Medulloblastoma in China: clinicopathologic analyses of SHH, WNT, and non-SHH/WNT molecular subgroups reveal different therapeutic responses to adjuvant chemotherapy.

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Zhen-Yu Zhang

Full Text Available Medulloblastoma (MB is one of the most common primary central nervous system tumors in children. Data is lacking of a large cohort of medulloblastoma patients in China. Also, our knowledge on the sensitivity of different molecular subgroups of MB to adjuvant radiation therapy (RT or chemotherapy (CHT is still limited. The authors performed a retrospective study of 173 medulloblastoma patients treated at two institutions from 2002 to 2011. Formalin-fixed paraffin embedded (FFPE tissues were available in all the cases and sections were stained to classify histological and molecular subgroups. Univariate and multivariate analyses were used to investigate prognostic factors. Of 173 patients, there were 118 children and 55 adults, 112 males and 61 females. Estimated 5-year overall survival (OS rates for all patients, children and adults were 52%, 48% and 63%, respectively. After multivariate analysis, postoperative primary radiation therapy (RT and chemotherapy (CHT were revealed as favorable prognostic factors influencing OS and EFS. Postoperative primary chemotherapy (CHT was found significantly improving the survival of children (p<0.001 while it was not a significant prognostic factor for adult patients. Moreover, patients in WNT subtype had better OS (p = 0.028 than others (SHH and Non-SHH/WNT subtypes given postoperative adjuvant therapies. Postoperative primary RT was found to be a strong prognostic factor influencing the survival in all histological and molecular subgroups (p<0.001. Postoperative primary CHT was found significantly to influence the survival of classic medulloblastoma (CMB (OS p<0.001, EFS p<0.001, SHH subgroup (OS p = 0.020, EFS p = 0.049 and WNT subgroup (OS p = 0.003, EFS p = 0.016 but not in desmoplastic/nodular medulloblastoma (DMB (OS p = 0.361, EFS p = 0.834 and Non-SHH/WNT subgroup (OS p = 0.127, EFS p = 0.055. Our study showed postoperative primary CHT significantly influence the

Finite groups in which some particular subgroups are TI-subgroups

DEFF Research Database (Denmark)

Shi, Jiangtao; Zhang, Cui

2013-01-01

We prove that G is a group in which all noncyclic subgroups are TI-subgroups if and only if all noncyclic subgroups of G are normal in G. Moreover, we classify groups in which all subgroups of even order are TI-subgroups....

Finite groups all of whose minimal subgroups are NE-subgroups

Indian Academy of Sciences (India)

Logo of the Indian Academy of Sciences. Indian Academy of Sciences ... In this article, we investigate the structure of under the assumption that subgroups of prime order are *-subgroups of . The finite groups, all of whose minimal subgroups of the generalized Fitting subgroup are *-subgroups are classified.

Finite groups all of whose minimal subgroups are NE∗ -subgroups

Indian Academy of Sciences (India)

subgroup of G if there exists a subnormal subgroup T of G such that G = HT and H ∩ T is a. NE-subgroup of G. In this article, we investigate the structure of G under the assump- tion that subgroups of prime order are NE∗-subgroups of G. The finite ...

The Immunohistochemical Analysis of SOCS3 Protein Identifies a Subgroup of Prostatic Cancer Biopsies With Aggressive Behavior.

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Pierconti, Francesco; Martini, Maurizio; Cenci, Tonia; Larocca, Luigi M

Recently, we demonstrated that hypermethylation of SOCS3 determines a significant reduction of its mRNA and protein expression and identifies a subgroup of prostate cancer with aggressive behavior. In this paper, our objective was to investigate whether the immunohistochemical expression of the SOCS3 protein could represent an alternative method to molecular analysis for the individualization of aggressive prostate carcinoma. We analyzed the SOCS3 immunohistochemical expression in 65 patients undergoing biopsies at the Institute of Urology of our hospital between September 2011 and October 2011 (median age, 66.4 y; range, 50 to 73 y), and in 35 cases, a subset of 65 cases originally used for the immunohistochemical study, we studied the methylation status of the SOCS3 promoter. We found that the percentage of cases with SOCS3 negativity (-) or with SOCS3 weak staining in <50% of the neoplastic glands (+/-) correlated to the worst prognosis in terms of the Gleason score (P=0.0001; Fisher's exact test), the pT stage (P=0.012; Fisher's exact test), and progression-free survival (P=0.0334; hazard ratio, 0.34; and 95% confidence interval, from 0.1261 to 0.9188). Moreover, some cases with an SOCS3 unmethylated pattern showed SOCS3-negative immunostaining (-) or SOCS3-negative glands with weak cytoplasmatic staining in <50% of the neoplastic glands (+/-). Our data suggest that in prostatic cancer biopsies, the immunohistochemical analysis of SOCS3 protein expression may provide a method that is less expensive and easier to apply than SOCS3 methylation analysis for the distinction of a subgroup of prostate cancer with a more aggressive behavior.

The benefit of microsatellite instability is attenuated by chemotherapy in stage II and stage III gastric cancer: Results from a large cohort with subgroup analyses.

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Kim, Soo Young; Choi, Yoon Young; An, Ji Yeong; Shin, Hyun Beak; Jo, Ara; Choi, Hyeji; Seo, Sang Hyuk; Bang, Hui-Jae; Cheong, Jae-Ho; Hyung, Woo Jin; Noh, Sung Hoon

2015-08-15

We previously reported that the prognosis of microsatellite instability high (MSI-H) gastric cancer is similar to that of MSI-low/microsatellite stable (MSI-L/MSS) gastric cancer. The reason for this seemed to be related to the effects of chemotherapy. To verify this hypothesis, we expanded the study population and reanalyzed the prognosis of MSI-H gastric cancer. Data from 1,276 patients with Stage II and III gastric cancer who underwent gastrectomy with curative intent between January 2005 and June 2010 were reviewed. The prognosis of MSI-H tumors in comparison with MSI-L/MSS tumors was analyzed, according to the administration of chemotherapy and other clinicopathologic features. A total of 361 (28.3%) patients did not receive chemotherapy (MSI-H = 47 and MSI-L/MSS = 314), whereas 915 (71.7%) patients did receive chemotherapy (MSI-H = 58 and MSI-L/MSS = 857). The hazard ratio of MSI-H versus MSI-L/MSS was 0.49 (95% confidence interval: 0.26-0.94, p = 0.031) when chemotherapy was not received and 1.16 (95% confidence interval: 0.78-1.71, p = 0.466) when chemotherapy was received. In subgroup analyses, the prognosis of MSI-H was better in Stage III, women, with lymph node metastasis, and undifferentiated histology subgroups when chemotherapy was not received. However, in patients treated with chemotherapy, prognosis was worse for MSI-H tumors in Stage III, undifferentiated histology, and diffuse type subgroups of gastric cancer. In conclusion, MSI-H tumors were associated with a good prognosis in Stage II and III gastric cancer when patients were treated by surgery alone, and the benefits of MSI-H status were attenuated by chemotherapy. © 2015 UICC.

Impact of BCL2 and p53 on postmastectomy radiotherapy response in high-risk breast cancer. A subgroup analysis of DBCG82 b

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Kyndi, M.; Sorensen, F.B.; Alsner, J.

2008-01-01

-Meier probability plots showed a significantly improved overall survival after PMRT for the BCL2 positive subgroup, whereas practically no survival improvement was seen after PMRT for the BCL2 negative subgroup. In multivariate analysis of OS, however, no significant interaction was found between BCL2......Purpose. To examine p53 and BCL2 expression in high-risk breast cancer patients randomized to postmastectomy radiotherapy (PMRT). Patients and methods. The present analysis included 1000 of 3 083 high-risk breast cancer patients randomly assigned to PMRT in the DBCG82 b&c studies. Tissue microarray......, Kaplan-Meier probability plots, Log-rank test, and Cox univariate and multivariate regression analyses. Results. p53 accumulation was not significantly associated with increased overall mortality, DM or LRR probability in univariate or multivariate Cox regression analyses. Kaplan-Meier probability plots...

Identifying and Assessing Interesting Subgroups in a Heterogeneous Population.

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Lee, Woojoo; Alexeyenko, Andrey; Pernemalm, Maria; Guegan, Justine; Dessen, Philippe; Lazar, Vladimir; Lehtiö, Janne; Pawitan, Yudi

2015-01-01

Biological heterogeneity is common in many diseases and it is often the reason for therapeutic failures. Thus, there is great interest in classifying a disease into subtypes that have clinical significance in terms of prognosis or therapy response. One of the most popular methods to uncover unrecognized subtypes is cluster analysis. However, classical clustering methods such as k-means clustering or hierarchical clustering are not guaranteed to produce clinically interesting subtypes. This could be because the main statistical variability--the basis of cluster generation--is dominated by genes not associated with the clinical phenotype of interest. Furthermore, a strong prognostic factor might be relevant for a certain subgroup but not for the whole population; thus an analysis of the whole sample may not reveal this prognostic factor. To address these problems we investigate methods to identify and assess clinically interesting subgroups in a heterogeneous population. The identification step uses a clustering algorithm and to assess significance we use a false discovery rate- (FDR-) based measure. Under the heterogeneity condition the standard FDR estimate is shown to overestimate the true FDR value, but this is remedied by an improved FDR estimation procedure. As illustrations, two real data examples from gene expression studies of lung cancer are provided.

Impact of BCL2 and p53 on postmastectomy radiotherapy response in high-risk breast cancer. A subgroup analysis of DBCG82 b&c

DEFF Research Database (Denmark)

Kyndi, Marianne; Sørensen, Flemming Brandt; Knudsen, Helle

2008-01-01

-Meier probability plots showed a significantly improved overall survival after PMRT for the BCL2 positive subgroup, whereas practically no survival improvement was seen after PMRT for the BCL2 negative subgroup. In multivariate analysis of OS, however, no significant interaction was found between BCL2......PURPOSE: To examine p53 and BCL2 expression in high-risk breast cancer patients randomized to postmastectomy radiotherapy (PMRT). PATIENTS AND METHODS: The present analysis included 1 000 of 3 083 high-risk breast cancer patients randomly assigned to PMRT in the DBCG82 b&c studies. Tissue...... tests, Kaplan-Meier probability plots, Log-rank test, and Cox univariate and multivariate regression analyses. RESULTS: p53 accumulation was not significantly associated with increased overall mortality, DM or LRR probability in univariate or multivariate Cox regression analyses. Kaplan...

Generalized Sum of Fuzzy Subgroup and α-cut Subgroup

OpenAIRE

Daher Waly Freh Al-Rekabi; Alia Shany Hassan

2012-01-01

p>In this paper we study some results of the generalized sum of a fuzzynbsp;subgroup and alpha;-cut subgroup, we define a alpha;-cut subset and alpha;-cut subgroup, and then. We study some of their properties./p>

Impact of BCL2 and p53 on postmastectomy radiotherapy response in high-risk breast cancer. A subgroup analysis of DBCG82 b and c

International Nuclear Information System (INIS)

Kyndi, M.; Alsner, J.; Nielsen, H.M.; Overgaard, J.; Soerensen, F.B.; Knudsen, H.; Overgaard, M.

2008-01-01

Purpose. To examine p53 and BCL2 expression in high-risk breast cancer patients randomized to postmastectomy radiotherapy (PMRT). Patients and methods. The present analysis included 1 000 of 3 083 high-risk breast cancer patients randomly assigned to PMRT in the DBCG82 b and c studies. Tissue microarray sections were stained with immunohistochemistry for p53 and BCL2. Median potential follow-up was 17 years. Clinical endpoints were locoregional recurrence (LRR), distant metastases (DM), overall mortality, and overall survival (OS). Statistical analyses included Kappa statistics, χ2 or exact tests, Kaplan-Meier probability plots, Log-rank test, and Cox univariate and multivariate regression analyses. Results. p53 accumulation was not significantly associated with increased overall mortality, DM or LRR probability in univariate or multivariate Cox regression analyses. Kaplan-Meier probability plots showed reduced OS and improved DM and LRR probabilities after PMRT within subgroups of both p53 negative and p53 positive patients. Negative BCL2 expression was significantly associated with increased overall mortality, DM and LRR probability in multivariate Cox regression analyses. Kaplan-Meier probability plots showed a significantly improved overall survival after PMRT for the BCL2 positive subgroup, whereas practically no survival improvement was seen after PMRT for the BCL2 negative subgroup. In multivariate analysis of OS, however, no significant interaction was found between BCL2 and randomization status. Significant reductions in LRR probability after PMRT were recorded within both the BCL2 positive and BCL2 negative subgroups. Conclusion. p53 was not associated with survival after radiotherapy in high-risk breast cancer, but BCL2 might be

Classification of breast cancer patients using somatic mutation profiles and machine learning approaches.

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Vural, Suleyman; Wang, Xiaosheng; Guda, Chittibabu

2016-08-26

The high degree of heterogeneity observed in breast cancers makes it very difficult to classify the cancer patients into distinct clinical subgroups and consequently limits the ability to devise effective therapeutic strategies. Several classification strategies based on ER/PR/HER2 expression or the expression profiles of a panel of genes have helped, but such methods often produce misleading results due to their dynamic nature. In contrast, somatic DNA mutations are relatively stable and lead to initiation and progression of many sporadic cancers. Hence in this study, we explore the use of gene mutation profiles to classify, characterize and predict the subgroups of breast cancers. We analyzed the whole exome sequencing data from 358 ethnically similar breast cancer patients in The Cancer Genome Atlas (TCGA) project. Somatic and non-synonymous single nucleotide variants identified from each patient were assigned a quantitative score (C-score) that represents the extent of negative impact on the gene function. Using these scores with non-negative matrix factorization method, we clustered the patients into three subgroups. By comparing the clinical stage of patients, we identified an early-stage-enriched and a late-stage-enriched subgroup. Comparison of the mutation scores of early and late-stage-enriched subgroups identified 358 genes that carry significantly higher mutations rates in the late stage subgroup. Functional characterization of these genes revealed important functional gene families that carry a heavy mutational load in the late state rich subgroup of patients. Finally, using the identified subgroups, we also developed a supervised classification model to predict the stage of the patients. This study demonstrates that gene mutation profiles can be effectively used with unsupervised machine-learning methods to identify clinically distinguishable breast cancer subgroups. The classification model developed in this method could provide a reasonable

Molecular Subtyping of Serous Ovarian Tumors Reveals Multiple Connections to Intrinsic Breast Cancer Subtypes

DEFF Research Database (Denmark)

Jönsson, Jenny-Maria; Johansson, Ida; Dominguez-Valentin, Mev

2014-01-01

expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal...

Conditions for Effective Application of Analysis of Symmetrically-Predicted Endogenous Subgroups

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Peck, Laura R.

2015-01-01

Several analytic strategies exist for opening up the "black box" to reveal more about what drives policy and program impacts. This article focuses on one of these strategies: the Analysis of Symmetrically-Predicted Endogenous Subgroups (ASPES). ASPES uses exogenous baseline data to identify endogenously-defined subgroups, keeping the…

Genome-Wide Association Study Reveals Four Loci for Lipid Ratios in the Korean Population and the Constitutional Subgroup.

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Kim, Taehyeung; Park, Ah Yeon; Baek, Younghwa; Cha, Seongwon

2017-01-01

Circulating lipid ratios are considered predictors of cardiovascular risks and metabolic syndrome, which cause coronary heart diseases. One constitutional type of Korean medicine prone to weight accumulation, the Tae-Eum type, predisposes the consumers to metabolic syndrome, hypertension, diabetes mellitus, etc. Here, we aimed to identify genetic variants for lipid ratios using a genome-wide association study (GWAS) and followed replication analysis in Koreans and constitutional subgroups. GWASs in 5,292 individuals of the Korean Genome and Epidemiology Study and replication analyses in 2,567 subjects of the Korea medicine Data Center were performed to identify genetic variants associated with triglyceride (TG) to HDL cholesterol (HDLC), LDL cholesterol (LDLC) to HDLC, and non-HDLC to HDLC ratios. For subgroup analysis, a computer-based constitution analysis tool was used to categorize the constitutional types of the subjects. In the discovery stage, seven variants in four loci, three variants in three loci, and two variants in one locus were associated with the ratios of log-transformed TG:HDLC (log[TG]:HDLC), LDLC:HDLC, and non-HDLC:HDLC, respectively. The associations of the GWAS variants with lipid ratios were replicated in the validation stage: for the log[TG]:HDLC ratio, rs6589566 near APOA5 and rs4244457 and rs6586891 near LPL; for the LDLC:HDLC ratio, rs4420638 near APOC1 and rs17445774 near C2orf47; and for the non-HDLC:HDLC ratio, rs6589566 near APOA5. Five of these six variants are known to be associated with TG, LDLC, and/or HDLC, but rs17445774 was newly identified to be involved in lipid level changes in this study. Constitutional subgroup analysis revealed effects of variants associated with log[TG]:HDLC and non-HDLC:HDLC ratios in both the Tae-Eum and non-Tae-Eum types, whereas the effect of the LDLC:HDLC ratio-associated variants remained only in the Tae-Eum type. In conclusion, we identified three log[TG]:HDLC ratio-associated variants, two LDLC

Genome-Wide Association Study Reveals Four Loci for Lipid Ratios in the Korean Population and the Constitutional Subgroup.

Directory of Open Access Journals (Sweden)

Taehyeung Kim

Full Text Available Circulating lipid ratios are considered predictors of cardiovascular risks and metabolic syndrome, which cause coronary heart diseases. One constitutional type of Korean medicine prone to weight accumulation, the Tae-Eum type, predisposes the consumers to metabolic syndrome, hypertension, diabetes mellitus, etc. Here, we aimed to identify genetic variants for lipid ratios using a genome-wide association study (GWAS and followed replication analysis in Koreans and constitutional subgroups. GWASs in 5,292 individuals of the Korean Genome and Epidemiology Study and replication analyses in 2,567 subjects of the Korea medicine Data Center were performed to identify genetic variants associated with triglyceride (TG to HDL cholesterol (HDLC, LDL cholesterol (LDLC to HDLC, and non-HDLC to HDLC ratios. For subgroup analysis, a computer-based constitution analysis tool was used to categorize the constitutional types of the subjects. In the discovery stage, seven variants in four loci, three variants in three loci, and two variants in one locus were associated with the ratios of log-transformed TG:HDLC (log[TG]:HDLC, LDLC:HDLC, and non-HDLC:HDLC, respectively. The associations of the GWAS variants with lipid ratios were replicated in the validation stage: for the log[TG]:HDLC ratio, rs6589566 near APOA5 and rs4244457 and rs6586891 near LPL; for the LDLC:HDLC ratio, rs4420638 near APOC1 and rs17445774 near C2orf47; and for the non-HDLC:HDLC ratio, rs6589566 near APOA5. Five of these six variants are known to be associated with TG, LDLC, and/or HDLC, but rs17445774 was newly identified to be involved in lipid level changes in this study. Constitutional subgroup analysis revealed effects of variants associated with log[TG]:HDLC and non-HDLC:HDLC ratios in both the Tae-Eum and non-Tae-Eum types, whereas the effect of the LDLC:HDLC ratio-associated variants remained only in the Tae-Eum type. In conclusion, we identified three log[TG]:HDLC ratio

Psychological impact of genetic counseling for hereditary nonpolyposis colorectal cancer: the role of cancer history, gender, age, and psychological distress.

Science.gov (United States)

Hasenbring, Monika I; Kreddig, Nina; Deges, Gabriele; Epplen, Joerg T; Kunstmann, Erdmute; Stemmler, Susanne; Schulmann, Karsten; Willert, Joerg; Schmiegel, Wolf

2011-04-01

We prospectively examined the impact of an initial interdisciplinary genetic counseling (human geneticist, oncologist, and psycho-oncologist) on feelings of anxiety with a special focus on subgroups related to personal cancer history, gender, age, and education. At baseline, cancer-affected men revealed a significantly higher level of anxiety than unaffected men (pDepression Scale-A cases can be predicted by general distress (Brief Symptom Inventory) as well as by hereditary nonpolyposis colorectal cancer-related cognitions of intrusion and avoidance (impact of event scale) with a correct classification of 86%. Although initial hereditary nonpolyposis colorectal cancer counseling leads to an overall reduction of anxiety, differential effects of cancer history, gender, and age focus on subgroups of cancer-affected men, who may display unexpectedly high anxiety scores at baseline. Especially younger men do not seem to reduce this high anxiety level. Baseline anxiety was mainly determined by maladaptive situation-specific cognitions. Therefore, consulters should be more aware of anxiety-related cognitions in cancer-affected younger men.

Discretization of Gene Expression Data Unmasks Molecular Subgroups Recurring in Different Human Cancer Types.

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Manfred Beleut

Full Text Available Despite the individually different molecular alterations in tumors, the malignancy associated biological traits are strikingly similar. Results of a previous study using renal cell carcinoma (RCC as a model pointed towards cancer-related features, which could be visualized as three groups by microarray based gene expression analysis. In this study, we used a mathematic model to verify the presence of these groups in RCC as well as in other cancer types. We developed an algorithm for gene-expression deviation profiling for analyzing gene expression data of a total of 8397 patients with 13 different cancer types and normal tissues. We revealed three common Cancer Transcriptomic Profiles (CTPs which recurred in all investigated tumors. Additionally, CTPs remained robust regardless of the functions or numbers of genes analyzed. CTPs may represent common genetic fingerprints, which potentially reflect the closely related biological traits of human cancers.

Is the performance of MRI in preoperative staging of breast cancer independent of clinical and histological factors? A subgroup analysis.

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Carreira Gómez, C; Zamora Romero, J; Gil de Miguel, A; Chiva de Agustín, M; Plana Farrás, M N; Martínez González, J

2015-01-01

To determine whether preoperative breast MRI is more useful in patients according to their breast density, age, menopausal status, and biopsy findings of carcinoma in situ. We retrospectively studied 264 patients treated for breast cancer who had undergone mammography, ultrasonography, and MRI. We compared the size of the tumor on the three techniques and the sensitivity of the techniques for detecting additional lesions both in the overall group and in subgroups of patients classified according to their breast density, age, menopausal status, and histological findings of intraductal carcinoma. The definitive histological diagnosis was used as the gold standard. MRI was the technique that was most concordant with the histological findings for the size of the lesion, and it was also the technique that detected the most additional lesions. With MRI, we observed no differences in lesion size between the overall group and the subgroups in which MRI provided added value. Likewise, we observed no differences in the number of additional lesions detected in the overall group except for multicentric lesions, which was larger in older patients (P=.02). In the subgroup of patients in which MRI provided added value, the sensitivity for bilateral lesions was higher in patients with fatty breasts (P=.04). Multifocal lesions were detected significantly better in premenopausal patients (P=.03). MRI is better than mammography and better than ultrasonography for establishing the size of the tumor and for detecting additional lesions. Our results did not identify any subgroups in which the technique was more useful. Copyright © 2013 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Pan-cancer stratification of solid human epithelial tumors and cancer cell lines reveals commonalities and tissue-specific features of the CpG island methylator phenotype.

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Sánchez-Vega, Francisco; Gotea, Valer; Margolin, Gennady; Elnitski, Laura

2015-01-01

The term CpG island methylator phenotype (CIMP) has been used to describe widespread DNA hypermethylation at CpG-rich genomic regions affecting clinically distinct subsets of cancer patients. Even though there have been numerous studies of CIMP in individual cancer types, a uniform analysis across tissues is still lacking. We analyze genome-wide patterns of CpG island hypermethylation in 5,253 solid epithelial tumors from 15 cancer types from TCGA and 23 cancer cell lines from ENCODE. We identify differentially methylated loci that define CIMP+ and CIMP- samples, and we use unsupervised clustering to provide a robust molecular stratification of tumor methylomes for 12 cancer types and all cancer cell lines. With a minimal set of 89 discriminative loci, we demonstrate accurate pan-cancer separation of the 12 CIMP+/- subpopulations, based on their average levels of methylation. Tumor samples in different CIMP subclasses show distinctive correlations with gene expression profiles and recurrence of somatic mutations, copy number variations, and epigenetic silencing. Enrichment analyses indicate shared canonical pathways and upstream regulators for CIMP-targeted regions across cancer types. Furthermore, genomic alterations showing consistent associations with CIMP+/- status include genes involved in DNA repair, chromatin remodeling genes, and several histone methyltransferases. Associations of CIMP status with specific clinical features, including overall survival in several cancer types, highlight the importance of the CIMP+/- designation for individual tumor evaluation and personalized medicine. We present a comprehensive computational study of CIMP that reveals pan-cancer commonalities and tissue-specific differences underlying concurrent hypermethylation of CpG islands across tumors. Our stratification of solid tumors and cancer cell lines based on CIMP status is data-driven and agnostic to tumor type by design, which protects against known biases that have hindered

Subgroup analysis in burnout: relations between fatigue, anxiety and depression

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Arno eVan Dam

2016-02-01

Full Text Available Several authors have suggested that burned out patients do not form a homogeneous group and that subgroups should be considered. The identification of these subgroups may contribute to a better understanding of the burnout construct and lead to more specific therapeutic interventions. Subgroup analysis may also help clarify whether burnout is a distinct entity and whether subgroups of burnout overlap with other disorders such as depression and chronic fatigue syndrome. In a group of 113 clinically-diagnosed burned out patients, levels of fatigue, depression and anxiety were assessed. In order to identify possible subgroups, we performed a two-step cluster analysis. The analysis revealed two clusters that differed from one another in terms of symptom severity on the three aforementioned measures. Depression appeared to be the strongest predictor of group membership. These results are considered in the light of the scientific debate on whether burnout can be distinguished from depression and whether burnout subtyping is useful. Finally, implications for clinical practice and future research are discussed.

Subgroup Analysis in Burnout: Relations Between Fatigue, Anxiety, and Depression

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van Dam, Arno

2016-01-01

Several authors have suggested that burned out patients do not form a homogeneous group and that subgroups should be considered. The identification of these subgroups may contribute to a better understanding of the burnout construct and lead to more specific therapeutic interventions. Subgroup analysis may also help clarify whether burnout is a distinct entity and whether subgroups of burnout overlap with other disorders such as depression and chronic fatigue syndrome. In a group of 113 clinically diagnosed burned out patients, levels of fatigue, depression, and anxiety were assessed. In order to identify possible subgroups, we performed a two-step cluster analysis. The analysis revealed two clusters that differed from one another in terms of symptom severity on the three aforementioned measures. Depression appeared to be the strongest predictor of group membership. These results are considered in the light of the scientific debate on whether burnout can be distinguished from depression and whether burnout subtyping is useful. Finally, implications for clinical practice and future research are discussed. PMID:26869983

Does mortality vary between Asian subgroups in New Zealand: an application of hierarchical Bayesian modelling.

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Santosh Jatrana

Full Text Available The aim of this paper was to see whether all-cause and cause-specific mortality rates vary between Asian ethnic subgroups, and whether overseas born Asian subgroup mortality rate ratios varied by nativity and duration of residence. We used hierarchical Bayesian methods to allow for sparse data in the analysis of linked census-mortality data for 25-75 year old New Zealanders. We found directly standardised posterior all-cause and cardiovascular mortality rates were highest for the Indian ethnic group, significantly so when compared with those of Chinese ethnicity. In contrast, cancer mortality rates were lowest for ethnic Indians. Asian overseas born subgroups have about 70% of the mortality rate of their New Zealand born Asian counterparts, a result that showed little variation by Asian subgroup or cause of death. Within the overseas born population, all-cause mortality rates for migrants living 0-9 years in New Zealand were about 60% of the mortality rate of those living more than 25 years in New Zealand regardless of ethnicity. The corresponding figure for cardiovascular mortality rates was 50%. However, while Chinese cancer mortality rates increased with duration of residence, Indian and Other Asian cancer mortality rates did not. Future research on the mechanisms of worsening of health with increased time spent in the host country is required to improve the understanding of the process, and would assist the policy-makers and health planners.

Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial.

Science.gov (United States)

Cortés, Javier; Rugo, Hope S; Awada, Ahmad; Twelves, Chris; Perez, Edith A; Im, Seock-Ah; Gómez-Pardo, Patricia; Schwartzberg, Lee S; Diéras, Veronique; Yardley, Denise A; Potter, David A; Mailliez, Audrey; Moreno-Aspitia, Alvaro; Ahn, Jin-Seok; Zhao, Carol; Hoch, Ute; Tagliaferri, Mary; Hannah, Alison L; O'Shaughnessy, Joyce

2017-09-01

Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. The phase 3 BEACON trial enrolled 852 women with heavily pretreated locally recurrent or metastatic breast cancer between 2011 and 2013. BEACON compared EP with treatment of physician's choice (TPC; eribulin, vinorelbine, gemcitabine, nab-paclitaxel, paclitaxel, ixabepilone, or docetaxel) in patients previously treated with anthracycline, taxane, and capecitabine, including those with treated, stable brain metastases. The primary endpoint, overall survival (OS), was assessed in a pre-defined subgroup of BCBM patients; an exploratory post hoc analysis adjusting for the diagnosis-specific graded prognostic assessment (GPA) index was also conducted. In the trial, 67 BCBM patients were randomized (EP, n = 36; TPC, n = 31). Treatment subgroups were balanced for baseline characteristics and GPA indices. EP was associated with a significant reduction in the risk of death (HR 0.51; P BEACON population, fewer patients on EP experienced grade ≥3 toxicity (50 vs. 70%). The significant improvement in survival in BCBM patients provides encouraging data for EP in this difficult-to-treat subgroup of patients. A phase three trial of EP in BCBM patients is underway (ClinicalTrials.gov NCT02915744).

SubID, a non-median dichotomization tool for heterogeneous populations, reveals the pan-cancer significance of INPP4B and its regulation by EVI1 in AML.

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Irakli Dzneladze

Full Text Available Our previous studies demonstrated that INPP4B, a member of the PI3K/Akt signaling pathway, is overexpressed in a subset of AML patients and is associated with lower response to chemotherapy and shorter survival. INPP4B expression analysis in AML revealed a right skewed frequency distribution with 25% of patients expressing significantly higher levels than the majority. The 75% low/25% high cut-off revealed the prognostic power of INPP4B expression status in AML, which would not have been apparent with a standard median cut-off approach. Our identification of a clinically relevant non-median cut-off for INPP4B indicated a need for a generalizable non-median dichotomization approach to optimally study clinically relevant genes. To address this need, we developed Subgroup Identifier (SubID, a tool which examines the relationship between a continuous variable (e.g. gene expression, and a test parameter (e.g. CoxPH or Fisher's exact P values. In our study, Fisher's exact SubID was used to reveal EVI1 as a transcriptional regulator of INPP4B in AML; a finding which was validated in vitro. Next, we used CoxPH SubID to conduct a pan-cancer analysis of INPP4B's prognostic significance. Our analysis revealed that INPP4Blow is associated with shorter survival in kidney clear cell, liver hepatocellular, and bladder urothelial carcinomas. Conversely, INPP4Blow was shown to be associated with increased survival in pancreatic adenocarcinoma in three independent datasets. Overall, our study describes the development and application of a novel subgroup identification tool used to identify prognostically significant rare subgroups based upon gene expression, and for investigating the association between a gene with skewed frequency distribution and potentially important upstream and downstream genes that relate to the index gene.

SubID, a non-median dichotomization tool for heterogeneous populations, reveals the pan-cancer significance of INPP4B and its regulation by EVI1 in AML.

Science.gov (United States)

Dzneladze, Irakli; Woolley, John F; Rossell, Carla; Han, Youqi; Rashid, Ayesha; Jain, Michael; Reimand, Jüri; Minden, Mark D; Salmena, Leonardo

2018-01-01

Our previous studies demonstrated that INPP4B, a member of the PI3K/Akt signaling pathway, is overexpressed in a subset of AML patients and is associated with lower response to chemotherapy and shorter survival. INPP4B expression analysis in AML revealed a right skewed frequency distribution with 25% of patients expressing significantly higher levels than the majority. The 75% low/25% high cut-off revealed the prognostic power of INPP4B expression status in AML, which would not have been apparent with a standard median cut-off approach. Our identification of a clinically relevant non-median cut-off for INPP4B indicated a need for a generalizable non-median dichotomization approach to optimally study clinically relevant genes. To address this need, we developed Subgroup Identifier (SubID), a tool which examines the relationship between a continuous variable (e.g. gene expression), and a test parameter (e.g. CoxPH or Fisher's exact P values). In our study, Fisher's exact SubID was used to reveal EVI1 as a transcriptional regulator of INPP4B in AML; a finding which was validated in vitro. Next, we used CoxPH SubID to conduct a pan-cancer analysis of INPP4B's prognostic significance. Our analysis revealed that INPP4Blow is associated with shorter survival in kidney clear cell, liver hepatocellular, and bladder urothelial carcinomas. Conversely, INPP4Blow was shown to be associated with increased survival in pancreatic adenocarcinoma in three independent datasets. Overall, our study describes the development and application of a novel subgroup identification tool used to identify prognostically significant rare subgroups based upon gene expression, and for investigating the association between a gene with skewed frequency distribution and potentially important upstream and downstream genes that relate to the index gene.

Molecular subgroups of medulloblastoma identification using noninvasive magnetic resonance spectroscopy.

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Blüml, Stefan; Margol, Ashley S; Sposto, Richard; Kennedy, Rebekah J; Robison, Nathan J; Vali, Marzieh; Hung, Long T; Muthugounder, Sakunthala; Finlay, Jonathan L; Erdreich-Epstein, Anat; Gilles, Floyd H; Judkins, Alexander R; Krieger, Mark D; Dhall, Girish; Nelson, Marvin D; Asgharzadeh, Shahab

2016-01-01

Medulloblastomas in children can be categorized into 4 molecular subgroups with differing clinical characteristics, such that subgroup determination aids in prognostication and risk-adaptive treatment strategies. Magnetic resonance spectroscopy (MRS) is a widely available, noninvasive tool that is used to determine the metabolic characteristics of tumors and provide diagnostic information without the need for tumor tissue. In this study, we investigated the hypothesis that metabolite concentrations measured by MRS would differ between molecular subgroups of medulloblastoma and allow accurate subgroup determination. MRS was used to measure metabolites in medulloblastomas across molecular subgroups (SHH = 12, Groups 3/4 = 17, WNT = 1). Levels of 14 metabolites were analyzed to determine those that were the most discriminant for medulloblastoma subgroups in order to construct a multivariable classifier for distinguishing between combined Group 3/4 and SHH tumors. Medulloblastomas across molecular subgroups revealed distinct spectral features. Group 3 and Group 4 tumors demonstrated metabolic profiles with readily detectable taurine, lower levels of lipids, and high levels of creatine. SHH tumors showed prominent choline and lipid with low levels of creatine and little or no evidence of taurine. A 5-metabolite subgroup classifier inclusive of creatine, myo-inositol, taurine, aspartate, and lipid 13a was developed that could discriminate between Group 3/4 and SHH medulloblastomas with excellent accuracy (cross-validated area under the curve [AUC] = 0.88). The data show that medulloblastomas of Group 3/4 differ metabolically as measured using MRS when compared with SHH molecular subgroups. MRS is a useful and accurate tool to determine medulloblastoma molecular subgroups. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Epigenetics and Colorectal Cancer

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Lao, Victoria Valinluck; Grady, William M.

2012-01-01

Colorectal cancer is a leading cause of cancer deaths in the world. It results from an accumulation of genetic and epigenetic changes in colon epithelial cells that transforms them into adenocarcinomas. There have been major advances in our understanding of cancer epigenetics over the last decade, particularly regarding aberrant DNA methylation. Assessment of the colon cancer epigenome has revealed that virtually all colorectal cancers have aberrantly methylated genes and the average colorectal cancer methylome has hundreds to thousands of abnormally methylated genes. As with gene mutations in the cancer genome, a subset of these methylated genes, called driver genes, is presumed to play a functional role in colorectal cancer. The assessment of methylated genes in colorectal cancers has also revealed a unique molecular subgroup of colorectal cancers called CpG Island Methylator Phenotype (CIMP) cancers; these tumors have a particularly high frequency of methylated genes. The advances in our understanding of aberrant methylation in colorectal cancer has led to epigenetic alterations being developed as clinical biomarkers for diagnostic, prognostic, and therapeutic applications. Progress in the assessment of epigenetic alterations in colorectal cancer and their clinical applications has shown that these alterations will be commonly used in the near future as molecular markers to direct the prevention and treatment of colorectal cancer. PMID:22009203

Subgroup Analysis of Trials Is Rarely Easy (SATIRE: a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials

Directory of Open Access Journals (Sweden)

Malaga German

2009-11-01

Full Text Available Abstract Background Subgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1 to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2 to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3 to examine the analysis, and interpretation of subgroup effects for each study's primary outcome. Methods We will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes. Discussion A clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize

SUBGR: A Program to Generate Subgroup Data for the Subgroup Resonance Self-Shielding Calculation

Energy Technology Data Exchange (ETDEWEB)

Kim, Kang Seog [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2016-06-06

The Subgroup Data Generation (SUBGR) program generates subgroup data, including levels and weights from the resonance self-shielded cross section table as a function of background cross section. Depending on the nuclide and the energy range, these subgroup data can be generated by (a) narrow resonance approximation, (b) pointwise flux calculations for homogeneous media; and (c) pointwise flux calculations for heterogeneous lattice cells. The latter two options are performed by the AMPX module IRFFACTOR. These subgroup data are to be used in the Consortium for Advanced Simulation of Light Water Reactors (CASL) neutronic simulator MPACT, for which the primary resonance self-shielding method is the subgroup method.

Perceived discrimination and chronic health in adults from nine ethnic subgroups in the USA.

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Carlisle, Shauna K

2015-01-01

This comparative analysis examines the association between chronic cardiovascular, respiratory and pain conditions, race, ethnicity, nativity, length of residency, and perceived discrimination among three racial and nine ethnic subgroups of Asian Americans (Vietnamese, Filipino, and Chinese), Latino-American (Cuban, Portuguese, and Mexican), and Afro-Caribbean American (Haitian, Jamaican, and Trinidadian/Tobagonian) respondents. Analysis used weighted Collaborative Psychiatric Epidemiology Surveys-merged data from the National Latino and Asian American Study and the National Survey of American Life. Logistic regression analysis was conducted to determine which groups within the model were more likely to report perceived discrimination effects. Afro-Caribbean subgroups were more likely to report perceived discrimination than Asian American and Latino-American subgroups were. Logistic regression revealed a significant positive association with perceived discrimination and chronic pain only for Latino-American respondents. Significant differences in reports of perceived discrimination emerged by race and ethnicity. Caribbean respondents were more likely to report high levels of perceived discrimination; however, they showed fewer significant associations related to chronic health conditions compared to Asian Americans and Latino-Americans. Examination of perceived discrimination across ethnic subgroups reveals large variations in the relationship between chronic health and discrimination by race and ethnicity. Examining perceived discrimination by ethnicity may reveal more complex chronic health patterns masked by broader racial groupings.

Gene expression analyses of the spatio-temporal relationships of human medulloblastoma subgroups during early human neurogenesis.

Directory of Open Access Journals (Sweden)

Cornelia M Hooper

Full Text Available Medulloblastoma is the most common form of malignant paediatric brain tumour and is the leading cause of childhood cancer related mortality. The four molecular subgroups of medulloblastoma that have been identified - WNT, SHH, Group 3 and Group 4 - have molecular and topographical characteristics suggestive of different cells of origin. Definitive identification of the cell(s of origin of the medulloblastoma subgroups, particularly the poorer prognosis Group 3 and Group 4 medulloblastoma, is critical to understand the pathogenesis of the disease, and ultimately for the development of more effective treatment options. To address this issue, the gene expression profiles of normal human neural tissues and cell types representing a broad neuro-developmental continuum, were compared to those of two independent cohorts of primary human medulloblastoma specimens. Clustering, co-expression network, and gene expression analyses revealed that WNT and SHH medulloblastoma may be derived from distinct neural stem cell populations during early embryonic development, while the transcriptional profiles of Group 3 and Group 4 medulloblastoma resemble cerebellar granule neuron precursors at weeks 10-15 and 20-30 of embryogenesis, respectively. Our data indicate that Group 3 medulloblastoma may arise through abnormal neuronal differentiation, whereas deregulation of synaptic pruning-associated apoptosis may be driving Group 4 tumorigenesis. Overall, these data provide significant new insight into the spatio-temporal relationships and molecular pathogenesis of the human medulloblastoma subgroups, and provide an important framework for the development of more refined model systems, and ultimately improved therapeutic strategies.

Subgroup complexes

CERN Document Server

Smith, Stephen D

2011-01-01

This book is intended as an overview of a research area that combines geometries for groups (such as Tits buildings and generalizations), topological aspects of simplicial complexes from p-subgroups of a group (in the spirit of Brown, Quillen, and Webb), and combinatorics of partially ordered sets. The material is intended to serve as an advanced graduate-level text and partly as a general reference on the research area. The treatment offers optional tracks for the reader interested in buildings, geometries for sporadic simple groups, and G-equivariant equivalences and homology for subgroup complexes.

Is axillary sonographic staging less accurate in invasive lobular breast cancer than in ductal breast cancer?

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Sankaye, Prashant; Chhatani, Sharmila; Porter, Gareth; Steel, Jim; Doyle, Sarah

2014-10-01

The purpose of this study was to determine whether axillary sonography is less accurate in invasive lobular breast cancer than in ductal breast cancer. Patients with invasive breast cancer were retrospectively identified from histologic records from 2010 to 2012. Staging axillary sonograms from 96 patients with primary breast cancer in each of 2 subgroups, invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC), were reviewed. Preoperative sonographically guided 14-gauge core biopsy was performed on morphologically abnormal lymph nodes. Thirty-one of 96 patients (32%) in each subgroup were node positive on final postoperative histopathologic analysis. Axillary staging sensitivity was 17 of 31 patients (54%) in the IDC subgroup and 15 of 31(48%) in the ILC subgroup. Further analysis of the data showed no statistically significant differences between these subgroups. We found that there was no statistically significant difference in the accuracy of axillary sonographic staging between ILC and IDC. © 2014 by the American Institute of Ultrasound in Medicine.

Topology based data analysis identifies a subgroup of breast cancers with a unique mutational profile and excellent survival.

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Nicolau, Monica; Levine, Arnold J; Carlsson, Gunnar

2011-04-26

High-throughput biological data, whether generated as sequencing, transcriptional microarrays, proteomic, or other means, continues to require analytic methods that address its high dimensional aspects. Because the computational part of data analysis ultimately identifies shape characteristics in the organization of data sets, the mathematics of shape recognition in high dimensions continues to be a crucial part of data analysis. This article introduces a method that extracts information from high-throughput microarray data and, by using topology, provides greater depth of information than current analytic techniques. The method, termed Progression Analysis of Disease (PAD), first identifies robust aspects of cluster analysis, then goes deeper to find a multitude of biologically meaningful shape characteristics in these data. Additionally, because PAD incorporates a visualization tool, it provides a simple picture or graph that can be used to further explore these data. Although PAD can be applied to a wide range of high-throughput data types, it is used here as an example to analyze breast cancer transcriptional data. This identified a unique subgroup of Estrogen Receptor-positive (ER(+)) breast cancers that express high levels of c-MYB and low levels of innate inflammatory genes. These patients exhibit 100% survival and no metastasis. No supervised step beyond distinction between tumor and healthy patients was used to identify this subtype. The group has a clear and distinct, statistically significant molecular signature, it highlights coherent biology but is invisible to cluster methods, and does not fit into the accepted classification of Luminal A/B, Normal-like subtypes of ER(+) breast cancers. We denote the group as c-MYB(+) breast cancer.

A Study of the Vaginal Microbiome in Healthy Canadian Women Utilizing cpn60-Based Molecular Profiling Reveals Distinct Gardnerella Subgroup Community State Types

Science.gov (United States)

Wagner, Emily C.; Schellenberg, John J.; Links, Matthew G.; van Schalkwyk, Julie; Reid, Gregor; Hemmingsen, Sean M.; Hill, Janet E.; Money, Deborah

2015-01-01

The vaginal microbiota is important in women’s reproductive and overall health. However, the relationships between the structure, function and dynamics of this complex microbial community and health outcomes remain elusive. The objective of this study was to determine the phylogenetic range and abundance of prokaryotes in the vaginal microbiota of healthy, non-pregnant, ethnically diverse, reproductive-aged Canadian women. Socio-demographic, behavioural and clinical data were collected and vaginal swabs were analyzed from 310 women. Detailed profiles of their vaginal microbiomes were generated by pyrosequencing of the chaperonin-60 universal target. Six community state types (CST) were delineated by hierarchical clustering, including three Lactobacillus-dominated CST (L. crispatus, L. iners, L. jensenii), two Gardnerella-dominated (subgroups A and C) and an “intermediate” CST which included a small number of women with microbiomes dominated by seven other species or with no dominant species but minority populations of Streptococcus, Staphylococcus, Peptoniphilus, E. coli and various Proteobacteria in co-dominant communities. The striking correspondence between Nugent score and deep sequencing CST continues to reinforce the basic premise provided by the simpler Gram stain method, while additional analyses reveal detailed cpn60-based phylogeny and estimated abundance in microbial communities from vaginal samples. Ethnicity was the only demographic or clinical characteristic predicting CST, with differences in Asian and White women (p = 0.05). In conclusion, this study confirms previous work describing four cpn60-based subgroups of Gardnerella, revealing previously undescribed CST. The data describe the range of bacterial communities seen in Canadian women presenting with no specific vaginal health concerns, and provides an important baseline for future investigations of clinically important cohorts. PMID:26266808

Human rotavirus subgroups and severity of associated diarrhoea in Ghana.

Science.gov (United States)

Armah, George E.; Hori, Hiroki; Anyanful, Akwasi; Addo, Julius A.; Commey, Joseph O.; Kamiya, Hitoshi; Nkrumah, Francis K.

1995-11-01

In a 12 month study of children with acute diarrhoea seeking medical care in 2 hospitals in Accra, Ghana, 16.3% were found to be infected with human rotaviruses (HRV). Vomiting and diarrhoea were the main symptoms observed. HRV infection was frequently associated with severe diarrhoea. Vomiting was however less frequent in HRV associated diarrhoea than in non HRV diarrhoea. No significant association was observed between the severity of dehydration and HRV infection. Subgroup II HRV was the predominant subgroup identified with the dominant serotypes being HRV serotypes 1 and 4. Poly-acrylamide gel electrophoresis of HRV RNAs isolated from 40 positive stool samples revealed the existence of 7 distinct electrophoretic migration patterns in the study population.

Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

International Nuclear Information System (INIS)

Ohri, Nitin; Garg, Madhur K.; Aparo, Santiago; Kaubisch, Andreas; Tome, Wolfgang; Kennedy, Timothy J.; Kalnicki, Shalom; Guha, Chandan

2013-01-01

Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy

Cytogenetic prognostication within medulloblastoma subgroups.

Science.gov (United States)

Shih, David J H; Northcott, Paul A; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M; Garzia, Livia; Peacock, John; Mack, Stephen C; Wu, Xiaochong; Rolider, Adi; Morrissy, A Sorana; Cavalli, Florence M G; Jones, David T W; Zitterbart, Karel; Faria, Claudia C; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G; Liau, Linda M; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K; Thompson, Reid C; Bailey, Simon; Lindsey, Janet C; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M C; Scherer, Stephen W; Phillips, Joanna J; Gupta, Nalin; Fan, Xing; Muraszko, Karin M; Vibhakar, Rajeev; Eberhart, Charles G; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F; Weiss, William A; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R; Rubin, Joshua B; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M; Gajjar, Amar; Packer, Roger J; Rutkowski, Stefan; Pomeroy, Scott L; French, Pim J; Kloosterhof, Nanne K; Kros, Johan M; Van Meir, Erwin G; Clifford, Steven C; Bourdeaut, Franck; Delattre, Olivier; Doz, François F; Hawkins, Cynthia E; Malkin, David; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T; Pfister, Stefan M; Taylor, Michael D

2014-03-20

Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials.

Identification of subgroups among fibromyalgia patients.

Science.gov (United States)

Auvinet, B; Chaleil, D

2012-09-28

This paper presents some hypotheses concerning the identification of homogeneous subgroups among fibromyalgia (FM) patients in order to improve the management of the disease. It also reviews the available literature about this subject. Three methods for subgrouping are discussed according to clinical features, biomarkers, and gait analysis. Clinical subgrouping based on cluster analysis has been used for the identification of homogeneous subgroups of patients and, more recently, homogeneous clinical features. So far, longitudinal studies using clinical subgroups to direct treatment and predict outcome are still required. Biomarkers in FM, which is a neurobiological disease, are of promising interest, nevertheless currently, none of them can be used to subgroup FM patients. Due to the fact that cortical and subcortical mechanisms of gait control share some cognitive functions which are involved in FM, gait markers have been proposed to evaluate and to subgroup FM patients, in clinical settings. Three out of 4 core FM symptoms are linked to gait markers. Kinesia measured by means of cranio-caudal power is correlated to pain, and could be proposed to assess pain behavior (kinesiophobia). Stride frequency, which is linked to physical component, allows the identification of a hyperkinetic subgroup. Moreover, SF has been correlated to fatigue during the 6 minute walking test. Stride regularity, which expresses the unsteadiness of gait, is correlated to cognitive dysfunction in FM. Decreased stride regularity allows the recognition of a homogeneous subgroup characterized by an increased anxiety and depression, and decreased cognitive functions. These results need further studies to be validated and so used in the daily clinical practice.

Identification of subgroups among fibromyalgia patients

Directory of Open Access Journals (Sweden)

D. Chaleil

2012-09-01

Full Text Available This paper presents some hypotheses concerning the identification of homogeneous subgroups among fibromyalgia (FM patients in order to improve the management of the disease. It also reviews the available literature about this subject. Three methods for subgrouping are discussed according to clinical features, biomarkers, and gait analysis. Clinical subgrouping based on cluster analysis has been used for the identification of homogeneous subgroups of patients and, more recently, homogeneous clinical features. So far, longitudinal studies using clinical subgroups to direct treatment and predict outcome are still required. Biomarkers in FM, which is a neurobiological disease, are of promising interest, nevertheless currently, none of them can be used to subgroup FM patients. Due to the fact that cortical and subcortical mechanisms of gait control share some cognitive functions which are involved in FM, gait markers have been proposed to evaluate and to subgroup FM patients, in clinical settings. Three out of 4 core FM symptoms are linked to gait markers. Kinesia measured by means of cranio-caudal power is correlated to pain, and could be proposed to assess pain behavior (kinesiophobia. Stride frequency, which is linked to physical component, allows the identification of a hyperkinetic subgroup. Moreover, SF has been correlated to fatigue during the 6 minute walking test. Stride regularity, which expresses the unsteadiness of gait, is correlated to cognitive dysfunction in FM. Decreased stride regularity allows the recognition of a homogeneous subgroup characterized by an increased anxiety and depression, and decreased cognitive functions. These results need further studies to be validated and so used in the daily clinical practice.

Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck Cancer Patients Based on Individual and Subgroup Normal Tissue Complication Probability Analysis

International Nuclear Information System (INIS)

Jakobi, Annika; Bandurska-Luque, Anna; Stützer, Kristin; Haase, Robert; Löck, Steffen; Wack, Linda-Jacqueline; Mönnich, David; Thorwarth, Daniela

2015-01-01

Purpose: The purpose of this study was to determine, by treatment plan comparison along with normal tissue complication probability (NTCP) modeling, whether a subpopulation of patients with head and neck squamous cell carcinoma (HNSCC) could be identified that would gain substantial benefit from proton therapy in terms of NTCP. Methods and Materials: For 45 HNSCC patients, intensity modulated radiation therapy (IMRT) was compared to intensity modulated proton therapy (IMPT). Physical dose distributions were evaluated as well as the resulting NTCP values, using modern models for acute mucositis, xerostomia, aspiration, dysphagia, laryngeal edema, and trismus. Patient subgroups were defined based on primary tumor location. Results: Generally, IMPT reduced the NTCP values while keeping similar target coverage for all patients. Subgroup analyses revealed a higher individual reduction of swallowing-related side effects by IMPT for patients with tumors in the upper head and neck area, whereas the risk reduction of acute mucositis was more pronounced in patients with tumors in the larynx region. More patients with tumors in the upper head and neck area had a reduction in NTCP of more than 10%. Conclusions: Subgrouping can help to identify patients who may benefit more than others from the use of IMPT and, thus, can be a useful tool for a preselection of patients in the clinic where there are limited PT resources. Because the individual benefit differs within a subgroup, the relative merits should additionally be evaluated by individual treatment plan comparisons

Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck Cancer Patients Based on Individual and Subgroup Normal Tissue Complication Probability Analysis

Energy Technology Data Exchange (ETDEWEB)

Jakobi, Annika, E-mail: Annika.Jakobi@OncoRay.de [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Bandurska-Luque, Anna [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Stützer, Kristin; Haase, Robert; Löck, Steffen [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Wack, Linda-Jacqueline [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); Mönnich, David [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); German Cancer Research Center, Heidelberg (Germany); German Cancer Consortium, Tübingen (Germany); Thorwarth, Daniela [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); and others

2015-08-01

Purpose: The purpose of this study was to determine, by treatment plan comparison along with normal tissue complication probability (NTCP) modeling, whether a subpopulation of patients with head and neck squamous cell carcinoma (HNSCC) could be identified that would gain substantial benefit from proton therapy in terms of NTCP. Methods and Materials: For 45 HNSCC patients, intensity modulated radiation therapy (IMRT) was compared to intensity modulated proton therapy (IMPT). Physical dose distributions were evaluated as well as the resulting NTCP values, using modern models for acute mucositis, xerostomia, aspiration, dysphagia, laryngeal edema, and trismus. Patient subgroups were defined based on primary tumor location. Results: Generally, IMPT reduced the NTCP values while keeping similar target coverage for all patients. Subgroup analyses revealed a higher individual reduction of swallowing-related side effects by IMPT for patients with tumors in the upper head and neck area, whereas the risk reduction of acute mucositis was more pronounced in patients with tumors in the larynx region. More patients with tumors in the upper head and neck area had a reduction in NTCP of more than 10%. Conclusions: Subgrouping can help to identify patients who may benefit more than others from the use of IMPT and, thus, can be a useful tool for a preselection of patients in the clinic where there are limited PT resources. Because the individual benefit differs within a subgroup, the relative merits should additionally be evaluated by individual treatment plan comparisons.

Prostate cancer revealed by skin metastasis: A case report in black ...

African Journals Online (AJOL)

Introduction: Prostate cancer is the most common male malignancy in Togo. Most patients present with advanced and metastatic disease. Skin metastasis from prostate cancer is very rare and it occurs late and often with a poor prognosis. We report a case in a 52-year-old Togolese man where the skin lesions reveal the ...

Background-cross-section-dependent subgroup parameters

International Nuclear Information System (INIS)

Yamamoto, Toshihisa

2003-01-01

A new set of subgroup parameters was derived that can reproduce the self-shielded cross section against a wide range of background cross sections. The subgroup parameters are expressed with a rational equation which numerator and denominator are expressed as the expansion series of background cross section, so that the background cross section dependence is exactly taken into account in the parameters. The advantage of the new subgroup parameters is that they can reproduce the self-shielded effect not only by group basis but also by subgroup basis. Then an adaptive method is also proposed which uses fitting procedure to evaluate the background-cross-section-dependence of the parameters. One of the simple fitting formula was able to reproduce the self-shielded subgroup cross section by less than 1% error from the precise evaluation. (author)

The value of heterogeneity for cost-effectiveness subgroup analysis: conceptual framework and application.

Science.gov (United States)

Espinoza, Manuel A; Manca, Andrea; Claxton, Karl; Sculpher, Mark J

2014-11-01

This article develops a general framework to guide the use of subgroup cost-effectiveness analysis for decision making in a collectively funded health system. In doing so, it addresses 2 key policy questions, namely, the identification and selection of subgroups, while distinguishing 2 sources of potential value associated with heterogeneity. These are 1) the value of revealing the factors associated with heterogeneity in costs and outcomes using existing evidence (static value) and 2) the value of acquiring further subgroup-related evidence to resolve the uncertainty given the current understanding of heterogeneity (dynamic value). Consideration of these 2 sources of value can guide subgroup-specific treatment decisions and inform whether further research should be conducted to resolve uncertainty to explain variability in costs and outcomes. We apply the proposed methods to a cost-effectiveness analysis for the management of patients with acute coronary syndrome. This study presents the expected net benefits under current and perfect information when subgroups are defined based on the use and combination of 6 binary covariates. The results of the case study confirm the theoretical expectations. As more subgroups are considered, the marginal net benefit gains obtained under the current information show diminishing marginal returns, and the expected value of perfect information shows a decreasing trend. We present a suggested algorithm that synthesizes the results to guide policy. © The Author(s) 2014.

Model-Based Recursive Partitioning for Subgroup Analyses.

Science.gov (United States)

Seibold, Heidi; Zeileis, Achim; Hothorn, Torsten

2016-05-01

The identification of patient subgroups with differential treatment effects is the first step towards individualised treatments. A current draft guideline by the EMA discusses potentials and problems in subgroup analyses and formulated challenges to the development of appropriate statistical procedures for the data-driven identification of patient subgroups. We introduce model-based recursive partitioning as a procedure for the automated detection of patient subgroups that are identifiable by predictive factors. The method starts with a model for the overall treatment effect as defined for the primary analysis in the study protocol and uses measures for detecting parameter instabilities in this treatment effect. The procedure produces a segmented model with differential treatment parameters corresponding to each patient subgroup. The subgroups are linked to predictive factors by means of a decision tree. The method is applied to the search for subgroups of patients suffering from amyotrophic lateral sclerosis that differ with respect to their Riluzole treatment effect, the only currently approved drug for this disease.

