Hydroxyurea regulates the development and survival of B16 Melanoma Cells by upregulating MiR-7013-3p

miRNAs are a family of short, noncoding RNAs that are involved in many processes in melanoma cells. MITF acts as a master regulator of melanocyte function, development and survival by modulating various genes. Hydroxyurea (HU) is used to treat melanoma, and miRNA expression is altered after HU treatment in B16 melanoma cells. In this study, we screened for miRNAs that were upregulated after HU treatment and that targeted the MITF gene. We found that miR-7013-3p exhibited increased expression after HU treatment and could bind to MITF. miR-7013-3p inhibited melanin production, proliferation, and migration and promoted apoptosis in B16 melanoma cells. The results may provide more information on the roles of miR-7013-3p in B16 melanoma cells.     

荒漠肉苁蓉水提液对羟基脲所致雄性小鼠睾丸毒性的缓解作用

羟基脲是一种抗肿瘤药物,具有潜在的生殖毒性,而荒漠肉苁蓉作为一种对生殖系统具有补益作用的中药已经有几千年的药用历史。本文曼在评价荒漠肉蕊簧水提液对羟基脲造成的睾丸毒性的缓解作用。60只小鼠随机分为5组,除了正常组小鼠外,其余各组小鼠每天上午灌胃羟基脲（400mg kg^-1体重）造模,而治疗组小鼠每天下午灌胃荒漠肉苁蓉水提液（剂量分别为1．5,3．0和6．0g生药公斤体重）,连续4周。结果发现羟基脲组小鼠出现严重的睾丸组织损伤,体重下降（P〈0．01,血清促黄体生成素水平下降（P〈0．01）,而荒漠肉苁蓉水提液可以缓解羟基脲造成的生精小管细胞退化,并在一定程度上调节血清性激素的水平。     

Hydroxycarbamide exposure and ovarian reserve in women with sickle cell disease in the Multicenter Study of Hydroxycarbamide

The application of modern ovarian reserve measures to women with sickle cell disease (SCD) may help answer longstanding questions about whether SCD or hydroxycarbamide (HC; also known as hydroxyurea) affect women’s reproductive lifespan. Anti-Müllerian hormone (AMH), an established marker of ovarian reserve, is used to assess the ovarian follicle pool. We used a standard clinical assay to measure AMH in 285 banked samples from 93 female subjects with haemoglobin SS from the historic Multicenter Study of Hydroxyurea (MSH), which led to the United States Food and Drug Administration approval of HC for adults with SCD. No samples from the randomised portion of the MSH remain, so samples from the decade-long MSH follow-up studies were analysed. Most subjects were exposed to HC (86/93). The median AMH levels were lower in study subjects than in age- and sex-matched reference values. The median AMH levels consistent with diminished ovarian reserve, a risk factor for infertility, occurred in subjects starting at the age of 25–30 years; in healthy women, this occurs after the age of 40 years. In multivariate analysis, taking HC was independently associated with a low AMH (β = 0·001, 95% confidence interval −0·002 to 0·000; P = 0·006). These results suggest that ovarian reserve is prematurely reduced in women with haemoglobin SS and raise the possibility that HC contributes to this finding.     

Regulation of granulocyte and macrophage colony-stimulating factor production by phytohaemagglutinin-treated blood mononuclear cells

The colony-stimulating activity (CSA) of medium conditioned by phytohaemagglutinin (PHA)-stimulated blood mononuclear cells was tested using granulocyte-macrophage colony-forming cells (GM-CFC) from normal bone marrow. Low concentrations of the conditioned medium stimulated granulocytic colony-forming cells (CFC) which formed colonies by the seventh day of incubation; higher concentrations stimulated the formation of macrophage colonies which were not seen until the end of the second week in culture.The colony-stimulating activities could not be demonstrated in adherent cell-depleted bone marrow cultures. This dependence of activity on adherent cells was confirmed by incubating different concentrations of conditioned medium with isolated adherent cells and then testing for colony-stimulating activity in cultures of non-adherent bone marrow cells. The activities of conditioned media following exposure to adherent cells corresponded to the results seen when the conditioned medium from PHA-stimulated mononuclear cell cultures was used to stimulate agar cultures of unseparated marrow. The results suggest that PHA-responsive mononuclear cells (probably T lymphocytes) may modulate the regulation of colony-stimulating factor (CSF) production by adherent colony-stimulating cells (CSC).     

Synthesis and X‐ray crystal structure study of the hydroxyurea and hydantoin derivatives of l‐valine

Abstract: The novel hydroxyurea 5 derivative of L ‐valine was prepared by aminolysis of N‐(1‐benzotriazolecarbonyl)‐L ‐valine cyclohexanemethylamide 4 with hydroxylamine. The corresponding hydantoin derivative 6 was synthesized by base catalyzed cyclization of the amide 4 . The exact stereostructure of hydantoin derivative 6 has been determined by X‐ray crystal structure analysis. The chiral atom of the hydantoin ring in 6 has S configuration what is in agreement with its configuration in the starting L ‐valine. The molecules of 6 are joined into infinite chains by N–H?O intermolecular hydrogen bond. The infinite chains are additionally linked by two C–H?O hydrogen bonds, thus forming two‐dimensional network. The hydantoin derivative of L ‐valine 6 and its L ‐leucine analogue LH have similar packing arrangements, so they are homostructural.     

Differential synchronization of leukemic cells in vivo by hydroxyurea

Flow cytometry (FCM) was used to monitor the cell cycle changes which occurred in the bone marrow cells of a patient with acute myeloblastic leukemia following pre-induction treatment with hydroxyurea. Flow cytometric and cytogenetic analysis showed two populations of cells: one hypertetraploid and presumably leukemic, and the other diploid and possibly normal. Sequential FCM monitoring of bone marrow cells after hydroxyurea demonstrated an early rise (after 24 h) in the S-phase component of diploid cells and a rise in the S-phase component of hypertetraploid cells 48–72 h later. Conventional induction therapy timed to coincide with this latter peak resulted in early remission.