Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “TAM”

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 721 records · Page 40Linked to original sources
PubMed1996

Postoperative adjuvant randomised trial comparing chemoendocrine therapy, chemotherapy and immunotherapy for patients with stage II breast cancer: 5-year results from the Nishinihon Cooperative Study Group of Adjuvant Chemoendocrine Therapy for Breast Cancer (ACETBC) of Japan.

Between 1985 and 1988, the effect of using ftorafur (FT) or PSK (an immunotherapy agent) in combination with the conventional postoperative adjuvant therapy using mitomycin (MMC) plus tamoxifen (TAM) was assessed in stage II, oestrogen receptor-positive (ER+) breast cancer patients. Furthermore, in ER- breast cancer stage II patients, the effects of postoperative adjuvant therapy using MMC plus FT were compared with the effects of postoperative adjuvant therapy using MMC plus PSK. Patients had primary stage II breast cancer and had undergone total mastectomy plus axillary dissection or more radical surgery. On the day of surgery, MMC (13 mg/m2) was administered intravenously. Then, ER+ patients received one of three regimens of drug therapy, starting 2 weeks after surgery: regimen A (daily oral treatment with 30 mg of TAM), regimen B (daily oral treatment with 30 mg of TAM and 600 mg of FT) or regimen C (daily oral treatment with 30 mg of TAM and 3 g of PSK) [corrected]. ER- patients received either regimen D (daily oral treatment with 600 mg of FT) or regimen E (daily oral treatment with 3 g of PSK), starting 2 weeks after surgery. Of the 540 ER+ patients registered, 525 were evaluated. The 5-year overall survival rate for ER+ patients was higher for patients who received regimen B (94.2%) than for those who received regimen A (86.9%) or regimen C (89.9%) (P = 0.063). The 5-year relapse-free survival rate was higher for regimen B (88.9%) than for regimen A (78.6%) and regimen C (77.2%) (P = 0.010). Stratified analysis revealed better results with the FT-combined therapy in patients positive for lymph node metastasis and premenopausal patients. These results indicate the effectiveness of using FT in combination with TAM. Of the 376 ER- patients registered, 364 were evaluated. The 5-year overall and relapse-free survival rate for ER- patients did not differ significantly between patients who received regimen D and those who received regimen E.

Adult↗
PubMed1990

Displacement by tamoxifen of the estradiol-estrogen receptor binding: a functional assay for breast cancer studies.

Displacement curves with estradiol (E2) and Tamoxifen (Tam) of the [3H]E2-ER binding in 49 ER+ mammary neoplasia showed a great heterogeneity suggesting the existence of more than one population of ER+ tumors when the relative binding affinity of both ligands for the ER was considered. The (D50E2/D50Tam) x 100 ratio was called Displacement Index (DI) with values asymmetrically distributed from 0.05 to 2.90. The range from 0.18 to 0.54 was adopted as central interval given by the median +/- SE (median: 0.36; SE: 0.09). DI values below 0.18 (24% of the tumors in our series) were considered as "lower", indicating that higher Tam doses would be necessary to displace the E2-ER binding. The potency of Tam as displacer is dependent not only of its own affinity for the ER, but also of that of E2 for the same receptor. The DI expresses their relative binding "strength". DI values were not correlated with ER and progesterone receptor content nor with the D50 Tam and D50E2 taken separately. Antiestrogen binding sites (AEBS) were determined in the cytosol (AEBSc) and in the microsomal fraction of 10 ER+ tumors from our series. The AEBSc/ER ratio was inversely correlated with the DI, that is, displacement of 3HE2 from the E2-ER complex by Tam would be lower in tumors with higher AEBSc/ER ratio. The DI is another parameter to be considered in the study of the sensitivity of breast neoplasias to antiestrogen treatments.

Breast Neoplasms↗
PubMed2006

Chronic exposure to estrogen and tamoxifen regulates synaptophysin and phosphorylated cAMP response element-binding (CREB) protein expression in CA1 of ovariectomized rat hippocampus.

