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

Researchers from the US National Cancer Institute compared data on 25-49 year old US women who died of primary liver cancer between 1985 and 1986 with data on age matched controls who died of causes other than liver conditions or oral contraceptive (OC) related conditions to determine the association between primary liver cancer and parity. Women who had experienced at least 1 live birth wear 1.9 times more likely to have died of primary liver cancer than were nulliparous women. The association was not significant (p=.22), however. The highest risks were among children with at least 6 children (odds ratio [OR]=2.9) and with 2 children (2.1). Further the risks were greater when the parents or spouse completed the questionnaire and the association almost reached significance (p=.07). This may have been due to parents and spouse providing more complete information than a friend or neighbor. The risks of developing primary liver cancer were higher among women who had never used OCs than they were among those who ever did. For example, the OR for never users past parity 2 was 3.6 compared with 1.3 for ever OC users. There was a higher risk associated with parity among long term OC users (=or 5 years) than with short-term OC users, however. The researchers concluded that since parity was positively associated with increased risk of primary liver cancer in the US (a low risk country), endogenous hormones may contribute to liver cancer development. The following facts add to this plausibility. Estrogen profiles of parous women are different from those of nulliparous women. Estrogen levels rise considerably during pregnancy. Estrogens alter liver metabolism. Pregnancy makes the body more defenseless against hepatitis and its sequelae. In low risk countries, the risk of primary liver cancer rises among women using exogenous hormones.
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PMID:Parity and primary liver cancer among young women. 161 86

Predisposing factors to cervical cancer development are age, smoking, socioeconomical status, parity, and number of sex partners. Long-term oral contraceptive (OC) use and less than 50 mg estrogen dose have been weakly linked to increased cancer risk. Regular examination and switching to other contraception in case of cervical intraepithelial neoplasia is recommended. Estrogen in sequential pills (Ovacon) increases the risks of uterine cancer by affecting the mucosa. Predisposing factors are: absence of pregnancy (nulliparity), postmenopause, hypertension, and diabetes. Parity reduces the risk. The risk is reduced in combined pills and after use of 1 year. Protection is offered by the progesterone component for 10-20 years after cessation of use. Ovarian cancer is prevented by parity and OC use even 10 years later. High estrogen levels inducing frequent ovulation damage the ovaries. Promoting factors are: old age, avoidance of breast feeding, and overweight. Breast cancer promoters are 1st pregnancy in older age, early menarche, and no pregnancy at all. OC use under age 25 and before 1st pregnancy are significant risk factors. High progesterone levels are associated with increased mitotic activity in the breast. Rare benign fibrocysts can develop into breast cancer. OC use is connected to hepatoma development mainly estrogen-induced. Liver cancer was found twice as high in OC users. Hepatoma often ruptures causing hemorrhage. 8% of liver tumors are malignant with a survival rate of 50% of patients to 4.8 years. The possible association of OCs to skin melanoma and hypophysial tumors could not be confirmed. OCs regulate menstruation, reduce bleeding, protect against uterine and ovarian cancer, but cervical and breast cancers have been influenced by them.
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PMID:[The contraceptive pill and cancer]. 207 68

We have assayed both estrogen and androgen receptors in hepatocellular carcinomas, in the surrounding noncancerous liver tissue, and in normal liver tissue. Estrogen receptors (ERs) were detected in 5 out of 22 HCC tissues, 14 out of 22 surrounding noncancerous tissues, and in 5 out of 6 normal liver tissues. Androgen receptors (Ars) were detected in 4 out of 21 HCC tissues, in 7 out of 21 surrounding noncancerous tissues, and in 2 out of 5 normal liver tissues. These results suggest that the pathogenesis of some HCC may be dependent on estrogen or androgen. Hence, it may be beneficial to provide hormonal therapy for HCC, especially in cases that show high concentrations of ER and/or AR.
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PMID:[Estrogen and androgen receptors in hepatocellular carcinoma and in noncancerous liver tissue]. 255 Jun 81

