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Chemical Compound Review

Novaldex     2-[4-[(Z)-1,2-diphenylbut-1- enyl]phenoxy]...

Synonyms: Nourytam, Citofen, Crisafeno, Istubol, tamoxifen, ...
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Disease relevance of Nolvadex

  • One trial was performed 45 min after the ingestion of caffeine citrate (CC) in an amount equal to 7.0 mg of anhydrous body weight [1].
  • CONCLUSIONS: In women with unexplained infertility undergoing COH with CC/hMG, the occurrence of a spontaneous LH surge is a favorable event associated with a significantly increased pregnancy rate [2].
  • The putative carcinogenicity of TAM and 4-hydroxy-TAM but not of 3-hydroxy-TAM, as implied by these in vitro transformation studies, is corroborated by recent reports on ovarian and Leydig cell tumors in mice and hepatocellular carcinomas in rats [3].
  • The sensitivity to medroxyprogesterone acetate (MPA) and tamoxifen (T) and their combination was assayed in 13 patients with untreated endometrial cancer by an in vitro ATP-bioluminescence method [4].
  • Expression of ERbeta is an independent marker for favorable prognosis after adjuvant tamoxifen treatment in ERalpha-negative breast cancer patients and involves a gene expression program distinct from ERalpha [5].
  • In light of the most recent clinical data, however, it is now clear that aromatase inhibitors are the preferred first line therapy for all stages of breast cancer in post-menopausal women, whether they have had previous tamoxifen exposure or resistance [6].
  • This is to our knowledge the first report in which tamoxifen has been successfully used in a TSC patient with multiple liver angiomyolipomas [7].
  • Aspirin decreased the proangiogenic effects of tamoxifen, suggesting that antiplatelet and/or antiangiogenic therapy might improve the effectiveness of tamoxifen in women with breast cancer [8].
  • I.p. or intratumoral injection of tamoxifen decreased cholangiocarcinoma tumorigenesis by 40% to 80% in nude mice [9].
  • Treatment with tamoxifen did not inhibit this hyperplasia; instead, such treatment exaggerated hyperplasia with an enhanced degree of alteration, indicative of hypersensitivity to tamoxifen [10].
  • Our data suggest that the 17HSD1/17HSD2 ratio might be useful as a predictive factor for tamoxifen treatment in ER-positive breast cancer patients [11].

Psychiatry related information on Nolvadex


High impact information on Nolvadex

  • In contrast to the facile interconversion of the hydroxytamoxifen isomers, there is no metabolism or interconversion of the parent compounds cis- and trans-tamoxifen in vitro [13].
  • For example, in yeast cells lacking the mitochondrial genome, the expression of several nuclear genes, such as CIT2 (citrate synthase), MRP13 (mitochondrial ribosomal protein), and DLD3 (d-lactate dehydrogenase) has been reported to be altered [14].
  • Ninety-six percent of patients had received TAM previously for early (adjuvant treatment) or advanced breast cancer [15].
  • Possible interactions with the SULT1A1 substrate tamoxifen (tam), an anti-estrogen applied in the therapy of breast cancer, were also studied [16].
  • A 6-day pretreatment of CG-5 cells with nIFN-alpha, at the above-mentioned doses, sensitized them to the growth-inhibiting activity of subsequent exposure to 10(-7) M TAM or MPA, which resulted in a synergistic effect, and could be explained on the basis of the observed enhancement of estrogen and progesterone receptors due to IFN activity [17].

Chemical compound and disease context of Nolvadex


Biological context of Nolvadex

  • PATIENTS: Thirty-six patients underwent follicular stimulation with low-dose GnRH-a and hMG and were compared with 34 patients undergoing ovulation induction with CC and hMG [21].
  • Maximal oxygen consumption did not differ significantly between the CC (60.3 +/- 5.2 and P (59.7 +/- 5.6 trials [1].
  • Adult female rats were treated with ZM (5 mg/kg/d) or TAM (5 mg/kg/d) and sacrificed at varying times during the estrous cycle [22].
  • In none of the clinical end points measured, however, was the classic CC and hMG non-down-regulation regime significantly less effective or troublesome than where down-regulation was used [23].
  • ZM induced a persistent diestrus whereas TAM led to a mixed picture in the vaginal smear [22].

