Pub Date : 2018-09-01DOI: 10.1097/JBR.0000000000000011
Menglin Jiang, Lanting Wang, Sheng-an Chen, Fanping Yang, H. Xiong, Yu Su, Huizhong Zhu, Z. Qi, Shengying Qin, Xiaoqun Luo, Q. Xing
Abstract The majority of patients who experience cutaneous adverse drug reactions (cADRs) concurrently receive multiple medications, meaning that the causative drug remains unidentified. We explored the association between human leukocyte antigen (HLA) alleles and cADRs, regardless of the allergenic drug, to investigate whether different drug-induced cADRs were associated with the same or similar risk alleles in a Han Chinese population. We genotyped a sample of 146 cADR patients and 230 population controls from the same hospital and systematically analyzed the association between HLA Class I genes and cADRs. The carrier frequency of HLA-B*46:01 in cADR patients was found to be significantly higher than that in population controls (P = .0021, odds ratio [OR] = 2.18, 95% confidence interval [CI]: 1.33–2.58). Subgroup analysis showed that HLA-B*46:01 was significantly associated with urticaria and erythema multiforme (P = .0077, OR = 2.53, 95% CI: 1.30–4.91; and P = .0049, OR = 2.77, 95% CI: 1.39–5.50, respectively). Furthermore, a significant association was also detected between HLA-A*02:01 and erythema multiforme (P = .0038, OR = 2.65, 95% CI: 1.31–5.33). This study is the first to demonstrate that HLA-B*46:01 is a risk allele for cADRs in a Han Chinese population, indicating that screening for HLA-B*46:01 prior to the administration of medication may predict the risk of developing cADRs.
大多数发生皮肤药物不良反应(cADRs)的患者同时接受多种药物治疗，这意味着致病药物仍未确定。我们探讨了人类白细胞抗原(HLA)等位基因与cadr之间的关系，而不考虑致敏药物，以研究不同药物诱导的cadr是否与汉族人群中相同或相似的风险等位基因相关。我们对来自同一医院的146例cADR患者和230例人群对照进行了基因分型，系统地分析了HLA I类基因与cADR之间的关系。发现cADR患者HLA-B*46:01的携带者频率显著高于人群对照组(P =。0021，优势比[OR] = 2.18, 95%可信区间[CI]: 1.33-2.58)。亚组分析显示，HLA-B*46:01与荨麻疹和多形性红斑显著相关(P =。0077, or = 2.53, 95% ci: 1.30-4.91;和P =。0049, OR = 2.77, 95% CI分别为1.39 ~ 5.50)。此外，HLA-A*02:01与多形性红斑之间也存在显著相关性(P =。0038, or = 2.65, 95% ci: 1.31-5.33)。本研究首次证实HLA-B*46:01是中国汉族人群中发生cadr的风险等位基因，表明在给药前筛查HLA-B*46:01可预测发生cadr的风险。
{"title":"Association between HLA-B*46: 01 and cutaneous adverse drug reactions in Han Chinese","authors":"Menglin Jiang, Lanting Wang, Sheng-an Chen, Fanping Yang, H. Xiong, Yu Su, Huizhong Zhu, Z. Qi, Shengying Qin, Xiaoqun Luo, Q. Xing","doi":"10.1097/JBR.0000000000000011","DOIUrl":"https://doi.org/10.1097/JBR.0000000000000011","url":null,"abstract":"Abstract The majority of patients who experience cutaneous adverse drug reactions (cADRs) concurrently receive multiple medications, meaning that the causative drug remains unidentified. We explored the association between human leukocyte antigen (HLA) alleles and cADRs, regardless of the allergenic drug, to investigate whether different drug-induced cADRs were associated with the same or similar risk alleles in a Han Chinese population. We genotyped a sample of 146 cADR patients and 230 population controls from the same hospital and systematically analyzed the association between HLA Class I genes and cADRs. The carrier frequency of HLA-B*46:01 in cADR patients was found to be significantly higher than that in population controls (P = .0021, odds ratio [OR] = 2.18, 95% confidence interval [CI]: 1.33–2.58). Subgroup analysis showed that HLA-B*46:01 was significantly associated with urticaria and erythema multiforme (P = .0077, OR = 2.53, 95% CI: 1.30–4.91; and P = .0049, OR = 2.77, 95% CI: 1.39–5.50, respectively). Furthermore, a significant association was also detected between HLA-A*02:01 and erythema multiforme (P = .0038, OR = 2.65, 95% CI: 1.31–5.33). This study is the first to demonstrate that HLA-B*46:01 is a risk allele for cADRs in a Han Chinese population, indicating that screening for HLA-B*46:01 prior to the administration of medication may predict the risk of developing cADRs.","PeriodicalId":150904,"journal":{"name":"Journal of Bio-X Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129721460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-01DOI: 10.1097/JBR.0000000000000015