The risk of contracting neoplastic liver disease after taking synthetic sex hormones, either estrogens or androgens, is discussed. Since the 1st reports that oral contraceptives were associated with liver neoplasms in the 1970s, tests on laboratory animals have suggested that sex steroids act as promoters of hepatocarcinogenesis in suitably initiated animals, and that some hormones act as weak complete carcinogens in certain lab hosts. It is known that oral contraceptives induce benign hepatic adenoma: hundreds of cases have been reported. These adenomas regress when women stop taking orals. The possible progression to malignant lesions is difficult to assess. Although a 1982 case review of women with hepatocellular carcinoma concluded that the association was a coincidence, 2 more recent epidemiological studies have proposed that there is a possible link between pills and hepatocarcinoma as well as cholangiosarcoma. In favor of the association is the finding that the histopathology of carcinoma in pill users differs from that in nonusers. Arguing against a causative role is the fact that natural cyclic estrogen levels are much higher than those found in pill users. Overall, the risk of developing liver cancer is far lower than the risk of other serious consequences of pill use, for example thromboembolism, and must be judged in the context of the many protective effects of the pill. The estrogen DES or diethylstilbestrol is no longer being used, but cases of clear-cell adenocarcinoma are still appearing in the daughters of its users. Anabolic androgens, prescribed therapeutically or abused, are known to cause liver neoplasms, primarily hepatocellular carcinoma, but also adenomas, focal nodular hyperplasia, cholangiosarcoma and angiosarcoma. The legitimate use of these steroids is on a much smaller scale, and for short periods of time, compared to oral contraceptives, so the causative role of androgens in neoplasia is less well known. With any of these drugs, especially in areas where potential cancer initiators such as oncogenes or viruses are endemic, careful screening is vital for safe use.
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PMID:Risk factors associated with the use of sex hormones. 282 3

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.
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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

The effect of estrogen withdrawal on energy metabolism was studied in four human breast cancer xenografts: the estrogen-dependent MCF-7 and ZR75-1 and the estrogen-independent ZR75/LCC-3 and MDA-MB-231. The tumors were grown in ovariectomized nude mice with a s.c. implanted estrogen pellet. After Gompertzian growth was verified, the estrogen pellet was removed from half of the animals. In vivo 31P magnetic resonance spectroscopy of the tumors was performed 1 day before and on days 2, 6, and 14 after estrogen removal. Estrogen withdrawal induced a significant increase in the nucleoside triphosphate:Pi ratio in the two estrogen-dependent xenografts, whereas this ratio remained unchanged in the estrogen-independent tumors. In ZR75/LCC-3 tumors a slight decrease in nucleoside triphosphate:Pi was observed following onset of estrogen stimulation after initial growth without estrogen. Extracts of freeze-clamped tumors prepared 14 days after estrogen removal were analyzed for ATP and phosphocreatine content. Our findings suggest a correlation between estrogen withdrawal and the steady-state concentrations of ATP, phosphocreatine, and Pi in human breast cancer xenografts. Discrimination analysis of the pretherapeutic spectra enabled us to identify the tumor line and the estrogen dependence of the tumors in 80-90% of all cases.
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PMID:Effect of estrogen withdrawal on energy-rich phosphates and prediction of estrogen dependence monitored by in vivo 31P magnetic resonance spectroscopy of four human breast cancer xenografts. 771 72

Exposure to estrogens is associated with an increased risk of developing breast, cervical, and liver cancer. Estrogens strongly induce the human granzyme B inhibitor, proteinase inhibitor 9 (PI-9). Because cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells use the granzyme pathway to induce apoptosis of target cells, we tested the ability of activated CTLs and the human NK cell line, YT cells, to lyse human liver cells. Estrogen induction of PI-9 protected the liver cells against CTL and NK cell-mediated, granzyme-dependent, apoptosis. Knockdown of PI-9 by RNA interference blocked the protective effect of estrogen. This work demonstrates that estrogens can act on target cells to control their destruction by immune system cells and shows that induction of PI-9 expression can inhibit both CTL and NK cell-mediated apoptosis. Estrogen induction of PI-9 may reduce the ability of cytolytic lymphocytes-mediated immune surveillance to destroy newly transformed cells, possibly providing a novel mechanism for an estrogen-mediated increase in tumor incidence.
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PMID:Estrogen induction of the granzyme B inhibitor, proteinase inhibitor 9, protects cells against apoptosis mediated by cytotoxic T lymphocytes and natural killer cells. 1630 80