Histopathological subgroups in knee osteoarthritis.

Science.gov (United States)

Wyatt, L A; Moreton, B J; Mapp, P I; Wilson, D; Hill, R; Ferguson, E; Scammell, B E; Walsh, D A

2017-01-01

Osteoarthritis (OA) is a heterogeneous, multi-tissue disease. We hypothesised that different histopathological features characterise different stages during knee OA progression, and that discrete subgroups can be defined based on validated measures of OA histopathological features. Medial tibial plateaux and synovium were from 343 post-mortem (PM) and 143 OA arthroplasty donations. A 'chondropathy/osteophyte' group (n = 217) was classified as PM cases with osteophytes or macroscopic medial tibiofemoral chondropathy lesions ≥grade 3 to represent pre-surgical (early) OA. 'Non-arthritic' controls (n = 48) were identified from the remaining PM cases. Mankin histopathological scores were subjected to Rasch analysis and supplemented with histopathological scores for subchondral bone marrow replacement and synovitis. Item weightings were derived by principle components analysis (PCA). Histopathological subgroups were sought using latent class analysis (LCA). Chondropathy, synovitis and osteochondral pathology were each associated with OA at arthroplasty, but each was also identified in some 'non-arthritic' controls. Tidemark breaching in the chondropathy/osteophyte group was greater than in non-arthritic controls. Three histopathological subgroups were identified, characterised as 'mild OA', or 'severe OA' with mild or moderate/severe synovitis. Presence and severity of synovitis helps define distinct histopathological OA subgroups. The absence of a discrete 'normal' subgroup indicates a pathological continuum between normality and OA status. Identifying specific pathological processes and their clinical correlates in OA subgroups has potential to accelerate the development of more effective therapies. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Model-based Recursive Partitioning for Subgroup Analyses

OpenAIRE

Seibold, Heidi; Zeileis, Achim; Hothorn, Torsten

2016-01-01

The identification of patient subgroups with differential treatment effects is the first step towards individualised treatments. A current draft guideline by the EMA discusses potentials and problems in subgroup analyses and formulated challenges to the development of appropriate statistical procedures for the data-driven identification of patient subgroups. We introduce model-based recursive partitioning as a procedure for the automated detection of patient subgroups that are identifiable by...

The infiltration, and prognostic importance, of Th1 lymphocytes vary in molecular subgroups of colorectal cancer.

Science.gov (United States)

Ling, Agnes; Lundberg, Ida V; Eklöf, Vincy; Wikberg, Maria L; Öberg, Åke; Edin, Sofia; Palmqvist, Richard

2016-01-01

Giving strong prognostic information, T-cell infiltration is on the verge of becoming an additional component in the routine clinical setting for classification of colorectal cancer (CRC). With a view to further improving the tools for prognostic evaluation, we have studied how Th1 lymphocyte infiltration correlates with prognosis not only by quantity, but also by subsite, within CRCs with different molecular characteristics (microsatellite instability, CpG island methylator phenotype status, and BRAF and KRAS mutational status). We evaluated the Th1 marker T-bet by immunohistochemistry in 418 archival tumour tissue samples from patients who underwent surgical resection for CRC. We found that a high number of infiltrating Th1 lymphocytes is strongly associated with an improved prognosis in patients with CRC, irrespective of intratumoural subsite, and that both extent of infiltration and patient outcome differ according to molecular subgroup. In brief, microsatellite instability, CpG island methylator phenotype-high and BRAF mutated tumours showed increased infiltration of Th1 lymphocytes, and the most pronounced prognostic effect of Th1 infiltration was found in these tumours. Interestingly, BRAF mutated tumours were found to be more highly infiltrated by Th1 lymphocytes than BRAF wild-type tumours whereas the opposite was seen for KRAS mutated tumours. These differences could be explained at least partly by our finding that BRAF mutated, in contrast to KRAS mutated, CRC cell lines and tumour specimens expressed higher levels of the Th1-attracting chemokine CXCL10, and reduced levels of CCL22 and TGFB1, stimulating Th2/Treg recruitment and polarisation. In conclusion, the strong prognostic importance of Th1 lymphocyte infiltration in CRC was found at all subsites evaluated, and it remained significant in multivariable analyses, indicating that T-bet may be a valuable marker in the clinical setting. Our results also indicate that T-bet is of value when analysed in

A prospective examination of circulating tumor cell profiles in non-small-cell lung cancer molecular subgroups.

Science.gov (United States)

Lindsay, C R; Faugeroux, V; Michiels, S; Pailler, E; Facchinetti, F; Ou, D; Bluthgen, M V; Pannet, C; Ngo-Camus, M; Bescher, G; Caramella, C; Billiot, F; Remon, J; Planchard, D; Soria, J-C; Besse, B; Farace, F

2017-07-01

We report the first study examining the clinical, numerical and biological properties of circulating tumor cells according to molecular subtypes of non-small-cell lung cancer. 125 patients with treatment-naïve stage IIIb-IV NSCLC were prospectively recruited for CellSearch analysis. Anti-vimentin antibody was included for examination of CTCs to assess their mesenchymal character. Associations of total CTCs and vimentin-positive (vim +) CTCs with clinical characteristics, tumor genotype, and survival were assessed. 51/125 patients (40.8%) were total CTC+ and 26/125 (20.8%) were vim CTC+ at baseline. Multivariate analysis showed patients with ≥5 total CTCs had significantly reduced OS (HR 0.55, 95% CI 0.33-0.92, P = 0.022) but not PFS (HR 0.68, 95% CI 0.42-1.1, P = 0.118) compared to patients with <5 total CTCs. No OS difference was evident between vim+ CTC and vim-negative CTC patients overall (HR 1.24, 95% CI 0.67-2.28, P = 0.494), but after subdivision according to NSCLC driver mutation, we found an increase of vim+ CTCs in the EGFR-mutated subgroup (N = 21/94 patients; mean 1.24 vs 1.22 vim+ CTCs, P = 0.013), a reduction of total CTCs in the ALK-rearranged subgroup (N = 13/90 patients; mean 1.69 vs 5.82 total CTCs, P = 0.029), and a total absence of vim+ CTCs in KRAS-mutated adenocarcinomas (N = 19/78 patients; mean 0 vs 1.4 vim+ CTCs, P = 0.006). We validate that the baseline presence of ≥5 total CTCs in advanced NSCLC confers a poor prognosis. CTCs from EGFR-mutant NSCLC express epithelial-mesenchymal transition characteristics, not seen in CTCs from patients with KRAS-mutant adenocarcinoma. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Progression-free survival results in postmenopausal Asian women: subgroup analysis from a phase III randomized trial of fulvestrant 500 mg vs anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON).

Science.gov (United States)

Noguchi, Shinzaburo; Ellis, Matthew J; Robertson, John F R; Thirlwell, Jackie; Fazal, Mehdi; Shao, Zhimin

2018-05-01

The international, phase III FALCON study (NCT01602380) in postmenopausal patients with hormone receptor-positive, locally advanced/metastatic breast cancer (LA/MBC) who had not received prior endocrine therapy, demonstrated statistically significant improvement in progression-free survival (PFS) for patients who received fulvestrant 500 mg vs anastrozole 1 mg. This subgroup analysis evaluated PFS in Asian (randomized in China, Japan, or Taiwan) and non-Asian patients from the FALCON study. Eligible patients (estrogen receptor- and/or progesterone receptor-positive LA/MBC; World Health Organization performance status 0-2; ≥ 1 measurable/non-measurable lesion[s]) were randomized. PFS was assessed via Response Evaluation Criteria in Solid Tumours version 1.1, surgery/radiotherapy for disease worsening, or death (any cause). Secondary endpoints included: objective response rate, clinical benefit rate, duration of response, and duration of clinical benefit. Consistency of effect across subgroups was assessed via hazard ratios and 95% confidence intervals (CIs) using a log-rank test. Adverse events (AEs) were evaluated. Of the 462 randomized patients, the Asian and non-Asian subgroups comprised 67 and 395 patients, respectively. In the Asian subgroup, median PFS was 16.6 and 15.9 months with fulvestrant and anastrozole, respectively (hazard ratio 0.81; 95% CI 0.44-1.50). In the non-Asian subgroup, median PFS was 16.5 and 13.8 months, respectively (hazard ratio 0.79; 95% CI 0.62-1.01). Secondary outcomes were numerically improved with fulvestrant vs anastrozole in both subgroups. AE profiles were generally consistent between Asian and non-Asian subgroups. Results of this subgroup analysis suggest that treatment effects in the Asian patient subgroup are broadly consistent with the non-Asian population.

Subgroup analysis of large trials can guide further research: a case study of vitamin E and pneumonia

Directory of Open Access Journals (Sweden)

Harri Hemilä

2011-02-01

Full Text Available Harri Hemilä, Jaakko KaprioDepartment of Public Health, University of Helsinki, Helsinki, FinlandBackground: Biology is complex and the effects of many interventions may vary between population groups. Subgroup analysis can give estimates for specific populations, but trials are usually too small for such analyses.Purpose: To test whether the effect of vitamin E on pneumonia risk is uniform over subgroups defined by smoking and exercise.Methods: The Alpha-Tocopherol Beta-Carotene Cancer Prevention Study examined the effects of vitamin E (50 mg per day and β-carotene (20 mg per day on lung cancer in 29,133 male smokers aged 50–69 years using a 2 × 2 factorial design. The trial was conducted among the general community in Finland during 1985–1993; the intervention lasted for 6.0 years (median. In the present study, we tested the uniformity of vitamin E effect on the risk of hospital-treated pneumonia (898 cases by adding a dummy variable to allow each subgroup its own vitamin E effect in a Cox model covering all participants.Results: Vitamin E effect was not uniform over eight subgroups defined by baseline smoking (5–19 vs ≥20 cigarettes per day, age of smoking initiation (≤20 vs ≥21 years, and exercise during leisure time (yes vs no. Vitamin E decreased pneumonia risk by 69% (95% CI: 43% to 83% among participants who had the least exposure to smoking and exercised during leisure time. Vitamin E increased pneumonia risk by 79% (95% CI: 27% to 150% among those who had the highest exposure to smoking and did not exercise.Limitations: Although the evidence of heterogeneity is strong, it is not evident to what extent the estimates of effect or the limits between the subgroups can be extrapolated to other populations.Conclusion: Subgroup analysis of large trials should be encouraged, though caution is needed in the interpretation of findings. The role of vitamin E in susceptibility to pneumonia in physically active nonsmokers warrants

Research methods for subgrouping low back pain

DEFF Research Database (Denmark)

Kent, Peter; Keating, Jennifer L; Leboeuf-Yde, Charlotte

2010-01-01

important distinctions in their treatment needs or prognoses. Due to a proliferation of research methods and variability in how subgrouping results are interpreted, it is timely to open discussion regarding a conceptual framework for the research designs and statistical methods available for subgrouping...... studies (a method framework). The aims of this debate article are: (1) to present a method framework to inform the design and evaluation of subgrouping research in low back pain, (2) to describe method options when investigating prognostic effects or subgroup treatment effects, and (3) to discuss...... the strengths and limitations of research methods suitable for the hypothesis-setting phase of subgroup studies....

On the subgroups of PR groups

International Nuclear Information System (INIS)

Lebedenko, V.M.

1979-01-01

The subgroups of PR-groups are being studied, i.e., the subgroups of connected and simply connected nonabelian Lie groups, their Lie algebras being defined by the commuting relations of the type [Hsub(i), Hsub(j)] = rsub(ij)Hsub(i) (i 1 of PR-group G there exists such complementary subgroup G 2 and that group G is expanded in semidirect product G = G 1 xG 2 [ru

Revealing the Determinants of Widespread Alternative Splicing Perturbation in Cancer

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Yongsheng Li

2017-10-01

Full Text Available It is increasingly appreciated that alternative splicing plays a key role in generating functional specificity and diversity in cancer. However, the mechanisms by which cancer mutations perturb splicing remain unknown. Here, we developed a network-based strategy, DrAS-Net, to investigate more than 2.5 million variants across cancer types and link somatic mutations with cancer-specific splicing events. We identified more than 40,000 driver variant candidates and their 80,000 putative splicing targets deregulated in 33 cancer types and inferred their functional impact. Strikingly, tumors with splicing perturbations show reduced expression of immune system-related genes and increased expression of cell proliferation markers. Tumors harboring different mutations in the same gene often exhibit distinct splicing perturbations. Further stratification of 10,000 patients based on their mutation-splicing relationships identifies subtypes with distinct clinical features, including survival rates. Our work reveals how single-nucleotide changes can alter the repertoires of splicing isoforms, providing insights into oncogenic mechanisms for precision medicine.

A multigene mutation classification of 468 colorectal cancers reveals a prognostic role for APC

Science.gov (United States)

Schell, Michael J.; Yang, Mingli; Teer, Jamie K.; Lo, Fang Yin; Madan, Anup; Coppola, Domenico; Monteiro, Alvaro N. A.; Nebozhyn, Michael V.; Yue, Binglin; Loboda, Andrey; Bien-Willner, Gabriel A.; Greenawalt, Danielle M.; Yeatman, Timothy J.

2016-01-01

Colorectal cancer (CRC) is a highly heterogeneous disease, for which prognosis has been relegated to clinicopathologic staging for decades. There is a need to stratify subpopulations of CRC on a molecular basis to better predict outcome and assign therapies. Here we report targeted exome-sequencing of 1,321 cancer-related genes on 468 tumour specimens, which identified a subset of 17 genes that best classify CRC, with APC playing a central role in predicting overall survival. APC may assume 0, 1 or 2 truncating mutations, each with a striking differential impact on survival. Tumours lacking any APC mutation carry a worse prognosis than single APC mutation tumours; however, two APC mutation tumours with mutant KRAS and TP53 confer the poorest survival among all the subgroups examined. Our study demonstrates a prognostic role for APC and suggests that sequencing of APC may have clinical utility in the routine staging and potential therapeutic assignment for CRC. PMID:27302369

Existence of a dictatorial subgroup in social choice with independent subgroup utility scales, an alternative proof

NARCIS (Netherlands)

Khmelnitskaya, Anna Borisovna; van Deemen, Adrian; Rusinowska, Agnieszka

2010-01-01

Social welfare orderings for different scales of individual utility measurement in distinct population subgroups are studied. In Khmelnitskaya (2000), employing the continuous version of Arrow’s impossibility theorem, it was shown that for combinations of independent subgroups scales every

Finite subgroups of SU(3)

International Nuclear Information System (INIS)

Bovier, A.; Lueling, M.; Wyler, D.

1980-12-01

We present a new class of finite subgroups of SU(3) of the form Zsub(m) s zsub(n) (semidirect product). We also apply the methods used to investigate semidirect products to the known SU(3) subgroups Δ(3n 2 ) and Δ(6n 2 ) and give analytic formulae for representations (characters) and Clebsch-Gordan coefficients. (orig.)

A Note on TI-Subgroups of Finite Groups

Indian Academy of Sciences (India)

A subgroup of a finite group is called a TI-subgroup if H ∩ H x = 1 or for any x ∈ G . In this short note, the finite groups all of whose nonabelian subgroups are TI-subgroups are classified. Author Affiliations. Jiakuan Lu1 Linna Pang1. Department of Mathematics, Guangxi Normal University, Guangxi, Guilin 541004, ...

Cancer risk in long-term users of valproate: a population-based case-control study

DEFF Research Database (Denmark)

Hallas, Jesper; Friis, Søren; Bjerrum, Lars

2009-01-01

logistic regression. RESULTS: Among the cases and controls, 81 (0.05%) and 260 (0.04%), respectively, were long-term users of valproate. For cancer overall, the crude and adjusted odds ratios were 1.25 [95% confidence interval (95% CI), 0.97-1.60] and 1.21 (95% CI, 0.95-1.56), respectively. Subgroup...... analyses revealed no dose or duration effect for overall cancer incidence, and no specific cancer site was found to be inversely associated with long-term use of valproate. For lung cancer, we found a positive but imprecise association (adjusted odds ratio, 2.32; 95% CI, 1.12-4.79). CONCLUSION: Long...

Atorvastatin in stroke: a review of SPARCL and subgroup analysis

Directory of Open Access Journals (Sweden)

Branko N Huisa

2010-03-01

Full Text Available Branko N Huisa, Andrew B Stemer, Justin A ZivinDepartment of Neuroscience University of California, San Diego, CA, USAAbstract: Statin therapy in patients with cardiovascular disease is associated with reduced incidence of stroke. The Stroke Prevention by Aggressive Reduction of Cholesterol Levels (SPARCL trial showed daily treatment with 80 mg of atorvastatin in patients with a recent stroke or transient ischemic attack (TIA reduced the incidence of fatal or nonfatal stroke by 16%. Several post hoc analyses of different subgroups followed the SPARCL study. They have not revealed any significant differences when patients were sorted by age, sex, presence of carotid disease or type of stroke, with the exception of intracranial hemorrhage as the entry event. Lower low-density lipoprotein cholesterol levels in addition to possible neuroprotective mechanisms due to atorvastatin treatment correlate with improved risk reduction. Although not predefined subgroups and subject to an insufficient power, these post hoc studies have generated new clinical questions. However, clinicians should avoid denying therapy based on such subgroup analysis. At this point, the best evidence powerfully demonstrates stroke and TIA patients should be prescribed high dose statin therapy for secondary stroke prevention.Keywords: statins, intracranial hemorrhage, neuroprotection, outcome, prevention, carotid stenosis, transient ischemic attack

Contents of Stereotypes toward Woman Subgroups: An Investigation in the Framework of Stereotype Content Model

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Timucin Aktan

2016-12-01

Full Text Available The aim of the study was to investigate the stereotype contents toward woman subgroups and relate these contents to social-structural predictors and sexism. In this respect, 119 university students were recruited for the first study and they were asked to rate 10 woman subgroups in terms of their competence and warmth, and their status and competitiveness. Participants' level of sexism was also measured using ambivalent sexism scale. The findings of the first study revealed that competence and warmth were the two fundamental dimensions of the stereotype contents, these stereotypes could be depicted in three clusters, the content of many women stereotypes were mixed, and status was linked to competence and competition was related to lack of warmth. Besides replicating the main hypotheses of stereotype content model, the findings supported its two basic assumptions, i.e. negative stereotypes are not necessary to reveal stereotype clusters and personal stereotypes are more open to motivational concerns. Finally, sexism was related only with competition, but not with stereotype contents. Since, high competent / high warm cluster was not observed in the first study, the number of woman subgroups was increased in the second study. Thus, 86 university students were asked to rate 18 women subgroups on the scales used in the first study. Results replicated the findings of the first study, supporting the main hypothesis of stereotype content model. The findings of the studies were discussed in the light of relevant literature.

Identifying subgroups of patients using latent class analysis

DEFF Research Database (Denmark)

Nielsen, Anne Mølgaard; Kent, Peter; Hestbæk, Lise

2017-01-01

BACKGROUND: Heterogeneity in patients with low back pain (LBP) is well recognised and different approaches to subgrouping have been proposed. Latent Class Analysis (LCA) is a statistical technique that is increasingly being used to identify subgroups based on patient characteristics. However......, as LBP is a complex multi-domain condition, the optimal approach when using LCA is unknown. Therefore, this paper describes the exploration of two approaches to LCA that may help improve the identification of clinically relevant and interpretable LBP subgroups. METHODS: From 928 LBP patients consulting...... of statistical performance measures, qualitative evaluation of clinical interpretability (face validity) and a subgroup membership comparison. RESULTS: For the single-stage LCA, a model solution with seven patient subgroups was preferred, and for the two-stage LCA, a nine patient subgroup model. Both approaches...

Hierarchical clustering of breast cancer methylomes revealed differentially methylated and expressed breast cancer genes.

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I-Hsuan Lin

Full Text Available Oncogenic transformation of normal cells often involves epigenetic alterations, including histone modification and DNA methylation. We conducted whole-genome bisulfite sequencing to determine the DNA methylomes of normal breast, fibroadenoma, invasive ductal carcinomas and MCF7. The emergence, disappearance, expansion and contraction of kilobase-sized hypomethylated regions (HMRs and the hypomethylation of the megabase-sized partially methylated domains (PMDs are the major forms of methylation changes observed in breast tumor samples. Hierarchical clustering of HMR revealed tumor-specific hypermethylated clusters and differential methylated enhancers specific to normal or breast cancer cell lines. Joint analysis of gene expression and DNA methylation data of normal breast and breast cancer cells identified differentially methylated and expressed genes associated with breast and/or ovarian cancers in cancer-specific HMR clusters. Furthermore, aberrant patterns of X-chromosome inactivation (XCI was found in breast cancer cell lines as well as breast tumor samples in the TCGA BRCA (breast invasive carcinoma dataset. They were characterized with differentially hypermethylated XIST promoter, reduced expression of XIST, and over-expression of hypomethylated X-linked genes. High expressions of these genes were significantly associated with lower survival rates in breast cancer patients. Comprehensive analysis of the normal and breast tumor methylomes suggests selective targeting of DNA methylation changes during breast cancer progression. The weak causal relationship between DNA methylation and gene expression observed in this study is evident of more complex role of DNA methylation in the regulation of gene expression in human epigenetics that deserves further investigation.

∗-supplemented subgroups of finite groups

Indian Academy of Sciences (India)

A subgroup H of a group G is said to be M∗-supplemented in G if ... normal subgroups and determined the structure of finite groups by using some ...... [12] Monakhov V S and Shnyparkov A V, On the p-supersolubility of a finite group with a.

Breast and cervical cancer screening disparity among Asian American women: does race/ethnicity matter [corrected]?

Science.gov (United States)

Lee, Hee Yun; Ju, Eunsu; Vang, Pa Der; Lundquist, Melissa

2010-10-01

Ethnic minorities are frequently considered as one homogeneous group in research, and this trend is particularly true for Asian Americans. This article seeks to uncover the intragroup differences in cancer screening behavior among subgroups of Asian American women by disaggregating them into six subgroups. The subgroups were compared with non-Latina white women to examine differences in breast and cancer screening rates and relevant factors associated with receiving these screenings. Three-year merged data from the 2001, 2003, and 2005 California Health Interview Survey (CHIS) were used to investigate the subgroup differences. Samples for the current study were restricted to non-Latina white and Asian American women whose age was ≥ 18 years (n = 58,000) for cervical cancer screening and ≥ 40 years (n = 43,518) for breast cancer screening at the time of the interview. Results showed marked differences in cancer screening rates among Asian American subgroups and between cancer types. Cervical cancer screening rates were noticeably higher than breast cancer screening rates in all groups. The Korean group consistently showed the lowest rates of both cancer screenings. Japanese ranked the highest (79.5%) in breast cancer screening but the second lowest (79.7%) in cervical cancer screening. Enabling factors, such as having private health insurance and a usual source of care, were found to be the strongest predictors of receiving both breast and cervical cancer screening. Screenings for both types of cancer increased if a woman was married or was born in the United States. The findings of this study illustrate the heterogeneity that exists among Asian American subgroups in their cancer screening behaviors. Further development of culturally relevant and ethnic-specific cancer prevention strategies and policies that address the subgroup differences within the larger racial/ethnic population are needed. Public health outreach and cancer education should be prioritized to

Long-term results of 2 adjuvant trials reveal differences in chemosensitivity and the pattern of metastases between colon cancer and rectal cancer.

Science.gov (United States)

Kornmann, Marko; Staib, Ludger; Wiegel, Thomas; Kron, Martina; Henne-Bruns, Doris; Link, Karl-Heinrich; Formentini, Andrea

2013-03-01

Two identical randomized controlled trials designed to optimize adjuvant treatment of colon cancer (CC) (n =855) and rectal cancer (RC) (n = 796) were performed. Long-term evaluation confirmed that the addition of folinic acid (FA) to 5-fluorouracil (5-FU) improved 7-year overall survival (OS) in CC but not in RC and revealed different patterns of recurrence in patients with CC and those with RC. Our aim was to compare long-term results of adjuvant treatment of colon cancer (CC) and rectal cancer (RC). Adjuvant chemotherapy of CC improved overall survival (OS), whereas that of RC remained at the level achieved by 5-fluorouracil (5-FU). We separately conducted 2 identically designed adjuvant trials in CC and RC. Patients were assigned to adjuvant chemotherapy with 5-FU alone, 5-FU + folinic acid (FA), or 5-FU + interferon-alfa. The first study enrolled patients with stage IIb/III CC, and the second study enrolled patients with stage II/III RC. All patients with RC received postoperative irradiation. Median follow-up for all patients with CC (n = 855) and RC (n = 796) was 4.9 years. The pattern and frequency of recurrence differed significantly, especially lung metastases, which occurred more frequently in RC (12.7%) than in CC (7.3%; P < .001). Seven-year OS rates for 5-FU, 5-FU + FA, and 5-FU + IFN-alfa were 54.1% (95% confidence interval [CI], 46.5-61.0), 66.8% (95% CI, 59.4-73.1), and 56.7% (95% CI, 49.3-63.4) in CC and 50.6% (95% CI, 43.0-57.7), 56.3% (95% CI, 49.4-62.7), and 54.8% (95% CI, 46.7-62.2) in RC, respectively. A subgroup analysis pointed to a reduced local recurrence (LR) rate and an increased OS by the addition of FA in stage II RC (n = 271) but not in stage III RC (n = 525). FA increased 7-year OS by 12.7 percentage points in CC but was not effective in RC. Based on these results and the pattern of metastases, our results suggest that the chemosensitivity of CC and RC may be different. Strategies different from those used in CC may be successful to

Different letter-processing strategies in diagnostic subgroups of developmental dyslexia.

Science.gov (United States)

Lachmann, Thomas; van Leeuwen, Cees

2008-07-01

Normally reading adults (N = 15) and primary school children (N = 24) and two diagnostic subgroups of children with developmental dyslexia (N = 21)-all native German speakers-performed a successive same-different task with pairs of letters and nonletters (pseudoletters or geometrical shapes). The first item of a pair was always presented on its own, and the second either on its own or surrounded by a congruent or incongruent nontarget shape. Adults showed congruence effects with nonletters but not with letters, and children with both types of stimuli. Frequent-word reading-impaired dyslexics (N = 11) in addition showed dramatically slower overall reaction times. Nonword reading-impaired dyslexics (N = 10) showed congruence effects with nonletters but negative congruence effects with letters. The results support the notion that normal readers have established a special visual processing strategy for letters. Processing speed rather than reading expertise seems crucial for this strategy to emerge. The contrasting effects between subgroups of dyslexics reveal specific underlying deficits.

Subgroups of GLn(R) for local rings R

International Nuclear Information System (INIS)

Kuku, A.O.; Mahdavi-Hezavehi, M.

2002-07-01

Let R be a local ring, with maximal ideal m, and residue class division ring R/m=D. Put A=M n (R)-n≥1, and denote by A*=GL n (R) the group of units of A. Here we investigate some algebraic structure of subnormal and maximal subgroups of A * . For instance, when D is of finite dimension over its center, it is shown that finitely generated subnormal subgroups of A* are central. It is also proved that maximal subgroups of A* are not finitely generated. Furthermore, assume that P is a nonabelian maximal subgroup of GL 1 (R) such that P contains a noncentral soluble normal subgroup of finite index, it is shown that D is a crossed product division algebra. (author)

Breast Cancer Suspicion in a Transgender Male-to-Female Patient on Hormone Replacement Therapy Presenting with Right Breast Mass: Breast Cancer Risk Assessment and Presentation of a Rare Lesion

Directory of Open Access Journals (Sweden)

Krystina Tongson

2017-01-01

Full Text Available There has been an increasing use of hormonal therapy among male-to-female (MtF transgender individuals. This long-term hormone replacement therapy (HRT renders MtF individuals a unique patient subgroup in terms of breast cancer risk. This case describes a MtF transgender who presented with a breast lesion concerning for malignancy following hormonal replacement therapy. The patient additionally had a strong family history of breast cancer. Final pathology revealed lobular hyperplasia in the setting of gynecomastia and pseudoangiomatous stromal hyperplasia (PASH. Both pathology findings are rare in biological females, let alone in the setting of hormone replacement therapy in a MtF individual. While the number of reported cases of suspicious breast lesions in this population remains scarce, it presents both a diagnostic and therapeutic challenge due to the nature of the treatment course and the lack of research in this recently growing subgroup of patients.

Subgroup-Elimination Transcriptomics Identifies Signaling Proteins that Define Subclasses of TRPV1-Positive Neurons and a Novel Paracrine Circuit

Science.gov (United States)

Isensee, Jörg; Wenzel, Carsten; Buschow, Rene; Weissmann, Robert; Kuss, Andreas W.; Hucho, Tim

2014-01-01

Normal and painful stimuli are detected by specialized subgroups of peripheral sensory neurons. The understanding of the functional differences of each neuronal subgroup would be strongly enhanced by knowledge of the respective subgroup transcriptome. The separation of the subgroup of interest, however, has proven challenging as they can hardly be enriched. Instead of enriching, we now rapidly eliminated the subgroup of neurons expressing the heat-gated cation channel TRPV1 from dissociated rat sensory ganglia. Elimination was accomplished by brief treatment with TRPV1 agonists followed by the removal of compromised TRPV1(+) neurons using density centrifugation. By differential microarray and sequencing (RNA-Seq) based expression profiling we compared the transcriptome of all cells within sensory ganglia versus the same cells lacking TRPV1 expressing neurons, which revealed 240 differentially expressed genes (adj. p1.5). Corroborating the specificity of the approach, many of these genes have been reported to be involved in noxious heat or pain sensitization. Beyond the expected enrichment of ion channels, we found the TRPV1 transcriptome to be enriched for GPCRs and other signaling proteins involved in adenosine, calcium, and phosphatidylinositol signaling. Quantitative population analysis using a recent High Content Screening (HCS) microscopy approach identified substantial heterogeneity of expressed target proteins even within TRPV1-positive neurons. Signaling components defined distinct further subgroups within the population of TRPV1-positive neurons. Analysis of one such signaling system showed that the pain sensitizing prostaglandin PGD2 activates DP1 receptors expressed predominantly on TRPV1(+) neurons. In contrast, we found the PGD2 producing prostaglandin D synthase to be expressed exclusively in myelinated large-diameter neurons lacking TRPV1, which suggests a novel paracrine neuron-neuron communication. Thus, subgroup analysis based on the elimination

Deciphering cancer heterogeneity: the biological space

Directory of Open Access Journals (Sweden)

Stephanie eRoessler

2014-04-01

Full Text Available Most lethal solid tumors including hepatocellular carcinoma (HCC are considered incurable due to extensive heterogeneity in clinical presentation and tumor biology. Tumor heterogeneity may result from different cells of origin, patient ethnicity, etiology, underlying disease and diversity of genomic and epigenomic changes which drive tumor development. Cancer genomic heterogeneity thereby impedes treatment options and poses a significant challenge to cancer management. Studies of the HCC genome have revealed that although various genomic signatures identified in different HCC subgroups share a common prognosis, each carries unique molecular changes which are linked to different sets of cancer hallmarks whose misregulation has been proposed by Hanahan and Weinberg to be essential for tumorigenesis. We hypothesize that these specific sets of cancer hallmarks collectively occupy different tumor biological space representing the misregulation of different biological processes. In principle, a combination of different cancer hallmarks can result in new convergent molecular networks that are unique to each tumor subgroup and represent ideal druggable targets. Due to the ability of the tumor to adapt to external factors such as treatment or changes in the tumor microenvironment, the tumor biological space is elastic. Our ability to identify distinct groups of cancer patients with similar tumor biology who are most likely to respond to a specific therapy would have a significant impact on improving patient outcome. It is currently a challenge to identify a particular hallmark or a newly emerged convergent molecular network for a particular tumor. Thus, it is anticipated that the integration of multiple levels of data such as genomic mutations, somatic copy number aberration, gene expression, proteomics, and metabolomics, may help us grasp the tumor biological space occupied by each individual, leading to improved therapeutic intervention and outcome.

Serum and urine metabolomics study reveals a distinct diagnostic model for cancer cachexia

Science.gov (United States)

Yang, Quan‐Jun; Zhao, Jiang‐Rong; Hao, Juan; Li, Bin; Huo, Yan; Han, Yong‐Long; Wan, Li‐Li; Li, Jie; Huang, Jinlu; Lu, Jin

2017-01-01

Abstract Background Cachexia is a multifactorial metabolic syndrome with high morbidity and mortality in patients with advanced cancer. The diagnosis of cancer cachexia depends on objective measures of clinical symptoms and a history of weight loss, which lag behind disease progression and have limited utility for the early diagnosis of cancer cachexia. In this study, we performed a nuclear magnetic resonance‐based metabolomics analysis to reveal the metabolic profile of cancer cachexia and establish a diagnostic model. Methods Eighty‐four cancer cachexia patients, 33 pre‐cachectic patients, 105 weight‐stable cancer patients, and 74 healthy controls were included in the training and validation sets. Comparative analysis was used to elucidate the distinct metabolites of cancer cachexia, while metabolic pathway analysis was employed to elucidate reprogramming pathways. Random forest, logistic regression, and receiver operating characteristic analyses were used to select and validate the biomarker metabolites and establish a diagnostic model. Results Forty‐six cancer cachexia patients, 22 pre‐cachectic patients, 68 weight‐stable cancer patients, and 48 healthy controls were included in the training set, and 38 cancer cachexia patients, 11 pre‐cachectic patients, 37 weight‐stable cancer patients, and 26 healthy controls were included in the validation set. All four groups were age‐matched and sex‐matched in the training set. Metabolomics analysis showed a clear separation of the four groups. Overall, 45 metabolites and 18 metabolic pathways were associated with cancer cachexia. Using random forest analysis, 15 of these metabolites were identified as highly discriminating between disease states. Logistic regression and receiver operating characteristic analyses were used to create a distinct diagnostic model with an area under the curve of 0.991 based on three metabolites. The diagnostic equation was Logit(P) = −400.53 – 481.88�

The impact of breast cancer biological subtyping on tumor size assessment by ultrasound and mammography - a retrospective multicenter cohort study of 6543 primary breast cancer patients

International Nuclear Information System (INIS)

Stein, Roland Gregor; Wollschläger, Daniel; Kreienberg, Rolf; Janni, Wolfgang; Wischnewsky, Manfred; Diessner, Joachim; Stüber, Tanja; Bartmann, Catharina; Krockenberger, Mathias; Wischhusen, Jörg; Wöckel, Achim; Blettner, Maria; Schwentner, Lukas

2016-01-01

Mammography and ultrasound are the gold standard imaging techniques for preoperative assessment and for monitoring the efficacy of neoadjuvant chemotherapy in breast cancer. Maximum accuracy in predicting pathological tumor size non-invasively is critical for individualized therapy and surgical planning. We therefore aimed to assess the accuracy of tumor size measurement by ultrasound and mammography in a multicentered health services research study. We retrospectively analyzed data from 6543 patients with unifocal, unilateral primary breast cancer. The maximum tumor diameter was measured by ultrasound and/or mammographic imaging. All measurements were compared to final tumor diameter determined by postoperative histopathological examination. We compared the precision of each imaging method across different patient subgroups as well as the method-specific accuracy in each patient subgroup. Overall, the correlation with histology was 0.61 for mammography and 0.60 for ultrasound. Both correlations were higher in pT2 cancers than in pT1 and pT3. Ultrasound as well as mammography revealed a significantly higher correlation with histology in invasive ductal compared to lobular cancers (p < 0.01). For invasive lobular cancers, the mammography showed better correlation with histology than ultrasound (p = 0.01), whereas there was no such advantage for invasive ductal cancers. Ultrasound was significantly superior for HR negative cancers (p < 0.001). HER2/neu positive cancers were also more precisely assessed by ultrasound (p < 0.001). The size of HER2/neu negative cancers could be more accurately predicted by mammography (p < 0.001). This multicentered health services research approach demonstrates that predicting tumor size by mammography and ultrasound provides accurate results. Biological tumor features do, however, affect the diagnostic precision

Subgroup analysis of East Asians in RAINBOW: A phase 3 trial of ramucirumab plus paclitaxel for advanced gastric cancer.

Science.gov (United States)

Muro, Kei; Oh, Sang Cheul; Shimada, Yasuhiro; Lee, Keun-Wook; Yen, Chia-Jui; Chao, Yee; Cho, Jae Yong; Cheng, Rebecca; Carlesi, Roberto; Chandrawansa, Kumari; Orlando, Mauro; Ohtsu, Atsushi

2016-03-01

East Asia has higher gastric cancer incidence and mortality rates than other regions. We present a subgroup analysis of East Asians in the positive study RAINBOW. Patients with advanced gastric or gastroesophageal junction adenocarcinoma previously treated with platinum and fluoropyrimidine received ramucirumab 8 mg/kg or placebo on days 1 and 15 plus paclitaxel 80 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. Of 665 intention-to-treat patients, 223 were East Asian. Median overall survival was 12.1 months for ramucirumab plus paclitaxel and 10.5 months for placebo plus paclitaxel (hazard ratio: 0.986, 95% confidence interval: 0.727-1.337, P = 0.929). Median progression-free survival was 5.5 months for ramucirumab plus paclitaxel and 2.8 months for placebo plus paclitaxel (hazard ratio: 0.628, 95% confidence interval: 0.473-0.834, P = 0.001). Objective response rates were 34% for ramucirumab plus paclitaxel and 20% for placebo plus paclitaxel. Grade ≥ 3 neutropenia (60% vs 28%) and leukopenia (34% vs 13%) were higher for ramucirumab plus paclitaxel. The rate of febrile neutropenia was low (4% vs 4%). Special interest adverse events included any grade bleeding/hemorrhage (55% vs 25%), proteinuria (27% vs 7%), and hypertension (22% vs 2%). Ramucirumab plus paclitaxel significantly improves progression-free survival and response rate, with prolonged median overall survival and an acceptable safety profile in East Asians with advanced gastric cancer. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Synthetic analysis of associations between IL-10 polymorphisms and skin cancer risk.

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Zhao, Hongbo; Yang, Jiaoli; Yu, Zhenzhen; Shen, Hui; Huang, Xinlin; Zhang, Mi; Long, Teng; Cailing, A; Wang, Wenhui

2018-01-23

The current study was designed to quantitatively summarize the evidence for the strength of the associations between common IL-10 functional polymorphisms and skin cancer risk. Relevant publications concerning the associations between common IL-10 functional polymorphisms(-1082G>A, -819C>T and -592C>A) and skin cancer were retrieved by a comprehensive electronic literature search in PubMed, Web of Science, EBSCO, Embase, China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Database (CBM). The odds ratio (OR) and 95% confidence interval (CI) were utilized to assess the strength of the relationship. A total of 26 studies including 4090 cases and 4133 controls (-1082G>A, 10 studies with 1809 cases and 1830 controls; -819C>T, 7 studies with 862 cases and 957 controls; -592C>A, 9 studies with 1419 cases and 1346 controls) were enrolled in the meta-analysis. Overall, the results revealed a borderline decreased risk of skin cancer in heterozygote model (OR = 0.82, 95CI = 0.67-1.00, p = 0.05). The subgroup analysis also presented similar association for non-melanoma skin cancer in heterozygote model (OR = 0.67, 95CI = 0.50-0.91, p = 0.01). Moreover, the further analysis based on the histological type of non-melanoma skin cancer indicated a significantly decreased risk of BCC in allele model (OR = 0.67, 95% CI = 0.50-0.91, p = 0.02) and dominant model (OR = 0.68, 95% CI = 0.48-0.98, p = 0.04). However, neither overall analysis nor subgroup analysis based on cancer subtype revealed a significant association of -1082G>A or -592C>A polymorphisms with skin cancer. The present study suggested a potential association between IL-10 -819C>T polymorphism and decreased risk of skin cancer, but a lack of association for -1082G>A and -592C>A polymorphisms. Further invalidation is urgently needed.

Internalin profiling and multilocus sequence typing suggest four Listeria innocua subgroups with different evolutionary distances from Listeria monocytogenes.

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Chen, Jianshun; Chen, Qiaomiao; Jiang, Lingli; Cheng, Changyong; Bai, Fan; Wang, Jun; Mo, Fan; Fang, Weihuan

2010-03-31

Ecological, biochemical and genetic resemblance as well as clear differences of virulence between L. monocytogenes and L. innocua make this bacterial clade attractive as a model to examine evolution of pathogenicity. This study was attempted to examine the population structure of L. innocua and the microevolution in the L. innocua-L. monocytogenes clade via profiling of 37 internalin genes and multilocus sequence typing based on the sequences of 9 unlinked genes gyrB, sigB, dapE, hisJ, ribC, purM, gap, tuf and betL. L. innocua was genetically monophyletic compared to L. monocytogenes, and comprised four subgroups. Subgroups A and B correlated with internalin types 1 and 3 (except the strain 0063 belonging to subgroup C) and internalin types 2 and 4 respectively. The majority of L. innocua strains belonged to these two subgroups. Subgroup A harbored a whole set of L. monocytogenes-L. innocua common and L. innocua-specific internalin genes, and displayed higher recombination rates than those of subgroup B, including the relative frequency of occurrence of recombination versus mutation (rho/theta) and the relative effect of recombination versus point mutation (r/m). Subgroup A also exhibited a significantly smaller exterior/interior branch length ratio than expected under the coalescent model, suggesting a recent expansion of its population size. The phylogram based on the analysis with correction for recombination revealed that the time to the most recent common ancestor (TMRCA) of L. innocua subgroups A and B were similar. Additionally, subgroup D, which correlated with internalin type 5, branched off from the other three subgroups. All L. innocua strains lacked seventeen virulence genes found in L. monocytogenes (except for the subgroup D strain L43 harboring inlJ and two subgroup B strains bearing bsh) and were nonpathogenic to mice. L. innocua represents a young species descending from L. monocytogenes and comprises four subgroups: two major subgroups A and B

Internalin profiling and multilocus sequence typing suggest four Listeria innocua subgroups with different evolutionary distances from Listeria monocytogenes

Science.gov (United States)

2010-01-01

Background Ecological, biochemical and genetic resemblance as well as clear differences of virulence between L. monocytogenes and L. innocua make this bacterial clade attractive as a model to examine evolution of pathogenicity. This study was attempted to examine the population structure of L. innocua and the microevolution in the L. innocua-L. monocytogenes clade via profiling of 37 internalin genes and multilocus sequence typing based on the sequences of 9 unlinked genes gyrB, sigB, dapE, hisJ, ribC, purM, gap, tuf and betL. Results L. innocua was genetically monophyletic compared to L. monocytogenes, and comprised four subgroups. Subgroups A and B correlated with internalin types 1 and 3 (except the strain 0063 belonging to subgroup C) and internalin types 2 and 4 respectively. The majority of L. innocua strains belonged to these two subgroups. Subgroup A harbored a whole set of L. monocytogenes-L. innocua common and L. innocua-specific internalin genes, and displayed higher recombination rates than those of subgroup B, including the relative frequency of occurrence of recombination versus mutation (ρ/θ) and the relative effect of recombination versus point mutation (r/m). Subgroup A also exhibited a significantly smaller exterior/interior branch length ratio than expected under the coalescent model, suggesting a recent expansion of its population size. The phylogram based on the analysis with correction for recombination revealed that the time to the most recent common ancestor (TMRCA) of L. innocua subgroups A and B were similar. Additionally, subgroup D, which correlated with internalin type 5, branched off from the other three subgroups. All L. innocua strains lacked seventeen virulence genes found in L. monocytogenes (except for the subgroup D strain L43 harboring inlJ and two subgroup B strains bearing bsh) and were nonpathogenic to mice. Conclusions L. innocua represents a young species descending from L. monocytogenes and comprises four subgroups: two

Quantitative proteomics reveals middle infrared radiation-interfered networks in breast cancer cells.

Science.gov (United States)

Chang, Hsin-Yi; Li, Ming-Hua; Huang, Tsui-Chin; Hsu, Chia-Lang; Tsai, Shang-Ru; Lee, Si-Chen; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

2015-02-06

Breast cancer is one of the leading cancer-related causes of death worldwide. Treatment of triple-negative breast cancer (TNBC) is complex and challenging, especially when metastasis has developed. In this study, we applied infrared radiation as an alternative approach for the treatment of TNBC. We used middle infrared (MIR) with a wavelength range of 3-5 μm to irradiate breast cancer cells. MIR significantly inhibited cell proliferation in several breast cancer cells but did not affect the growth of normal breast epithelial cells. We performed iTRAQ-coupled LC-MS/MS analysis to investigate the MIR-triggered molecular mechanisms in breast cancer cells. A total of 1749 proteins were identified, quantified, and subjected to functional enrichment analysis. From the constructed functionally enriched network, we confirmed that MIR caused G2/M cell cycle arrest, remodeled the microtubule network to an astral pole arrangement, altered the actin filament formation and focal adhesion molecule localization, and reduced cell migration activity and invasion ability. Our results reveal the coordinative effects of MIR-regulated physiological responses in concentrated networks, demonstrating the potential implementation of infrared radiation in breast cancer therapy.

Germinal and somatic mutations in cancer

International Nuclear Information System (INIS)

Knudson, A.G. Jr.

1977-01-01

The role of germinal and somatic mutations in carcinogenesis leads to the conclusion that environmental carcinogens probably exert their effects via somatic mutations. Susceptibility to this process may itself be genetically determined, so we may deduce that two groups, one genetic and one non-genetic, are included in the 'environmental' class. Other individuals seem to acquire cancer even in the absence of such environmental agents, and these too may be classified into a genetic and a non-genetic group. It has been estimated that in industrial countries, the environmental groups include 70-80% of all cancer cases, but we are only beginning to know how to separate the genetic and non-genetic subgroups. The genetic subgroup of the 'non-environmental' group is very small, probably of the order of magnitude of 1-2% for cancer as a whole. The remainder, about 25%, comprises a non-genetic, non-environmental subgroup that seems to arise as a consequence of 'spontaneous' somatic mutations. The incidence of these 'background' cancers is what we should combat with preventive and therapeutic measures

Health care expenditures among Asian American subgroups.

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Chen, Jie; Vargas-Bustamante, Arturo; Ortega, Alexander N

2013-06-01

Using two nationally representative data sets, this study examined health care expenditure disparities between Caucasians and different Asian American subgroups. Multivariate analyses demonstrate that Asian Americans, as a group, have significantly lower total expenditures compared with Caucasians. Results also point to considerable heterogeneities in health care spending within Asian American subgroups. Findings suggest that language assistance programs would be effective in reducing disparities among Caucasians and Asian American subgroups with the exception of Indians and Filipinos, who tend to be more proficient in English. Results also indicate that citizenship and nativity were major factors associated with expenditure disparities. Socioeconomic status, however, could not explain expenditure disparities. Results also show that Asian Americans have lower physician and pharmaceutical costs but not emergency department or hospital expenditures. These findings suggest the need for culturally competent policies specific to Asian American subgroups and the necessity to encourage cost-effective treatments among Asian Americans.

Drug-perturbation-based stratification of blood cancer

Science.gov (United States)

Dietrich, Sascha; Lu, Junyan; Wu, Bian; Hüllein, Jennifer; da Silva Liberio, Michelle; Walther, Tatjana; Wagner, Lena; Rabe, Sophie; Ghidelli-Disse, Sonja; Bantscheff, Marcus; Słabicki, Mikołaj; Mock, Andreas; Oakes, Christopher C.; Wang, Shihui; Oppermann, Sina; Lukas, Marina; Kim, Vladislav; Sill, Martin; Jauch, Anna; Sutton, Lesley Ann; Rosenquist, Richard; Liu, Xiyang; Jethwa, Alexander; Lee, Kwang Seok; Lewis, Joe; Putzker, Kerstin; Lutz, Christoph; Rossi, Davide; Oellerich, Thomas; Herling, Marco; Nguyen-Khac, Florence; Plass, Christoph; von Kalle, Christof; Ho, Anthony D.; Hensel, Manfred; Dürig, Jan; Ringshausen, Ingo; Huber, Wolfgang

2017-01-01

As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer. Within chronic lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an important driver of CLL. Based on drug responses, the disease could be organized into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR, or MEK signaling and associated with mutations, gene expression, and DNA methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non–BCR-dependent manner. Multivariate modeling revealed immunoglobulin heavy chain variable gene (IGHV) mutation status and trisomy 12 as the most important modulators of response to kinase inhibitors in CLL. Ex vivo drug responses were associated with outcome. This study overcomes the perception that most mutations do not influence drug response of cancer, and points to an updated approach to understanding tumor biology, with implications for biomarker discovery and cancer care. PMID:29227286

Physician social networks and variation in prostate cancer treatment in three cities.

Science.gov (United States)

Pollack, Craig Evan; Weissman, Gary; Bekelman, Justin; Liao, Kaijun; Armstrong, Katrina

2012-02-01

To examine whether physician social networks are associated with variation in treatment for men with localized prostate cancer. 2004-2005 Surveillance, Epidemiology and End Results-Medicare data from three cities. We identified the physicians who care for patients with prostate cancer and created physician networks for each city based on shared patients. Subgroups of urologists were defined as physicians with dense connections with one another via shared patients. Subgroups varied widely in their unadjusted rates of prostatectomy and the racial/ethnic and socioeconomic composition of their patients. There was an association between urologist subgroup and receipt of prostatectomy. In city A, four subgroups had significantly lower odds of prostatectomy compared with the subgroup with the highest rates of prostatectomy after adjusting for patient clinical and sociodemographic characteristics. Similarly, in cities B and C, subgroups had significantly lower odds of prostatectomy compared with the baseline. Using claims data to identify physician networks may provide an insight into the observed variation in treatment patterns for men with prostate cancer. © Health Research and Educational Trust.

Potential microRNA-mediated oncogenic intercellular communication revealed by pan-cancer analysis

Science.gov (United States)

Li, Yue; Zhang, Zhaolei

2014-11-01

Carcinogenesis consists of oncogenesis and metastasis, and intriguingly microRNAs (miRNAs) are involved in both processes. Although aberrant miRNA activities are prevalent in diverse tumor types, the exact mechanisms for how they regulate cancerous processes are not always clear. To this end, we performed a large-scale pan-cancer analysis via a novel probabilistic approach to infer recurrent miRNA-target interactions implicated in 12 cancer types using data from The Cancer Genome Atlas. We discovered ~20,000 recurrent miRNA regulations, which are enriched for cancer-related miRNAs/genes. Notably, miRNA 200 family (miR-200/141/429) is among the most prominent miRNA regulators, which is known to be involved in metastasis. Importantly, the recurrent miRNA regulatory network is not only enriched for cancer pathways but also for extracellular matrix (ECM) organization and ECM-receptor interactions. The results suggest an intriguing cancer mechanism involving miRNA-mediated cell-to-cell communication, which possibly involves delivery of tumorigenic miRNA messengers to adjacent cells via exosomes. Finally, survival analysis revealed 414 recurrent-prognostic associations, where both gene and miRNA involved in each interaction conferred significant prognostic power in one or more cancer types. Together, our comprehensive pan-cancer analysis provided not only biological insights into metastasis but also brought to bear the clinical relevance of the proposed recurrent miRNA-gene associations.

Applying a gender lens on human papillomavirus infection: cervical cancer screening, HPV DNA testing, and HPV vaccination.

Science.gov (United States)

Branković, Ivan; Verdonk, Petra; Klinge, Ineke

2013-02-08

Our aim is to provide a state-of-the-art overview of knowledge on sex (biological) and gender (sociocultural) aspects of Human papillomavirus (HPV) and cervical cancer for educational purposes. Considerable disparities exist in cervical cancer incidences between different subgroups of women. We provide an outline on the crucial issues and debates based on the recent literature published in leading gender medicine journals. Intersectionality was applied in order to help categorise the knowledge. Key terms (HPV, cervical cancer) were screened in Gender Medicine, Journal of Women's Health and Women & Health from January 2005-June 2012. Additional searches were conducted for topics insufficiently mentioned, such as HPV vaccination of boys. In total, 71 publications were included (56 original papers, four reviews, six reports, three commentaries, one editorial and one policy statement). Research reveals complexity in the way various subgroups of women adhere to cervical screening. Less educated women, older women, uninsured women, homeless women, migrant women facing language barriers, women who have sex with women and obese women participate in Pap smears less frequently. A series of barriers can act to impede decisions to vaccinate against HPV. Both male and female controlled preventive methods and treatment measures should be developed in order to tackle HPV infection and different strategies are needed for different subgroups. A substantial discussion and research on alternative methods of prevention was and is lacking. In future research, sex and gender aspects of HPV-related diseases of boys and men as well as subgroup differences in HPV risk need to be addressed.

Anti-cancer agents in Saudi Arabian herbals revealed by automated high-content imaging

KAUST Repository

Hajjar, Dina

2017-06-13

Natural products have been used for medical applications since ancient times. Commonly, natural products are structurally complex chemical compounds that efficiently interact with their biological targets, making them useful drug candidates in cancer therapy. Here, we used cell-based phenotypic profiling and image-based high-content screening to study the mode of action and potential cellular targets of plants historically used in Saudi Arabia\\'s traditional medicine. We compared the cytological profiles of fractions taken from Juniperus phoenicea (Arar), Anastatica hierochuntica (Kaff Maryam), and Citrullus colocynthis (Hanzal) with a set of reference compounds with established modes of action. Cluster analyses of the cytological profiles of the tested compounds suggested that these plants contain possible topoisomerase inhibitors that could be effective in cancer treatment. Using histone H2AX phosphorylation as a marker for DNA damage, we discovered that some of the compounds induced double-strand DNA breaks. Furthermore, chemical analysis of the active fraction isolated from Juniperus phoenicea revealed possible anti-cancer compounds. Our results demonstrate the usefulness of cell-based phenotypic screening of natural products to reveal their biological activities.

Subgroup-specific intrinsic disorder profiles of arabidopsis NAC transcription factors

DEFF Research Database (Denmark)

Stender, Emil G.; O'Shea, Charlotte; Skriver, Karen

2015-01-01

disordered but contain short, functionally important regions with structure propensities known as molecular recognition features. Here, we analyze for NAC subgroup-specific ID patterns. Some subgroups, such as the VND subgroup implicated in secondary cell wall biosynthesis, and the NAP/SHYG subgroup have...... highly conserved ID profiles. For the stress-associated ATAF1 subgroup and the CUC/ORE1 subgroup involved in development, only sub clades have similar ID patterns. For similar ID profiles, conserved molecular recognition features and sequence motifs represent likely functional determinants of e.......g. transcriptional activation and interactions. Based on our analysis, we suggest that ID profiling of regulatory proteins in general can be used to guide identification of interaction partners of network proteins....

Internalin profiling and multilocus sequence typing suggest four Listeria innocua subgroups with different evolutionary distances from Listeria monocytogenes

Directory of Open Access Journals (Sweden)

Wang Jun

2010-03-01

Full Text Available Abstract Background Ecological, biochemical and genetic resemblance as well as clear differences of virulence between L. monocytogenes and L. innocua make this bacterial clade attractive as a model to examine evolution of pathogenicity. This study was attempted to examine the population structure of L. innocua and the microevolution in the L. innocua-L. monocytogenes clade via profiling of 37 internalin genes and multilocus sequence typing based on the sequences of 9 unlinked genes gyrB, sigB, dapE, hisJ, ribC, purM, gap, tuf and betL. Results L. innocua was genetically monophyletic compared to L. monocytogenes, and comprised four subgroups. Subgroups A and B correlated with internalin types 1 and 3 (except the strain 0063 belonging to subgroup C and internalin types 2 and 4 respectively. The majority of L. innocua strains belonged to these two subgroups. Subgroup A harbored a whole set of L. monocytogenes-L. innocua common and L. innocua-specific internalin genes, and displayed higher recombination rates than those of subgroup B, including the relative frequency of occurrence of recombination versus mutation (ρ/θ and the relative effect of recombination versus point mutation (r/m. Subgroup A also exhibited a significantly smaller exterior/interior branch length ratio than expected under the coalescent model, suggesting a recent expansion of its population size. The phylogram based on the analysis with correction for recombination revealed that the time to the most recent common ancestor (TMRCA of L. innocua subgroups A and B were similar. Additionally, subgroup D, which correlated with internalin type 5, branched off from the other three subgroups. All L. innocua strains lacked seventeen virulence genes found in L. monocytogenes (except for the subgroup D strain L43 harboring inlJ and two subgroup B strains bearing bsh and were nonpathogenic to mice. Conclusions L. innocua represents a young species descending from L. monocytogenes and

Etiological Subgroups of Small-for-Gestational-Age: Differential Neurodevelopmental Outcomes

Science.gov (United States)

Li, Xiuhong; Eiden, Rina D.; Epstein, Leonard H.; Shenassa, Edmond D.; Xie, Chuanbo; Wen, Xiaozhong

2016-01-01

Objectives It remains unclear why substantial variations in neurodevelopmental outcomes exist within small-for-gestational-age (SGA) children. We prospectively compared 5-y neurodevelopmental outcomes across SGA etiological subgroups. Methods Children born SGA (N = 1050) from U.S. Early Childhood Longitudinal Study-Birth Cohort (2001–2007) was divided into etiological subgroups by each of 7 well-established prenatal risk factors. We fit linear regression models to compare 5-y reading, math, gross motor and fine motor scores across SGA subgroups, adjusting for socio-demographic confounders. Results Compared to singleton SGA subgroup, multiple-birth SGA subgroup had lower mean reading (adjusted mean difference, -4.08 [95% confidence interval, -6.10, -2.06]) and math (-2.22 [-3.61, -0.84]) scores. These disadvantages in reading and math existed only among multiple-birth SGA subgroup without ovulation stimulation (reading, -4.50 [-6.64, -2.36]; math, -2.91 [-4.37, -1.44]), but not among those with ovulation stimulation (reading, -2.33 [-6.24, 1.57]; math 0.63 [-1.86, 3.12]). Compared to singleton SGA subgroup without maternal smoking and inadequate gestational weight gain, singleton SGA subgroup with co-occurrence of maternal smoking and inadequate gestational weight gain (GWG) had lower mean reading (-4.81 [-8.50, -1.12]) and math (-2.95 [-5.51, -0.38]) scores. These differences were not mediated by Apgar score. Conclusions Multiple-birth SGA subgroups (vs. singleton SGA) or singleton SGA subgroup with co-occurrence of smoking and inadequate GWG (vs. singleton SGA subgroup without maternal smoking and inadequate gestational weight gain) have poorer cognitive development up to 5 y. PMID:27501456

Etiological Subgroups of Small-for-Gestational-Age: Differential Neurodevelopmental Outcomes.