We report here the in vivo effects of estrogen (E2) on modulation of synaptic plasticity and the agonistic (estrogen-like) role of selective estrogen receptor modulator (SERM), tamoxifen (TAM) in the CA1 of the rat hippocampus. Effects on synaptophysin (SYP), a presynaptic vesicular protein, and phosphorylated cyclic AMP responsive element-binding (p-CREB) protein, a signal transduction pathway molecule, were studied using the ovariectomized (OVX) experimental rat model. Bilateral ovariectomy was performed on 40 rats and these were divided into 4 groups based on the treatment they received (at 2 weeks post-ovariectomy, a subcutaneous injection daily for 4 weeks) viz., OVX+E2 (0.1 mg/kg body weight), OVX+TAM (0.05 mg/kg body weight), OVX+vehicle and one group served as OVX control. An additional 10 animals served as the ovary intact control group. At the end of the treatment schedule, five animals/group were used for immunohistochemical staining of SYP and p-CREB using specific antibodies with peroxidase anti-peroxidase technique on paraformaldehyde-fixed cryostat sections. Protein estimation and Western blot analysis coupled with densitometric analysis (using gel-documentation system and image analysis software) were performed on unfixed hippocampus collected from rest of the five animals/group. Serum estradiol levels were estimated with radioimmunoassay prior to sacrifice. The results revealed that ovariectomy reduced SYP and p-CREB expression whereas E2 or TAM administration resulted in their upregulation. Serum estradiol levels of E2 administered animals were comparable with the ovary intact group whereas those of TAM administered group persisted in the range of OVX controls. To conclude, long-term estrogen therapy modulates the synaptic plasticity of hippocampal neurons and presumably, the agonist biocharacter of TAM as observed in the present investigations, may in the long run have a potential in the treatment and prevention of various estrogen-related disorders.

Animals↗
PubMed2006

The role of tamoxifen in combination with cisplatin on oral squamous cell carcinoma cell lines.

The purpose of this study was to evaluate the effect of tamoxifen (TAM) when used in combination with cisplatin on oral squamous cell carcinoma (OSCC). For this, the relation between estrogen receptor (ER) expression level and the cytotoxic effect of TAM, the apoptotic effect and its molecular mechanisms of TAM were investigated using OSCC cell lines. Combination treatment demonstrated a superior cytotoxic and apoptotic effect on OSCC cell lines. Considerable amount of ER was detected in some OSCC cell lines, but there were no significant differences of cytotoxic effect of TAM. TAM inhibited PKC activity and up-regulated TGF-beta1 secretion.

Antineoplastic Agents↗
PubMed2004

Differences in the hepatic P450-dependent metabolism of estrogen and tamoxifen in response to treatment of rats with 3,3'-diindolylmethane and its parent compound indole-3-carbinol.

Indole-3-carbinol (I3C), present in cruciferous vegetables, and its major in vivo product 3,3'-diindolylmethane (DIM), have been reported to suppress estrogen-responsive cancers. This effect may be mediated through the modification of cytochrome P450 (CYP) complement and activities leading to estrogen detoxification. We examined the effects of a 4-day treatment of female Sprague-Dawley rats with DIM at 8.4 and 42 mg/kg body weight (bwt), on the hepatic CYP protein level, CYP1A1, 1A2, 2B1/2 and 3A1/2 probe activities and CYP-dependent metabolism of 17beta-estradiol (E2) and estrone (E1). At 42 mg/kg bwt, DIM effected a small increase (2.8-fold) in CYP1A1 activity, and at both dose levels it reduced CYP3A1/2 activity by approximately 40%. At the higher dose level, DIM decreased the rates of oxidation of E2 to 4-OH-E2, 4-OH-E1, 6alpha-OH-E2 and 6(alpha+beta)-OH-E1 by 39, 44, 71 and 60%, respectively, and E1 to 6(alpha+beta)-OH-E1 by 39%. These effects were considerably different from those of I3C reported by us previously. We also examined the effects of DIM and I3C on the hepatic microsomal metabolism of tamoxifen (TAM). Whereas metabolism of TAM was unaffected by DIM, formation of N-desmethyl-TAM (and its presumed derivative) was increased approximately 3-fold by I3C at 250 mg/kg bwt. Since N-desmethyl-TAM is transformed to a genotoxic metabolite, dietary exposure to I3C may enhance hepatic carcinogenicity of TAM in the rat. The differences between I3C and DIM in CYP-mediated activities and metabolism indicate that DIM is not a proximate intermediate in the mechanism of action of I3C.

