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PubMed1993

The estrogenic and antiestrogenic activities of droloxifene in human breast cancers.

The effects of a new antiestrogen, droloxifene (DROL, (E)-alpha-[p-[2-(dimethylamino)ethoxy]-phenyl]-alpha'-ethyl-3- stilbenol), on human breast cancer cells in vitro and in vivo were studied. Since phenol red has a binding affinity to the estrogen receptor (ER), we studied the activities of drugs in medium with or without this indicator. Estradiol-17 beta (E2) stimulated the growth of ER-positive breast cancer cells, MCF-7, ZR-75-1 and T-47D, in medium without phenol red, but not in medium containing this indicator. In medium without phenol red, DROL had no marked effects on the growth of MCF-7 and ZR-75-1, but slightly stimulated the growth of T-47D. Tamoxifen (TAM) stimulated the growth of these 3 cells. DROL dose-dependently inhibited the E2-induced stimulation of growth of these cells in medium without phenol red, but TAM inhibited the growth only at high concentrations. The growth of ER-negative breast cancer cells, MDA-MB-231, was not influenced by E2, DROL or TAM. DROL was more effective than TAM against ER-positive Br-10 breast carcinoma in nude mice, but neither drug had effects on ER-negative MX-1 breast carcinoma. These results suggest that DROL shows an antitumor effect on ER-positive breast cancers, being less estrogenic and more antiestrogenic than TAM.

Animals↗
PubMed2003

The effects of tamoxifen and toremifene on bone cells involve changes in plasma membrane ion conductance.

Selective estrogen receptor modulators (SERMs), tamoxifen (Tam) and toremifene (Tor), are widely used in the treatment of breast cancer. In addition, they have been demonstrated to prevent estrogen deficiency-induced bone loss in postmenopausal women. These effects are thought to be caused by the interaction of the SERMs with the estrogen receptor, although SERMs have also been shown to conduct non-receptor-mediated effects such as rapid changes in membrane functions. We compared the effects of Tam, Tor, and 17beta-estradiol (E2) on the viability of rat osteoclasts and osteoblasts. Both Tam and Tor were found to cause osteoclast apoptosis in in vitro cultures, which was reversed by E2. In addition, at higher concentration (10 microM), both SERMs had an estrogen receptor-independent effect, which involved interaction with the plasma membrane as demonstrated with UMR-108 osteosarcoma cells by Tam and Tor, but not E2. A leak of protons leading to changes in intracellular pH was shown both in medullary bone derived membrane vesicles and in intact cells. These effects were followed by a rapid loss of cell viability and subsequent cell lysis. Our results show that both Tam and Tor have an ionophoric effect on the plasma membranes of bone cells and that these SERMs differed in this ability: Tor induced rapid membrane depolarization only in the presence of high concentration of potassium. These non-receptor-mediated effects may be involved in therapeutic responses and explain some clinical side effects associated with the treatment of patients with these SERMs.

Animals↗
PubMed2004

The interaction of oestrogen receptor status and pathological features with adjuvant treatment in relation to survival in patients with operable breast cancer: a retrospective study of 2660 patients.

The oestrogen receptor (ER) status of 2660 patients with primary breast cancer has been related to the effect of different adjuvant systemic therapies on survival. However, as patients in the various treatment groups also had different prognostic features comparison between treatments was difficult. Over 90% of patients receiving tamoxifen (Tam) were postmenopausal compared with <20% of those receiving chemotherapy (CT). The latter had more positive nodes (85% vs 54%) and grade III tumours (54% vs 30%) than the Tam group. The combined CT and Tam group had similar characteristics to the CT alone group. The current reported increase in the proportion of women with ER+ tumours is explained by immunohistochemical analysis of ER and screening programmes. ER status was unrelated to survival in patients with small, low grade, node-negative tumours which was no different from that expected for age-matched women taken from the general population. The value of adjuvant treatment in these patients is therefore questionable. In those given any adjuvant treatment, survival of women with ER+ tumours was prolonged, with the greatest effect being seen in those receiving Tam. Patients with ER- tumours benefited from CT but the addition of Tam to CT improved survival only in those with ER+ tumours. ER status is now established as a major predictive factor for treatment selection in primary disease. Studies of prognostic and predictive markers may be invalidated by use of adjuvant therapy and selection criteria for different treatments. Survival will be influenced by both tumour biology and therapy. This important consideration must be remembered when analysing new markers, particularly in small studies.

