Enhanced detection and comprehensive in situ phenotypic characterization of circulating and disseminated heteroploid epithelial and glioma tumor cells

Conventional strategy of anti-EpCAM capture and immunostaining of cytokeratins (CKs) to detect circulating tumor cells (CTCs) is limited by highly heterogeneous and dynamic expression or absence of EpCAM and/or CKs in CTCs. In this study, a novel integrated cellular and molecular approach of subtraction enrichment (SE) and immunostaining-FISH (iFISH) was successfully developed. Both large or small size CTCs and circulating tumor microemboli (CTM) in various biofluid samples including cerebrospinal fluid (CSF) of cancer patients and patient-derived-xenograft (PDX) mouse models were efficiently enriched and comprehensively identified and characterized by SE-iFISH. Non-hematopoietic CTCs with heteroploid chromosome 8 were detected in 87–92% of lung, esophageal and gastric cancer patients. Characterization of CTCs performed by CK18-iFISH showed that CK18, the dual epithelial marker and tumor biomarker, was strong positive in only 14% of lung and 24% of esophageal CTCs, respectively. Unlike conventional methodologies restricted only to the large and/or both EpCAM and CK positive CTCs, SE-iFISH enables efficient enrichment and performing in situ phenotypic and karyotypic identification and characterization of the highly heterogeneous CTC subtypes classified by both chromosome ploidy and the expression of various tumor biomarkers. Each CTC subtype may possess distinct clinical significance relative to tumor metastasis, relapse, therapeutic drug sensitivity or resistance, etc.     

Head and neck cancer subtypes with biological and clinical relevance: Meta-analysis of gene-expression data

Head and neck squamous cell carcinoma (HNSCC) is a disease with heterogeneous clinical behavior and response to therapies. Despite the introduction of multimodality treatment, 40–50% of patients with advanced disease recur. Therefore, there is an urgent need to improve the classification beyond the current parameters in clinical use to better stratify patients and the therapeutic approaches. Following a meta-analysis approach we built a large training set to whom we applied a Disease-Specific Genomic Analysis (DSGA) to identify the disease component embedded into the tumor data. Eleven independent microarray datasets were used as validation sets.Six different HNSCC subtypes that summarize the aberrant alterations occurring during tumor progression were identified. Based on their main biological characteristics and de-regulated signaling pathways, the subtypes were designed as immunoreactive, inflammatory, human papilloma virus (HPV)-like, classical, hypoxia associated, and mesenchymal. Our findings highlighted a more aggressive behavior for mesenchymal and hypoxia-associated subtypes. The Genomics Drug Sensitivity Project was used to identify potential associations with drug sensitivity and significant differences were observed among the six subtypes.To conclude, we report a robust molecularly defined subtype classification in HNSCC that can improve patient selection and pave the way to the development of appropriate therapeutic strategies.     

Clinical Characteristics of the Respiratory Subtype in Panic Disorder Patients

Objective

Panic disorder has been suggested to be divided into the respiratory and non-respiratory subtypes in terms of its clinical presentations. The present study aimed to investigate whether there are any differences in treatment response and clinical characteristics between the respiratory and non-respiratory subtypes of panic disorder patients.

Methods

Among the 48 patients those who completed the study, 25 panic disorder patients were classified as the respiratory subtype, whereas 23 panic disorder patients were classified as the non-respiratory subtype. All patients were treated with escitalopram or paroxetine for 12 weeks. We measured clinical and psychological characteristics before and after pharmacotherapy using the Panic Disorder Severity Scale (PDSS), Albany Panic and Phobic Questionnaire (APPQ), Anxiety Sensitivity Index-Revised (ASI-R), State-Trait Anxiety Inventory (STAI-T, STAI-S), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HAM-D).

Results

The prevalence of the agoraphobia was significantly higher in the respiratory group than the non-respiratory group although there were no differences in gender and medication between the two groups. The respiratory group showed higher scores on the fear of respiratory symptoms of the ASI-R. In addition, after pharmacotherapy, the respiratory group showed more improvement in panic symptoms than the non-respiratory group.

Conclusion

Panic disorder patients with the respiratory subtype showed more severe clinical presentations, but a greater treatment response to SSRIs than those with non-respiratory subtype. Thus, classification of panic disorder patients as respiratory and non-respiratory subtypes may be useful to predict clinical course and treatment response to SSRIs.     

Ethnic variation of the histological subtypes of renal cell carcinoma in Singapore