Directory of Open Access Journals (Sweden)

Xiuhong Li

Full Text Available It remains unclear why substantial variations in neurodevelopmental outcomes exist within small-for-gestational-age (SGA children. We prospectively compared 5-y neurodevelopmental outcomes across SGA etiological subgroups.Children born SGA (N = 1050 from U.S. Early Childhood Longitudinal Study-Birth Cohort (2001-2007 was divided into etiological subgroups by each of 7 well-established prenatal risk factors. We fit linear regression models to compare 5-y reading, math, gross motor and fine motor scores across SGA subgroups, adjusting for socio-demographic confounders.Compared to singleton SGA subgroup, multiple-birth SGA subgroup had lower mean reading (adjusted mean difference, -4.08 [95% confidence interval, -6.10, -2.06] and math (-2.22 [-3.61, -0.84] scores. These disadvantages in reading and math existed only among multiple-birth SGA subgroup without ovulation stimulation (reading, -4.50 [-6.64, -2.36]; math, -2.91 [-4.37, -1.44], but not among those with ovulation stimulation (reading, -2.33 [-6.24, 1.57]; math 0.63 [-1.86, 3.12]. Compared to singleton SGA subgroup without maternal smoking and inadequate gestational weight gain, singleton SGA subgroup with co-occurrence of maternal smoking and inadequate gestational weight gain (GWG had lower mean reading (-4.81 [-8.50, -1.12] and math (-2.95 [-5.51, -0.38] scores. These differences were not mediated by Apgar score.Multiple-birth SGA subgroups (vs. singleton SGA or singleton SGA subgroup with co-occurrence of smoking and inadequate GWG (vs. singleton SGA subgroup without maternal smoking and inadequate gestational weight gain have poorer cognitive development up to 5 y.

Integrative Analysis of Subcellular Quantitative Proteomics Studies Reveals Functional Cytoskeleton Membrane-Lipid Raft Interactions in Cancer.

Science.gov (United States)

Shah, Anup D; Inder, Kerry L; Shah, Alok K; Cristino, Alexandre S; McKie, Arthur B; Gabra, Hani; Davis, Melissa J; Hill, Michelle M

2016-10-07

Lipid rafts are dynamic membrane microdomains that orchestrate molecular interactions and are implicated in cancer development. To understand the functions of lipid rafts in cancer, we performed an integrated analysis of quantitative lipid raft proteomics data sets modeling progression in breast cancer, melanoma, and renal cell carcinoma. This analysis revealed that cancer development is associated with increased membrane raft-cytoskeleton interactions, with ∼40% of elevated lipid raft proteins being cytoskeletal components. Previous studies suggest a potential functional role for the raft-cytoskeleton in the action of the putative tumor suppressors PTRF/Cavin-1 and Merlin. To extend the observation, we examined lipid raft proteome modulation by an unrelated tumor suppressor opioid binding protein cell-adhesion molecule (OPCML) in ovarian cancer SKOV3 cells. In agreement with the other model systems, quantitative proteomics revealed that 39% of OPCML-depleted lipid raft proteins are cytoskeletal components, with microfilaments and intermediate filaments specifically down-regulated. Furthermore, protein-protein interaction network and simulation analysis showed significantly higher interactions among cancer raft proteins compared with general human raft proteins. Collectively, these results suggest increased cytoskeleton-mediated stabilization of lipid raft domains with greater molecular interactions as a common, functional, and reversible feature of cancer cells.

Efficacy and safety of palbociclib in combination with letrozole as first-line treatment of ER-positive, HER2-negative, advanced breast cancer: expanded analyses of subgroups from the randomized pivotal trial PALOMA-1/TRIO-18.

Science.gov (United States)

Finn, Richard S; Crown, John P; Ettl, Johannes; Schmidt, Marcus; Bondarenko, Igor M; Lang, Istvan; Pinter, Tamas; Boer, Katalin; Patel, Ravindranath; Randolph, Sophia; Kim, Sindy T; Huang, Xin; Schnell, Patrick; Nadanaciva, Sashi; Bartlett, Cynthia Huang; Slamon, Dennis J

2016-06-28

Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6. In the randomized, open-label, phase II PALOMA-1/TRIO-18 trial, palbociclib in combination with letrozole improved progression-free survival (PFS) compared with letrozole alone as first-line treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, advanced breast cancer (20.2 months versus 10.2 months; hazard ratio (HR) = 0.488, 95 % confidence interval (CI) 0.319-0.748; one-sided p = 0.0004). Grade 3-4 neutropenia was the most common adverse event (AE) in the palbociclib + letrozole arm. We now present efficacy and safety analyses based on several specific patient and tumor characteristics, and present in detail the clinical patterns of neutropenia observed in the palbociclib + letrozole arm of the overall safety population. Postmenopausal women (n = 165) with ER+, HER2-negative, advanced breast cancer who had not received any systemic treatment for their advanced disease were randomized 1:1 to receive either palbociclib in combination with letrozole or letrozole alone. Treatment continued until disease progression, unacceptable toxicity, consent withdrawal, or death. The primary endpoint was PFS. We now analyze the difference in PFS for the treatment populations by subgroups, including age, histological type, history of prior neoadjuvant/adjuvant systemic treatment, and sites of distant metastasis, using the Kaplan-Meier method. HR and 95 % CI are derived from a Cox proportional hazards regression model. A clinically meaningful improvement in median PFS and clinical benefit response (CBR) rate was seen with palbociclib + letrozole in every subgroup evaluated. Grade 3-4 neutropenia was the most common AE with palbociclib + letrozole in all subgroups. Analysis of the frequency of neutropenia by grade during the first six cycles of treatment showed that there was a downward trend in Grade 3-4 neutropenia

Meta-Analysis of Public Microarray Datasets Reveals Voltage-Gated Calcium Gene Signatures in Clinical Cancer Patients.

Directory of Open Access Journals (Sweden)

Chih-Yang Wang

Full Text Available Voltage-gated calcium channels (VGCCs are well documented to play roles in cell proliferation, migration, and apoptosis; however, whether VGCCs regulate the onset and progression of cancer is still under investigation. The VGCC family consists of five members, which are L-type, N-type, T-type, R-type and P/Q type. To date, no holistic approach has been used to screen VGCC family genes in different types of cancer. We analyzed the transcript expression of VGCCs in clinical cancer tissue samples by accessing ONCOMINE (www.oncomine.org, a web-based microarray database, to perform a systematic analysis. Every member of the VGCCs was examined across 21 different types of cancer by comparing mRNA expression in cancer to that in normal tissue. A previous study showed that altered expression of mRNA in cancer tissue may play an oncogenic role and promote tumor development; therefore, in the present findings, we focus only on the overexpression of VGCCs in different types of cancer. This bioinformatics analysis revealed that different subtypes of VGCCs (CACNA1C, CACNA1D, CACNA1B, CACNA1G, and CACNA1I are implicated in the development and progression of diverse types of cancer and show dramatic up-regulation in breast cancer. CACNA1F only showed high expression in testis cancer, whereas CACNA1A, CACNA1C, and CACNA1D were highly expressed in most types of cancer. The current analysis revealed that specific VGCCs likely play essential roles in specific types of cancer. Collectively, we identified several VGCC targets and classified them according to different cancer subtypes for prospective studies on the underlying carcinogenic mechanisms. The present findings suggest that VGCCs are possible targets for prospective investigation in cancer treatment.

Effect of visceral metastases on the efficacy and safety of everolimus in postmenopausal women with advanced breast cancer: subgroup analysis from the BOLERO-2 study.

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Campone, Mario; Bachelot, Thomas; Gnant, Michael; Deleu, Ines; Rugo, Hope S; Pistilli, Barbara; Noguchi, Shinzaburo; Shtivelband, Mikhail; Pritchard, Kathleen I; Provencher, Louise; Burris, Howard A; Hart, Lowell; Melichar, Bohuslav; Hortobagyi, Gabriel N; Arena, Francis; Baselga, José; Panneerselvam, Ashok; Héniquez, Aurelia; El-Hashimyt, Mona; Taran, Tetiana; Sahmoud, Tarek; Piccart, Martine

2013-08-01

Everolimus (EVE; an inhibitor of mammalian target of rapamycin [mTOR]) enhances treatment options for postmenopausal women with hormone-receptor-positive (HR(+)), human epidermal growth factor receptor-2-negative (HER2(-)) advanced breast cancer (ABC) who progress on a non-steroidal aromatase inhibitor (NSAI). This is especially true for patients with visceral disease, which is associated with poor prognosis. The BOLERO-2 (Breast cancer trial of OraLEveROlimus-2) trial showed that combination treatment with EVE and exemestane (EXE) versus placebo (PBO)+EXE prolonged progression-free survival (PFS) by both investigator (7.8 versus 3.2 months, respectively) and independent (11.0 versus 4.1 months, respectively) central assessment in postmenopausal women with HR(+), HER2(-) ABC recurring/progressing during/after NSAI therapy. The BOLERO-2 trial included a substantial proportion of patients with visceral metastases (56%). Prespecified exploratory subgroup analysis conducted to evaluate the efficacy and safety of EVE+EXE versus PBO+EXE in a prospectively defined subgroup of patients with visceral metastases. At a median follow-up of 18 months, EVE+EXE significantly prolonged median PFS compared with PBO+EXE both in patients with visceral metastases (N=406; 6.8 versus 2.8 months) and in those without visceral metastases (N=318; 9.9 versus 4.2 months). Improvements in PFS with EVE+EXE versus PBO+EXE were also observed in patients with visceral metastases regardless of Eastern Cooperative Oncology Group performance status (ECOG PS). Patients with visceral metastases and ECOG PS 0 had a median PFS of 6.8 months with EVE+EXE versus 2.8 months with PBO+EXE. Among patients with visceral metastases and ECOG PS ≥1, EVE+EXE treatment more than tripled median PFS compared with PBO+EXE (6.8 versus 1.5 months). Adding EVE to EXE markedly extended PFS by ≥4 months among patients with HR(+) HER2(-) ABC regardless of the presence of visceral metastases. Copyright © 2013 The

Urinary infection caused by Micrococcus subgroup 3

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Kerr, Helen

1973-01-01

The laboratory findings and clinical presentations in urinary infections in 23 nurses, 10 caused by Micrococcus subgroup 3 and 13 by Escherichia coli, were studied, and the symptoms and possible predisposing factors compared. There were no important differences between the two groups. The infections caused by Micrococcus subgroup 3 were symptomatically severe, as were those caused by Escherichia coli. PMID:4593863

Suicide Gene-Engineered Stromal Cells Reveal a Dynamic Regulation of Cancer Metastasis

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Shen, Keyue; Luk, Samantha; Elman, Jessica; Murray, Ryan; Mukundan, Shilpaa; Parekkadan, Biju

2016-02-01

Cancer-associated fibroblasts (CAFs) are a major cancer-promoting component in the tumor microenvironment (TME). The dynamic role of human CAFs in cancer progression has been ill-defined because human CAFs lack a unique marker needed for a cell-specific, promoter-driven knockout model. Here, we developed an engineered human CAF cell line with an inducible suicide gene to enable selective in vivo elimination of human CAFs at different stages of xenograft tumor development, effectively circumventing the challenge of targeting a cell-specific marker. Suicide-engineered CAFs were highly sensitive to apoptosis induction in vitro and in vivo by the addition of a simple small molecule inducer. Selection of timepoints for targeted CAF apoptosis in vivo during the progression of a human breast cancer xenograft model was guided by a bi-phasic host cytokine response that peaked at early timepoints after tumor implantation. Remarkably, we observed that the selective apoptosis of CAFs at these early timepoints did not affect primary tumor growth, but instead increased the presence of tumor-associated macrophages and the metastatic spread of breast cancer cells to the lung and bone. The study revealed a dynamic relationship between CAFs and cancer metastasis that has counter-intuitive ramifications for CAF-targeted therapy.

Frequency of hereditary colorectal cancer in Uruguayans patients with non polipotic colorectal cancer; Frecuencia de cancer colorrectal hereditario no polipotico en pacientes uruguayos con cancer colorrectal

Energy Technology Data Exchange (ETDEWEB)

Sarroca, C.; Della Valle, A.; Fresco, R.; Peltomaki, P.; Lynch, H. [Hospital Central de las Fuerzas Armadas, Montevideo (Uruguay)

2010-12-15

Full text: Colonic Cancer Family Polipótic not (CCFNP) is a syndrome transmission autosomal dominant characterized by the aggregation of colorectal cancer (CCR), frequently associated with other solid tumors. Few studies have investigated CCFNP frequency in colorectal cancer patients. these have shown marked geographic variation (0.3% to 13%). The objective of this study is to estimate the frequency of a population CCFNP CCR carriers Uruguayan cancer patients. All patients consecutively operated CRC were included in the Hospital Central Armed Forces (Montevideo, Uruguay) between 1987 and 2003. The cases were classified into 3 groups: 1) those who met the criteria Amsterdam (CCFNP), 2) those who did not meet these criteria but considered as a population of increased risk of cancer based on family history / staff (PRI), and 3) sporadic CRC. Genetic analysis was performed for Detection of mutations in hMLH1, hMSH2 and hMSH6 gene in patients subgroup 1. 461 patients were included, with a median age of 66 years. The subgroup 1 represented 2.5% 2 5.6% and 91.8% sporadic CRC. 75% of cases CCFNP were classified as under 55. Mutations in hMLH1 / hMSH2/hMSH6 were found in 16.6% of cases included in the subgroup 1 (2 in hMLH1, 1 in hMSH2, hMSH6 none). The proportion of patients who met the Amsterdam criteria matches with that observed by other authors. However, the percentage of cases classified CCFNP identified as carriers of mutations is lower than that reported (16.6% vs. ~ 70%). This may reflect a different genetic profile Uruguayan population.

Optimisation of colorectal cancer treatment

NARCIS (Netherlands)

Broek, Colette Bernadine Maria-Theresia van den

2014-01-01

Colorectal cancer is one of the most common cancers worldwide. Although there have been several improvements in screening, staging, and treatment in the past decades, survival differences remain. For example among certain subgroups of patients, such as elderly patients and patients with

Subgroup analysis in burnout : Relations between fatigue, anxiety, and depression.

NARCIS (Netherlands)

van Dam, A.

2016-01-01

Several authors have suggested that burned out patients do not form a homogeneous group and that subgroups should be considered. The identification of these subgroups may contribute to a better understanding of the burnout construct and lead to more specific therapeutic interventions. Subgroup

Sequential formation of subgroups in OB associations

International Nuclear Information System (INIS)

Elmegreen, B.G.; Lada, C.J.

1977-01-01

We reconsider the structure and formation of OB association in view of recent radio and infrared observations of the adjacent molecular clouds. As a result of this reexamination, we propose that OB subgroups are formed in a step-by-step process which involves the propagation of ionization (I) and shock (S) fronts through a molecular cloud complex. OB stars formed at the edge of a molecular cloud drive these I-S fronts into the cloud. A layer of dense neutral material accumulates between the I and S fronts and eventually becomes gravitationally unstable. This process is analyzed in detail. Several arguments concerning the temperature and mass of this layer suggest that a new OB subgroup will form. After approximately one-half million years, these stars will emerge from and disrupt the star-forming layer. A new shock will be driven into the remaining molecular cloud and will initiate another cycle of star formation.Several observed properties of OB associations are shown to follow from a sequential star-forming mechanism. These include the spatial separation and systematic differences in age of OB subgroups in a given association, the regularity of subgroup masses, the alignment of subgroups along the galactic plane, and their physical expansion. Detailed observations of ionization fronts, masers, IR sources, and molecular clouds are also in agreement with this model. Finally, this mechanism provides a means of dissipating a molecular cloud and exposing less massive stars (e.g., T Tauri stars) which may have formed ahead of the shock as part of the original cloud collapsed and fragmented

Proteome-metabolome profiling of ovarian cancer ascites reveals novel components involved in intercellular communication.

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Shender, Victoria O; Pavlyukov, Marat S; Ziganshin, Rustam H; Arapidi, Georgij P; Kovalchuk, Sergey I; Anikanov, Nikolay A; Altukhov, Ilya A; Alexeev, Dmitry G; Butenko, Ivan O; Shavarda, Alexey L; Khomyakova, Elena B; Evtushenko, Evgeniy; Ashrafyan, Lev A; Antonova, Irina B; Kuznetcov, Igor N; Gorbachev, Alexey Yu; Shakhparonov, Mikhail I; Govorun, Vadim M

2014-12-01

Ovarian cancer ascites is a native medium for cancer cells that allows investigation of their secretome in a natural environment. This medium is of interest as a promising source of potential biomarkers, and also as a medium for cell-cell communication. The aim of this study was to elucidate specific features of the malignant ascites metabolome and proteome. In order to omit components of the systemic response to ascites formation, we compared malignant ascites with cirrhosis ascites. Metabolome analysis revealed 41 components that differed significantly between malignant and cirrhosis ascites. Most of the identified cancer-specific metabolites are known to be important signaling molecules. Proteomic analysis identified 2096 and 1855 proteins in the ovarian cancer and cirrhosis ascites, respectively; 424 proteins were specific for the malignant ascites. Functional analysis of the proteome demonstrated that the major differences between cirrhosis and malignant ascites were observed for the cluster of spliceosomal proteins. Additionally, we demonstrate that several splicing RNAs were exclusively detected in malignant ascites, where they probably existed within protein complexes. This result was confirmed in vitro using an ovarian cancer cell line. Identification of spliceosomal proteins and RNAs in an extracellular medium is of particular interest; the finding suggests that they might play a role in the communication between cancer cells. In addition, malignant ascites contains a high number of exosomes that are known to play an important role in signal transduction. Thus our study reveals the specific features of malignant ascites that are associated with its function as a medium of intercellular communication. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Temporal relationship between cancer and myositis identifies two distinctive subgroups of cancers: impact on cancer risk and survival in patients with myositis.

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Kang, Eun Ha; Lee, Sang Jin; Ascherman, Dana P; Lee, Yun Jong; Lee, Eun Young; Lee, Eun Bong; Song, Yeong Wook

2016-09-01

The aim was to compare standardized incidence ratios (SIRs) of cancers temporally related and unrelated to active myositis in patients with myositis. Fifty-two cancer cases were identified in 281 myositis patients. SIRs of cancers having temporal overlap with the active phase of myositis [cancers concurrent with active myositis (CAM), n = 30] and cancers not having such temporal overlap [cancers non-concurrent with active myositis (CNM), n = 22] were compared in 281 patients. Patients with CAM were older at diagnosis of myositis, had a greater tendency to be male, more frequent dysphagia and less frequent interstitial lung disease than patients with CNM. CAM SIR (95% CI) was 1.78 (1.19, 2.56) and CNM SIR 1.23 (0.75, 1.90). The peak SIR was observed in the seventh decade of life for CAM and in the third decade for CNM. When stratified by myositis-cancer intervals, CAM SIR was 9.94 (6.43, 14.67) within 1 year of myositis diagnosis, whereas no temporal relationship was found for CNM. Elevated SIRs were observed for oesophageal cancer [57.77 (11.91, 168.82)], non-Hodgkin's lymphoma [41.43 (13.45, 96.69)], adenocarcinoma of unknown primary origin [67.6 (18.42, 173.07]), lung cancer [7.27 (1.98, 18.61)] and ovarian cancer [19.15 (2.32, 69.17)] within 3 years of CAM diagnosis. The cancer stage at the time of diagnosis was more advanced in CAM than CNM (P < 0.001), with a correspondingly increased hazard ratio of mortality [4.3 (1.5, 12.7)] in patients with CAM vs CNM. A significantly elevated SIR was found for CAM, whereas there was a comparable SIR for CNM relative to the general population. Multiple types of cancers showed elevated SIRs among CAM, but none among CNM. Given that cancer stages in CAM were far advanced at diagnosis, mortality risk was greater in patients with CAM. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Novel personalized pathway-based metabolomics models reveal key metabolic pathways for breast cancer diagnosis

DEFF Research Database (Denmark)

Huang, Sijia; Chong, Nicole; Lewis, Nathan

2016-01-01

diagnosis. We applied this method to predict breast cancer occurrence, in combination with correlation feature selection (CFS) and classification methods. Results: The resulting all-stage and early-stage diagnosis models are highly accurate in two sets of testing blood samples, with average AUCs (Area Under.......993. Moreover, important metabolic pathways, such as taurine and hypotaurine metabolism and the alanine, aspartate, and glutamate pathway, are revealed as critical biological pathways for early diagnosis of breast cancer. Conclusions: We have successfully developed a new type of pathway-based model to study...... metabolomics data for disease diagnosis. Applying this method to blood-based breast cancer metabolomics data, we have discovered crucial metabolic pathway signatures for breast cancer diagnosis, especially early diagnosis. Further, this modeling approach may be generalized to other omics data types for disease...

Intertumoral Heterogeneity within Medulloblastoma Subgroups.

Science.gov (United States)

Cavalli, Florence M G; Remke, Marc; Rampasek, Ladislav; Peacock, John; Shih, David J H; Luu, Betty; Garzia, Livia; Torchia, Jonathon; Nor, Carolina; Morrissy, A Sorana; Agnihotri, Sameer; Thompson, Yuan Yao; Kuzan-Fischer, Claudia M; Farooq, Hamza; Isaev, Keren; Daniels, Craig; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Lee, Ji Yeoun; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Vasiljevic, Alexandre; Faure-Conter, Cecile; Jouvet, Anne; Giannini, Caterina; Nageswara Rao, Amulya A; Li, Kay Ka Wai; Ng, Ho-Keung; Eberhart, Charles G; Pollack, Ian F; Hamilton, Ronald L; Gillespie, G Yancey; Olson, James M; Leary, Sarah; Weiss, William A; Lach, Boleslaw; Chambless, Lola B; Thompson, Reid C; Cooper, Michael K; Vibhakar, Rajeev; Hauser, Peter; van Veelen, Marie-Lise C; Kros, Johan M; French, Pim J; Ra, Young Shin; Kumabe, Toshihiro; López-Aguilar, Enrique; Zitterbart, Karel; Sterba, Jaroslav; Finocchiaro, Gaetano; Massimino, Maura; Van Meir, Erwin G; Osuka, Satoru; Shofuda, Tomoko; Klekner, Almos; Zollo, Massimo; Leonard, Jeffrey R; Rubin, Joshua B; Jabado, Nada; Albrecht, Steffen; Mora, Jaume; Van Meter, Timothy E; Jung, Shin; Moore, Andrew S; Hallahan, Andrew R; Chan, Jennifer A; Tirapelli, Daniela P C; Carlotti, Carlos G; Fouladi, Maryam; Pimentel, José; Faria, Claudia C; Saad, Ali G; Massimi, Luca; Liau, Linda M; Wheeler, Helen; Nakamura, Hideo; Elbabaa, Samer K; Perezpeña-Diazconti, Mario; Chico Ponce de León, Fernando; Robinson, Shenandoah; Zapotocky, Michal; Lassaletta, Alvaro; Huang, Annie; Hawkins, Cynthia E; Tabori, Uri; Bouffet, Eric; Bartels, Ute; Dirks, Peter B; Rutka, James T; Bader, Gary D; Reimand, Jüri; Goldenberg, Anna; Ramaswamy, Vijay; Taylor, Michael D

2017-06-12

While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials. Copyright © 2017 Elsevier Inc. All rights reserved.

An inverse association between tea consumption and colorectal cancer risk.

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Chen, Yuetong; Wu, Yuan; Du, Mulong; Chu, Haiyan; Zhu, Lingjun; Tong, Na; Zhang, Zhengdong; Wang, Meilin; Gu, Dongying; Chen, Jinfei

2017-06-06

It is well known that the tea extracts, mainly polyphenols as chemo-preventive elements, could act as cancer progression blockers. Although the association between tea consumption and colorectal cancer risk has been widely investigated, the results still remain inconsistent. We conducted a dose-response meta-analysis to evaluate their relationships by enrolling qualified 29 literatures. The summary odds ratio (OR) of colorectal cancer for the highest vs. lowest tea consumption was 0.93 with 0.87-1.00 of 95% confidence intervals (CIs) among all studies with modest heterogeneity (P = 0.001, I2 = 43.4%). Stratified analysis revealed that tea, especially green tea, had a protective effect among female and rectal cancer patients. Particularly, the dose-response analysis showed that there was a significant inverse association between an increment of 1 cup/day of tea consumption and colorectal cancer risk in the subgroup of the green tea drinking (OR = 0.98, 95% CI = 0.96-1.01, Pnonlinear = 0.003) and female (OR = 0.68, 95% CI = 0.56-0.81, Pnonlinear colorectal cancer risk, which may have significant public health implications in the prevention of colorectal cancer and further similar researches.

GOBO: gene expression-based outcome for breast cancer online.

Directory of Open Access Journals (Sweden)

Markus Ringnér

Full Text Available Microarray-based gene expression analysis holds promise of improving prognostication and treatment decisions for breast cancer patients. However, the heterogeneity of breast cancer emphasizes the need for validation of prognostic gene signatures in larger sample sets stratified into relevant subgroups. Here, we describe a multifunctional user-friendly online tool, GOBO (http://co.bmc.lu.se/gobo, allowing a range of different analyses to be performed in an 1881-sample breast tumor data set, and a 51-sample breast cancer cell line set, both generated on Affymetrix U133A microarrays. GOBO supports a wide range of applications including: 1 rapid assessment of gene expression levels in subgroups of breast tumors and cell lines, 2 identification of co-expressed genes for creation of potential metagenes, 3 association with outcome for gene expression levels of single genes, sets of genes, or gene signatures in multiple subgroups of the 1881-sample breast cancer data set. The design and implementation of GOBO facilitate easy incorporation of additional query functions and applications, as well as additional data sets irrespective of tumor type and array platform.

NHSBSP type 1 interval cancers: a scientifically valid grouping?

International Nuclear Information System (INIS)

Porter, G.J.R.; Evans, A.J.; Burrell, H.C.; Lee, A.H.S.; Chakrabarti, J.

2007-01-01

Aim: To assess whether there are differences in the pathological features or survival between the new National Health Service Breast Screening Programme (NHSBSP) interval cancer classification system category of type 1 interval cancers, and the previously used, separate categories of occult, unclassified, and true interval cancers. Materials and methods: The prognostic pathological features (grade, lymph node stage, size, vascular invasion, oestrogen receptor status, and histological type) and survival of 428 type 1 interval invasive breast cancers were analysed by subgroup (occult, unclassified and true interval). Results: Occult cancers compared with other type 1 interval cancers were of significantly lower grade [38 of 52 (73%) versus 151 of 340 (44%) grade 1 or 2, p = 0.0005], more likely to be smaller size [37 of 51 (73%) versus 158 of 341 (46%) <20 mm, p = 0.0003] and more frequently of lobular type at histology [14 of 42 (32%) versus 50 of 286 (17%), p = 0.03]. There was no significant difference in pathological features of unclassified tumours compared with other type 1 tumours. There was no significant survival difference between different type 1 subgroups (p = 0.12). Conclusion: The NHSBSP type 1 interval cancers are a heterogeneous grouping with markedly differing pathological features. However, no significant survival difference is seen between the different type 1 subgroups

NHSBSP type 1 interval cancers: a scientifically valid grouping?

Energy Technology Data Exchange (ETDEWEB)

Porter, G.J.R. [Nottingham Breast Institute, City Hospital, Nottingham (United Kingdom)]. E-mail: garethporter@doctors.org.uk; Evans, A.J. [Nottingham Breast Institute, City Hospital, Nottingham (United Kingdom); Burrell, H.C. [Nottingham Breast Institute, City Hospital, Nottingham (United Kingdom); Lee, A.H.S. [Nottingham Breast Institute, City Hospital, Nottingham (United Kingdom); Chakrabarti, J. [Nottingham Breast Institute, City Hospital, Nottingham (United Kingdom)

2007-03-15

Aim: To assess whether there are differences in the pathological features or survival between the new National Health Service Breast Screening Programme (NHSBSP) interval cancer classification system category of type 1 interval cancers, and the previously used, separate categories of occult, unclassified, and true interval cancers. Materials and methods: The prognostic pathological features (grade, lymph node stage, size, vascular invasion, oestrogen receptor status, and histological type) and survival of 428 type 1 interval invasive breast cancers were analysed by subgroup (occult, unclassified and true interval). Results: Occult cancers compared with other type 1 interval cancers were of significantly lower grade [38 of 52 (73%) versus 151 of 340 (44%) grade 1 or 2, p = 0.0005], more likely to be smaller size [37 of 51 (73%) versus 158 of 341 (46%) <20 mm, p = 0.0003] and more frequently of lobular type at histology [14 of 42 (32%) versus 50 of 286 (17%), p = 0.03]. There was no significant difference in pathological features of unclassified tumours compared with other type 1 tumours. There was no significant survival difference between different type 1 subgroups (p = 0.12). Conclusion: The NHSBSP type 1 interval cancers are a heterogeneous grouping with markedly differing pathological features. However, no significant survival difference is seen between the different type 1 subgroups.

The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile

Directory of Open Access Journals (Sweden)

Eng Alvin KH

2008-10-01

Full Text Available Abstract Background Overall gastric cancer survival remains poor mainly because there are no reliable methods for identifying highly curable early stage disease. Multi-protein profiling of gastric fluids, obtained from the anatomic site of pathology, could reveal diagnostic proteomic fingerprints. Methods Protein profiles were generated from gastric fluid samples of 19 gastric cancer and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on multiple ProteinChip arrays. Proteomic features were compared by significance analysis of microarray algorithm and two-way hierarchical clustering. A second blinded sample set (24 gastric cancers and 29 clinically benign gastritides was used for validation. Results By significance analysyis of microarray, 60 proteomic features were up-regulated and 46 were down-regulated in gastric cancer samples (p Conclusion This simple and reproducible multimarker proteomic assay could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy for gastric cancer and pre-malignant lesions.

Subgroup conflicts? Try the psychodramatic "double triad method".

Science.gov (United States)

Verhofstadt-Denève, Leni M F

2012-04-01

The present article suggests the application of a psychodramatic action method for tackling subgroup conflicts in which the direct dialogue between representatives of two opposing subgroups is prepared step by step through an indirect dialogue strategy within two triads, a strategy known as the Double Triad Method (DTM). In order to achieve integration in the group as a whole, it is important that all the members of both subgroups participate actively during the entire process. The first part of the article briefly explores the theoretical background, with a special emphasis on the Phenomenological-Dialectical Personality Model (Phe-Di PModel). In the second part, the DTM procedure is systematically described through its five action stages, each accompanied with 1) a spatial representation of the consecutive actions, 2) some illustrative statements for each stage, and 3) a theoretical interpretation of the dialectically involved personality dimensions in both protagonists. The article concludes with a discussion and suggestions for more extensive applications of the DTM method, including the question of its relationships to Agazarian's functional subgrouping, psychodrama, and sociodrama.

Multi-region and single-cell sequencing reveal variable genomic heterogeneity in rectal cancer.

Science.gov (United States)

Liu, Mingshan; Liu, Yang; Di, Jiabo; Su, Zhe; Yang, Hong; Jiang, Beihai; Wang, Zaozao; Zhuang, Meng; Bai, Fan; Su, Xiangqian

2017-11-23

Colorectal cancer is a heterogeneous group of malignancies with complex molecular subtypes. While colon cancer has been widely investigated, studies on rectal cancer are very limited. Here, we performed multi-region whole-exome sequencing and single-cell whole-genome sequencing to examine the genomic intratumor heterogeneity (ITH) of rectal tumors. We sequenced nine tumor regions and 88 single cells from two rectal cancer patients with tumors of the same molecular classification and characterized their mutation profiles and somatic copy number alterations (SCNAs) at the multi-region and the single-cell levels. A variable extent of genomic heterogeneity was observed between the two patients, and the degree of ITH increased when analyzed on the single-cell level. We found that major SCNAs were early events in cancer development and inherited steadily. Single-cell sequencing revealed mutations and SCNAs which were hidden in bulk sequencing. In summary, we studied the ITH of rectal cancer at regional and single-cell resolution and demonstrated that variable heterogeneity existed in two patients. The mutational scenarios and SCNA profiles of two patients with treatment naïve from the same molecular subtype are quite different. Our results suggest each tumor possesses its own architecture, which may result in different diagnosis, prognosis, and drug responses. Remarkable ITH exists in the two patients we have studied, providing a preliminary impression of ITH in rectal cancer.

MLH1-Silenced and Non-Silenced Subgroups of Hypermutated Colorectal Carcinomas Have Distinct Mutational Landscapes

Science.gov (United States)

Donehower, Lawrence A.; Creighton, Chad J.; Schultz, Nikolaus; Shinbrot, Eve; Chang, Kyle; Gunaratne, Preethi H.; Muzny, Donna; Sander, Chris; Hamilton, Stanley R.; Gibbs, Richard A.; Wheeler, David

2014-01-01

Approximately 15% of colorectal carcinomas (CRC) exhibit a hypermutated genotype accompanied by high levels of microsatellite instability (MSI-H) and defects in DNA mismatch repair. These tumors, unlike the majority of colorectal carcinomas, are often diploid, exhibit frequent epigenetic silencing of the MLH1 DNA mismatch repair gene, and have a better clinical prognosis. As an adjunct study to The Cancer Genome Atlas consortium that recently analyzed 224 colorectal cancers by whole exome sequencing, we compared the 35 CRC (15.6%) with a hypermutated genotype to those with a non-hypermutated genotype. We found that 22 (63%) of hypermutated CRC exhibited transcriptional silencing of the MLH1 gene, a high frequency of BRAF V600E gene mutations and infrequent APC and KRAS mutations, a mutational pattern significantly different from their non-hypermutated counterparts. However, the remaining 13 (37%) hypermutated CRC lacked MLH1 silencing, contained tumors with the highest mutation rates (“ultramutated” CRC), and exhibited higher incidences of APC and KRAS mutations, but infrequent BRAF mutations. These patterns were confirmed in an independent validation set of 250 exome-sequenced CRC. Analysis of mRNA and microRNA expression signatures revealed that hypermutated CRC with MLH1 silencing had greatly reduced levels of WNT signaling and increased BRAF signaling relative non-hypermutated CRC. Our findings suggest that hypermutated CRC include one subgroup with fundamentally different pathways to malignancy than the majority of CRC. Examination of MLH1 expression status and frequencies of APC, KRAS, and BRAF mutation in CRC may provide a useful diagnostic tool that could supplement the standard microsatellite instability assays and influence therapeutic decisions. PMID:22899370

Different demographic, genetic, and longitudinal traits in language versus memory Alzheimer's subgroups.

Science.gov (United States)

Mez, Jesse; Cosentino, Stephanie; Brickman, Adam M; Huey, Edward D; Mayeux, Richard

2013-01-01

The study's objective was to compare demographics, APOE genotypes, and rate of rise over time in functional impairment in neuropsychologically defined language, typical, and memory subgroups of clinical Alzheimer's disease (AD). 1,368 participants from the National Alzheimer's Coordinating Center database with a diagnosis of probable AD (CDR 0.5-1.0) were included. A language subgroup (n = 229) was defined as having language performance >1 SD worse than memory performance. A memory subgroup (n = 213) was defined as having memory performance >1 SD worse than language performance. A typical subgroup (n = 926) was defined as having a difference in language and memory performance of memory subgroup, the language subgroup was 3.7 years older and more frequently self-identified as African American (OR = 3.69). Under a dominant genetic model, the language subgroup had smaller odds of carrying at least one APOEε4 allele relative to the memory subgroup. While this difference was present for all ages, it was more striking at a younger age (OR = 0.19 for youngest tertile; OR = 0.52 for oldest tertile). Compared with the memory subgroup, the language subgroup rose 35% faster on the Functional Assessment Questionnaire and 44% faster on CDR sum of boxes over time. Among a subset of participants who underwent autopsy (n = 98), the language, memory, and typical subgroups were equally likely to have an AD pathologic diagnosis, suggesting that variation in non-AD pathologies across subtypes did not lead to the observed differences. The study demonstrates that a language subgroup of AD has different demographics, genetic profile, and disease course in addition to cognitive phenotype.

Frequency of hereditary colorectal cancer in Uruguayans patients with non polipotic colorectal cancer

International Nuclear Information System (INIS)

Sarroca, C.; Della Valle, A.; Fresco, R.; Peltomaki, P.; Lynch, H.

2010-01-01

Full text: Colonic Cancer Family Polipótic not (CCFNP) is a syndrome transmission autosomal dominant characterized by the aggregation of colorectal cancer (CCR), frequently associated with other solid tumors. Few studies have investigated CCFNP frequency in colorectal cancer patients. these have shown marked geographic variation (0.3% to 13%). The objective of this study is to estimate the frequency of a population CCFNP CCR carriers Uruguayan cancer patients. All patients consecutively operated CRC were included in the Hospital Central Armed Forces (Montevideo, Uruguay) between 1987 and 2003. The cases were classified into 3 groups: 1) those who met the criteria Amsterdam (CCFNP), 2) those who did not meet these criteria but considered as a population of increased risk of cancer based on family history / staff (PRI), and 3) sporadic CRC. Genetic analysis was performed for Detection of mutations in hMLH1, hMSH2 and hMSH6 gene in patients subgroup 1. 461 patients were included, with a median age of 66 years. The subgroup 1 represented 2.5% 2 5.6% and 91.8% sporadic CRC. 75% of cases CCFNP were classified as under 55. Mutations in hMLH1 / hMSH2/hMSH6 were found in 16.6% of cases included in the subgroup 1 (2 in hMLH1, 1 in hMSH2, hMSH6 none). The proportion of patients who met the Amsterdam criteria matches with that observed by other authors. However, the percentage of cases classified CCFNP identified as carriers of mutations is lower than that reported (16.6% vs. ~ 70%). This may reflect a different genetic profile Uruguayan population

Intratumoral heterogeneity: Role of differentiation in a potentially lethal phenotype of testicular cancer.

Science.gov (United States)

Tu, Shi-Ming; Bilen, Mehmet Asim; Hess, Kenneth R; Broaddus, Russell R; Kopetz, Scott; Wei, Chongjuan; Pagliaro, Lance C; Karam, Jose A; Ward, John F; Wood, Christopher G; Rao, Priya; Tu, Zachary H; General, Rosale; Chen, Adrienne H; Nieto, Yago L; Yeung, Sai-Ching J; Lin, Sue-Hwa; Logothetis, Christopher J; Pisters, Louis L

2016-06-15

Intratumoral heterogeneity presents a major obstacle to the widespread implementation of precision medicine. The authors assessed the origin of intratumoral heterogeneity in nonseminomatous germ cell tumor of the testis (NSGCT) and identified distinct tumor subtypes and a potentially lethal phenotype. In this retrospective study, all consecutive patients who had been diagnosed with an NSGCT between January 2000 and December 2010 were evaluated. The histologic makeup of primary tumors and the clinical course of disease were determined for each patient. A Fine and Gray proportional hazards regression analysis was used to determine the prognostic risk factors, and the Gray test was used to detect differences in the cumulative incidence of cancer death. In a separate prospective study, next-generation sequencing was performed on tumor samples from 9 patients to identify any actionable mutations. Six hundred fifteen patients were included in this study. Multivariate analysis revealed that the presence of yolk sac tumor in the primary tumor (P = .0003) was associated with an unfavorable prognosis. NSGCT could be divided into 5 subgroups. Patients in the yolk sac-seminoma subgroup had the poorest clinical outcome (P = .0015). These tumors tended to undergo somatic transformation (P Cancer 2016;122:1836-43. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2016 American Cancer Society.

Genome-scale analysis of aberrant DNA methylation in colorectal cancer

Science.gov (United States)

Hinoue, Toshinori; Weisenberger, Daniel J.; Lange, Christopher P.E.; Shen, Hui; Byun, Hyang-Min; Van Den Berg, David; Malik, Simeen; Pan, Fei; Noushmehr, Houtan; van Dijk, Cornelis M.; Tollenaar, Rob A.E.M.; Laird, Peter W.

2012-01-01

Colorectal cancer (CRC) is a heterogeneous disease in which unique subtypes are characterized by distinct genetic and epigenetic alterations. Here we performed comprehensive genome-scale DNA methylation profiling of 125 colorectal tumors and 29 adjacent normal tissues. We identified four DNA methylation–based subgroups of CRC using model-based cluster analyses. Each subtype shows characteristic genetic and clinical features, indicating that they represent biologically distinct subgroups. A CIMP-high (CIMP-H) subgroup, which exhibits an exceptionally high frequency of cancer-specific DNA hypermethylation, is strongly associated with MLH1 DNA hypermethylation and the BRAFV600E mutation. A CIMP-low (CIMP-L) subgroup is enriched for KRAS mutations and characterized by DNA hypermethylation of a subset of CIMP-H-associated markers rather than a unique group of CpG islands. Non-CIMP tumors are separated into two distinct clusters. One non-CIMP subgroup is distinguished by a significantly higher frequency of TP53 mutations and frequent occurrence in the distal colon, while the tumors that belong to the fourth group exhibit a low frequency of both cancer-specific DNA hypermethylation and gene mutations and are significantly enriched for rectal tumors. Furthermore, we identified 112 genes that were down-regulated more than twofold in CIMP-H tumors together with promoter DNA hypermethylation. These represent ∼7% of genes that acquired promoter DNA methylation in CIMP-H tumors. Intriguingly, 48/112 genes were also transcriptionally down-regulated in non-CIMP subgroups, but this was not attributable to promoter DNA hypermethylation. Together, we identified four distinct DNA methylation subgroups of CRC and provided novel insight regarding the role of CIMP-specific DNA hypermethylation in gene silencing. PMID:21659424

Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup

DEFF Research Database (Denmark)

Wilson, M K; Pujade-Lauraine, E; Aoki, D

2017-01-01

This manuscript reports the consensus statements regarding recurrent ovarian cancer (ROC), reached at the fifth Ovarian Cancer Consensus Conference (OCCC), which was held in Tokyo, Japan, in November 2015. Three important questions were identified: (i) What are the subgroups for clinical trials i...... including pre-defined patient reported outcomes (PROs), time to second subsequent therapy (TSST), or time until definitive deterioration of quality of life (TUDD)....

MiR-146a rs2910164 polymorphism increases the risk of digestive system cancer: A meta-analysis.

Science.gov (United States)

Xie, Wen Qun; Wang, Xiao Fan

2017-02-01

There is merging evidence suggesting that the miR-146a polymorphism might be associated with susceptibility to digestive system cancer. However, previous published studies have failed to achieve a definitive conclusion. To address this issue, an updated meta-analysis was performed. A comprehensive electronic search was conducted using the following source to identify the eligible studies: PubMed, Embase, China BioMedicine, the Cochrane Library, and Google Scholar. Odds ratios and its corresponding 95% confidence interval (CI) was used in the quantitative synthesis. The database search identified 1344 eligible studies, of which 32 (comprising 12,541 cases and 15,925 controls) were included. The results indicate that the miR-146a rs2910164 polymorphism was significantly associated with increased risk of digestive system cancer in heterozygote comparison (GC vs. CC: OR=1.15, 95% CI: 1.02-1.30, P=0.02), and recessive model (GG vs. GC+CC: OR=1.11, 95% CI: 1.04-1.17, P=0.006). Subgroup analysis by cancer site revealed increased risk in gastric cancer above heterozygote comparison (GG vs. GC: OR=1.13, 95% CI: 1.02-1.25, P=0.02), and recessive model (GG vs. GC+CC: OR=1.15, 95% CI: 1.04-1.26, P=0.006). Similarly, increased cancer risk was observed in hepatocellular carcinoma when compared with homozygote comparison (GG vs. CC: OR=1.21, 95% CI: 1.04-1.42, P=0.02), heterozygote comparison (GC vs. CC: OR=1.15, 95% CI: 1.02-1.29, P=0.02), and dominant model (GG+GC vs. CC: OR=1.16, 95% CI: 1.04-1.29, P=0.009). When stratified by ethnicity and quality score, increased cancer risks were also observed among Asians, Caucasians and high quality studies subgroup. The current study revealed that miR-146a G/C genetic polymorphism was more likely to be associated with digestive system cancer risk. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

PAX2 is activated by estradiol in breast cancer cells of the luminal subgroup selectively, to confer a low invasive phenotype

Science.gov (United States)

2011-01-01

Background Metastasis is the leading cause of death among breast cancer patients. Identifying key cellular factors controlling invasion and metastasis of breast cancer cells should pave the way to new therapeutic strategies efficiently interfering with the metastatic process. PAX2 (paired box 2) transcription factor is expressed by breast cancer cells in vivo and recently, it was shown to negatively regulate the expression of ERBB2 (erythroblastic leukemia viral oncogene homolog 2, HER-2/neu), a well-documented pro-invasive and pro-metastastic gene, in luminal/ERalpha-positive (ERα+) breast cancer cells. The objective of the present study was to investigate a putative role for PAX2 in the control of luminal breast cancer cells invasion, and to begin to characterize its regulation. Results PAX2 activity was higher in cell lines from luminal compared to non-luminal subtype, and activation of PAX2 by estradiol was selectively achieved in breast cancer cell lines of the luminal subtype. This process was blocked by ICI 182780 and could be antagonized by IGF-1. Knockdown of PAX2 in luminal MCF-7 cells completely abrogated estradiol-induced downregulation of ERBB2 and decrease of cell invasion, whereas overexpression of PAX2 in these cells enhanced estradiol effects on ERBB2 levels and cell invasion. Conclusions The study demonstrates that PAX2 activation by estradiol is selectively achieved in breast cancer cells of the luminal subtype, via ERα, and identifies IGF-1 as a negative regulator of PAX2 activity in these cells. Further, it reveals a new role for PAX2 in the maintenance of a low invasive behavior in luminal breast cancer cells upon exposure to estradiol, and shows that overexpression and activation of PAX2 in these cells is sufficient to reduce their invasive ability. PMID:22168360

Molecular subgroups of medulloblastoma

OpenAIRE

Northcott, Paul A; Dubuc, Adrian M; Pfister, Stefan; Taylor, Michael D

2012-01-01

Recent efforts at stratifying medulloblastomas based on their molecular features have revolutionized our understanding of this morbidity. Collective efforts by multiple independent groups have subdivided medulloblastoma from a single disease into four distinct molecular subgroups characterized by disparate transcriptional signatures, mutational spectra, copy number profiles and, most importantly, clinical features. We present a summary of recent studies that have contributed to our understand...

Identities on maximal subgroups of GLn(D)

International Nuclear Information System (INIS)

Kiani, D.; Mahdavi-Hezavehi, M.

2002-04-01

Let D be a division ring with centre F. Assume that M is a maximal subgroup of GL n (D), n≥1 such that Z(M) is algebraic over F. Group identities on M and polynomial identities on the F-linear hull F[M] are investigated. It is shown that if F[M] is a PI-algebra, then [D:F] n (D) and M is a maximal subgroup of N. If M satisfies a group identity, it is shown that M is abelian-by-finite. (author)

[Polymyalgia rheumatica revealing a lung cancer].

Science.gov (United States)

Cocquempot, K; Defuentes, G; Duron-Martineau, S; Berets, O; Vaylet, F; Margery, J

2013-01-01

Polymyalgia rheumatica is an inflammatory condition belonging to the connective tissue diseases, which occurs quite frequently in the elderly. Previously, cases have been reported in association with malignant tumours, in a synchronous fashion or prior to the appearance of the cancer. In these cases, the polymyalgia rheumatica is considered to be a paraneoplastic syndrome. We report the cases of a 63-year-old woman and a 58-year-old man with severe proximal girdle pain associated to a high-level of systemic inflammatory markers and a diagnosis of polymyalgia rheumatica was made. In the face of a lack of ineffectiveness of analgesic and anti-inflammatory treatments, an intensive investigation was undertaken which in both cases revealed an adenocarcinoma of the lung. The rheumatic manifestations responded well to chemotherapy targeting the lung tumour. We present here a review of the literature to give prominence to the diagnostic pitfalls that can occur around paraneoplastic polymyalgia rheumatica. The presence of therapeutic resistance at the onset of treatment and other atypical features may suggest the presence of an occult malignancy. Copyright © 2012 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Adjuvant tamoxifen influences the lipid profile in breast cancer patients.

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Lin, Che; Chen, Li-Sheng; Kuo, Shou-Jen; Chen, Dar-Ren

2014-02-01

Currently there is a debate regarding whether tamoxifen used in breast cancer has an impact on lipid profiles. The aim of this study was to determine whether tamoxifen has an impact on the serum lipid profile in Taiwanese women. Data of 109 patients were collected from the routine clinical follow-up for women with hormone receptor-positive breast cancer who were treated between July 2005 and March 2008. These patients were divided into 2 subgroups, based on their tumor grade and lymph node status. Subgroup 1 patients had tumor grade I/II and a negative lymph node status. Those patients with tumor grade III or a positive lymph node status were defined as subgroup 2. In the 109 patients, the mean serum total cholesterol (TC) levels after tamoxifen treatment, as well as the serum low-density lipoprotein cholesterol (LDL-C) levels, were lower than the baseline levels, with statistically significant differences. Treatment with tamoxifen lowered the serum TC and LDL-C levels in both subgroups. The results indicate that tamoxifen has an impact on the serum lipid profile of breast cancer patients in Taiwan. Physicians should follow up the lipid profile in these patients.

Qualitative interaction trees: A tool to identify qualitative treatment-subgroup interactions

NARCIS (Netherlands)

Dusseldorp, E.; Mechelen, I. van

2014-01-01

When two alternative treatments (A and B) are available, some subgroup of patients may display a better outcome with treatment A than with B, whereas for another subgroup, the reverse may be true. If this is the case, a qualitative (i.e., disordinal) treatment-subgroup interaction is present. Such

On the growth of rank for subgroups of finitely generated groups

International Nuclear Information System (INIS)

Osin, D V

1999-01-01

In [1] and [2] the functions of rank growth were independently introduced and investigated for subgroups of a finitely generated free group. In the present paper the concept of growth of rank is extended to subgroups of an arbitrary finitely generated group G, and the dependence of the asymptotic behaviour of the above functions on the choice of a finite generating set in G is studied. For a broad class of groups (which includes, in particular, the free polynilpotent groups) estimates for the growth of rank for subgroups are obtained that generalize the wellknown Baumslag-Eidel'kind result on finitely generated normal subgroups. Some problems related to the realization of arbitrary functions as functions of rank growth for subgroups of soluble groups are treated

Anatomic and Physiologic Heterogeneity of Subgroup-A Auditory Sensory Neurons in Fruit Flies.

Science.gov (United States)

Ishikawa, Yuki; Okamoto, Natsuki; Nakamura, Mizuki; Kim, Hyunsoo; Kamikouchi, Azusa

2017-01-01

The antennal ear of the fruit fly detects acoustic signals in intraspecific communication, such as the courtship song and agonistic sounds. Among the five subgroups of mechanosensory neurons in the fly ear, subgroup-A neurons respond maximally to vibrations over a wide frequency range between 100 and 1,200 Hz. The functional organization of the neural circuit comprised of subgroup-A neurons, however, remains largely unknown. In the present study, we used 11 GAL4 strains that selectively label subgroup-A neurons and explored the diversity of subgroup-A neurons by combining single-cell anatomic analysis and Ca 2+ imaging. Our findings indicate that the subgroup-A neurons that project into various combinations of subareas in the brain are more anatomically diverse than previously described. Subgroup-A neurons were also physiologically diverse, and some types were tuned to a narrow frequency range, suggesting that the response of subgroup-A neurons to sounds of a wide frequency range is due to the existence of several types of subgroup-A neurons. Further, we found that an auditory behavioral response to the courtship song of flies was attenuated when most subgroup-A neurons were silenced. Together, these findings characterize the heterogeneous functional organization of subgroup-A neurons, which might facilitate species-specific acoustic signal detection.

Cluster Analysis of Clinical Data Identifies Fibromyalgia Subgroups

Science.gov (United States)

Docampo, Elisa; Collado, Antonio; Escaramís, Geòrgia; Carbonell, Jordi; Rivera, Javier; Vidal, Javier; Alegre, José

2013-01-01

Introduction Fibromyalgia (FM) is mainly characterized by widespread pain and multiple accompanying symptoms, which hinder FM assessment and management. In order to reduce FM heterogeneity we classified clinical data into simplified dimensions that were used to define FM subgroups. Material and Methods 48 variables were evaluated in 1,446 Spanish FM cases fulfilling 1990 ACR FM criteria. A partitioning analysis was performed to find groups of variables similar to each other. Similarities between variables were identified and the variables were grouped into dimensions. This was performed in a subset of 559 patients, and cross-validated in the remaining 887 patients. For each sample and dimension, a composite index was obtained based on the weights of the variables included in the dimension. Finally, a clustering procedure was applied to the indexes, resulting in FM subgroups. Results Variables clustered into three independent dimensions: “symptomatology”, “comorbidities” and “clinical scales”. Only the two first dimensions were considered for the construction of FM subgroups. Resulting scores classified FM samples into three subgroups: low symptomatology and comorbidities (Cluster 1), high symptomatology and comorbidities (Cluster 2), and high symptomatology but low comorbidities (Cluster 3), showing differences in measures of disease severity. Conclusions We have identified three subgroups of FM samples in a large cohort of FM by clustering clinical data. Our analysis stresses the importance of family and personal history of FM comorbidities. Also, the resulting patient clusters could indicate different forms of the disease, relevant to future research, and might have an impact on clinical assessment. PMID:24098674

Cluster analysis of clinical data identifies fibromyalgia subgroups.

Directory of Open Access Journals (Sweden)

Elisa Docampo

Full Text Available INTRODUCTION: Fibromyalgia (FM is mainly characterized by widespread pain and multiple accompanying symptoms, which hinder FM assessment and management. In order to reduce FM heterogeneity we classified clinical data into simplified dimensions that were used to define FM subgroups. MATERIAL AND METHODS: 48 variables were evaluated in 1,446 Spanish FM cases fulfilling 1990 ACR FM criteria. A partitioning analysis was performed to find groups of variables similar to each other. Similarities between variables were identified and the variables were grouped into dimensions. This was performed in a subset of 559 patients, and cross-validated in the remaining 887 patients. For each sample and dimension, a composite index was obtained based on the weights of the variables included in the dimension. Finally, a clustering procedure was applied to the indexes, resulting in FM subgroups. RESULTS: VARIABLES CLUSTERED INTO THREE INDEPENDENT DIMENSIONS: "symptomatology", "comorbidities" and "clinical scales". Only the two first dimensions were considered for the construction of FM subgroups. Resulting scores classified FM samples into three subgroups: low symptomatology and comorbidities (Cluster 1, high symptomatology and comorbidities (Cluster 2, and high symptomatology but low comorbidities (Cluster 3, showing differences in measures of disease severity. CONCLUSIONS: We have identified three subgroups of FM samples in a large cohort of FM by clustering clinical data. Our analysis stresses the importance of family and personal history of FM comorbidities. Also, the resulting patient clusters could indicate different forms of the disease, relevant to future research, and might have an impact on clinical assessment.

Irreducible geometric subgroups of classical algebraic groups

CERN Document Server

Burness, Timothy C; Testerman, Donna M

2016-01-01

Let G be a simple classical algebraic group over an algebraically closed field K of characteristic p \\ge 0 with natural module W. Let H be a closed subgroup of G and let V be a non-trivial irreducible tensor-indecomposable p-restricted rational KG-module such that the restriction of V to H is irreducible. In this paper the authors classify the triples (G,H,V) of this form, where H is a disconnected maximal positive-dimensional closed subgroup of G preserving a natural geometric structure on W.

Second cancers following radiotherapy

International Nuclear Information System (INIS)

Tubiana, M.