Analysis of Variance↗
PubMed2005

Bioenhancement of cadmium transfer along a multi-level food chain.

Previous studies have shown that metal partitioned to a subcellular compartment containing trophically available metal (TAM) is readily available to predators and may be enhanced by increased binding of metal to heat-stable proteins (HSP - e.g., metallothioneins). The aim of the current investigation was to determine the influence of TAM on the trophic transfer of Cd along an experimental, three-level food chain: Artemia franciscana (brine shrimp)-->Palaemonetes pugio (grass shrimp)-->Fundulus heteroclitus (mummichog). P. pugio were fed for 7 days on A. franciscana exposed to Cd in solution (including (109)Cd as radiotracer) and subjected to subcellular fractionation or fed to F. heteroclitus. An HSP-driven increase in the percentage of Cd associated with TAM (TAM-Cd%) in A. franciscana exposed to 1 muM Cd resulted in a bioenhancement (i.e., a greater than linear increase with respect to A. franciscana exposure) of Cd trophic transfer to P. pugio. Increased dietary Cd exposure did not affect TAM-Cd% in P. pugio nor trophic transfer to F. heteroclitus.

Animals↗
PubMed2006

Neural correlates of transformational apparent motion.

UNLABELLED: When a figure discretely and instantaneously changes its shape, observers typically do not perceive the abrupt transition between shapes that in fact occurs. Rather, a continuous shape change is perceived. Although this illusory "transformational apparent motion" (TAM) is a faulty construction of the visual system, it is not arbitrary. From the many possible shape changes that could have been inferred, usually just one is perceived because only one is consistent with the shape-based rules that the visual system uses to (1) segment figures from one another within a scene and (2) match figures to themselves across successive scenes. TAM requires an interaction between neuronal circuits that process form relationships with circuits that compute motion trajectories. In particular, this form-motion interaction must happen before TAM is perceived because the direction of perceived motion is dictated by form relationships among figures in successive images. The present fMRI study (n = 19) provides the first evidence that both form (LOC, posterior fusiform gyrus) and motion (hMT+) processing areas are more active when TAM is perceived than in a control stimulus where it is not. Retinotopic areas (n = 10), hMT+ (n = 7), and LOC (n = 7) were mapped in a subset of subjects. RESULTS: There is greater BOLD response to TAM than to the control condition in V1 and all subsequent retinotopic areas, as well as in hMT+ and the LOC, suggesting that areas that process form interact with hMT+ to construct the perception of moving figures.

Adolescent↗
PubMed2005

Effects of prolonged tamoxifen treatment on receptor expression and apoptosis of ovarian cancer cells.

OBJECTIVE: Tamoxifen, which is widely used in the treatment of breast cancer, also has a beneficial effect on cisplatin-refractory ovarian cancer. In this study, we investigated the long-term effects of this drug on estrogen-receptor-positive ovarian cancer cells. METHODS: We performed an in vitro selection process by long-term treatment of BG-1 ovarian cancer cells with 4-hydroxy tamoxifen (4-OH TAM). Drug effects on cell growth were determined by measurement of relative cell numbers (MTS assay), the apoptotic effects of 4-OH TAM were determined by analysis of poly (ADP-ribose) polymerase (PARP) cleavage and by ELISA measurement of DNA-histone complexes in cytoplasm. RESULTS: Analysis of BG-1(LT) ovarian cancer cells isolated after 5 months of long-term treatment with 4-OH TAM revealed both a significantly reduced apoptotic and antiproliferative effect of this drug. Further experiments to examine expression changes of the receptor tyrosine kinases EGFR, HER2 and estrogen receptor alpha did not reveal any alterations in BG-1(LT) if compared to wild-type cells. In contrast, in this cell line, a significant alteration in the expression of estrogen receptor beta was observed. CONCLUSION: Our findings indicate that long-term treatment with 4-OH TAM is able to diminish both the antiproliferative and apoptotic action of this drug on BG-1 ovarian cancer cells. Our data suggest that the responsiveness of ovarian cancer cells to 4-OH TAM decreases after long-term treatment with this drug in vitro like previously observed after long-term treatment of breast cancer cells.