Lingyan Zhu, C. Qiu, C. Qiu, Ying Wang, Yuan Dong, Linxia Zhang, Weihui Fu, Jun Wei, Xiaoyan Zhang, Jianqing Xu
Abstract Human immunodeficiency virus (HIV)-infected individuals exhibit remarkable transcriptomic variation. Transcriptome analyses of antiretroviral therapy (ART)-free chronically infected HIV-1 patients with different clinical outcomes are likely to aid the development of vaccine and immune therapies. Here, we performed microarray analyses on whole-blood derived RNA from 89 ART-free HIV-1-infected individuals from 2 cohorts. The differentially expressed genes were analyzed between long-term non-progressors, viremic non-progressors and typical progressors, and between elite controllers and non-elite controllers among the long-term non-progressors. Several genes related to T-cell growth, proliferation and differentiation and antiapoptosis were upregulated, whereas interferon-stimulated genes and inflammatory genes were significantly downregulated in long-term non-progressors and viremic non-progressors. The observations above were further confirmed in the set of 261 genes that correlated with disease progression during a 5-year follow-up, which included 51 genes significantly associated with slower disease progression, and 210 genes associated with aggressive disease progression. Overall, our data suggest that it is vital to maintain the homeostasis of the immune system when mounting antiviral immune responses. Immune therapeutics able to reconstruct immune homeostasis are likely to be required for immune reconstitution in the context of ART, such as the administration of interleukin-7, healthy allogenic CD4+ T cells (providing CD4+ T-cell growth factors), or Tregs.
{"title":"Seeking “protective” and “harmful” immune genes during chronic HIV-1 infection by transcriptome analysis","authors":"Lingyan Zhu, C. Qiu, C. Qiu, Ying Wang, Yuan Dong, Linxia Zhang, Weihui Fu, Jun Wei, Xiaoyan Zhang, Jianqing Xu","doi":"10.1097/JBR.0000000000000015","DOIUrl":"https://doi.org/10.1097/JBR.0000000000000015","url":null,"abstract":"Abstract Human immunodeficiency virus (HIV)-infected individuals exhibit remarkable transcriptomic variation. Transcriptome analyses of antiretroviral therapy (ART)-free chronically infected HIV-1 patients with different clinical outcomes are likely to aid the development of vaccine and immune therapies. Here, we performed microarray analyses on whole-blood derived RNA from 89 ART-free HIV-1-infected individuals from 2 cohorts. The differentially expressed genes were analyzed between long-term non-progressors, viremic non-progressors and typical progressors, and between elite controllers and non-elite controllers among the long-term non-progressors. Several genes related to T-cell growth, proliferation and differentiation and antiapoptosis were upregulated, whereas interferon-stimulated genes and inflammatory genes were significantly downregulated in long-term non-progressors and viremic non-progressors. The observations above were further confirmed in the set of 261 genes that correlated with disease progression during a 5-year follow-up, which included 51 genes significantly associated with slower disease progression, and 210 genes associated with aggressive disease progression. Overall, our data suggest that it is vital to maintain the homeostasis of the immune system when mounting antiviral immune responses. Immune therapeutics able to reconstruct immune homeostasis are likely to be required for immune reconstitution in the context of ART, such as the administration of interleukin-7, healthy allogenic CD4+ T cells (providing CD4+ T-cell growth factors), or Tregs.","PeriodicalId":150904,"journal":{"name":"Journal of Bio-X Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117234050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Breast cancer metastasis is the root cause of deaths from breast cancer. Currently, endocrine therapy resistance in estrogen receptor (ER)-positive (ER+) breast cancer remains a major clinical issue. Moreover, ER-negative (ER−) breast cancer is often associated with distant recurrence and death. G-protein-coupled ER (GPER1) participates in endocrine therapy