UMLS:C0345904 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

Tamoxifen is a nonsteroidal antiestrogen that has found successful applications for each stage of breast cancer in the treatment of selected patients. Tamoxifen was originally introduced for the treatment of advanced disease in postmenopausal women; however, the drug is now also available for the palliative treatment of premenopausal women with estrogen receptor (ER) positive disease. The proven efficacy of tamoxifen and the low incidence of side effects made the drug an ideal agent to test as an adjuvant therapy for women with node-positive breast cancer. Laboratory studies indicate that long-term treatment schedules may provide maximal benefit in preventing recurrence, and recent analysis of clinical trials demonstrates that between 2 and 5 years of adjuvant tamoxifen therapy provides a survival advantage for postmenopausal women with node-positive disease. Similarly, adjuvant studies in node-negative breast cancer have demonstrated an increase in the disease-free survival of both pre- and postmenopausal patients with ER-positive tumors. However, the extended use of tamoxifen has raised questions about the long-term safety of antiestrogen therapy. Of special concern is the impact of tamoxifen on ovarian function in premenopausal women and the potential risks to the fetus if pregnancy occurs. Fortunately, there are no reports about the teratogenicity of tamoxifen in the human, but it is important that physicians counsel women about the risk of pregnancy. Tamoxifen should not be used if a patient is pregnant. Initial concerns that the long-term administration of an antiestrogen would increase bone loss and increase the risks of coronary heart disease appear to be unwarranted. Tamoxifen has some estrogen-like activities in postmenopausal women and causes a preservation of bone in the lumbar spine and a decrease in circulating cholesterol. Indeed, a reduction in fatal myocardial infarction (MI) has been noted during 5 years of tamoxifen therapy, possibly the direct result of a prolonged reduction in circulating cholesterol. However, the estrogen-like qualities of tamoxifen that could be valuable as a hormone replacement therapy for all postmenopausal women following a diagnosis of breast cancer may also increase the risk for developing endometrial carcinoma. To date, there are only a few reports of endometrial carcinoma being diagnosed during adjuvant therapy with tamoxifen; however, any instances of uterine bleeding or spotting should be followed up with an endometrial biopsy. There are some concerns about large doses of tamoxifen promoting liver cancer in rats. These results are of particular concern if tamoxifen is to be used as a preventive in normal women.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:The role of tamoxifen in the treatment and prevention of breast cancer. 158 40

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.
...
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.
...
PMID:[Experimental analysis of postoperative early recurrence of liver cancer]. 259 75

Estrogen withdrawal versus tamoxifen (TAM) treatment was compared in two human breast cancer xenografts, the estrogen-dependent ZR75-1 and its estrogen-independent subline ZR75/LCC-3. The following parameters were determined: tumor growth, NTP:P(i) by 31P magnetic resonance spectroscopy, apoptotic index, and creatine kinase (CK) activity. Tumors of each line were grown in ovariectomized nude mice during stimulation from a s.c. 17 beta-estradiol pellet. At a tumor size of approximately 350 mm3, the pellet was removed from one-half of the animals. The remaining one-half served as controls. In parallel experiments, injections of TAM were initiated instead of estrogen withdrawal. Estrogen withdrawal as well as TAM induced growth inhibition of ZR75-1 tumors, whereas ZR75/LCC-3 was resistant to both types of therapy. Growth inhibition of ZR75-1 by estrogen withdrawal, but not by TAM, was accompanied by an 80% increase of the NTP:P(i) ratio (P < 0.01) and a significantly decreased cytosolic CK activity (P < 0.01). No significant change in pH was observed. These changes seemed not to be related to changes in apoptotic index. None of the described changes occurred in ZR75/LCC-3. The present data indicate: (a) ZR75-1 and ZR75/LCC-3 xenografts respond differently to estrogen withdrawal and TAM with regard to growth inhibition, 31P magnetic resonance spectroscopy, and CK activity; (b) estrogen withdrawal, but not TAM, induced a decrease in the CK activity of estrogen-dependent tumor tissue, and (c) increased apoptosis did not explain the growth inhibition and the increase in NTP:P(i) induced by estrogen withdrawal. The results indicate other growth inhibitory mechanisms of TAM in addition to competitive inhibition of the estrogen receptor.
...
PMID:Growth inhibition in response to estrogen withdrawal and tamoxifen therapy of human breast cancer xenografts evaluated by in vivo 31P magnetic resonance spectroscopy, creatine kinase activity, and apoptotic index. 766 92

