Evaluation of anti-tumor activity of Momordica cymbalaria fenzl.

Background: The aim of the current study is to evaluate the anti-tumor activity of saponins isolated from the roots of Momordica cymbalaria (MC) against dimethylbenz[a]anthracene (DMBA) induced rats. Methods: A steroidal saponin MC (SMC) was isolated from MC fenzl and purified by preparative high-performance liquid chromatography. Breast cancer was induced in 50-day-old female Sprague-Dawley rats by injecting DMBA (6 mg/kg intravenous) in three doses on day 50, 54, and 57. The rats were randomized into four groups; control, DMBA, SMC (100 mg/kg), and tamoxifen (6.6 mg/kg) to DMBA breast cancer rats. The tumor size, volume, hormonal, antioxidant, and whole mount parameters were estimated. Results: Mean tumor size and volume, luteinizing hormone, and progesterone with superoxide dismutases, catalase, and glutathione levels increased significantly (p<0.001); serum estradiol, follicle stimulating hormone with lipid peroxidation decreased significantly (p<0.001) in DMBA-induced breast cancer and vice versa in SMC and tamoxifen. Terminal end buds, terminal ducts, alveolar buds, and lobules decreased significantly (p<0.001) in DMBA-induced breast cancer whereas increased significantly in SMC and tamoxifen. Histological necrosis and hemorrhage along with focal desmoplastic reaction in DMBA-induced breast cancer; ductile elongation and hyperplasia of both ducts and alveoli were prominent, with increased secretory activity in SMC group. The results confirmed the chemopreventive effect of SMC and tamoxifen in DMBA-induced breast cancer. Conclusions: The SMC exhibited anti-tumor activity against mammary cancer, which may be due to its anti-estrogenic, antioxidant activity.

Effects of perinatal period administration of clomiphene citrate in sexual behavior, organ weights and hormone concentration of Wistar male and female rats / Efeito da administração do citrato de clomifeno durante o período perinatal no comportamento sexual, peso dos órgãos e concentração hormonal de ratos Wistar machos e fêmeas

The effects of prenatal exposure to clomiphene citrate in sexual behavior, organ weight and hormone concentrations of male and female rats was evaluated. The animals received four doses of clomiphene citrate 2 mg/mL each during the prenatal period (21 days of gestation DG21) on days 1 (DN1), 2 (DN2) and 3 (DN3) after the birth of the puppies. The treatment led to the development of polycystic ovaries in 70% of the females, masculinization of female sexual behavior and changes in sexual behavior of males evidenced by the reduction in the number of ejaculations. In regards to hormone levels, a decrease in the FSH levels in male offspring was observed. It was concluded that clomiphene citrate interferes with the reproductive capacity of male and female rats and female sexual orientation when prenatally administered.

Foram investigados os efeitos da exposição perinatal ao citrato de clomifeno no comportamento sexual, peso dos órgãos e concentração hormonal de ratos machos e fêmeas. Os animais receberam quatro doses de 2 mg/mL de citrato de clomifeno, no período perinatal (21 dias de gestação DG21), nos dias 1 (DN1), 2 (DN2) e 3 (DN3) após o nascimento dos filhotes. O tratamento causou desenvolvimento de ovário policístico em 70% das fêmeas, masculinização do comportamento sexual das fêmeas e alteração do comportamento sexual dos machos evidenciado pela redução no número de ejaculações. Em relação aos níveis hormonais, observou-se diminuição de FSH na prole masculina. Concluiu-se que o citrato de clomifeno interfere na capacidade reprodutiva de ratos machos e fêmeas, e na orientação sexual de fêmeas, quando administrado perinatalmente.

Estrogen, anti-estrogen drugs, and thyroid cancer / 中华内分泌代谢杂志

Several researches have suggested that estrogen contributes to the initiation and development of thyroid cancer by binding to estrogen receptors (estrogen receptor α,estrogen receptor β,and G-protein-coupled receptor 30),activating gene or non-genomic pathways and regulating proliferation of thyroid cells.Studies on antiestrogen drugs based on inhibiting thyroid cell proliferation may provide a new target in treating thyroid cancer.

