血康口服液与他莫昔芬联合治疗免疫性血小板减少性紫癜疗效观察

联合应用血康口服液和他莫昔芬治疗成人免疫性血小板减少性紫癜(ITP)20例。疗程超过2月。15例患者的血小板(BPC)计数明显上升,有效率为75％(15/20),对于激素治疗无效者,仍有良效。对月经过多者和不适合应用激素者尤为适应。两药合用无明显副作用。治疗起效时间较快,平均13天。疗效持续时间较长,长者已达一年以上。     

Lack of modifying effects of atrazine and/or tamoxifen on thyroid carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine (DHPN)

The modifying effects of atrazine, and/or tamoxifen, on thyroid carcinogenesis were investigated in a rat two-stage carcinogenesis model following N-bis(2-hydroxypropyl)nitrosamine (DHPN) initiation. Five-week-old male F344 rats were given a single subcutaneous injection of DHPN (2800 mg/kg, body weight) or vehicle alone. Starting 1 week later, the animals were fed a diet supplemented with 0, 5, 50 or 500 ppm of atrazine, 500 ppm atrazine plus 5 ppm tamoxifen, or 5 ppm tamoxifen in the DHPN-treated groups, and 0 or 500 ppm of atrazine in the DHPN-untreated groups for 24 weeks. At autopsy major organs, including the thyroid, pituitary, liver, kidney, testis, epididymis, and brain, were collected and histopathologically examined. Body weights were significantly (P<0.05) decreased by the high doses of atrazine or tamoxifen, the effect being enhanced in combination. Relative thyroid weights were significantly increased (P<0.05) only in the tamoxifen-treated group and pituitary weights were elevated with 500 ppm atrazine plus tamoxifen (P<0.05). Relative liver weights were increased by the high dose of atrazine. However, the atrazine and/or tamoxifen treatments did not induce significant histopathological changes in the major organs, including the thyroid, nor cause significant changes in serum TSH levels. These results suggest that neither atrazine nor tamoxifen may promote thyroid carcinogenesis, alone as well as in combination.     

Tamoxifen induces ultrastructural alterations in membranes of Bacillus Stearothermophilus

Tamoxifen (TAM), a non-steroid antiestrogen, is the mostly used drug for chemotherapy and chemoprevention of breast cancer. However, the mechanisms by which TAM inhibits cell proliferation in breast cancer are not fully understood. TAM strongly incorporates in biomembranes and a variety of effects have been assigned to biophysical and biochemical interactions with membranes. Therefore, a better understanding of the physicochemical basis of interaction of TAM with biomembranes is essential to elucidate the molecular mechanisms of action. A strain of Bacillus stearothermophilus has been used as a model to clarify the interaction of TAM with the cell membrane. TAM effects on the ultrastructure of membranes of this bacterium were evaluated by electron microscopy. Important ultrastructural alterations were observed in B. stearothermophilus treated with TAM, namely change in the geometry of the membrane profile from asymmetric to symmetric, disaggregation of ribosomes, coagulation of the cytoplasmic matrix, occurrence of mesossomes, appearance of fractures in membranes and the alteration of the ultrastructure of cell wall. These ultrastructural alterations confirm that TAM is a membrane-active drug and that membrane damage may be involved in molecular mechanisms of cell death induced by this drug.     

Tamoxifen induces ultrastructural alterations in membranes of Bacillus Stearothermophilus.

Tamoxifen (TAM), a non-steroid antiestrogen, is the mostly used drug for chemotherapy and chemoprevention of breast cancer. However, the mechanisms by which TAM inhibits cell proliferation in breast cancer are not fully understood. TAM strongly incorporates in biomembranes and a variety of effects have been assigned to biophysical and biochemical interactions with membranes. Therefore, a better understanding of the physicochemical basis of interaction of TAM with biomembranes is essential to elucidate the molecular mechanisms of action. A strain of Bacillus stearothermophilus has been used as a model to clarify the interaction of TAM with the cell membrane. TAM effects on the ultrastructure of membranes of this bacterium were evaluated by electron microscopy. Important ultrastructural alterations were observed in B. stearothermophilus treated with TAM, namely change in the geometry of the membrane profile from asymmetric to symmetric, disaggregation of ribosomes, coagulation of the cytoplasmic matrix, occurrence of mesossomes, appearance of fractures in membranes and the alteration of the ultrastructure of cell wall. These ultrastructural alterations confirm that TAM is a membrane-active drug and that membrane damage may be involved in molecular mechanisms of cell death induced by this drug.     