Estrogen receptor mRNA was detected by a non-radioactive in situ hybridization assay in tumor and non-neoplastic liver tissues. A synthetic oligonucleotide complementary to the human estrogen receptor mRNA was 3'-labeled with digoxigenin-deoxyuridine triphosphate (dUTP). Hybrids were revealed by an alkaline phosphatase-conjugated anti-digoxigenin antibody. Fourteen primary hepatocellular carcinoma tissues (and one metastatic) were obtained at surgery from 15 patients. The corresponding non-neoplastic liver tissues were available in 13 cases. The estrogen receptor mRNA was detected in 11 tumorous and 7 non-tumorous liver specimens. The staining was cytoplasmic and involved the majority of transformed hepatocytes, whereas a less widespread and weaker signal was found in normal hepatocytes. Within non-neoplastic tissue, bile duct epithelial cells could also be occasionally stained, whereas other cell types, such as vasal endothelial cells, were negative. Appropriate controls established the specificity of the reaction. Detection of the estrogen receptor protein by immunohistochemistry in these same specimens was invariably negative. This in situ hybridization assay can therefore be used as a complementary tool to evaluate the estrogen receptor expression within liver cancer.
...
PMID:Expression of estrogen receptor mRNA in tumorous and non-tumorous liver tissue as detected by in situ hybridization. 838 61

The past four decades of epidemiological research have yielded valuable information on the risks of populations to environmental exposures such as tobacco, asbestos, and dietary components. Prevention efforts have been focused on large-scale population-based interventions to minimize exposure to such external carcinogens. While some cancers are beginning to show a decline from changing environmental exposures, hormone-related cancers, such as breast and prostate, are becoming more prevalent. The development of these cancers appears to be closely related to endogenous exposures to circulating steroid hormones. Although prevention trials using antihormone agents are proving successful in some instances, the long-term control of these cancers necessitates a clearer understanding of the metabolism and transport of the relevant hormone in vivo. The revolution in molecular biology has provided powerful genetic tools for evaluating mechanisms of cancer causation as well as the potential to better define individual susceptibility. Using tobacco exposure as an example, we and others have demonstrated that polymorphisms in genes controlling aromatic amine metabolism provide at least a partial explanation for ethnic and individual susceptibility to bladder cancer. Similar studies have examined genetic polymorphisms in the metabolism of tobacco smoke and lung cancer risk, red meat and colorectal cancer, and aflatoxin and liver cancer. Our current studies have pursued a similar paradigm of genetic polymorphism and individual cancer susceptibility in prostate and breast carcinogenesis. We are evaluating polymorphisms in the steroid 5 alpha-reductase type II and androgen receptor genes in relation to prostate cancer based on the evidence that intracellular dihydrotestosterone is the critical "carcinogen." We are pursuing genetic polymorphisms affecting estradiol metabolism, including those in the 17 beta-hydroxysteroid dehydrogenase 2 and estrogen receptor genes as they relate to susceptibility to breast cancer. The potential role of a polymorphism in the cytochrome P450c 17 alpha gene in both breast and prostate cancers is also being examined.
...
PMID:Genetic susceptibility to cancer from exogenous and endogenous exposures. 902 93

The expression of hepatocyte nuclear estrogen receptor (ER) in putative preneoplastic foci, adenomas and carcinomas, induced by the rat liver carcinogen tamoxifen, has been examined immunohistologically. ER staining of normal rat liver shows between 30-50% of hepatocyte nuclei to be positive, depending on fixation. Depletion of ER was defined as <10% of cells in foci or tumours staining for nuclear ER. A proportion of all but the smallest glutathione-S-transferase, placental form (GST-P) expressing foci had depleted expression of nuclear ER. The percentage of GST-P expressing foci with depletion of nuclear ER increased with the size of the foci. The liver adenomas and carcinomas induced by tamoxifen showed a high incidence (90%) of depletion of ER. This suggests that abnormal expression of the ER is associated with the promotion of putative preneoplastic foci to adenomas and carcinomas in tamoxifen exposed rat livers. Dysfunction of the ER could contribute to selective continued stimulation of initiated cells that would be consistent with a role for modification of the ER in target cells and the promotion stage of liver cancer. Liver tumours induced by other carcinogens in both sexes of rat were also found to have a high incidence of ER depletion, indicating that this could be a general regulatory mechanism for rat liver tumour promotion, irrespective of the possible estrogen like action of individual carcinogens.
...
PMID:Depletion of hepatocyte nuclear estrogen receptor expression is associated with promotion of tamoxifen induced GST-P foci to tumours in rat liver. 916 3