resistance and is involved in the malignant progression of breast cancer. However, the underlying detailed mechanisms remain obscure. Here we investigated the role and mechanism of GPER1 in the activation of focal adhesion kinase (FAK) using ER+ or ER− breast cancer cell lines. In SK-Br-3 cells (ER&agr;−/&bgr;−/GPER1+), both 17&bgr;-estradiol (E2) and the GPER1 agonist G1 resulted in rapid FAK phosphorylation. This action is due to GPER1 interaction with the non-receptor tyrosine kinase c-Src and subsequent activation of nuclear factor kappa B (NF-&kgr;B) signaling. Silencing of GPER1, c-Src or the nuclear factor kappa B p65 subunit blocked E2- or G1-induced SK-Br-3 cell migration and invasion. In MCF-7 cells (ER&agr;+/&bgr;+/GPER1+), silencing of GPER1, but not ER&agr; or ER&bgr;, abolished FAK phosphorylation induced by E2 or G1. In MDA-MB-231 cells (ER&agr;−/&bgr;+/GPER1−), E2 or G1 was also unable to stimulate E2-induced FAK phosphorylation. However, E2 and G1 regained the ability to induce FAK phosphorylation under conditions of overexpression of GPER1. In conclusion, we demonstrated that GPER1, but not ER&agr; or ER&bgr;, mediates FAK phosphorylation induced by E2 via the c-Src/p65 signaling pathway, which enhances cell migration and invasion. These findings may shed light on novel therapeutic strategies based on GPER1/FAK signaling pathways in suppression of breast cancer metastasis.
乳腺癌转移是乳腺癌死亡的根本原因。目前，雌激素受体(ER)阳性(ER+)乳腺癌的内分泌治疗抵抗仍然是一个主要的临床问题。此外，ER阴性(ER−)乳腺癌通常与远处复发和死亡有关。g蛋白偶联内质网(GPER1)参与内分泌治疗抵抗，参与乳腺癌的恶性进展。然而，潜在的详细机制仍然不清楚。本研究利用ER+或ER -乳腺癌细胞系研究了GPER1在局灶黏附激酶(FAK)活化中的作用和机制。在SK-Br-3细胞(ER&agr;−/&bgr;−/GPER1+)中，17&bgr;-雌二醇(E2)和GPER1激动剂G1均导致FAK快速磷酸化。这种作用是由于GPER1与非受体酪氨酸激酶c-Src相互作用以及随后激活核因子κ B (NF-&kgr;B)信号传导。沉默GPER1、c-Src或核因子κ B p65亚基可阻断E2-或g1诱导的SK-Br-3细胞迁移和侵袭。在MCF-7细胞(ER&agr +/&bgr +/GPER1+)中，GPER1沉默，而ER&agr不沉默;或ER&bgr;，消除E2或G1诱导的FAK磷酸化。在MDA-MB-231细胞(ER&agr;−/&bgr;+/GPER1−)中，E2或G1也不能刺激E2诱导的FAK磷酸化。然而，在GPER1过表达的条件下，E2和G1恢复了诱导FAK磷酸化的能力。总之，我们证明了GPER1，而不是ER&agr;或ER&bgr;通过c-Src/p65信号通路介导E2诱导的FAK磷酸化，从而增强细胞迁移和侵袭。这些发现可能揭示了基于GPER1/FAK信号通路抑制乳腺癌转移的新治疗策略。
{"title":"GPER1 promotes estrogen receptor negative breast cancer cell migration and invasion via non-genomic activation of c-Src/NF-&kgr;B/focal adhesion kinase cascade","authors":"Xiaosa Li, Qing Yan, Xingyan Xu, Weiyu Chen, Ping Li, Qiumei Xiang, Xiaoyang Xu, Xiaodong Fu","doi":"10.1097/JBR.0000000000000010","DOIUrl":"https://doi.org/10.1097/JBR.0000000000000010","url":null,"abstract":"Abstract Breast cancer metastasis is the root cause of deaths from breast cancer. Currently, endocrine therapy resistance in estrogen receptor (ER)-positive (ER+) breast cancer remains a major clinical issue. Moreover, ER-negative (ER−) breast cancer is often associated with distant recurrence and death. G-protein-coupled ER (GPER1) participates in endocrine therapy resistance and is involved in the malignant progression of breast cancer. However, the underlying detailed mechanisms remain obscure. Here we investigated the role and mechanism of GPER1 in the activation of focal adhesion kinase (FAK) using ER+ or ER− breast cancer cell lines. In SK-Br-3 cells (ER&agr;−/&bgr;−/GPER1+), both 17&bgr;-estradiol (E2) and the GPER1 agonist G1 resulted in rapid FAK phosphorylation. This action is due to GPER1 interaction with the non-receptor tyrosine kinase c-Src and subsequent activation of nuclear factor kappa B (NF-&kgr;B) signaling. Silencing of GPER1, c-Src or the nuclear factor kappa B p65 subunit blocked E2- or G1-induced SK-Br-3 cell migration and invasion. In MCF-7 cells (ER&agr;+/&bgr;+/GPER1+), silencing of GPER1, but not ER&agr; or ER&bgr;, abolished FAK phosphorylation induced by E2 or G1. In MDA-MB-231 cells (ER&agr;−/&bgr;+/GPER1−), E2 or G1 was also unable to stimulate E2-induced FAK phosphorylation. However, E2 and G1 regained the ability to induce FAK phosphorylation under conditions of overexpression of GPER1. In conclusion, we demonstrated that GPER1, but not ER&agr; or ER&bgr;, mediates FAK phosphorylation induced by E2 via the c-Src/p65 signaling pathway, which enhances cell migration and invasion. These findings may shed light on novel therapeutic strategies based on GPER1/FAK signaling pathways in suppression of breast cancer metastasis.","PeriodicalId":150904,"journal":{"name":"Journal of Bio-X Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122993104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-01DOI: 10.1097/JBR.0000000000000009