1983-01-01

Published reports have shown that there is an increased incidence of second malignancies, particularly sarcomas, following high dose radiotherapy in cancer treatment. However, this increased risk is very small and is relatively negligeable when one considers the beneficial effects of radiotherapy in cancer treatment. This incidence of radiation induced cancer appears to be higher in certain groups of patients, such as children and patients with Hodgkin's disease. In view of scarcity of published data, controlled surveys remain necessary for the quantitative assessment of the cancer risk in various subgroups of irradited patients [fr

nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: a subgroup analysis of the Western European cohort of the MPACT trial

Directory of Open Access Journals (Sweden)

Tabernero J

2017-02-01

Full Text Available Josep Tabernero,1 Volker Kunzmann,2 Werner Scheithauer,3 Michele Reni,4 Jack Shiansong Li,5 Stefano Ferrara,6 Kamel Djazouli7 1Medical Oncology Department, Vall d’Hebron University Hospital, Barcelona, Spain; 2Medizinische Klinik und Poliklinik II, University of Würzburg, Würzburg, Germany; 3Medizinische Universität Wien, Wien, Austria; 4San Raffaele Scientific Institute, Milan, Italy; 5Celgene Corporation, Summit, NJ, USA; 6Celgene Corporation, Boudry, Switzerland; 7Celgene Corporation, Paris, France Purpose: The global Phase III MPACT trial demonstrated superior efficacy of nab-paclitaxel plus gemcitabine over gemcitabine alone as first-line treatment for metastatic pancreatic cancer. Region was a randomization stratification factor in the MPACT trial. This subgroup analysis of MPACT examined efficacy and safety of patients treated in Western Europe.Patients and methods: Patients received nab-paclitaxel plus gemcitabine or gemcitabine alone as first-line treatment for metastatic pancreatic cancer as previously described. A total of 76 patients were included in this analysis (n=38 for each arm.Results: Differences between the overall Western European cohort and the intention-to-treat population included lower percentages of male patients (46% and 58%, respectively and patients with biliary stents (8% and 17%, and higher percentages of patients with Karnofsky performance status of 90–100 (78% and 60% and primary tumors in the body of the pancreas (48% and 31%. The median overall survival was 10.7 months with nab-paclitaxel plus gemcitabine vs 6.9 months with gemcitabine alone (hazard ratio [HR]: 0.82 [95% confidence interval (CI: 0.48–1.40]; P=0.471. Median progression-free survival was 5.3 vs 3.7 months, respectively (HR: 0.70 [95% CI: 0.37–1.33]; P=0.277. The independently assessed overall response rate was 18% vs 5% (response rate ratio, 3.50 [95% CI: 0.78–15.78]; P=0.076. The most common grade ≥3 adverse events with nab

Correlation between Ureaplasma subgroup 2 and genitourinary tract disease outcomes revealed by an expanded multilocus sequence typing (eMLST) scheme.

Science.gov (United States)

Zhang, Jun; Kong, Yingying; Ruan, Zhi; Huang, Jun; Song, Tiejun; Song, Jingjuan; Jiang, Yan; Yu, Yunsong; Xie, Xinyou

2014-01-01

The multilocus sequence typing (MLST) scheme of Ureaplasma based on four housekeeping genes (ftsH, rpL22, valS, and thrS) was described in our previous study; here we introduced an expanded MLST (eMLST) scheme with improved discriminatory power, which was developed by adding two putative virulence genes (ureG and mba-np1) to the original MLST scheme. To evaluate the discriminatory power of eMLST, a total of 14 reference strains of Ureaplasma serovars and 269 clinical strains (134 isolated from symptomatic patients and 135 obtained from asymptomatic persons) were investigated. Our study confirmed that all 14 serotype strains could successfully be differentiated into 14 eMLST STs (eSTs), while some of them could not even be differentiated by the MLST, and a total of 136 eSTs were identified among the clinical isolates we investigated. In addition, phylogenetic analysis indicated that two genetically significantly distant clusters (cluster I and II) were revealed and most clinical isolates were located in cluster I. These findings were in accordance with and further support for the concept of two well-known genetic lineages (Ureaplasma parvum and Ureaplasma urealyticum) in our previous study. Interestingly, although both clusters were associated with clinical manifestation, the sub-group 2 of cluster II had pronounced and adverse effect on patients and might be a potential risk factor for clinical outcomes. In conclusion, the eMLST scheme offers investigators a highly discriminative typing tool that is capable for precise epidemiological investigations and clinical relevance of Ureaplasma.

Correlation between Ureaplasma subgroup 2 and genitourinary tract disease outcomes revealed by an expanded multilocus sequence typing (eMLST scheme.

Directory of Open Access Journals (Sweden)

Jun Zhang

Full Text Available The multilocus sequence typing (MLST scheme of Ureaplasma based on four housekeeping genes (ftsH, rpL22, valS, and thrS was described in our previous study; here we introduced an expanded MLST (eMLST scheme with improved discriminatory power, which was developed by adding two putative virulence genes (ureG and mba-np1 to the original MLST scheme. To evaluate the discriminatory power of eMLST, a total of 14 reference strains of Ureaplasma serovars and 269 clinical strains (134 isolated from symptomatic patients and 135 obtained from asymptomatic persons were investigated. Our study confirmed that all 14 serotype strains could successfully be differentiated into 14 eMLST STs (eSTs, while some of them could not even be differentiated by the MLST, and a total of 136 eSTs were identified among the clinical isolates we investigated. In addition, phylogenetic analysis indicated that two genetically significantly distant clusters (cluster I and II were revealed and most clinical isolates were located in cluster I. These findings were in accordance with and further support for the concept of two well-known genetic lineages (Ureaplasma parvum and Ureaplasma urealyticum in our previous study. Interestingly, although both clusters were associated with clinical manifestation, the sub-group 2 of cluster II had pronounced and adverse effect on patients and might be a potential risk factor for clinical outcomes. In conclusion, the eMLST scheme offers investigators a highly discriminative typing tool that is capable for precise epidemiological investigations and clinical relevance of Ureaplasma.

[Risk factors for cancer in patients with myositis. Clinical, immunological characteristics and the role of the anti-p155/140 antibody].

Science.gov (United States)

Szankai, Zsuzsanna; Nagy-Vincze, Melinda; Bodoki, Levente; Jakab, András; Betteridge, Zoe; Dankó, Katalin

2014-09-07

Idiopathic inflammatory myopathies are systemic autoimmune diseases characterized by progressive proximal muscle weakness. Cancer-associated myositis represents the worst prognostic group within this heterogeneous disease. The aim of this study was to reveal factors which increase the risk factors for association of cancerous disease in patients with myositis. Furthermore, the authors explored the most common types of associated malignancies in their patients with myositis and characterize the clinical findings in a sub-group of anti-p155/140 positive patients. In this retrospective study, myositis patients with and without associated cancer were analysed (32 and 64 patients, respectively). In addition, anti-p155/140 positive and negative groups were compared, irrespective to the presence of associated malignancies. The risk for associated malignancy was higher in patients with severe muscle and skin symptoms and those with dermatomyositis. Furthermore, increased risk for malignancy was noted in the presence of particular skin symptoms and the absence of systemic symptoms. The anti-p155/140 antibody was proved to be a feasible marker of an independent clinical sub-group which overlapped clinical characteristics with cancer-associated myositis. These results may help the identification of patients with myositis with a higher risk for associated malignancy.

Predictive and prognostic factors associated with soft tissue sarcoma response to chemotherapy: a subgroup analysis of the European Organisation for Research and Treatment of Cancer 62012 study.

Science.gov (United States)

Young, Robin J; Litière, Saskia; Lia, Michela; Hogendoorn, Pancras C W; Fisher, Cyril; Mechtersheimer, Gunhild; Daugaard, Søren; Sciot, Raf; Collin, Françoise; Messiou, Christina; Grünwald, Viktor; Gronchi, Alessandro; van der Graaf, Winette; Wardelmann, Eva; Judson, Ian

2017-07-01

The European Organization for Research and Treatment of Cancer (EORTC) 62012 study was a Phase III trial of doxorubicin versus doxorubicin-ifosfamide chemotherapy in 455 patients with advanced soft tissue sarcoma (STS). Analysis of the main study showed that combination chemotherapy improved tumor response and progression-free survival, but differences in overall survival (OS) were not statistically significant. We analyzed factors prognostic for tumor response and OS, and assessed histological subgroup and tumor grade as predictive factors to identify patients more likely to benefit from combination chemotherapy. Central pathology review was performed by six reference pathologists. Gender, age, performance status, time from first presentation with sarcoma to starting palliative chemotherapy, tumor grade, histological subgroup, primary tumor site involvement, and sites of metastases were assessed as prognostic factors. Three hundred and ten patients were included in this study. Discordance between local and central pathology opinion of tumor histology and tumor grade was observed in 98 (32%) and 122 (39%) cases, respectively. In multivariate analysis, liposarcoma patients had improved tumor response compared to other histological subgroups, whilst patients with metastases other than lung, liver or bone had a poorer response [odds ratio (OR) 0.42, 95% confidence interval (CI) 0.23-0.78; p = 0.006]. Patients with bone metastases had reduced OS [hazard ratio (HR) 1.56, 95% CI 1.16-2.09; p = 0.003]. By central pathology review, patients with undifferentiated pleomorphic sarcoma (UPS) had improved tumor response and OS with doxorubicin-ifosfamide compared to single-agent doxorubicin (OR 9.90, 95% CI 1.93-50.7 and HR 0.44, 95% CI 0.26-0.79, respectively). Grade III tumors had improved response with combination chemotherapy but there was no interaction between chemotherapy and grade on OS. Prospective central pathology review of tumor histology should be

Therapeutic Strategies for Hereditary Kidney Cancer.

Science.gov (United States)

Sidana, Abhinav; Srinivasan, Ramaprasad

2016-08-01

The study of hereditary forms of kidney cancer has vastly increased our understanding of metabolic and genetic pathways involved in the development of both inherited and sporadic kidney cancers. The recognition that diverse molecular events drive different forms of kidney cancers has led to the preclinical and clinical development of specific pathway-directed strategies tailored to treat distinct subgroups of kidney cancer. Here, we describe the molecular mechanisms underlying the pathogenesis of several different types of hereditary renal cancers, review their clinical characteristics, and summarize the treatment strategies for the management of these cancers.

Sodium intake in US ethnic subgroups and potential impact of a new sodium reduction technology: NHANES Dietary Modeling.

Science.gov (United States)

Fulgoni, Victor L; Agarwal, Sanjiv; Spence, Lisa; Samuel, Priscilla

2014-12-18

Because excessive dietary sodium intake is a major contributor to hypertension, a reduction in dietary sodium has been recommended for the US population. Using the National Health and Nutrition Examination Survey (NHANES) 2007-2010 data, we estimated current sodium intake in US population ethnic subgroups and modeled the potential impact of a new sodium reduction technology on sodium intake. NHANES 2007-2010 data were analyzed using The National Cancer Institute method to estimate usual intake in population subgroups. Potential impact of SODA-LO® Salt Microspheres sodium reduction technology on sodium intake was modeled using suggested sodium reductions of 20-30% in 953 foods and assuming various market penetrations. SAS 9.2, SUDAAN 11, and NHANES survey weights were used in all calculations with assessment across age, gender and ethnic groups. Current sodium intake across all population subgroups exceeds the Dietary Guidelines 2010 recommendations and has not changed during the last decade. However, sodium intake measured as a function of food intake has decreased significantly during the last decade for all ethnicities. "Grain Products" and "Meat, Poultry, Fish, & Mixtures" contribute about 2/3rd of total sodium intake. Sodium reduction, using SODA-LO® Salt Microspheres sodium reduction technology (with 100% market penetration) was estimated to be 185-323 mg/day or 6.3-8.4% of intake depending upon age, gender and ethnic group. Current sodium intake in US ethnic subgroups exceeds the recommendations and sodium reduction technologies could potentially help reduce dietary sodium intake among those groups.

Gambaran Populasi Golongan Darah Subgroup A (A1, A2 di PMI Kulon Progo

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Hieronymus Rayi Prasetya

2017-08-01

Full Text Available Subgroup A1 and A2 are the most important in the blood group A. Subgroup A1 has the A antigen more than A2 subgroup, the A2 subgroup can cause misidentification of blood group due to poor A antigen and genetic variation possessed. Misidentification of the blood group will increase the risk of transfusion reactions. This research aims to describe the A1 and A2 subgroup population in Kulon Progo district. This study was conducted with a cross sectional sampling technique. The sample in this study were taken from donors of blood group A in Kulon Progo Red Cross. Identification of A1 and A2 subgroup is done by using lectin (Dolichos biflorus extract. The result of the examination of 53 samples showed that 96,2% was A1 subgroup and 3,8% was A2 subgroup. Key words : Subgroup A1, Subgroup A2, Population, Kulon Progo

Considerations for subgroups and phenocopies in complex disease genetics.

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Ryan Ramanujam

Full Text Available The number of identified genetic variants associated to complex disease cannot fully explain heritability. This may be partially due to more complicated patterns of predisposition than previously suspected. Diseases such as multiple sclerosis (MS may consist of multiple disease causing mechanisms, each comprised of several elements. We describe how the effect of subgroups can be calculated using the standard association measurement odds ratio, which is then manipulated to provide a formula for the true underlying association present within the subgroup. This is sensitive to the initial minor allele frequencies present in both cases and the subgroup of patients. The methodology is then extended to the χ(2 statistic, for two related scenarios. First, to determine the true χ(2 when phenocopies or disease subtypes reduce association and are reclassified as controls when calculating statistics. Here, the χ(2 is given by (1 + σ * (a + b/(c + d/(1 - σ, or (1 + σ/(1 - σ for equal numbers of cases and controls. Second, when subgroups corresponding to heterogeneity mask the true effect size, but no reclassification is made. Here, the proportion increase in total sample size required to attain the same χ(2 statistic as the subgroup is given as γ = (1 - σ/2/((1 - σ(1 - σc/(a + c(1 - σd/(b + d, and a python script to calculate and plot this value is provided at kirc.se. Practical examples show how in a study of modest size (1000 cases and 1000 controls, a non-significant SNP may exceed genome-wide significance when corresponding to a subgroup of 20% of cases, and may occur in heterozygous form in all cases. This methodology may explain the modest association found in diseases such as MS wherein heterogeneity confounds straightforward measurement of association.

Korean women: breast cancer knowledge, attitudes and behaviors

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Ryujin Lisa T

2001-08-01

Full Text Available Abstract Introduction Clustered within the nomenclature of Asian American are numerous subgroups, each with their own ethnic heritage, cultural, and linguistic characteristics. An understanding of the prevailing health knowledge, attitudes, and screening behaviors of these subgroups is essential for creating population-specific health promotion programs. Methods Korean American women (123 completed baseline surveys of breast cancer knowledge, attitudes, and screening behaviors as part of an Asian grocery store-based breast cancer education program evaluation. Follow-up telephone surveys, initiated two weeks later, were completed by 93 women. Results Low adherence to the American Cancer Society's breast cancer screening guidelines and insufficient breast cancer knowledge were reported. Participants' receptiveness to the grocery store-based breast cancer education program underscores the importance of finding ways to reach Korean women with breast cancer early detection information and repeated cues for screening. The data also suggest that the Asian grocery store-based cancer education program being tested may have been effective in motivating a proportion of the women to schedule a breast cancer screening between the baseline and follow-up surveys. Conclusion The program offers a viable strategy to reach Korean women that addresses the language, cultural, transportation, and time barriers they face in accessing breast cancer early detection information.

Meta-Analysis of the Association between Mir-196a-2 Polymorphism and Cancer Susceptibility

International Nuclear Information System (INIS)

Zhang, Huan; Su, Yu-liang; Yu, Herbert; Qian, Bi-yun

2012-01-01

MicroRNA plays a vital role in gene expression, and microRNA dysregulation is involved in carcinogenesis. The miR-196a-2 polymorphism rs11614913 is reportedly associated with cancer susceptibility. This meta-analysis was performed to assess the overall association of miR-196a-2 with cancer risk. A total of 27 independent case-control studies involving 10,435 cases and 12,075 controls were analyzed for the rs11614913 polymorphism. A significant association was found between rs11614913 polymorphism and cancer risk in four genetic models (CT vs. TT, OR=1.15, 95%CI=1.05–1.27; CC vs. TT, OR=1.23, 95%CI=1.08–1.39; Dominant model, OR=1.17, 95%CI=1.06–1.30; Additive model, OR=1.08, 95%CI=1.01–1.14). In the subgroup analysis of different tumor types, the C allele was associated with increased risk of lung, breast, and colorectal cancer, but not with liver, gastric, or esophageal cancer. In the subgroup analysis by ethnicity, a significantly increased risk of cancer was found among Asians in all genetic models, but no associations were found in the Caucasian subgroup. The meta-analysis demonstrated that the miR-196a-2 polymorphism is associated with cancer susceptibility, especially lung cancer, colorectal cancer, and breast cancer among Asian populations

A method for generating subgroup parameters from resonance tables

International Nuclear Information System (INIS)

Devan, K.; Mohanakrishnan, P.

1993-01-01

A method for generating subgroup or band parameters from resonance tables is described. A computer code SPART was written using this method. This code generates the subgroup parameters for any number of bands within the specified broad groups at different temperatures by reading the required input data from the binary cross section library in the Cadarache format. The results obtained with SPART code for two bands were compared with that obtained from GROUPIE code and a good agreement was obtained. Results of the generation of subgroup parameters in four bands for sample case of 239 Pu from resonance tables of Cadarache Ver.2 library is also presented. (author). 8 refs., 2 tabs

Endogenous molecular network reveals two mechanisms of heterogeneity within gastric cancer

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Li, Site; Zhu, Xiaomei; Liu, Bingya; Wang, Gaowei; Ao, Ping

2015-01-01

Intratumor heterogeneity is a common phenomenon and impedes cancer therapy and research. Gastric cancer (GC) cells have generally been classified into two heterogeneous cellular phenotypes, the gastric and intestinal types, yet the mechanisms of maintaining two phenotypes and controlling phenotypic transition are largely unknown. A qualitative systematic framework, the endogenous molecular network hypothesis, has recently been proposed to understand cancer genesis and progression. Here, a minimal network corresponding to such framework was found for GC and was quantified via a stochastic nonlinear dynamical system. We then further extended the framework to address the important question of intratumor heterogeneity quantitatively. The working network characterized main known features of normal gastric epithelial and GC cell phenotypes. Our results demonstrated that four positive feedback loops in the network are critical for GC cell phenotypes. Moreover, two mechanisms that contribute to GC cell heterogeneity were identified: particular positive feedback loops are responsible for the maintenance of intestinal and gastric phenotypes; GC cell progression routes that were revealed by the dynamical behaviors of individual key components are heterogeneous. In this work, we constructed an endogenous molecular network of GC that can be expanded in the future and would broaden the known mechanisms of intratumor heterogeneity. PMID:25962957

Association between dietary pattern scores and the prevalence of colorectal adenoma considering population subgroups.

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Haslam, Alyson; Wagner Robb, Sara; Hébert, James R; Huang, Hanwen; Ebell, Mark H

2018-04-01

The purpose of the current study is to examine the dietary patterns in a diverse cohort of individuals and to see if the identified dietary patterns predict the prevalence of adenoma in a cross-sectional study. Factor analysis was used to derive both sex- and population subgroup-specific dietary patterns among participants in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Logistic regression was used to assess associations between identified factor scores and colorectal adenoma (CRA) in sex-specific subgroups. Three diet patterns were observed in this cohort: 'Fruits and vegetables', 'Western' and 'Sweet and salty'. Foods that loaded on each factor were similar between the racial subgroups. In men, being in the highest quintile of 'Western' dietary scores was associated with higher odds of any (adjusted odds ratio (aOR) = 1.21; 95% confidence interval (CI) = 1.03-1.42), advanced (aOR = 1.32; 95% CI = 1.07-1.63) or multiple (>1; aOR = 1.51; 95% CI = 1.17-1.94) adenoma, compared to those in the lowest quintile. These results were most notably seen in Caucasian men. In women, having a 'Fruits and vegetable' score in the highest quintile was associated with lower odds of multiple adenoma (>1; aOR = 0.53; 95% CI = 0.28-1.00). Of the three dietary factors, the 'Western' diet pattern was most strongly associated with prevalent CRA in Caucasian men. Further research is needed to examine the association between dietary factor scores and adenomas in the proximal colon, where there are larger racial disparities in prevalence. © 2017 Dietitians Association of Australia.

Finite Groups with Given Quantitative Non-Nilpotent Subgroups II

DEFF Research Database (Denmark)

Shi, Jiangtao; Zhang, Cui

2014-01-01

As an extension of Shi and Zhang's 2011 article [4], we prove that any finite group having at most 23 non-normal non-nilpotent proper subgroups is solvable except for G ≅ A 5 or SL(2, 5), and any finite group having at most three conjugacy classes of non-normal non-nilpotent proper subgroups is s...

Cancer Mortality among Asians and Pacific Islanders in New York City, 2001–2010

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Vivian Huang

2013-01-01

Full Text Available Asians and Pacific Islanders’ (APIs leading cause of death is cancer. We compared APIs’ age-adjusted cancer mortality rates to other racial/ethnic groups and by API subgroup (i.e., Chinese, Koreans, Asian Indians, and Filipinos using New York City (NYC Mortality data and Census Bureau population estimates for 2001–2010. While other racial/ethnic groups’ overall cancer mortality rates declined in NYC during the last decade, APIs remained stable. APIs overall had the lowest mortality rates for more common cancer types (i.e., lung, colorectal, breast, and prostate, but the highest mortality rates for certain less common cancers (i.e., nasopharyngeal, stomach, and liver. Chinese New Yorkers’ lung cancer death rates were very high compared to other APIs and comparable to non-Hispanic whites (47.1/100,000 versus 49.5/100,000, resp.. Chinese men had much higher nasopharyngeal cancer mortality rates (4.5/100,000 versus 0.3/100,000 for non-Hispanic whites. Korean men had the highest liver and stomach cancer mortality rates (25.3/100,000 and 27.7/100,000, resp., versus 7.9/100,000 and 6.0/100,000 for non-Hispanic whites. Analysis of cancer rates by API subgroup provides the detailed information needed to plan cancer prevention efforts. These findings warrant consideration of targeted cancer mortality prevention efforts for affected subgroups, including hepatitis vaccination, screening, and treatment; smoking cessation; and cancer screening.

Subgroup analyses in confirmatory clinical trials: time to be specific about their purposes

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Julien Tanniou

2016-02-01

Full Text Available Abstract Background It is well recognized that treatment effects may not be homogeneous across the study population. Subgroup analyses constitute a fundamental step in the assessment of evidence from confirmatory (Phase III clinical trials, where conclusions for the overall study population might not hold. Subgroup analyses can have different and distinct purposes, requiring specific design and analysis solutions. It is relevant to evaluate methodological developments in subgroup analyses against these purposes to guide health care professionals and regulators as well as to identify gaps in current methodology. Methods We defined four purposes for subgroup analyses: (1 Investigate the consistency of treatment effects across subgroups of clinical importance, (2 Explore the treatment effect across different subgroups within an overall non-significant trial, (3 Evaluate safety profiles limited to one or a few subgroup(s, (4 Establish efficacy in the targeted subgroup when included in a confirmatory testing strategy of a single trial. We reviewed the methodology in line with this “purpose-based” framework. The review covered papers published between January 2005 and April 2015 and aimed to classify them in none, one or more of the aforementioned purposes. Results In total 1857 potentially eligible papers were identified. Forty-eight papers were selected and 20 additional relevant papers were identified from their references, leading to 68 papers in total. Nineteen were dedicated to purpose 1, 16 to purpose 4, one to purpose 2 and none to purpose 3. Seven papers were dedicated to more than one purpose, the 25 remaining could not be classified unambiguously. Purposes of the methods were often not specifically indicated, methods for subgroup analysis for safety purposes were almost absent and a multitude of diverse methods were developed for purpose (1. Conclusions It is important that researchers developing methodology for subgroup analysis

Racial, ethnic, and gender variations in cancer risk: considerations for future epidemiologic research.

OpenAIRE

Zahm, S H; Fraumeni, J F

1995-01-01

There is no question that the risk of many cancers varies substantially by race, ethnic group, and gender. Although important clues to cancer etiology may come from investigating the differences in risk across subgroups of the population, epidemiologic research has often focused on white men. More descriptive and analytic studies are needed to identify and explain variations in risk among population subgroups. Especially important are studies to clarify the role of differential exposures, sus...

Personalized dementia care: proven effectiveness of psychosocial interventions in subgroups

NARCIS (Netherlands)

van Mierlo, L.D.; van der Roest, H.G.; Meiland, F.J.M.; Dröes, R.M.

2010-01-01

Many psychosocial intervention studies report effects in subgroups of people with dementia. Insight into the characteristics of these subgroups is important for care practice. This study reviews personal characteristics of people with dementia (living in the community or in an institution) that are

Subgroup analyses in randomised controlled trials: cohort study on trial protocols and journal publications.

Science.gov (United States)

Kasenda, Benjamin; Schandelmaier, Stefan; Sun, Xin; von Elm, Erik; You, John; Blümle, Anette; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J; Stegert, Mihaela; Olu, Kelechi K; Tikkinen, Kari A O; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M; Mertz, Dominik; Akl, Elie A; Bassler, Dirk; Busse, Jason W; Ferreira-González, Ignacio; Lamontagne, Francois; Nordmann, Alain; Gloy, Viktoria; Raatz, Heike; Moja, Lorenzo; Rosenthal, Rachel; Ebrahim, Shanil; Vandvik, Per O; Johnston, Bradley C; Walter, Martin A; Burnand, Bernard; Schwenkglenks, Matthias; Hemkens, Lars G; Bucher, Heiner C; Guyatt, Gordon H; Briel, Matthias

2014-07-16

To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. Cohort of protocols of randomised controlled trial and subsequent full journal publications. Six research ethics committees in Switzerland, Germany, and Canada. 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P<0.001). Of 515 identified journal publications, 246 (47.8%) reported at least one subgroup analysis. In 81 (32.9%) of the 246 publications reporting subgroup analyses, authors stated that subgroup analyses were prespecified, but this was not supported by 28 (34.6%) corresponding protocols. In 86 publications, authors claimed a subgroup effect, but only 36 (41.9%) corresponding protocols reported a planned subgroup analysis. Subgroup analyses are insufficiently described in the protocols of randomised controlled trials submitted to research ethics committees, and investigators rarely specify the anticipated direction of subgroup effects. More than one third of statements in publications of randomised controlled trials about subgroup prespecification had no documentation in the corresponding protocols. Definitive judgments regarding credibility of claimed subgroup effects are not possible without access to protocols and analysis plans of randomised controlled trials. © The DISCO study group 2014.

Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin

DEFF Research Database (Denmark)

Hoadley, Katherine A; Yau, Christina; Wolf, Denise M

2014-01-01

Recent genomic analyses of pathologically defined tumor types identify "within-a-tissue" disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform...... on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head and neck, and a subset...

Adrenocortical cancer

DEFF Research Database (Denmark)

Payabyab, Eden C.; Balasubramaniam, Sanjeeve; Edgerly, Maureen

2016-01-01

The development of new therapies has lagged behind for rare cancers without defined therapeutic targets. Adrenocortical cancer is no exception. Mitotane, an older agent considered "adrenolytic," is used both to control symptoms in advanced disease and as adjuvant therapy after surgical resection....... Molecular characterization of adrenocortical cancer has deepened our understanding of this genetically complex disease while identifying subgroups whose importance remains to be determined. Unfortunately, such studies have yet to demonstrate a therapeutic target for drug development, and to date......, no targeted therapy has achieved meaningful outcomes. Consequently, first-line therapy for metastatic disease remains a combination regimen of etoposide, doxorubicin, and cisplatinum established in a randomized clinical trial. In addition to evaluating recent studies in adrenocortical cancer, we raise one...

Genetically meaningful phenotypic subgroups in autism spectrum disorders.

Science.gov (United States)

Veatch, O J; Veenstra-Vanderweele, J; Potter, M; Pericak-Vance, M A; Haines, J L

2014-03-01

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with strong evidence for genetic susceptibility. However, the effect sizes for implicated chromosomal loci are small, hard to replicate and current evidence does not explain the majority of the estimated heritability. Phenotypic heterogeneity could be one phenomenon complicating identification of genetic factors. We used data from the Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, Vineland Adaptive Behavior Scales, head circumferences, and ages at exams as classifying variables to identify more clinically similar subgroups of individuals with ASD. We identified two distinct subgroups of cases within the Autism Genetic Resource Exchange dataset, primarily defined by the overall severity of evaluated traits. In addition, there was significant familial clustering within subgroups (odds ratio, OR ≈ 1.38-1.42, P definition that should increase power to detect genetic factors influencing risk for ASD. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Heterogeneity in chronic fatigue syndrome - empirically defined subgroups from the PACE trial.

Science.gov (United States)

Williams, T E; Chalder, T; Sharpe, M; White, P D

2017-06-01

Chronic fatigue syndrome is likely to be a heterogeneous condition. Previous studies have empirically defined subgroups using combinations of clinical and biological variables. We aimed to explore the heterogeneity of chronic fatigue syndrome. We used baseline data from the PACE trial, which included 640 participants with chronic fatigue syndrome. Variable reduction, using a combination of clinical knowledge and principal component analyses, produced a final dataset of 26 variables for 541 patients. Latent class analysis was then used to empirically define subgroups. The most statistically significant and clinically recognizable model comprised five subgroups. The largest, 'core' subgroup (33% of participants), had relatively low scores across all domains and good self-efficacy. A further three subgroups were defined by: the presence of mood disorders (21%); the presence of features of other functional somatic syndromes (such as fibromyalgia or irritable bowel syndrome) (21%); or by many symptoms - a group which combined features of both of the above (14%). The smallest 'avoidant-inactive' subgroup was characterized by physical inactivity, belief that symptoms were entirely physical in nature, and fear that they indicated harm (11%). Differences in the severity of fatigue and disability provided some discriminative validation of the subgroups. In addition to providing further evidence for the heterogeneity of chronic fatigue syndrome, the subgroups identified may aid future research into the important aetiological factors of specific subtypes of chronic fatigue syndrome and the development of more personalized treatment approaches.

Effectiveness of lifestyle intervention in subgroups of obese infertile women : a subgroup analysis of a RCT

NARCIS (Netherlands)

van Oers, A M; Groen, H; Mutsaerts, M A Q; Burggraaff, J M; Kuchenbecker, W K H; Perquin, D A M; Koks, C A M; van Golde, R; Kaaijk, E M; Schierbeek, J M; Oosterhuis, G J E; Broekmans, F J; Vogel, N E A; Land, J A; Mol, B W J; Hoek, A

2016-01-01

STUDY QUESTION: Do age, ovulatory status, severity of obesity and body fat distribution affect the effectiveness of lifestyle intervention in obese infertile women? SUMMARY ANSWER: We did not identify a subgroup in which lifestyle intervention increased the healthy live birth rate however it did

A polymorphism at the 3'-UTR region of the aromatase gene defines a subgroup of postmenopausal breast cancer patients with poor response to neoadjuvant letrozole

International Nuclear Information System (INIS)

Garcia-Casado, Zaida; Cervera-Deval, Jose; Campos, Josefina; Albaladejo, Carlos Vazquez; Llombart-Bosch, Antonio; Guillem, Vicente; Lopez-Guerrero, Jose A; Guerrero-Zotano, Angel; Llombart-Cussac, Antonio; Calatrava, Ana; Fernandez-Serra, Antonio; Ruiz-Simon, Amparo; Gavila, Joaquin; Climent, Miguel A; Almenar, Sergio

2010-01-01

Aromatase (CYP19A1) regulates estrogen biosynthesis. Polymorphisms in CYP19A1 have been related to the pathogenesis of breast cancer (BC). Inhibition of aromatase with letrozole constitutes the best option for treating estrogen-dependent BC in postmenopausal women. We evaluate a series of polymorphisms of CYP19A1 and their effect on response to neoadjuvant letrozole in early BC. We analyzed 95 consecutive postmenopausal women with stage II-III ER/PgR [+] BC treated with neoadjuvant letrozole. Response to treatment was measured by radiology at 4 th month by World Health Organization (WHO) criteria. Three polymorphisms of CYP19A1, one in exon 7 (rs700519) and two in the 3'-UTR region (rs10046 and rs4646) were evaluated on DNA obtained from peripheral blood. Thirty-five women (36.8%) achieved a radiological response to letrozole. The histopathological and immunohistochemical parameters, including hormonal receptor status, were not associated with the response to letrozole. Only the genetic variants (AC/AA) of the rs4646 polymorphism were associated with poor response to letrozole (p = 0.03). Eighteen patients (18.9%) reported a progression of the disease. Those patients carrying the genetic variants (AC/AA) of rs4646 presented a lower progression-free survival than the patients homozygous for the reference variant (p = 0.0686). This effect was especially significant in the group of elderly patients not operated after letrozole induction (p = 0.009). Our study reveals that the rs4646 polymorphism identifies a subgroup of stage II-III ER/PgR [+] BC patients with poor response to neoadjuvant letrozole and poor prognosis. Testing for the rs4646 polymorphism could be a useful tool in order to orientate the treatment in elderly BC patients

Latino Male Ethnic Subgroups: Patterns in College Enrollment and Degree Completion

Science.gov (United States)

Ponjuan, Luis; Palomin, Leticia; Calise, Angela

2015-01-01

This chapter examines Latino male ethnic subgroups and their college enrollment and degree completion patterns. The chapter also offers recommendations to improve Latino male ethnic subgroups' educational achievement.

Genetic variation of clock genes and cancer risk: a field synopsis and meta-analysis.

Science.gov (United States)

Benna, Clara; Helfrich-Förster, Charlotte; Rajendran, Senthilkumar; Monticelli, Halenya; Pilati, Pierluigi; Nitti, Donato; Mocellin, Simone

2017-04-04

The number of studies on the association between clock genes' polymorphisms and cancer susceptibility has increased over the last years but the results are often conflicting and no comprehensive overview and quantitative summary of the evidence in this field is available. Literature search identified 27 eligible studies comprising 96756 subjects (cases: 38231) and investigating 687 polymorphisms involving 14 clock genes. Overall, 1025 primary and subgroup meta-analyses on 366 gene variants were performed. Study distribution by tumor was as follows: breast cancer (n=15), prostate cancer (n=3), pancreatic cancer (n=2), non-Hodgkin's lymphoma (n=2), glioma (n=1), chronic lymphocytic leukemia (n=1), colorectal cancer (n=1), non-small cell lung cancer (n=1) and ovarian cancer (n=1).We identified 10 single nucleotide polymorphisms (SNPs) significantly associated with cancer risk: NPAS2 rs10165970 (mixed and breast cancer shiftworkers), rs895520 (mixed), rs17024869 (breast) and rs7581886 (breast); CLOCK rs3749474 (breast) and rs11943456 (breast); RORA rs7164773 (breast and breast cancer postmenopausal), rs10519097 (breast); RORB rs7867494 (breast cancer postmenopausal), PER3 rs1012477 (breast cancer subgroups) and assessed the level of quality evidence to be intermediate. We also identified polymorphisms with lower quality statistically significant associations (n=30). Our work supports the hypothesis that genetic variation of clock genes might affect cancer risk. These findings also highlight the need for more efforts in this research field in order to fully establish the contribution of clock gene variants to the risk of developing cancer. We conducted a systematic review and meta-analysis of the evidence on the association between clock genes' germline variants and the risk of developing cancer. To assess result credibility, summary evidence was graded according to the Venice criteria and false positive report probability (FPRP) was calculated to further validate

Differences in Psychosocial Predictors of Obesity Among LGBT Subgroups.

Science.gov (United States)

Warren, Jacob C; Smalley, K Bryant; Barefoot, K Nikki

2016-08-01

The purpose of the current study was to examine the overall presence of and differences in rates of overweight/obesity among a large, nationally diverse sample of lesbian, gay, bisexual, transgender (LGBT)-identified individuals (i.e., cisgender lesbians, cisgender gay men, cisgender bisexual women, cisgender bisexual men, transgender women, and transgender men) and to identify specific psychosocial predictors of obesity within each of the six LGBT subgroups. A total of 2702 LGBT-identified participants participated in the online study. Participants completed a series of demographic questions (including weight and height) and the Depression Anxiety Stress Scale 21. The percentage of participants who were overweight/obese did not differ significantly across LGBT subgroups, with 61.1% of the total sample being overweight/obese. However, the percentage of participants who self-reported body mass indexes in the obese range differed significantly across the six LGBT subgroups, with the highest prevalence in transgender men (46.0%). In addition, the predictors of obesity varied by subgroup, with age a significant predictor for cisgender lesbians, cisgender gay men, and cisgender bisexual women, relationship status for cisgender bisexual women, employment status for both cisgender gay men and cisgender bisexual women, education level for cisgender lesbians, and depression, anxiety, and stress for cisgender gay men. None of the examined psychosocial factors emerged as predictors of obesity for cisgender bisexual men, transgender women, or transgender men. These findings suggest that there are substantial variations in the presence and predictors of obesity across LGBT subgroups that support the need for culturally tailored healthy weight promotion efforts within the LGBT community.

Identification of subgroups of patients with low back pain using Latent Class Analysis

DEFF Research Database (Denmark)

Nielsen, Anne Mølgaard

questionnaire and the clinicians’ findings on a standardised examination of the low back. By using pattern recognition, subgroups of patients were identified within which their responses and scores are similar, and therefore the patients are more alike within the subgroups than across the subgroups. Latent......, the optimal application of the LCA method in this context is unknown and therefore, two methodological considerations were addressed during the process. Firstly, when using existing questionnaire data, whether using each single item or the summary scores would provide better subgroup information. Secondly...... the questionnaires was preferred, due to the more nuanced description available within the resulting subgroups. Therefore, the single‐item strategy was used in the subsequent single‐stage and two‐stage LCA, which identified seven and nine patient subgroups, respectively, with similar face validity and adequate...

Germ cell tumours in neonates and infants: a distinct subgroup?

NARCIS (Netherlands)

Veltman, I.M.; Schepens, M.T.M.; Looijenga, L.H.J.; Strong, L.C.; Geurts van Kessel, A.H.M.

2003-01-01

Human germ cell tumours (GCTs) constitute a heterogeneous group of tumours that can be classified into four major subgroups. One of these subgroups encompasses (immature) teratomas and yolk sac tumours of patients under the age of 5 years. In this paper we review the various clinical, histological

High BRAF Mutation Frequency and Marked Survival Differences in Subgroups According to KRAS/BRAF Mutation Status and Tumor Tissue Availability in a Prospective Population-Based Metastatic Colorectal Cancer Cohort

DEFF Research Database (Denmark)

Sorbye, Halfdan; Dragomir, Anca; Sundström, Magnus

2015-01-01

were analyzed in a prospectively collected unselected population-based cohort of 798 non-resectable mCRC patients. The cohort contained many patients with poor performance status (39% PS 2-4) and elderly (37% age>75), groups usually not included in clinical trials. Patients without available tissue...... patients. Median survival in this cohort varied from 1 month in BRAF mutated patients not given chemotherapy to 26 months in wildtype KRAS/BRAF patients availability, BRAF mutation and KRAS mutation were all independent prognostic factors for survival. The observed 21% BRAF......CRC patients. Survival in unselected metastatic colorectal cancer patients is extremely variable and subgroups have an extremely short survival compared to trial patients. Patients without available TMA had worse prognostic factors and shorter survival, which questions the total generalizability of present TMA...

Podoplanin-positive cancer-associated fibroblast recruitment within cancer stroma is associated with a higher number of single nucleotide variants in cancer cells in lung adenocarcinoma.

Science.gov (United States)

Nakasone, Shoko; Mimaki, Sachiyo; Ichikawa, Tomohiro; Aokage, Keiju; Miyoshi, Tomohiro; Sugano, Masato; Kojima, Motohiro; Fujii, Satoshi; Kuwata, Takeshi; Ochiai, Atsushi; Tsuboi, Masahiro; Goto, Koichi; Tsuchihara, Katsuya; Ishii, Genichiro

2018-05-01

Podoplanin-positive cancer-associated fibroblasts (CAFs) play an essential role in tumor progression. However, it is still unclear whether specific genomic alterations of cancer cells are required to recruit podoplanin-positive CAFs. The aim of this study was to investigate the relationship between the mutation status of lung adenocarcinoma cells and the presence of podoplanin-positive CAFs. Ninety-seven lung adenocarcinomas for which whole exome sequencing data were available were enrolled. First, we analyzed the clinicopathological features of the cases, and then, evaluated the relationship between genetic features of cancer cells (major driver mutations and the number of single nucleotide variants, SNVs) and the presence of podoplanin-positive CAFs. The presence of podoplanin-positive CAFs was associated with smoking history, solid predominant subtype, and lymph node metastasis. We could not find any significant correlations between major genetic mutations (EGFR, KRAS, TP53, MET, ERBB2, BRAF, and PIC3CA) in cancer cells and the presence of podoplanin-positive CAFs. However, cases with podoplanin-positive CAFs had a significantly higher number of SNVs in cancer cells than the podoplanin-negative CAFs cases (median 84 vs 37, respectively; p = 0.001). This was also detected in a non-smoker subgroup (p = 0.037). Multivariate analyses revealed that the number of SNVs in cancer cells was the only statistically significant independent predictor for the presence of podoplanin-positive CAFs (p = 0.044). In lung adenocarcinoma, the presence of podoplanin-positive CAFs was associated with higher numbers of SNVs in cancer cells, suggesting a relationship between accumulations of SNVs in cancer cells and the generation of a tumor-promoting microenvironment.

The interest of gait markers in the identification of subgroups among fibromyalgia patients

OpenAIRE

Auvinet, Bernard; Chaleil, Denis; Cabane, Jean; Dumolard, Anne; Hatron, Pierre; Juvin, Robert; Lanteri-Minet, Michel; Mainguy, Yves; Negre-Pages, Laurence; Pillard, Fabien; Riviere, Daniel; Maugars, Yves-Michel

2011-01-01

Abstract Background Fibromyalgia (FM) is a heterogeneous syndrome and its classification into subgroups calls for broad-based discussion. FM subgrouping, which aims to adapt treatment according to different subgroups, relies in part, on psychological and cognitive dysfunctions. Since motor control of gait is closely related to cognitive function, we hypothesized that gait markers could be of interest in the identification of FM patients' subgroups. This controlled study aimed at characterizin...

Clebsch-Gordan coefficients of discrete groups in subgroup bases

Science.gov (United States)

Chen, Gaoli

2018-04-01

We express each Clebsch-Gordan (CG) coefficient of a discrete group as a product of a CG coefficient of its subgroup and a factor, which we call an embedding factor. With an appropriate definition, such factors are fixed up to phase ambiguities. Particularly, they are invariant under basis transformations of irreducible representations of both the group and its subgroup. We then impose on the embedding factors constraints, which relate them to their counterparts under complex conjugate and therefore restrict the phases of embedding factors. In some cases, the phase ambiguities are reduced to sign ambiguities. We describe the procedure of obtaining embedding factors and then calculate CG coefficients of the group 𝒫𝒮ℒ2(7) in terms of embedding factors of its subgroups S4 and 𝒯7.

Raman spectroscopy reveals biophysical markers in skin cancer surgical margins

Science.gov (United States)

Feng, Xu; Moy, Austin J.; Nguyen, Hieu T. M.; Zhang, Yao; Fox, Matthew C.; Sebastian, Katherine R.; Reichenberg, Jason S.; Markey, Mia K.; Tunnell, James W.

2018-02-01

The recurrence rate of nonmelanoma skin cancer is highly related to the residual tumor after surgery. Although tissueconserving surgery, such as Mohs surgery, is a standard method for the treatment of nonmelanoma skin cancer, they are limited by lengthy and costly frozen-section histopathology. Raman spectroscopy (RS) is proving to be an objective, sensitive, and non-destructive tool for detecting skin cancer. Previous studies demonstrated the high sensitivity of RS in detecting tumor margins of basal cell carcinoma (BCC). However, those studies rely on statistical classification models and do not elucidate the skin biophysical composition. As a result, we aim to discover the biophysical differences between BCC and primary normal skin structures (including epidermis, dermis, hair follicle, sebaceous gland and fat). We obtained freshly resected ex vivo skin samples from fresh resection specimens from 14 patients undergoing Mohs surgery. Raman images were acquired from regions containing one or more structures using a custom built 830nm confocal Raman microscope. The spectra were grouped using K-means clustering analysis and annotated as either BCC or each of the five normal structures by comparing with the histopathology image of the serial section. The spectral data were then fit by a previously established biophysical model with eight primary skin constituents. Our results show that BCC has significant differences in the fit coefficients of nucleus, collagen, triolein, keratin and elastin compared with normal structures. Our study reveals RS has the potential to detect biophysical changes in resection margins, and supports the development of diagnostic algorithms for future intraoperative implementation of RS during Mohs surgery.

Association of Inflammatory Cytokines With the Symptom Cluster of Pain, Fatigue, Depression, and Sleep Disturbance in Chinese Patients With Cancer.

Science.gov (United States)

Ji, Yan-Bo; Bo, Chun-Lu; Xue, Xiu-Juan; Weng, En-Ming; Gao, Guang-Chao; Dai, Bei-Bei; Ding, Kai-Wen; Xu, Cui-Ping

2017-12-01

Pain, fatigue, depression, and sleep disturbance are common in patients with cancer and usually co-occur as a symptom cluster. However, the mechanism underlying this symptom cluster is unclear. This study aimed to identify subgroups of cluster symptoms, compare demographic and clinical characteristics between subgroups, and examine the associations between inflammatory cytokines and cluster symptoms. Participants were 170 Chinese inpatients with cancer from two tertiary hospitals. Inflammatory markers including interleukin-6 (IL-6), interleukin-1 receptor antagonist, and tumor necrosis factor alpha were measured. Intergroup differences and associations of inflammatory cytokines with the cluster symptoms were examined with one-way analyses of variance and logistic regression. Based on cluster analysis, participants were categorized into Subgroup 1 (all low symptoms), Subgroup 2 (low pain and moderate fatigue), or Subgroup 3 (moderate-to-high on all symptoms). The three subgroups differed significantly in Eastern Cooperative Oncology Group (ECOG) performance status, sex, residence, current treatment, education, economic status, and inflammatory cytokines levels (all P cluster symptoms in cancer patients. Clinicians should identify patients at risk for more severe symptoms and formulate novel target interventions to improve symptom management. Copyright © 2017. Published by Elsevier Inc.

Subgrouping Poor Readers on the Basis of Individual Differences in Reading-Related Abilities

OpenAIRE

Catts, Hugh W.; Hogan, Tiffany; Fey, Marc E.

2003-01-01

The present study investigated the use of the Reading Component Model to subgroup poor readers. A large sample of poor readers was identified in second grade and subgrouped on the basis of relative strengths and weaknesses in word recognition and listening comprehension. Although homogeneous subgroups were not identified, poor readers could be classified into four subgroups that differed significantly in reading-related abilities. Further analyses showed that poor readers' strengths and weakn...

Analyzing proteasomal subunit expression reveals Rpt4 as a prognostic marker in stage II colorectal cancer.

LENUS (Irish Health Repository)

2012-02-01

Colorectal cancer is a leading cause of cancer-related deaths worldwide. Early diagnosis and treatment of colorectal cancer is the key to improving survival rates and as such a need exists to identify patients who may benefit from adjuvant chemotherapy. The dysregulation of the ubiquitin-proteasome system (UPS) has been implicated in oncogenesis and cancer cell survival, and proteasome inhibitors are in clinical use for a number of malignancies including multiple myeloma. In our study, we examined the protein expression of several key components of the UPS in colorectal cancer using immunohistochemistry to determine expression levels of ubiquitinylated proteins and the proteasomal subunits, 20S core and Rpt4 in a cohort of 228 patients with colon cancer. Multivariate Cox analysis revealed that neither the intensity of either ubiquitinylated proteins or the 20S core was predictive in either Stage II or III colon cancer for disease free survival or overall survival. In contrast, in Stage II patients increased Rpt4 staining was significantly associated with disease free survival (Cox proportional hazard ratio 0.605; p = 0.0217). Our data suggest that Rpt4 is an independent prognostic variable for Stage II colorectal cancer and may aid in the decision of which patients undergo adjuvant chemotherapy.

Demonstration of Microbial Subgroups among Normal Vaginal Microbiota Data

OpenAIRE

Lee, M.-L. T.

2011-01-01

In this study we identified subgroups of observations relating to the healthy vaginal microbiota. This microbiota resides in a dynamic environment that undergoes cyclic change during the menstrual cycle. Cluster analysis procedures were applied to divide a set of 226 normal microbiota observations into groups. Three subgroups containing 100, 65, and 61 observations were identified. Plots of principal components determined by canonical analysis were obtained to demonstrate graphically the clus...

The exploration of contrasting pathways in Triple Negative Breast Cancer (TNBC).

Science.gov (United States)

Narrandes, Shavira; Huang, Shujun; Murphy, Leigh; Xu, Wayne

2018-01-04

Triple Negative Breast Cancers (TNBCs) lack the appropriate targets for currently used breast cancer therapies, conferring an aggressive phenotype, more frequent relapse and poorer survival rates. The biological heterogeneity of TNBC complicates the clinical treatment further. We have explored and compared the biological pathways in TNBC and other subtypes of breast cancers, using an in silico approach and the hypothesis that two opposing effects (Yin and Yang) pathways in cancer cells determine the fate of cancer cells. Identifying breast subgroup specific components of these opposing pathways may aid in selecting potential therapeutic targets as well as further classifying the heterogeneous TNBC subtype. Gene expression and patient clinical data from The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) were used for this study. Gene Set Enrichment Analysis (GSEA) was used to identify the more active pathways in cancer (Yin) than in normal and the more active pathways in normal (Yang) than in cancer. The clustering analysis was performed to compare pathways of TNBC with other types of breast cancers. The association of pathway classified TNBC sub-groups to clinical outcomes was tested using Cox regression model. Among 4729 curated canonical pathways in GSEA database, 133 Yin pathways (FDR pathways (p-value pathway while PPARα is the top Yang pathway in TNBC. The TNBC and other types of breast cancers showed different pathways enrichment significance profiles. Using top Yin and Yang pathways as classifier, the TNBC can be further subtyped into six sub-groups each having different clinical outcomes. We first reported that the FOMX1 pathway is the most upregulated and the PPARα pathway is the most downregulated pathway in TNBC. These two pathways could be simultaneously targeted in further studies. Also the pathway classifier we performed in this study provided insight into the TNBC heterogeneity.

MPACT Subgroup Self-Shielding Efficiency Improvements

International Nuclear Information System (INIS)

Stimpson, Shane; Liu, Yuxuan; Collins, Benjamin S.; Clarno, Kevin T.

2016-01-01

Recent developments to improve the efficiency of the MOC solvers in MPACT have yielded effective kernels that loop over several energy groups at once, rather that looping over one group at a time. These kernels have produced roughly a 2x speedup on the MOC sweeping time during eigenvalue calculation. However, the self-shielding subgroup calculation had not been reevaluated to take advantage of these new kernels, which typically requires substantial solve time. The improvements covered in this report start by integrating the multigroup kernel concepts into the subgroup calculation, which are then used as the basis for further extensions. The next improvement that is covered is what is currently being termed as ''Lumped Parameter MOC''. Because the subgroup calculation is a purely fixed source problem and multiple sweeps are performed only to update the boundary angular fluxes, the sweep procedure can be condensed to allow for the instantaneous propagation of the flux across a spatial domain, without the need to sweep along all segments in a ray. Once the boundary angular fluxes are considered to be converged, an additional sweep that will tally the scalar flux is completed. The last improvement that is investigated is the possible reduction of the number of azimuthal angles per octant in the shielding sweep. Typically 16 azimuthal angles per octant are used for self-shielding and eigenvalue calculations, but it is possible that the self-shielding sweeps are less sensitive to the number of angles than the full eigenvalue calculation.

Comparative mRNA and microRNA expression profiling of three genitourinary cancers reveals common hallmarks and cancer-specific molecular events.

Directory of Open Access Journals (Sweden)

Xianxin Li

Full Text Available Genome-wide gene expression profile using deep sequencing technologies can drive the discovery of cancer biomarkers and therapeutic targets. Such efforts are often limited to profiling the expression signature of either mRNA or microRNA (miRNA in a single type of cancer.Here we provided an integrated analysis of the genome-wide mRNA and miRNA expression profiles of three different genitourinary cancers: carcinomas of the bladder, kidney and testis.Our results highlight the general or cancer-specific roles of several genes and miRNAs that may serve as candidate oncogenes or suppressors of tumor development. Further comparative analyses at the systems level revealed that significant aberrations of the cell adhesion process, p53 signaling, calcium signaling, the ECM-receptor and cell cycle pathways, the DNA repair and replication processes and the immune and inflammatory response processes were the common hallmarks of human cancers. Gene sets showing testicular cancer-specific deregulation patterns were mainly implicated in processes related to male reproductive function, and general disruptions of multiple metabolic pathways and processes related to cell migration were the characteristic molecular events for renal and bladder cancer, respectively. Furthermore, we also demonstrated that tumors with the same histological origins and genes with similar functions tended to group together in a clustering analysis. By assessing the correlation between the expression of each miRNA and its targets, we determined that deregulation of 'key' miRNAs may result in the global aberration of one or more pathways or processes as a whole.This systematic analysis deciphered the molecular phenotypes of three genitourinary cancers and investigated their variations at the miRNA level simultaneously. Our results provided a valuable source for future studies and highlighted some promising genes, miRNAs, pathways and processes that may be useful for diagnostic or

QUINT : A tool to detect qualitative treatment-subgroup interactions in randomized controlled trials

NARCIS (Netherlands)

Doove, L.L.; Van Deun, K.; Dusseldorp, E.; van Mechelen, I.

2016-01-01

Objective: The detection of subgroups involved in qualitative treatment–subgroup interactions (i.e., for one subgroup of clients treatment A outperforms treatment B, whereas for another the reverse holds true) is crucial for personalized health. In typical Randomized Controlled Trials (RCTs), the

Research Article Cancer Mortality among Asians and Pacific Islanders in New York City, 2001–2010

International Nuclear Information System (INIS)

Huang, V.; Li, W.; Tsai, J.; Begier, E.

2013-01-01

Asians and Pacific Islanders’ (APIs) leading cause of death is cancer. We compared APIs’ age-adjusted cancer mortality rates to other racial/ethnic groups and by API subgroup (i.e., Chinese, Koreans, Asian Indians, and Filipinos) using New York City (NYC) Mortality data and Census Bureau population estimates for 2001-2010. While other racial/ethnic groups’ overall cancer mortality rates declined in NYC during the last decade, APIs remained stable. APIs overall had the lowest mortality rates for more common cancer types (i.e., lung, colorectal, breast, and prostate), but the highest mortality rates for certain less common cancers (i.e., nasopharyngeal, stomach, and liver). Chinese New Yorkers’ lung cancer death rates were very high compared to other APIs and comparable to non-Hispanic whites (47.1/100,000 versus 49.5/100,000, resp.). Chinese men had much higher nasopharyngeal cancer mortality rates (4.5/100,000 versus 0.3/100,000 for non-Hispanic whites). Korean men had the highest liver and stomach cancer mortality rates (25.3/100,000 and 27.7/100,000, resp., versus 7.9/100,000 and 6.0/100,000 for non-Hispanic whites). Analysis of cancer rates by API subgroup provides the detailed information needed to plan cancer prevention efforts. These findings warrant consideration of targeted cancer mortality prevention efforts for affected subgroups, including hepatitis vaccination, screening, and treatment; smoking cessation; and cancer screening.

The structure of EAP-groups and self-autopermutable subgroups.

Science.gov (United States)

Housieni, Shima; Moghaddam, Mohammad Reza Rajabzadeh

2014-01-01

A subgroup H of a given group G is said to be autopermutable, if HH(α) = H(α)H for all α ∈ Aut(G). We also call H a self-autopermutable subgroup of G, when HH(α) = H(α)H implies that H(α) = H. Moreover, G is said to be EAP-group, if every subgroup of G is autopermutable. One notes that if α runs over the inner automorphisms of the group, one obtains the notions of conjugate-permutability, self-conjugate-permutability, and ECP-groups, which were studied by Foguel in 1997, Li and Meng in 2007, and Xu and Zhang in 2005, respectively. In the present paper, we determine the structure of a finite EAP-group when its centre is of index 4 in G. We also show that self-autopermutability and characteristic properties are equivalent for nilpotent groups.

Everolimus in advanced, progressive, well-differentiated, non-functional neuroendocrine tumors: RADIANT-4 lung subgroup analysis.

Science.gov (United States)

Fazio, Nicola; Buzzoni, Roberto; Delle Fave, Gianfranco; Tesselaar, Margot E; Wolin, Edward; Van Cutsem, Eric; Tomassetti, Paola; Strosberg, Jonathan; Voi, Maurizio; Bubuteishvili-Pacaud, Lida; Ridolfi, Antonia; Herbst, Fabian; Tomasek, Jiri; Singh, Simron; Pavel, Marianne; Kulke, Matthew H; Valle, Juan W; Yao, James C

2018-01-01

In the phase III RADIANT-4 study, everolimus improved median progression-free survival (PFS) by 7.1 months in patients with advanced, progressive, well-differentiated (grade 1 or grade 2), non-functional lung or gastrointestinal neuroendocrine tumors (NETs) vs placebo (hazard ratio, 0.48; 95% confidence interval [CI], 0.35-0.67; P < .00001). This exploratory analysis reports the outcomes of the subgroup of patients with lung NETs. In RADIANT-4, patients were randomized (2:1) to everolimus 10 mg/d or placebo, both with best supportive care. This is a post hoc analysis of the lung subgroup with PFS, by central radiology review, as the primary endpoint; secondary endpoints included objective response rate and safety measures. Ninety of the 302 patients enrolled in the study had primary lung NET (everolimus, n = 63; placebo, n = 27). Median PFS (95% CI) by central review was 9.2 (6.8-10.9) months in the everolimus arm vs 3.6 (1.9-5.1) months in the placebo arm (hazard ratio, 0.50; 95% CI, 0.28-0.88). More patients who received everolimus (58%) experienced tumor shrinkage compared with placebo (13%). Most frequently reported (≥5% incidence) grade 3-4 drug-related adverse events (everolimus vs. placebo) included stomatitis (11% vs. 0%), hyperglycemia (10% vs. 0%), and any infections (8% vs. 0%). In patients with advanced, progressive, well-differentiated, non-functional lung NET, treatment with everolimus was associated with a median PFS improvement of 5.6 months, with a safety profile similar to that of the overall RADIANT-4 cohort. These results support the use of everolimus in patients with advanced, non-functional lung NET. The trial is registered with ClinicalTrials.gov (no. NCT01524783). © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

A comparison of cancer burden and research spending reveals discrepancies in the distribution of research funding

Directory of Open Access Journals (Sweden)

Carter Ashley JR

2012-07-01

Full Text Available Abstract Background Ideally, the distribution of research funding for different types of cancer should be equitable with respect to the societal burden each type of cancer imposes. These burdens can be estimated in a variety of ways; “Years of Life Lost” (YLL measures the severity of death in regard to the age it occurs, "Disability-Adjusted Life-Years" (DALY estimates the effects of non-lethal disabilities incurred by disease and economic metrics focus on the losses to tax revenue, productivity or direct medical expenses. We compared research funding from the National Cancer Institute (NCI to a variety of burden metrics for the most common types of cancer to identify mismatches between spending and societal burden. Methods Research funding levels were obtained from the NCI website and information for societal health and economic burdens were collected from government databases and published reports. We calculated the funding levels per unit burden for a wide range of different cancers and burden metrics and compared these values to identify discrepancies. Results Our analysis reveals a considerable mismatch between funding levels and burden. Some cancers are funded at levels far higher than their relative burden suggests (breast cancer, prostate cancer, and leukemia while other cancers appear underfunded (bladder, esophageal, liver, oral, pancreatic, stomach, and uterine cancers. Conclusions These discrepancies indicate that an improved method of health care research funding allocation should be investigated to better match funding levels to societal burden.

