Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Toremifene”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources
PubMed1992

Genotoxic potential of tamoxifen and analogues in female Fischer F344/n rats, DBA/2 and C57BL/6 mice and in human MCL-5 cells.

Chronic administration of tamoxifen to female rats causes hepatocellular carcinomas. We have investigated damage to liver DNA caused by the administration of tamoxifen to female Fischer F344/N rats or C57B1/6 or DBA/2 mice using 32P-postlabelling. Following the administration of tamoxifen for 7 days (45 mg/kg/day) and extraction of hepatic DNA, up to 7 radiolabelled adduct spots could be detected after PEI-cellulose chromatography of the 32P-labelled DNA digests. Tamoxifen caused a time-dependent increase in the level of adduct detected up to a value of at least 1 adduct/10(6) nucleotides after 7 days dosing. A dose response relationship was demonstrated over the range of 5-45 mg/kg/day (0.013-0.12 mmol/kg/day). On cessation of dosing there was a loss of adducts from the liver DNA. These adducts were not detected in DNA from vehicle-dosed controls or in DNA from kidney, lung, spleen, uterus or peripheral lymphocytes. Pyrrolidinotamoxifen caused a similar level of adduct formation as tamoxifen. In contrast, no significant adduct formation could be detected in liver DNA from rats given droloxifene or toremifene. Mice given tamoxifen (45 mg/kg/day for 4 days) showed levels of adducts in the liver which were 30-40% of those present in rats. Exposure of rat hepatocytes to tamoxifen in vitro, resulted in induction of unscheduled DNA synthesis, when preparations from rats which had been pretreated with tamoxifen in vivo were used. No such increase could be detected in hepatocytes from control rats, suggesting tamoxifen may induce enzymes responsible for its own activation. Tamoxifen induced a significant increase in micronucleus formation in a dose dependent manner in cultures of MCL-5 cells, a human cell line that expresses 5 different human cytochrome P450 isoenzymes, as well as epoxide hydrolase.

Animals↗
PubMed1994

A mechanistic hypothesis for DNA adduct formation by tamoxifen following hepatic oxidative metabolism.

A mechanism for the generation of electrophilic alkylating agents from tamoxifen by hepatic alpha-oxidation of its ethyl group is presented which accounts for the formation of covalent DNA adducts associated with its hepatic carcinogenicity. The key process leading to the generation of electrophilic alkylating agents from tamoxifen is postulated to be alpha-hydroxylation in conjunction with 4-hydroxylation or secondary metabolic conjugation. The mechanism explains the lack of DNA adducts observed for the tamoxifen analogues toremifene, droloxifene and idoxifene and accounts for the species variation in hepatic carcinogenicity of tamoxifen.

Animals↗
PubMed1999

Lack of evidence from HPLC 32P-post-labelling for tamoxifen-DNA adducts in the human endometrium.

Tamoxifen is associated with an increased incidence of endometrial cancer in women. It is also a potent carcinogen in rat liver and forms covalent DNA adducts in this tissue. A previous study exploring DNA adducts in human endometria, utilizing thin layer chromatography 32P-postlabelling, found no evidence for adducts in tamoxifen-treated women [Carmichael,P.L., Ugwumadu,A.H.N., Neven,P., Hewer,A.J., Poon,G.K. and Phillips,D.H. (1996) Cancer Res., 56, 1475-1479]. However, subsequent work utilizing HPLC 32P-post-labelling [Hemminki,K., Ranjaniemi,H., Lindahl,B. and Moberger,B. (1996) Cancer Res., 56, 4374-4377] suggested that very low levels could be detected. We have sought to investigate this question further by reproducing the HPLC methodology at two centres, and analysing endometrial DNA from 20 patients treated with 20 mg/day tamoxifen for between 22 and 65 months. Liver DNA isolated from tamoxifen-treated rats was used as a positive control. We found no convincing evidence for tamoxifen-derived DNA adducts in human endometrium. HPLC elution profiles of post-labelled DNA from tamoxifen-treated women were indistinguishable from those obtained with DNA from 14 untreated women and from six women taking toremifene, an analogue of tamoxifen.

Aged↗
PubMed1991

Treatment of metastatic breast cancer and its complications.

