FNC, a novel nucleoside analogue inhibits cell proliferation and tumor growth in a variety of human cancer cells

Inhibition of cellular DNA synthesis is a strategy to block cancer cell division. Nucleoside analogues can incorporate into DNA and terminate DNA strand elongation. So far, several nucleoside analogues have been successfully used as anticancer drugs. FNC, 2′-deoxy-2′-β-fluoro-4′-azidocytidine is a novel cytidine analogue which demonstrated potent activity against hepatitis C virus (HCV). To investigate the therapeutic potential of FNC in human cancers we studied its activity in a number of cancer cells in vitro and in vivo. FNC potently inhibited cell proliferation with an IC₅₀ of 0.95–4.55 μM in a variety of aggressive human cancer cell lines including B-cell non-Hodgkin's lymphomas, lung adenocarcinoma and acute myeloid leukemia. Cells treated with FNC exhibited G1 and S cell cycle arrest at high and low dose, respectively, which confirms the mechanism of action of nucleoside analogues. Treatment of B-NHL cell lines with FNC induced apoptosis in a dose and time dependent manner. Finally, mouse xenograft models of hepatocarcinoma (H22), sarcoma (S180) and gastric carcinoma (SGC7901) demonstrated that FNC had significant tumor growth inhibition activity in a dose-dependent manner with low toxicity. Together, our results suggest that FNC may be a valuable therapy in cancer patients and warrant early phase clinical trial evaluation.     

获得性血友病A动物模型的建立及应用评价

目的建立获得性血友病A兔模型并评价其意义。方法输注获得性血友病A患者血浆入健康新西兰兔体内，测定注射血浆前30min及注射血浆后30min、60min、90min、120min时间点兔血浆活化部分凝血活酶时间（aPTT），观察获得性血友病A患者体内FⅧ抑制物对兔血浆aPTT值的影响，以等量正常人血浆注入新西兰兔作为对照。结果输注患者血浆入新西兰兔体内，兔血浆aPTT明显延长，且以时间依赖性方式抑制兔血浆FⅧ：C活性，输注正常人血浆对兔aPTT及BT值无明显影响。结论采用输注患者血浆入健康新西兰兔体内可成功建立获得性血友病动物模型，为进一步探讨获得性血友病A的新药物治疗，提供了药物试验的动物疾病模型。     

Identification of novel long non-coding RNAs in triple-negative breast cancer

Triple-negative breast carcinomas (TNBC) are characterized by particularly poor outcomes, and there are no established markers significantly associated with prognosis. Long non-coding RNAs (lncRNAs) are subclass of noncoding RNAs that have been recently shown to play critical roles in cancer biology. However, little is known about their mechanistic role in TNBC pathogenesis. In this report, we investigated the expression patterns of lncRNAs from TNBC tissues and matched normal tissues with Agilent Human lncRNA array. We identified 1,758 lncRNAs and 1,254 mRNAs that were differentially expressed (≥ 2-fold change), indicating that many lncRNAs are significantly upregulated or downregulated in TNBC. Among these, {"type":"entrez-nucleotide","attrs":{"text":"XR_250621.1","term_id":"530359780","term_text":"XR_250621.1"}}XR_250621.1 and NONHSAT125629 were the most upregulated and downregulated lncRNAs respectively. qRT-PCR was employed to validate the microarray analysis findings, and results were consistent with the data from the microarrays. GO and KEGG pathway analysis were applied to explore the potential lncRNAs functions, some pathways including microtubule motor activity and DNA replication were identified in TNBC pathogenesis. Our study revealed that a set of lncRNAs were differentially expressed in TNBC tissues, suggesting that they may play role in TNBC. These results shed light on lncRNAs’ biological functions and provide useful information for exploring potential therapeutic targets for breast cancer.     

Ki-67和人表皮生长因子受体-2在Ⅲ~ⅣA期唾液腺导管癌中的临床价值

目的 探讨Ki-67和人表皮生长因子受体-2(HER-2)在Ⅲ~Ⅳ_A期唾液腺导管癌(SDC)中的临床价值。方法 回顾性分析2012年1月至2020年12月确诊的52例Ⅲ~Ⅳ_A期SDC病例资料。全部患者均进行根治性手术及术后放疗,其中,15.4%局部区域复发,28.8%远处转移,17.3%区域复发伴远处转移。分析临床特征和Ki-67、HER-2等病理特征与局部复发、远处转移等预后的关系。χ²检验或Fisher''s精确概率法检验组间比较、Kaplan-Meier法生存分析,Cox模型多因素预后分析。结果 全组中位随访时间为37.6(10.7~77.5)个月。1年和2年局部区域无复发生存(LRRFS)、无远处转移生存(DMFS)、无进展生存(PFS)率分别为 86.5%、73.1%、65.4%和67.3%、55.8%、46.2%,3年无进展生存率(PFS)为33.3%。组间比较显示,年龄≥65岁,T分期、TNM分期、脉管癌栓、放疗剂量<60 Gy、Ki-67阳性指数、HER-2阳性与不同的预后分层有关。多因素分析显示,年龄、 Ki-67阳性指数≥60%和HER-2蛋白(3+)是 Ⅲ~Ⅳ_A 期SDC独立的预后不良因素(t =5.16、9.84、8.23, P<0.05)。结论 Ⅲ~Ⅳ_A期SDC仅进行根治性手术及术后放射治疗的远处转移率较高,Ki-67阳性指数和HER-2阳性是其独立的预后不良因素。