Substitutions between dairy product subgroups and risk of type 2 diabetes

DEFF Research Database (Denmark)

Ibsen, Daniel B; Laursen, Anne Sofie D; Lauritzen, Lotte

2017-01-01

The aim of this study was to investigate the associations for specified substitutions between different subgroups of dairy products and the risk of type 2 diabetes. We used data from the Danish Diet, Cancer and Health cohort including 54 277 men and women aged 50-64 years at baseline. Information...... regarding intake of dairy products was obtained from a validated FFQ, and cases of type 2 diabetes were identified through the Danish National Diabetes Register. Cox proportional hazards regressions were used to estimate associations. During a median follow-up of 15·3 years, 7137 cases were identified. Low......-fat yogurt products in place of whole-fat yogurt products were associated with a higher rate of type 2 diabetes (hazard ratio (HR) 1·17; 95 % CI 1·06, 1·29) per serving/d substituted. Whole-fat yogurt products in place of low-fat milk, whole-fat milk or buttermilk were associated with a lower rate of type 2...

Lifestyle behaviors, obesity, and perceived health among men with and without a diagnosis of prostate cancer: A population-based, cross-sectional study

Directory of Open Access Journals (Sweden)

Markwell Stephen J

2008-01-01

Full Text Available Abstract Background A better understanding of how prostate cancer survivors differ from men without prostate cancer and whether these potential differences vary across demographic subgroups will help to focus and prioritize future public health interventions for improving the health and well-being of prostate cancer survivors. Therefore, our study aims were to compare lifestyle behaviors, body mass index (BMI, and perceived health in men with and without a diagnosis of prostate cancer in a national, population-based sample and to explore whether these comparisons differ for demographic subgroups. Methods In a cross-sectional study, men aged ≥ 40 were identified from the Behavioral Risk Factor Surveillance System (BRFSS 2002 data (n = 63,662. Respondents reporting history of prostate cancer (n = 2,524 were compared with non prostate cancer controls (n = 61,138 with regard to daily fruit and vegetable servings (FVPD, smoking, alcohol, sedentary behavior, BMI, and perceived health. Multivariable logistic regression calculated adjusted odds ratios (OR and 95% confidence intervals (CI for the entire sample and for age, race, education, and urbanicity subgroups. Results Men with prostate cancer did not differ from men without prostate cancer with regard to smoking, alcohol, sedentary behavior, and obesity but were more likely to consume ≥ 5 FVPD (OR, 95% CI: 1.30, 1.09–1.56 and report poor or fair health (OR, 95% CI: 1.62, 1.33–1.97. Subgroup analyses demonstrated attenuation of the higher likelihood of ≥ 5 FVPD among prostate cancer survivors in rural respondents (OR, 95% CI: 0.98, 0.72–1.33. Poorer perceived health was greatest if ≤ 65 years of age (OR, 95% CI: 2.54, 1.79–3.60 and nonsignificant if black (OR, 95% CI: 1.41, 0.70–2.82. Smoking and alcohol which were not significant for the sample as a whole, demonstrated significant associations in certain subgroups. Conclusion Although efforts to enhance perceived health and healthy

Functional proteomic analysis reveals the involvement of KIAA1199 in breast cancer growth, motility and invasiveness

International Nuclear Information System (INIS)

Jami, Mohammad-Saeid; Huang, Xin; Peng, Hong; Fu, Kai; Li, Yan; Singh, Rakesh K; Ding, Shi-Jian; Hou, Jinxuan; Liu, Miao; Varney, Michelle L; Hassan, Hesham; Dong, Jixin; Geng, Liying; Wang, Jing; Yu, Fang

2014-01-01

KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness. We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to study the role of this protein in cell proliferation, migration and apoptosis in vitro. We studied the effects of KIAA1199 knockdown in vivo in two groups of mice (n = 5). We carried out the SILAC LC-MS/MS based proteomic studies on the involvement of KIAA1199 in breast cancer. KIAA1199 mRNA and protein was significantly overexpressed in breast tumor specimens and cell lines as compared with non-neoplastic breast tissues from large-scale microarray and studies of breast cancer cell lines and tumors. To gain deeper insights into the novel role of KIAA1199 in breast cancer, we modulated KIAA1199 expression using shRNA-mediated knockdown in two breast cancer cell lines (MDA-MB-231 and HS578T), expressing higher levels of KIAA1199. The KIAA1199 knockdown cells showed reduced motility and cell proliferation in vitro. Moreover, when the knockdown cells were injected into the mammary fat pads of female athymic nude mice, there was a significant decrease in tumor incidence and growth. In addition, quantitative proteomic analysis revealed that knockdown of KIAA1199 in breast cancer (MDA-MB-231) cells affected a broad range of cellular functions including apoptosis, metabolism and cell motility. Our findings indicate that KIAA1199 may play an important role in breast tumor growth and invasiveness, and that it

The role of secreted frizzled-related protein 2 expression in prostate cancer.

LENUS (Irish Health Repository)

O'Hurley, Gillian

2012-02-01

AIMS: Improved prostate cancer (PCa)-specific biomarkers are urgently required to distinguish between indolent and aggressive disease, in order to avoid overtreatment. In this study, we investigated the prostatic tissue expression of secreted frizzled-related protein (SFRP)-2. METHODS AND RESULTS: Following immunohistochemical analysis on PCa tissue microarrays with samples from 216 patients, strong\\/moderate SFRP-2 expression was observed in epithelial cells of benign prostatic hyperplasia, and negative\\/weak SFRP-2 expression was observed in the majority of tumour epithelia. However, among Gleason grade 5 carcinomas, 40% showed strong\\/moderate SFRP-2 expression and 60% showed negative SFRP-2 expression in epithelial cells. Further microscopic evaluation of Gleason grade 5 tumours revealed different morphological patterns, corresponding with differential SFRP-2 expression. The first subgroup (referred to as Type A) appeared to have a morphologically solid growth pattern, whereas the second subgroup (referred to as Type B) appeared to have a more diffuse pattern. Furthermore, 100% (4\\/4) of Type A patients experienced biochemical recurrence, as compared with 0% (0\\/6) of Type B patients. CONCLUSIONS: These results imply: (i) that there is a loss of SFRP-2 expression from benign to malignant prostate glands; and (ii) differential SFRP-2 expression among two possible subgroups of Gleason grade 5 tumours.

Biomarker screening of oral cancer cell lines revealed sub-populations of CD133-, CD44-, CD24- and ALDH1- positive cancer stem cells

Directory of Open Access Journals (Sweden)

Kendall K

2013-05-01

Full Text Available Head and neck squamous cell carcinoma (HNSCC ranks sixth worldwide for cancer-related mortality. For the past several decades the mainstay of treatment for HNSCC has been surgery and external beam radiation, although more recent trials combining chemotherapy and radiation have demonstrated improvements. However, cancer recurrence and treatment failures continue to occur in a significant percentage of patients. Recent advances in tumor biology have led to the discovery that many cancers, including HNSCC, may contain subpopulations of cells with stem cell-like properties that may explain relapse and recurrence. The objective of this study was to screen existing oral cancer cell lines for biomarkers specific for cells with stem cell-like properties. RNA was isolated for RT-PCR screening using primers for specific mRNA of the biomarkers: CD44, CD24, CD133, NANOG, Nestin, ALDH1, and ABCG2 in CAL27, SCC25 and SCC15 cells. This analysis revealed that some oral cancer cell lines (CAL27 and SCC25 may contain small subpopulations of adhesion- and contact-independent cells (AiDC that also express tumor stem cell markers, including CD44, CD133, and CD24. In addition, CAL27 cells also expressed the intracellular tumor stem cell markers, ALDH1 and ABCG2. Isolation and culture of the adhesion- and contact-independent cells from CAL27 and SCC25 populations revealed differential proliferation rates and more robust inhibition by the MEK inhibitor PD98059, as well as the chemotherapeutic agents Cisplatin and Paclitaxel, within the AiDC CAL27 cells. At least one oral cancer cell line (CAL27 contained subpopulations of cells that express specific biomarkers associated with tumor stem cells which were morphologically and phenotypically distinct from other cells within this cell line.

Expression analysis of cancer-testis genes in prostate cancer reveals candidates for immunotherapy.

Science.gov (United States)

Faramarzi, Sepideh; Ghafouri-Fard, Soudeh

2017-09-01

Prostate cancer is a prevalent disorder among men with a heterogeneous etiological background. Several molecular events and signaling perturbations have been found in this disorder. Among genes whose expressions have been altered during the prostate cancer development are cancer-testis antigens (CTAs). This group of antigens has limited expression in the normal adult tissues but aberrant expression in cancers. This property provides them the possibility to be used as cancer biomarkers and immunotherapeutic targets. Several CTAs have been shown to be immunogenic in prostate cancer patients and some of the have entered clinical trials. Based on the preliminary data obtained from these trials, it is expected that CTA-based therapeutic options are beneficial for at least a subset of prostate cancer patients.

Breast cancer subtype distribution is different in normal weight, overweight, and obese women.

Science.gov (United States)

Gershuni, Victoria; Li, Yun R; Williams, Austin D; So, Alycia; Steel, Laura; Carrigan, Elena; Tchou, Julia

2017-06-01

Obesity is associated with tumor promoting pathways related to insulin resistance and chronic low-grade inflammation which have been linked to various disease states, including cancer. Many studies have focused on the relationship between obesity and increased estrogen production, which contributes to the pathogenesis of estrogen receptor-positive breast cancers. The link between obesity and other breast cancer subtypes, such as triple-negative breast cancer (TNBC) and Her2/neu+ (Her2+) breast cancer, is less clear. We hypothesize that obesity may be associated with the pathogenesis of specific breast cancer subtypes resulting in a different subtype distribution than normal weight women. A single-institution, retrospective analysis of tumor characteristics of 848 patients diagnosed with primary operable breast cancer between 2000 and 2013 was performed to evaluate the association between BMI and clinical outcome. Patients were grouped based on their BMI at time of diagnosis stratified into three subgroups: normal weight (BMI = 18-24.9), overweight (BMI = 25-29.9), and obese (BMI > 30). The distribution of breast cancer subtypes across the three BMI subgroups was compared. Obese and overweight women were more likely to present with TNBC and normal weight women with Her2+ breast cancer (p = 0.008). We demonstrated, for the first time, that breast cancer subtype distribution varied significantly according to BMI status. Our results suggested that obesity might activate molecular pathways other than the well-known obesity/estrogen circuit in the pathogenesis of breast cancer. Future studies are needed to understand the molecular mechanisms that drive the variation in subtype distribution across BMI subgroups.

Symptom clustering and quality of life in patients with ovarian cancer undergoing chemotherapy.

Science.gov (United States)

Nho, Ju-Hee; Reul Kim, Sung; Nam, Joo-Hyun

2017-10-01

The symptom clusters in patients with ovarian cancer undergoing chemotherapy have not been well evaluated. We investigated the symptom clusters and effects of symptom clusters on the quality of life of patients with ovarian cancer. We recruited 210 ovarian cancer patients being treated with chemotherapy and used a descriptive cross-sectional study design to collect information on their symptoms. To determine inter-relationships among symptoms, a principal component analysis with varimax rotation was performed based on the patient's symptoms (fatigue, pain, sleep disturbance, chemotherapy-induced peripheral neuropathy, anxiety, depression, and sexual dysfunction). All patients had experienced at least two domains of concurrent symptoms, and there were two types of symptom clusters. The first symptom cluster consisted of anxiety, depression, fatigue, and sleep disturbance symptoms, while the second symptom cluster consisted of pain and chemotherapy-induced peripheral neuropathy symptoms. Our subgroup cluster analysis showed that ovarian cancer patients with higher-scoring symptoms had significantly poorer quality of life in both symptom cluster 1 and 2 subgroups, with subgroup-specific patterns. The symptom clusters were different depending on age, age at disease onset, disease duration, recurrence, and performance status of patients with ovarian cancer. In addition, ovarian cancer patients experienced different symptom clusters according to cancer stage. The current study demonstrated that there is a specific pattern of symptom clusters, and symptom clusters negatively influence the quality of life in patients with ovarian cancer. Identifying symptom clusters of ovarian cancer patients may have clinical implications in improving symptom management. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diffuse Muscular Pain, Skin Tightening, and Nodular Regenerative Hyperplasia Revealing Paraneoplastic Amyopathic Dermatomyositis due to Testicular Cancer

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Sarah Norrenberg

2012-01-01

Full Text Available Paraneoplastic dermatomyositis (DM associated with testicular cancer is extremely rare. We report the case of a patient with skin tightening, polymyalgia, hypereosinophilia, and nodular regenerative hyperplasia revealing seminoma and associated paraneoplastic DM.

Use of benzodiazepines or benzodiazepine related drugs and the risk of cancer: a population-based case-control study

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Pottegård, Anton; Friis, Søren; Andersen, Morten

2013-01-01

AIM: Studies of the carcinogenic potential of benzodiazepines and related drugs (BZRD) have been equivocal. A recent study reported a 35% excess cancer risk among users of hypnotics, including benzodiazepines. METHOD: Using Danish nationwide registers, we conducted a matched case-control study...... of the association between BZRD and cancer risk. During 1 January 2002 and 31 December 2009, we identified 152 510 cases with a first time cancer who were matched (1:8) by age and gender to 1,220,317 cancer-free controls. A new-user design was applied by excluding all subjects who had used anxiolytics, hypnotics.......02), liver 1.81 (95% CI 1.18, 2.80), lung 1.38 (95% CI 1.23, 1.54), pancreas 1.35 (95% CI 1.02, 1.79) and kidney 1.39 (95% CI 1.01, 1.91). For tobacco-related cancers, the OR was 1.15 (95% CI 1.09, 1.22) and for the remaining cancer sites 1.01 (95% CI 0.94, 1.08). Sub-group analyses revealed only small...

Analysis of the individual radio sensitivity of breast cancer patients

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Auer, Judith

2013-01-01

Individual radiosensitivity has a crucial impact on radiotherapy related side effects. A prediction of individual radiosensitivity could avoid these side effects. Our aim was to study a breast cancer collective for its variation of individual radiosensitivity. Peripheral blood samples were obtained from 129 individuals. 67 breast cancer patients and 62 healthy and age matched individuals were looked at and their individual radiosensitivity was estimated by a 3-color Fluorescence in situ hybridization approach. Blood samples were obtained (i) before starting adjuvant radiotherapy and were in vitro irradiated by 2 Gy; (ii) after 5 single doses of 1.8 Gy and after 72 h had elapsed. DNA of lymphocytes was probed with whole chromosome painting for chromosomes 1, 2 and 4. The rate of breaks per metaphase was analyzed and used as a predictor of individual radiosensitivity. Breast cancer patients were distinctly more radio-sensitive compared to healthy controls. Additionally the distribution of the cancer patients' radiosensitivity was broader. A subgroup of 9 rather radio-sensitive and 9 rather radio-resistant patients was identified. A subgroup of patients aged between 40 and 50 was distinctly more radio-sensitive than younger or older patients. The in vivo irradiation approach was not applicable to detect individual radiosensitivity. In the breast cancer collective a distinctly resistant and sensitive subgroup is identified, which could be subject for treatment adjustment. Especially in the range of age 40 to 50 patients have an increased radiosensitivity. An in vivo irradiation in a breast cancer collective is not suitable to estimate individual radiosensitivity due to a low deposed dose.

Radiation Dose Escalation in Esophageal Cancer Revisited: A Contemporary Analysis of the National Cancer Data Base, 2004 to 2012

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Brower, Jeffrey V.; Chen, Shuai; Bassetti, Michael F.; Yu, Menggang; Harari, Paul M.; Ritter, Mark A.; Baschnagel, Andrew M.

2016-01-01

Purpose: To evaluate the effect of radiation dose escalation on overall survival (OS) for patients with nonmetastatic esophageal cancer treated with concurrent radiation and chemotherapy. Methods and Materials: Patients diagnosed with stage I to III esophageal cancer treated from 2004 to 2012 were identified from the National Cancer Data Base. Patients who received concurrent radiation and chemotherapy with radiation doses of ≥50 Gy and did not undergo surgery were included. OS was compared using Cox proportional hazards regression and propensity score matching. Results: A total of 6854 patients were included; 3821 (55.7%) received 50 to 50.4 Gy and 3033 (44.3%) received doses >50.4 Gy. Univariate analysis revealed no significant difference in OS between patients receiving 50 to 50.4 Gy and those receiving >50.4 Gy (P=.53). The dose analysis, binned as 50 to 50.4, 51 to 54, 55 to 60, and >60 Gy, revealed no appreciable difference in OS within any group compared with 50 to 50.4 Gy. Subgroup analyses investigating the effect of dose escalation by histologic type and in the setting of intensity modulated radiation therapy also failed to reveal a benefit. Propensity score matching confirmed the absence of a statistically significant difference in OS among the dose levels. The factors associated with improved OS on multivariable analysis included female sex, lower Charlson-Deyo comorbidity score, private insurance, cervical/upper esophagus location, squamous cell histologic type, lower T stage, and node-negative status (P 50.4 Gy did not result in improved OS among patients with stage I to III esophageal cancer treated with definitive concurrent radiation and chemotherapy. These data suggest that despite advanced contemporary treatment techniques, OS for patients with esophageal cancer remains unaltered by escalation of radiation dose >50.4 Gy, consistent with the results of the INT-0123 trial. Furthermore, these data highlight that many radiation

Radiation Dose Escalation in Esophageal Cancer Revisited: A Contemporary Analysis of the National Cancer Data Base, 2004 to 2012

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Brower, Jeffrey V. [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Chen, Shuai [Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Bassetti, Michael F. [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Yu, Menggang [Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Harari, Paul M.; Ritter, Mark A. [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Baschnagel, Andrew M., E-mail: baschnagel@humonc.wisc.edu [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States)

2016-12-01

Purpose: To evaluate the effect of radiation dose escalation on overall survival (OS) for patients with nonmetastatic esophageal cancer treated with concurrent radiation and chemotherapy. Methods and Materials: Patients diagnosed with stage I to III esophageal cancer treated from 2004 to 2012 were identified from the National Cancer Data Base. Patients who received concurrent radiation and chemotherapy with radiation doses of ≥50 Gy and did not undergo surgery were included. OS was compared using Cox proportional hazards regression and propensity score matching. Results: A total of 6854 patients were included; 3821 (55.7%) received 50 to 50.4 Gy and 3033 (44.3%) received doses >50.4 Gy. Univariate analysis revealed no significant difference in OS between patients receiving 50 to 50.4 Gy and those receiving >50.4 Gy (P=.53). The dose analysis, binned as 50 to 50.4, 51 to 54, 55 to 60, and >60 Gy, revealed no appreciable difference in OS within any group compared with 50 to 50.4 Gy. Subgroup analyses investigating the effect of dose escalation by histologic type and in the setting of intensity modulated radiation therapy also failed to reveal a benefit. Propensity score matching confirmed the absence of a statistically significant difference in OS among the dose levels. The factors associated with improved OS on multivariable analysis included female sex, lower Charlson-Deyo comorbidity score, private insurance, cervical/upper esophagus location, squamous cell histologic type, lower T stage, and node-negative status (P<.01 for all analyses). Conclusions: In this large national cohort, dose escalation >50.4 Gy did not result in improved OS among patients with stage I to III esophageal cancer treated with definitive concurrent radiation and chemotherapy. These data suggest that despite advanced contemporary treatment techniques, OS for patients with esophageal cancer remains unaltered by escalation of radiation dose >50.4 Gy, consistent with the results of

Decreased survival in patients with carcinoma of axillary tail versus upper outer quadrant breast cancers: a SEER population-based study

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Gou ZC

2018-05-01

Full Text Available Zong-Chao Gou,1,2,* Xi-Yu Liu,1,2,* Yi Xiao,1,2 Shen Zhao,1,2 Yi-Zhou Jiang,1,2 Zhi-Ming Shao1–3 1Department of Breast Surgery, Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Institutes of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Carcinoma of the axillary tail of Spence (CATS is a poorly studied type of breast cancer. The clinicopathological characteristics and prognostic features of CATS are unclear. Methods: Using the Surveillance, Epidemiology, and End Results database, we identified 149,026 patients diagnosed with upper outer quadrant breast cancer (UOBC (n=146,343 or CATS (n=2,683. The median follow-up was 88 months. The primary and secondary outcomes were breast cancer-specific survival (BCSS and overall survival. The survival outcomes of UOBC and CATS were compared using competing risks analysis, log-rank test, Cox proportional hazards regression model, and propensity score matching method. Multivariate logistic regression was utilized to present the relationship between CATS and lymph node (LN metastasis. Results: CATS presented a higher grade, higher negative hormone receptor rate, and more positive nodal metastasis. The 10-year BCSS rate was worse for CATS than for UOBC (85.1% vs 87.3%, P=0.001. The multivariate Cox analysis showed a higher hazard ratio (HR for CATS over UOBC (BCSS: HR =1.20, P=0.001; overall survival: HR =1.11, P=0.019. The difference in the BCSS was also observed in a 1:1 matched cohort (BCSS P=0.019. A subgroup analysis revealed the inferior outcomes of CATS in the metastatic LN subgroup and the hormone receptor-negative subgroup. The multivariate logistic regression indicated that CATS is an independent contributing factor to LN metastasis. Conclusion: CATS

The central subgroup of the nonabelian tensor square of Bieberbach ...

African Journals Online (AJOL)

A Bieberbach group with point group C2 xC2 is a free torsion crystallographic group. A central subgroup of a nonabelian tensor square of a group G, denoted by ∇(G) is a normal subgroup generated by generator g⊗g for all g∈G and essentially depends on the abelianization of the group. In this paper, the formula of the ...

Discovering subgroups using descriptive models of adverse outcomes in medical care.

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Stiglic, Gregor; Kokol, P

2012-01-01

Hospital discharge databases store hundreds of thousands of patients. These datasets are usually used by health insurance companies to process claims from hospitals, but they also represent a rich source of information about the patterns of medical care. The proposed subgroup discovery method aims to improve the efficiency of detecting interpretable subgroups in data. Supervised descriptive rule discovery techniques can prove inefficient in cases when target class samples represent only an extremely small amount of all available samples. Our approach aims to balance the number of samples in target and control groups prior to subgroup discovery process. Additionally, we introduce some improvements to an existing subgroup discovery algorithm enhancing the user experience and making the descriptive data mining process and visualization of rules more user friendly. Instance-based subspace subgroup discovery introduced in this paper is demonstrated on hospital discharge data with focus on medical errors. In general, the number of patients with a recorded diagnosis related to a medical error is relatively small in comparison to patients where medical errors did not occur. The ability to produce comprehensible and simple models with high degree of confidence, support, and predictive power using the proposed method is demonstrated. This paper introduces a subspace subgroup discovery process that can be applied in all settings where a large number of samples with relatively small number of target class samples are present. The proposed method is implemented in Weka machine learning environment and is available at http://ri.fzv.uni-mb.si/ssd.

Early breast cancer

International Nuclear Information System (INIS)

Dongen, J.A. van

1989-01-01

The therapy of early breast cancer has been changing during the last decennium. It requires a multi-disciplinary approach and in each of these disciplines improvements have been implemented. The result is that treatment schedules can now be adapted to specific subgroups. In this review early breast cancer is defined as operable disease, using the criteria set out by Haagensen. Emphasis is given to describing the new developments in prognostic criteria, since these form the basis for creating subgroups for specific treatment schedules. Distinction is made between the factors relating to growth rate and those relating to metastatic potential. Data on screening promises a beneficial effect of the implementation of screening in national health care programs. Important shifts are seen in treatment schedules; the place of postoperative radiotherapy after classic ablative treatment is being challenged, whereas it plays a major role in the new breast conserving therapy schedules. The data mentioned in the review suggest that a large proportion of 'operable' cases can be treated with breast conservation but details in the technique of breast conserving therapy are still under investigation. They form a major part of the coming prospective studies in breast cancer. Improvements in reconstruction techniques, creating better cosmetic results, make reconstruction more competitive with breast conserving therapy. The use of chemotherapy and endocrine manipulation in early breast cancer has now been clearly confirmed by the overview technique by the Peto-group, thanks to all efforts of individual trialists together. (orig.)

Could yoga practice improve treatment-related side effects and quality of life for women with breast cancer? A systematic review and meta-analysis.

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Pan, Yuanqing; Yang, Kehu; Wang, Yuliang; Zhang, Laiping; Liang, Haiqing

2017-04-01

To determine if yoga as a complementary and alternative therapy was associated with enhanced health and treatment-related side effects in patients with breast cancer. This systematic review examines whether yoga practice provides any measurable benefit, both physically and psychologically, for women with breast cancer. PubMed, EMBASE and the Cochrane Library for randomized controlled trials (RCTs) throughout June 2013. We evaluated the quality of the included studies by the Cochrane Handbook 5.2 standards and analyzed the data using the Stata software, version 10.0. Meta-regression and subgroup analysis were also performed to identify additional predictors of outcome and to assess heterogeneity. Sixteen RCTs with a total of 930 participants were included. Comparing yoga groups to control groups, there was a statistically significant difference in overall health-related quality of life, depression, anxiety and gastrointestinal symptoms. Meta-regression analyses revealed that the duration of yoga practice and type of control group partly explained the heterogeneity. Subgroup analyses revealed that yoga had a positive effect on anxiety only when it had been practiced for longer than 3 months. Only the wait-list control group showed an effect of yoga on physical well-being. The current evidence demonstrates that yoga practice could be effective in enhancing health and managing some treatment-related side effects for patients recovering from breast cancer. In future clinical studies, clinicians should consider the patient's wishes along with the current best evidence of the effects of yoga practice in their clinical decision-making. © 2015 Wiley Publishing Asia Pty Ltd.

Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome.

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Nagy-Szakal, Dorottya; Williams, Brent L; Mishra, Nischay; Che, Xiaoyu; Lee, Bohyun; Bateman, Lucinda; Klimas, Nancy G; Komaroff, Anthony L; Levine, Susan; Montoya, Jose G; Peterson, Daniel L; Ramanan, Devi; Jain, Komal; Eddy, Meredith L; Hornig, Mady; Lipkin, W Ian

2017-04-26

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling. Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the

Cancer gene profiling in non-small cell lung cancers reveals activating mutations in JAK2 and JAK3 with therapeutic implications

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Shuyu D. Li

2017-10-01

Full Text Available Abstract Background Next-generation sequencing (NGS of cancer gene panels are widely applied to enable personalized cancer therapy and to identify novel oncogenic mutations. Methods We performed targeted NGS on 932 clinical cases of non-small-cell lung cancers (NSCLCs using the Ion AmpliSeq™ Cancer Hotspot panel v2 assay. Results Actionable mutations were identified in 65% of the cases with available targeted therapeutic options, including 26% of the patients with mutations in National Comprehensive Cancer Network (NCCN guideline genes. Most notably, we discovered JAK2 p.V617F somatic mutation, a hallmark of myeloproliferative neoplasms, in 1% (9/932 of the NSCLCs. Analysis of cancer cell line pharmacogenomic data showed that a high level of JAK2 expression in a panel of NSCLC cell lines is correlated with increased sensitivity to a selective JAK2 inhibitor. Further analysis of TCGA genomic data revealed JAK2 gain or loss due to genetic alterations in NSCLC clinical samples are associated with significantly elevated or reduced PD-L1 expression, suggesting that the activating JAK2 p.V617F mutation could confer sensitivity to both JAK inhibitors and anti-PD1 immunotherapy. We also detected JAK3 germline activating mutations in 6.7% (62/932 of the patients who may benefit from anti-PD1 treatment, in light of recent findings that JAK3 mutations upregulate PD-L1 expression. Conclusion Taken together, this study demonstrated the clinical utility of targeted NGS with a focused hotspot cancer gene panel in NSCLCs and identified activating mutations in JAK2 and JAK3 with clinical implications inferred through integrative analysis of cancer genetic, genomic, and pharmacogenomic data. The potential of JAK2 and JAK3 mutations as response markers for the targeted therapy against JAK kinases or anti-PD1 immunotherapy warrants further investigation.

Race/Ethnicity, Gender, Weight Status, and Colorectal Cancer Screening

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Heather Bittner Fagan

2011-01-01

The literature on colorectal cancer (CRC screening is contradictory regarding the impact of weight status on CRC screening. This study was intended to determine if CRC screening rates among 2005 National Health Interview Survey (NHIS respondent racial/ethnic and gender subgroups were influenced by weight status. Methods. Univariable and multivariable logistic regression analyses were performed to determine if CRC screening use differed significantly among obese, overweight, and normal-weight individuals in race/ethnic and gender subgroups. Results. Multivariable analyses showed that CRC screening rates did not differ significantly for individuals within these subgroups who were obese or overweight as compared to their normal-weight peers. Conclusion. Weight status does not contribute to disparities in CRC screening in race/ethnicity and gender subgroups.

No improvement in the reporting of clinical trial subgroup effects in high-impact general medical journals.

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Gabler, Nicole B; Duan, Naihua; Raneses, Eli; Suttner, Leah; Ciarametaro, Michael; Cooney, Elizabeth; Dubois, Robert W; Halpern, Scott D; Kravitz, Richard L

2016-07-16

When subgroup analyses are not correctly analyzed and reported, incorrect conclusions may be drawn, and inappropriate treatments provided. Despite the increased recognition of the importance of subgroup analysis, little information exists regarding the prevalence, appropriateness, and study characteristics that influence subgroup analysis. The objective of this study is to determine (1) if the use of subgroup analyses and multivariable risk indices has increased, (2) whether statistical methodology has improved over time, and (3) which study characteristics predict subgroup analysis. We randomly selected randomized controlled trials (RCTs) from five high-impact general medical journals during three time periods. Data from these articles were abstracted in duplicate using standard forms and a standard protocol. Subgroup analysis was defined as reporting any subgroup effect. Appropriate methods for subgroup analysis included a formal test for heterogeneity or interaction across treatment-by-covariate groups. We used logistic regression to determine the variables significantly associated with any subgroup analysis or, among RCTs reporting subgroup analyses, using appropriate methodology. The final sample of 416 articles reported 437 RCTs, of which 270 (62 %) reported subgroup analysis. Among these, 185 (69 %) used appropriate methods to conduct such analyses. Subgroup analysis was reported in 62, 55, and 67 % of the articles from 2007, 2010, and 2013, respectively. The percentage using appropriate methods decreased over the three time points from 77 % in 2007 to 63 % in 2013 (p < 0.05). Significant predictors of reporting subgroup analysis included industry funding (OR 1.94 (95 % CI 1.17, 3.21)), sample size (OR 1.98 per quintile (1.64, 2.40), and a significant primary outcome (OR 0.55 (0.33, 0.92)). The use of appropriate methods to conduct subgroup analysis decreased by year (OR 0.88 (0.76, 1.00)) and was less common with industry funding (OR 0.35 (0.18, 0

Data-Independent Acquisition-Based Quantitative Proteomic Analysis Reveals Potential Biomarkers of Kidney Cancer.

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Song, Yimeng; Zhong, Lijun; Zhou, Juntuo; Lu, Min; Xing, Tianying; Ma, Lulin; Shen, Jing

2017-12-01

Renal cell carcinoma (RCC) is a malignant and metastatic cancer with 95% mortality, and clear cell RCC (ccRCC) is the most observed among the five major subtypes of RCC. Specific biomarkers that can distinguish cancer tissues from adjacent normal tissues should be developed to diagnose this disease in early stages and conduct a reliable prognostic evaluation. Data-independent acquisition (DIA) strategy has been widely employed in proteomic analysis because of various advantages, including enhanced protein coverage and reliable data acquisition. In this study, a DIA workflow is constructed on a quadrupole-Orbitrap LC-MS platform to reveal dysregulated proteins between ccRCC and adjacent normal tissues. More than 4000 proteins are identified, 436 of these proteins are dysregulated in ccRCC tissues. Bioinformatic analysis reveals that multiple pathways and Gene Ontology items are strongly associated with ccRCC. The expression levels of L-lactate dehydrogenase A chain, annexin A4, nicotinamide N-methyltransferase, and perilipin-2 examined through RT-qPCR, Western blot, and immunohistochemistry confirm the validity of the proteomic analysis results. The proposed DIA workflow yields optimum time efficiency and data reliability and provides a good choice for proteomic analysis in biological and clinical studies, and these dysregulated proteins might be potential biomarkers for ccRCC diagnosis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Household-level disparities in cancer risks from vehicular air pollution in Miami

International Nuclear Information System (INIS)

Collins, Timothy W; Grineski, Sara E; Chakraborty, Jayajit

2015-01-01

Environmental justice (EJ) research has relied on ecological analyses of socio-demographic data from areal units to determine if particular populations are disproportionately burdened by toxic risks. This article advances quantitative EJ research by (a) examining whether statistical associations found for geographic units translate to relationships at the household level; (b) testing alternative explanations for distributional injustices never before investigated; and (c) applying a novel statistical technique appropriate for geographically-clustered data. Our study makes these advances by using generalized estimating equations to examine distributive environmental inequities in the Miami (Florida) metropolitan area, based on primary household-level survey data and census block-level cancer risk estimates of hazardous air pollutant (HAP) exposure from on-road mobile emission sources. In addition to modeling determinants of on-road HAP cancer risk among all survey participants, two subgroup models are estimated to examine whether determinants of risk differ based on disadvantaged minority (Hispanic and non-Hispanic Black) versus non-Hispanic white racial/ethnic status. Results reveal multiple determinants of risk exposure disparities. In the model including all survey participants, renter-occupancy, Hispanic and non-Hispanic black race/ethnicity, the desire to live close to work/urban services or public transportation, and higher risk perception are associated with greater on-road HAP cancer risk; the desire to live in an amenity-rich environment is associated with less risk. Divergent subgroup model results shed light on the previously unexamined role of racial/ethnic status in shaping determinants of risk exposures. While lower socioeconomic status and higher risk perception predict significantly greater on-road HAP cancer risk among disadvantaged minorities, the desire to live near work/urban services or public transport predict significantly greater risk among

Colonoscopy surveillance for dysplasia and colorectal cancer in patients with inflammatory bowel disease

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Aalykke, Claus; Jensen, Michael Dam; Fallingborg, Jan

2015-01-01

The risk of colorectal cancer (CRC) and dysplasia in patients with inflammatory bowel disease (IBD) has been highly debated as risk estimates from different studies vary greatly. The present national Danish guideline on colonoscopy surveillance for dysplasia and colorectal cancer in patients......, in some subgroups of patients the risk is increased. These subgroups of patients, who should be offered colonoscopy surveillance, include patients with ulcerative colitis having extensive disease and a long disease duration (10-13 years); early age at onset (less than 19 years of age) of ulcerative...... colitis; and patients with ulcerative colitis as well as Crohn´s disease with a concomitant diagnosis of primary sclerosing cholangitis. A colonoscopy surveillance program is recommended in these subgroups with intervals ranging from every 3-6 months to every 5 years, using chromoendoscopy with targeted...

Association of matrix metalloproteinase-3 -1171(5A>6A polymorphism with cancer risk: a meta-analysis of 41 studies.

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Xin Yang

Full Text Available BACKGROUND AND OBJECTIVE: Evidence has shown that matrix metalloproteinases-3 (MMP3 is important for cancer progression. Recent studies about the association between the -1171(5A>6A polymorphism in MMP3 promoter region and cancer risk have yielded conflicting results. METHODOLOGY/PRINCIPAL FINDINGS: We performed a meta-analysis of 41 studies including 11112 cases and 11091 controls to determine whether the -1171(5A>6A polymorphism of MMP3 was associated with cancer risk. We assessed the strength of association and performed sub-group analyses by cancer types, ethnicity, smoking status, genotyping method, source of controls and sample size. The pooled results revealed that no significant association of the -1171(5A>6A polymorphism with overall cancer risk in any of four models. Further sub-group analysis revealed that individuals with the 6A allele had lower risk of gastrointestinal cancer in two models: heterozygote comparison (6A/5A vs. 5A/5A: OR=0.74, 95%CI: 0.60-0.91; I(2=1.9%, and dominant model (6A/6A+6A/5A vs. 5A/5A: OR=0.77, 95%CI: 0.64-0.94; I(2=29.0%. Additionally, the associations were significant in Asian populations for three models: homozygote comparison (6A/6A vs. 5A/5A, OR=0.68, 95%CI: 0.52-0.90; I(2=26.7%, heterozygote comparison (6A/5A vs. 5A/5A: OR=0.75, 95%CI: 0.58-0.98; I(2=0.0%, and dominant model (6A/6A+6A/5A vs. 5A/5A: OR=0.69, 95%CI: 0.54-0.88; I(2=0.5%. It was noteworthy that we had a contrary finding in non-smokers: the variant 6A/6A homozygote might statistically increase cancer risk compared with 6A/5A+5A/5A genotype (OR=1.92, 95%CI: 1.25-2.96; I(2=72.7%. CONCLUSION: This meta-analysis suggests that the -1171(5A>6A polymorphism in MMP3 promoter region is not associated with overall cancer risk, but it may contribute to decreased cancer risk in Asian population when compared with Caucasian population and significantly reduce the risk of gastrointestinal cancer.

Different HLA-DRB1 allele distributions in distinct clinical subgroups of sarcoidosis patients

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Nisell Magnus

2010-02-01

Full Text Available Abstract Background A strong genetic influence by the MHC class II region has been reported in sarcoidosis, however in many studies with different results. This may possibly be caused by actual differences between distinct ethnic groups, too small sample sizes, or because of lack of accurate clinical subgrouping. Subjects and methods In this study we HLA typed a large patient population (n = 754 recruited from one single centre. Patients were sub-grouped into those with Löfgren's syndrome (LS (n = 302 and those without (non-Löfgren's (n = 452, and the majority of them were clinically classified into those with recovery within two years (resolving and those with signs of disease for more than two years (non-resolving. PCR was used for determination of HLA-DRB1 alleles. Swedish healthy blood donors (n = 1366 served as controls. Results There was a dramatic difference in the distribution of HLA alleles in LS compared to non-LS patients (p = 4 × 10-36. Most notably, DRB1*01, DRB1*03 and DRB1*14, clearly differed in LS and non-LS patients. In relation to disease course, DRB1*07, DRB1*14 and DRB1*15 generally associated with, while DRB1*01 and DRB1*03 protected against, a non-resolving disease. Interestingly, the clinical influence of DRB1*03 (good prognosis dominated over that of DRB1*15 (bad prognosis. Conclusions We found several significant differences between LS and non-LS patients and we therefore suggest that genetic association studies in sarcoidosis should include a careful clinical characterisation and sub-grouping of patients, in order to reveal true genetic associations. This may be particularly accurate to do in the heterogeneous non-LS group of patients.

A single test for rejecting the null hypothesis in subgroups and in the overall sample.

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Lin, Yunzhi; Zhou, Kefei; Ganju, Jitendra

2017-01-01

In clinical trials, some patient subgroups are likely to demonstrate larger effect sizes than other subgroups. For example, the effect size, or informally the benefit with treatment, is often greater in patients with a moderate condition of a disease than in those with a mild condition. A limitation of the usual method of analysis is that it does not incorporate this ordering of effect size by patient subgroup. We propose a test statistic which supplements the conventional test by including this information and simultaneously tests the null hypothesis in pre-specified subgroups and in the overall sample. It results in more power than the conventional test when the differences in effect sizes across subgroups are at least moderately large; otherwise it loses power. The method involves combining p-values from models fit to pre-specified subgroups and the overall sample in a manner that assigns greater weight to subgroups in which a larger effect size is expected. Results are presented for randomized trials with two and three subgroups.

Post hoc subgroups in clinical trials: Anathema or analytics?

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Weisberg, Herbert I; Pontes, Victor P

2015-08-01

There is currently much interest in generating more individualized estimates of treatment effects. However, traditional statistical methods are not well suited to this task. Post hoc subgroup analyses of clinical trials are fraught with methodological problems. We suggest that the alternative research paradigm of predictive analytics, widely used in many business contexts, can be adapted to help. We compare the statistical and analytics perspectives and suggest that predictive modeling should often replace subgroup analysis. We then introduce a new approach, cadit modeling, that can be useful to identify and test individualized causal effects. The cadit technique is particularly useful in the context of selecting from among a large number of potential predictors. We describe a new variable-selection algorithm that has been applied in conjunction with cadit. The cadit approach is illustrated through a reanalysis of data from the Randomized Aldactone Evaluation Study trial, which studied the efficacy of spironolactone in heart-failure patients. The trial was successful, but a serious adverse effect (hyperkalemia) was subsequently discovered. Our reanalysis suggests that it may be possible to predict the degree of hyperkalemia based on a logistic model and to identify a subgroup in which the effect is negligible. Cadit modeling is a promising alternative to subgroup analyses. Cadit regression is relatively straightforward to implement, generates results that are easy to present and explain, and can mesh straightforwardly with many variable-selection algorithms. © The Author(s) 2015.

Plasma YKL-40: a potential new cancer biomarker?

DEFF Research Database (Denmark)

Johansen, Julia S; Schultz, Nicolai A; Jensen, Benny V

2009-01-01

tissue remodeling. Plasma levels of YKL-40 are elevated in a subgroup of patients with primary or advanced cancer compared with age-matched healthy subjects, but also in patients with many different diseases characterized by inflammation. Elevated plasma YKL-40 levels are an independent prognostic...... by inflammation. Large prospective, longitudinal clinical cancer studies are needed to determine if plasma YKL-40 is a new cancer biomarker, or is mainly a biomarker of inflammation....

Clinimetrics corner: choosing appropriate study designs for particular questions about treatment subgroups

DEFF Research Database (Denmark)

Kent, Peter; Hancock, Mark; Petersen, Ditte H.D

2010-01-01

that are inappropriate given the randomized controlled trial design used. The research design to choose, when developing a study protocol that investigates the effect of treatment subgroups, depends on the particular research question. Similarly, the inferences that can be drawn from an existing study will vary...... receive the same treatment?'; and (4) 'Are outcomes for a number of treatments better if those treatments are matched to patients in specific subgroups, than if the SAME treatments are randomly given to patients?'. Illustrative examples of these studies are provided. Conclusion: If the clinical usefulness......Background: Many clinicians and researchers believe that there are subgroups of people with spinal pain who respond differently to treatment and have different prognoses. There has been considerable interest in this topic recently. However, problems occur when conclusions about subgroups are made...

Extraction-differential-photometric method to determine rare earths of cerium subgroup

International Nuclear Information System (INIS)

Askerov, D.N.; Gusejnov, I.K.; Melikov, A.A.

1985-01-01

The extraction - photometric method to determine great quantities of rare earths of the cerium subgroup as a complex with antipyrine A and diphenylguanidine is developed. Isobutyl and n-butyl alcohols are used as extractants. It is established that proportional dependence between relative optical density and concentration of rare earths of the cerium subgroup in the solution takes place in the concentration interval of 10.3-14.7 μg of rare earths in 1 ml of the solution. Determination error is+-1.12%. The technique is used to determine rare earths of the cerium subgroup in rare earth oxides of a mixed composition, as well as in monozite and loparite

Latent class analysis derived subgroups of low back pain patients - do they have prognostic capacity?

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Molgaard Nielsen, Anne; Hestbaek, Lise; Vach, Werner; Kent, Peter; Kongsted, Alice

2017-08-09

Heterogeneity in patients with low back pain is well recognised and different approaches to subgrouping have been proposed. One statistical technique that is increasingly being used is Latent Class Analysis as it performs subgrouping based on pattern recognition with high accuracy. Previously, we developed two novel suggestions for subgrouping patients with low back pain based on Latent Class Analysis of patient baseline characteristics (patient history and physical examination), which resulted in 7 subgroups when using a single-stage analysis, and 9 subgroups when using a two-stage approach. However, their prognostic capacity was unexplored. This study (i) determined whether the subgrouping approaches were associated with the future outcomes of pain intensity, pain frequency and disability, (ii) assessed whether one of these two approaches was more strongly or more consistently associated with these outcomes, and (iii) assessed the performance of the novel subgroupings as compared to the following variables: two existing subgrouping tools (STarT Back Tool and Quebec Task Force classification), four baseline characteristics and a group of previously identified domain-specific patient categorisations (collectively, the 'comparator variables'). This was a longitudinal cohort study of 928 patients consulting for low back pain in primary care. The associations between each subgroup approach and outcomes at 2 weeks, 3 and 12 months, and with weekly SMS responses were tested in linear regression models, and their prognostic capacity (variance explained) was compared to that of the comparator variables listed above. The two previously identified subgroupings were similarly associated with all outcomes. The prognostic capacity of both subgroupings was better than that of the comparator variables, except for participants' recovery beliefs and the domain-specific categorisations, but was still limited. The explained variance ranged from 4.3%-6.9% for pain intensity and

Childhood Liver Cancer Treatment (PDQ®)—Health Professional Version

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Childhood liver cancer has two major histologic subgroups: hepatoblastoma and hepatocellular carcinoma. Less common histologies are undifferentiated embryonal sarcoma of the liver, infantile choriocarcinoma, and vascular liver tumors. Get detailed information about newly diagnosed and recurrent childhood liver cancers including tumor biology, presentation, prognosis, staging, and treatment in this summary for clinicians.

Identification and prognostic value of anterior gradient protein 2 expression in breast cancer based on tissue microarray.

Science.gov (United States)

Guo, Jilong; Gong, Guohua; Zhang, Bin

2017-07-01

Breast cancer has attracted substantial attention as one of the major cancers causing death in women. It is crucial to find potential biomarkers of prognostic value in breast cancer. In this study, the expression pattern of anterior gradient protein 2 in breast cancer was identified based on the main molecular subgroups. Through analysis of 69 samples from the Gene Expression Omnibus database, we found that anterior gradient protein 2 expression was significantly higher in non-triple-negative breast cancer tissues compared with normal tissues and triple-negative breast cancer tissues (p gradient protein 2 expression pattern. Furthermore, we performed immunohistochemical analysis. The quantification results revealed that anterior gradient protein 2 is highly expressed in non-triple-negative breast cancer (grade 3 excluded) and grade 1 + 2 (triple-negative breast cancer excluded) tumours compared with normal tissues. Anterior gradient protein 2 was significantly highly expressed in non-triple-negative breast cancer (grade 3 excluded) and non-triple-negative breast cancer tissues compared with triple-negative breast cancer tissues (p gradient protein 2 was significantly highly expressed in grade 1 + 2 (triple-negative breast cancer excluded) and grade 1 + 2 tissues compared with grade 3 tissues (p gradient protein 2 expression was significantly associated with histologic type, histological grade, oestrogen status and progesterone status. Univariate analysis of clinicopathological variables showed that anterior gradient protein 2 expression, tumour size and lymph node status were significantly correlated with overall survival in patients with grade 1 and 2 tumours. Cox multivariate analysis revealed anterior gradient protein 2 as a putative independent indicator of unfavourable outcomes (p = 0.031). All these data clearly showed that anterior gradient protein 2 is highly expressed in breast cancer and can be regarded as a putative biomarker for

Development of gastric cancer in nonatrophic stomach with highly active inflammation identified by serum levels of pepsinogen and Helicobacter pylori antibody together with endoscopic rugal hyperplastic gastritis.

Science.gov (United States)

Watanabe, Mika; Kato, Jun; Inoue, Izumi; Yoshimura, Noriko; Yoshida, Takeichi; Mukoubayashi, Chizu; Deguchi, Hisanobu; Enomoto, Shotaro; Ueda, Kazuki; Maekita, Takao; Iguchi, Mikitaka; Tamai, Hideyuki; Utsunomiya, Hirotoshi; Yamamichi, Nobutake; Fujishiro, Mitsuhiro; Iwane, Masataka; Tekeshita, Tatsuya; Mohara, Osamu; Ushijima, Toshikazu; Ichinose, Masao

2012-12-01

This study aimed to elucidate groups at high risk of developing cancer among patients with serologically identified Helicobacter pylori infection and nonatrophic stomach. Annual endoscopy was performed for a mean of 5.4 years in 496 asymptomatic middle-aged men who were H. pylori antibody-positive and pepsinogen (PG) test-negative. Subjects were stratified according to the activity of H. pylori-associated gastritis measured by serum levels of PG and H. pylori antibody, and/or by endoscopic findings of rugal hyperplastic gastritis (RHG), and cancer development was investigated. During the study period, seven cases of cancer developed in the cohort (incidence rate, 261/100,000 person-years), with 85.7% developing in the group showing a PGI/II ratio ≤ 3.0, reflecting active inflammation-based high PGII levels. Cancer incidence was significantly higher in this group (750/100,000 person-years) than in groups with less active gastritis. Furthermore, cancer incidence for this group was significantly higher in the subgroup with high H. pylori antibody titers than in the low-titer subgroup. Meanwhile, endoscopic findings revealed that 11.7% of subjects showed RHG reflecting localized highly active inflammation, and cancer risk was significantly higher in patients with RHG than in patients without. Combining the two serum tests and endoscopic examination for RHG allowed identification of subjects with more active gastritis and higher cancer risk. No cancer development was observed in these high-risk subjects after H. pylori eradication. Subjects with highly active gastritis identified by the two serological tests and endoscopic RHG constitute a group at high risk of cancer development with H. pylori-infected nonatrophic stomach. Copyright © 2012 UICC.

A Landscape of Therapeutic Cooperativity in KRAS Mutant Cancers Reveals Principles for Controlling Tumor Evolution

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Grace R. Anderson

2017-07-01

Full Text Available Combinatorial inhibition of effector and feedback pathways is a promising treatment strategy for KRAS mutant cancers. However, the particular pathways that should be targeted to optimize therapeutic responses are unclear. Using CRISPR/Cas9, we systematically mapped the pathways whose inhibition cooperates with drugs targeting the KRAS effectors MEK, ERK, and PI3K. By performing 70 screens in models of KRAS mutant colorectal, lung, ovarian, and pancreas cancers, we uncovered universal and tissue-specific sensitizing combinations involving inhibitors of cell cycle, metabolism, growth signaling, chromatin regulation, and transcription. Furthermore, these screens revealed secondary genetic modifiers of sensitivity, yielding a SRC inhibitor-based combination therapy for KRAS/PIK3CA double-mutant colorectal cancers (CRCs with clinical potential. Surprisingly, acquired resistance to combinations of growth signaling pathway inhibitors develops rapidly following treatment, but by targeting signaling feedback or apoptotic priming, it is possible to construct three-drug combinations that greatly delay its emergence.

Type 2 diabetes: identifying high risk Asian American subgroups in a clinical population.

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Wang, Elsie J; Wong, Eric C; Dixit, Anjali A; Fortmann, Stephen P; Linde, Randolph B; Palaniappan, Latha P

2011-08-01

We compared the prevalence and treatment of type 2 diabetes across Asian American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and Non-Hispanic Whites (NHWs) in a Northern California healthcare system. A three-year, cross-sectional sample of patient electronic health records was accessed to compare diabetes prevalence in 21,816 Asian and 73,728 NHWs aged 35+ years. Diabetes was classified through ICD-9 codes, abnormal laboratory values, or use of oral anti-diabetic medication. Multivariate adjusted prevalence rates for each Asian subgroup, and adjusted odds ratios (OR) relative to NHWs, were compared. Age-adjusted prevalence ranged from 5.8% to 18.2% (women) and 8.1 to 25.3% (men). Age-adjusted ORs of Asian subgroups ranged 1.11-3.94 (women) and 1.14-4.56 (men). The odds of diabetes were significantly higher in Asian Indians (women OR 3.44, men OR 3.54) and Filipinos (women OR 3.94, men OR 4.56), compared to NHWs. Results for Asian Indians and Filipinos were similar with age-and-BMI adjustment. Treatment rates across subgroups were 59.7-82.0% (women) and 62.9-79.4% (men). Heterogeneity exists in the prevalence of diabetes across Asian subgroups, independent of obesity prevalence. Asian Indian and Filipino subgroups had particularly high prevalence of diabetes when compared to NHWs. Future studies should explore these clinically important differences among Asian subgroups. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Geographic Variations in Cardiovascular Disease Mortality Among Asian American Subgroups, 2003-2011.

Science.gov (United States)

Pu, Jia; Hastings, Katherine G; Boothroyd, Derek; Jose, Powell O; Chung, Sukyung; Shah, Janki B; Cullen, Mark R; Palaniappan, Latha P; Rehkopf, David H

2017-07-12

There are well-documented geographical differences in cardiovascular disease (CVD) mortality for non-Hispanic whites. However, it remains unknown whether similar geographical variation in CVD mortality exists for Asian American subgroups. This study aims to examine geographical differences in CVD mortality among Asian American subgroups living in the United States and whether they are consistent with geographical differences observed among non-Hispanic whites. Using US death records from 2003 to 2011 (n=3 897 040 CVD deaths), age-adjusted CVD mortality rates per 100 000 population and age-adjusted mortality rate ratios were calculated for the 6 largest Asian American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, and Vietnamese) and compared with non-Hispanic whites. There were consistently lower mortality rates for all Asian American subgroups compared with non-Hispanic whites across divisions for CVD mortality and ischemic heart disease mortality. However, cerebrovascular disease mortality demonstrated substantial geographical differences by Asian American subgroup. There were a number of regional divisions where certain Asian American subgroups (Filipino and Japanese men, Korean and Vietnamese men and women) possessed no mortality advantage compared with non-Hispanic whites. The most striking geographical variation was with Filipino men (age-adjusted mortality rate ratio=1.18; 95% CI, 1.14-1.24) and Japanese men (age-adjusted mortality rate ratio=1.05; 95% CI: 1.00-1.11) in the Pacific division who had significantly higher cerebrovascular mortality than non-Hispanic whites. There was substantial geographical variation in Asian American subgroup mortality for cerebrovascular disease when compared with non-Hispanic whites. It deserves increased attention to prioritize prevention and treatment in the Pacific division where approximately 80% of Filipinos CVD deaths and 90% of Japanese CVD deaths occur in the United States. © 2017 The Authors

Progressive Amalgamation of Building Clusters for Map Generalization Based on Scaling Subgroups

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Xianjin He

2018-03-01

Full Text Available Map generalization utilizes transformation operations to derive smaller-scale maps from larger-scale maps, and is a key procedure for the modelling and understanding of geographic space. Studies to date have largely applied a fixed tolerance to aggregate clustered buildings into a single object, resulting in the loss of details that meet cartographic constraints and may be of importance for users. This study aims to develop a method that amalgamates clustered buildings gradually without significant modification of geometry, while preserving the map details as much as possible under cartographic constraints. The amalgamation process consists of three key steps. First, individual buildings are grouped into distinct clusters by using the graph-based spatial clustering application with random forest (GSCARF method. Second, building clusters are decomposed into scaling subgroups according to homogeneity with regard to the mean distance of subgroups. Thus, hierarchies of building clusters can be derived based on scaling subgroups. Finally, an amalgamation operation is progressively performed from the bottom-level subgroups to the top-level subgroups using the maximum distance of each subgroup as the amalgamating tolerance instead of using a fixed tolerance. As a consequence of this step, generalized intermediate scaling results are available, which can form the multi-scale representation of buildings. The experimental results show that the proposed method can generate amalgams with correct details, statistical area balance and orthogonal shape while satisfying cartographic constraints (e.g., minimum distance and minimum area.

Prognostic value of PLR in various cancers: a meta-analysis.

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Xin Zhou

Full Text Available BACKGROUND: Recently, more and more studies investigated the association of inflammation parameters such as the Platelet Lymphocyte Ratio (PLR and the prognosis of various cancers. However, the prognostic role of PLR in cancer remains controversial. METHODS: We conducted a meta-analysis of published studies to evaluate the prognostic value of PLR in various cancers. In order to investigate the association between PLR and overall survival (OS, the hazard ratio (HR and its 95% confidence interval (CI were calculated. RESULTS: A total of 13,964 patients from 26 studies were included in the analysis. The summary results showed that elevated PLR was a negative predictor for OS with HR of 1.60 (95%CI: 1.35-1.90; Pheterogeneity <0.001. Subgroup analysis revealed that increased PLR was a negative prognostic marker in patients with gastric cancer (HR = 1.35, 95%CI: 0.80-2.25, Pheterogeneity = 0.011, colorectal cancer (HR = 1.65, 95%CI: 1.33-2.05, Pheterogeneity = 0.995, hepatocellular carcinoma (HR = 3.07, 95% CI: 2.04-4.62, Pheterogeneity = 0.133, ovarian cancer (HR = 1.57, 95%CI: 1.07-2.31, Pheterogeneity = 0.641 and non-small cell lung cancer (NSCLC (HR = 1.85, 95% CI: 1.42-2.41, Pheterogeneity = 0.451 except for pancreatic cancer (HR = 1.00, 95%CI: 0.92-1.09, Pheterogeneity = 0.388. CONCLUSION: The meta-analysis demonstrated that PLR could act as a significant biomarker in the prognosis of various cancers.