Ke Li, Y. Mao, Wenhan Qiu, Jianwen He, Dejuan Wang, Cheng Hu, Wen-tao Huang, S. Jie, J. Qiu
Abstract Metastasis is the main cause of cancer-specific death in patients with prostate cancer (PCa). Acyl-coenzyme A synthetase long-chain family member 3 (ACSL3) is involved in the metabolic reprogramming of multiple types of cancer cells, but its role in PCa metastasis remains largely unknown. Here, we determined the effect of overexpression or small interfering RNA-mediated depletion of ACSL3 on the migratory and invasive abilities of human PCa cell lines. We also conducted phospho-protein microarray analysis to identify signaling pathway components affected by ACSL3 modulation. Overexpression of ACSL3 promoted the migration and invasion of PCa cells, whereas ACSL3 downregulation had the opposite effects. Mechanistically, phospho-protein analysis showed that ACSL3 regulated the phosphorylation of AKT and the expression of matrix metalloproteinase9. Our results support a potential role for ACSL3 in promoting the metastatic behavior of PCa, possibly via AKT/matrix metalloproteinase9 pathways. Thus, ACSL3 could be a novel target for the development of treatments for PCa.
{"title":"Acyl-CoA synthetase long-chain 3 regulates AKT phosphorylation and the functional activity of human prostate cancer cells","authors":"Ke Li, Y. Mao, Wenhan Qiu, Jianwen He, Dejuan Wang, Cheng Hu, Wen-tao Huang, S. Jie, J. Qiu","doi":"10.1097/JBR.0000000000000009","DOIUrl":"https://doi.org/10.1097/JBR.0000000000000009","url":null,"abstract":"Abstract Metastasis is the main cause of cancer-specific death in patients with prostate cancer (PCa). Acyl-coenzyme A synthetase long-chain family member 3 (ACSL3) is involved in the metabolic reprogramming of multiple types of cancer cells, but its role in PCa metastasis remains largely unknown. Here, we determined the effect of overexpression or small interfering RNA-mediated depletion of ACSL3 on the migratory and invasive abilities of human PCa cell lines. We also conducted phospho-protein microarray analysis to identify signaling pathway components affected by ACSL3 modulation. Overexpression of ACSL3 promoted the migration and invasion of PCa cells, whereas ACSL3 downregulation had the opposite effects. Mechanistically, phospho-protein analysis showed that ACSL3 regulated the phosphorylation of AKT and the expression of matrix metalloproteinase9. Our results support a potential role for ACSL3 in promoting the metastatic behavior of PCa, possibly via AKT/matrix metalloproteinase9 pathways. Thus, ACSL3 could be a novel target for the development of treatments for PCa.","PeriodicalId":150904,"journal":{"name":"Journal of Bio-X Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124505298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-01DOI: 10.1097/JBR.0000000000000012
Jie Wang, Jiaqi Liu, Z. Xing, X. Meng, Menglu Zhang, X. Wang, Xiang Wang
Abstract Male breast cancer accounts for less than 0.5% of all breast cancer, and Paget disease of the breast in males is extremely rare. Here, we report 2 cases of Paget disease of the nipple areola complex with invasive ductal carcinoma as typical examples of male PDB. Case 1 was a 64-year-old man with an altered appearance of the left nipple, itching and redness, without a palpable breast mass at first. Case 2 was a 55-year-old man with a palpable mass in the left breast and histologically confirmed Paget disease of the nipple with invasive ductal carcinoma. Both patients underwent modified radical mastectomy but with different adjuvant therapies and remained well during follow-up with no recurrence. Furthermore, we reviewed all the sporadic cases of male PDB from the literature. This may help contribute to the development of diagnostic strategies and appropriate interventions for male Paget disease of the breast.
