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Gene Review

TAM  -  Myeloproliferative syndrome, transient...

Homo sapiens

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Disease relevance of TAM

  • Any single type-1 thymidine analogue mutation (TAM; M41L, L210W, T215Y) had a negative effort on the change in HIV RNA at 6 months, whereas among type-2 TAMs (D67N, K70R, K219Q), only D67N showed a trend for a negative effect [1].
  • MATERIALS AND METHODS: Six hundred forty-eight patients with hormone receptor-positive or -unknown metastatic breast cancer were randomly assigned to receive TAM (n = 215), TOR60 (n = 221), or TOR200 (n = 212) [2].
  • CONCLUSION: The addition of CMF to TAM adds no benefit and considerable toxicity in this group of women [3].
  • Compared to placebo, significant reductions in HIV-1 RNA were observed for tenofovir DF-treated patients who had thymidine analog- (TAM), lamivudine- (M184V), NNRTI- or protease inhibitor-associated mutations [4].
  • Thirty-four patients with progressive advanced renal cell carcinoma (RCC) were treated with high-dose tamoxifen (HD-TAM) 100 mg/m2 p.o. daily until progression [5].

Psychiatry related information on TAM

  • On the other hand, the temporo-occipital junction (i.e. human MT (middle temporal area) / MST (medial superior temporal area) complex) was activated in dynamic stereopsis [6].
  • The estimates of the directionality (median Id = 0.97) of STPa cells was similar to that reported for posterior motion processing areas (the middle temporal area, MT, and the medial superior temporal area, MST) [7].
  • The early response latency and directional selectivity indicate that motion sensitivity in STPa cells derives from the dorsal visual pathway via MT/MST [7].
  • In light of the similarities between the problems of delinquency and adolescent substance abuse, MST holds promise as an effective treatment of the latter [8].

High impact information on TAM

  • Components of this disulfide linked heterodimeric complex, Ig-alpha and Ig-beta, contain an approximately 26 residue sequence motif termed ARH1, also known as TAM, which binds to cytoplasmic effectors, including src-family tyrosine kinases, and contains all structural information needed for signal transduction [9].
  • BACKGROUND: Human sulfotransferase 1A1 (SULT1A1) catalyzes the sulfation of a variety of phenolic and estrogenic compounds, including 4-hydroxytamoxifen (4-OH TAM), the active metabolite of tamoxifen [10].
  • We investigated the hypothesis that that high sulfation activity would increase the elimination of 4-OH TAM by examining whether the presence of this polymorphism affects the efficacy of tamoxifen therapy [10].
  • CONCLUSIONS: Sulfation of 4-OH TAM provides a previously unanticipated benefit, possibly due to alterations in the bioavailability of the active metabolite or to undefined estrogen receptor-mediated events [10].
  • We reported previously that a synthetic compound, MT-21, induced apoptosis by activating c-Jun-NH2-terminal kinase via the Krs/MST protein, which is activated by caspase-3 cleavage dependent on reactive oxygen species production [11].

Chemical compound and disease context of TAM


Biological context of TAM

  • The effects of adding an antiestrogen (tamoxifen, TAM) and 17 beta-estradiol alone or simultaneously on cell growth were assessed [15].
  • In transient transfection analyses using a luciferase reporter plasmid containing two copies of the Xenopus vitellogenin A2 estrogen response element, estradiol stimulated luciferase transcription through both the wild type and mutant estrogen receptors, while (fr) 4-OH TAM stimulated transcription to a greater extent through the mutant receptor [16].
  • TAM significantly suppressed MCF-7 growth over wk 2-5, reducing proliferation detected by immunocytochemistry and fluorescence-activated cell sorter cell cycle analysis [17].
  • When cells were preincubated with either E2, TAM or 4OHT at a high, fixed concentration to block the ER or AE binding sites (AEBS), respectively, displaceable binding of [3H]ICI 182,780 was still observed, indicating binding at a site other than the classical ER or previously described AEBS [18].
  • CONCLUSION: Electron transport simulations were conducted in 4 different 3D voxel models of trabecular bone for sources localized in the active marrow (TAM), bone volume (TBV), bone endosteum (TBE), and bone surfaces (TBS) [19].