IntroductionThe purpose of this study is to determine how the histological subtypes of renal cell carcinoma (RCC) vary among the heterogeneous Singaporean population and how this affects the survival rate.Patients and methodsThe data analyzed in this retrospective study of the histological subtypes of RCC cases treated in Singapore General Hospital over a ten year period (2001–2010) were obtained from the Cancer Registry of the hospital's department of urology. Statistical analysis was done using the Statistical Package Service Solution (SPSS) version 17.0 software. Chi Square and z-tests were used where appropriate; a p value <0.05 was considered significant.ResultsThe records of 676 patients studied showed that 80.8% of the patients were Chinese, while Malays, Indians and other minor groups accounted for 6.5%, 4.6% and 8.1%, respectively. The mean age (SD) at presentation was 58.1 (12.1), 57.6 (10) and 55.1 (9.6) years for the Chinese, Indians and Malays, respectively. The commonest histological variant in each of the ethnic groups, irrespective of sex, was clear cell carcinoma which accounted for 79.7% of all the histological subtypes found in Chinese, for 70.5% in Malaysian and 77.4% in Indian patients. The sarcomatoid histological subtype was found in 4.3% of the studied population with a high prevalence in the Indian ethnicity (9.7%). The worst survival rate (33.3%) was recorded among Malays with the papillary cell subtype, and also in the Chinese population the highest mortality rate was found in cases with the papillary cell subtype (16.9%).ConclusionThe commonest histological subtype of RCC in each of the studied ethnic groups in Singapore is clear cell carcinoma. However, most of the cancer deaths in Chinese (16.9%) and Malays (66.7%) were associated with the papillary cell type, while in Indians the sarcomatoid component prevailed (9.7%). Thus, the usual prognostic trend for RCC subtypes cannot be applied to all Singaporean ethnicities, necessitating individualization of prognosis for each group.     

苓槐丸治疗慢性湿疹的临床观察及实验研究

目的：观察应用苓槐丸（Ling Huai Wan,LHW）治疗慢性湿疹临床效果,检测T细胞亚群在治疗过程中的变化,初步探讨苓槐丸治疗慢性湿疹的可能机制。方法：将120例慢性湿疹患者按随机数字表法分成苓槐丸组、联合用药组（咪唑斯汀＋苦参片）各60例,观察两组患者的临床疗效。并对苓槐丸组中随机抽取的20例患者（实验组）治疗前后T细胞亚群进行检测,与健康成年人（正常组）比较,观察苓槐丸治疗后对湿疹患者T细胞亚群的影响。结果：苓槐丸组的总有效率96.67%,与联合用药组（78.33%）比较差异有统计学意义（P〈0.05）。实验结果显示,实验组经苓槐丸治疗后,其T细胞亚群数量与正常组比较差异无统计学意义（P〉0.05）。结论：苓槐丸治疗慢性湿疹疗效显著,其作用机理与恢复T细胞亚群比例、改善T细胞免疫功能有关。     

The expression of calpain-1 and androgen receptor in breast cancer and their correlation with clinicopathological characteristics: An immunohistochemical retrospective study

Breast cancer is a heterogeneous disease with different biological outcome and ability to acquire resistance to therapy. The calpain family of proteases and androgen receptor (AR) are implicated in breast cancer pathogenesis and progression and are potential targets for novel treatment regimens. The aim of this study was to investigate the expression of calpain-1 and AR in breast cancer and to correlate their expression with clinicopathological variables and prognosis of patients.In this study we enrolled 219 breast cancer patients with long term follow-up information available. Immunohistochemical methods on a tissue microarray were used to investigate expression of calpain-1 and AR in tumor cells.The expression of calpain-1 and AR both differed significantly between the tumor subtypes of patients (p = 0.002 and p = 0.042 respectively). High calpain-1 expression was associated with patient’s age over 50 years (p = 0.005) and positive ER status (p = 0.009), but not with other clinicopathological variables. Women with AR negative breast cancers were more likely to be older (p = 0.016), to have bigger tumors (p = 0.032), higher stage of the disease (p = 0.026), presence of exulceration (p = 0.017), negative ER status (p = 0.007) and higher Ki-67 proliferative index (p = 0.027). Calpain-1 expression was not associated with breast cancer specific overall survival in the total cohort of patients, however low calpain-1 expression was associated with adverse survival (p = 0.018) in triple negative subgroup of patients. Low calpain-1 expression was also associated with significantly shorter 5-year disease-free survival in total cohort of patients (p = 0.03). AR status was not associated with overall and disease-free survival of patients.This study has demonstrated that the expression of calpain-1 and androgen receptors are associated with important clinicopathological variables. The expression of calpain-1 was associated with improved disease-free survival of all analyzed patients and with improved overall survival of triple negative breast cancer patients.     

人血VitD含量与CD4+T-淋巴细胞的相关性研究

目的研究人血25-(OH)-VitD含量与CD4+T-淋巴细胞绝对计数的相关性,了解VitD对人体免疫系统的作用和影响。方法采用高档LC-MS/MS质谱仪,利用生物芯片技术测定CD4+T-淋巴细胞绝对计数,利用25-(OH)-VitD金标准方法测定284例病人血中25-(OH)-VitD总含量、25-(OH)-VitD2含量和25-(OH)-VitD3含量,并采用统计学方法,研究其与CD4+T-淋巴细胞的相关性。结果与CD4+T-淋巴细胞绝对计数的Pearson相关系数分别为:25-(OH)-VitD总含量0.172,P=0.004;25-(OH)-VitD2含量0.0034,P=0.660;25-(OH)-VitD3含量0.192,P=0.001。结论 25-(OH)-VitD总含量及25-(OH)-VitD3含量与CD4+T-淋巴细胞绝对计数密切相关,而25-(OH)-VitD2含量与CD4+T-淋巴细胞绝对计数无关;VitD对人体免疫系统具有一定作用和影响。