97 days after transplantation and then succumbed to recurrence. The survival time of the four rats in the OLT Day 134 group was 7.3 +/- 5.0 days after transplantation. The survival time of the three rats in the OLT Day 70 group was 145.3 +/- 70.0 days after transplantation, with a maximum survival of 221 days until death. Significantly prolonged survival, as compared with that in the non-OLT group, was observed in the OLT Day 70 and OLT Day 120 groups (p < 0.01), while there was no significant prolongation in the OLT Day 134 group (NS). The timing of liver transplantation is a very important factor. Preoperative assessment of factors potentially affecting recurrence in HCC patients is imperative for selecting the most appropriate candidates for OLT. Careful selection of candidates for OLT should always be considered the key to successful liver transplantation (i.e., long-term survival) for patients with liver cancer.
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PMID:The outcome of liver transplantation at various times (70, 120, and 134 days) after the initiation of carcinogenesis in rats. 961 50

The influence of the biological medium on high-intensity focused ultrasound (HIFU) therapy for ablating experimental liver cancer was studied. In study 1, the temperature rise in the focal zone in the presence of iodized oil or castor oil was observed in vitro. The results showed that HIFU with iodized oil produced a higher and faster temperature rise than did HIFU with castor oil, whether high-power (500 W/cm2) or relatively low-power (136 W/cm2) conditions were used (P = 0.0008 and P = 0.0004 respectively). With the excised liver samples, the temperature also rose higher and more rapidly after injection of iodized oil into the liver than when castor oil was injected (P = 0.0239), and the target liver tissue revealed more radically and extensive destruction with iodized oil than with castor oil. In study 2, 48 nude mice, bearing primary liver cancer LTNM4 implanted subcutaneously, were randomly divided into four groups. Group I (n = 12) were the controls, group II (n = 12) were injected with iodized oil alone, group III (n = 12) received HIFU treatment, and group IV (n = 12) were exposed to HIFU after iodized oil injection. Significant inhibition of tumor growth was seen in groups III and IV as compared with group I or group II (P < 0.05), the tumor growth inhibition rate on the 28th day after treatment being 87% and 93% respectively. Significantly improved survival was noted in groups III and IV compared with groups I and II (P < 0.05). Histologically, group IV showed more complete tumor necrosis than did group III. These data suggest that HIFU combined with iodized oil might have achieve of synergism, location and targeting in the treatment of liver cancer.
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PMID:Iodized oil enhances the thermal effect of high-intensity focused ultrasound on ablating experimental liver cancer. 962 Feb 23

