Identifying cell and molecular stress after radiation in a three-dimensional (3-D) model of oral mucositis

Mature adipocytes are excellent candidates to influence tumor behavior through heterotypic signaling processes since these cells produce hormones, growth factors, cytokines and other molecules, a heterogeneous group of molecules named adipokines. Using a 2D coculture system, we demonstrate that breast tumor cells previously co-cultivated with mature adipocytes exhibit radioresistance and an earlier and higher increase in the effector kinase Chk1, a phenotype that was associated with decreased cell death as compared to tumor cells grown alone. Interestingly, the adipocytes-induced tumor changes taking place during the coculture time preceding the exposure to IR were sufficient to confer the radioresistant effect. Notorious among the changes brought by adipocytes was the significant increase of IL-6 expression in tumor cells, whose activity may well account for the observed tumor cell protection from IR toxicity. Indeed, our data confirmed the protective role of this cytokine as tumor cells incubated after irradiation with recombinant IL-6 exhibit an increased in Chk1 phosphorylation and a radioresistant phenotype, thus far recapitulating the effects observed in the presence of adipocytes. Our current study sheds light on a new role of tumor-surrounding adipocytes in fostering a radioresistant phenotype in breast tumors, a finding that might have important clinical implications in obese patients that frequently exhibit aggressive diseases.     

乳腺错构瘤X线及病理特征分析

目的：探讨乳腺错构瘤的病理及影像学特征。方法：对11例乳腺错构瘤患者的临床特征、X线征象及病理表现进行回顾性分析。结果：患者平均年龄为46岁（26-58岁）,10例可触及肿块（9例患者自己发现,1例体检摄片时发现）,还有1例未能触及肿块。左乳7例,右乳4例,5／11（45．5％）肿块位于外上象限。11例钼靶X线平片均发现乳腺肿块,多数肿块呈卵圆形,边界清楚。肿块平均最大直径为6．Ocm（2．5-13．0cm）,6／11（54．5％）肿块呈混合密度影。4／11例（36．4％）术前X线确诊。镜下：肿瘤由数量不等、杂乱无章的乳腺导管、小叶和成熟的脂肪细胞及纤维纽织混杂组成。结论：混合密度影是其特异性X线表现,不同个体肿瘤各成分比例的不同导致X线表现差异较大。     

MicroRNA-30a sensitizes tumor cells to cis-platinum via suppressing beclin 1-mediated autophagy

Autophagy is activated in cancer cells during chemotherapy and often contributes to tumor chemotherapy resistance. In this study, we characterized the role of microRNA-30a (miR-30a) in the coordination of cancer cell apoptosis and autophagy, which determines the sensitivity of cancer cells to chemotherapy. First, the autophagy activity in cancer cells increased after cis-dichloro-diamine platinum (cis-DDP) or Taxol treatment, as indicated by the enhanced expression of beclin 1, a key regulator of autophagy, and increased number of LC3-positive autophagosomes. Second, miRNA screening using a TaqMan probe-based quantitative RT-PCR assay identified that miR-30a, a miRNA that targets beclin 1, was significantly reduced in tumor cells by cis-DDP treatment. Forced expression of miR-30a significantly reduced beclin 1 and the autophagy activity of tumor cells induced by cis-DDP. Third, the blockade of tumor cell autophagy activity by miR-30a expression or 3-methyladenine significantly increased tumor cell apoptosis induced by cis-DDP treatment. Finally, an in vivo tumor implantation mouse model clearly showed that elevation of miR-30a in implanted tumor cells by administration of the recombinant lentivirus expressing miR-30a strongly enhanced cis-DDP-induced apoptosis of tumor cells. In conclusion, our results demonstrate for the first time that miR-30a can sensitize tumor cells to cis-DDP via reducing beclin 1-mediated autophagy and that increasing miR-30a level in tumor cells represents a novel approach to enhance the efficacy of chemotherapy during cancer treatment.     

