Safety and Efficacy of Tien-Hsien Liquid Practical in Patients with Refractory Metastatic Breast Cancer: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase IIa Trial

To evaluate the safety and efficacy of Tien-Hsien Liquid Practical (THL-P), a Chinese herbal mixture, in patients with refractory metastatic breast cancer, we performed a randomized, double-blind, placebo-controlled, parallel-group, phase IIa pilot trial. Patients were randomly assigned to either receive THL-P or matching placebo and followed up every 4 weeks for 24 weeks. The primary endpoint was changes in the global health status/quality of life (GHS/QOL) scale. The secondary endpoints were changes in functional and symptom scales, immunomodulating effects, and adverse events. Sixty-three patients were enrolled between June 2009 and June 2011. The intent-to-treat population included 28 patients in the THL-P group and 11 patients in the placebo group. Compared to the placebo group, the THL-P group had significant improvement from baseline to last visit in GHS/QOL (41.7 versus −33.3; P < 0.05), CD3, CD4/CD8, CD19, CD16+56 positive cells (P < 0.05), and higher levels of physical, role, emotional, and cognitive functioning, as well as decreased fatigue and systemic side effects. Treatment-related adverse events were mild constipation and localized itching, and no serious adverse events were reported. THL-P appears to be a safe alternative adjuvant treatment for patients with refractory metastatic breast cancer, as it effectively improves QOL and palliates cancer-related symptoms

Efficacy of Mammographic Evaluation of Breast Cancer in Women Less Than 40 Years of Age: Experience from a Single Medical Center in Taiwan

Background/PurposeMammography is the standard imaging modality for breast cancer diagnosis. However, the value of mammographic diagnosis in breast cancer patients aged less than 40 years old has not been well assessed. The goal of our study was to determine the diagnostic efficacy of mammography for the detection of breast cancer in women under 40 years of age in a single medical center in Taiwan.MethodsOf 1766 women diagnosed with breast cancer in one medical center between 1999 and 2005, 227 (12.9%) who were younger than 40 years of age were enrolled, and 105 of these 227 patients had pre-biopsy mammograms available for analysis. The sensitivities for mammography at first (prospective) and second (retrospective) readings and for corresponding ultrasound were calculated. The distribution of different breast composition between the mammographic true-positive (TP) and false-negative (FN) lesions at the first and second readings was analyzed.ResultsOf the 105 patients, 104 presented with a palpable mass and the other one was asymptomatic. There were 109 pathologically proven breast cancers from the 105 patients; 92 of 109 cancerous lesions were detected at the first mammographic reading (sensitivity 84.4%), and the most common mammographic sign was microcalcifications (40.2%). The second reading detected seven additional cancers (99 of 109 lesions; sensitivity 90.8%). There was no significant difference between mammographic TP and FN lesions for the different breast composition on first and second readings. Ninety patients also had ultrasound available for correlation with 94 cancers diagnosed from them. The diagnostic sensitivity of ultrasound was 94.7% (89 of 94 lesions).ConclusionMammography has an acceptable sensitivity for the detection of breast cancer in women aged less than 40 years, regardless of different breast composition. Breast ultrasound can offer a higher sensitivity for such a population

Effects of Yoga on Psychological Health, Quality of Life, and Physical Health of Patients with Cancer: A Meta-Analysis

Yoga is one of the most widely used complementary and alternative medicine therapies to manage illness. This meta-analysis aimed to determine the effects of yoga on psychological health, quality of life, and physical health of patients with cancer. Studies were identified through a systematic search of seven electronic databases and were selected if they used a randomized controlled trial design to examine the effects of yoga in patients with cancer. The quality of each article was rated by two of the authors using the PEDro Scale. Ten articles were selected; their PEDro scores ranged from 4 to 7. The yoga groups compared to waitlist control groups or supportive therapy groups showed significantly greater improvements in psychological health: anxiety (P = .009), depression (P = .002), distress (P = .003), and stress (P = .006). However, due to the mixed and low to fair quality and small number of studies conducted, the findings are preliminary and limited and should be confirmed through higher-quality, randomized controlled trials

Strategically examining the full-genome of dengue virus type 3 in clinical isolates reveals its mutation spectra

BACKGROUND: Previous studies presented the quasispecies spectrum of the envelope region of dengue virus type 3 (DENV-3) from either clinical specimens or field-caught mosquitoes. However, the extent of sequence variation among full genomic sequences of DENV within infected individuals remains largely unknown. RESULTS: Instead of arbitrarily choosing one genomic region in this study, the full genomic consensus sequences of six DENV-3 isolates were used to locate four genomic regions that had a higher potential of sequence heterogeneity at capsid-premembrane (C-prM), envelope (E), nonstructural protein 3 (NS3), and NS5. The extentof sequence heterogeneity revealed by clonal sequencing was genomic region-dependent, whereas the NS3 and NS5 had lower sequence heterogeneity than C-prM and E. Interestingly, the Phylogenetic Analysis by Maximum Likelihood program (PAML) analysis supported that the domain III of E region, the most heterogeneous region analyzed, was under the influence of positive selection. CONCLUSION: This study confirmed previous reports that the most heterogeneous region of the dengue viral genome resided at the envelope region, of which the domain III was under positive selection pressure. Further studies will need to address the influence of these mutations on the overall fitness in different hosts (i.e., mosquito and human) during dengue viral transmission