The Influences of Mifepristone, Norethisterone and Tamoxifen on the Glycosph

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On the role of additive hormone monotherapy with tamoxifen,medroxyprogesterone acetate and aminoglutethimide,in advanced breast cancer

Summary We analyzed the results of clinical studies on the therapeutic efficacy of hormone monotherapy with tamoxifen, medroxyprogesterone acetate, and aminoglutethimide in metastatic breast cancer, which were published between 1971 and 1986 and involved altogether 7000 patients. The overall response rates in patients treated with these hormonal single agents at various dose levels ranged from 31%–42%. When only estrogen receptor-positive patients were considered, the response rates lay between 41% and 54% in groups which were treated with the antiestrogenic agents tamoxifen or aminoglutethimide. The duration of remission was 12 months for tamoxifen- and aminoglutethimide-treated women, whereas medroxy-progesterone acetate effected remissions lasting from 6–16 months. The overall mean survival from start of therapy in tamoxifen- and aminoglutethimide-treated groups was 20 months, whereas information concerning this therapeutic parameter was available only in a minority of medroxyprogesterone acetate-treated groups. With respect to the response by site of metastatic lesions, all three agents caused a significantly higher degree of remissions in the soft tissue as compared to visceral disease.Abbreviations AG Aminoglutethimide - MPA Medroxyprogesterone acetate - TAM Tamoxifen     

A 23-pS Ca2+-activated K+ channel in MCF-7 human breast carcinoma cells: an apparent correlation of channel incidence with the rate of cell proliferation

In studies on the apical membranes of cultured MCF-7 human breast carcinoma cells, we found two conspicuous K⁺ channel types with conductances of 23 and 70 pS, respectively. Of these, the 23-pS K⁺ channel was most conspicuous. In cell-attached patches with KCl in the pipette, it had a linear current/voltage (I/V) relation and was activated by depolarisation and in excised insideout patches it was highly selective for K⁺ over Na⁺ (permeability ratio of Na⁺ to K⁺, P _Na/P _K=0.02). Rubidium (Rb⁺) had a similar permeability to K⁺, although it was only conducted at 20% of the rate of K⁺, and cesium (Cs⁺) had a permeability less than 30% that of K⁺ and was not conducted at all. Both Cs⁺ and Rb⁺ acted as partial blockers when applied internally but the channel was not blocked by external tetraethylammonium (TEA, 10 mmol/l), quinidine (200 mol/l) or apamin (50 nmol/l). It was activated by Ca^{2 +} in the range 10^–7–10^–6 mol/l. In cell-attached patches at a pipette potential of 0 mV, the open-time histogram was described by a single exponential (time constant 1.6 ms) and the closed-time histogram by two exponentials (time constants 0.5 and 1.5 ms). The incidence of the 23-pS but not the 70-pS channel depended on the rate of cell proliferation. Thus, in studies on cell-attached patches from cells in the exponential growth phase, the 23-pS channel was observed in 78% of patches. However, when the proliferation rate was decreased, whether as a result of allowing the monolayer to reach confluence, or of cell treatment with an anti-oestrogen (tamoxifen, 10 mol/l), or a phorbol ester [phorbol 12-myristate 13-acetate (TPA), 2.6 nmol/l], the channel incidence was reduced to 42%, 60% and 42%, respectively. The activity of the 23-pS channel is not obligatory for cell division, however, since the rate of cell proliferation remained the same in MCF-7 cultures in which the channel was not expressed.     

Lack of effect of high-dose antioestrogen on the maturation and in-vitro fertilization of human oocytes

Thirty-four women requesting laparoscopic sterilization underwenta fixed schedule regimen for multiple follicular developmentwhich included norethisterone and clomiphene citrate. Follicleaspiration for oocyte recovery was attempted laparoscopically34 h after administration of 5000 IU human chononic gonadotrophin(HCG). Nineteen women were given 80 mg tamoxifen orally 4 hprior to HCG injection, while 15 acted as controls. There wasno statistical difference in fertilization rates in vitro betweentamoxifen-treated patients and controls (80 and 68% respectively).In addition, the morphological characteristics of the oocytes,the rates of cleavage, and the concentrations of oestradiol,progesterone and androstenedione in follicular fluid were similarin the two groups. Tamoxifen was detected in substantial amountsin follicular fluids of patients given tamoxifen. These resultssuggest that high-dose tamoxifeii, in clinically used doses,does not adversely affect the final stages of maturation orthe fertilization and early cleavage of human oocytes.