Enhanced intrinsic migration of aggressive breast cancer cells by inhibition of Rac1 GTPase

Rac GTPases are known to play a crucial role in regulating cytoskeletal changes necessary for cell migration. Migration has been shown to be positively regulated by Rac in most cell types. However, there is also a large body of conflicting evidence in some other cell types with respect to the role of Rac in migration, suggesting that Rac GTPases regulate cell migration in a cell type-dependent manner. In the present study, we have characterized the effects of Rac1 GTPase inhibition on the migratory abilities of a number of breast cancer cell lines with differential degrees of tumorigenic and metastatic potentials. We show that Rac1 inhibition in non-metastatic (MCF-7, T-47D) or moderately metastatic (Hs578T) cell lines results in inhibition of migration, whereas in highly metastatic cell lines (MDA-MB-435, MDA-MB-231, and C3L5) Rac1 inhibition results in stimulation of migration. This stimulation of migration following Rac1 inhibition is also accompanied by the enhanced RhoA activity, suggesting a possible existence of a dominating role of RhoA over Rac1 in regulating intrinsic migration of the highly metastatic breast cancer cells.     

白花蛇舌草醇提取物对乳腺癌T-47D细胞株生长的抑制作用

目的：观察白花蛇舌草醇提取物对乳腺癌细胞T-47D生长的影响。方法：采用平皿克隆形成实验、软琼脂集落形成实验和BrdUrd（溴脱氧尿苷）掺入实验,观察不同浓度的白花蛇舌草醇提取物（1.0μg/mL,3.0μg/mL,10μg/mL,30μg/mL,100μg/mL）对T-47D细胞锚定依赖性生长和软琼脂集落形成能力及核酸合成的抑制作用。结果：①随着白花蛇舌草醇提取物浓度的升高,对T-47D细胞的生长呈现明显抑制作用;②白花蛇舌草醇提取物可呈浓度依赖性抑制对数生长期T-47D细胞核酸合成。结论：白花蛇舌草醇提取物可能通过影响肿瘤细胞核酸合成而抑制T-47D细胞生长。     

Antitumor effects of fusions composed of dendritic cells and fibroblasts transfected with genomic DNA from tumor cells

Based on several previous studies indicating that transfection of genomic DNA can stably alter the character of the cells that take up the exogenous DNA, we investigated antitumor immunity conferred by fusions of syngeneic dendritic cells (DCs) and allogeneic fibroblasts (NIH3T3) transfected with genomic DNA from B16 tumor cells. Fusion cells (FCs) composed of dendritic and genetically engineered NIH3T3 cells were prepared with polyethylene glycol, and fusion efficiency was 30.3%. Prior immunization with FCs prevented tumor formation upon challenge with B16 tumor cells. Efficacy was reduced when studies were performed in mice depleted of NK cells. Vaccination with FCs containing DCs and fibroblasts transfected with denatured DNA did not inhibit tumor growth. Cytotoxic T cell (CTL) activity of spleen cells from immunized mice against both Yac-1 and tumor cells was also stimulated by administration of FCs compared with the activity observed for cells obtained from naïve mice. These data demonstrate the therapeutic efficacy of fusion cell–based vaccine therapy using syngeneic DCs and allogeneic fibroblasts transfected with tumor-derived genomic DNA.     

母乳微生物及其对婴幼儿健康影响的研究进展

母乳是新生儿最佳的营养来源,不仅提供丰富的营养物质,还能通过自身独特的微生物群影响新生儿肠道细菌的初始定植和机体健康。培养法和基因组测序法均揭示了母乳微生物的多样性和稳定性,除双歧杆菌和乳杆菌外,母乳中还含有多种潜在的益生菌。人乳低聚糖（human milk oligosaccharides,HMOs）是母乳中仅次于乳糖和脂类的第三丰富的营养物质。作为一种天然益生元,HMOs可以选择性地促进有益细菌的生长,从而在促进母乳喂养婴幼儿健康发育方面起着关键作用。本文总结了母乳中微生物的种类、来源、哺乳期间的变化及其与HMOs之间的关系,讨论了母乳微生物对婴幼儿健康的潜在影响,包括抑制病原体入侵肠道、促进免疫系统发育、调节婴幼儿代谢和改善早期认知发育等,以期为母乳源益生菌的开发提供理论指导。