Anatomical context of TAM

  • TAM receptor function in the retinal pigment epithelium [20].
  • Cell growth and 3H-thymidine incorporation by the follicular thyroid carcinoma cells were inhibited when the cells were exposed to TAM (1.5 mumol/L) [21].
  • The specific reactivity of TAM with superoxide, which leads to loss of EPR signal, was utilized to detect the generation of superoxide in various chemical (light/riboflavin/electron/donor), enzymatic (xanthine/xanthine oxidase), and cellular (stimulated neutrophils) model systems [22].
  • Although in vitro experiments have implicated Gas6 as the critical TAM ligand for this process, we find that Gas6 mutant mice have a histologically intact retina with no photoreceptor degeneration [20].
  • Here we report on an experimental system for generating TAM in vitro by culturing human MO and MO-derived macrophages (MAC) within 3-dimensional multicellular tumor spheroids (MCS) [23].

Associations of TAM with chemical compounds

  • The simultaneous addition of 17 beta-estradiol (10(-8) M) neutralized the inhibitory effect of TAM (10(-6) M) in the majority of tumors [15].
  • In conclusion, TAM is able to bind to a specific receptor on this follicular thyroid carcinoma cell line, and a natural circulating ligand present in ethanol extracts of human serum interferes with its binding [21].
  • It addresses whether the anti-EGFR agent gefitinib (ZD1839/Iressa; TKI: 1 mum) combined with the antihormones 4-hydroxytamoxifen (TAM: 0.1 mum) or fulvestrant (Faslodex; 0.1 mum) enhances growth inhibition and prevents resistance [17].
  • Among 27 patients who received DTIC/DDP/BCNU/TAM and rIL-2/rIFN-alpha, there were 3 (11%) complete remissions and 12 (44.5%) partial remissions [24].
  • Using 4-hydroxy tamoxifen (4-OH TAM) and diethylstilbestrol (DES) as input queries, we employed this scheme to search a sample database of approximately 200,000 commercially available organic chemicals for matches (hits) [25].

Regulatory relationships of TAM

  • (fr)4-OH TAM reduced the growth rate in cell lines containing mutant estrogen receptors, while the cell line containing the wild type estrogen receptor is minimally influenced by (fr)4-OH TAM [26].
  • Treatment of both parental and resistant MCF-7 cells with TAM induces apoptosis and clusterin [27].
  • The treatment with TAM induced a significant decrease in the fraction of S-phase cells and an increase in those with a DNA content typical of G0/1 phase [28].
  • TAM suppressed carcinogenesis to 0% incidence like TAM+MEL in both the NMU and DMBA models [29].

Other interactions of TAM

  • In summary, anti-IRS1 RNAi strategy could become a potent tool to induce breast cancer cell death, especially if combined with standard TAM therapy [30].
  • The addition of TAM (10(-6) M) to the medium resulted in a significant decrease in cell growth in 26 of 36 (72%) estrogen receptor (ER)-positive tumors and in one of 5 ER-negative tumors (20%) [15].
  • Comparison of side-chain packing in ligand-free TrpRS and the TAM complex, using identification of nonpolar nuclei (Ilyin VA, 1994, Protein Eng 7:1189-1195), shows that significant repacking occurs between three relatively stable core regions, one of which acts as a bearing between the other two [31].
  • CD33 was detected in four TAM and five AMKL cases [32].
  • 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) [33].

Analytical, diagnostic and therapeutic context of TAM

  • We suggest that clinical evaluation of the combination of 9cRA and TAM, either for chemoprevention or for adjuvant therapy, should be considered [13].
  • The combination of 9cRA with low levels of tamoxifen (TAM; fed at either 1.0 or 0.5 mg/kg of diet) was particularly effective; addition of 9cRA to a TAM regimen doubled the number of animals that were tumor-free at autopsy and significantly diminished tumor number and tumor burden [13].
  • The antiestrogen GW5638 (1.5 mg daily), tamoxifen (0.5 mg or 1.5 mg daily), and raloxifene (1.5 mg daily) were given p.o. The pure antiestrogen ICI182,780 (5 mg once a week) was given s.c. Western blots from MCF-7 TAM breast tumors were performed to demonstrate the regulation of estrogen receptor alpha expression by different ligands [34].
  • The established breast cancer xenografts 3366 and 3366/TAM offer the possibility of investigating mechanisms of anti-oestrogen resistance in an in vivo situation [35].
  • The patient groups were then stratified according to adjuvant treatment [radiotherapy (RT) versus radiotherapy and tamoxifen (RT + TAM)] [36].


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