Anatomical context of Nolvadex

  • The treatment of animals bearing tumors (5 mm in diameter) orally with TX or TO or with LAK cells i.p. resulted in tumor suppression [24].
  • Partial inhibition of resorption was seen in the presence of 2 microM trans-tamoxifen, whereas complete abolition of resorption and osteoclast viability occurred with 10 microM trans-tamoxifen; survival of mononuclear cells was unimpaired at either concentration [25].
  • A higher percentage of oocytes possessed a polar body at egg retrieval with these stimulation regimens compared with rates reported previously for FSH, FSH/hMG, and CC/hMG stimulations [26].
  • DROL and TAM decreased the levels of 3H-E2 in the tumors, uteri and vaginae, but had no effect in the hearts [27].
  • Both drugs inhibited the binding of 125I-estradiol-17 beta to ER in the cytosol of the tumor in vitro, and the effect of DROL was much stronger than that of TAM [27].

Associations of Nolvadex with other chemical compounds

  • The present study was undertaken to compare the effects of the pure antiestrogen ZM 182780 (ZM) and the partial agonist tamoxifen (TAM) on ovulation and peripheral hormone levels in the rat [22].
  • DESIGN: A randomized prospective study compared patients receiving low-dose GnRH-a and hMG therapy to clomiphene citrate (CC) and hMG cycles [21].
  • ER and PR predicted the response in vitro in 62% of the tumours exposed to the combined hormones, and in 38% and 33% of those exposed to T and MPA, respectively [28].
  • Time-lapse video observations indicated that osteoclast death occurred rapidly (within 2-3 h) following exposure to 10 microM of either trans-tamoxifen or cis-tamoxifen [25].
  • Patients with ER expression at second biopsy were subsequently treated with 20 mg TAM daily [29].
  • The increase in serum VEGF from baseline to 12 weeks was significantly different between anastrozole and tamoxifen (anastrozole versus tamoxifen, 6% versus 38%; P = 0.047) [30].

Gene context of Nolvadex

  • Treatment with 10(-7) M ICI or 10(-7) M Tam leads to a time dependent increase of TNFR1 and TRADD steady-state mRNA levels in MCF-7 cells [19].
  • A statistically significant reduction of these values was observed when 20 nM DOX was added to medium with E2 - 39.24 +/- 7.6%, TAM - 48.34 +/- 2.05% and ATRA - 21.98 +/- 1.69%, respectively; the percentage of PCNA- and Ki-67-positive cells was also reduced [31].
  • Similarly, enhanced tumor suppression occurred when TX- or TO-treated P815 cells were mixed with LAK cells and injected s.c. into normal DBA2 recipients [24].
  • E2 (1-100 nM) significantly inhibited PTHrP secretion, whereas both TAM (0.1-10 microM) and ICI (1-100 nM) significantly stimulated it [32].
  • Coincubation of MCF-7 cells with antiestrogens (ICI or Tam) and blocking TNFR1 antibodies lead to an increase in cell viability [19].
  • Eight (7%) individuals had genotypes consistent with poor metabolizer status, and 4 (3.5%) individuals took CYP2D6 inhibitor drugs concomitant with their tamoxifen and were also considered poor metabolizer [33].
  • Tamoxifen significantly increased the expression of coactivators in normal and malignant tissue irrespective of dose, especially for SRC-3/AIB1 (P < 0.001 tamoxifen-treated versus nontreated subjects) [34].

Analytical, diagnostic and therapeutic context of Nolvadex

  • Rats treated with the combination of TAM and bromocryptine also showed a significant reduction in tumor incidence and number, but a 5-fold greater percentage of hormone-independent tumors after ovariectomy [35].
  • PATIENTS: Seventeen women with CC-resistant PCOD were included randomly in the study to either laparoscopic ovarian cautery or GnRH-a and OC therapy for 3 months [36].
  • Ovarian stimulation with clomiphene citrate (CC; six women) was without effect on these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)[37]
  • After treatment failure, patients from groups A and C received Adriamycin (doxorubicin) (ADX) vincristine (VCR), and TMX and patients from group B received ADM, VCR, and MAP [38].


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