Apoptosis↗
PubMed2002

Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis.

Formation of lymphatic metastasis is the initial step of generalized spreading of tumor cells and predicts poor clinical prognosis. Lymphatic vessels generally arise within the peritumoral stroma, although the lymphangiopoietic vascular endothelial growth factors (VEGF)-C and -D are produced by tumor cells. In a carefully selected collection of human cervical cancers (stage pT1b1) we demonstrate by quantitative immunohistochemistry and in situ hybridization that density of lymphatic microvessels is significantly increased in peritumoral stroma, and that a subset of stromal cells express large amounts of VEGF-C and VEGF-D. The density of cells producing these vascular growth factors correlates with peritumoral inflammatory stroma reaction, lymphatic microvessel density, and indirectly with peritumoral carcinomatous lymphangiosis and frequency of lymph node metastasis. The VEGF-C- and VEGF-D-producing stroma cells were identified in situ as a subset of activated tumor-associated macrophages (TAMs) by expression of a panel of macrophage-specific markers, including CD68, CD23, and CD14. These TAMs also expressed the VEGF-C- and VEGF-D-specific tyrosine kinase receptor VEGFR-3. As TAMs are derived from monocytes in the circulation, a search in peripheral blood for candidate precursors of VEGFR-3-expressing TAMs revealed a subfraction of CD14-positive, VEGFR-3-expressing monocytes, that, however, failed to express VEGF-C and VEGF-D. Only after in vitro incubation with tumor necrosis factor-alpha, lipopolysaccharide, or VEGF-D did these monocytes start to synthesize VEGF-C de novo. In conclusion VEGF-C-expressing TAMs play a novel role in peritumoral lymphangiogenesis and subsequent dissemination in human cancer.

Antigens, CD↗
PubMed2001

Regulation of sex hormone-binding globulin secretion in human hepatoma G2 cells.

Our purpose was to examine the roles of natural (estradiol (E2) and estrone (E1)) and synthetic estrogens (ethinyl estradiol (EE), moxestrol (MOX), and tamoxifene (TAM)) in regulating production of sex hormone-binding globulin (SHBG) by human hepatoma G2 (Hep G2) cells, the rationale being that synthetic estrogens are less rapidly metabolized than natural estrogens and, thus, may alter SHBG levels more readily. In Hep G2 cells, E2, E1, and EE at 10(-7) M did not result in significantly greater SHBG secretion compared to control cells. The synthetic estrogens, MOX and TAM, caused significant, P < 0.001, increases of 30% and 51% in SHBG secretion at 10(-7) M compared to controls. However, when TAM and E2 were added together, each at 10(-7) M, no increase in SHBG secretion was noted. We conclude that natural estrogens at physiologic concentrations do not increase SHBG secretion by Hep G2 cells, but the increase of SHBG secretion caused by MOX and TAM suggests that the lack of effect of E2 and E1 may, in part, be due to their rapid metabolism. In addition, TAM stimulates SHBG secretion by interaction with the genome that is different, in certain respects, from that of E2.

Antineoplastic Agents, Hormonal↗
PubMed2002

Tamoxifen and toremifene impair retrieval, but not acquisition, of spatial information processing in mice.

The present study examines the effects of tamoxifen (TAM) or toremifene (TOR), two triphenylethylene antiestrogen agents, on spatial information in mice by using Morris water maze. In a 30-s free swim trial, the TAM- or TOR-treated mice (intraperitoneally, 30 min before test) spent shorter time than the blank control mice in target quadrant. Compared to saline control group, animals exposed to TAM (1-10 mg/kg i.p., once a day for 5 days) or TOR (3-30 mg/kg i.p., once a day for 5 days) did not show significant difference on the acquisition of place task in Morris water maze. These results suggest that TAM, at the doses of 1-10 mg/kg, and TOR, at the doses of 3-30 mg/kg, impair the retrieval, but not the acquisition, of spatial information task in Morris water maze. It seems, however, that TOR is more potent than TAM on impairing memory retrieval.

Animals↗
PubMed1999

Traditional African medicine: theory and pharmacology explored.