Mutations in the tumor suppressor p53 are a common event in hepatocellular carcinoma (HCC). Because HCCs typically occur in livers with chronic injury and impaired function, we have explored the role of wild-type p53 in regulating the growth and differentiation of Hep 3B hepatoma cells, a p53-negative line derived from a liver cancer. Stable Hep 3B cell lines were generated in which inducible p53 was introduced using either a temperature-sensitive mutant (p53val135) or a tamoxifen-regulated p53-estrogen receptor chimera (p53-mERtm-pBabepuro). In both cell lines, induction of transcriptionally active p53 was confirmed by assessing several p53 targets: Mdm2 protein, p21waf1 mRNA and protein, and the cyclin G promoter. Despite marked induction of p21waf1, cells with active p53 failed to undergo growth arrest, which is probably due to the presence of a non-functional retinoblastoma protein (pRb) in these cells. Apoptosis also was not observed, even after prolonged (48 h) serum starvation or exposure to cisplatinum. Lack of apoptosis was correlated with unchanged bax mRNA levels following p53 induction. Additionally, albumin mRNA levels remained unchanged, and there was no change in basal transactivation of a reporter containing the promoter of the haptoglobin gene, encoding an acute phase protein. This suggests that growth arrest may be required to promote liver-specific gene expression. Overall, our data demonstrate that introduction of transcriptionally active p53 does not alter the malignant, dedifferentiated phenotype of Hep 3B hepatoma cells. Hence, not all cancer cells are equally responsive to the re-activation of wild-type 53. The ability of a cancer cell to undergo p53-mediated phenotypic alterations may depend on the retention of functional downstream effector pathways.
...
PMID:Resistance to p53-mediated growth arrest and apoptosis in Hep 3B hepatoma cells. 923 78

Ethinylestradiol (EE) has evident paradoxical effects on cancer risk for human breast and hepatic cancer which parallel in some respects its effects on estrogen-induced neoplasms in the hamster kidney and liver. EE has been shown to be only weakly carcinogenic in the hamster kidney, but the most potent carcinogenic estrogen in the hamster liver following prolonged treatment. Unexpectedly, when EE and potent carcinogenic estrogens, such as diethylstilbestrol (DES), 17beta-estradiol (E2) and Moxestrol (MOX), are administered concomitantly, estrogen-induced carcinogenesis in the kidney is completely prevented. In studying this novel finding, we found that, compared with E2 exposure alone, EE at 0.05 and 1.0 nM significantly (P < 0.001) inhibited the rise in proliferation of cultured primary hamster proximal renal tubular (PRT) cells in the presence of E2 (1.0 nM). Consistent with these findings, combined EE + DES treatment for 5.0 months reduced hamster kidney c-myc, c-fos and c-jun RNA expression to 43, 37 and 52%, respectively, compared with levels observed after DES treatment alone. Interestingly, TAM + DES treatment for the same period also resulted in the same low level of RNA expression of these proto-oncogenes. c-MYC, c-FOS and c-JUN protein products were comparably reduced after either EE + DES or TAM + DES treatment. It appears that c-fos expression and c-FOS protein levels in the hamster kidney were more responsive to TAM inhibition. These data demonstrate that EE possesses unique anti-tumorigenic properties in vivo in the hamster kidney. Additionally, the observed anti-estrogen-like effect of EE on cell proliferation of cultured PRT cells suggests that EE may interfere critically with estrogen receptor (ER)-mediated mitogenic pathway(s) affected by potent carcinogenic estrogens, thus preventing subsequent gene dysregulation and, hence, tumor development. Based on competition studies, the differential binding of EE to hamster kidney ER relative to that of the other estrogens (E2, DES, MOX) appears not to contribute to the prevention of estrogen carcinogenesis at this organ site by EE.
...
PMID:Prevention of estrogen carcinogenesis in the hamster kidney by ethinylestradiol: some unique properties of a synthetic estrogen. 952 82

The LCC15-MB cell line was established from a femoral bone metastasis that arose in a 29-year-old woman initially diagnosed with an infiltrating ductal mammary adenocarcinoma. The tumor had a relatively high (8%) S-phase fraction and 1/23 positive lymph nodes (LN). Both the primary tumor and LN metastasis were positive for estrogen receptor (ER) and progesterone receptor (PgR), but lacked erbB2 expression. Approximately one year later, the patient presented with a 0.8 cm comedo-type intraductal mammary adenocarcinoma in the left breast that was negative for ER and PgR, but positive for erbB2. Thirty-five months after the initial diagnosis she was treated for acute skeletal metastasis, and stabilized with a hip replacement. At this time, tumor cells were removed from surplus involved bone, inoculated into cell culture, and developed into the LCC 15-MB cell line. The bone metastasis was a poorly differentiated adenocarcinoma lacking ER, PgR, and erbB2, characteristics shared by the LCC15-MB cells, although ER can be re-expressed by treatment of the LCC15-MB cells for 5 days with 75 microM 5-aza-2'-deoxycytidine. The LCC15-MB cell line is tumorigenic when implanted subcutaneously in NCr nu/nu mice and produces long-bone metastases after intracardiac injection. Although the bone metastasis from which the LCC15-MB cell line was derived lacked vimentin (VIM) expression, the original primary tumor and lymph node metastasis were strongly VIM positive, as are LCC15-MB cells in vitro and in nude mice. The karyotype and isozyme profiles of LCC15-MB cells are consistent with its origin from a human female, with most chromosome counts in the hypertriploid range. Thirty-two marker chromosomes are present. These cells provide an in vitro/in vivo model in which to study the inter-relationships between ER, VIM, and bone metastasis in human breast cancer.
...
PMID:LCC15-MB: a vimentin-positive human breast cancer cell line from a femoral bone metastasis. 1043 4

1 2 3 4 5 6 Next >>