Cancer Stem Cells and Circulatory Tumor Cells Promote Breast Cancer Metastasis

Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC.     

Single-dose combination nanovaccine induces both rapid and durable humoral immunity and toxin neutralizing antibody responses against Bacillus anthracis

Bacillus anthracis, the causative agent of anthrax, continues to be a prominent biological warfare and bioterrorism threat. Vaccination is likely to remain the most effective and user-friendly public health measure to counter this threat in the foreseeable future. The commercially available AVA BioThrax vaccine has a number of shortcomings where improvement would lead to a more practical and effective vaccine for use in the case of an exposure event. Identification of more effective adjuvants and novel delivery platforms is necessary to improve not only the effectiveness of the anthrax vaccine, but also enhance its shelf stability and ease-of-use. Polyanhydride particles have proven to be an effective platform at adjuvanting the vaccine-associated adaptive immune response as well as enhancing stability of encapsulated antigens. Another class of adjuvants, the STING pathway-targeting cyclic dinucleotides, have proven to be uniquely effective at inducing a beneficial inflammatory response that leads to the rapid induction of high titer antibodies post-vaccination capable of providing protection against bacterial pathogens. In this work, we evaluate the individual contributions of cyclic di-GMP (CDG), polyanhydride nanoparticles, and a combination thereof towards inducing neutralizing antibody (nAb) against the secreted protective antigen (PA) from B. anthracis. Our results show that the combination nanovaccine elicited rapid, high titer, and neutralizing IgG anti-PA antibody following single dose immunization that persisted for at least 108 DPI.     

血小板GPⅡb/Ⅲa 受体抑制剂(A辅剂)在血栓弹力图血小板聚集功能检测中的应用

目的评估以功能性纤维蛋白原(功纤杯)检测结果为标准的血栓弹力图(TEG)血小板聚集功能检测中在巴曲酶杯(A杯)内加入血小板GPⅡb/Ⅲa受体抑制剂(A辅剂)对检测结果的影响。方法从2019年12月~2020年5月在本院神经内科、心内科、综合科和康复科就诊、做TEG血小板聚集功能检测的患者中收集100(人)份全血标本,根据TEG测得的A杯血块强度(MA)值(mm)将血标本分为MA<25组(n=50)和MA≥25组(n=50),2组再各细分为A杯组(各自为n=50)、A辅剂组(在A杯中加入A辅剂)(各自为n=50)、功纤杯组(各自为n=50)3个亚组,各亚组均检测2次;比较各亚组间的血小板二磷酸腺苷(ADP)与花生四烯酸(AA)途径抑制率的线性相关(R2)、血小板抑制率的差异,以及3个亚组间ADP与AA途径药物疗效判读结果的一致性。结果 1)MA<25 mm组,血小板ADP及AA途径抑制率(%)A杯、A辅剂与功纤杯3个亚组分别为32.00±17.44 vs 30.19±17.44 vs 30.07±16.18,24.3±33.53 vs 22.53±30.9 vs 22.37±31.2(均为R2>0.975);2)MA≥25 mm组,血小板ADP及AA途径抑制率(%)A杯、A辅剂与功纤杯3个亚组分别为34.34±33.59 vs 18.45±24.42 vs 18.01±24.33,23.19±39.33 vs 8.48±21.75 vs 8.31±21.7(其中A杯组与A辅剂组比较均为R2<0.8,A辅剂组与功纤杯组均为R2>0.975);3)以功纤杯组检测结果为标准,A杯组与A辅剂组间ADP和AA途径药物疗效判读正确率分别为82%(41/50)vs 100%(50/50)、84%(42/50)vs 100%(50/50)(P<0.05),而A辅剂组与功纤杯组之间2种途径药物疗效判读结果一致(P>0.05)。结论在TEG的血小板聚集功能检测中A杯内添加A辅剂可以有效抑制A杯中非特异激活的血小板,真实反映纤维蛋白原的功能,故提高了其血小板抑制率检测结果的准确性。     

Endocrine Therapy for Breast Cancer

Endocrine therapy is the primary treatment for the most common types of breast cancer. Endocrine agents work by inhibiting the tumor-stimulating effects of estrogen in hormone-sensitive tumors. A new class of targeted drugs synergize with endocrine agents to improve survival for patients with metastatic disease. Endocrine therapy is continued for years, and long-term survival is common, although toxicities often occur due to the alteration of the physiologic effects of estrogen. It is important, therefore, that primary care providers remain knowledgeable about patient needs during and after treatment.     

Bevacizumab plus erlotinib in Chinese patients with untreated,EGFR-mutated,advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study

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雄激素受体调控基因组表达与去势抵抗性前列腺癌关系探索

目的探索雄激素受体调控基因与前列腺癌发生去势抵抗的关系。方法选取80例经病理检查和临床资料证实并采用内分泌治疗的前列腺癌患者,随访获取发生去势抵抗时间,定量即时聚合酶链锁反应(qRT-PCR)检测确诊时穿刺标本的六个雄激素受体调控基因KLK3(PSA),PMEPA1,NKX3.1,ODC1,AMD1和ERG表达并分析两者之间的关系。结果将六个雄激素受体调控基因相对表达量进行Z分数标准化处理,将所有病例按去势抵抗时间由短向长排列,分析六个基因Z分数及累积强度(CI),发现六个基因的表达情况与患者去势抵抗时间无明显相关性。结论初诊前列腺癌时患者雄激素受体功能与前列腺癌去势抵抗性无直接关系。