Breast Neoplasms↗
PubMed1998

Preparation and evaluation of beads made of different calcium alginate compositions for oral sustained release of tiaramide.

This study was undertaken to develop a sustained-release formulation of tiaramide (TAM), a non-steroidal anti-inflammatory drug with a short half-life, using alginate of different chemical compositions. Alginate gel beads containing TAM were prepared using a gelation of alginate with calcium cations. Bead performance was evaluated in vitro for different dissolution media and beads were also subjected to coating. TAM release was dependent both on its solubility in dissolution medium and the guluronate residue content of the alginate used. The release rate was in the following order: in pH 1.2 > pH 6.8 > water. The fast release rate in pH 1.2 is the result of the high solubility of TAM in acidic medium. Beads based on alginate rich in guluronate residue had the lowest release rate, which can be attributed to the compact structure formed by guluronate residues through cooperative interaction with calcium ions. Alginate beads were administered to beagle dogs, and pharmacokinetic parameters (mean residence time [MRT], tmax, Cmax, and AUC) were calculated. In vivo results were in good agreement with in vitro dissolution characteristics. Beads with high guluronate content gave the best controlled results. In addition, coated beads showed a more satisfactory sustained-release pattern. Calcium alginate appears to be a potential carrier for controlling drug release rate, even for water-soluble drugs such as TAM.

Administration, Oral↗
PubMed2003

Efficacy of passive sand filtration in reducing exposure of salmonids to the actinospore of Myxobolus cerebralis.

The aquatic oligochaete Tubifex tubifex parasitized by Myxobolus cerebralis releases triactinomyxon (TAM) actinospores that can infect some species of salmonids and cause salmonid whirling disease. Silica sand was tested as a filtration medium for removal of TAMs from water containing the parasite. Laboratory tests indicated sand filtration removed > 99.99% of TAMs. In 2 different field tests, groups of 1 mo old rainbow trout Oncorhynchus mykiss were exposed for 2 wk to filtered and unfiltered water from a spring-fed pond enzootic for M. cerebralis. In November 2000, the exposure dose was estimated as between 3 and 5 TAMs fish(-1). During a March 2001 exposure, the estimated dose was between 286 and 404 TAMs fish(-1). Fish were held for 6 mo post exposure (p.e.) in laboratory aquaria for observation and evidence of clinical signs of whirling disease. We used 4 diagnostic techniques to assess the prevalence and severity of infection by M. cerebralis among fish exposed to filtered and unfiltered water. These included polymerase chain reaction (PCR) for genomic DNA of the parasite, histological evaluation for tissue damage, tissue digestion for quantification of cranial myxospores of the parasite, and total non-sampling mortality that occurred over 6 mo p.e. All diagnostic tests verified that the prevalence and severity of infection was significantly reduced among fish in treatment groups exposed to filtered water compared to those exposed to unfiltered water in both the low-dose and high-dose exposures.

Animals↗
PubMed2005

Significance and relationship between infiltrating inflammatory cell and tumor angiogenesis in hepatocellular carcinoma tissues.

AIM: To investigate the relationship between infiltrating inflammatory cell and tumor angiogenesis in hepatocellular carcinoma (HCC) tissues and their clinicopathological features. METHODS: The paraffin-embedded specimens from 70 cases with HCC were stained using EliVision immunohistochemistry with mAbs against CD68, tryptase, and CD34. The counts of tumor-associated macrophage (TAM), mast cell (MC) and tumor microvessel (MV) were performed in the tissue sections. RESULTS: The mean counts of TAM, MC, and MV in HCC tissues were significantly higher than those in pericarcinomatous liver tissues (TAM: 69.31+/-11.58 vs 40.23+/-10.36; MC:16.74+/-5.67 vs 7.59+/-4.18; MV: 70.11+/-12.45 vs 38.52+/-11.16, P<0.01). The MV count in the patients with metastasis was markedly higher than that with non-metastasis (P<0.01). In addition, the MC count in the patients with poorly differentiated HCC was obviously higher than that with well differentiated HCC (P<0.01). The correlation analysis showed that the TAM count was significantly correlated with the count of MV (r=0.712, P<0.01), and the MC count was obviously correlated with the MV count (r=0.336, P<0.05). CONCLUSION: TAM and MC might be closely related to the enhancement of tumor angiogenesis. The MV count might be associated with tumor invasion and metastasis. Moreover, the MC count might be associated with tumor differentiation and prognosis of HCC.