A Systems-Level Analysis Reveals Circadian Regulation of Splicing in Colorectal Cancer.

Science.gov (United States)

El-Athman, Rukeia; Fuhr, Luise; Relógio, Angela

2018-06-20

Accumulating evidence points to a significant role of the circadian clock in the regulation of splicing in various organisms, including mammals. Both dysregulated circadian rhythms and aberrant pre-mRNA splicing are frequently implicated in human disease, in particular in cancer. To investigate the role of the circadian clock in the regulation of splicing in a cancer progression context at the systems-level, we conducted a genome-wide analysis and compared the rhythmic transcriptional profiles of colon carcinoma cell lines SW480 and SW620, derived from primary and metastatic sites of the same patient, respectively. We identified spliceosome components and splicing factors with cell-specific circadian expression patterns including SRSF1, HNRNPLL, ESRP1, and RBM 8A, as well as altered alternative splicing events and circadian alternative splicing patterns of output genes (e.g., VEGFA, NCAM1, FGFR2, CD44) in our cellular model. Our data reveals a remarkable interplay between the circadian clock and pre-mRNA splicing with putative consequences in tumor progression and metastasis. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Differential diagnosis of feline leukemia virus subgroups using pseudotype viruses expressing green fluorescent protein.

Science.gov (United States)

Nakamura, Megumi; Sato, Eiji; Miura, Tomoyuki; Baba, Kenji; Shimoda, Tetsuya; Miyazawa, Takayuki

2010-06-01

Feline leukemia virus (FeLV) is classified into three receptor interference subgroups, A, B and C. In this study, to differentiate FeLV subgroups, we developed a simple assay system using pseudotype viruses expressing green fluorescent protein (GFP). We prepared gfp pseudotype viruses, named gfp(FeLV-A), gfp(FeLV-B) and gfp(FeLV-C) harboring envelopes of FeLV-A, B and C, respectively. The gfp pseudotype viruses completely interfered with the same subgroups of FeLV reference strains on FEA cells (a feline embryonic fibroblast cell line). We also confirmed that the pseudotype viruses could differentiate FeLV subgroups in field isolates. The assay will be useful for differential diagnosis of FeLV subgroups in veterinary diagnostic laboratories in the future.

Intra-Tumour Signalling Entropy Determines Clinical Outcome in Breast and Lung Cancer

Science.gov (United States)

Banerji, Christopher R. S.; Severini, Simone; Caldas, Carlos; Teschendorff, Andrew E.

2015-01-01

The cancer stem cell hypothesis, that a small population of tumour cells are responsible for tumorigenesis and cancer progression, is becoming widely accepted and recent evidence has suggested a prognostic and predictive role for such cells. Intra-tumour heterogeneity, the diversity of the cancer cell population within the tumour of an individual patient, is related to cancer stem cells and is also considered a potential prognostic indicator in oncology. The measurement of cancer stem cell abundance and intra-tumour heterogeneity in a clinically relevant manner however, currently presents a challenge. Here we propose signalling entropy, a measure of signalling pathway promiscuity derived from a sample’s genome-wide gene expression profile, as an estimate of the stemness of a tumour sample. By considering over 500 mixtures of diverse cellular expression profiles, we reveal that signalling entropy also associates with intra-tumour heterogeneity. By analysing 3668 breast cancer and 1692 lung adenocarcinoma samples, we further demonstrate that signalling entropy correlates negatively with survival, outperforming leading clinical gene expression based prognostic tools. Signalling entropy is found to be a general prognostic measure, valid in different breast cancer clinical subgroups, as well as within stage I lung adenocarcinoma. We find that its prognostic power is driven by genes involved in cancer stem cells and treatment resistance. In summary, by approximating both stemness and intra-tumour heterogeneity, signalling entropy provides a powerful prognostic measure across different epithelial cancers. PMID:25793737

Intra-tumour signalling entropy determines clinical outcome in breast and lung cancer.

Directory of Open Access Journals (Sweden)

Christopher R S Banerji

2015-03-01

Full Text Available The cancer stem cell hypothesis, that a small population of tumour cells are responsible for tumorigenesis and cancer progression, is becoming widely accepted and recent evidence has suggested a prognostic and predictive role for such cells. Intra-tumour heterogeneity, the diversity of the cancer cell population within the tumour of an individual patient, is related to cancer stem cells and is also considered a potential prognostic indicator in oncology. The measurement of cancer stem cell abundance and intra-tumour heterogeneity in a clinically relevant manner however, currently presents a challenge. Here we propose signalling entropy, a measure of signalling pathway promiscuity derived from a sample's genome-wide gene expression profile, as an estimate of the stemness of a tumour sample. By considering over 500 mixtures of diverse cellular expression profiles, we reveal that signalling entropy also associates with intra-tumour heterogeneity. By analysing 3668 breast cancer and 1692 lung adenocarcinoma samples, we further demonstrate that signalling entropy correlates negatively with survival, outperforming leading clinical gene expression based prognostic tools. Signalling entropy is found to be a general prognostic measure, valid in different breast cancer clinical subgroups, as well as within stage I lung adenocarcinoma. We find that its prognostic power is driven by genes involved in cancer stem cells and treatment resistance. In summary, by approximating both stemness and intra-tumour heterogeneity, signalling entropy provides a powerful prognostic measure across different epithelial cancers.

Interpretation of Subgroup Effects in Published Trials

DEFF Research Database (Denmark)

Hancock, Mark J; Kjær, Per; Korsholm, Lars

2013-01-01

With the rapidly expanding number of studies reporting on treatment subgroups come new challenges in analyzing and interpreting this sometimes complex area of the literature. This article discusses 3 important issues regarding the analysis and interpretation of existing trials or systematic revie...

Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and EINSTEIN-PE): a pooled subgroup analysis of two randomised controlled trials.

Science.gov (United States)

Prins, Martin H; Lensing, Anthonie W A; Brighton, Tim A; Lyons, Roger M; Rehm, Jeffrey; Trajanovic, Mila; Davidson, Bruce L; Beyer-Westendorf, Jan; Pap, Ákos F; Berkowitz, Scott D; Cohen, Alexander T; Kovacs, Michael J; Wells, Philip S; Prandoni, Paolo

2014-10-01

Patients with venous thromboembolism and cancer have a substantial risk of recurrent venous thromboembolism and bleeding during anticoagulant therapy. Although monotherapy with low-molecular-weight heparin is recommended in these patients, in clinical practice many patients with venous thromboembolism and cancer do not receive this treatment. We aimed to assess the efficacy and safety of a single-drug regimen with oral rivaroxaban compared with enoxaparin followed by vitamin K antagonists, in the subgroup of patients with cancer enrolled in the EINSTEIN-DVT and EINSTEIN-PE randomised controlled trials. We did a subgroup analysis of patients with active cancer (either at baseline or diagnosed during the study), a history of cancer, or no cancer who were enrolled in the EINSTEIN-DVT and EINSTEIN-PE trials. Eligible patients with deep-vein thrombosis (EINSTEIN-DVT) or pulmonary embolism (EINSTEIN-PE) were randomly assigned in a 1:1 ratio to receive rivaroxaban (15 mg twice daily for 21 days, followed by 20 mg once daily) or standard therapy (enoxaparin 1·0 mg/kg twice daily and warfarin or acenocoumarol; international normalised ratio 2·0-3·0). Randomisation with a computerised voice-response system was stratified according to country and intended treatment duration (3, 6, or 12 months). The prespecified primary efficacy and safety outcomes of both the trials and this subanalysis were symptomatic recurrent venous thromboembolism and clinically relevant bleeding, respectively. We did efficacy and mortality analyses in the intention-to-treat population, and bleeding analyses for time spent receiving treatment plus 2 days in the safety population (all patients who received at least one dose of study drug). The EINSTEIN-DVT and EINSTEIN-PE studies are registered at ClinicalTrials.gov, numbers NCT00440193 and NCT00439777. In patients with active cancer (diagnosed at baseline or during treatment), recurrent venous thromboembolism occurred in 16 (5%) of 354 patients

Use of next-generation sequencing in oral cavity cancer

DEFF Research Database (Denmark)

Tabatabaeifar, Siavosh; Kruse, Torben A; Thomassen, Mads

Background: Oral cavity cancer is a subgroup of head and neck cancer which is the world’s 6th most common cancer form. Oral squamous cell carcinomas (OSCC) constitute almost all oral cavity cancers, and OSCC are primarily attributed by excessive alcohol consumption and tobacco exposure...... of tumour cells exists. Conclusions: Use of next generation sequencing in oral cavity cancer can give valuable insight into the biology of the disease. By investigating intra tumour heterogeneity we see that the different tumour specimens in each patient are quite homogenous, but evidence of heterogeneous...

Intergroup Leadership Across Distinct Subgroups and Identities.

Science.gov (United States)

Rast, David E; Hogg, Michael A; van Knippenberg, Daan

2018-03-01

Resolving intergroup conflict is a significant and often arduous leadership challenge, yet existing theory and research rarely, if ever, discuss or examine this situation. Leaders confront a significant challenge when they provide leadership across deep divisions between distinct subgroups defined by self-contained identities-The challenge is to avoid provoking subgroup identity distinctiveness threat. Drawing on intergroup leadership theory, three studies were conducted to test the core hypothesis that, where identity threat exists, leaders promoting an intergroup relational identity will be better evaluated and are more effective than leaders promoting a collective identity; in the absence of threat, leaders promoting a collective identity will prevail. Studies 1 and 2 ( N = 170; N = 120) supported this general proposition. Study 3 ( N = 136) extended these findings, showing that leaders promoting an intergroup relational identity, but not a collective identity, improved intergroup attitudes when participants experienced an identity distinctiveness threat.

Cross-species epigenetics identifies a critical role for VAV1 in SHH subgroup medulloblastoma maintenance.

Science.gov (United States)

Lindsey, J C; Kawauchi, D; Schwalbe, E C; Solecki, D J; Selby, M P; McKinnon, P J; Olson, J M; Hayden, J T; Grundy, R G; Ellison, D W; Williamson, D; Bailey, S; Roussel, M F; Clifford, S C

2015-09-03

The identification of key tumorigenic events in Sonic Hedgehog (SHH) subgroup medulloblastomas (MBSHH) will be essential for the development of individualized therapies and improved outcomes. However, beyond confirmation of characteristic SHH pathway mutations, recent genome-wide sequencing studies have not revealed commonly mutated genes with widespread relevance as potential therapeutic targets. We therefore examined any role for epigenetic DNA methylation events in MBSHH using a cross-species approach to candidate identification, prioritization and validation. MBSHH-associated DNA methylation events were first identified in 216 subgrouped human medulloblastomas (50 MBSHH, 28 Wnt/Wingless, 44 Group 3 and 94 Group 4) and their conservation then assessed in tumors arising from four independent murine models of Shh medulloblastoma, alongside any role in tumorigenesis using functional assessments in mouse and human models. This strategy identified widespread regional CpG hypo-methylation of VAV1, leading to its elevated expression, as a conserved aberrant epigenetic event, which characterizes the majority of MBSHH tumors in both species, and is associated with a poor outcome in MBSHH patients. Moreover, direct modulation of VAV1 in mouse and human models revealed a critical role in tumor maintenance, and its abrogation markedly reduced medulloblastoma growth. Further, Vav1 activity regulated granule neuron precursor germinal zone exit and migration initiation in an ex vivo model of early postnatal cerebellar development. These findings establish VAV1 as a critical epigenetically regulated oncogene with a key role in MBSHH maintenance, and highlight its potential as a validated therapeutic target and prognostic biomarker for the improved therapy of medulloblastoma.

Genetic analysis of the vitamin D receptor gene in two epithelial cancers: melanoma and breast cancer case-control studies

International Nuclear Information System (INIS)

Barroso, Eva; Arias, Jose I; Zamora, Pilar; Blanco, Monserrat; Lazaro, Pablo; Benitez, Javier; Ribas, Gloria; Fernandez, Lara P; Milne, Roger L; Pita, Guillermo; Sendagorta, Elena; Floristan, Uxua; Feito, Marta; Aviles, Jose A; Martin-Gonzalez, Manuel

2008-01-01

Vitamin D serum levels have been found to be related to sun exposure and diet, together with cell differentiation, growth control and consequently, cancer risk. Vitamin D receptor (VDR) genotypes may influence cancer risk; however, no epidemiological studies in sporadic breast cancer (BC) or malignant melanoma (MM) have been performed in a southern European population. In this study, the VDR gene has been evaluated in two epithelial cancers BC and MM. We have conducted an analysis in 549 consecutive and non-related sporadic BC cases and 556 controls, all from the Spanish population, and 283 MM cases and 245 controls. Genotyping analyses were carried out on four putatively functional SNPs within the VDR gene. An association with the minor allele A of the non-synonymous SNP rs2228570 (rs10735810, FokI, Met1Thr) was observed for BC, with an estimated odds ratio (OR) of 1.26 (95% CI = 1.02–1.57; p = 0.036). The synonymous variant rs731236 (TaqI) appeared to be associated with protection from BC (OR = 0.80, 95%CI = 0.64–0.99; p = 0.047). No statistically significant associations with MM were observed for any SNP. Nevertheless, sub-group analyses revealed an association between rs2228570 (FokI) and absence of childhood sunburns (OR = 0.65, p = 0.003), between the 3'utr SNP rs739837 (BglI) and fair skin (OR = 1.31, p = 0.048), and between the promoter SNP rs4516035 and the more aggressive tumour location in head-neck and trunk (OR = 1.54, p = 0.020). In summary, we observed associations between SNPs in the VDR gene and BC risk, and a comprehensive analysis using clinical and tumour characteristics as outcome variables has revealed potential associations with MM. These associations required confirmation in independent studies

Mitochondrial dysfunction and risk of cancer

DEFF Research Database (Denmark)

Lund, M; Melbye, M; Diaz, L J

2015-01-01

matrilineal relatives to a cohort member with a genetically confirmed maternally inherited mDNA mutation. Information on cancer was obtained by linkage to the Danish Cancer Register. Standardised incidence ratios (SIRs) were used to assess the relative risk of cancer. RESULTS: During 7334 person......-years of follow-up, 19 subjects developed a primary cancer. The corresponding SIR for any primary cancer was 1.06 (95% confidence interval 0.68-1.63). Subgroup analyses according to mutational subtype yielded similar results, for example, a SIR of 0.94 (95% CI 0.53 to 1.67) for the m.3243A>G maternally inherited...... mDNA mutation, cases=13. CONCLUSIONS: Patients with mitochondrial dysfunction do not appear to be at increased risk of cancer compared with the general population....

Controversies in breast cancer: adjuvant and neoadjuvant therapy.

Science.gov (United States)

Montemurro, Filippo; Redana, Stefania; Valabrega, Giorgio; Aglietta, Massimo

2005-06-01

Initial randomised studies of chemotherapy and endocrine therapy showed that systemic treatments had a substantial impact on the survival of women with early breast cancer. The original assumption was that the efficacy of these treatments was limited to those patients presenting with more adverse prognostic features. Subsequently, meta-analyses of randomised trials revealed that the benefits of chemotherapy and endocrine therapy are not mutually exclusive and extend to all the prognostic subgroups. However, the absolute benefit varies according to baseline characteristics such as tumour stage and other biological factors. Over the last 10 years, considerable progress has been made with the introduction of new drugs into the adjuvant and neoadjuvant treatment of women with breast cancer. Taxanes and third-generation aromatase inhibitors are providing proof of additional benefits compared with standard reference treatments. In parallel, research on the biology of breast cancer is establishing novel prognostic and predictive factors, which may allow better treatment tailoring. Currently, however, women with early breast cancer and their doctors face the difficult task of making therapeutic decisions often based on early results from positive studies. In a disease where follow up is crucial to fully assess the benefit and long-term toxicities of an intervention, current knowledge leaves unanswered questions that generate debate and controversy. This review will summarise recent results from randomised trials of adjuvant and neoadjuvant therapy in women with early breast cancer and focus on the current controversies.

Identification of colonic fibroblast secretomes reveals secretory factors regulating colon cancer cell proliferation.

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Chen, Sun-Xia; Xu, Xiao-En; Wang, Xiao-Qing; Cui, Shu-Jian; Xu, Lei-Lei; Jiang, Ying-Hua; Zhang, Yang; Yan, Hai-Bo; Zhang, Qian; Qiao, Jie; Yang, Peng-Yuan; Liu, Feng

2014-10-14

Stromal microenvironment influences tumor cell proliferation and migration. Fibroblasts represent the most abundant stromal constituents. Here, we established two pairs of normal fibroblast (NF) and cancer-associated fibroblast (CAF) cultures from colorectal adenocarcinoma tissues and the normal counterparts. The NFs and CAFs were stained positive for typical fibroblast markers and inhibited colon cancer (CC) cell proliferation in in vitro cocultures and in xenograft mouse models. The fibroblast conditioned media were analyzed using LC-MS and 227 proteins were identified at a false discovery rate of 1.3%, including 131 putative secretory and 20 plasma membrane proteins. These proteins were enriched for functional categories of extracellular matrix, adhesion, cell motion, inflammatory response, redox homeostasis and peptidase inhibitor. Secreted protein acidic and rich in cysteine, transgelin, follistatin-related protein 1 (FSTL1) and decorin was abundant in the fibroblast secretome as confirmed by Western blot. Silencing of FSTL1 and transgelin in colonic fibroblast cell line CCD-18Co induced an accelerated proliferation of CC cells in cocultures. Exogenous FSTL1 attenuates CC cell proliferation in a negative fashion. FSTL1 was upregulated in CC patient plasma and cancerous tissues but had no implication in prognosis. Our results provided novel insights into the molecular signatures and modulatory role of CC associated fibroblasts. In this study, a label-free LC-MS was performed to analyze the secretomes of two paired primary fibroblasts, which were isolated from fresh surgical specimen of colorectal adenocarcinoma and adjacent normal colonic tissues and exhibited negative modulatory activity for colon cancer cell growth in in vitro cocultures and in vivo xenograph mouse models. Follistatin-related protein 1 was further revealed to be one of the stroma-derived factors of potential suppression role for colon cancer cell proliferation. Our results provide novel

Life of Pizza Pie: The Implications of Sub-Group Comparisons in Education

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Thomas, Tara N.

2013-01-01

Current educational statistics have pitted subgroups against one another without consideration of the actual population sizes of each group. This paper is intended to provided a clearer understanding of the current usage of sub-group comparisons in American education. (Contains 4 figures.)

Mapping the HLA ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation.

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Löffler, Markus W; Kowalewski, Daniel J; Backert, Linus; Bernhardt, Jörg; Adam, Patrick; Schuster, Heiko; Dengler, Florian; Backes, Daniel; Kopp, Hans-Georg; Beckert, Stefan; Wagner, Silvia; Königsrainer, Ingmar; Kohlbacher, Oliver; Kanz, Lothar; Königsrainer, Alfred; Rammensee, Hans-Georg; Stevanovic, Stefan; Haen, Sebastian P

2018-05-22

Immune cell infiltrates have proven highly relevant for colorectal carcinoma (CRC) prognosis, making CRC a promising candidate for immunotherapy. Since tumors interact with the immune system via HLA-presented peptide ligands, exact knowledge of the peptidome constitution is fundamental for understanding this relationship. Here we comprehensively describe the naturally presented HLA-ligandome of CRC and corresponding non-malignant colon (NMC) tissue. Mass spectrometry identified 35,367 and 28,132 HLA-class I ligands on CRC and NMC, attributable to 7,684 and 6,312 distinct source proteins, respectively. Cancer-exclusive peptides were assessed on source protein level using Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein analysis through evolutionary relationships (PANTHER), revealing pathognomonic CRC-associated pathways including Wnt, TGF-β, PI3K, p53, and RTK-RAS. Relative quantitation of peptide presentation on paired CRC and NMC tissue further identified source proteins from cancer- and infection-associated pathways to be over-represented merely within the CRC ligandome. From the pool of tumor-exclusive peptides, a selected HLA-ligand subset was assessed for immunogenicity, with the majority exhibiting an existing T cell repertoire. Overall, these data show that the HLA-ligandome reflects cancer-associated pathways implicated in CRC oncogenesis, suggesting that alterations in tumor cell metabolism could result in cancer-specific, albeit not mutation-derived tumor-antigens. Hence, a defined pool of unique tumor peptides, attributable to complex cellular alterations that are exclusive to malignant cells might comprise promising candidates for immunotherapeutic applications. Copyright ©2018, American Association for Cancer Research.

The Role of Chromosomal Instability and Epigenetics in Colorectal Cancers Lacking β-Catenin/TCF Regulated Transcription

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Wael M. Abdel-Rahman

2016-01-01

Full Text Available All colorectal cancer cell lines except RKO displayed active β-catenin/TCF regulated transcription. This feature of RKO was noted in familial colon cancers; hence our aim was to dissect its carcinogenic mechanism. MFISH and CGH revealed distinct instability of chromosome structure in RKO. Gene expression microarray of RKO versus 7 colon cancer lines (with active Wnt signaling and 3 normal specimens revealed 611 differentially expressed genes. The majority of the tested gene loci were susceptible to LOH in primary tumors with various β-catenin localizations as a surrogate marker for β-catenin activation. The immunohistochemistry of selected genes (IFI16, RGS4, MCTP1, DGKI, OBCAM/OPCML, and GLIPR1 confirmed that they were differentially expressed in clinical specimens. Since epigenetic mechanisms can contribute to expression changes, selected target genes were evaluated for promoter methylation in patient specimens from sporadic and hereditary colorectal cancers. CMTM3, DGKI, and OPCML were frequently hypermethylated in both groups, whereas KLK10, EPCAM, and DLC1 displayed subgroup specificity. The overall fraction of hypermethylated genes was higher in tumors with membranous β-catenin. We identified novel genes in colorectal carcinogenesis that might be useful in personalized tumor profiling. Tumors with inactive Wnt signaling are a heterogeneous group displaying interaction of chromosomal instability, Wnt signaling, and epigenetics.

Interaction between body mass index and hormone-receptor status as a prognostic factor in lymph-node-positive breast cancer.

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Il Yong Chung

Full Text Available The aim of this study was to determine the relationship between the body mass index (BMI at a breast cancer diagnosis and various factors including the hormone-receptor, menopause, and lymph-node status, and identify if there is a specific patient subgroup for which the BMI has an effect on the breast cancer prognosis. We retrospectively analyzed the data of 8,742 patients with non-metastatic invasive breast cancer from the research database of Asan Medical Center. The overall survival (OS and breast-cancer-specific survival (BCSS outcomes were compared among BMI groups using the Kaplan-Meier method and Cox proportional-hazards regression models with an interaction term. There was a significant interaction between BMI and hormone-receptor status for the OS (P = 0.029, and BCSS (P = 0.013 in lymph-node-positive breast cancers. Obesity in hormone-receptor-positive breast cancer showed a poorer OS (adjusted hazard ratio [HR] = 1.51, 95% confidence interval [CI] = 0.92 to 2.48 and significantly poorer BCSS (HR = 1.80, 95% CI = 1.08 to 2.99. In contrast, a high BMI in hormone-receptor-negative breast cancer revealed a better OS (HR = 0.44, 95% CI = 0.16 to 1.19 and BCSS (HR = 0.53, 95% CI = 0.19 to 1.44. Being underweight (BMI < 18.50 kg/m2 with hormone-receptor-negative breast cancer was associated with a significantly worse OS (HR = 1.98, 95% CI = 1.00-3.95 and BCSS (HR = 2.24, 95% CI = 1.12-4.47. There was no significant interaction found between the BMI and hormone-receptor status in the lymph-node-negative setting, and BMI did not interact with the menopause status in any subgroup. In conclusion, BMI interacts with the hormone-receptor status in a lymph-node-positive setting, thereby playing a role in the prognosis of breast cancer.

Sexual quality of life, body image distress, and psychosocial outcomes in colorectal cancer: a longitudinal study.

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Reese, Jennifer Barsky; Handorf, Elizabeth; Haythornthwaite, Jennifer A

2018-04-20

The objectives were to assess changes in sexual QOL and body image distress over time and to examine longitudinal associations between sexual QOL and body image variables with psychosocial outcomes in a sample of colorectal cancer patients. Participants (N = 141) completed a mail-based survey assessing sexual QOL [sexual distress (ISS), treatment impact on sexual function (SFQ), sexual function (FSFI; IIEF)], body image distress (BIS), and psychosocial outcomes [relationship quality (DAS-4), depressive symptoms (CESD-SF), and health-related QOL (HRQOL; FACT-C)]; 88 patients completed 6-month follow-up surveys (62%). Gender and cancer subgroups (male vs. female; rectal vs. colon cancer) were compared and longitudinal models examined associations between sexual QOL and body image variables with psychosocial outcomes over time and by subgroup. Impairments in sexual QOL and body image distress were common. Women and patients with rectal cancer reported worse body image distress compared to men (p = .005) and those with colon cancer (p = .03), respectively; compared to patients with colon cancer, those with rectal cancer reported worse treatment impact (p image distress decreased (p = .02), while sexual QOL was stable (e.g., 58% classified as dysfunctional at both time points, p = .13). For most sexual and body image predictors, worse impairment was associated with worse psychosocial outcomes over time. Several significant gender and cancer subgroup effects were found. Sexual QOL and body image are compromised after colorectal cancer and tend to remain impaired if unaddressed. Sexual concerns should be addressed early to limit broader-reaching psychosocial effects.

Streptococcus pneumoniae PspC Subgroup Prevalence in Invasive Disease and Differences in Contribution to Complement Evasion.

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van der Maten, Erika; van den Broek, Bryan; de Jonge, Marien I; Rensen, Kim J W; Eleveld, Marc J; Zomer, Aldert L; Cremers, Amelieke J H; Ferwerda, Gerben; de Groot, Ronald; Langereis, Jeroen D; van der Flier, Michiel

2018-04-01

The pneumococcal capsular serotype is an important determinant of complement resistance and invasive disease potential, but other virulence factors have also been found to contribute. Pneumococcal surface protein C (PspC), a highly variable virulence protein that binds complement factor H to evade C3 opsonization, is divided into two subgroups: choline-bound subgroup I and LPxTG-anchored subgroup II. The prevalence of different PspC subgroups in invasive pneumococcal disease (IPD) and functional differences in complement evasion are unknown. The prevalence of PspC subgroups in IPD isolates was determined in a collection of 349 sequenced strains of Streptococcus pneumoniae isolated from adult patients. pspC deletion mutants and isogenic pspC switch mutants were constructed to study differences in factor H binding and complement evasion in relation to capsule thickness. Subgroup I pspC was far more prevalent in IPD isolates than subgroup II pspC The presence of capsule was associated with a greater ability of bound factor H to reduce complement opsonization. Pneumococcal subgroup I PspC bound significantly more factor H and showed more effective complement evasion than subgroup II PspC in isogenic encapsulated pneumococci. We conclude that variation in the PspC subgroups, independent of capsule serotypes, affects pneumococcal factor H binding and its ability to evade complement deposition. Copyright © 2018 American Society for Microbiology.

Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis.

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Thompson, Eric M; Hielscher, Thomas; Bouffet, Eric; Remke, Marc; Luu, Betty; Gururangan, Sridharan; McLendon, Roger E; Bigner, Darell D; Lipp, Eric S; Perreault, Sebastien; Cho, Yoon-Jae; Grant, Gerald; Kim, Seung-Ki; Lee, Ji Yeoun; Rao, Amulya A Nageswara; Giannini, Caterina; Li, Kay Ka Wai; Ng, Ho-Keung; Yao, Yu; Kumabe, Toshihiro; Tominaga, Teiji; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Low, David C Y; Seow, Wan Tew; Chang, Kenneth T E; Mora, Jaume; Pollack, Ian F; Hamilton, Ronald L; Leary, Sarah; Moore, Andrew S; Ingram, Wendy J; Hallahan, Andrew R; Jouvet, Anne; Fèvre-Montange, Michelle; Vasiljevic, Alexandre; Faure-Conter, Cecile; Shofuda, Tomoko; Kagawa, Naoki; Hashimoto, Naoya; Jabado, Nada; Weil, Alexander G; Gayden, Tenzin; Wataya, Takafumi; Shalaby, Tarek; Grotzer, Michael; Zitterbart, Karel; Sterba, Jaroslav; Kren, Leos; Hortobágyi, Tibor; Klekner, Almos; László, Bognár; Pócza, Tímea; Hauser, Peter; Schüller, Ulrich; Jung, Shin; Jang, Woo-Youl; French, Pim J; Kros, Johan M; van Veelen, Marie-Lise C; Massimi, Luca; Leonard, Jeffrey R; Rubin, Joshua B; Vibhakar, Rajeev; Chambless, Lola B; Cooper, Michael K; Thompson, Reid C; Faria, Claudia C; Carvalho, Alice; Nunes, Sofia; Pimentel, José; Fan, Xing; Muraszko, Karin M; López-Aguilar, Enrique; Lyden, David; Garzia, Livia; Shih, David J H; Kijima, Noriyuki; Schneider, Christian; Adamski, Jennifer; Northcott, Paul A; Kool, Marcel; Jones, David T W; Chan, Jennifer A; Nikolic, Ana; Garre, Maria Luisa; Van Meir, Erwin G; Osuka, Satoru; Olson, Jeffrey J; Jahangiri, Arman; Castro, Brandyn A; Gupta, Nalin; Weiss, William A; Moxon-Emre, Iska; Mabbott, Donald J; Lassaletta, Alvaro; Hawkins, Cynthia E; Tabori, Uri; Drake, James; Kulkarni, Abhaya; Dirks, Peter; Rutka, James T; Korshunov, Andrey; Pfister, Stefan M; Packer, Roger J; Ramaswamy, Vijay; Taylor, Michael D

2016-04-01

benefit for gross total resection compared with near-total resection (HR 1·05, 0·71-1·53, p=0·8158 for progression-free survival and HR 1·14, 0·75-1·72, p=0·55 for overall survival). No significant survival benefit existed for greater extent of resection for patients with WNT, SHH, or group 3 tumours (HR 1·03, 0·67-1·58, p=0·89 for sub-total resection vs gross total resection). For patients with group 4 tumours, gross total resection conferred a benefit to progression-free survival compared with sub-total resection (HR 1·97, 1·22-3·17, p=0·0056), especially for those with metastatic disease (HR 2·22, 1·00-4·93, p=0·050). However, gross total resection had no effect on overall survival compared with sub-total resection in patients with group 4 tumours (HR 1·67, 0·93-2·99, p=0·084). The prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. Although maximum safe surgical resection should remain the standard of care, surgical removal of small residual portions of medulloblastoma is not recommended when the likelihood of neurological morbidity is high because there is no definitive benefit to gross total resection compared with near-total resection. Canadian Cancer Society Research Institute, Terry Fox Research Institute, Canadian Institutes of Health Research, National Institutes of Health, Pediatric Brain Tumor Foundation, and the Garron Family Chair in Childhood Cancer Research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cholecystectomy can increase the risk of colorectal cancer: A meta-analysis of 10 cohort studies.

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Yong Zhang

Full Text Available This study aimed to elucidate the effects of cholecystectomy on the risk of colorectal cancer (CRC by conducting a meta-analysis of 10 cohort studies.The eligible cohort studies were selected by searching the PubMed and EMBASE databases from their origination to June 30, 2016, as well as by consulting the reference lists of the selected articles. Two authors individually collected the data from the 10 papers. When the data showed marked heterogeneity, we used a random-effects model to estimate the overall pooled risk; otherwise, a fixed effects model was employed.The final analysis included ten cohort studies. According to the Newcastle-Ottawa Scale (NOS, nine papers were considered high quality. After the data of these 9 studies were combined, an increased risk of CRC was found among the individuals who had undergone cholecystectomy (risk ratio (RR 1.22; 95% confidence interval (CI 1.08-1.38. In addition, we also found a promising increased risk for colon cancer (CC (RR 1.30, 95% CI 1.07-1.58, but no relationship between cholecystectomy and rectum cancer (RC (RR 1.09; 95% CI 0.89-1.34 was observed. Additionally, in the sub-group analysis of the tumor location in the colon, a positive risk for ascending colon cancer (ACC was found (RR 1.18, 95% CI 1.11-1.26. After combining the ACC, transverse colon cancer (TCC, sigmoid colon cancer (SCC and descending colon cancer (DCC patients, we found a positive relationship with cholecystectomy (RR 1.18, 95% CI 1.11-1.26. Furthermore, after combining the ACC and DCC patients, we also found a positive relationship with cholecystectomy (RR 1.28; 95% CI 1.11-1.26 in the sub-group analysis. In an additional sub-group analysis of patients from Western countries, there was a positive relationship between cholecystectomy and the risk of CRC (RR 1.20; 95% CI 1.05-1.36. Furthermore, a positive relationship between female gender and CRC was also found (RR 1.17; 95% CI 1.03-1.34. However, there was no relationship

Favorable response to doxorubicin combination chemotherapy does not yield good clinical outcome in patients with metastatic breast cancer with triple-negative phenotype

International Nuclear Information System (INIS)

Yi, Seong Yoon; Cho, Eun Yoon; La Choi, Yoon; Park, Yeon Hee; Im, Young-Hyuck; Ahn, Jin Seok; Uhm, Ji Eun; Lim, Do Hyoung; Ji, Sang Hoon; Jun, Hyun Jung; Kim, Kyoung Ha; Chang, Myung Hee; Park, Min Jae

2010-01-01

We analyzed the responses to first line treatment and clinical outcomes of metastatic breast cancer patients treated with palliative doxorubicin/cyclophosphamide (AC) according to molecular cancer subtype. A retrospective analysis was performed for 110 metastatic breast cancer patients selected on the basis of palliative AC treatment and the availability of immunohistochemical data for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2/neu) status. Of the 110 patients analyzed, 71 (64.5%) were hormone receptor positive (HR+), 14 (12.7%) were HER2+, and 25 (22.7%) were triple negative (TN). There were no differences in age, stage at diagnosis, total number of cycles of palliative chemotherapy, incidence of visceral metastasis, and metastatic sites with the exception of liver among breast cancer subtypes. The overall response rates to AC were 55.9% for the HR+ subgroup, 42.9% for the HER2+ subgroup, and 56.5% for the TN subgroup. The progression-free survival (PFS) in patients with HER2+ and TN were significantly shorter than in the HR+ (median PFS, 9.1 vs 8.1 vs 11.5 months, respectively; p = 0.0002). The overall survival (OS) was 25.4 months in the TN subgroup and 27.3 months in HER2+ subgroup. The median OS for these two groups was significantly shorter than for patients in the HR+ subgroup (median, 38.5 months; 95% CI, 30.1-46.9 months; p < 0.0001). The response to palliative AC chemotherapy did not differ among breast cancer subtypes. Despite chemosensitivity for palliative AC, the TN subtype has a shorter overall survival than non-TN subtypes. Innovative treatment strategies should be developed to slow the course of disease

Favorable response to doxorubicin combination chemotherapy does not yield good clinical outcome in patients with metastatic breast cancer with triple-negative phenotype

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La Choi Yoon

2010-10-01

Full Text Available Abstract Background We analyzed the responses to first line treatment and clinical outcomes of metastatic breast cancer patients treated with palliative doxorubicin/cyclophosphamide (AC according to molecular cancer subtype. Methods A retrospective analysis was performed for 110 metastatic breast cancer patients selected on the basis of palliative AC treatment and the availability of immunohistochemical data for estrogen receptor (ER, progesterone receptor (PR, and human epidermal growth factor receptor-2 (HER-2/neu status. Results Of the 110 patients analyzed, 71 (64.5% were hormone receptor positive (HR+, 14 (12.7% were HER2+, and 25 (22.7% were triple negative (TN. There were no differences in age, stage at diagnosis, total number of cycles of palliative chemotherapy, incidence of visceral metastasis, and metastatic sites with the exception of liver among breast cancer subtypes. The overall response rates to AC were 55.9% for the HR+ subgroup, 42.9% for the HER2+ subgroup, and 56.5% for the TN subgroup. The progression-free survival (PFS in patients with HER2+ and TN were significantly shorter than in the HR+ (median PFS, 9.1 vs 8.1 vs 11.5 months, respectively; p = 0.0002. The overall survival (OS was 25.4 months in the TN subgroup and 27.3 months in HER2+ subgroup. The median OS for these two groups was significantly shorter than for patients in the HR+ subgroup (median, 38.5 months; 95% CI, 30.1-46.9 months; p Conclusions The response to palliative AC chemotherapy did not differ among breast cancer subtypes. Despite chemosensitivity for palliative AC, the TN subtype has a shorter overall survival than non-TN subtypes. Innovative treatment strategies should be developed to slow the course of disease.

Radiation-induced breast cancer

International Nuclear Information System (INIS)

Finnerty, N.A.; Buzdar, A.U.; Blumenschein, G.R.

1984-01-01

Between 1975 and 1983, sixteen patients with a history of irradiation at an early age to the head, neck, or chest areas for a variety of conditions in whom breast cancer subsequently developed were seen at out institute. The median latent period between the irradiation and the development of breast cancer was 420 months. The distribution of patients by stage of the disease and the median age at diagnosis of this subgroup was similar to the breast cancer observed in the general population. The subsequent course of this disease was also similar to the breast cancer observed in the general population. A substantial number of women have been exposed to irradiation at a young age, and these women are at a higher risk of having breast cancer develop. These women should be closely observed to discover the disease in an early curable stage

The interest of gait markers in the identification of subgroups among fibromyalgia patients.

Science.gov (United States)

Auvinet, Bernard; Chaleil, Denis; Cabane, Jean; Dumolard, Anne; Hatron, Pierre; Juvin, Robert; Lanteri-Minet, Michel; Mainguy, Yves; Negre-Pages, Laurence; Pillard, Fabien; Riviere, Daniel; Maugars, Yves-Michel

2011-11-11

Fibromyalgia (FM) is a heterogeneous syndrome and its classification into subgroups calls for broad-based discussion. FM subgrouping, which aims to adapt treatment according to different subgroups, relies in part, on psychological and cognitive dysfunctions. Since motor control of gait is closely related to cognitive function, we hypothesized that gait markers could be of interest in the identification of FM patients' subgroups. This controlled study aimed at characterizing gait disorders in FM, and subgrouping FM patients according to gait markers such as stride frequency (SF), stride regularity (SR), and cranio-caudal power (CCP) which measures kinesia. A multicentre, observational open trial enrolled patients with primary FM (44.1 ± 8.1 y), and matched controls (44.1 ± 7.3 y). Outcome measurements and gait analyses were available for 52 pairs. A 3-step statistical analysis was carried out. A preliminary single blind analysis using k-means cluster was performed as an initial validation of gait markers. Then in order to quantify FM patients according to psychometric and gait variables an open descriptive analysis comparing patients and controls were made, and correlations between gait variables and main outcomes were calculated. Finally using cluster analysis, we described subgroups for each gait variable and looked for significant differences in self-reported assessments. SF was the most discriminating gait variable (73% of patients and controls). SF, SR, and CCP were different between patients and controls. There was a non-significant association between SF, FIQ and physical components from Short-Form 36 (p = 0.06). SR was correlated to FIQ (p = 0.01) and catastrophizing (p = 0.05) while CCP was correlated to pain (p = 0.01). The SF cluster identified 3 subgroups with a particular one characterized by normal SF, low pain, high activity and hyperkinesia. The SR cluster identified 2 distinct subgroups: the one with a reduced SR was distinguished by high FIQ

The interest of gait markers in the identification of subgroups among fibromyalgia patients

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Auvinet Bernard

2011-11-01

Full Text Available Abstract Background Fibromyalgia (FM is a heterogeneous syndrome and its classification into subgroups calls for broad-based discussion. FM subgrouping, which aims to adapt treatment according to different subgroups, relies in part, on psychological and cognitive dysfunctions. Since motor control of gait is closely related to cognitive function, we hypothesized that gait markers could be of interest in the identification of FM patients' subgroups. This controlled study aimed at characterizing gait disorders in FM, and subgrouping FM patients according to gait markers such as stride frequency (SF, stride regularity (SR, and cranio-caudal power (CCP which measures kinesia. Methods A multicentre, observational open trial enrolled patients with primary FM (44.1 ± 8.1 y, and matched controls (44.1 ± 7.3 y. Outcome measurements and gait analyses were available for 52 pairs. A 3-step statistical analysis was carried out. A preliminary single blind analysis using k-means cluster was performed as an initial validation of gait markers. Then in order to quantify FM patients according to psychometric and gait variables an open descriptive analysis comparing patients and controls were made, and correlations between gait variables and main outcomes were calculated. Finally using cluster analysis, we described subgroups for each gait variable and looked for significant differences in self-reported assessments. Results SF was the most discriminating gait variable (73% of patients and controls. SF, SR, and CCP were different between patients and controls. There was a non-significant association between SF, FIQ and physical components from Short-Form 36 (p = 0.06. SR was correlated to FIQ (p = 0.01 and catastrophizing (p = 0.05 while CCP was correlated to pain (p = 0.01. The SF cluster identified 3 subgroups with a particular one characterized by normal SF, low pain, high activity and hyperkinesia. The SR cluster identified 2 distinct subgroups: the one with a

The interest of gait markers in the identification of subgroups among fibromyalgia patients

Science.gov (United States)

2011-01-01

Background Fibromyalgia (FM) is a heterogeneous syndrome and its classification into subgroups calls for broad-based discussion. FM subgrouping, which aims to adapt treatment according to different subgroups, relies in part, on psychological and cognitive dysfunctions. Since motor control of gait is closely related to cognitive function, we hypothesized that gait markers could be of interest in the identification of FM patients' subgroups. This controlled study aimed at characterizing gait disorders in FM, and subgrouping FM patients according to gait markers such as stride frequency (SF), stride regularity (SR), and cranio-caudal power (CCP) which measures kinesia. Methods A multicentre, observational open trial enrolled patients with primary FM (44.1 ± 8.1 y), and matched controls (44.1 ± 7.3 y). Outcome measurements and gait analyses were available for 52 pairs. A 3-step statistical analysis was carried out. A preliminary single blind analysis using k-means cluster was performed as an initial validation of gait markers. Then in order to quantify FM patients according to psychometric and gait variables an open descriptive analysis comparing patients and controls were made, and correlations between gait variables and main outcomes were calculated. Finally using cluster analysis, we described subgroups for each gait variable and looked for significant differences in self-reported assessments. Results SF was the most discriminating gait variable (73% of patients and controls). SF, SR, and CCP were different between patients and controls. There was a non-significant association between SF, FIQ and physical components from Short-Form 36 (p = 0.06). SR was correlated to FIQ (p = 0.01) and catastrophizing (p = 0.05) while CCP was correlated to pain (p = 0.01). The SF cluster identified 3 subgroups with a particular one characterized by normal SF, low pain, high activity and hyperkinesia. The SR cluster identified 2 distinct subgroups: the one with a reduced SR was

Subgroup analysis of telehealthcare for patients with chronic obstructive pulmonary disease

DEFF Research Database (Denmark)

Witt Udsen, Flemming; Lilholt, Pernille H.; Hejlesen, Ole K.

2017-01-01

-to-pay threshold values. The purpose of this article was to assess potential sources of variation across subgroups, which could explain overall cost-effectiveness results or be utilized in future economic studies in telehealthcare research. METHODS: First, the cost-structures and cost-effectiveness across COPD......PURPOSE: Results from the Danish cluster-randomized trial of telehealthcare to 1,225 patients with chronic obstructive pulmonary disease (COPD), the Danish Telecare North Trial, concluded that the telehealthcare solution was unlikely to be cost-effective, by applying international willingness...... severities were analyzed. Second, five additional subgroup analyses were conducted, focusing on differences in cost-effectiveness across a set of comorbidities, age-groups, genders, resource patterns (resource use in the social care sector prior to randomization), and delivery sites. All subgroups were...

Treatment implications of posterior fossa ependymoma subgroups.

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Ramaswamy, Vijay; Taylor, Michael D

2016-11-15

Posterior fossa ependymoma comprises two distinct molecular entities, ependymoma_posterior fossa A (EPN_PFA) and ependymoma_posterior fossa B (EPN_PFB), with differentiable gene expression profiles. As yet, the response of the two entities to treatment is unclear. To determine the relationship between the two molecular subgroups of posterior fossa ependymoma and treatment, we studied a cohort of 820 patients with molecularly profiled, clinically annotated posterior fossa ependymomas. We found that the strongest predictor of poor outcome in patients with posterior fossa ependymoma across the entire age spectrum was molecular subgroup EPN_PFA, which was recently reported in the paper entitled "Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: a retrospective multicohort analysis" in the Journal of Clinical Oncology. Patients with incompletely resected EPN_PFA tumors had a very poor outcome despite receiving adjuvant radiation therapy, whereas a substantial proportion of patients with EPN_PFB tumors can be cured with surgery alone.

Identification of Personalized Chemoresistance Genes in Subtypes of Basal-Like Breast Cancer Based on Functional Differences Using Pathway Analysis.

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Tong Wu

Full Text Available Breast cancer is a highly heterogeneous disease that is clinically classified into several subtypes. Among these subtypes, basal-like breast cancer largely overlaps with triple-negative breast cancer (TNBC, and these two groups are generally studied together as a single entity. Differences in the molecular makeup of breast cancers can result in different treatment strategies and prognoses for patients with different breast cancer subtypes. Compared with other subtypes, basal-like and other ER+ breast cancer subtypes exhibit marked differences in etiologic factors, clinical characteristics and therapeutic potential. Anthracycline drugs are typically used as the first-line clinical treatment for basal-like breast cancer subtypes. However, certain patients develop drug resistance following chemotherapy, which can lead to disease relapse and death. Even among patients with basal-like breast cancer, there can be significant molecular differences, and it is difficult to identify specific drug resistance proteins in any given patient using conventional variance testing methods. Therefore, we designed a new method for identifying drug resistance genes. Subgroups, personalized biomarkers, and therapy targets were identified using cluster analysis of differentially expressed genes. We found that basal-like breast cancer could be further divided into at least four distinct subgroups, including two groups at risk for drug resistance and two groups characterized by sensitivity to pharmacotherapy. Based on functional differences among these subgroups, we identified nine biomarkers related to drug resistance: SYK, LCK, GAB2, PAWR, PPARG, MDFI, ZAP70, CIITA and ACTA1. Finally, based on the deviation scores of the examined pathways, 16 pathways were shown to exhibit varying degrees of abnormality in the various subgroups, indicating that patients with different subtypes of basal-like breast cancer can be characterized by differences in the functional status of

A Newborn Case of “c” Subgroup Mismatch Presenting with Severe Hemolysis and Anemia

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Ezgi Yangın Ergon

2017-12-01

Full Text Available Hemolysis and jaundice related to Rh incompatibility in the neonatal period has decreased substantially due to the widespread use of anti-D gammaglobulin in recent years. Nevertheless, the rate of subgroup mismatch in the etiology of hemolytic diseases of the newborn has increased significantly. In this article an 8-day-old newborn infant with “c” subgroup incompatibility and presenting with severe anemia, in whom hemolysis could be controlled with intravenous immunoglobulin infusion and subgroup appropriate blood transfusion, has been presented. Scientific studies have demonstrated that the hemolytic disease of patients who don’t have major blood group incompatibility but carry anti-C antibodies can be rather serious. Therefore, subgroup mismatch should always be kept in mind for newborns presenting with severe hemolytic anemia, and transfusion or if necessary exchange transfusion should be provided with subgroup matched blood products.

MicroRNA profiling in Muc2 knockout mice of colitis-associated cancer model reveals epigenetic alterations during chronic colitis malignant transformation.

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Yonghua Bao

Full Text Available Our previous studies have demonstrated that genetic deletion of the Muc2 gene causes colorectal cancers in mice. The current study further showed that at the early stage (3 months the mice exhibited colorectal cancer, including a unique phenotype of rectal prolapsed (rectal severe inflammation and adenocarcinoma. Thus, the age of 3 months might be the key point of the transition from chronic inflammation to cancer. To determine the mechanisms of the malignant transformation, we conducted miRNA array on the colonic epithelial cells from the 3-month Muc2-/- and +/+ mice. MicroRNA profiling showed differential expression of miRNAs (i.e. lower or higher expression enrichments in Muc2-/- mice. 15 of them were validated by quantitative PCR. Based on relevance to cytokine and cancer, 4 miRNAs (miR-138, miR-145, miR-146a, and miR-150 were validate and were found significantly downregulated in human colitis and colorectal cancer tissues. The network of the targets of these miRNAs was characterized, and interestedly, miRNA-associated cytokines were significantly increased in Muc2-/-mice. This is the first to reveal the importance of aberrant expression of miRNAs in dynamically transformation from chronic colitis to colitis-associated cancer. These findings shed light on revealing the mechanisms of chronic colitis malignant transformation.

Prevalence of papillomaviruses, polyomaviruses, and herpesviruses in triple-negative and inflammatory breast tumors from algeria compared with other types of breast cancer tumors.

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Marilys Corbex

Full Text Available The possible role of viruses in breast cancer etiology remains an unresolved question. We hypothesized that if some viruses are involved, it may be in a subgroup of breast cancers only. Epidemiological arguments drove our interest in breast cancer subgroups that are more frequent in Africa, namely inflammatory breast cancer (IBC and triple-negative breast cancer. We tested whether viral prevalence was significantly higher in these subgroups.One hundred fifty-five paraffin-embedded malignant breast tumors were randomly selected at the pathology laboratory of the University Hospital of Annaba (Algeria to include one third of IBC and two thirds of non-IBC. They were tested for the presence of DNA from 61 viral agents (46 human papillomaviruses, 10 polyomaviruses, and 5 herpesviruses using type-specific multiplex genotyping assays, which combine multiplex PCR and bead-based Luminex technology.Viral DNA was found in 22 (17.9% of 123 tumors. The most prevalent viruses were EBV1 and HPV16. IBC tumors carried significantly more viruses (any type than non-IBC tumors (30% vs. 13%, p<0.04. Similarly, triple-negative tumors displayed higher virus-positivity than non-triple-negative tumors (44% vs. 14%, p<0.009.Our results suggest an association between the presence of viral DNA and aggressive breast cancer phenotypes (IBC, triple-negative. While preliminary, they underline the importance of focusing on subgroups when studying viral etiology in breast cancer. Further studies on viruses in breast cancer should be conducted in much larger samples to confirm these initial findings.

Measuring the Speed of Aging across Population Subgroups

Science.gov (United States)

2014-01-01

People in different subgroups age at different rates. Surveys containing biomarkers can be used to assess these subgroup differences. We illustrate this using hand-grip strength to produce an easily interpretable, physical-based measure that allows us to compare characteristic-based ages across educational subgroups in the United States. Hand-grip strength has been shown to be a good predictor of future mortality and morbidity, and therefore a useful indicator of population aging. Data from the Health and Retirement Survey (HRS) were used. Two education subgroups were distinguished, those with less than a high school diploma and those with more education. Regressions on hand-grip strength were run for each sex and race using age and education, their interactions and other covariates as independent variables. Ages of identical mean hand-grip strength across education groups were compared for people in the age range 60 to 80. The hand-grip strength of 65 year old white males with less education was the equivalent to that of 69.6 (68.2, 70.9) year old white men with more education, indicating that the more educated men had aged more slowly. This is a constant characteristic age, as defined in the Sanderson and Scherbov article “The characteristics approach to the measurement of population aging” published 2013 in Population and Development Review. Sixty-five year old white females with less education had the same average hand-grip strength as 69.4 (68.2, 70.7) year old white women with more education. African-American women at ages 60 and 65 with more education also aged more slowly than their less educated counterparts. African American men with more education aged at about the same rate as those with less education. This paper expands the toolkit of those interested in population aging by showing how survey data can be used to measure the differential extent of aging across subpopulations. PMID:24806337

The impact of PET/CT on the management of hepatic and extra hepatic metastases from gastrointestinal cancers

Energy Technology Data Exchange (ETDEWEB)

Polat, Erdal, E-mail: erdal066@yahoo.com [Kartal Kosuyolu High Specialty Training and Research Hospital, Department of Gastrointestinal Surgery, Istanbul (Turkey); Bostanci, Erdal Birol [Sakarya University, Faculty of Medicine, Department of General Surgery, Sakarya (Turkey); Aksoy, Erol [Turkiye Yuksek Ihtisas Teaching and Research Hospital, Department of Gastroenterological Surgery, Ankara (Turkey); Karaman, Kerem [Sakarya University, Faculty of Medicine, Department of General Surgery, Sakarya (Turkey); Poyraz, Nilufer Yildirim [Ataturk Teaching and Research Hospital, Department of Nuclear Medicine, Ankara (Turkey); Duman, Ugur [Sevket Yilmaz Training and Research Hospital, Department of General Surgery, Bursa (Turkey); Gencturk, Zeynep Biyikli [Ankara University, Faculty of Medicine, Department of Biostatistics, Ankara (Turkey); Yol, Sinan [Medeniyet University, Faculty of Medicine, Department of General surgery, Istanbul (Turkey)

2015-06-15

Highlights: • CT is more sensitive than PET/CT in detecting hepatic metastases. • PET/CT is more specific in detecting hepatic metastases. • CT and PET/CT have equal sensitivity in detecting extra hepatic metastases. • PET/CT is more specific in detecting extra hepatic metastases. • PET/CT has an impact of about 40% on changing the management strategies. - Abstract: Purpose: To investigate the efficacy of positron emission tomography/computed tomography (PET/CT) in detection and management of hepatic and extrahepatic metastases from gastrointestinal cancers. Materials and methods: Between February 2008 and July 2010, patients histopathologically diagnosed with gastrointestinal cancer and showing suspected metastasis on CT screening were subsequently evaluated with PET/CT. All patients were subgrouped according to histopathological origin and localization of the primary tumor. Localization of gastrointestinal cancers was further specified as lower gastrointestinal system (GIS), upper GIS, or hepato-pancreato-biliary (HPB). Both accuracy and impact of CT and PET/CT on patient management were retrospectively evaluated. Results: One hundred and thirteen patients diagnosed histopathologically with gastrointestinal cancers were retrospectively evaluated. Seventy-nine patients had adenocarcinoma and 34 patients other gastrointestinal tumors. Forty-one patients were in the upper GIS group, 30 patients in the HPB group, and 42 patients in the lower GIS group. Evaluation the diagnostic performance of PET/CT for suspected metastasis according to histopathological origin of the tumor, revealed that the sensitivity of PET/CT – although statistically not different – was higher in adenocarcinomas than in non-adenocarcinomas (90% (95% CI, 0.78–0.96) vs. 71.4% (95% CI, 0.45–0.88), P = 0.86). The specificity was not significantly different (85.7% (95% CI, 0.70–0.93) vs. 85% (95% CI, 0.63–0.94), P = 1.00). In the overall patient group; CT was significantly more

Awareness of Cancer Susceptibility Genetic Testing

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Mai, Phuong L.; Vadaparampil, Susan Thomas; Breen, Nancy; McNeel, Timothy S.; Wideroff, Louise; Graubard, Barry I.

2014-01-01

Background Genetic testing for several cancer susceptibility syndromes is clinically available; however, existing data suggest limited population awareness of such tests. Purpose To examine awareness regarding cancer genetic testing in the U.S. population aged ≥25 years in the 2000, 2005, and 2010 National Health Interview Surveys. Methods The weighted percentages of respondents aware of cancer genetic tests, and percent changes from 2000–2005 and 2005–2010, overall and by demographic, family history, and healthcare factors were calculated. Interactions were used to evaluate the patterns of change in awareness between 2005 and 2010 among subgroups within each factor. To evaluate associations with awareness in 2005 and 2010, percentages were adjusted for covariates using multiple logistic regression. The analysis was performed in 2012. Results Awareness decreased from 44.4% to 41.5% (pAwareness increased between 2005 and 2010 in most subgroups, particularly among individuals in the South (p-interaction=0.03) or with a usual place of care (p-interaction=0.01). In 2005 and 2010, awareness was positively associated with personal or family cancer history and high perceived cancer risk, and inversely associated with racial/ethnic minorities, age 25–39 or ≥60 years, male gender, lower education and income levels, public or no health insurance, and no provider contact in 12 months. Conclusions Despite improvement from 2005 to 2010, ≤50% of the U.S. adult population was aware of cancer genetic testing in 2010. Notably, disparities persist for racial/ethnic minorities and individuals with limited health care access or income. PMID:24745633

Latent class analysis derived subgroups of low back pain patients - do they have prognostic capacity?

DEFF Research Database (Denmark)

Mølgaard Nielsen, Anne; Hestbaek, Lise; Vach, Werner

2017-01-01

. Previously, we developed two novel suggestions for subgrouping patients with low back pain based on Latent Class Analysis of patient baseline characteristics (patient history and physical examination), which resulted in 7 subgroups when using a single-stage analysis, and 9 subgroups when using a two...