Measurement of quality of life is becoming increasingly important in the evaluation of treatment for metastatic breast cancer. New approaches to endocrine treatment include use of toremifene and trilostane. The addition of fluoxymesterone to tamoxifen is reported to enhance response frequency. The relationship between dose and response for anthracycline treatment has been reaffirmed. Measurement of left ventricular ejection fraction may not be a useful predictor of clinical cardiotoxicity. The new anthracyclines, idarubicin and pirarubicin, are active in breast cancer, the former being suitable for oral administration. Several new cytotoxic drug combinations have been reported, but have no clear advantages over existing regimens. Intensification of chemotherapy facilitated by autologous bone marrow transplantation or hematopoietic growth factors is feasible; high response rates can be achieved, but with severe toxicity. This approach remains investigational and has not yet achieved an established place in routine treatment. Progress has been made in the reduction of morbidity from bone metastases by use of bisphosphonates and therapeutic isotopes.

Antibiotics, Antineoplastic↗
PubMed2001

Sex hormone dependency of diethylnitrosamine-induced liver tumors in mice and chemoprevention by leuprorelin.

The prevalence of liver tumors throughout the world makes it imperative to seek chemopreventive agents. This tumor appears to be hormone-responsive and hormonal manipulations may therefore be beneficial. On this basis, both sexes of 12-day-old B6C3F(1) mice were injected i.p. with diethylnitrosamine (DEN) at the dose of 2.5 mg / g body weight and observed for 32 weeks (males) or 36 weeks (females). In 100% of male mice, liver tumors were observed with an average diameter of 2.72 mm and multiplicity of 60.8. Orchidectomy at 6 weeks of age in these mice inhibited the incidence, multiplicity and size to 63%, 5.6 and 1.54 mm, respectively. By further implantation with an E(2) pellet at monthly intervals, these parameters were reduced to 26%, 0.6 and 0.61 mm, respectively. Administration of a gonadotropin-blocking chemical, leuprorelin, to DEN-treated male mice significantly reduced the multiplicity and size of tumors to 18.3 and 2.54 mm (P < 0.01 compared to those of DEN only). In female mice, the incidence of liver tumor was significantly smaller than that of males. However, ovariectomy and / or testosterone supplement significantly increased the occurrence of liver tumor. An anti-estrogen, toremifene, caused a marked further decrease of liver tumors. Mitotic indices with bromodeoxyuridine in tumor tissues paralleled the occurrence of liver tumors. Serum testosterone levels were significantly reduced by orchidectomy or by leuprorelin administration. These results further confirm that liver tumor is testosterone-responsive and hormonal manipulation by surgical orchidectomy or by chemical orchidectomy i.e. by leuprorelin, could substantially prevent the appearance of liver tumors.

Animals↗
PubMed2001

Use of SERMs for the adjuvant therapy of early-stage breast cancer.

Tamoxifen was the first in a class of drugs now commonly referred to as selective estrogen receptor modulators or SERMs. SERMs exhibit tissue-specific estrogenic agonist/antagonist activity through their ability to bind to the estrogen receptor alpha (ER) protein and interact with coregulatory proteins, thereby modulating transcription of estrogen target genes. Since its first approval by the United States Food and Drug Administration (FDA) in 1977, tamoxifen has been found to (a) lower the risk of recurrence and death for women with early-stage hormone receptor-positive breast cancer, irrespective of menopausal and node status or use of adjuvant chemotherapy; (b) reduce the risk of invasive breast cancer following breast conservation in women with ductal carcinoma in situ (DCIS); and (c) reduce the risk of breast cancer in high-risk women. Toremifene is the only other SERM approved by the FDA for breast cancer treatment. However, it offers no clear clinical advantage over tamoxifen in the adjuvant or metastatic settings. Several other SERMs are in various phases of clinical development. In addition, strategies to combine SERMs with other endocrine therapy like ovarian suppression or aromatase inhibitors are active areas of investigations. At present, SERMs are recognized as the first targeted and relatively nontoxic medical therapy for women with high-risk or steroid hormone receptor-positive breast cancer.

Breast Neoplasms↗
PubMed1999

[Effect of selective estrogen receptor modulators on estrogen-sensitive tissues].