{"title":"Paget's disease of the nipple in males: two case reports and literature review","authors":"Jie Wang, Jiaqi Liu, Z. Xing, X. Meng, Menglu Zhang, X. Wang, Xiang Wang","doi":"10.1097/JBR.0000000000000012","DOIUrl":"https://doi.org/10.1097/JBR.0000000000000012","url":null,"abstract":"Abstract Male breast cancer accounts for less than 0.5% of all breast cancer, and Paget disease of the breast in males is extremely rare. Here, we report 2 cases of Paget disease of the nipple areola complex with invasive ductal carcinoma as typical examples of male PDB. Case 1 was a 64-year-old man with an altered appearance of the left nipple, itching and redness, without a palpable breast mass at first. Case 2 was a 55-year-old man with a palpable mass in the left breast and histologically confirmed Paget disease of the nipple with invasive ductal carcinoma. Both patients underwent modified radical mastectomy but with different adjuvant therapies and remained well during follow-up with no recurrence. Furthermore, we reviewed all the sporadic cases of male PDB from the literature. This may help contribute to the development of diagnostic strategies and appropriate interventions for male Paget disease of the breast.","PeriodicalId":150904,"journal":{"name":"Journal of Bio-X Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133243751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-06-01DOI: 10.1097/JBR.0000000000000007
Ruirui Wang, Lei Zhang, Jingjuan Xu, Zhan Gu, Li Zhang, G. Ji, Bao-cheng Liu
Abstract The human microbiome has become a new frontier of life sciences and plays a crucial role in determining individual and population health. Over thousands of years of medical practice, practitioners of traditional Chinese medicine (TCM) developed an understanding of the importance and activity of commensal microorganisms without access to modern technology. In this review, we examine the theoretical similarities between modern studies of the human microbiome and TCM, and propose feasible strategies to integrate the 2 fields. Advances in our understanding of the human microbiome will also help to modernize the practice of TCM, thereby providing a basis for bridging the gap between modern medicine and TCM.
{"title":"Human microbiome brings new insights to traditional Chinese medicine","authors":"Ruirui Wang, Lei Zhang, Jingjuan Xu, Zhan Gu, Li Zhang, G. Ji, Bao-cheng Liu","doi":"10.1097/JBR.0000000000000007","DOIUrl":"https://doi.org/10.1097/JBR.0000000000000007","url":null,"abstract":"Abstract The human microbiome has become a new frontier of life sciences and plays a crucial role in determining individual and population health. Over thousands of years of medical practice, practitioners of traditional Chinese medicine (TCM) developed an understanding of the importance and activity of commensal microorganisms without access to modern technology. In this review, we examine the theoretical similarities between modern studies of the human microbiome and TCM, and propose feasible strategies to integrate the 2 fields. Advances in our understanding of the human microbiome will also help to modernize the practice of TCM, thereby providing a basis for bridging the gap between modern medicine and TCM.","PeriodicalId":150904,"journal":{"name":"Journal of Bio-X Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123090000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-06-01DOI: 10.1097/JBR.0000000000000008
Z. Pan, Kai Chen, Peixian Chen, Liling Zhu, Shunrong Li, Qian Li, Fengtao Liu, M. Peng, F. Su, Qiang Liu, G. Ye, M. Zeng, E. Song
Abstract The accurate prediction of overall survival (OS) is important in clinical decision-making for breast cancer treatment. We developed a model to predict the OS of non-metastatic breast cancer patients in China. This multicenter study included 1844 non-metastatic breast cancer patients who underwent breast cancer surgery between January 2009 and December 2011 in 3 tertiary teaching hospitals in China. Data were collected retrospectively from the database of each hospital. We used univariate and multivariate Cox proportional hazard regression analyses to screen for predictors. A nomogram was developed in the training cohort (from Sun Yat-sen Memorial Hospital [SYSMH]), externally validated in 2 validation cohorts (from the First People's Hospital of Foshan [FPHF] and Sun Yat-sen University Cancer Center (SYUCC)), and compared with CancerMath, a mathematical-based model. We used