Hepatocellular carcinoma (HCC), the major manifestation of primary liver cancer, is one of the most frequent and malignant cancers worldwide, especially in Taiwan. Estrogen receptors (ERs) have been reported to play either a proliferation- or apoptosis-enhancing role in the differentiation of cancers, including HCC. In a previous experiment, we showed that transient overexpressed estrogen receptor-alpha induced early stage HCC cell line Hep 3B cell apoptosis by increasing the hTNF-alpha gene expression in a ligand-independent manner. To further clarify if the apoptotic effect occurs in poorly differentiated HCC cell line, HA22T, and elucidate the roles of ERs and TNF-alpha, DNA fragmentation and caspase activity were measured in late stage HCC cell line, HA22T, by measuring the expression of hER-alpha and hER-beta using a Tetracycline-inducible system (Tet-on). Increased DNA fragmentation and caspase-3 activity were found in hERbeta-overexpressed HA22T cells treated with estrogen (10(-8) M) but not in hERalpha-overexpressed HA22T cells. Using RT-PCR/PCR and western blotting in HA22T cells, overexpressed hER-beta was also found to increase the expression of hTNF-alpha mRNA and induce hTNF-alpha-dependent luciferase activity in a ligand-dependent manner. Additionally, LPS treatment and hER-beta overexpression both enhance caspase-8 activities, whereas neither hER-beta nor E2 treatment affected caspase-9 activities. In addition, the overexpressed hER-beta plus E2 enhanced DNA fragmentation and caspase-8 activities were only partially reduced by anti-hTNF-alpha (0.1 ng/ml), which was possibly due to the involvement of P53 and TGF-beta. Taken together, our data indicates that overexpressed hER-beta but not hER-alpha may induce caspase-8-mediated apoptosis by increasing the hTNF-alpha gene expression in a ligand-dependent manner in poorly differentiated HA22T cells.
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PMID:Opposing action of estrogen receptors alpha and beta on tumor necrosis factor-alpha gene expression and caspase-8-mediated apoptotic effects in HA22T cells. 1663 37

Hepatocellular carcinoma (HCC), the most common liver cancer, occurs mainly in men. Similar gender disparity is seen in mice given a chemical carcinogen, diethylnitrosamine (DEN). DEN administration caused greater increases in serum interleukin-6 (IL-6) concentration in males than it did in females. Furthermore, ablation of IL-6 abolished the gender differences in hepatocarcinogenesis in mice. DEN exposure promoted production of IL-6 in Kupffer cells (KCs) in a manner dependent on the Toll-like receptor adaptor protein MyD88, ablation of which also protected male mice from DEN-induced hepatocarcinogenesis. Estrogen inhibited secretion of IL-6 from KCs exposed to necrotic hepatocytes and reduced circulating concentrations of IL-6 in DEN-treated male mice. We propose that estrogen-mediated inhibition of IL-6 production by KCs reduces liver cancer risk in females, and these findings may be used to prevent HCC in males.
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PMID:Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. 1803 65

Hepatocellular carcinoma (HCC), the most common liver cancer, occurs mainly in men. Similar gender disparity is seen in mice given a chemical carcinogen, diethylnitrosamine (DEN). DEN administration caused greater increases in serum interleukin-6 (IL-6) concentration in males than it did in females. Furthermore, ablation of IL-6 abolished the gender differences in hepatocarcinogenesis in mice. DEN exposure promoted production of IL-6 in Kupffer cells (KCs) in a manner dependent on the Toll-like receptor adaptor protein MyD88, ablation of which also protected male mice from DEN-induced hepatocarcinogenesis. Estrogen inhibited secretion of IL-6 from KCs exposed to necrotic hepatocytes and reduced circulating concentrations of IL-6 in DEN-treated male mice. We propose that estrogen-mediated inhibition of IL-6 production by KCs reduces liver cancer risk in females, and these findings may be used to prevent HCC in males.
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PMID:Is interleukin-6 a gender-specific risk factor for liver cancer? 1789 15


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