Adult↗
PubMed2000

Promising results with exemestane in the first-line treatment of metastatic breast cancer: a randomized phase II EORTC trial with a tamoxifen control.

Because tamoxifen (TAM), a nonsteroidal antiestrogen, is routinely used in the adjuvant setting, other hormone therapies are needed as alternatives for first-line treatment of metastatic breast cancer (MBC). Currently, exemestane (EXE) and other antiaromatase agents are indicated for use in patients who experience failure of TAM. In this multicenter, randomized, open-label, TAM-controlled (20 mg/day), phase II trial, we examined the activity and tolerability of EXE 25 mg/day for the first-line treatment of MBC in postmenopausal women. Exemestane was well tolerated and demonstrated substantial first-line antitumor activity based on intent-to-treat analysis of peer-reviewed responses. In the EXE arm, values for complete, partial, and objective response, clinical benefit, and time to tumor progression (TTP) exceeded those reported for TAM although no statistical comparison was made. Based on these encouraging results, a phase III trial will compare EXE and TAM.

Administration, Oral↗
PubMed1998

Effects of short-term pre-operative tamoxifen on steroid receptor and Ki-67 expression in primary breast cancer: an immunocytochemical study.

The effects of the short-term pre-operative administration of tamoxifen (TAM, 20 mg once daily) on the tumor levels of steroid receptors and the nuclear proliferation Ki-67 antigen, were investigated in 32 elderly patients with hormone-sensitive, operable primary breast cancer by means of fine-needle aspiration biopsy (FNAB). The FNAB smears before (pre-TAM) and after six weeks of treatment (post-TAM) were stained immunocytochemically in order to obtain an H-score for steroid receptors, and the percentage of cellular nuclei containing Ki-67. The mean oestrogen receptor (ER) score between the pre- and post-TAM specimens fell from 181.2 9.7 ( SEM) to 148.1 7.9 (Wilcoxon's matched-pairs signed-rank test, p=0. 01) and there was also a significant decrease in both the mean progesterone receptor (PgR) score (178.4 10.6 vs 148.5 10.6; p=0.01) and mean Ki-67 index (8.2% 1.2 vs 4.9% 0.9; p=0.0002). The reliability of FNAB as a sampling method was checked by comparing the results of the immunocytochemical assay (ICA) of the post-TAM biopsies with those of the immunohistochemical assay (IHA) of the corresponding excised tumors. There was a positive correlation between the ICA and IHA scores: ER (Spearman's correlation coefficient, rho=0.66, p<0.001), PgR (rho=0.84, p<0.001) and Ki-67 (rho=0.96, p<0.001). We conclude that the sequential use of FNAB is a reliable means of assessing the behaviour of within-tumor biomarkers during endocrine therapy.

Aged↗
PubMed2001

Blood monocytes and tumor-associated macrophages in human cancer: differences in activation levels.

This study was performed to investigate functional properties of mononuclear phagocytes isolated from ascitic fluid in patients with peritoneal carcinomatosis (PC), and potential immunomodulatory effects of soluble factors produced or induced by human metastatic malignant cells. Phagocytic activity and nitric oxide production of peripheral blood monocytes (PBMo) and tumor-associated macrophages (TAM) or peritoneal macrophages (PEM) were synchronously examined in cancer patients and control individuals. Our results showed that contrary to peripheral blood monocytes, where phagocytic activity was not altered, TAM had impaired phagocytic activity. Moreover, dilutions of crude supernatant from short-term cultures of the peritoneal cells obtained from ascitic fluid of patient with PC, cause a significant, dose dependent inhibition of control PBMo and PEM phagocytosis, comparable to those in TAM, indicating that a soluble factor(s) plays a prominent role in this alteration. Next, we investigated the potential of cancer patients mononuclear phagocytes to produce nitric oxide (NO). It was found that TAM produce fourfold lower levels of NO than PEM from control subject, whereas monocytes produce NO at levels comparable to those of corresponding controls. These data support the hypothesis that depressed TAM function may contribute to the mechanisms of tumor escape from immune destruction.

Adjuvants, Immunologic↗
PubMed2002

Mutations in HIV-1 reverse transcriptase during therapy with abacavir, lamivudine and zidovudine in HIV-1-infected adults with no prior antiretroviral therapy.