Receiver Operating Characteristic curves and calibration plots to assess the models. At median follow-ups of 65.9, 68.6, and 66.2 months, the 5-year OS rates were 93.0%, 86.7%, and 91.0% in the SYSMH, FPHF, and SYUCC cohorts, respectively. We identified age, T stage, lymph node status, estrogen receptor, and human epidermal growth factor receptor 2 statuses as significant prognostic factors. A nomogram was developed and externally validated in the FPHF (area under the curve = 0.74) and SYUCC (area under the curve = 0.77) cohorts. Calibration plots showed that the predicted OS was consistent with the actual OS. The nomogram outperformed CancerMath in our study population. In summary, we developed a nomogram to predict survival among non-metastatic breast cancer patientsin China. This nomogram is superior to the CancerMath model in Chinese populations.
{"title":"Development of a nomogram to predict overall survival among non-metastatic breast cancer patients in China: a retrospective multicenter study","authors":"Z. Pan, Kai Chen, Peixian Chen, Liling Zhu, Shunrong Li, Qian Li, Fengtao Liu, M. Peng, F. Su, Qiang Liu, G. Ye, M. Zeng, E. Song","doi":"10.1097/JBR.0000000000000008","DOIUrl":"https://doi.org/10.1097/JBR.0000000000000008","url":null,"abstract":"Abstract The accurate prediction of overall survival (OS) is important in clinical decision-making for breast cancer treatment. We developed a model to predict the OS of non-metastatic breast cancer patients in China. This multicenter study included 1844 non-metastatic breast cancer patients who underwent breast cancer surgery between January 2009 and December 2011 in 3 tertiary teaching hospitals in China. Data were collected retrospectively from the database of each hospital. We used univariate and multivariate Cox proportional hazard regression analyses to screen for predictors. A nomogram was developed in the training cohort (from Sun Yat-sen Memorial Hospital [SYSMH]), externally validated in 2 validation cohorts (from the First People's Hospital of Foshan [FPHF] and Sun Yat-sen University Cancer Center (SYUCC)), and compared with CancerMath, a mathematical-based model. We used Receiver Operating Characteristic curves and calibration plots to assess the models. At median follow-ups of 65.9, 68.6, and 66.2 months, the 5-year OS rates were 93.0%, 86.7%, and 91.0% in the SYSMH, FPHF, and SYUCC cohorts, respectively. We identified age, T stage, lymph node status, estrogen receptor, and human epidermal growth factor receptor 2 statuses as significant prognostic factors. A nomogram was developed and externally validated in the FPHF (area under the curve = 0.74) and SYUCC (area under the curve = 0.77) cohorts. Calibration plots showed that the predicted OS was consistent with the actual OS. The nomogram outperformed CancerMath in our study population. In summary, we developed a nomogram to predict survival among non-metastatic breast cancer patientsin China. This nomogram is superior to the CancerMath model in Chinese populations.","PeriodicalId":150904,"journal":{"name":"Journal of Bio-X Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114037162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-06-01DOI: 10.1097/JBR.0000000000000001
Q. You, H. Su, Jingchao Wang, Jue Jiang, Guoliang Qing, Hudan Liu
Abstract T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous group of hematological tumors composed of distinct subtypes that vary in their genetic abnormalities. In the past decade, large-scale genomic analysis has shed new light on providing potentially important oncogenic or tumor suppressive candidates involved in the disease progression. Following in silico analysis, functional studies are usually performed to vigorously investigate the biological roles of candidate genes. For this purpose, animal models faithfully recapitulating the human disease are widely applied to decipher the mechanism underlying T-cell transformation. Conversely, an increased understanding of T-ALL biology, including identification of oncogene NOTCH1, TAL1 and MYC as well as tumor suppressor phosphatase and tensin homolog (PTEN), has significantly improved the development of T-ALL animal models. These progresses have opened opportunities for development of new therapeutic strategy to benefit T-ALL patients. In this review, we particularly summarize the mouse and zebrafish models used in T-ALL research and also the most recent advances from these in vivo studies.
