Morphological sex change upon treatment by endocrine modulators in meiogynogenetic tench (Tinca tinca L.)

Exogenous steroids alter sex differentiation in fish substantially. In the present study we have evaluated the effects of 17α-methyltestosterone (MT) and oestrogen receptor antagonist Tamoxifen (TA) on gonadal development and skewness of the sex ratio in all-female tench juveniles. In the first two experiments, sexually undifferentiated juveniles were orally treated with three doses of MT and TA (50, 100 and 150 mg kg⁻¹). Both the treatments resulted in a moderate dose-dependent masculinization, with neomale production ranging from 17% (50 mg kg⁻¹) to 26% (150 mg kg⁻¹) for the MT only treatment, and from 0% (50 mg kg⁻¹) to 27% (100 mg kg⁻¹) only for the TA treatment respectively. In the third experiment treatment of sexually differentiated tench females with single steroid treatments or combinations of the two resulted in populations composed of females and intersex individuals. The significantly highest occurrence of intersex individuals (45.5%) was found in the group subjected to combine treatment of MT+TA (150+200 mg kg⁻¹). No masculinization effect of the single or the combined treatment occurred. It can be concluded that oral treatment with MT or TA only slightly modifies the normal process of sex differentiation in gynogenetic tench juvenile, but treatment with the above-mentioned combinations has a highly significant potential to skew the sex ratio in sexually differentiated tench females. However, from an applied point of view, the treatment procedure will need optimization before use at a commercial level.     

维拉帕米和三苯氧胺逆转卵巢癌细胞对阿霉素耐药性的实验研究

目的 了解维拉帕米和三苯氧胺体外逆转卵巢癌细胞阿霉素耐药性的效果及临床意义.方法 分别以阿霉素、维拉帕米和三苯氧胺作用于人卵巢癌亲本细胞SKOV3和阿霉素耐药细胞SKOV3/ADM后,采用MTI法检测药物对癌细胞的抑制作用,以细胞内阿霉素聚集量测定和流式细胞术检测凋亡.结果 维拉帕米和三苯氧胺能部分逆转耐药细胞对阿霉素的耐药性,且维拉帕米能显著增加耐药细胞内阿霉素的聚集量并促进其凋亡.结论 虽然维拉帕米和三苯氧胺能部分逆转耐药细胞对阿霉素的耐药性,但用于临床的意义不大.     

芳香化酶抑制剂于乳腺癌新辅助治疗最新进展

随着临床工作者对患者生活质量的关注,术前新辅助内分泌治疗被应用于晚期乳腺癌患者。大量临床试验证明在新辅助内分泌治疗中芳香化酶抑制剂(Aromatase inhibitors,AIs)应用于激素受体阳性乳腺癌患者可提高客观缓解率(Objective response,OR)和保乳手术率(Breast concerving rate,BCR),尤其在HER-2+和Ki-67+对TAM和化疗新辅助治疗可能存在抵抗时。AIs应用于新辅助治疗最佳治疗期限仍未确定,然而治疗延长至4个月以上时部分患者也取得良好疗效。最新研究表明AIs与COX-2抑制剂(COX-2 inhibitors,COX-2 I)或信号转导阻滞剂(Signal transduction inhibitors,STI)联合应用于新辅助内分泌治疗可以改善AIs耐药的情况。然而AIs应用于新辅助内分泌治疗仍需要临床工作者进一步的探索以取得其最佳的治疗效果。     

Tamoxifen induces apoptosis and inhibits respiratory burst in equine neutrophils independently of estrogen receptors

Neutrophils play an important role in the exacerbation and maintenance of severe equine asthma; persistent neutrophil activity and delayed apoptosis can be harmful to surrounding tissues. Tamoxifen (TX) is a nonsteroidal estrogen receptor modulator with immunomodulatory effects and induces early apoptosis of blood and bronchoalveolar lavage neutrophils from horses with acute lung inflammation. This study investigated if the in vitro effects of tamoxifen are produced by its action on nuclear (α and β) and membrane (GPR30) estrogen receptors in healthy equine neutrophils. Results showed that TX inhibits neutrophil respiratory burst induced by opsonized zymosan in a dose‐dependent manner. Nuclear (17‐β‐Estradiol) and GPR30 cell membrane (G1) estrogen receptor agonists and their antagonists (ICI 182,780 and G15, respectively) do not block or reproduce the effect of TX. Therefore, TX does not inhibit respiratory burst through estrogen receptors. TX (8.5 μM) also increased phosphatidylserine translocation, a marker of early apoptosis, which did not occur with any of the estrogen receptor agonists or antagonists . Thus, tamoxifen generates dose‐dependent inhibition of respiratory burst and increased early apoptosis in healthy equine neutrophils, independently of nuclear or membrane estrogen receptors. Further studies are necessary to explore the signaling pathways of tamoxifen‐induced ROS inhibition and phosphatidylserine translocation.     

全固态他莫昔芬选择电极的研制与应用

首次报道了一种以拘橼酸他莫昔芬与浓氢溴酸反应生成的衍生物的碘化物与碘化 的缔合物为电活性物的全固态他莫昔芬选择电极，电极的线性响应范围为１．０×１０－２～１０×１０－５ｍｏｌ／Ｌ斜率为４８ｍＶ／ｐＣ，检测限为８．０× １０－６ｍｏｌ／Ｌ，此电极响应迅速，重视性好，用此电极以标准曲线法对药物中的他莫昔芬进行了测定，此法简便，结果与分光光度法相符。