OBJECTIVE: To evaluate HIV-1 reverse transcriptase (RT) drug resistance in patients receiving abacavir, lamivudine and zidovudine therapy. METHODS: In a randomized, double-blind study, 173 antiretroviral treatment-naive HIV-1-infected adults received abacavir/lamivudine/zidovudine or lamivudine/zidovudine for up to 48 weeks. After week 16, patients could switch to open-label abacavir/lamivudine/zidovudine, and those with plasma HIV-1 RNA (vRNA) > 400 copies/ml could add other antiretrovirals. From weeks 11 to 48, samples with vRNA > 400 copies/ml were collected for genotyping and phenotyping. RESULTS: At baseline, 90% of isolates were wild-type (WT). At week 16, vRNA was > 400 copies/ml in seven of 72 (10% patients receiving abacavir/lamivudine/zidovudine and in 41 of 66 (62%) receiving lamivudine/ zidovudine. At week 16, the genotypes in isolates from the abacavir/lamivudine/zidovudine group were M184V alone (n = 3 cases), WT (n = 3) and M184V plus thymidine analogue mutations (TAMs) (n = 1). The genotypes in isolates from the lamivudine/zidovudine group were M184V alone (n = 37), WT ( n= 1) and M184V plus TAMs (n = 3). In the four cases where M184V plus TAMs were detected some mutations were present at baseline. Despite detectable M184V in 74% of patients on lamivudine/zidovudine, addition of abacavir with or without another antiretroviral therapy resulted in a reduction in vRNA, with 42 of 65 (65%) patients having week 48 vRNA < 400 copies/ml (intent-to-treat with missing = failure). At week 48, the most common genotype was M184V alone in the abacavir/ lamivudine/zidovudine group (median vRNA 1-2 log,10 below baseline), and M184V with or without TAMs in patients originally assigned to lamivudine/zidovudine. At week 48, phenotypic results were obtained for 11 isolates for patients from both arms, and all had reduced susceptibility to lamivudine but all remained sensitive to stavudine, all protease inhibitors and all non-nucleoside reverse transcriptase inhibitors. Three, three and two isolates had reduced susceptibility to abacavir, didanosine and zidovudine, respectively. CONCLUSIONS: Abacavir retained efficacy against isolates with the M184V genotype alone. TAMs did not develop during 48 weeks of abacavir/lamivudine/zidovudine therapy and were uncommon when abacavir was added after 16 weeks of lamivudine/zidovudine therapy. Limited mutations upon rebound on this triple nucleoside combination allows for several subsequent treatment options.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Role of tumor-associated macrophage in malignant tumors: should the location of the infiltrated macrophages be taken into account during evaluation?

Tumor-associated macrophages (TAMs) have a complex relationship with the tumor cells. Because TAMs have various functions according to the microenvironment, the results of many analyses have not led to a general consensus regarding the role of TAMs in solid tumor tissue and the prognostic significance for patients. In this review, we discuss whether the recently published data can help to explain the apparent paradoxical effects of TAMs in cancers. We address this question on the basis of the histological location of TAMs in solid malignant tumors.

Animals↗
PubMed2003

Glivec enhances the down-regulated cytotoxicity of adriamycin in acquired tamoxifen-resistant MCF-7 cell line.

OBJECTIVE: To study the alteration of bax, bcl-2, p170 expressing and the second effect on the adriamycin (ADR) induced cytotoxicity in acquired tamoxifen (TAM)-resistant MCF-7 cell line. METHODS: The bax, bcl-2, p170 protein expressions were detected by flow cytometry respectively, as well as the content of intracellular ADR. The in vitro adenosine triphosphate tumor chemosensitivity assay (ATP-TCA) was performed to evaluate the cytotoxicity of ADR, and also the effect of Glivec on the cytotoxicity of ADR. RESULTS: The percentages of bax, bcl-2 expressions in the acquired TAM resistant MCF-7 were down-regulated from 53.17+/-1.45% to 28.70+/-1.41% (P <0.01), 41.53+/-2.17% to 37.87+/-1.86% P >0.05 respectively, the p170 was up-regulated from 27.43+/-2.16% to 32.13+/-1.31% (P <0.05), after a 16-week-treatment with 1 x 10(-7) mol/L TAM. Accordingly, the chemosensitivity and the fluorescence intensity of intracellular ADR declined, both of them can be significantly reversed by 10 microg/ml Glivec. CONCLUSION: The acquired TAM resistant MCF-7 accompanied with a declined ADR cytotoxicity, down-regulation of bcl-2/bax-induced apoptosis and up-regulation of p170-induced drug efflux may had a synergic devotion. Glivec may enhance the cytotoxicity of ADR on the acquired TAM-resistant MCF-7 cell line.