{"title":"Animal models of T-cell acute lymphoblastic leukemia: mimicking the human disease","authors":"Q. You, H. Su, Jingchao Wang, Jue Jiang, Guoliang Qing, Hudan Liu","doi":"10.1097/JBR.0000000000000001","DOIUrl":"https://doi.org/10.1097/JBR.0000000000000001","url":null,"abstract":"Abstract T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous group of hematological tumors composed of distinct subtypes that vary in their genetic abnormalities. In the past decade, large-scale genomic analysis has shed new light on providing potentially important oncogenic or tumor suppressive candidates involved in the disease progression. Following in silico analysis, functional studies are usually performed to vigorously investigate the biological roles of candidate genes. For this purpose, animal models faithfully recapitulating the human disease are widely applied to decipher the mechanism underlying T-cell transformation. Conversely, an increased understanding of T-ALL biology, including identification of oncogene NOTCH1, TAL1 and MYC as well as tumor suppressor phosphatase and tensin homolog (PTEN), has significantly improved the development of T-ALL animal models. These progresses have opened opportunities for development of new therapeutic strategy to benefit T-ALL patients. In this review, we particularly summarize the mouse and zebrafish models used in T-ALL research and also the most recent advances from these in vivo studies.","PeriodicalId":150904,"journal":{"name":"Journal of Bio-X Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129734010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-06-01DOI: 10.1097/JBR.0000000000000003
Huidan Zhang, Naiwen Cui, Yamei Cai, F. Lei, D. Weitz
Understanding the complexity of biological systems requires a comprehensive analysis of their cell populations. Ideally, this should be done at the single cell level, because bulk analysis of the full population obscured many critical details due to artifacts introduced by averaging. However, this has been technically challenging due to the cumbersome procedure, low throughput, and high costs of performing analysis on a single-cell basis. Excitingly, technical improvements in single-cell RNA sequencing are making it economically practical to profile the transcriptomics of large populations of cells at the single-cell level, and have yielded numerous results that address important biological and medical questions. Further development of the technology and data analysis will significantly benefit the biomedical field by unraveling the function of individual cells in their microenvironments and modeling their transcriptional dynamics. Key words: cell transcriptomics; CEL-Seq; Hi-SCL; MARS-Seq; SCRB-Seq; single-cell RNA sequencing; Smart-Seq2; sNuc-seq
{"title":"Single-cell sequencing leads a new era of profiling transcriptomic landscape","authors":"Huidan Zhang, Naiwen Cui, Yamei Cai, F. Lei, D. Weitz","doi":"10.1097/JBR.0000000000000003","DOIUrl":"https://doi.org/10.1097/JBR.0000000000000003","url":null,"abstract":"Understanding the complexity of biological systems requires a comprehensive analysis of their cell populations. Ideally, this should be done at the single cell level, because bulk analysis of the full population obscured many critical details due to artifacts introduced by averaging. However, this has been technically challenging due to the cumbersome procedure, low throughput, and high costs of performing analysis on a single-cell basis. Excitingly, technical improvements in single-cell RNA sequencing are making it economically practical to profile the transcriptomics of large populations of cells at the single-cell level, and have yielded numerous results that address important biological and medical questions. Further development of the technology and data analysis will significantly benefit the biomedical field by unraveling the function of individual cells in their microenvironments and modeling their transcriptional dynamics. \u0000 \u0000 \u0000Key words: \u0000cell transcriptomics; CEL-Seq; Hi-SCL; MARS-Seq; SCRB-Seq; single-cell RNA sequencing; Smart-Seq2; sNuc-seq","PeriodicalId":150904,"journal":{"name":"Journal of Bio-X Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116116118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Lung cancer is a leading cause of cancer-related deaths worldwide. It mainly consists of 2 histological types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC, including squamous cell carcinoma and adenocarcinoma). The present study aimed to assess the role of serum progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), and carcinoembryonic antigen (CEA) and their combinations in the