Evaluation of the diagnostic performance of infrared imaging of the breast: a preliminary study

<p>Abstract</p> <p>Background</p> <p>The study was conducted to investigate the diagnostic performance of infrared (IR) imaging of the breast using an interpretive model derived from a scoring system.</p> <p>Methods</p> <p>The study was approved by the Institutional Review Board of our hospital. A total of 276 women (mean age = 50.8 years, SD 11.8) with suspicious findings on mammograms or ultrasound received IR imaging of the breast before excisional biopsy. The interpreting radiologists scored the lesions using a scoring system that combines five IR signs. The ROC (receiver operating characteristic) curve and AUC (area under the ROC curve) were analyzed by the univariate logistic regression model for each IR sign and an age-adjusted multivariate logistic regression model including 5 IR signs. The cut-off values and corresponding sensitivity, specificity, Youden's Index (Index = sensitivity+specificity-1), positive predictive value (PPV), negative predictive value (NPV) were estimated from the age-adjusted multivariate model. The most optimal cut-off value was determined by the one with highest Youden's Index.</p> <p>Results</p> <p>For the univariate model, the AUC of the ROC curve from five IR signs ranged from 0.557 to 0.701, and the AUC of the ROC from the age-adjusted multivariate model was 0.828. From the ROC derived from the multivariate model, the sensitivity of the most optimal cut-off value would be 72.4% with the corresponding specificity 76.6% (Youden's Index = 0.49), PPV 81.3% and NPV 66.4%.</p> <p>Conclusions</p> <p>We established an interpretive age-adjusted multivariate model for IR imaging of the breast. The cut-off values and the corresponding sensitivity and specificity can be inferred from the model in a subpopulation for diagnostic purpose.</p> <p>Trial Registration</p> <p>NCT00166998.</p

Major Functional Transcriptome of an Inferred Center Regulator of an ER(−) Breast Cancer Model System

We aimed to find clinically relevant gene activities ruled by the signal transducer and activator of transcription 3 (STAT3) proteins in an ER(−) breast cancer population via network approach. STAT3 is negatively associated with both lymph nodal category and stage. MYC is a component of STAT3 network. MYC and STAT3 may co-regulate gene expressions for Warburg effect, stem cell like phenotype, cell proliferation and angiogenesis. We identified a STAT3 network in silico showing its ability in predicting its target gene expressions primarily for specific tumor subtype, tumor progression, treatment options and prognostic features. The aberrant expressions of MYC and STAT3 are enriched in triple negatives (TN). They promote histological grade, vascularity, metastasis and tumor anti-apoptotic activities. VEGFA, STAT3, FOXM1 and METAP2 are druggable targets. High levels of METAP2, MMP7, IGF2 and IGF2R are unfavorable prognostic factors. STAT3 is an inferred center regulator at early cancer development predominantly in TN

Statistical identification of gene association by CID in application of constructing ER regulatory network

<p>Abstract</p> <p>Background</p> <p>A variety of high-throughput techniques are now available for constructing comprehensive gene regulatory networks in systems biology. In this study, we report a new statistical approach for facilitating <it>in silico </it>inference of regulatory network structure. The new measure of association, coefficient of intrinsic dependence (CID), is model-free and can be applied to both continuous and categorical distributions. When given two variables X and Y, CID answers whether Y is dependent on X by examining the conditional distribution of Y given X. In this paper, we apply CID to analyze the regulatory relationships between transcription factors (TFs) (X) and their downstream genes (Y) based on clinical data. More specifically, we use estrogen receptor α (ERα) as the variable X, and the analyses are based on 48 clinical breast cancer gene expression arrays (48A).</p> <p>Results</p> <p>The analytical utility of CID was evaluated in comparison with four commonly used statistical methods, Galton-Pearson's correlation coefficient (GPCC), Student's <it>t</it>-test (STT), coefficient of determination (CoD), and mutual information (MI). When being compared to GPCC, CoD, and MI, CID reveals its preferential ability to discover the regulatory association where distribution of the mRNA expression levels on X and Y does not fit linear models. On the other hand, when CID is used to measure the association of a continuous variable (Y) against a discrete variable (X), it shows similar performance as compared to STT, and appears to outperform CoD and MI. In addition, this study established a two-layer transcriptional regulatory network to exemplify the usage of CID, in combination with GPCC, in deciphering gene networks based on gene expression profiles from patient arrays.</p> <p>Conclusion</p> <p>CID is shown to provide useful information for identifying associations between genes and transcription factors of interest in patient arrays. When coupled with the relationships detected by GPCC, the association predicted by CID are applicable to the construction of transcriptional regulatory networks. This study shows how information from different data sources and learning algorithms can be integrated to investigate whether relevant regulatory mechanisms identified in cell models can also be partially re-identified in clinical samples of breast cancers.</p> <p>Availability</p> <p>the implementation of CID in R codes can be freely downloaded from <url>http://homepage.ntu.edu.tw/~lyliu/BC/</url>.</p