ATP Binding Cassette Transporter, Subfamily B↗
PubMedDate not supplied

Growth effects of tamoxifen on Lovo colon carcinoma cells and cultured cells from normal colonic mucosa.

The growth effects of tamoxifen (TAM) were studied using normal and malignant colonic epithelial cells. Addition of TAM (0.8 to 10 microM) to cultured normal human colon epithelial cells and Lovo colon adenocarcinoma cells produced a dose response decrease in growth of 42 to 76%. Histamine (1 to 10 microM) did not affect cell growth and did not negate the TAM effect. Calmodulin (2 micrograms/ml) totally blocked growth inhibitory effects of a calmodulin antagonist, trifluoperazine (10 microM), but did not block the TAM inhibitory effect. These data suggest that antiestrogen binding sites (AEBS) may play an important role in the growth-inhibitory effects of TAM on colon cells. Competition with estrogen and antagonism with histamine or calmodulin do not appear to be significant in this regard.

Adenocarcinoma↗
PubMedDate not supplied

Synergistic cytotoxic effects of tumor necrosis factor, interferon-gamma and tamoxifen on breast cancer cell lines.

The combined effects of recombinant human tumor necrosis factor (TNF), interferon-gamma (IFN) and tamoxifen (TAM) on the proliferation of human breast cancer cell lines were investigated. In estrogen receptor positive MCF-7 cells, relatively resistant to TAM or TNF, cytotoxicity significantly increased in combinations of TNF and IFN, and of a cytokine and TAM. The cytotoxicity of TNF increased when cells were pretreated with IFN, but not vice versa. Sequential treatment with IFN following TNF and TAM also exhibited significant antiproliferative effect on both cell lines. The combined or sequential cytokines and TAM treatments are possible modalities to overcome breast cancers unresponsive to endocrine treatment.

Antineoplastic Agents↗
PubMed2003

Comparison of the selective estrogen receptor modulator arzoxifene (LY353381) with tamoxifen on tumor growth and biomarker expression in an MCF-7 human breast cancer xenograft model.

Arzoxifene (ARZ) is a selective estrogen receptor (ER) modulator with greater bioavailability than raloxifene which is being developed as treatment for breast cancer. We have used an in vivo model of hormone-sensitive breast cancer to study the growth-inhibitory and pharmacodynamic effects of ARZ in comparison with the most widely used antiestrogen, tamoxifen (TAM). We compared the abilities of ARZ and TAM to antagonize the estrogen (E2)-dependent growth of MCF-7 human breast cancer xenografts in oophorectomized athymic mice. At four different time points over 28 days, we studied their time-related pharmacodynamic effects on biomarkers of tumor growth (cell proliferation/death measured by Ki-67 and apoptosis scores), cell cycle activity (cyclin D1 and p27(kip1)), and hormone-regulated gene expression (ERalpha, progesterone receptor, and pS2). Although maximal growth inhibition was seen after E2 withdrawal, ARZ and TAM induced significant and similar inhibition of E2-stimulated tumor growth. Inhibition of growth was reflected by changes in the tumor growth index (ratio posttreatment/pretreatment Ki-67/apoptosis scores). ARZ and TAM resulted in a significant (P < 0.001) increase in ER expression and reduction in progesterone receptor expression, whereas changes in cyclin D1 score were inversely related to p27(kip1) score. A significant but delayed biological effect was observed with a 10-fold lower dose of ARZ. These results show that ARZ is an effective antagonist of E2-stimulated breast cancer growth with similar growth-inhibitory and pharmacodynamic effects to TAM in this model.

Animals↗
PubMed2003

Tamoxifen combined with octreotide or regular chemotherapeutic agents in treatment of primary liver cancer: a randomized controlled trial.