Effects of hydroxyethyl starch in subgroups of patients with severe sepsis

DEFF Research Database (Denmark)

Müller, Rasmus G; Haase, Nicolai; Wetterslev, Jørn

2013-01-01

It has been speculated that certain subgroups of sepsis patients may benefit from treatment with hydroxyethyl starch (HES) 130/0.42, specifically in the earlier resuscitation of patients with more severely impaired circulation.......It has been speculated that certain subgroups of sepsis patients may benefit from treatment with hydroxyethyl starch (HES) 130/0.42, specifically in the earlier resuscitation of patients with more severely impaired circulation....

Combined group ECC protection and subgroup parity protection

Science.gov (United States)

Gara, Alan G.; Chen, Dong; Heidelberger, Philip; Ohmacht, Martin

2013-06-18

A method and system are disclosed for providing combined error code protection and subgroup parity protection for a given group of n bits. The method comprises the steps of identifying a number, m, of redundant bits for said error protection; and constructing a matrix P, wherein multiplying said given group of n bits with P produces m redundant error correction code (ECC) protection bits, and two columns of P provide parity protection for subgroups of said given group of n bits. In the preferred embodiment of the invention, the matrix P is constructed by generating permutations of m bit wide vectors with three or more, but an odd number of, elements with value one and the other elements with value zero; and assigning said vectors to rows of the matrix P.

Breast Cancer Molecular Subtypes Among Moroccan Women

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Wissal Mahir

2016-12-01

Full Text Available Introduction: Breast cancer remains despite the therapeutic progress, the leading cause of death by cancer among women. It represents a group of very heterogeneous clinical, histopathological and molecular diseases. Molecular heterogeneity has been demonstrated by genomic analysis, even for similar histology cancers. Four subgroups of breast carcinomas are distinguished: Luminal A, Luminal B, HER2 over expression and Basal - like. The Immuno-histo-chemical analysis useip (estrogen receptors RE, the PR (progesterone receptors, the ((Human Epidermal Growth Factor Receptor-2, the Ki67 (proliferation marker HER2, CK5/6 has shown a subdivision into subgroups similar to those found by genomic analysis. These subgroups are different from the point of view of clinical course and response to adjuvant treatment.Objectives: The aim of this work is to study the molecular profile of the breast cancers by immunostaining on Moroccan series to a classification with a prognostic value allowing a treatment tailored to each group of patients. Furthermore, the molecular subgroups were correlated to other clinical and histological factors.Material and methods: It is a prospective study of the laboratory of Anatomy and Pathologic cytology of the children's Hospital, the service I of the maternity hospital in Rabat and in cooperation with the United Nations Centre of pathological anatomy. To do this, 88 cases of breast cancer together were diagnosed between January 1, 2010 and December 31, 2014, taking a period of five years. All tissue samples made subject study of Immuno-histo-chemistry with the following markers: RE, PR, HER2 and Ki67. Only negative triple cases (HR and HER2 negative benefited from an additional marking with CK5/6 and EGFR to set the basal profile.Results: Series of 88 cases of mammary carcinomas observed on operating parts, ranged in age between 28 and 84 years old, with an average of 51 ± 12, 8. Carcinoma infiltrating non-specific (DOCTORS was

Subgroups of class groups of algebraic quadratic function fields

International Nuclear Information System (INIS)

Wang Kunpeng; Zhang Xianke

2001-09-01

Ideal class groups H(K) of algebraic quadratic function fields K are studied, by using mainly the theory of continued fractions of algebraic functions. Properties of such continued fractions are discussed first. Then a necessary and sufficient condition is given for the class group H(K) to contain a cyclic subgroup of any order n, this criterion condition holds true for both real and imaginary fields K. Furthermore, several series of function fields K, including real, inertia imaginary, as well as ramified imaginary quadratic function fields, are given, and their class groups H(K) are proved to contain cyclic subgroups of order n. (author)

Recent mass spectrometry-based proteomics for biomarker discovery in lung cancer, COPD, and asthma.

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Fujii, Kiyonaga; Nakamura, Haruhiko; Nishimura, Toshihide

2017-04-01

Lung cancer and related diseases have been one of the most common causes of deaths worldwide. Genomic-based biomarkers may hardly reflect the underlying dynamic molecular mechanism of functional protein interactions, which is the center of a disease. Recent developments in mass spectrometry (MS) have made it possible to analyze disease-relevant proteins expressed in clinical specimens by proteomic challenges. Areas covered: To understand the molecular mechanisms of lung cancer and its subtypes, chronic obstructive pulmonary disease (COPD), asthma and others, great efforts have been taken to identify numerous relevant proteins by MS-based clinical proteomic approaches. Since lung cancer is a multifactorial disease that is biologically associated with asthma and COPD among various lung diseases, this study focused on proteomic studies on biomarker discovery using various clinical specimens for lung cancer, COPD, and asthma. Expert commentary: MS-based exploratory proteomics utilizing clinical specimens, which can incorporate both experimental and bioinformatic analysis of protein-protein interaction and also can adopt proteogenomic approaches, makes it possible to reveal molecular networks that are relevant to a disease subgroup and that could differentiate between drug responders and non-responders, good and poor prognoses, drug resistance, and so on.

Prognostic factors associated with the success rates of posterior orthodontic miniscrew implants: A subgroup meta-analysis.

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Hong, Sung-Bin; Kusnoto, Budi; Kim, Eun-Jeong; BeGole, Ellen A; Hwang, Hyeon-Shik; Lim, Hoi-Jeong

2016-03-01

To systematically review previous studies and to assess, via a subgroup meta-analysis, the combined odds ratio (OR) of prognostic factors affecting the success of miniscrew implants (MIs) inserted into the buccal posterior region. Three electronic searches that were limited to articles on clinical human studies using MIs that were published in English prior to March 2015 were conducted. The outcome measure was the success of MIs. Patient factors included age, sex, and jaw of insertion (maxilla vs. mandible), while the MI factors included length and diameter. A meta-analysis was performed on 17 individual studies. The quality of each study was assessed for non-randomized studies and quantified using the Newcastle-Ottawa Scale. The meta-analysis outcome was a combined OR. Subgroup and sensitivity analyses based on the study design, study quality, and sample size of miniscrews implanted were performed. Significantly higher success rates were revealed for MIs inserted in the maxilla, for patients ≥ 20 years of age, and for long MIs (≥ 8 mm) and MIs with a large diameter (> 1.4 mm). All subgroups acquired homogeneity, and the combined OR of the prospective studies (OR, 3.67; 95% confidence interval [CI], 2.10-6.44) was significantly higher in the maxilla than that in the retrospective studies (OR, 2.10; 95% CI, 1.60-2.74). When a treatment plan is made, these risk factors, i.e. jaw of insertion, age, MI length, and MI diameter, should be taken into account, while sex is not critical to the success of MIs.

Prevention of pancreatic cancer

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Stefan Kuroczycki-Saniutycz

2017-02-01

Full Text Available Pancreatic ductal adenocarcinoma (PDA accounts for 95% of all pancreatic cancers. About 230,000 PDA cases are diagnosed worldwide each year. PDA has the lowest five-year survival rate as compared to others cancers. PDA in Poland is the fifth leading cause of death after lung, stomach, colon and breast cancer. In our paper we have analysed the newest epidemiological research, some of it controversial, to establish the best practical solution for pancreatic cancer prevention in the healthy population as well as treatment for patients already diagnosed with pancreatic cancer. We found that PDA occurs quite frequently but is usually diagnosed too late, at its advanced stage. Screening for PDA is not very well defined except in subgroups of high-risk individuals with genetic disorders or with chronic pancreatitis. We present convincing, probable, and suggestive risk factors associated with pancreatic cancer, many of which are modifiable and should be introduced and implemented in our society.

Isolation and characterization of a novel Betacoronavirus subgroup A coronavirus, rabbit coronavirus HKU14, from domestic rabbits.

Science.gov (United States)

Lau, Susanna K P; Woo, Patrick C Y; Yip, Cyril C Y; Fan, Rachel Y Y; Huang, Yi; Wang, Ming; Guo, Rongtong; Lam, Carol S F; Tsang, Alan K L; Lai, Kenneth K Y; Chan, Kwok-Hung; Che, Xiao-Yan; Zheng, Bo-Jian; Yuen, Kwok-Yung

2012-05-01

We describe the isolation and characterization of a novel Betacoronavirus subgroup A coronavirus, rabbit coronavirus HKU14 (RbCoV HKU14), from domestic rabbits. The virus was detected in 11 (8.1%) of 136 rabbit fecal samples by reverse transcriptase PCR (RT-PCR), with a viral load of up to 10(8) copies/ml. RbCoV HKU14 was able to replicate in HRT-18G and RK13 cells with cytopathic effects. Northern blotting confirmed the production of subgenomic mRNAs coding for the HE, S, NS5a, E, M, and N proteins. Subgenomic mRNA analysis revealed a transcription regulatory sequence, 5'-UCUAAAC-3'. Phylogenetic analysis showed that RbCoV HKU14 formed a distinct branch among Betacoronavirus subgroup A coronaviruses, being most closely related to but separate from the species Betacoronavirus 1. A comparison of the conserved replicase domains showed that RbCoV HKU14 possessed N-protein-based Western blot assay, whereas neutralizing antibody was detected in 1 of these 20 rabbits.

Use of fertility drugs and risk of ovarian cancer.

Science.gov (United States)

Diergaarde, Brenda; Kurta, Michelle L

2014-06-01

The purpose of this review is to highlight recent research and insights into the relationship between fertility drug use and ovarian cancer risk. Results from two large case-control studies provided further evidence that fertility drug use does not significantly contribute to risk of ovarian cancer among the majority of women when adjusting for known confounding factors. However, questions regarding the effect on certain subgroups, including long-term fertility drug users, women who remain nulligravid after fertility treatment, women with BRCA1 or BRCA2 mutations and borderline ovarian tumours, still remain. In addition, it may currently just be too early to determine whether there is an association between fertility drug use and ovarian cancer risk given that many of the exposed women are only now beginning to reach the ovarian cancer age range. Whether use of fertility drugs increases the risk of ovarian cancer is an important question that requires further investigation, in particular given the large number of women utilizing fertility treatments. Fortunately, results from recent studies have been mainly reassuring. Large well designed studies with sufficient follow-up time are needed to further evaluate the effects of fertility treatments within subgroups defined by patient and tumour characteristics.

Post-treatment problems of African American breast cancer survivors.

Science.gov (United States)

Barsevick, Andrea M; Leader, Amy; Bradley, Patricia K; Avery, Tiffany; Dean, Lorraine T; DiCarlo, Melissa; Hegarty, Sarah E

2016-12-01

African American breast cancer survivors (AABCS) have a lower survival rate across all disease stages (79 %) compared with White survivors (92 %) and often have more aggressive forms of breast cancer requiring multimodality treatment, so they could experience a larger burden of post-treatment quality of life (QOL) problems. This paper reports a comprehensive assessment of the number, severity, and domains of problems faced by AABCS within 5 years after treatment completion and identifies subgroups at risk for these problems. A population-based random sample was obtained from the Pennsylvania Cancer Registry of African American females over 18 years of age who completed primary treatment for breast cancer in the past 5 years. A mailed survey was used to document survivorship problems. Two hundred ninety-seven AABCS completed the survey. The median number of survivor problems reported was 15. Exploratory factor analysis of the problem scale revealed four domains: emotional problems, physical problems, lack of resources, and sexuality problems. Across problem domains, younger age, more comorbid conditions, and greater medical mistrust were risk factors for more severe problems. The results demonstrated that AABCS experienced significant problem burden in the early years after diagnosis and treatment. In addition to emotional and physical problem domains that were documented in previous research, two problem domains unique to AABCS included lack of resources and sexuality concerns. At risk groups should be targeted for intervention. The study results reported in this manuscript will inform future research to address problems of AABCS as they make the transition from cancer patient to cancer survivor.

Differences in neighborhood social cohesion and aerobic physical activity by Latino subgroup

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Rosenda Murillo

2016-12-01

Full Text Available Previous research has examined the role of neighborhood social cohesion in physical activity outcomes; however, less is known about this relationship across Latino subgroups. The purpose of our study was to examine the association between neighborhood social cohesion and aerobic leisure-time physical activity (LTPA among Latino adults and to determine whether these associations differ by Latino subgroup. We used cross-sectional 2013–2014 National Health Interview Survey (NHIS data on Latinos originating from 5 countries/regions (i.e., Latinos of Puerto Rican, Mexican/Mexican-American, Cuban/Cuban-American, Dominican and Central or South American origin aged ≥18 years (n=11,126. Multivariable logistic regression models were used to estimate associations between self-reported neighborhood social cohesion and meeting aerobic LTPA guidelines. Models were adjusted for age, sex, education, and acculturation. We also investigated whether associations varied by Latino subgroup. In adjusted models for all Latino adults, compared with those reporting low social cohesion, individuals who reported high social cohesion (Odds Ratio [OR]: 1.33; 95% Confidence Interval [CI]: 1.17–1.52 were significantly more likely to meet the aerobic physical activity guideline. When stratified by Latino subgroups, among Mexican/Mexicans-Americans (OR: 1.39; 95% CI: 1.16, 1.66 and Cuban/Cuban Americans (OR: 1.73; 95% CI: 1.00, 2.97 high social cohesion was associated with meeting the aerobic activity guideline. Among Dominicans, those who reported medium social cohesion (OR: 0.52, 95% CI: 0.29, 0.93 were less likely to meet the aerobic activity guideline. When examining aerobic physical activity outcomes in the Latino population, the role of neighborhood social cohesion and the variability among Latino subgroups should be considered. Keywords: Neighborhood social cohesion, Physical activity, Latinos, subgroups

Clinical implications of medulloblastoma subgroups: incidence of CSF diversion surgery.

Science.gov (United States)

Schneider, Christian; Ramaswamy, Vijay; Kulkarni, Abhaya V; Rutka, James T; Remke, Marc; Tabori, Uri; Hawkins, Cynthia; Bouffet, Eric; Taylor, Michael D

2015-03-01

While medulloblastoma was initially thought to comprise a single homogeneous entity, it is now accepted that it in fact comprises 4 discrete subgroups, each with its own distinct demographics, clinical presentation, transcriptomics, genetics, and outcome. Hydrocephalus is a common complication of medulloblastoma and not infrequently requires CSF diversion. The authors report the incidence of CSF diversion surgery in each of the subgroups of medulloblastoma (Wnt, Shh, Group 3, and Group 4). The medical and imaging records for patients who underwent surgery for medulloblastoma at The Hospital for Sick Children were retrospectively reviewed. The primary outcome was the requirement for CSF diversion surgery either before or within 60 days of tumor resection. The modified Canadian Preoperative Prediction Rule for Hydrocephalus (mCPPRH) was compared among subgroups. Of 143 medulloblastoma patients, treated from 1991 to 2013, sufficient data were available for 130 patients (15 with Wnt, 30 with Shh, 30 with Group 3, and 55 with Group 4 medulloblastomas). Of these, 28 patients (22%) ultimately underwent CSF diversion surgery: 0% with Wnt, 29% with Shh, 29% with Group 3, and 43% with Group 4 tumors. Patients in the Wnt subgroup had a lower incidence of CSF diversion than all other patients combined (p = 0.04). Wnt patients had a lower mCPPRH score (lower risk of CSF diversion, p = 0.045), were older, had smaller ventricles at diagnosis, and had no leptomeningeal metastases. The overall rate of CSF diversion surgery for Shh, Group 3, and Group 4 medulloblastomas is around 30%, but no patients in the present series with a Wnt medulloblastoma required shunting. The low incidence of hydrocephalus in patients with Wnt medulloblastoma likely reflects both host factors (age) and disease factors (lack of metastases). The absence of hydrocephalus in patients with Wnt medulloblastomas likely contributes to their excellent rate of survival and may also contribute to a higher quality

Human Papilloma Virus as a Biomarker for Personalized Head and Neck Cancer Radiotherapy

DEFF Research Database (Denmark)

Eriksen, Jesper Grau; Lassen, Pernille

2016-01-01

A dramatic increase in the incidence of HPV-related oropharyngeal cancer has been reported in some parts of the western world over the past 30 years. They constitute a clinically distinct subgroup of cancers in terms of molecular biology, patient characteristics, and treatment outcome. This chapt...

Delay of Treatment Initiation Does Not Adversely Affect Survival Outcome in Breast Cancer.

Science.gov (United States)

Yoo, Tae-Kyung; Han, Wonshik; Moon, Hyeong-Gon; Kim, Jisun; Lee, Jun Woo; Kim, Min Kyoon; Lee, Eunshin; Kim, Jongjin; Noh, Dong-Young

2016-07-01

Previous studies examining the relationship between time to treatment and survival outcome in breast cancer have shown inconsistent results. The aim of this study was to analyze the overall impact of delay of treatment initiation on patient survival and to determine whether certain subgroups require more prompt initiation of treatment. This study is a retrospective analysis of stage I-III patients who were treated in a single tertiary institution between 2005 and 2008. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to evaluate the impact of interval between diagnosis and treatment initiation in breast cancer and various subgroups. A total of 1,702 patients were included. Factors associated with longer delay of treatment initiation were diagnosis at another hospital, medical comorbidities, and procedures performed before admission for surgery. An interval between diagnosis and treatment initiation as a continuous variable or with a cutoff value of 15, 30, 45, and 60 days had no impact on disease-free survival (DFS). Subgroup analyses for hormone-responsiveness, triple-negative breast cancer, young age, clinical stage, and type of initial treatment showed no significant association between longer delay of treatment initiation and DFS. Our results show that an interval between diagnosis and treatment initiation of 60 days or shorter does not appear to adversely affect DFS in breast cancer.

Planar algebra of the subgroup-subfactor

Indian Academy of Sciences (India)

We think of R α G as the II1-factor (R ∪{ug: g ∈ G}) ⊂ L(L2(R)), where ug(ˆx) ..... define a global trace on P, where for 0± the trace for P0± ∼= C is the obvious identity .... function for strings is either a local maximum or a local minimum. ..... In order to understand how the inclusion tangles act on the subgroup-subfactor planar.

Adjuvant brachytherapy removes survival disadvantage of local disease extension in stage IIIC endometrial cancer: a SEER registry analysis.

Science.gov (United States)

Rossi, Peter J; Jani, Ashesh B; Horowitz, Ira R; Johnstone, Peter A S

2008-01-01

To assess the role of radiotherapy (RT) in women with Stage IIIC endometrial cancer. The 17-registry Survival, Epidemiology, and End Results (SEER) database was searched for patients with lymph node-positive non-Stage IV epithelial endometrial cancer diagnosed and treated between 1988 and 1998. Two subgroups were identified: those with organ-confined Stage IIIC endometrial cancer and those with Stage IIIC endometrial cancer with direct extension of the primary tumor. RT was coded as external beam RT (EBRT) or brachytherapy (BT). Observed survival (OS) was reported with a minimum of 5 years of follow-up; the survival curves were compared using the log-rank test. The therapy data revealed 611 women with Stage IIIC endometrial cancer during this period. Of these women, 51% were treated with adjuvant EBRT, 21% with EBRT and BT, and 28% with no additional RT (NAT). Of the 611 patients, 293 had organ-confined Stage IIIC endometrial cancer and 318 patients had Stage IIIC endometrial cancer with direct extension of the primary tumor. The 5-year OS rate for all patients was 40% with NAT, 56% after EBRT, and 64% after EBRT/BT. Adjuvant RT improved survival compared with NAT (p primary tumor was present, the addition of BT to EBRT was even more beneficial.

Myasthenia gravis: subgroup classification and therapeutic strategies.

Science.gov (United States)

Gilhus, Nils Erik; Verschuuren, Jan J

2015-10-01

Myasthenia gravis is an autoimmune disease that is characterised by muscle weakness and fatigue, is B-cell mediated, and is associated with antibodies directed against the acetylcholine receptor, muscle-specific kinase (MUSK), lipoprotein-related protein 4 (LRP4), or agrin in the postsynaptic membrane at the neuromuscular junction. Patients with myasthenia gravis should be classified into subgroups to help with therapeutic decisions and prognosis. Subgroups based on serum antibodies and clinical features include early-onset, late-onset, thymoma, MUSK, LRP4, antibody-negative, and ocular forms of myasthenia gravis. Agrin-associated myasthenia gravis might emerge as a new entity. The prognosis is good with optimum symptomatic, immunosuppressive, and supportive treatment. Pyridostigmine is the preferred symptomatic treatment, and for patients who do not adequately respond to symptomatic therapy, corticosteroids, azathioprine, and thymectomy are first-line immunosuppressive treatments. Additional immunomodulatory drugs are emerging, but therapeutic decisions are hampered by the scarcity of controlled studies. Long-term drug treatment is essential for most patients and must be tailored to the particular form of myasthenia gravis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Finite groups with the set of the number of subgroups of possible ...

Indian Academy of Sciences (India)

Finite group; the number of subgroups of possible order. 1. Introduction. Throughout this paper, groups mentioned are finite and p is a prime. An important topic in the group theory is to investigate the number of subgroups of possible order, and con- versely it is also an important subject to determine the structure of a finite ...

Discrimination of multilocus sequence typing-based Campylobacter jejuni subgroups by MALDI-TOF mass spectrometry.

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Zautner, Andreas Erich; Masanta, Wycliffe Omurwa; Tareen, Abdul Malik; Weig, Michael; Lugert, Raimond; Groß, Uwe; Bader, Oliver

2013-11-07

Campylobacter jejuni, the most common bacterial pathogen causing gastroenteritis, shows a wide genetic diversity. Previously, we demonstrated by the combination of multi locus sequence typing (MLST)-based UPGMA-clustering and analysis of 16 genetic markers that twelve different C. jejuni subgroups can be distinguished. Among these are two prominent subgroups. The first subgroup contains the majority of hyperinvasive strains and is characterized by a dimeric form of the chemotaxis-receptor Tlp7(m+c). The second has an extended amino acid metabolism and is characterized by the presence of a periplasmic asparaginase (ansB) and gamma-glutamyl-transpeptidase (ggt). Phyloproteomic principal component analysis (PCA) hierarchical clustering of MALDI-TOF based intact cell mass spectrometry (ICMS) spectra was able to group particular C. jejuni subgroups of phylogenetic related isolates in distinct clusters. Especially the aforementioned Tlp7(m+c)(+) and ansB+/ ggt+ subgroups could be discriminated by PCA. Overlay of ICMS spectra of all isolates led to the identification of characteristic biomarker ions for these specific C. jejuni subgroups. Thus, mass peak shifts can be used to identify the C. jejuni subgroup with an extended amino acid metabolism. Although the PCA hierarchical clustering of ICMS-spectra groups the tested isolates into a different order as compared to MLST-based UPGMA-clustering, the isolates of the indicator-groups form predominantly coherent clusters. These clusters reflect phenotypic aspects better than phylogenetic clustering, indicating that the genes corresponding to the biomarker ions are phylogenetically coupled to the tested marker genes. Thus, PCA clustering could be an additional tool for analyzing the relatedness of bacterial isolates.

Evaluation of a compliance device in a subgroup of adult patients receiving specific immunotherapy with grass allergen tablets (GRAZAX) in a randomized, open-label, controlled study: an a priori subgroup analysis.

NARCIS (Netherlands)

Jansen, A.P.H.; Andersen, K.F.; Bruning, H.

2009-01-01

OBJECTIVES: This a priori subgroup analysis was conducted to assess patients' experience with a compliance device for the administration of sublingual specific immunotherapy for grass pollen-induced rhinoconjunctivitis. METHODS: The present paper reports the results of a subgroup analysis of a

Challenging the Cancer Molecular Stratification Dogma: Intratumoral Heterogeneity Undermines Consensus Molecular Subtypes and Potential Diagnostic Value in Colorectal Cancer.

Science.gov (United States)

Dunne, Philip D; McArt, Darragh G; Bradley, Conor A; O'Reilly, Paul G; Barrett, Helen L; Cummins, Robert; O'Grady, Tony; Arthur, Ken; Loughrey, Maurice B; Allen, Wendy L; McDade, Simon S; Waugh, David J; Hamilton, Peter W; Longley, Daniel B; Kay, Elaine W; Johnston, Patrick G; Lawler, Mark; Salto-Tellez, Manuel; Van Schaeybroeck, Sandra

2016-08-15

A number of independent gene expression profiling studies have identified transcriptional subtypes in colorectal cancer with potential diagnostic utility, culminating in publication of a colorectal cancer Consensus Molecular Subtype classification. The worst prognostic subtype has been defined by genes associated with stem-like biology. Recently, it has been shown that the majority of genes associated with this poor prognostic group are stromal derived. We investigated the potential for tumor misclassification into multiple diagnostic subgroups based on tumoral region sampled. We performed multiregion tissue RNA extraction/transcriptomic analysis using colorectal-specific arrays on invasive front, central tumor, and lymph node regions selected from tissue samples from 25 colorectal cancer patients. We identified a consensus 30-gene list, which represents the intratumoral heterogeneity within a cohort of primary colorectal cancer tumors. Using a series of online datasets, we showed that this gene list displays prognostic potential HR = 2.914 (confidence interval 0.9286-9.162) in stage II/III colorectal cancer patients, but in addition, we demonstrated that these genes are stromal derived, challenging the assumption that poor prognosis tumors with stem-like biology have undergone a widespread epithelial-mesenchymal transition. Most importantly, we showed that patients can be simultaneously classified into multiple diagnostically relevant subgroups based purely on the tumoral region analyzed. Gene expression profiles derived from the nonmalignant stromal region can influence assignment of colorectal cancer transcriptional subtypes, questioning the current molecular classification dogma and highlighting the need to consider pathology sampling region and degree of stromal infiltration when employing transcription-based classifiers to underpin clinical decision making in colorectal cancer. Clin Cancer Res; 22(16); 4095-104. ©2016 AACRSee related commentary by Morris and

Change in health-related quality of life over 1 month in cancer patients with high initial levels of symptoms and problems

DEFF Research Database (Denmark)

Lund Rasmussen, Charlotte; Johnsen, Anna Thit; Petersen, Morten Aagaard

2016-01-01

PURPOSE: To investigate the mean changes over time in health-related quality of life among advanced cancer patients who did not receive any intervention, comparing changes among all patients versus changes in subgroups of patients with high initial symptom scores. METHODS: Patients with advanced...... of change over a 1-month period in health-related quality of life in advanced cancer patients, and in subgroups selected according to certain initial symptom levels. This information may help the interpretation of longitudinal studies of patients selected via screening....... cancer answered two questionnaires, containing the EORTC QLQ-C30 (15 multi- or single-item scales), with approximately 1 month in between and received no known intervention in between. For each QLQ-C30 scale, we estimated the mean change among all patients and in subgroups of patients scoring at least 33...

Clinically distinct trajectories of fatigue and their longitudinal relationship with the disturbance of personal goals following a cancer diagnosis

NARCIS (Netherlands)

Müller, Fabiola; Tuinman, Marrit A.; Janse, Moniek; Almansa, Josué; Sprangers, Mirjam A. G.; Smink, Ans; Ranchor, Adelita V.; Fleer, Joke; Hagedoorn, Mariët

Objectives. Most studies on fatigue in patients with cancer aggregate its prevalence and severity on a group level, ignoring the possibility that subgroups of patients may differ widely in their development of fatigue. This study aimed to identify subgroups of patients with clinically distinct

On the same side of the faultline: Inclusion in the leader’s subgroup and employee performance

NARCIS (Netherlands)

Meyer, B.; Shemla, M.; Li, J.; Wegge, J.

Extending theory on faultlines and subgroups, we argue that faultlines splitting a team into homogeneous subgroups can have different effects on team members' individual performance, depending on different intra-subgroup processes. Specifically, we propose that the effect of faultline strength on

Pan-cancer analysis of TCGA data reveals notable signaling pathways

International Nuclear Information System (INIS)

Neapolitan, Richard; Horvath, Curt M.; Jiang, Xia

2015-01-01

A signal transduction pathway (STP) is a network of intercellular information flow initiated when extracellular signaling molecules bind to cell-surface receptors. Many aberrant STPs have been associated with various cancers. To develop optimal treatments for cancer patients, it is important to discover which STPs are implicated in a cancer or cancer-subtype. The Cancer Genome Atlas (TCGA) makes available gene expression level data on cases and controls in ten different types of cancer including breast cancer, colon adenocarcinoma, glioblastoma, kidney renal papillary cell carcinoma, low grade glioma, lung adenocarcinoma, lung squamous cell carcinoma, ovarian carcinoma, rectum adenocarcinoma, and uterine corpus endometriod carcinoma. Signaling Pathway Impact Analysis (SPIA) is a software package that analyzes gene expression data to identify whether a pathway is relevant in a given condition. We present the results of a study that uses SPIA to investigate all 157 signaling pathways in the KEGG PATHWAY database. We analyzed each of the ten cancer types mentioned above separately, and we perform a pan-cancer analysis by grouping the data for all the cancer types. In each analysis several pathways were found to be markedly more significant than all the other pathways. We call them notable. Research has already established a connection between many of these pathways and the corresponding cancer type. However, some of our discovered pathways appear to be new findings. Altogether there were 37 notable findings in the separate analyses, 26 of them occurred in 7 pathways. These 7 pathways included the 4 notable pathways discovered in the pan-cancer analysis. So, our results suggest that these 7 pathways account for much of the mechanisms of cancer. Furthermore, by looking at the overlap among pathways, we identified possible regions on the pathways where the aberrant activity is occurring. We obtained 37 notable findings concerning 18 pathways. Some of them appear to be

On approximation of Lie groups by discrete subgroups

Indian Academy of Sciences (India)

1Department of Mathematics, Faculty of Sciences at Sfax, University of Sfax,. Route Soukra ... Let S (G) denote the space of discrete co-compact subgroup of a Lie group G. We ..... For example, it suffices to apply the following fact: The mapping.

Cancer-specific mortality of Asian Americans diagnosed with cancer: a nationwide population-based assessment.

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Trinh, Quoc-Dien; Nguyen, Paul L; Leow, Jeffrey J; Dalela, Deepansh; Chao, Grace F; Mahal, Brandon A; Nayak, Manan; Schmid, Marianne; Choueiri, Toni K; Aizer, Ayal A

2015-06-01

Racial disparities in cancer survival outcomes have been primarily attributed to underlying biologic mechanisms and the quality of cancer care received. Because prior literature shows little difference exists in the socioeconomic status of non-Hispanic whites and Asian Americans, any difference in cancer survival is less likely to be attributable to inequalities of care. We sought to examine differences in cancer-specific survival between whites and Asian Americans. The Surveillance, Epidemiology, and End Results Program was used to identify patients with lung (n = 130 852 [16.9%]), breast (n = 313 977 [40.4%]), prostate (n = 166 529 [21.4%]), or colorectal (n = 165 140 [21.3%]) cancer (the three leading causes of cancer-related mortality within each sex) diagnosed between 1991 and 2007. Fine and Gray's competing risks regression compared the cancer-specific mortality (CSM) of eight Asian American groups (Chinese, Filipino, Hawaiian/Pacific Islander, Japanese, Korean, other Asian, South Asian [Indian/Pakistani], and Vietnamese) to non-Hispanic white patients. All P values were two-sided. In competing risks regression, the receipt of definitive treatment was an independent predictor of CSM (hazard ratio [HR] = 0.37, 95% confidence interval [CI] = 0.35 to 0.40; HR = 0.55, 95% CI = 0.53 to 0.58; HR = 0.61, 95% CI = 0.60 to 0.62; and HR = 0.27, 95% CI = 0.25 to 0.29) for prostate, breast, lung, and colorectal cancers respectively, all P < .001). In adjusted analyses, most Asian subgroups (except Hawaiians and Koreans) had lower CSM relative to white patients, with hazard ratios ranging from 0.54 (95% CI = 0.38 to 0.78) to 0.88 (95% CI = 0.84 to 0.93) for Japanese patients with prostate and Chinese patients with lung cancer, respectively. Despite adjustment for potential confounders, including the receipt of definitive treatment and tumor characteristics, most Asian subgroups had better CSM than non-Hispanic white patients. These findings suggest that underlying genetic

Intrinsic subtypes and benefit from postmastectomy radiotherapy in node-positive premenopausal breast cancer patients who received adjuvant chemotherapy - results from two independent randomized trials

DEFF Research Database (Denmark)

Laurberg, Tinne; Tramm, Trine; Nielsen, Torsten

2018-01-01

BACKGROUND: The study of the intrinsic molecular subtypes of breast cancer has revealed differences among them in terms of prognosis and response to chemotherapy and endocrine therapy. However, the ability of intrinsic subtypes to predict benefit from adjuvant radiotherapy has only been examined...... randomized to adjuvant radiotherapy or not. All patients received adjuvant chemotherapy and a subgroup of patients underwent ovarian ablation. Tumors were classified into intrinsic subtypes: Luminal A, Luminal B, HER2-enriched, Basal-like and Normal-like using the research-based PAM50 classifier. RESULTS...

Checkpoint inhibitors in breast cancer

DEFF Research Database (Denmark)

Polk, Anne; Svane, Inge-Marie; Andersson, Michael

2018-01-01

INTRODUCTION: An increasing number of compounds directed against immune checkpoints are currently under clinical development. In this review we summarize current research in breast cancer. MATERIAL AND METHODS: A computer-based literature search was carried out using PubMed and EMBASE; data...... reported at international meetings and clinicaltrials.gov were included as well. RESULTS: The obtained overall response rate of PD-1/PD-L1 monotherapy varied from 5 to 30% in heavily pretreated triple negative breast cancer (TNBC). The median duration of progression free survival and overall survival were...... and induce long standing anti-tumor immunity in a subgroup of breast cancer patients. However, the identification of predictive biomarkers is crucial for further development of this treatment modality....

Comparison of cerebral metabolism of glucose in normal human and cancer patients

International Nuclear Information System (INIS)

Si, M.

2007-01-01

Full text: Objective: To determine whether the cerebral metabolism in various regions of the normal human brain differs from those of cancer patients in aging by using 18F-FDG PET instrument and SPM software. Materials and Methods We reviewed clinical information of 295 healthy normal samples so called 'normal group' (ranging 21 to 88; mean age+/-SD: 50+/-14) and 290 cancer patients called 'cancer group' (ranging 21 to 85; mean age+/-SD: 54+/-14) who were examined by a whole body GE Discovery LS PET-CT instrument in our center from Aug. 2004 to Dec. 2005.They were selected with: (i) absence of clear focal brain lesions (epilepsy, cerebrovascular diseases etc.); (ii) absence of metabolic diseases, such as hyperthyroidism, hypothyroidism and diabetes; (iii) absence of psychiatric disorders and abuse of drugs and alcohol;( iiii) cancer patients were diagnosed definitely of variable cancers except brain cancer or brain metastasis. Both groups were sub grouped into six with the interval of 10 years old starting from 21, and the gender, educational background and serum glucose are matched. All 12 subgroups were compared to the subgroup of normal 31-40 years old called 'control subgroup' (84 samples; mean age+/-SD: 37.15+/- 2.63). All samples were injected with 18F-FDG (5.55MBq/kg), 45-60 minutes later; their brains were scanned for 10 minutes. Pixel-by-pixel t-statistic analysis was applied to all brain images using the Statistical parametric mapping (SPM2). The hypometabolic areas (p < 0. 01 or p<0.001, uncorrected) were identified in the Stereotaxic coordinate human brain atlas and three dimensional localized by MNI Space utility (MSU) software. Results:1.With increasing of age interval, similar hypometabolic brain areas are detected in both 'normal group' and 'cancer group', they are mainly in the cortical structures such as bilateral prefrontal cortex (BA9), superior temporal gyrus (BA22), parietal cortex (inferior parietal lobule and precuneus(BA40), insula (BA13

Relationship between body mass index and the expression of hormone receptors or human epidermal growth factor receptor 2 with respect to breast cancer survival

International Nuclear Information System (INIS)

Jeon, Ye Won; Kang, Su Hwan; Park, Min Ho; Lim, Woosung; Cho, Se Heun; Suh, Young Jin

2015-01-01

The association between body mass index (BMI) at the time of breast cancer diagnosis and the prognosis of breast cancer patients remains controversial. Furthermore, the association between BMI and prognosis with respect to different breast cancer subtypes is not clearly defined. We analyzed data from 41,021 invasive breast cancer patients between January 1988 and February 2008 from the Korean Breast Cancer Registry (KBCR) database. Overall survival (OS) and breast cancer-specific survival (BCSS) were analyzed using the Kaplan-Meier method and Cox’s proportional hazard regression model among all patients and specific breast cancer subtypes with respect to BMI categories. A U-shaped association between BMI and mortality was observed in the total cohort. Underweight and obese individuals exhibited worse OS (hazard ratio, 1.23 [95 % confidence interval {CI}, 1.05 to 1.44] and 1.29 [1.13 to 1.48], respectively) and BCSS (1.26 [1.03 to 1.54] and 1.21 [1.02 to 1.43], respectively) than normal-weight individuals. In the estrogen receptor (ER) and/or progesterone receptor (PR)+/human epidermal growth factor receptor 2 (HER2) - subgroup, obese individuals exhibited worse OS (1.48 [1.18 to 1.85]) and BCSS (1.31 [1.13 to 1.52]) than normal-weight individuals. Conversely, in the ER and PR-/HER2+ subgroup, underweight individuals exhibited worse OS (1.68 [1.12 to 2.47]) and BCSS (1.79 [1.11 to 2.90]) than normal-weight individuals. We observed a U-shaped relationship between BMI at diagnosis and poor OS and BCSS among all breast cancer patients. However, obesity in the ER and/or PR+/HER2- subgroup and underweight in the ER and PR-/HER2+ subgroup were poor prognostic factors. Therefore, BMI at diagnosis and breast cancer subtype should be considered simultaneously in various treatment decision processes and surveillance schedules

Peritumoral vascular invasion and NHERF1 expression define an immunophenotype of grade 2 invasive breast cancer associated with poor prognosis

International Nuclear Information System (INIS)

Malfettone, Andrea; Saponaro, Concetta; Paradiso, Angelo; Simone, Giovanni; Mangia, Annita

2012-01-01

Traditional determinants proven to be of prognostic importance in breast cancer include the TNM staging, histological grade, proliferative activity, hormone receptor status and HER2 overexpression. One of the limitations of the histological grading scheme is that a high percentage of breast cancers are still classified as grade 2, a category with ambiguous clinical significance. The aim of this study was to best characterize tumors scored as grade 2. We investigated traditional prognostic factors and a panel of tumor markers not used in routine diagnosis, such as NHERF1, VEGFR1, HIF-1α and TWIST1, in 187 primary invasive breast cancers by immunohistochemistry, stratifying patients into good and poor prognostic groups by the Nottingham Prognostic Index. Grade 2 subgroup analysis showed that the PVI (p = 0.023) and the loss of membranous NHERF1 (p = 0.028) were adverse prognostic factors. Relevantly, 72% of grade 2 tumors were associated to PVI+/membranous NHERF1- expression phenotype, characterizing an adverse prognosis (p = 0.000). Multivariate logistic regression analysis in the whole series revealed poor prognosis correlated with PVI and MIB1 (p = 0.000 and p = 0.001, respectively). Furthermore, in the whole series of breast cancers we found cytoplasmic NHERF1 expression positively correlated to VEGFR1 (r = 0.382, p = 0.000), and in VEGFR1-overexpressing tumors the oncogenic receptor co-localized with NHERF1 at cytoplasmic level. The PVI+/membranous NHERF1- expression phenotype identifies a category of grade 2 tumors with the worst prognosis, including patient subgroup with a family history of breast cancer. These observations support the idea of the PVI+/membranous NHERF1- expression immunophenotype as a useful marker, which could improve the accuracy of predicting clinical outcome in grade 2 tumors

The Direct Assignment Option as a Modular Design Component: An Example for the Setting of Two Predefined Subgroups

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Ming-Wen An

2015-01-01

Full Text Available Background. A phase II design with an option for direct assignment (stop randomization and assign all patients to experimental treatment based on interim analysis, IA for a predefined subgroup was previously proposed. Here, we illustrate the modularity of the direct assignment option by applying it to the setting of two predefined subgroups and testing for separate subgroup main effects. Methods. We power the 2-subgroup direct assignment option design with 1 IA (DAD-1 to test for separate subgroup main effects, with assessment of power to detect an interaction in a post-hoc test. Simulations assessed the statistical properties of this design compared to the 2-subgroup balanced randomized design with 1 IA, BRD-1. Different response rates for treatment/control in subgroup 1 (0.4/0.2 and in subgroup 2 (0.1/0.2, 0.4/0.2 were considered. Results. The 2-subgroup DAD-1 preserves power and type I error rate compared to the 2-subgroup BRD-1, while exhibiting reasonable power in a post-hoc test for interaction. Conclusion. The direct assignment option is a flexible design component that can be incorporated into broader design frameworks, while maintaining desirable statistical properties, clinical appeal, and logistical simplicity.

Novel cancer gene variants and gene fusions of triple-negative breast cancers (TNBCs) reveal their molecular diversity conserved in the patient-derived xenograft (PDX) model.

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Jung, Jaeyun; Jang, Kiwon; Ju, Jung Min; Lee, Eunji; Lee, Jong Won; Kim, Hee Jung; Kim, Jisun; Lee, Sae Byul; Ko, Beom Seok; Son, Byung Ho; Lee, Hee Jin; Gong, Gyungyup; Ahn, Sei Yeon; Choi, Jung Kyoon; Singh, Shree Ram; Chang, Suhwan

2018-04-20

Despite the improved 5-year survival rate of breast cancer, triple-negative breast cancer (TNBC) remains a challenge due to lack of effective targeted therapy and higher recurrence and metastasis than other subtypes. To identify novel druggable targets and to understand its unique biology, we tried to implement 24 patient-derived xenografts (PDXs) of TNBC. The overall success rate of PDX implantation was 45%, much higher than estrogen receptor (ER)-positive cases. Immunohistochemical analysis revealed conserved ER/PR/Her2 negativity (with two exceptions) between the original and PDX tumors. Genomic analysis of 10 primary tumor-PDX pairs with Ion AmpliSeq CCP revealed high degree of variant conservation (85.0% to 96.9%) between primary and PDXs. Further analysis showed 44 rare variants with a predicted high impact in 36 genes including Trp53, Pten, Notch1, and Col1a1. Among them, we confirmed frequent Notch1 variant. Furthermore, RNA-seq analysis of 24 PDXs revealed 594 gene fusions, of which 163 were in-frame, including AZGP1-GJC3 and NF1-AARSD1. Finally, western blot analysis of oncogenic signaling proteins supporting molecular diversity of TNBC PDXs. Overall, our report provides a molecular basis for the usefulness of the TNBC PDX model in preclinical study. Copyright © 2018. Published by Elsevier B.V.

Universal primers that amplify RNA from all three flavivirus subgroups

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Barnard Ross T

2008-01-01

Full Text Available Abstract Background Species within the Flavivirus genus pose public health problems around the world. Increasing cases of Dengue and Japanese encephalitis virus in Asia, frequent outbreaks of Yellow fever virus in Africa and South America, and the ongoing spread of West Nile virus throughout the Americas, show the geographical burden of flavivirus diseases. Flavivirus infections are often indistinct from and confused with other febrile illnesses. Here we review the specificity of published primers, and describe a new universal primer pair that can detect a wide range of flaviviruses, including viruses from each of the recognised subgroups. Results Bioinformatic analysis of 257 published full-length Flavivirus genomes revealed conserved regions not previously targeted by primers. Two degenerate primers, Flav100F and Flav200R were designed from these regions and used to generate an 800 base pair cDNA product. The region amplified encoded part of the methyltransferase and most of the RNA-dependent-RNA-polymerase (NS5 coding sequence. One-step RT-PCR testing was successful using standard conditions with RNA from over 60 different flavivirus strains representing about 50 species. The cDNA from each virus isolate was sequenced then used in phylogenetic analyses and database searches to confirm the identity of the template RNA. Conclusion Comprehensive testing has revealed the broad specificity of these primers. We briefly discuss the advantages and uses of these universal primers.

Clinical Significance of POU5F1P1 rs10505477 Polymorphism in Chinese Gastric Cancer Patients Receving Cisplatin-Based Chemotherapy after Surgical Resection

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Lili Shen

2014-07-01

Full Text Available This study aimed to investigate the association between POU class5 homeobox 1 pseudogene 1 gene (POU5F1P1 rs10505477 polymorphism and the prognosis of Chinese gastric cancer patients, who received cisplatin-based chemotherapy after surgical resection. POU5F1P1 rs10505477 was genotyped using the SNaPshot method in 944 gastric cancer patients who received gastrectomy. The association of rs10505477 G > A polymorphism with the progression and prognosis in gastric cancer patients was statistically analyzed using the SPSS version 18.0 for Windows. The results reveal that rs10505477 polymorphism has a negatively effect on the overall survival of gastric cancer patients in cisplatin-based chemotherapy subgroup (HR = 1.764, 95% CI = 1.069–2.911, p = 0.023. Our preliminary study indicates for the first time that POU5F1P1 rs10505477 is correlated with survival of gastric cancer patients who receving cisplatin-based chemotherapy after gastrectomy. Further studies are warranted to investigate the mechanism and to verify our results in different populations.

A method for generating subgroup parameters from resonance tables and the SPART code

International Nuclear Information System (INIS)

Devan, K.; Mohanakrishnan, P.

1995-01-01

A method for generating subgroup or band parameters from resonance tables is described. A computer code SPART was written using this method. This code generates the subgroup parameters for any number of bands within the specified broad groups at different temperatures by reading the required input data from the binary cross section library in the Cadarache format. The results obtained with SPART code for two bands were compared with that obtained from GROUPIE code and a good agreement was obtained. Results of the generation of subgroup parameters in four bands for sample case of 239 Pu from resonance tables of Cadarache Ver.2 library is also presented. 6 refs, 2 tabs

Some topics on permutable subgroups in infinite groups

OpenAIRE

Ialenti, Roberto

2017-01-01

The aim of this thesis is to study permutability in different aspects of the theory of infinite groups. In particular, it will be studied the structure of groups in which all the members of a relevant system of subgroups satisfy a suitable generalized condition of permutability.

Genetic variations in a PTEN/AKT/mTOR axis and prostate cancer risk in a Chinese population.

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Jiawei Chen

Full Text Available Genetic variations in a PTEN/AKT/mTOR signaling axis may influence cellular functions including cell growth, proliferation and apoptosis, and then increase the individual's risk of cancer. Accordingly, we explore the association between single nucleotide polymorphisms (SNPs of these genes and prostate cancer (PCa in our Chinese population.Subjects were recruited from 666 PCa patients and 708 cancer-free controls, and eight SNPs in the PTEN/AKT/mTOR axis were determined by the TaqMan assay. Odds ratios (OR and 95% confidence intervals (95% CI were evaluated by logistic regression.We observed significant associations between PCa risk and mTOR rs2295080 [P = 0.027, OR = 0.85, 95%CI = 0.74-0.98], and AKT2 rs7254617 (P = 0.003, OR = 1.35, 95%CI = 1.11-1.64. When estimated these two SNPs together, the combined genotypes with 2-4 risk alleles (rs2295080 T and rs7254617 A alleles were associated with an increased risk of PCa compared with 0-1 risk alleles, which was more pronounced among subgroups of age >71 years, smokers, drinkers and no family history of cancer. Results of stratified analyses by cliniopathological parameters revealed that the frequencies of the combined genotypes with 2-4 risk alleles in advanced stage were significantly higher than in localized stage (P = 0.022, but there was no significant association in Gleason score and PSA level.Our results indicate, for the first time that the two variants in AKT2 and mTOR, particularly the joint genotypes with 2-4 risk alleles may influence PCa susceptibility and progression in Chinese, and the association appeared to be more strong in the subgroup of smokers and drinkers.

Cancer experiences and health-related quality of life among racial and ethnic minority survivors of young adult cancer: a mixed methods study.

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Munoz, Alexis R; Kaiser, Karen; Yanez, Betina; Victorson, David; Garcia, Sofia F; Snyder, Mallory A; Salsman, John M

2016-12-01

Young adult (YA) racial and ethnic minority survivors of cancer (diagnosed ages 18-39) experience significant disparities in health outcomes and survivorship compared to non-minorities of the same age. However, little is known about the survivorship experiences of this population. The purpose of this study is to explore the cancer experiences and health-related quality of life (HRQOL) among YA racial/ethnic minorities in an urban US city. Racial and ethnic minority YA cancer survivors (0 to 5 years posttreatment) were recruited from a comprehensive cancer center using a purposive sampling approach. Participants (n = 31) completed semi-structured interviews, the FACT-G (physical, emotional, social well-being) and the FACIT-Sp (spiritual well-being). Mixed methods data were evaluated using thematic analysis and analysis of covariance (ANCOVA). The majority of survivors were women (65 %), single (52 %), and Hispanic (42 %). Across interviews, the most common themes were the following: "changes in perspective," "emotional impacts," "received support," and "no psychosocial changes." Other themes varied by racial/ethnic subgroups, including "treatment effects" (Hispanics), "behavior changes" (Blacks), and "appreciation for life" (Asians). ANCOVAs (controlling for gender and ECOG performance status scores) revealed that race/ethnicity had a significant main effect on emotional (P = 0.05), but not physical, social, or spiritual HRQOL (P > 0.05). Our findings suggest that minority YA cancer survivors report complex positive and negative experiences. In spite of poor health outcomes, survivors report experiencing growth and positive change due to cancer. Variations in experiences and HRQOL highlight the importance of assessing cultural background to tailor survivorship care among YA racial and ethnic minorities.

Trajectories of personal control in cancer patients receiving psychological care

NARCIS (Netherlands)

Zhu, Lei; Schroevers, Maya J.; van der Lee, Marije; Garssen, Bert; Stewart, Roy E.; Sanderman, Robbert; Ranchor, Adelita V.

Objective: This study aimed to (1) identify subgroups of cancer patients with distinct personal control trajectories during psychological care, (2) examine whether socio-demographic, clinical, and psychological care characteristics could distinguish trajectories, and (3) examine differential

Subgroups of some Fuchsian groups defined by two linear congruences

Science.gov (United States)

Yayenie, Omer

In this article we define a new family of subgroups of Fuchsian groups H(√{m}) , for a squarefree positive integer m , and calculate their index in H(√{m}) and their parabolic class number. Moreover, we will show that the index of these subgroups is closely related to the solvability of a quadratic congruence x2≡ m(mod n) and the number of inequivalent solutions of a quadratic congruence x2≡ 1(mod n) . Finally, we will show that the results obtained by Yilmaz and Keskin [Acta Math. Sin 25 (2005), 215-222] are immediate corollaries of one of the main theorems of this article.

Enrollment Trends and Disparity Among Patients With Lung Cancer in National Clinical Trials, 1990 to 2012

Science.gov (United States)

Pang, Herbert H.; Stinchcombe, Thomas E.; Wong, Melisa L.; Cheng, Perry; Ganti, Apar Kishor; Sargent, Daniel J.; Zhang, Ying; Hu, Chen; Mandrekar, Sumithra J.; Redman, Mary W.; Manola, Judith B.; Schilsky, Richard L.; Cohen, Harvey J.; Bradley, Jeffrey D.; Adjei, Alex A.; Gandara, David; Ramalingam, Suresh S.; Vokes, Everett E.

2016-01-01

Purpose Under-representation of elderly, women, and racial/ethnic minority patients with cancer in clinical trials is of national concern. The goal of this study was to characterize enrollment trends and disparities by age, sex, and race/ethnicity in lung cancer trials. Methods We analyzed data for 23,006 National Cancer Institute cooperative group lung cancer trial participants and 578,476 patients with lung cancer from the SEER registry from 1990 to 2012. The enrollment disparity difference (EDD) and enrollment disparity ratio (EDR) were calculated on the basis of the proportion of each subgroup in the trial population and the US lung cancer population. Annual percentage changes (APCs) in the subgroup proportions in each population were compared over time. Results Enrollment disparity for patients ≥ 70 years of age with non–small-cell lung cancer improved from 1990 to 2012 (test of parallelism, P = .020), with a remaining EDD of 0.22 (95% CI, 0.19 to 0.25) and EDR of 1.65 (95% CI, 1.51 to 1.82) in 2010 to 2012. No improvement was seen for elderly patients with small-cell lung cancer (SCLC), with an APC of 0.20 (P = .714) among trial participants, despite a rising proportion of elderly patients with SCLC in the US population (APC, 0.32; P = .020). Enrollment disparity for women with lung cancer improved overall, with the gap closing by 2012 (EDD, 0.03 [95% CI, 0.00 to 0.06]; EDR, 1.07 [95% CI, 1.00 to 1.16]). Enrollment disparities persisted without significant improvement for elderly women, blacks, Asians/Pacific Islanders, and Hispanics. Conclusion Under-representation in lung cancer trials improved significantly from 1990 to 2012 for elderly patients with non–small-cell lung cancer and for women, but ongoing efforts to improve the enrollment of elderly patients with SCLC and minorities are needed. Our study highlights the importance of addressing enrollment disparities by demographic and disease subgroups to better target under-represented groups of

The burden of breast cancer in Italy: mastectomies and quadrantectomies performed between 2001 and 2008 based on nationwide hospital discharge records

Directory of Open Access Journals (Sweden)

Piscitelli Prisco

2012-11-01

Full Text Available Abstract Background Where population coverage is limited, the exclusive use of Cancer Registries might limit ascertainment of incident cancer cases. We explored the potentials of Nationwide hospital discharge records (NHDRs to capture incident breast cancer cases in Italy. Methods We analyzed NHDRs for mastectomies and quadrantectomies performed between 2001 and 2008. The average annual percentage change (AAPC and related 95% Confidence Interval (CI in the actual number of mastectomies and quadrantectomies performed during the study period were computed for the full sample and for subgroups defined by age, surgical procedure, macro-area and singular Region. Re-admissions of the same patients were separately presented. Results The overall number of mastectomies decreased, with an AAPC of −2.1% (−2.3 -1.8. This result was largely driven by the values observed for women in the 45 to 64 and 65 to 74 age subgroups (−3.0%, -3.4 -3.6 and −3.3%, -3.8 -2.8, respectively. We observed no significant reduction in mastectomies for women in the remaining age groups. Quadrantectomies showed an overall +4.7 AAPC (95%CI:4.5–4.9, with no substantial differences by age. Analyses by geographical area showed a remarkable decrease in mastectomies, with inter-regional discrepancies possibly depending upon variability in mammography screening coverage and adherence. Quadrantectomies significantly increased, with Southern Regions presenting the highest average rates. Data on repeat admissions within a year revealed a total number of 46,610 major breast surgeries between 2001 and 2008, with an overall +3.2% AAPC (95%CI:2.8-3.6. Conclusions In Italy, NHDRs might represent a valuable supplemental data source to integrate Cancer Registries in cancer surveillance.

Avian metapneumovirus subgroup C infection in chickens, China.

Science.gov (United States)

Wei, Li; Zhu, Shanshan; Yan, Xv; Wang, Jing; Zhang, Chunyan; Liu, Shuhang; She, Ruiping; Hu, Fengjiao; Quan, Rong; Liu, Jue

2013-07-01

Avian metapneumovirus causes acute respiratory tract infection and reductions in egg production in various avian species. We isolated and characterized an increasingly prevalent avian metapneumovirus subgroup C strain from meat-type commercial chickens with severe respiratory signs in China. Culling of infected flocks could lead to economic consequences.

Avian Metapneumovirus Subgroup C Infection in Chickens, China

OpenAIRE

Wei, Li; Zhu, Shanshan; Yan, Xv; Wang, Jing; Zhang, Chunyan; Liu, Shuhang; She, Ruiping; Hu, Fengjiao; Quan, Rong; Liu, Jue

2013-01-01

Avian metapneumovirus causes acute respiratory tract infection and reductions in egg production in various avian species. We isolated and characterized an increasingly prevalent avian metapneumovirus subgroup C strain from meat-type commercial chickens with severe respiratory signs in China. Culling of infected flocks could lead to economic consequences.

A comprehensive custom panel design for routine hereditary cancer testing: preserving control, improving diagnostics and revealing a complex variation landscape.

Science.gov (United States)

Castellanos, Elisabeth; Gel, Bernat; Rosas, Inma; Tornero, Eva; Santín, Sheila; Pluvinet, Raquel; Velasco, Juan; Sumoy, Lauro; Del Valle, Jesús; Perucho, Manuel; Blanco, Ignacio; Navarro, Matilde; Brunet, Joan; Pineda, Marta; Feliubadaló, Lidia; Capellá, Gabi; Lázaro, Conxi; Serra, Eduard

2017-01-04

We wanted to implement an NGS strategy to globally analyze hereditary cancer with diagnostic quality while retaining the same degree of understanding and control we had in pre-NGS strategies. To do this, we developed the I2HCP panel, a custom bait library covering 122 hereditary cancer genes. We improved bait design, tested different NGS platforms and created a clinically driven custom data analysis pipeline. The I2HCP panel was developed using a training set of hereditary colorectal cancer, hereditary breast and ovarian cancer and neurofibromatosis patients and reached an accuracy, analytical sensitivity and specificity greater than 99%, which was maintained in a validation set. I2HCP changed our diagnostic approach, involving clinicians and a genetic diagnostics team from panel design to reporting. The new strategy improved diagnostic sensitivity, solved uncertain clinical diagnoses and identified mutations in new genes. We assessed the genetic variation in the complete set of hereditary cancer genes, revealing a complex variation landscape that coexists with the disease-causing mutation. We developed, validated and implemented a custom NGS-based strategy for hereditary cancer diagnostics that improved our previous workflows. Additionally, the existence of a rich genetic variation in hereditary cancer genes favors the use of this panel to investigate their role in cancer risk.

