Xinmei Kang

Immunoglobulin G against myelin oligodendrocyte glycoprotein (MOG-IgG) is detectable in neuromyelitis optica spectrum disorder (NMOSD) without aquaporin-4 IgG (AQP4-IgG), but its pathogenicity remains unclear. In this study, we explored the pathogenic mechanisms of MOG-IgG in vitro and in vivo and compared them with those of AQP4-IgG. MOG-IgG-positive serum induced complement activation and cell death in human embryonic kidney (HEK)-293T cells transfected with human MOG. In C57BL/6 mice and Sprague-Dawley rats, MOG-IgG only caused lesions in the presence of complement. Interestingly, AQP4-IgG induced astroglial damage, while MOG-IgG mainly caused myelin loss. MOG-IgG also induced astrocyte damage in mouse brains in the presence of complement. Importantly, we also observed ultrastructural changes induced by MOG-IgG and AQP4-IgG. These findings suggest that MOG-IgG directly mediates cell death by activating complement in vitro and producing NMOSD-like lesions in vivo. AQP4-IgG directly targets astrocytes, while MOG-IgG mainly damages oligodendrocytes.

Cancer stem cells are enriched in triple‑negative breast cancer (TNBC) tumor tissues, which present strong capacities of proliferation and tumorigenicity. The present study detected the distribution of cancer stem cell markers cluster of differentiation (CD)44/CD24 and analyzed the clinical outcomes of different CD44/CD24 phenotypes in patients with TNBC. Multivariate Cox regression analyses were performed with regard to the prognostic value of cancer stem cell markers CD44/CD24, aldehyde dehydrogenase 1 and other baseline clinical characteristics, including tumor size, lymph node involved, adjuvant chemotherapy, Ki‑67, breast cancer susceptibility gene 1, cellular tumor antigen p53, vimentin and basal‑like status. The multivariate analyses showed that three of these factors, CD44/CD24 phenotype, basal‑like status and number of lymph nodes involved, had an impact on overall survival. Furthermore, patients with CD44+/CD24‑ phenotype, basal‑like tumors and ≥4 lymph nodes involved had a significantly worse prognosis. The expression of CD44 and CD24 was detected by double‑staining immunohistochemistry, which can locate cancer stem cells individually. Overall, the present results indicated that CD44/CD24 status evaluated by double‑staining immunohistochemistry constitutes an independent prognostic factor for TNBC.

Prognostic value of long non-coding RNA TUG1 in various tumors Prognostic value of long non-coding RNA TUG1 in various tumors

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Wei Li1, Na Li2, Xinmei Kang1, Ke Shi1 and Qiong Chen1 1Department of Geriatrics, Xiangya Hospital of Central South University, Changsha, Hunan Province, People’s Republic of China 2Department of Pathology, The First Affiliated Hospital of Hunan University of Medicine, Huaihua, Hunan Province, People’s Republic of China Correspondence to: Qiong Chen, email: qiongch@163.com Ke Shi, email: csushike@163.com Keywords: HOTTIP, lncRNA, cancer, clinical outcome, meta-analysis Received: March 28, 2017 Accepted: June 28, 2017 Published: July 11, 2017 ABSTRACT Human Homeobox A transcript at the distal tip (HOTTIP) is a putative oncogene in solid tumors. We performed a meta-analysis to investigate the association between HOTTIP expression and clinical outcomes in cancer patients. Eligible studies were collected from a literature search of the online electronic databases of Embase, Web of Science, PubMed and the China National Knowledge Infrastructure (up to January 2, 2017). Fixed-effects models were used to compute pooled odds ratios (ORs) and hazard ratios (HRs). In total, we analyzed nine studies that included 800 patients with seven tumor types. Overall survival was lower for patients with high HOTTIP expression than for those with low expression (HR = 2.30, 95% confidence interval [CI]: 1.81–2.91, P < 0.001). High HOTTIP expression was also associated with lymph node metastasis (OR = 2.40, 95% CI: 1.70–3.37, P < 0.001), distant metastasis (OR = 3.30, 95% CI: 1.78–6.12, P < 0.001), poor tumor differentiation (OR = 1.55, 95% CI: 1.03–2.32, P = 0.036) and a poor clinical stage (OR = 3.28, 95% CI: 2.22–4.83, P < 0.001). This meta-analysis demonstrated that high HOTTIP expression in cancer patients is associated with poor clinical outcomes. Thus, HOTTIP is a potential predictive biomarker of cancer.

Scientific Reports 7: Article number: 42069; published online: 03 February 2017; updated: 11 April 2017 The original version of this Article contained an error in the order of the authors, where “Xinmei Kang, Ximing Guo, Xingjian Niu, Weiwei An, Suhan Li, Zhaoliang Liu, Yue Yang, Na Wang, Qicheng Jiang, Caichuan Yan, Hui Wang and Qingyuan Zhang” was incorrectly given as “Xinmei Kang, Ximing Guo, Weiwei An, Xingjian Niu, Suhan Li, Zhaoliang Liu, Yue Yang, Na Wang, Qicheng Jiang, Caichuan Yan, Hui Wang and Qingyuan Zhang”.