OBJECTIVE: To evaluate the effect of tamoxifen (TAM) combined with a somatostatin analogue, octretide (OCT) on advanced liver cancer and whether tamoxifen combined with OCT is superior to regular chemotherapeutic agents 5-Fu and mitomycin C (MMC). METHODS: Thirty-nine patients with inoperable liver cancer were randomly subdivided into TAM+OCT group (n=24) and regular chemotherapeutic group (n=15). They received treatment for three months respectively. Blood cell count, liver function, immunologic function, blood alpha-FP was regularly measured. Liver lump and extrahepatic metastasis were examined by CT. The patients were followed up after treatment and conducted survival analysis. RESULTS: In the TAM+OCT group, complete response is 4 patients, partial response is 7 patients, no change is 9 patients and progressive disease is 4 patients; blood level of ALT and AST had no noticeable change, IgE and IgG increased (P<0.01), and alpha-FP lowered (P<0.05). In regular chemotherapeutic group, no change is 4 patients and progressive disease is 11 patients. There was conspicuous statistical difference in the two groups. The accumulative survival rates of 6 months, 1 year and 2 years were 95.7% vs 41.2% (P<0.01), 63.7% vs 21.1% (P<0.01), 25.4% vs 0 (P<0.01), respectively. Medium survival time was 12.8 months in TAM+OCT group and 5.5 months in chemotherapeutic group. CONCLUSIONS: TAM+OCT excerts reliable therapeutic effect on patients with inoperable ER(+) hepatocellular cancer. It is superior to 5-Fu and MMC in increasing the survival rate, prolonging survival time, and reducing side-effects.

Adult↗
PubMed2004

Expression of p65 gene in experimental colon cancer under the influence of 5-fluorouracil given alone and in combination with hormonal modulation.

The effect of tamoxifen (TAM), lanreotide (LAN) and 5-fluorouracil (5-FU), given separately or together, on p65 gene expression in murine Colon 38 cancer was investigated by RT-PCR method. The findings were compared with cell proliferation determined by bromodeoxyuridine (BrdU) labeling index, apoptosis visualized by TUNEL method and tumor mass. It was found that in the control group (mice bearing colon cancer without treatment) the expression of p65 gene was present in 57% of investigated samples. In the groups treated with TAM or LAN p65 gene expression was detected in 87.5% and 83.3% of analyzed cases, respectively. Both these substances increased apoptotic index in Colon 38 cancer and LAN also decreased the proliferation index. After a combined treatment with TAM and LAN a percentage of p65 positive cases was similar to that of the control group and equaled approximately 60%. This treatment did not increase proapoptotic effects of these drugs, and even reduced the antiproliferogenic effect of LAN. In the group treated with 5-FU and LAN p65 gene expression was also close to the control value (about 66%). Similarly in this group the combined treatment with these two drugs did not cause any favorable effect on proliferation and apoptosis. Moreover, in this group even reduced antiproliferogenic effect of LAN was observed. In the group with 5-FU alone the expression of p65 was present in about 80% of samples. The treatment with 5-FU increased apoptotic index and did not change proliferation. In the group treated with a combination of TAM and 5-FU all analyzed cases showed the presence of p65 gene expression. Previously, we observed in this group the most pronounced and synergistic effect of these substances on the inhibition of cell proliferation and tumor mass reduction. Based on these findings we conclude that p65 gene expression in murine Colon 38 cancer tissues can be modulated via chemotherapy (5-FU) and also via hormonal modulation (TAM and LAN).

Animals↗
PubMed1992

[Experimental study of combination medical endocrine therapy on DMBA-induced mammary tumor, with special reference to the effect of drug-dose on various factors].

Changes of various factors associated with the antitumor effect of medroxyprogesterone acetate (MPA) and tamoxifen (TAM) against the DMBA-induced mammary tumor in rats were studied. Tumor bearing SD rats were divided into control group and experimental groups, consisting of single therapy group and combination therapy groups; TAM----MPA (T----M) group and MPA----TAM (M----T) group. A much higher degree of suppression of tumor growth was observed in the combination groups than in the single group. A significant reduction of spleen weight was observed in all of the experimental groups. The reduction of ER-expression in mammary tumor was observed in MPA groups (M, T----M) and in TAM groups (T, M----T), whereas the reduction of PgR was seen in two kinds of combination groups. The serum level of luteinizing hormone was decreased in M, but not in the combination groups. No change was observed in the percentage of pan T, CD4+ and CD8+, T cell subsets, except Thy 1+T cell was decreased depending on the MPA dose. In the combination group, using high dose MPA, the reduction of the degree of inflammatory cell infiltration into the adenocarcinomatous foci was observed immunohistochemically. These findings indicate that the combination medical endocrine therapy for mammary tumor might be much more effective for the tumor regression than single use, without inducing any detectable side effects on either hormonal or immune systems, when a low dose of MPA less than 1.5 mg/100g B.W. was combined with TAM.

9,10-Dimethyl-1,2-benzanthracene↗