Traditional African medicine (TAM) is a shorthand reference to indigenous forms of healing that are practiced all over Africa. Although TAM is based on the accumulated experience of ancient Africans, its mode of transmission by word-of-mouth has hindered emergence of a generally accepted theory and hence of the systematic development of TAM as a self-regulating profession. A major therapeutic objective in the treatment of illness in TAM is diffusion of emotional stress. This article summarizes the argument for such a therapy, and suggests that TAM is a distinct system of health care and not a rudimentary form of modern Western medicine.

Africa↗
PubMed2001

Chemically induced rat mammary tumor treated with tamoxifen showed decreased expression of cyclin D1, cyclin E, and p21(Cip1).

We studied the effects of tamoxifen (TAM) on the growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumor and the expression of cyclin D1, cyclin E, p21(Cip1), and estrogen receptors (ER) by performing immunohistochemistry and Western blot analysis. When tumor size reached between 10 and 15mm in the largest dimension, the rats were divided into a DMBA-control group and a DMBA-TAM group. The administration of TAM markedly decreased the tumor development and showed decreased expression of bromodeoxyuridine, cyclin D1, cyclin E, and p21(Cip1) when compared with those of the DMBA-control group; however, a few tumors showed progressive growth in spite of TAM treatment. These tumors had decreased expression of ER. This study suggests that TAM suppresses tumor development through the down-expression of cyclin D1 and cyclin E.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Tamoxifen inhibits prolactin signal transduction in ER - NOG-8 mammary epithelial cells.

Tamoxifen (TAM), an antiestrogen, also acts as an antilactogen in mammary cells. In the present study we analyze the effect of TAM on the signal transduction pathway for prolactin (Prl). TAM bound specifically to NOG-8, an estrogen receptor-negative mammary cell line. Within 5 min of Prl treatment, raf-1, MEK and MAP kinase were induced 2-3-fold over the control level. TAM completely inhibited this Prl-induced activation of kinases as well as Prl binding and cell growth. These results indicate the potential role of TAM as an antilactogen in Prl responsive systems.

Animals↗
PubMed2003

Pre-validation study for OECD enhanced test guideline 407 protocol by gavage for 4 weeks using propylthiouracil and tamoxifen.

To develop and pre-validate an enhanced protocol for OECD Test Guideline 407, we performed a 28-day repeated-dose toxicity study using the administration of propylthiouracil (PTU) and tamoxifen (TAM) in Sprague-Dawley (SD) rats. Six male and female SD rats were treated orally with PTU in corn oil at the dose of 0, 0.1, 1, or 10 mg/kg per day and TAM at dose of 0, 5, 30 or 200 microg/kg per day for 4 weeks. In the study using PTU, the body weights were reduced from the third week of the study in 10 mg/kg per day group. In clinical biochemistry, the levels of 3,5,3'-triiodothyronine (T3) and thyroxine (T4, 3,5,3',5'-tetraiodothyrosine) were also significantly decreased in 10 mg/kg per day group. Also, thyroid glands in 10 mg/kg per day group were bigger than those in the control group. In the histopathological examination, diffuse hyperplasia and hypertrophy of thyroid follicular cells were observed in all treatment groups, leading to the reduction of lumen size and papillary enfolding of lining epithelium. In the study using TAM, the body weights were reduced from the first week of the study in 200 microg/kg per day group. Relative testes and epididymes weights were increased and relative right ovary and uterus weights were reduced in 200 microg/kg per day group. Also, in the histopathological finding severe endometrial squamous metaplasia and endometrial gland atrophy and severe follicular cystic change were observed in TAM 200 microg/kg per day-treated group. On the basis of the results, the thyroid hormone levels, gross findings, and histopathological findings may be useful parameters for the detection of the endocrine-related effect of PTU and also reproductive organ weight and histopathological findings may be good parameters to detect the effect of TAM. Therefore, it is concluded that enhanced OECD TG407 might be useful for screening and detecting endocrine disrupters.

Animals↗
PubMed1997

Direct liquid chromatographic micro-measurement of tamoxifen in plasma of cancer patients.