Selective estrogen receptor modulators (SERMs) act exclusively through estrogen receptors and possess tissue-specific agonistic or antagonistic properties. The effects of all referred SERMs in bone and cardiovascular system are estrogenic, namely they inhibit postmenopausal bone loss and favorably influence plasma lipoproteins and some coagulation factors. The aim of this paper is to review the effects of SERMs on estrogen-dependent breast tissues and on the endometrium. There are two types of SERMs in clinical use, based on their chemical structure: the triphenylethylenes and the benzothiophenes. The prototype of the SERMs with triphenylethylene structure is tamoxifen. Tamoxifen, like all other SERMs, is an estrogen antagonist in the breast and is widely used for adjuvant treatment of breast cancer. A recent study suggests that tamoxifen also may prevent breast cancer in patients at risk. Because of the partial estrogenic activity of tamoxifen in the endometrium, its clinical use is associated with uterine hypertrophy and an increased risk of endometrial cancer. Other triphenylethylene SERMs, droloxifene, toremifene, and idoxifene, also show efficacy in the treatment of breast cancer, in a manner similar to tamoxifen. A better toxicology profile and a decreased endometrial estrogen agonism may be advantages of the new triphenylethylene SERMs. Raloxifene is a SERM with a chemical structure different from triphenylethylenes. Raloxifene, a benzothiophene, possesses an estrogen-antagonistic effect in the breast similar to triphenylethylenes. Clinical studies on postmenopausal osteoporotic women on raloxifene as compared with placebo show a significant decrease in the rate of newly diagnosed breast cancers. In clinical studies, in contrast to tamoxifen, no stimulatory effect in the endometrium could be observed with raloxifene.

Animals↗
PubMed1992

Potential applications of high-dose megestrol acetate in breast cancer.

Empiric clinical trials have revealed new mechanisms by which hormonal therapies may exert their antitumor effects. Initial studies using escalated doses of agents like toremifene and megestrol acetate have yielded interesting results, showing responses in hormone-receptor-negative patients and in patients progressing after standard doses, respectively. A trial by Cancer and Leukemia Group B randomizing patients with advanced breast cancer to standard-dose (160 mg) megestrol acetate or to 5 or 10 times the standard dose (800 and 1,600 mg) has completed accrual. It is hoped that these results will provide a definitive answer to the dose-response issue for breast cancer. However, regardless of this trial's ultimate outcome, higher doses of megestrol acetate have demonstrated important new effects on appetite stimulation and weight gain; ongoing laboratory research promises potential roles for megestrol acetate in the reversal of chemotherapeutic drug-induced tumor resistance.

Adult↗
PubMed2001

Adjuvant clodronate treatment does not reduce the frequency of skeletal metastases in node-positive breast cancer patients: 5-year results of a randomized controlled trial.

PURPOSE: Bisphosphonates have effectively reduced the development and progression of bone metastases in advanced breast cancer. The aim of this study was to determine whether bone metastases could be prevented by adjuvant clodronate treatment in patients with primary breast cancer. PATIENTS AND METHODS: Between 1990 and 1993, 299 women with primary node-positive breast cancer were randomized to clodronate (n = 149) or control groups (n = 150). Clodronate 1,600 mg daily was given orally for 3 years. All patients received adjuvant therapy: premenopausal six cycles of CMF chemotherapy and postmenopausal antiestrogens (randomized to tamoxifen 20 mg or toremifene 60 mg/d for 3 years). Seventeen patients were excluded from the analyses because of major protocol violations. The final population was 282 patients. Intent-to-treat analyses were also performed for all major end points. The follow-up time was 5 years for all patients. RESULTS: Bone metastases were detected equally often in the clodronate and control groups: 29 patients (21%) versus 24 patients (17%) (P: = .27). The development of nonskeletal recurrence was significantly higher in the clodronate group compared with controls: 60 patients (43%) versus 36 patients (25%) (P: = .0007). The overall survival (OS) and disease-free survival (DFS) rates were also significantly lower in the clodronate group than in the controls (OS, 70% v 83%, P: = .009; DFS, 56% v 71%, P: = .007, respectively). In multivariate analyses, clodronate remained significantly associated with DFS (P: = .009). CONCLUSION: Adjuvant clodronate treatment does not prevent the development of bone metastases in node-positive breast cancer patients. However, clodronate seems to have a negative effect on DFS by increasing the development of nonskeletal metastases.

Adult↗
PubMed2004

Fulvestrant: a new type of estrogen receptor antagonist for the treatment of advanced breast cancer.