Expression and significance of BCAR1 in endometrial carcinomas / 中国综合临床

Objective To investigate the expression and significance of BCAR1 protein in endometrial carcinoma.Methods The level of BCAR1 was measured by immunohistochemistry in 50 endometrial carcinoma samples and 30 normal proliferative endometrium samples.Estrogen receptor (ER) and progesterone receptor (PR) expression was investigated in endometrial carcinoma samples.Results The level of BCAR1 was higher in endometrial carcinoma than that in normal proliferative endometrium (64.0％ (32/50) vs.40.0％ (12/30) ;x2 =4.364,P =0.037).In endometrial cancer,increased BCAR1 expression was significantly correlated with relatively higher age,poor differentiation,positive expression of ER (x2 =6.272,r =0.354 ; x2 =5.640,r =0.366 and x2 =4.217,r =0.290 ; P ＜ 0.05).Conclusion BCAR1 promote carcinogenesis and positively correlate with poor differentiation and ER status in endometrial carcinoma.

Estrogen Antagonist and Development of Macular Hole

To describe the clinical and optical coherence tomography (OCT) features of a macular hole (MH) or its precursor lesion in patients treated with systemic antiestrogen agents. We reviewed the medical history of the patient, ophthalmic examination, and both fundus and OCT findings. Three female patients receiving antiestrogen therapy sought treatment for visual disturbance. All of the patients showed foveal cystic changes with outer retinal defect upon OCT. Visual improvement was achieved through surgery for the treatment of MH in two patients. Antiestrogen therapy may result in MH or its precursor lesion, in addition to perifoveal refractile deposits. OCT examination would be helpful for early detection in such cases.

Study for the Synthesis of 123IIdoxifene and Its Uptake in the Breast Cancer Cell / 대한핵의학회잡지

PURPOSE: Idoxifene is currently entering phase II clinical trials for the treatment of advanced breast cancer. The radiolabeled idoxifene using 123I provides an opportunity for clinical pharmacology with single photon emission computed tomography (SPECT). The purpose of this study was to prepare radiolabeled idoxifene using 123I and to determine its cell uptake of breast cancer cell line. MATERIALS AND METHODS: With a view to evaluating new anticancer drugs, we are investigating the novel antiestrogen pyrrolidino- 4-iodotamoxifen (idoxifene). [123I]Idoxifene has been prepared in no-carrier-added form using a tributyl stannylated precursor which has been synthesized by means of (2-chloroethoxy)benzene with (+/-)-2- phenylbutanoic acid on the basis of previously reported standard methods. The biodistribution and dynamic behavior of the compound were investigated using the comparative breast cancer cell line, MCF-7 (estrogen receptor-positive) and MDA-MB-468 (non-estrogen receptor). RESULTS AND CONCLUSION: Acylation of (2-chloroethoxy)benzene with (+/-)-2-phenylbutanoic acid gave the versatile ketone (81%) which reacted with 1,4-diiodobenzene to give triphenylethylene as a mixture of E and Z geometric isomers, which were separated by the recrystallization in ethanol. The E-isomer was treated with pyrrolidine to give idoxifene (67%). In order to incorporate radioactive iodine into the 4-position, the 4-stannylated precursor was prepared (30%). The yield of radioiodination was 90-92% with a high radiochemical purity greater than 98%. The ratio of tumor uptake of the breast cancer cell line between MCF-7 and MDA-MB-468 was about 1.7.

Antifertility effect of tamoxifen as tested in the female bonnet monkey (Macaca radiata).

The administration of a potent antiestrogen, tamoxifen at a dose of 3 mg/kg body weight/day orally post-coitally to cycling mated bonnet monkeys (Macaca radiata) from days 18–30 of cycle resulted in inhibition of establishment of pregnancy in 9 out of 10 monkeys. Tamoxifen effect was not due to interference with luteal function. The effect was specific to tamoxifen as exogenously administered progesterone could not reverse it. In addition to suggesting a role for estrogen in maintenance of early pregnancy in the primate the present study could be a prelude to the development of an effective post-ovulatory approach for regulation of fertility in the human female.