Gold nanorods are effective photothermal agents in diagnosis and treatment of cancer due to their specific near-infrared laser absorption. However, tumor photothermal therapy by nanorods alone is lack of targeting. Here, we described a novel nanocomplex made up of gold nanorods, porphyrin, and trastuzumab, called TGNs and investigated the TGN-mediated photothermal therapy as a potential alternative treatment of targeting HER2-positive breast cancers. By conjugating trastuzumab and porphyrin to the surface of gold nanorods, we have increased the targeting specificity and amplified the detecting effectiveness at the same time. TGN-mediated photothermal ablation by near-infrared laser led to a selective destruction of HER2-positive cancer cells and significantly inhibited tumor growth in mouse models bearing HER2 over-expressed breast cancer xenograft with less toxicity. Moreover, TGNs provided better therapeutic efficacy in comparison with the conventional molecule targeted therapy. Our current data suggest a highly promising future of TGNs for its therapeutic application in trastuzumab-resistant breast cancers.

It is believed that breast cancer stem cells (BCSCs), like normal stem cell counterparts, have the capacity of self-renewal and differentiation. Simultaneously, estrogen receptor (ER)-negative (-) BCSCs are affected by surrounding differentiated ER-positive (+) tumor cells by virtue of paracrine signaling within the tumor micro-environment. Genistein (GEN), as a sort of phytoestrogen, can act on ER+ breast cancer cells but the role of GEN in the differentiation of neighboring ER- BCSCs has not been defined. Transwell co-culture system was utilized so as to elaborate the interaction between well-differentiated ER+ breast cancer cells (MCF-7) and ER- breast cancer stem/progenitor cells (mammospheres derived from MDA-MB-231 cells). GEN-induced differentiation of BCSCs was analyzed by mammospheres formation assay, flow cytometry and RT-PCR after a 3 day solo-culture or co-culture. We find that GEN sized 2 µM, and 40 nM, effectively promotes morphological alteration of mammospheres, reduces the ratio of subset of CD44+/CD24-/ESA+ cells and upregulates the expression of differentiated cell markers of mammospheres in co-culture system, but not in solo-culture condition. Besides, we demonstrate that the differentiation-inducing effect of GEN on mammospheres is associated with PI3K/Akt and MEK/ERK signaling pathways which are activated by amphiregulin released from ER+ cancer cells. These results indicate that GEN was able to induce the differentiation of breast cancer stem/progenitor cells through interaction with ER+ cancer cells by a paracrine mechanism.

Glycometabolism is a distinctive aspect of energy metabolism in breast cancer, and key glycometabolism enzymes/pathways (glycolysis, hexosamine biosynthetic pathway, and pentose phosphate pathway) may directly or indirectly affect the clinical features. In this study, we analyzed the particular correlation between the altered glycometabolism and clinical features of breast cancer to instruct research and clinical treatment. Tissue microarrays containing 189 hollow needle aspiration samples and 295 triple-negative breast cancer tissues were used to test the expression of M2 isoform of pyruvate kinase (PKM2), glutamine-fructose-6-phosphate transaminase 1 (GFPT1), glucose-6-phosphate dehydrogenase (G6PD), and p53 by immunohistochemistry and the intensity of these glycometabolism-related protein was evaluated. Chi-square test, Kaplan-Meier estimates, and Cox proportional hazards model were used to analyze the relationship between the expression of these factors and major clinical features. PKM2, GFPT1, and G6PD affect the pathologic complete response rate of neoadjuvant chemotherapy patients in different ways; pyruvate kinase muscle isozyme 2 (PKM2) and G6PD are closely associated with the molecular subtypes, whereas GFPT1 is correlated with cancer size. All these three factors as well as p53 have impacts on the progression-free survival and overall survival of triple-negative breast cancer patients. Cancer size shows significant association with PKM2 and GFPT1 expression, while the pN stage and grade are associated with PKM2 and G6PD expression. Our study support that clinical characteristics are reflections of specific glycometabolism pathways, so their relationships may shed light on the orientation of research or clinical treatment. The expression of PKM2, GFPT1, and G6PD are hazardous factors for prognosis: high expression of these proteins predict worse progression-free survival and overall survival in triple-negative breast cancer, as well as worse pathologic complete response rate in neoadjuvant chemotherapy breast cancer. However, p53 appears as a protective factor only in the patients receiving neoadjuvant chemotherapy. All the four proteins, PKM2, GFPT1, G6PD and p53, are prognostic markers of breast cancer. The correlation among them suggests that there may be crosstalk of the four proteins in breast cancer.