We describe in this report a sensitive and direct method for the analysis of tamoxifen (TAM) in microsamples of plasma. The drug and internal standard (quinine bisulfate, I.S.) were separated on a 10-microm particle, 10 cm X 8 mm CN cartridge in conjunction with a radial compression system. The mobile phase was a mixture of 0.1 M sodium acetate in 0.001 M tetrabutylammonium phosphate solution (pH 6) and methanol (30:70, v/v) at a flow-rate of 4 ml/min. After addition of I.S. and o-phosphoric acid in acetonitrile (0.6 M) to the plasma (30 microl), the mixture was placed in an ultraviolet shortwave transluminator for 2 min prior to injection into the chromatograph. The compounds were detected in the effluent fluorometrically at excitation and emission wavelengths of 258 and 378 nm, respectively. Under these conditions, no interference in the assay from any endogenous substance or other concurrently used drugs was observed and the retention times of I.S. and TAM were 4.4 and 10.15 min, respectively. The concentration of TAM in plasma was linearly (r>0.9983) related to the peak height ratio (TAM/I.S.) in the range 0.01-2.0 microg ml(-1) and C.V. at 0.075, 0.4 and 1.2 microg ml(-1) was < or = 4.96%. We are currently using this assay for monitoring TAM in plasma and investigating its pharmacokinetics in cancer patients receiving cytotoxic drugs in addition to TAM as a multi-drug resistance modifier.

Antineoplastic Agents, Hormonal↗
PubMedDate not supplied

Toxic effects of tamoxifen on the growth and respiratory activity of Bacillus stearothermophilus.

The anticancer drug tamoxifen (TAM) is used as first line therapy in breast cancer. Although tamoxifen is usually considered an estrogen antagonist, several studies suggest alternative mechanisms of action. Bacillus stearothermophilus has been used as a model to clarify the antiproliferative action of tamoxifen putatively related with drug-membrane interaction. According to previous data, TAM induces perturbation of membrane structure along with impairment of bacterial growth. The aim of this work was to correlate the effects of TAM on growth of intact B. stearothermophilus with the respiratory activity of isolated protoplasts of this bacteria. TAM inhibits bacterial growth and oxygen consumption of protoplasts as a function of concentration. Effects on oxygen consumption depend on the substrate used: NADH, allowing to study the full respiratory chain and ascorbate-TMPD to probe the final oxidase segment. The interaction of TAM with the respiratory components occurs at a level preceding the cytochrome oxidase segment.

Antineoplastic Agents, Hormonal↗
PubMedDate not supplied

Comparison of the changes in adenine nucleotides of rat liver mitochondria induced by tamoxifen and 4-hydroxytamoxifen.

The antiestrogen tamoxifen (TAM) inhibits the growth of different estrogen receptor (ER)-negative cells. Recently, multiple effects of TAM on mitochondrial bioenergetic functions have been pointed to explain its ER-independent cell death mechanisms. We have shown that TAM and its major active metabolite 4-hydroxytamoxifen (OHTAM) induce depolarization of the mitochondrial membrane potential (DeltaPsi) and uncouple the mitochondrial respiration, depressing the oxidative phosphorylation efficiency. To clarify the biochemical mechanisms underlying the changes in the regulation of ATP synthesis and yield, in this work we evaluated the alterations of mitochondrial adenine nucleotides induced by both drugs and ascertained whether such changes could reflect a specific inhibition of either the adenine nucleotide translocase (ANT) or the phosphate carrier, as well as the activation of ATP hydrolysis due to DeltaPsi depolarization. We found that both antiestrogens caused a concentration-dependent decrease in mitochondrial ATP levels. Mitochondrial ADP and AMP were concomitantly increased with a subsequent decrease in the ATP/ADP or ATP/AMP ratios. The total concentration of adenine nucleotides also changed. Additionally, both drugs decreased the ANT content of mitochondria, inhibited the phosphate carrier and induced ATP hydrolysis. However, the effects of TAM were more drastic than those induced by OHTAM. Therefore, the depletion of ATP might result from an activation of ATP catabolism, as well as from a decrease in the mitochondrial content of ANT and partial inhibition of the phosphate carrier. Our data may explain the ER-independent effects and cytotoxicity of both drugs and, in agreement with other previous studies, suggest that OHTAM is much less toxic to mitochondria than TAM.

Adenine Nucleotides↗