Postmenopausal women with hormone receptor- positive tumors are candidates for endocrine treatment. Current treatment options include the selective estrogen receptor modulators (e.g., tamoxifen and toremifene), which inhibit estrogen receptor signaling, and the aromatase inhibitors (e.g., anastrozole and letrozole), which prevent the conversion of androgens into estrogen in postmenopausal women. As most patients eventually become resistant to endocrine agents, there is a need for new treatments that are effective, well tolerated and lack cross-resistance with currently available therapies. This review describes the development of fulvestrant (Faslodex), a new type of endocrine agent, which is an estrogen receptor antagonist with no agonist effects. Phase III clinical trials have found that fulvestrant is as effective and well tolerated as anastrozole for treating postmenopausal patients with advanced breast cancer who have progressed on one prior endocrine therapy. In addition, fulvestrant has first-line efficacy similar to that of tamoxifen in patients with estrogen receptor-positive and/or progesterone receptor-positive breast cancer. Moreover, in a compassionate-use program, it has become clear that fulvestrant is not cross-resistant with other therapies. Therefore, fulvestrant is a versatile new treatment option for postmenopausal women with advanced breast cancer who have progressed on prior endocrine therapy.

Animals↗
PubMed2006

Lasofoxifene: a new type of selective estrogen receptor modulator for the treatment of osteoporosis.

Selective estrogen receptor modulators (SERMs) are structurally different compounds that interact with intracellular estrogen receptors in target organs as estrogen agonists and antagonists. Thus far SERMs have proven to be a highly versatile group and are being evaluated primarily for conditions associated with aging, including hormone-responsive cancer and osteoporosis. Tamoxifen and toremifene are currently used to treat advanced breast cancer and also have beneficial effects on bone mineral density and serum lipids in postmenopausal women. Raloxifene is the only SERM compound actually approved worldwide for the prevention and treatment of postmenopausal osteoporosis and fragility fractures. Unfortunately, although these SERMs possess many benefits, they are also responsible for some very serious side effects, such as thromboembolic disorders and, in the case of tamoxifen, uterine cancer. These contraindications represent a major concern for the type of long-term, chronic therapy that is required to prevent osteoporosis. Moreover, both preclinical and clinical reports suggest that these SERMs are considerably less potent than estrogen, probably due to their reduced bioavailability. Lasofoxifene (CP 336,156) is a naphthalene-derivative, third-generation SERM, structurally distinct from the first- and second-generation SERMs. This compound selectively binds to both estrogen receptor subtypes (estrogen receptor-alpha or -beta) with high affinity. It has a half-inhibition concentration similar to that seen with estradiol and thus at least 10-fold higher than those reported for raloxifene and tamoxifen. Moreover, due to increased resistance to intestinal wall glucuronidation, lasofoxifene has a remarkably improved oral bioavailability with respect to other SERMs. In both preclinical and short-term clinical studies lasofoxifene has shown a proven efficacy in preventing bone loss and lowering cholesterol levels. Dose modeling from phase II studies allowed the selection of lasofoxifene 0.25 mg/day as the lowest fully effective dose. The compound shows a favorable safety profile and is currently in phase III development for the prevention and treatment of osteoporosis in postmenopausal women.

Animals↗
PubMed1992

[New drugs in endocrine treatment of breast cancer].

Therapeutic access in the treatment of breast cancer with the antiestrogen tamoxifen has been established by world-wide clinical trials since the drug was introduced by Cole et al, in 1971. In recent years, however, a new series of antiestrogens (the derivatives of tamoxifen) such as trioxifene, toremifene and droloxifene have been studied with regard to clinical efficacy as a first-line treatment for postmenopausal patients with breast cancer and occasionally even for patients who previously responded to tamoxifen and then relapsed. Luteinizing hormone releasing hormone (LHRH) agonists are now available for premenopausal patients that will produce a medical castration, when given continuously, by down-regulation of the pituitary LHRH receptors. Four compounds, leuprolide, buserelin, tryptorelin and goserelin have been available for clinical use, but goserelin (Zoladex) is now widely used by long-acting depot preparations, which are given subcutaneously once every 4 weeks. Another series of drugs which inhibit estrogen synthesis in postmenopausal patients and are termed "aromatase inhibitors" have been developed. The pure aromatase inhibitors newly developed include two types of both a steroidal compound (4-hydroxyandrostenedione) and a non-steroidal one which is a tetrahydroimidazopyrimidine derivative (CGS 16949A). This review describes the pharmacological and clinical aspects of these new agents.