Since 1975-80, worldwide but mostly in Europe and Japan, sonography has become the imaging technique of choice for guiding percutaneous interventional procedures for diagnostic or therapeutic purposes. In the last 10 years, the most important advances in interventional ultrasound have occurred in therapeutic applications, fostering and facilitating the development of the so-called minimally-invasive techniques. Among all these new applications for the treatment of fluid collections, inflammatory diseases, benign and malignant tumors, the most recent dramatic advances have occurred in primary and secondary liver malignancies, which will be the focus of this review. The rationale for the local treatment of primary and secondary liver cancers differs according to the success of conventional treatments (e.g. surgery and chemotherapy) and to the survival rates of such conditions, depending on clinical stage, patient age, associated diseases, and so on. Ultrasound-guided percutaneous therapies for liver cancer can be divided into: (1) direct intratumoral injection of chemical agents, such as ethanol, hot saline and acetic acid; and (2) thermally-mediated techniques, such as radiofrequency ablation, interstitial laser photocoagulation, microwave therapy or cryotherapy. Through different mechanisms of action, all these methods induce cell death by coagulative necrosis. The clinical efficacy of some of these techniques has been clearly established, like percutaneous ethanol injection in the treatment of hepatocellular carcinoma. In contrast, experience with the other techniques is much more preliminary, mostly due to the limited availability of sufficient clinical trials and to the fascinating speed of technological development. We review the state-of-the-art of the two most promising techniques, namely radiofrequency ablation and interstitial laser photocoagulation, and the present preliminary clinical data in the treatment of hepatocellular carcinomas and liver metastases. Radiofrequency energy is delivered to the tumors by means of electrode-needles (14-17 G) electrically insulated along all but the distal portion of the shaft and percutaneously introduced into the targets under ultrasound guidance. In the short history of this method, several technologies have been tested and used, but 'multiple-hook' and 'internal-cooling' electrodes are currently the leading choices, providing large necrosis volumes (up to 5 cm in diameter for a single 12-min application with an array of three internal-cooling electrodes) in short sessions, under local or general anesthesia. Radiofrequency ablation has proved its usefulness in the treatment of hepatocellular carcinomas, achieving complete necrosis in over 85-90% of cases in lesions smaller than 5 cm in diameter and in single sessions, with a low rate (< 10%) of local recurrences. In the treatment of liver metastases, whose very poor responsiveness to percutaneous ethanol injection and other 'chemical' therapies is extensively reported in the literature, radiofrequency ablation has 65-75% reported complete efficacy in the control of local tumor growth in lesions not exceeding 4 cm. Such great efficacy has been so far coupled with very low rates of major side-effects (< 2%), most of them requiring no surgical repair. Interstitial laser photocoagulation induces thermally-mediated coagulation through thin optic (Nd:YAG) fibers percutaneously inserted into the target under ultrasound guidance. Multiple fibers (beam splitters) are usually required to achieve a sufficiently wide necrosis volume. The reported success rate (complete necrosis and local control of tumor growth) ranges 45-75%) of the lesions, mostly liver metastates from colorectal carcinoma. An equally low rate of complications is reported for interstitial laser photocoagulation as for radiofrequency ablation, that is no more than 2-3% of cases. (ABSTRACT TRUNCATED)
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PMID:New applications of ultrasonography: interventional ultrasound. 965 23

This study demonstrates a novel role for the Fas pathway in the promotion of local tumor growth by inducing apoptotic cell death in normal hepatocytes at the tumor margin in colorectal hepatic metastases. Our results show that >85% of lymphocytes infiltrating colorectal liver cancer express high levels of Fas-ligand (Fas-L) by flow cytometry. Using immunohistochemistry of tumor tissue we showed strong Fas expression in noninvolved hepatocytes, whereas Fas-L expression was restricted to tumor cells and infiltrating lymphocytes at the tumor margin. Apoptosis was observed in 45 +/- 13% of the Fas(high) hepatocytes at the tumor margin whereas only 7 +/- 3% tumor cells were apoptotic (n = 10). In vitro, primary human hepatocytes expressed Fas receptor and crosslinking with anti-Fas antibody induced apoptosis in 44 +/- 5% of the cells compared with 4. 6 +/- 1.0% in untreated controls (P = 0.004). Both tumor-infiltrating lymphocytes (TIL) and human metastatic colon cancer cells cells are able to induce Fas-mediated apoptosis of primary human hepatocytes in coculture cytotoxic assays. TIL induced apoptosis in 47 +/- 9% hepatocytes compared with control 4.3 +/- 1. 0% (P = 0.009) and this effect was reduced by anti-human Fas-L mAb (18.7 +/- 1.3%, P = 0.009). SW620 cells induced apoptosis in 26 +/- 2% hepatocytes compared with control 5.6 +/- 1.7% (P = 0.004) and this was reduced to 11.2 +/- 1.8% (P = 0.004) in the presence of anti-human Fas-L mAb. These data suggest that the inflammatory response at the margin of colorectal liver metastases induces Fas expression in surrounding hepatocytes, allowing them to be killed by Fas-L-bearing TIL or tumor cells and facilitating the invasion of the tumor into surrounding liver tissue.
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PMID:Fas/Fas ligand interaction in human colorectal hepatic metastases: A mechanism of hepatocyte destruction to facilitate local tumor invasion. 1007 47