histological diagnosis of lung cancer (specially SCLC), which is of great importance for the initiation of treatment and prognostic implications. Serum ProGRP, NSE, and CEA were determined by the electrochemiluminescence immunoassay (ECLIA) in 66 patients with SCLC, 73 with adenocarcinoma, 44 with squamous cell carcinoma, 45 with non-malignant pulmonary diseases, and 50 healthy controls. Receiver operating characteristic curves were constructed to compare the predictive ability of each biochemical marker and their combined detection models to discriminate among the patients with lung cancers of different histological groups, benign pulmonary diseases and healthy individuals. In the ECLIA detection system, ProGRP showed the sensitivity and specificity for SCLC diagnosis were 71.2% and 91.1% to 93.2%, respectively. Among the markers, the largest area under the ROCs was for ProGRP in discriminating SCLC from benign pulmonary diseases, squamous cell carcinoma and adenocarcinoma (0.815, 0.859, and 0.835, respectively), which indicated that ProGRP was the most efficient marker for identifying SCLC. Besides, ProGRP and NSE exhibited almost equivalent diagnostic performance in discriminating SCLC from benign diseases. As for squamous cell carcinoma, we recommended proGRP, while for adenocarcinoma, the combination of proGRP and CEA was preferred. Remarkably, when ProGRP ⩽ 66 pg/mL, CEA was of great value in diagnosing SCLC and adenocarcinoma. If CEA ⩽ 5 ng/mL, the patient was at higher risk for SCLC, whereas the patient was more likely to be diagnosed with adenocarcinoma. Our study provided promising information about the diagnostic values of serum ProGRP, NSE, CEA in distinguishing SCLC from benign pulmonary diseases and NSCLC, which was of crucial clinical significance in the early diagnosis and therapy of SCLC.
{"title":"Choice of serum tumor markers in patients with small cell lung cancer: progastrin-releasing peptide, neuron-specific enolase, and carcinoembryonic antigen","authors":"Lisi Huang, Hai-yan Yan, Longqiaozi Sun, Ying Xu, Donghao Cai, Xiao-hui Li, Xinliang Chen, Xiao-hong Luo, C. Duan","doi":"10.1097/JBR.0000000000000002","DOIUrl":"https://doi.org/10.1097/JBR.0000000000000002","url":null,"abstract":"Abstract Lung cancer is a leading cause of cancer-related deaths worldwide. It mainly consists of 2 histological types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC, including squamous cell carcinoma and adenocarcinoma). The present study aimed to assess the role of serum progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), and carcinoembryonic antigen (CEA) and their combinations in the histological diagnosis of lung cancer (specially SCLC), which is of great importance for the initiation of treatment and prognostic implications. Serum ProGRP, NSE, and CEA were determined by the electrochemiluminescence immunoassay (ECLIA) in 66 patients with SCLC, 73 with adenocarcinoma, 44 with squamous cell carcinoma, 45 with non-malignant pulmonary diseases, and 50 healthy controls. Receiver operating characteristic curves were constructed to compare the predictive ability of each biochemical marker and their combined detection models to discriminate among the patients with lung cancers of different histological groups, benign pulmonary diseases and healthy individuals. In the ECLIA detection system, ProGRP showed the sensitivity and specificity for SCLC diagnosis were 71.2% and 91.1% to 93.2%, respectively. Among the markers, the largest area under the ROCs was for ProGRP in discriminating SCLC from benign pulmonary diseases, squamous cell carcinoma and adenocarcinoma (0.815, 0.859, and 0.835, respectively), which indicated that ProGRP was the most efficient marker for identifying SCLC. Besides, ProGRP and NSE exhibited almost equivalent diagnostic performance in discriminating SCLC from benign diseases. As for squamous cell carcinoma, we recommended proGRP, while for adenocarcinoma, the combination of proGRP and CEA was preferred. Remarkably, when ProGRP ⩽ 66 pg/mL, CEA was of great value in diagnosing SCLC and adenocarcinoma. If CEA ⩽ 5 ng/mL, the patient was at higher risk for SCLC, whereas the patient was more likely to be diagnosed with adenocarcinoma. Our study provided promising information about the diagnostic values of serum ProGRP, NSE, CEA in distinguishing SCLC from benign pulmonary diseases and NSCLC, which was of crucial clinical significance in the early diagnosis and therapy of SCLC.","PeriodicalId":150904,"journal":{"name":"Journal of Bio-X Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128136065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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