Breast Neoplasms↗
PubMed1999

Effects of liver disease on pharmacokinetics. An update.

Liver disease can modify the kinetics of drugs biotransformed by the liver. This review updates recent developments in this field, with particular emphasis on cytochrome P450 (CYP). CYP is a rapidly expanding area in clinical pharmacology. The information currently available on specific isoforms involved in drug metabolism has increased tremendously over the latest years, but knowledge remains incomplete. Studies on the effects of liver disease on specific isoenzymes of CYP have shown that some isoforms are more susceptible than others to liver disease. A detailed knowledge of the particular isoenzyme involved in the metabolism of a drug and the impact of liver disease on that enzyme can provide a rational basis for dosage adjustment in patients with hepatic impairment. The capacity of the liver to metabolise drugs depends on hepatic blood flow and liver enzyme activity, both of which can be affected by liver disease. In addition, liver failure can influence the binding of a drug to plasma proteins. These changes can occur alone or in combination; when they coexist their effect on drug kinetics is synergistic, not simply additive. The kinetics of drugs with a low hepatic extraction are sensitive to hepatic failure rather than to liver blood flow changes, but drugs having a significant first-pass effect are sensitive to alterations in hepatic blood flow. The drugs examined in this review are: cardiovascular agents (angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, calcium antagonists, ketanserin, antiarrhythmics and hypolipidaemics), diuretics (torasemide), psychoactive and anticonvulsant agents (benzodiazepines, flumazenil, antidepressants and tiagabine), antiemetics (metoclopramide and serotonin antagonists), antiulcers (acid pump inhibitors), anti-infectives and antiretroviral agents (grepafloxacin, ornidazole, pefloxacin, stavudine and zidovudine), immunosuppressants (cyclosporin and tacrolimus), naltrexone, tolcapone and toremifene. According to the available data, the kinetics of many drugs are altered by liver disease to an extent that requires dosage adjustment; the problem is to quantify the required changes. Obviously, this requires the evaluation of the degree of hepatic impairment. At present there is no satisfactory test that gives a quantitative measure of liver function and its impairment. A critical evaluation of these methods is provided. Guidelines providing a rational basis for dosage adjustment are illustrated. Finally, it is important to consider that liver disease not only affects pharmacokinetics but also pharmacodynamics. This review also examines drugs with altered pharmacodynamics.

Animals↗
PubMed2003

Tamoxifen: is it safe? Comparison of activation and detoxication mechanisms in rodents and in humans.

Tamoxifen, a non-steroidal antiestrogen, is the class representative of a group of drugs that include toremifene, droloxifene and idoxifene. Tamoxifen has been successfully used worldwide as adjuvant therapy in the treatment of women with breast cancer. However, such therapy results in a slightly increased risk of endometrial cancers. Lifetime exposure of rats to high doses of tamoxifen results in a high incidence of liver tumors. Tamoxifen itself is not genotoxic but is activated in the liver to alpha-hydroxytamoxifen. This is further conjugated to form the sulfate ester as the putative reactive intermediate. Studies with recombinant human CYPs show only CYP3A4 is able to catalyze the formation of alpha-hydroxytamoxifen and the irreversible binding of [(14)C]tamoxifen to DNA. CYP3A4 and CYP2D6 convert tamoxifen to N-desmethyltamoxifen. The formation 4-hydroxytamoxifen is catalyzed by CYP2D6 and at a much lower level by CYP2C19. In women, detoxication of alpha-hydroxytamoxifen via a stable glucuronide occurs at a rate in the order of 100 fold higher than in rats whereas rates of sulfation are 3 fold lower than in rats. These factors, together with the low dose of tamoxifen used therapeutically in women, indicates a minimum risk of liver cancers. Results from (32)P-postlabeling and accelerator mass spectrometry suggest that low levels of uterine DNA binding does occur but this is probably too low to play a role in uterine tumor development and it is more likely to be the estrogen agonist action of this class of drug that is the most important factor in tumor development in humans.

Animals↗
PubMed2006

Controversies in adjuvant endocrine treatment of premenopausal women.