In various types of human malignant tumors, the presence or absence of expression of apoptosis-associated gene products (p53 protein and Bcl-2 protein) and the tumor proliferation activity-related factor (Ki-67) was assessed by immunohistochemical staining and the correlation between this expression and chemosensitivity to anticancer drugs was investigated. Study subjects comprised 55 preoperative patients with untreated malignant tumors (9 with esophageal cancer, 11 with stomach cancer, 11 with colon cancer, 13 with hepatic cancer and 11 with breast cancer). A chemosensitivity test was carried out with the histoculture drug response assay (HDRA) method using 4 drugs, mitomycin C (MMC), 5-fluorouracil (5-FU), doxorubicin hydrochloride (ADM), and cisplatin (CDDP). Immunohistochemical staining was used to assess expression of p53 protein, Bcl-2 protein and Ki-67. The tumor growth inhibition index (I.I.) of the 4 drugs was significantly lower in a group of the patients with p53 protein overexpression-type (mutant p53 protein positive expression-type) tumors than in a group with p53 protein negative expression-type tumors (p<0.05). No significant correlation was found between the expression of the Bcl-2 protein by and the I.I. of any drug studied in any type of cancer. A negative correlation was found between the labeling index (L.I.) for Ki-67 in all cases and I.I. for MMC and ADM and thus, chemosensitivity of the tumors with high growth activity was lower. Furthermore, a positive correlation existed between the L.I. for Ki-67 and that for p53 protein. The patients with p53 protein overexpression-type (mutant p53 protein positive) tumors showed low chemosensitivity. In addition, overexpression of p53 protein is suggested to be one of the factors involved in the lowered chemosensitivity of the tumors with high growth activity. Summarizing these findings, the p53 protein can play an important role in cancer therapy.
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PMID:Usefulness of p53 protein, Bcl-2 protein and Ki-67 as predictors of chemosensitivity of malignant tumors. 1020 14

Dietary glycine inhibited hepatocyte proliferation in response to the carcinogen WY-14,643. Since increased cell replication is associated with hepatic cancer caused by WY-14,643, glycine may have anti-cancer properties. Therefore, these experiments were designed to test the hypothesis that dietary glycine would inhibit the growth of tumors arising from B16 melanoma cells implanted subcutaneously in mice. C57BL/6 mice were fed diet supplemented with 5% glycine and 15% casein or control diet (20% casein) for 3 days prior to subcutaneous implantation of B16 tumor cells. Tumor volume was estimated from tumor diameter for 14 days. Tumors were excised, weighed and sectioned for histology post-mortem. B16 cells and endothelial cells were cultured in vitro to assess effects of glycine on cell growth. Statistical tests were two-sided and a P-value of 0.05 was defined as a significant difference between groups. Weight gain did not differ between mice fed control and glycine-containing diets. B16 tumors grew rapidly in mice fed control diet; however, in mice fed glycine diet, tumor size was 50-75% less. At the time of death, tumors from glycine-fed mice weighed nearly 65% less than tumors from mice fed control diet (P < 0.05). Glycine (0.01-10 mM) did not effect growth rates of B16 cells in vitro. Moreover, tumor volume and mitotic index of B16 tumors in vivo did not differ 2 days after implantation when tumors were small enough to be independent of vascularization. After 14 days, tumors from mice fed dietary glycine had 70% fewer arteries (P < 0.05). Furthermore, glycine (0.01-10 mM) inhibited the growth of endothelial cells in vitro in a dose-dependent manner (P < 0.05; IC50 = 0.05 mM). These data support the hypothesis that dietary glycine prevents tumor growth in vivo by inhibiting angiogenesis through mechanisms involving inhibition of endothelial cell proliferation.
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PMID:Dietary glycine inhibits the growth of B16 melanoma tumors in mice. 1033 95

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