For patients with hormone receptor-positive breast cancer, some form of endocrine therapy is central to the management of their disease. For premenopausal patients in whom estrogen synthesis occurs primarily in the ovaries, current treatment options include ovarian ablation or suppression and selective estrogen receptor modulators such as tamoxifen and toremifene. Ovarian ablation and tamoxifen have demonstrated their effectiveness in the adjuvant setting, reducing the risk of recurrence and death. However, although some studies suggest ovarian ablation results in an equivalent outcome to chemotherapy alone, studies examining the combination have not demonstrated a clear benefit with the addition of ovarian suppression to standard chemotherapy. Results from trials combining ovarian suppression with tamoxifen have also been inconclusive. Finally, although aromatase inhibitors cannot be used as monotherapy in premenopausal patients, the reduction in the risk of recurrence observed with the integration of these agents into adjuvant regimens in postmenopausal patients when compared with the standard 5 years of tamoxifen has stimulated interest in evaluating the combination of ovarian suppression with an aromatase inhibitor in premenopausal women. Several ongoing trials will investigate these combinations as well as ovarian suppression plus tamoxifen.

Adult↗
PubMed1999

[A case of multiple bone metastases from advanced breast cancer effectively treated with pamidronate].

A 57-year-old woman, with bone, lymph node and skin metastases underwent mastectomy and extirpation of skin tumors. Chemoenderine-therapy was performed from the 15th day after operation, with a toremifene and CEF regimen consisting of cyclophosphamide, epirubicin and 5-fluorouracil. She had nausea and neurological symptoms from hypercalcemia (21.5 mg/dl) on the 28th day after operation. Her serum PTHrP level was found to be high at 214 pmol/l. We administered pamidronate in a dose of 45 mg biweekly, and she improved. The CEF regimen and pamidronate therapy was continued for 6 cycles and the regions of bone metastases were reduced on the bone scintography. Thereafter she has been administered pamidronate 30 mg/4 weeks as an outpatient with no further symptoms, and serum Ca and PTHrP have remained normal. In conclusion, pamidronate combined with chemotherapy can be a therapeutic option for not only hypercalcemia but also bone metastases of breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

[A case of hepatic arterial infusion chemotherapy with docetaxel for liver metastasis from breast cancer].

We experienced a case of hepatic arterial infusion chemotherapy using docetaxel for liver metastasis, which showed no response to CEF therapy, from breast cancer. A 63-year-old woman had undergone modified radical mastectomy for right breast cancer (T2aN1bM0: Stage II) in October, 1995. Six-cycle CMF therapy and toremifene citrate (40 mg/day) were administered as adjuvant therapy, but multiple recurrent tumors in liver, lung, and local site were detected in February 1997. Six-cycle CEF therapy was given for recurrent disease and there was a complete response for lung and local recurrence, but no change in liver metastasis. Chemoendocrine therapies using 5'-DFUR or CMitF in addition to TAM and fadrozole hydrochloride hydrate had developed progressive disease for liver metastasis. A catheter and port kit were operatively inserted and implanted in March 1998. Hepatic arterial infusion of docetaxel (30-40 mg/body/month, one hour administration) was repeated 4 times, once in our clinic. Leukopenia, general fatigue and fever, which were mild and did not require any treatment, appeared as side effects. This treatment reduced multiple liver metastatic sites on abdominal CT finding and was thought to be a partial response. However, the patient had multiple brain metastasis and died on August 2, 1998. While docetaxel, even by systemic administration, has a 36-77% response rate for liver metastasis, arterial infusion might have a good response and mild side effect with a lower dose than by intravenous administration.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Estrogen receptors in human myeloma cells.

It has recently been reported that the human myeloma cell line U266 proceeds to undergo apoptosis after cultivation with the antiestrogen tamoxifen, thus raising the possibility that antiestrogens may be candidates for use in myeloma therapy. To obtain basic information on the effects of antiestrogens on myeloma cells, we investigated the mRNA expression levels of estrogen receptor (ER)-alpha, ER-beta, and coactivators and corepressors in nine human myeloma cell lines and compared them with those of seven human breast cancer cell lines including four ER-positive and three ER-negative lines. The alterations in cell growth and mRNA expression of the target genes of ER or those of cytokines in the myeloma lines by estradiol or antiestrogens (tamoxifen and toremifene) were also investigated. In addition, effects on membrane Fas expression, appearance of apoptosis, and cell cycle perturbation were analyzed. It was revealed that ER-beta and corepressors were dominantly expressed in myeloma cells, and antiestrogens induced growth inhibition through apoptosis mediated by a Fas-related pathway and G1 arrest of the cell cycle in myeloma cell lines.

Antineoplastic Agents, Hormonal↗