Trajectories of personal control in cancer patients receiving psychological care

NARCIS (Netherlands)

Zhu, Lei; Schroevers, Maya J.; van der Lee, Marije; Garssen, Bert; Stewart, Roy E.; Sanderman, Robbert; Ranchor, A.V.

2015-01-01

Objective This study aimed to (1) identify subgroups of cancer patients with distinct personal control trajectories during psychological care, (2) examine whether socio-demographic, clinical, and psychological care characteristics could distinguish trajectories, and (3) examine differential patterns

Analysis of the individual radio sensitivity of breast cancer patients; Untersuchungen zur individuellen Strahlenempfindlichkeit von Brustkrebspatientinnen

Energy Technology Data Exchange (ETDEWEB)

Auer, Judith

2013-04-04

Individual radiosensitivity has a crucial impact on radiotherapy related side effects. A prediction of individual radiosensitivity could avoid these side effects. Our aim was to study a breast cancer collective for its variation of individual radiosensitivity. Peripheral blood samples were obtained from 129 individuals. 67 breast cancer patients and 62 healthy and age matched individuals were looked at and their individual radiosensitivity was estimated by a 3-color Fluorescence in situ hybridization approach. Blood samples were obtained (i) before starting adjuvant radiotherapy and were in vitro irradiated by 2 Gy; (ii) after 5 single doses of 1.8 Gy and after 72 h had elapsed. DNA of lymphocytes was probed with whole chromosome painting for chromosomes 1, 2 and 4. The rate of breaks per metaphase was analyzed and used as a predictor of individual radiosensitivity. Breast cancer patients were distinctly more radio-sensitive compared to healthy controls. Additionally the distribution of the cancer patients' radiosensitivity was broader. A subgroup of 9 rather radio-sensitive and 9 rather radio-resistant patients was identified. A subgroup of patients aged between 40 and 50 was distinctly more radio-sensitive than younger or older patients. The in vivo irradiation approach was not applicable to detect individual radiosensitivity. In the breast cancer collective a distinctly resistant and sensitive subgroup is identified, which could be subject for treatment adjustment. Especially in the range of age 40 to 50 patients have an increased radiosensitivity. An in vivo irradiation in a breast cancer collective is not suitable to estimate individual radiosensitivity due to a low deposed dose.

Comprehensive analysis of miRNAs expression profiles revealed potential key miRNA/mRNAs regulating colorectal cancer stem cell self-renewal.

Science.gov (United States)

Xu, Peng; Wang, Junhua; Sun, Bo; Xiao, Zhongdang

2018-05-20

Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood. Recently, miRNAs are reported to be relevant to the self-renewal ability of cancer stem cells. In this study, we first isolated colorectal cancer stem cell from colorectal cancer cell line HCT-116 by 1% low serum culture. Then we conducted a comprehensive analysis based on the miRNAs profiles data of both colorectal cancer stem cells and normal cultured colorectal cancer cells. Pathway analysis revealed multiple pathways including Jak-STAT, TGF-beta, PI3K-Akt and MAPK signaling pathway that are correlated to colorectal cancer. Further, we constructed a miRNA-mRNA network, based on which, several miRNA/mRNA pairs were ranked according to their impact index to the self-renewal of colorectal cancer stem cells. Further biological experiment showed that up-regulation of miR-92a-3p led to cell cycle arrest and reduced colony formation. This work provides clues to find the new potential biomarkers for colorectal cancer stem cell diagnosis and select effective miRNAs for targeted therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Risk for non-smoking-related cancer in atherosclerotic patients

DEFF Research Database (Denmark)

Dreyer, L; Olsen, J H

1999-01-01

Some studies have suggested that the pathogenesis of atherosclerosis and that of cancer have common features, and in addition to tobacco smoking, oxidative stress, diet, and sex hormones have been considered as common etiological factors. To investigate whether there is an association between...... in this group was calculated by linkage to the Danish Cancer Registry for the period 1977-1993. No consistent excesses over the expected figures were seen for cancer at any site unrelated to tobacco smoking in either the total cohort or in subgroups. Specifically, we found no association at the individual level...

Can quality of life assessments differentiate heterogeneous cancer patients?

Directory of Open Access Journals (Sweden)

Ryan M McCabe

Full Text Available PURPOSE: This research conducted a face validation study of patient responses to the application of an HRQOL assessment research tool in a comprehensive community cancer program setting across a heterogeneous cohort of cancer patients throughout the natural history of diagnosed malignant disease, many of whom would not be considered candidates for clinical research trial participation. METHODS: Cancer registries at two regional cancer treatment centers identified 11072 cancer patients over a period of nine years. The EORTC QLQ-C30 was administered to patients at the time of their initial clinical presentation to these centers. To determine the significance of differences between patient subgroups, two analytic criteria were used. The Mann-Whitney test was used to determine statistical significance; clinical relevance defined a range of point differences that could be perceived by patients with different health states. RESULTS: Univariate analyses were conducted across stratification variables for population, disease severity and demographic characteristics. The largest differences were associated with cancer diagnosis and recurrence of disease. Large differences were also found for site of origin, mortality and stage; minimal differences were observed for gender and age. Consistently sensitive QoL scales were appetite loss, fatigue and pain symptoms, and role (work-related, social and physical functions. CONCLUSIONS: 1 The EORTC QLQ-C30 collected meaningful patient health assessments in the context of non-research based clinical care, 2 patient assessment differences are manifested disparately across 15 QoL domains, and 3 in addition to indicating how a patient may feel at a point in time, QoL indicators may also reveal information about underlying biological responses to disease progression, treatments, and prospective survival.

Patterns of alcohol use and consequences among empirically derived sexual minority subgroups.

Science.gov (United States)

Talley, Amelia E; Sher, Kenneth J; Steinley, Douglas; Wood, Phillip K; Littlefield, Andrew K

2012-03-01

The current study develops an empirically determined classification of sexual orientation developmental patterns based on participants' annual reports of self-identifications, sexual attractions, and sexual behaviors during the first 4 years of college. A secondary aim of the current work was to examine trajectories of alcohol involvement among identified subgroups. Data were drawn from a subsample of a longitudinal study of incoming first-time college students at a large, public university (n = 2,068). Longitudinal latent class analysis was used to classify sexual minority participants into empirically derived subgroups based on three self-reported facets of sexual orientation. Multivariate repeated-measures analyses were conducted to examine how trajectories of alcohol involvement varied by sexual orientation class membership. Four unique subclasses of sexual orientation developmental patterns were identified for males and females: one consistently exclusively heterosexual group and three sexual minority groups. Despite generally similar alcohol use patterns among subclasses, certain sexual minority subgroups reported elevated levels of alcohol-related negative consequences and maladaptive motivations for use throughout college compared with their exclusively heterosexual counterparts. Elevations in coping and conformity motivations for alcohol use were seen among those subgroups that also evidenced heightened negative alcohol-related consequences. Implications and limitations of the current work are discussed.

Objectives and tasks for sub-group B: Plutonium management and recycle

International Nuclear Information System (INIS)

1978-01-01

The paper restates the prime objectives of Working Group 4 and explains that in order to accomplish their objectives two sub-groups (A and B) have been established. The Co-Chairmen suggested that sub group B take as their terms of reference those tasks remitted to them by Working Group 4 as a whole. The paper identifies and comments on 11 tasks into which the work of the sub-group is divided. The paper also includes a number of annexes giving the guidelines for data input to each task

Validation of the online prediction tool PREDICT v. 2.0 in the Dutch breast cancer population

NARCIS (Netherlands)

Maaren, M.C. van; Steenbeek, C.D. van; Pharoah, P.D.; Witteveen, A.; Sonke, G.S.; Strobbe, L.J.A.; Poortmans, P.; Siesling, S.

2017-01-01

BACKGROUND: PREDICT version 2.0 is increasingly used to estimate prognosis in breast cancer. This study aimed to validate this tool in specific prognostic subgroups in the Netherlands. METHODS: All operated women with non-metastatic primary invasive breast cancer, diagnosed in 2005, were selected

Validation of the online prediction tool PREDICT v. 2.0 in the Dutch breast cancer population

NARCIS (Netherlands)

van Maaren, M. C.; van Steenbeek, C. D.; Pharoah, P. D.P.; Witteveen, A.; Sonke, Gabe S.; Strobbe, L.J.A.; Poortmans, P.M.P.; Siesling, S.

2017-01-01

Background PREDICT version 2.0 is increasingly used to estimate prognosis in breast cancer. This study aimed to validate this tool in specific prognostic subgroups in the Netherlands. Methods All operated women with non-metastatic primary invasive breast cancer, diagnosed in 2005, were selected from

Estimation of Future Cancer Burden Among Rescue and Recovery Workers Exposed to the World Trade Center Disaster.

Science.gov (United States)

Singh, Ankura; Zeig-Owens, Rachel; Moir, William; Hall, Charles B; Schwartz, Theresa; Vossbrinck, Madeline; Jaber, Nadia; Webber, Mayris P; Kelly, Kerry J; Ortiz, Viola; Koffler, Ellen; Prezant, David J

2018-06-01

Elevated rates of cancer have been reported in individuals exposed to the World Trade Center (WTC) disaster, including Fire Department of the City of New York (FDNY) rescue and recovery workers. To project the future burden of cancer in WTC-exposed FDNY rescue and recovery workers by estimating the 20-year cancer incidence. A total of 14 474 WTC-exposed FDNY employees who were cancer-free on January 1, 2012; subgroup analyses were conducted of the cohort's white male population (n = 12 374). In this closed-cohort study, we projected cancer incidence for the January 1, 2012, to December 31, 2031, period. Simulations were run using demographic-specific New York City (NYC) cancer and national mortality rates for each individual, summed for the whole cohort, and performed 1000 times to produce mean estimates. Additional analyses in the subgroup of white men compared case counts produced by using 2007-2011 FDNY WTC Health Program (FDNY-WTCHP) cancer rates vs NYC rates. Average and 20-year aggregate costs of first-year cancer care were estimated using claims data. World Trade Center disaster exposure defined as rescue and recovery work at the WTC site at any time from September 11, 2001, to July 25, 2002. (1) Projected number of incident cancers in the full cohort, based on NYC cancer rates; (2) cancer incidence estimates in the subgroup projected using FDNY-WTCHP vs NYC rates; and (3) estimated first-year treatment costs of incident cancers. On January 1, 2012, the cohort was 96.8% male, 87.1% white, and had a mean (SD) age of 50.2 (9.2) years. The projected number of incident cancer cases was 2960 (95% CI, 2883-3037). In our subgroup analyses using FDNY-WTCHP vs NYC cancer rates, the projected number of new cases in white men was elevated (2714 [95% CI, 2638-2786] vs 2596 [95% CI, 2524-2668]). Accordingly, we expect more prostate (1437 [95% CI, 1383-1495] vs 863 [95% CI, 816-910]), thyroid (73 [95% CI, 60-86] vs 57 [95% CI, 44-69]), and melanoma cases (201 [95

Applying a gender lens on human papillomavirus infection: cervical cancer screening, HPV DNA testing, and HPV vaccination

NARCIS (Netherlands)

Brankovic, I; Verdonk, P.; Klinge, I.

2013-01-01

Background: Our aim is to provide a state-of-the-art overview of knowledge on sex (biological) and gender (sociocultural) aspects of Human papillomavirus (HPV) and cervical cancer for educational purposes. Considerable disparities exist in cervical cancer incidences between different subgroups of

Fine-Scale Mapping of the 5q11.2 Breast Cancer Locus Reveals at Least Three Independent Risk Variants Regulating MAP3K1

NARCIS (Netherlands)

Glubb, Dylan M.; Maranian, Mel J.; Michailidou, Kyriaki; Pooley, Karen A.; Meyer, Kerstin B.; Kar, Siddhartha; Carlebur, Saskia; O'Reilly, Martin; Betts, Joshua A.; Hillman, Kristine M.; Kaufmann, Susanne; Beesley, Jonathan; Canisius, Sander; Hopper, John L.; Southey, Melissa C.; Tsimiklis, Helen; Apicella, Carmel; Schmidt, Marjanka K.; Broeks, Annegien; Hogervorst, Frans B.; van der Schoot, C. Ellen; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A.; Ruebner, Matthias; Ekici, Arif B.; Beckmann, Matthias W.; Peto, Julian; Dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Pharoah, Paul D. P.; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Burwinkel, Barbara; Marme, Frederik; Yang, Rongxi; Surowy, Harald; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; González-Neira, Anna; Benitez, Javier; Zamora, M. Pilar; Arias Perez, Jose Ignacio; Anton-Culver, Hoda; Neuhausen, Susan L.; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Schmutzler, Rita K.; Brauch, Hiltrud; Ko, Yon-Dschun; Brüning, Thomas; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tanaka, Hideo; Dörk, Thilo; Bogdanova, Natalia V.; Helbig, Sonja; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Wu, Anna H.; Tseng, Chiu-Chen; van den Berg, David; Stram, Daniel O.; Lambrechts, Diether; Zhao, Hui; Weltens, Caroline; van Limbergen, Erik; Chang-Claude, Jenny; Flesch-Janys, Dieter; Rudolph, Anja; Seibold, Petra; Radice, Paolo; Peterlongo, Paolo; Barile, Monica; Capra, Fabio; Couch, Fergus J.; Olson, Janet E.; Hallberg, Emily; Vachon, Celine; Giles, Graham G.; Milne, Roger L.; McLean, Catriona; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; teo, Soo Hwang; Yip, Cheng Har; See, Mee-Hoong; Cornes, Belinda; Cheng, Ching-Yu; Ikram, M. Kamran; Kristensen, Vessela; Zheng, Wei; Halverson, Sandra L.; Shrubsole, Martha; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A. E. M.; Seynaeve, Caroline; van Asperen, Christi J.; García-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J.; Lissowska, Jolanta; Czene, Kamila; Klevebring, Daniel; Darabi, Hatef; Eriksson, Mikael; Hooning, Maartje J.; Hollestelle, Antoinette; Martens, John W. M.; Collée, J. Margriet; Hall, Per; Li, Jingmei; Humphreys, Keith; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Blot, William; Signorello, Lisa B.; Cai, Qiuyin; Shah, Mitul; Ghoussaini, Maya; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.; Noh, Dong-Young; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Tang, Anthony; Hamann, Ute; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Olswold, Curtis; Slager, Susan; Toland, Amanda E.; Yannoukakos, Drakoulis; Shen, Chen-Yang; Wu, Pei-Ei; Yu, Jyh-Cherng; Hou, Ming-Feng; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Pita, Guillermo; Alonso, M. Rosario; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Healey, Catherine S.; Brown, Melissa A.; Ponder, Bruce A. J.; Chenevix-Trench, Georgia; Thompson, Deborah J.; Edwards, Stacey L.; Easton, Douglas F.; Dunning, Alison M.; French, Juliet D.

2015-01-01

Genome-wide association studies (GWASs) have revealed SNP rs889312 on 5q11.2 to be associated with breast cancer risk in women of European ancestry. In an attempt to identify the biologically relevant variants, we analyzed 909 genetic variants across 5q11.2 in 103,991 breast cancer individuals and

Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1

NARCIS (Netherlands)

D.M. Glubb (Dylan); M. Maranian (Melanie); K. Michailidou (Kyriaki); K.A. Pooley (Karen); K.B. Meyer (Kerstin); S. Kar (Siddhartha); A.F.C. Carlebur; M. O'Reilly (Marian); J.A. Betts (Joshua); K.M. Hillman (Kristine); S. Kaufmann (Susanne); J. Beesley (Jonathan); S. Canisius (Sander); J.L. Hopper (John); M.C. Southey (Melissa); H. Tsimiklis (Helen); C. Apicella (Carmel); M.K. Schmidt (Marjanka); A. Broeks (Annegien); F.B.L. Hogervorst (Frans); C.E. van der Schoot (Ellen); K.R. Muir (K.); A. Lophatananon (Artitaya); S. Stewart-Brown (Sarah); P. Siriwanarangsan (Pornthep); P.A. Fasching (Peter); M. Ruebner (Matthias); A.B. Ekici (Arif); M.W. Beckmann (Matthias); J. Peto (Julian); I. dos Santos Silva (Isabel); O. Fletcher (Olivia); N. Johnson (Nichola); P.D.P. Pharoah (Paul D.P.); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); B. Burwinkel (Barbara); F. Marme (Federick); R. Yang (Rongxi); H. Surowy (Harald); P. Guénel (Pascal); T. Truong (Thérèse); F. Menegaux (Florence); M. Sanchez (Marie); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune); H. Flyger (Henrik); A. González-Neira (Anna); J. Benítez (Javier); M.P. Zamora (Pilar); J.I. Arias Pérez (José Ignacio); H. Anton-Culver (Hoda); S.L. Neuhausen (Susan); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); C. Stegmaier (Christa); A. Meindl (Alfons); R.K. Schmutzler (Rita); H. Brauch (Hiltrud); Y.-D. Ko (Yon-Dschun); T. Brüning (Thomas); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); K. Matsuo (Keitaro); H. Ito (Hidemi); H. Iwata (Hisato); H. Tanaka (Hideo); T. Dörk (Thilo); N.V. Bogdanova (Natalia); S. Helbig (Sonja); A. Lindblom (Annika); S. Margolin (Sara); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); A.H. Wu (Anna H.); C.-C. Tseng (Chiu-Chen); D. Van Den Berg (David); D.O. Stram (Daniel O.); D. Lambrechts (Diether); H. Zhao (Hui); C. Weltens (Caroline); E. van Limbergen (Erik); J. Chang-Claude (Jenny); D. Flesch-Janys (Dieter); A. Rudolph (Anja); P. Seibold (Petra); P. Radice (Paolo); P. Peterlongo (Paolo); M. Barile (Monica); F. Capra (Fabio); F.J. Couch (Fergus); J.E. Olson (Janet); B. Hallberg (Boubou); C. Vachon (Celine); G.G. Giles (Graham); R.L. Milne (Roger); C.A. McLean (Catriona Ann); C.A. Haiman (Christopher); B.E. Henderson (Brian); F.R. Schumacher (Fredrick); L. Le Marchand (Loic); J. Simard (Jacques); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); S.-H. Teo (Soo-Hwang); C.H. Yip (Cheng Har); M.-H. See (Mee-Hoong); B.K. Cornes (Belinda); C-Y. Cheng (Ching-Yu); M.K. Ikram (Kamran); V. Kristensen (Vessela); W. Zheng (Wei); S.L. Halverson (Sandra L.); M. Shrubsole (Martha); J. Long (Jirong); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); S. Kauppila (Saila); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); S. Tchatchou (Sandrine); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); C.J. van Asperen (Christi); M. García-Closas (Montserrat); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); J. Lissowska (Jolanta); K. Czene (Kamila); D. Klevebring (Daniel); H. Darabi (Hatef); M. Eriksson (Mikael); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); J.W.M. Martens (John W. M.); J.M. Collée (Margriet); P. Hall (Per); J. Li (Jingmei); K. Humphreys (Keith); X.-O. Shu (Xiao-Ou); W. Lu (Wei); Y.-T. Gao (Yu-Tang); H. Cai (Hui); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); W.J. Blot (William); L.B. Signorello (Lisa B.); Q. Cai (Qiuyin); M. Shah (Mitul); M. Ghoussaini (Maya); D. Kang (Daehee); J.-Y. Choi (J.); S.K. Park (Sue); D-Y. Noh (Dong-Young); M. Hartman (Mikael); X. Miao; W.-Y. Lim (Wei-Yen); A. Tang (Anthony); U. Hamann (Ute); D. Torres (Diana); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska (Katarzyna); K. Durda (Katarzyna); S. Sangrajrang (Suleeporn); V. Gaborieau (Valerie); P. Brennan (Paul); J.D. McKay (James); C. Olswold (Curtis); S. Slager (Susan); A.E. Toland (Amanda); D. Yannoukakos (Drakoulis); C-Y. Shen (Chen-Yang); P.-E. Wu (Pei-Ei); J-C. Yu (Jyh-Cherng); M.-F. Hou (Ming-Feng); A.J. Swerdlow (Anthony ); A. Ashworth (Alan); N. Orr (Nick); M. Jones (Michael); G. Pita (Guillermo); M.R. Alonso (Rosario); N. Álvarez (Nuria); D. Herrero (Daniel); D.C. Tessier (Daniel C.); D. Vincent (Daniel); F. Bacot (Francois); C. Luccarini (Craig); C. Baynes (Caroline); S. Ahmed (Shahana); S. Healey (Sue); M. Brown (Melissa); B.A.J. Ponder (Bruce A.J.); G. Chenevix-Trench (Georgia); D. Thompson (Deborah); S.L. Edwards (Stacey); D.F. Easton (Douglas); A.M. Dunning (Alison); J.D. French (Juliet)

2015-01-01

textabstractGenome-wide association studies (GWASs) have revealed SNP rs889312 on 5q11.2 to be associated with breast cancer risk in women of European ancestry. In an attempt to identify the biologically relevant variants, we analyzed 909 genetic variants across 5q11.2 in 103,991 breast cancer

Survival outcomes for oligometastasis in resected non-small cell lung cancer.

Science.gov (United States)

Shimada, Yoshihisa; Saji, Hisashi; Kakihana, Masatoshi; Kajiwara, Naohiro; Ohira, Tatsuo; Ikeda, Norihiko

2015-10-01

We investigated the factors associated with post-recurrence survival and the treatment for non-small-cell lung cancer patients with postoperative distant recurrence, especially oligometastasis. We reviewed the data of 272 patients with distant recurrence who underwent resection of non-small-cell lung cancer from January 2000 through December 2011. The type of distant recurrence was classified as oligometastasis (n = 76, 28%) or polymetastasis (n = 196, 72%). Forty-seven (62%) patients with oligometastasis received local therapy (surgery 5, radiotherapy 9, sequential local and systemic therapy 28, chemoradiotherapy 5). Multivariate analysis revealed older age, non-adenocarcinoma, shorter disease-free interval, no pulmonary metastasis, liver metastases, bone metastases, and polymetastasis had significant associations with unfavorable post-recurrence survival. Subgroup analysis of patients with oligometastasis showed histology and disease-free interval had a great impact on survival. Smoking history and histology were associated with survival in patients with lung oligometastasis, whereas systemic treatment and longer disease-free interval were related to increased post-recurrence survival in those with brain oligometastasis. This study showed that an oligometastatic state per se was a significant favorable factor. Optimization of personalized systemic treatment and adding local treatment are important in the management of patients with non-small-cell lung cancer and oligometastasis. © The Author(s) 2015.

Integrative Genomics Reveals Mechanisms of Copy Number Alterations Responsible for Transcriptional Deregulation in Colorectal Cancer

Science.gov (United States)

Camps, Jordi; Nguyen, Quang Tri; Padilla-Nash, Hesed M.; Knutsen, Turid; McNeil, Nicole E.; Wangsa, Danny; Hummon, Amanda B.; Grade, Marian; Ried, Thomas; Difilippantonio, Michael J.

2016-01-01

To evaluate the mechanisms and consequences of chromosomal aberrations in colorectal cancer (CRC), we used a combination of spectral karyotyping, array comparative genomic hybridization (aCGH), and array-based global gene expression profiling on 31 primary carcinomas and 15 established cell lines. Importantly, aCGH showed that the genomic profiles of primary tumors are recapitulated in the cell lines. We revealed a preponderance of chromosome breakpoints at sites of copy number variants (CNVs) in the CRC cell lines, a novel mechanism of DNA breakage in cancer. The integration of gene expression and aCGH led to the identification of 157 genes localized within high-level copy number changes whose transcriptional deregulation was significantly affected across all of the samples, thereby suggesting that these genes play a functional role in CRC. Genomic amplification at 8q24 was the most recurrent event and led to the overexpression of MYC and FAM84B. Copy number dependent gene expression resulted in deregulation of known cancer genes such as APC, FGFR2, and ERBB2. The identification of only 36 genes whose localization near a breakpoint could account for their observed deregulated expression demonstrates that the major mechanism for transcriptional deregulation in CRC is genomic copy number changes resulting from chromosomal aberrations. PMID:19691111

[Psychosocial issues of long-term cancer survivors].

Science.gov (United States)

Weis, J; Faller, H

2012-04-01

Although cancer incidence rates are increasing, recent statistical studies suggest that cancer patients are showing higher cure rates as well as improved overall survival rates for most cancer locations. These advances are explained by improved strategies in early diagnoses as well as improved cancer therapies. Therefore, the number of long-term cancer survivors has also increased, but only few studies, especially within the last years, have focused on psychosocial issues of this subgroup. Some studies show that overall quality of life of long-term cancer survivors is quite high and comparable to that of the normal population. Nevertheless, a substantial percentage of former patients shows reduced quality of life and suffers from various sequelae of cancer and its treatment. This review focuses on the most common psychosocial issue of long-term survivors such as reduced psychological wellbeing, neuropsychological deficits and cancer-related fatigue syndrome. Finally, recommendations for problem-oriented interventions as well as improvement of psychosocial care of long-term survivors are given.

Lymph node status as a prognostic factor after palliative resection of primary tumor for patients with metastatic colorectal cancer.

Science.gov (United States)

Li, Qingguo; Wang, Changjian; Li, Yaqi; Li, Xinxiang; Xu, Ye; Cai, Guoxiang; Lian, Peng; Cai, Sanjun

2017-07-18

Lymph node (LN) status is one of the most important predictors for M0 colorectal cancer patients. However, its clinical impact on stage IV colorectal cancer remains unclear. The study aimed to explore the prognostic value of LN status after palliative resection of primary tumor for patients with metastatic colorectal cancer (mCRC). We combined analyses of mCRC patients in Surveillance, Epidemiology and End Results (SEER) database and Fudan University Shanghai Cancer Center (FUSCC).A total of 17,553 patients with mCRC were identified in SEER database. X-tile program was adopted to identify 2 and 10 as optimal cutoff values for negative lymph node (NLN) count to divide patients into 3 subgroups of high, middle and low risk of cancer related death. N stage and NLN count were verified as independent prognostic factors in multivariate analyses of patients in whole cohort and in subgroup analyses of each N stage (Pcolorectal cancer. Advanced N stage and small number of NLN were correlated with high risk of cancer related death after palliative resection of primary tumor.

Prospective Genomic Profiling of Prostate Cancer Across Disease States Reveals Germline and Somatic Alterations That May Affect Clinical Decision Making.

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Abida, Wassim; Armenia, Joshua; Gopalan, Anuradha; Brennan, Ryan; Walsh, Michael; Barron, David; Danila, Daniel; Rathkopf, Dana; Morris, Michael; Slovin, Susan; McLaughlin, Brigit; Curtis, Kristen; Hyman, David M; Durack, Jeremy C; Solomon, Stephen B; Arcila, Maria E; Zehir, Ahmet; Syed, Aijazuddin; Gao, Jianjiong; Chakravarty, Debyani; Vargas, Hebert Alberto; Robson, Mark E; Joseph, Vijai; Offit, Kenneth; Donoghue, Mark T A; Abeshouse, Adam A; Kundra, Ritika; Heins, Zachary J; Penson, Alexander V; Harris, Christopher; Taylor, Barry S; Ladanyi, Marc; Mandelker, Diana; Zhang, Liying; Reuter, Victor E; Kantoff, Philip W; Solit, David B; Berger, Michael F; Sawyers, Charles L; Schultz, Nikolaus; Scher, Howard I

2017-07-01

A long natural history and a predominant osseous pattern of metastatic spread are impediments to the adoption of precision medicine in patients with prostate cancer. To establish the feasibility of clinical genomic profiling in the disease, we performed targeted deep sequencing of tumor and normal DNA from patients with locoregional, metastatic non-castrate, and metastatic castration-resistant prostate cancer (CRPC). Patients consented to genomic analysis of their tumor and germline DNA. A hybridization capture-based clinical assay was employed to identify single nucleotide variations, small insertions and deletions, copy number alterations and structural rearrangements in over 300 cancer-related genes in tumors and matched normal blood. We successfully sequenced 504 tumors from 451 patients with prostate cancer. Potentially actionable alterations were identified in DNA damage repair (DDR), PI3K, and MAP kinase pathways. 27% of patients harbored a germline or a somatic alteration in a DDR gene that may predict for response to PARP inhibition. Profiling of matched tumors from individual patients revealed that somatic TP53 and BRCA2 alterations arose early in tumors from patients who eventually developed metastatic disease. In contrast, comparative analysis across disease states revealed that APC alterations were enriched in metastatic tumors, while ATM alterations were specifically enriched in CRPC. Through genomic profiling of prostate tumors representing the disease clinical spectrum, we identified a high frequency of potentially actionable alterations and possible drivers of disease initiation, metastasis and castration-resistance. Our findings support the routine use of tumor and germline DNA profiling for patients with advanced prostate cancer, for the purpose of guiding enrollment in targeted clinical trials and counseling families at increased risk of malignancy.

Reports of MC and A system design workshop subgroups

International Nuclear Information System (INIS)

Hatcher, C.R.

1984-01-01

A summary of subgroup reports from the workshop on design of a materials control and accounting system for a low-enrichment fuel fabrication facility is presented. Responses to a MC and A design system questionnaire are also summarized

Detecting treatment-subgroup interactions in clustered data with generalized linear mixed-effects model trees.

Science.gov (United States)

Fokkema, M; Smits, N; Zeileis, A; Hothorn, T; Kelderman, H

2017-10-25

Identification of subgroups of patients for whom treatment A is more effective than treatment B, and vice versa, is of key importance to the development of personalized medicine. Tree-based algorithms are helpful tools for the detection of such interactions, but none of the available algorithms allow for taking into account clustered or nested dataset structures, which are particularly common in psychological research. Therefore, we propose the generalized linear mixed-effects model tree (GLMM tree) algorithm, which allows for the detection of treatment-subgroup interactions, while accounting for the clustered structure of a dataset. The algorithm uses model-based recursive partitioning to detect treatment-subgroup interactions, and a GLMM to estimate the random-effects parameters. In a simulation study, GLMM trees show higher accuracy in recovering treatment-subgroup interactions, higher predictive accuracy, and lower type II error rates than linear-model-based recursive partitioning and mixed-effects regression trees. Also, GLMM trees show somewhat higher predictive accuracy than linear mixed-effects models with pre-specified interaction effects, on average. We illustrate the application of GLMM trees on an individual patient-level data meta-analysis on treatments for depression. We conclude that GLMM trees are a promising exploratory tool for the detection of treatment-subgroup interactions in clustered datasets.

Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer

DEFF Research Database (Denmark)

Francavilla, Chiara; Lupia, Michela; Tsafou, Kalliopi

2017-01-01

Our understanding of the molecular determinants of cancer is still inadequate because of cancer heterogeneity. Here, using epithelial ovarian cancer (EOC) as a model system, we analyzed a minute amount of patient-derived epithelial cells from either healthy or cancerous tissues by single-shot mas...

Verification of a Subgroup Generation Method for Thorium Fuel Assemblies

International Nuclear Information System (INIS)

Sim, Ohsung; Kim, Myunghyun

2013-01-01

Resonance parameter consists of subgroup level and weight. The subgroup weight is obtained by solving the ultrafine slowing down equation and fixed source problem. That means this cross section library procedure considers conservation of the shielded cross section for pin-cell in order to obtain subgroup parameters. There are some isotopes to be concerned for research such as actinides and thorium. Minor actinides(MA) are existing with very small amount in a spent fuel, but effect is not negligible in a high burnup fuel assemblies. Some MAs have high fission cross sections under thermal neutron spectrum. Thorium isotopes was not investigated as much as uranium, but it has high potential for future application. In this study, a new cross section library to be replaced with HELIOS library was generated and compared for the assembly calculation, specially for assembly with thorium. An average capture cross section value at a certain fuel pin and multiplication factor of assembly were compared with nTRACER calculation with HELIOS library and Monte Carlo calculation of MCNP with ENDF-B/II. The accuracy of library data generated for thorium isotope in nTRACER calculation was tested for WASB model. There was a great improvement in K-eff and capture cross section for this assembly compared with old library, HELIOS library

Characteristics of Differently Located Colorectal Cancers Support Proximal and Distal Classification: A Population-Based Study of 57,847 Patients.

Directory of Open Access Journals (Sweden)

Jiao Yang

Full Text Available It has been suggested that colorectal cancer be regarded as several subgroups defined according to tumor location rather than as a single entity. The current study aimed to identify the most useful method for grouping colorectal cancer by tumor location according to both baseline and survival characteristics.Cases of pathologically confirmed colorectal adenocarcinoma diagnosed from 2000 to 2012 were identified from the Surveillance, Epidemiology, and End Results database and categorized into three groups: right colon cancer (RCC, left colon cancer (LCC, and rectal cancer (ReC. Adjusted hazard ratios for known predictors of disease-specific survival (DSS in colorectal cancer were obtained using a Cox proportional hazards regression model.The study included 57847 patients: 43.5% with RCC, 37.7% with LCC, and 18.8% with ReC. Compared with LCC and ReC, RCC was more likely to affect old patients and women, and to be at advanced stage, poorly differentiated or un-differentiated, and mucinous. Patients with LCC or ReC had better DSS than those with RCC in subgroups including stage III or IV disease, age ≤70 years and non-mucinous adenocarcinoma. Conversely, patients with LCC or ReC had worse DSS than those with RCC in subgroups including age ˃70 years and mucinous adenocarcinoma.RCC differed from both LCC and ReC in several clinicopathologic characteristics and in DSS. It seems reasonable to group colorectal cancer into right-sided (i.e., proximal and left-sided (i.e., distal ones.

Current adjuvant treatment modalities for gastric cancer: From history to the future

Science.gov (United States)

Kilic, Leyla; Ordu, Cetin; Yildiz, Ibrahim; Sen, Fatma; Keskin, Serkan; Ciftci, Rumeysa; Pilanci, Kezban Nur

2016-01-01

The discrepancy between the surgical technique and the type of adjuvant chemotherapy used in clinical trials and patient outcomes in terms of overall survival rates has led to the generation of different adjuvant treatment protocols in distinct parts of the world. The adjuvant treatment recommendation is generally chemoradiotherapy in the United States, perioperative chemotherapy in the United Kingdom and parts of Europe, and chemotherapy in Asia. These options mainly rely on the United States Intergroup-0116, United Kingdom British Medical Research Council Adjuvant Gastric Infusional Chemotherapy, and the Asian Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer and Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer trials. However, the benefits were evident for only certain patients, which were not very homogeneous regarding the type of surgery, chemotherapy regimens, and stage of disease. Whether the dissimilarities in survival are attributable to surgical technique or intrinsic biological differences is a subject of debate. Regardless of the extent of surgery, multimodal therapy may offer modest survival advantage at least for diseases with lymph node involvement. Moreover, in the era of individualized treatment for most of the other cancer types, identification of special subgroups comprising those who will derive more or no benefit from adjuvant therapy merits further investigation. The aim of this review is to reveal the historical evolution and future reflections of adjuvant treatment modalities for resected gastric cancer patients. PMID:27190583

The subgroups in the special linear group over a skew field that contain the group of diagonal matrices

International Nuclear Information System (INIS)

Bui Xuan Hai.

1990-05-01

For an arbitrary skew field T we study the lattice of subgroups of the special linear group Γ=SL(n,T) that contain the subgroup Δ-SD(n,T) of diagonal matrices with Dieudonne's determinant equal to 1. We show that the description of these subgroups is standard in the following sense: For any subgroup H,Δ≤H≤Γ there exists a unique unital net such that Γ(σ) ≤H≤N(σ), where Γ(σ) is the net subgroup that corresponds to the net σ and N(σ) is the normalizer of Γ(σ) in Γ. (author). 11 refs

Clinical aspects and perspectives of erlotinib in the treatment of patients with biliary tract cancer

DEFF Research Database (Denmark)

Jensen, Lars Henrik

2016-01-01

INTRODUCTION: Patients with non-resectable biliary tract cancer have a poor prognosis even if treated with systemic chemotherapy. One hope for improving treatment is through molecular biology and the characterization of specific cancer driving alterations followed by the design of targeted drugs...... of patients benefitting from erlotinib. Until this subgroup has been defined, erlotinib has no value to biliary tract cancer patients in the daily clinic....

Divide and Conquer: Sub-Grouping of ASD Improves ASD Detection Based on Brain Morphometry

Science.gov (United States)

Baum, Stefi A.; Cahill, Nathan D.; Michael, Andrew M.

2016-01-01

Low success (ASD) classification using brain morphometry from the large multi-site ABIDE dataset and inconsistent findings on brain morphometric abnormalities in ASD can be attributed to the ASD heterogeneity. In this study, we show that ASD brain morphometry is highly heterogeneous, and demonstrate that the heterogeneity can be mitigated and classification improved if autism severity (AS), verbal IQ (VIQ) and age are used with morphometric features. Morphometric features from structural MRIs (sMRIs) of 734 males (ASD: 361, controls: 373) of ABIDE were derived using FreeSurfer. Applying the Random Forest classifier, an AUC of 0.61 was achieved. Adding VIQ and age to morphometric features, AUC improved to 0.68. Sub-grouping the subjects by AS, VIQ and age improved the classification with the highest AUC of 0.8 in the moderate-AS sub-group (AS = 7–8). Matching subjects on age and/or VIQ in each sub-group further improved the classification with the highest AUC of 0.92 in the low AS sub-group (AS = 4–5). AUC decreased with AS and VIQ, and was the lowest in the mid-age sub-group (13–18 years). The important features were mainly from the frontal, temporal, ventricular, right hippocampal and left amygdala regions. However, they highly varied with AS, VIQ and age. The curvature and folding index features from frontal, temporal, lingual and insular regions were dominant in younger subjects suggesting their importance for early detection. When the experiments were repeated using the Gradient Boosting classifier similar results were obtained. Our findings suggest that identifying brain biomarkers in sub-groups of ASD can yield more robust and insightful results than searching across the whole spectrum. Further, it may allow identification of sub-group specific brain biomarkers that are optimized for early detection and monitoring, increasing the utility of sMRI as an important tool for early detection of ASD. PMID:27065101

Development of ultra-short PCR assay to reveal BRAF V600 mutation status in Thai colorectal cancer tissues.

Science.gov (United States)

Chat-Uthai, Nunthawut; Vejvisithsakul, Pichpisith; Udommethaporn, Sutthirat; Meesiri, Puttarakun; Danthanawanit, Chetiya; Wongchai, Yannawan; Teerapakpinyo, Chinachote; Shuangshoti, Shanop; Poungvarin, Naravat

2018-01-01

The protein kinase BRAF is one of the key players in regulating cellular responses to extracellular signals. Somatic mutations of the BRAF gene, causing constitutive activation of BRAF, have been found in various types of human cancers such as malignant melanoma, and colorectal cancer. BRAF V600E and V600K, most commonly observed mutations in these cancers, may predict response to targeted therapies. Many techniques suffer from a lack of diagnostic sensitivity in mutation analysis in clinical samples with a low cancer cell percentage or poor-quality fragmented DNA. Here we present allele-specific real-time PCR assay for amplifying 35- to 45-base target sequences in BRAF gene. Forward primer designed for BRAF V600E detection is capable of recognizing both types of BRAF V600E mutation, i.e. V600E1 (c.1799T>A) and V600E2 (c.1799_1800delTGinsAA), as well as complex tandem mutation caused by nucleotide changes in codons 600 and 601. We utilized this assay to analyze Thai formalin-fixed paraffin-embedded tissues. Forty-eight percent of 178 Thai colorectal cancer tissues has KRAS mutation detected by highly sensitive commercial assays. Although these DNA samples contain low overall yield of amplifiable DNA, our newly-developed assay successfully revealed BRAF V600 mutations in 6 of 93 formalin-fixed paraffin-embedded colorectal cancer tissues which KRAS mutation was not detected. Ultra-short PCR assay with forward mutation-specific primers is potentially useful to detect BRAF V600 mutations in highly fragmented DNA specimens from cancer patients.

Subtypes of depression in cancer patients : An empirically driven approach

NARCIS (Netherlands)

Zhu, Lei; Ranchor, Adelita V; van der Lee, Marije; Garssen, Bert; Sanderman, Robbert; Schroevers, Maya J

PURPOSE: This study aimed to (1) identify subgroups of cancer patients with distinct subtypes of depression before the start of psychological care, (2) examine whether socio-demographic and medical characteristics distinguished these subtypes, and (3) examine whether people with distinct subtypes

Subtypes of depression in cancer patients: an empirically driven approach

NARCIS (Netherlands)

Zhu, Lei; Ranchor, A.V.; van der Lee, Marije; Garssen, Bert; Sanderman, Robbert; Schroevers, Maya J.

2016-01-01

Purpose This study aimed to (1) identify subgroups of cancer patients with distinct subtypes of depression before the start of psychological care, (2) examine whether socio-demographic and medical characteristics distinguished these subtypes, and (3) examine whether people with distinct subtypes

Causes of death in long-term lung cancer survivors: a SEER database analysis.

Science.gov (United States)

Abdel-Rahman, Omar

2017-07-01

Long-term (>5 years) lung cancer survivors represent a small but distinct subgroup of lung cancer patients and information about the causes of death of this subgroup is scarce. The Surveillance, Epidemiology and End Results (SEER) database (1988-2008) was utilized to determine the causes of death of long-term survivors of lung cancer. Survival analysis was conducted using Kaplan-Meier analysis and multivariate analysis was conducted using a Cox proportional hazard model. Clinicopathological characteristics and survival outcomes were assessed for the whole cohort. A total of 78,701 lung cancer patients with >5 years survival were identified. This cohort included 54,488 patients surviving 5-10 years and 24,213 patients surviving >10 years. Among patients surviving 5-10 years, 21.8% were dead because of primary lung cancer, 10.2% were dead because of other cancers, 6.8% were dead because of cardiac disease and 5.3% were dead because of non-malignant pulmonary disease. Among patients surviving >10 years, 12% were dead because of primary lung cancer, 6% were dead because of other cancers, 6.9% were dead because of cardiac disease and 5.6% were dead because of non-malignant pulmonary disease. On multivariate analysis, factors associated with longer cardiac-disease-specific survival in multivariate analysis include younger age at diagnosis (p death from primary lung cancer is still significant among other causes of death even 20 years after diagnosis of lung cancer. Moreover, cardiac as well as non-malignant pulmonary causes contribute a considerable proportion of deaths in long-term lung cancer survivors.

Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.

Science.gov (United States)

Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D; Eeles, Rosalind A; Chatterjee, Nilanjan; Schumacher, Fredrick R; Schildkraut, Joellen M; Lindström, Sara; Brennan, Paul; Bickeböller, Heike; Houlston, Richard S; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Amin Al Olama, Ali; Berndt, Sonja I; Giovannucci, Edward L; Grönberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir J; Stevens, Victoria L; Wiklund, Fredrik; Willett, Walter C; Goode, Ellen L; Permuth, Jennifer B; Risch, Harvey A; Reid, Brett M; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T; Chang-Claude, Jenny; Hudson, Thomas J; Kocarnik, Jonathan K; Newcomb, Polly A; Schoen, Robert E; Slattery, Martha L; White, Emily; Adank, Muriel A; Ahsan, Habibul; Aittomäki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; Dos-Santos-Silva, Isabel; Eliassen, A Heather; Figueroa, Jonine D; Flesch-Janys, Dieter; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M; Johnson, Nichola; Hall, Per; Hazra, Aditi; Hein, Rebecca; Hofman, Albert; Hopper, John L; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Müller-Myhsok, Bertram; Muranen, Taru A; Nevanlinna, Heli; Peeters, Petra H; Peto, Julian; Prentice, Ross L; Rahman, Nazneen; Sanchez, Maria Jose; Schmidt, Daniel F; Schmutzler, Rita K; Southey, Melissa C; Tamimi, Rulla; Travis, Ruth C; Turnbull, Clare; Uitterlinden, Andre G; Wang, Zhaoming; Whittemore, Alice S; Yang, Xiaohong R; Zheng, Wei; Buchanan, Daniel D; Casey, Graham; Conti, David V; Edlund, Christopher K; Gallinger, Steven; Haile, Robert W; Jenkins, Mark; Le Marchand, Loïc; Li, Li; Lindor, Noralene M; Schmit, Stephanie L; Thibodeau, Stephen N; Woods, Michael O; Rafnar, Thorunn; Gudmundsson, Julius; Stacey, Simon N; Stefansson, Kari; Sulem, Patrick; Chen, Y Ann; Tyrer, Jonathan P; Christiani, David C; Wei, Yongyue; Shen, Hongbing; Hu, Zhibin; Shu, Xiao-Ou; Shiraishi, Kouya; Takahashi, Atsushi; Bossé, Yohan; Obeidat, Ma'en; Nickle, David; Timens, Wim; Freedman, Matthew L; Li, Qiyuan; Seminara, Daniela; Chanock, Stephen J; Gong, Jian; Peters, Ulrike; Gruber, Stephen B; Amos, Christopher I; Sellers, Thomas A; Easton, Douglas F; Hunter, David J; Haiman, Christopher A; Henderson, Brian E; Hung, Rayjean J

2016-09-01

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103-14. ©2016 AACR. ©2016 American Association for Cancer Research.

Standardized assessment of tumor-infiltrating lymphocytes in breast cancer

DEFF Research Database (Denmark)

Tramm, Trine; Di Caterino, Tina; Jylling, Anne-Marie B

2018-01-01

INTRODUCTION: In breast cancer, there is a growing body of evidence that tumor-infiltrating lymphocytes (TILs) may have clinical utility and may be able to direct clinical decisions for subgroups of patients. Clinical utility is, however, not sufficient for warranting the implementation of a new...

Clinically distinct trajectories of fatigue and their longitudinal relationship with the disturbance of personal goals following a cancer diagnosis.

Science.gov (United States)

Müller, Fabiola; Tuinman, Marrit A; Janse, Moniek; Almansa, Josué; Sprangers, Mirjam A G; Smink, Ans; Ranchor, Adelita V; Fleer, Joke; Hagedoorn, Mariët

2017-09-01

Most studies on fatigue in patients with cancer aggregate its prevalence and severity on a group level, ignoring the possibility that subgroups of patients may differ widely in their development of fatigue. This study aimed to identify subgroups of patients with clinically distinct trajectories of fatigue from diagnosis to 18 months post-diagnosis. As fatigue might trigger goal disturbance, the study also identified trajectories of concrete and abstract goal disturbance and longitudinally examined their co-occurrence with fatigue. Prospective design with quantitative and qualitative method of data collection. Patients with colorectal cancer (n = 183) reported on their levels of fatigue and goal disturbance shortly after diagnosis (T 1 ) and at 7 months (T 2 ) and 18 months (T 3 ) post-diagnosis. Growth mixture model analyses were performed to identify trajectories of fatigue and goal disturbance. Guidelines for the clinical relevance of fatigue were applied. Four clinically distinct trajectories of fatigue were identified as follows: (1) persistent severe fatigue (25.4%), (2) moderate fatigue (56.1%), (3) no fatigue (13.8%), and (4) rapidly improving fatigue (4.7%). The majority of patients with cancer reported high disturbance of their concrete goals, while high disturbance of abstract goals was less evident. Fatigue and concrete goal disturbance co-occurred longitudinally. The fatigue and goal disturbance experienced from diagnosis to 18 months post-diagnosis differ considerably for subgroups of patients with cancer. Fatigue and concrete goal disturbance are persistent burdens in the majority of patients. Investigating symptom burden beyond average trends can guide clinicians to identify patients most in need for treatment. Targeting goal disturbance might benefit the psychological well-being in patients suffering from persistent symptoms. Statement of contribution What is already known on this subject? Fatigue is a common and distressing symptom at all

Caregiving associated with selected cancer risk behaviors and screening utilization among women: cross-sectional results of the 2009 BRFSS

Directory of Open Access Journals (Sweden)

Reeves Katherine W

2012-08-01

Full Text Available Abstract Background Informal caregiving is increasingly common as the U.S. population ages, and there is concern that caregivers are less likely than non-caregivers to practice health-promoting behaviors, including cancer screening. We examined caregiving effects on cancer risk behaviors and breast and cervical cancer screening in the 2009 Behavioral Risk Factor Surveillance System. Methods Women age ≥41 with data on breast and cervical cancer screening were included (weighted frequency 3,478,000 women. Cancer screening was classified according to American Cancer Society guidelines. We evaluated the association of caregiving with cancer risk behaviors (obesity, physical activity, alcohol intake, smoking status, and fruit/vegetable consumption and cancer screening (mammography, clinical breast exam [CBE], and Pap test using logistic regression overall and with stratification on age ( Results Caregivers had greater odds of being obese, physically active, and current smokers. Subgroup analyses revealed that caregiving was associated with obesity in younger women and whites, and with less obesity in older women. Also, caregiving was associated with smoking only among younger women and non-whites. Caregivers had greater odds of ever having had a mammogram or CBE, yet there was no association with mammogram, CBE, or Pap test within guidelines. Conclusions Caregiving was associated with some health behaviors that increase cancer risk, yet not with cancer screening within guidelines. Effects of caregiving by age and race require confirmation by additional studies.

Brain cortical structural differences between non-central nervous system cancer patients treated with and without chemotherapy compared to non-cancer controls: a cross-sectional pilot MRI study using clinically indicated scans

Science.gov (United States)

Shiroishi, Mark S.; Gupta, Vikash; Bigjahan, Bavrina; Cen, Steven Y.; Rashid, Faisal; Hwang, Darryl H.; Lerner, Alexander; Boyko, Orest B.; Liu, Chia-Shang Jason; Law, Meng; Thompson, Paul M.; Jahanshad, Neda

2017-11-01

Background: Increases in cancer survival have made understanding the basis of cancer-related cognitive impairment (CRCI) more important. CRCI neuroimaging studies have traditionally used dedicated research brain MRIs in breast cancer survivors with small sample sizes; little is known about other non-CNS cancers. However, there is a wealth of unused data from clinically-indicated MRIs that could be used to study CRCI. Objective: Evaluate brain cortical structural differences in those with non-CNS cancers using clinically-indicated MRIs. Design: Cross-sectional Patients: Adult non-CNS cancer and non-cancer control (C) patients who underwent clinically-indicated MRIs. Methods: Brain cortical surface area and thickness were measured using 3D T1-weighted images. An age-adjusted linear regression model was used and the Benjamini and Hochberg false discovery rate (FDR) corrected for multiple comparisons. Group comparisons were: cancer cases with chemotherapy (Ch+), cancer cases without chemotherapy (Ch-) and subgroup of lung cancer cases with and without chemotherapy vs C. Results: Sixty-four subjects were analyzed: 22 Ch+, 23 Ch- and 19 C patients. Subgroup analysis of 16 LCa was also performed. Statistically significant decreases in either cortical surface area or thickness were found in multiple ROIs primarily within the frontal and temporal lobes for all comparisons. Limitations: Several limitations were apparent including a small sample size that precluded adjustment for other covariates. Conclusions: Our preliminary results suggest that various types of non-CNS cancers, both with and without chemotherapy, may result in brain structural abnormalities. Also, there is a wealth of untapped clinical MRIs that could be used for future CRCI studies.

Ethnic Identity and Major Depression in Asian American Subgroups Nationwide: Differential Findings in Relation to Subcultural Contexts.

Science.gov (United States)

Ai, Amy L; Nicdao, Ethel G; Appel, Hoa B; Lee, Daniel Hyung Jik

2015-12-01

Asian Americans (AA) are the fastest growing minority population in the United States. Leading AA scholars have highlighted the unmet service needs and the necessity to investigate subgroup variations in the mental health of AAs. This study addressed a research gap of whether racial and ethnic identity (REI) in three AA subgroups (Chinese, Filipino, and Vietnamese) consistently protects against major depressive disorder (MDD), counteracting the deleterious role of discrimination. Using the National Latino and Asian American Study (NLAAS), we explored the varying and incremental predictive values of REI, above and beyond the effects of known demographic and acculturation predictors, alongside other potentially protective factors. In three sets of two-step logistic regressions, REI had an inverse relationship with MDD in the Filipino subgroup only but a positive association in the Chinese subgroup. The damaging role of negative REI moderated the effect of discrimination. The longest stay in the United States and discrimination predicted a higher likelihood of a MDD diagnosis in the Filipino subgroup. Social support contributed to the lower odds of MDD in Chinese and Vietnamese subgroups, had lower odds of having MDD, and religious attendance may act as a protective factor in the Vietnamese subgroup. Our findings do not reinforce uniform protection of REI but lend partial support for two underlying rationales. Based on cultural psychologists' framework, inconsistent findings are interpreted within the sociocultural contexts of the 3 subgroups. © 2015 Wiley Periodicals, Inc.

Clinico-Epidemiological Comparison of Delusion-Prominent and Hallucination-Prominent Clinical Subgroups of Paranoid Schizophrenia.

Science.gov (United States)

Kreinin, Anatoly; Krishtul, Vladimir; Kirsh, Zvi; Menuchin, Michael

2015-01-01

Though hallucinations and delusions are prominent basic impairments in schizophrenia, reports of the relationship between hallucinatory and delusional symptoms among schizophrenia patients are scant. To examine the epidemiological and clinical differences between mainly hallucinatory and mainly delusional subgroups of paranoid schizophrenia patients. One hundred schizophrenia patients, paranoid type, were recruited. In a cross-sectional study, participants were divided into Mainly Hallucinatory (H) and Mainly Delusional (D) subgroups. Demographic variables were compared and clinical characteristics were evaluated using the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, and the Clinical Global Impression Scale. The Quality-of-Life Enjoyment and Satisfaction Questionnaire-18 was used to assess quality of life. Clinically, the H group was more heterogeneous as expressed by the broader range of scores that described the clinical picture of patients in that subgroup (in 43 of 78 variables, 55.13%) and similar ranges of scores (31 of 78 variables, 39.74%) for patients in the D group. Duration of hospitalization was significantly longer in group H than in group D (p=0.047). There was no statistically significant difference between the H and D subgroups in demographic characteristics. There are distinct epidemiological and clinical differences between the H and D subgroups, with more severe positive and negative symptoms and greater functional impairment in the H group. Paranoid schizophrenia patients with prominent hallucinations have poorer prognosis and need intensive therapeutic rehabilitation beginning with onset-of-illness. Further genetic studies and comparisons of fMRI and/or PET findings are warranted to investigate additional distinctive characteristics of these subgroups.

Occupational exposure to hexavalent chromium and cancers of the gastrointestinal tract: a meta-analysis.

Science.gov (United States)

Gatto, Nicole M; Kelsh, Michael A; Mai, Diem Ha; Suh, Mina; Proctor, Deborah M

2010-08-01

We conducted a systematic literature review and meta-analysis of oral cavity, esophageal, stomach, small intestine, colon, and rectal cancers among workers occupationally exposed to Cr(VI). Using PubMed, studies published from 1950 to 2009 evaluating the relationship between Cr(VI) exposure and GI cancers were identified. Measures of effect and variability were extracted from 32 studies meeting specific inclusion criteria, and meta-analysis summary relative risk measures were calculated using random effects models and inverse variance weighting methods. Meta-standardized mortality ratios (SMRs) were, for cancer of the: oral cavity [1.02 (95% CI=0.77-1.34)]; esophagus [1.17 (95% CI=0.90-1.51)]; stomach [1.09 (95% CI=0.93-1.28)]; colon [0.89 (95% CI=0.70-1.12)]; and rectum [1.17 (95% CI=0.98-1.39)]. Analyses of more highly exposed subgroups included in the studies or subgroups based on geographic region or by industry with recognized Cr(VI) exposures (welding, chrome plating, chromate production, and pigment production) did not result in elevated meta-SMRs except for esophageal cancer among US cohorts [meta-SMR=1.49 (95% CI=1.06-2.09)]. However, that finding was based on a subgroup of only four studies, one of which was a PMR study. Potential confounding by socioeconomic status (SES), diet and/or smoking, or limitations due to the healthy-worker effect (HWE) were evaluated, and while smoking, diet and SES may be important factors that may have upwardly biased the meta-SMRs, HWE is not likely to have significantly affected the summary results. None of three studies reporting small intestine cancers observed a statistically significant increased risk. These meta-analyses and literature review indicate that Cr(VI)-exposed workers are not at a greater risk of GI cancers than the general population.

Positive and negative meanings are simultaneously ascribed to colorectal cancer: relationship to quality of life and psychosocial adjustment.

Science.gov (United States)

Camacho, Aldo Aguirre; Garland, Sheila N; Martopullo, Celestina; Pelletier, Guy

2014-08-01

Experiencing cancer can give rise to existential concerns causing great distress, and consequently drive individuals to make sense of what cancer may mean to their lives. To date, meaning-based research in the context of cancer has largely focused on one possible outcome of this process, the emergence of positive meanings (e.g. post-traumatic growth). However, negative meanings may also be ascribed to cancer, simultaneously with positive meanings. This study focused on the nature of the co-existence of positive and negative meanings in a sample of individuals diagnosed with colorectal cancer to find out whether negative meaning had an impact on quality of life and psychosocial adjustment above and beyond positive meaning. Participants were given questionnaires measuring meaning-made, quality of life, and psychological distress. Semi structured interviews were conducted with a subgroup from the original sample. Hierarchical multiple regression analyses revealed that negative meaning-made (i.e. helplessness) was a significant predictor of poor quality of life and increased levels of depression/anxiety above and beyond positive meaning-made (i.e. life meaningfulness, acceptance, and perceived benefits). Correlational analyses and interview data revealed that negative meaning-made was mainly associated with physical and functional disability, while positive meaning-made was mostly related to emotional and psychological well-being. Meanings of varying valence may simultaneously be ascribed to cancer as it impacts different life dimensions, and they may independently influence quality of life and psychosocial adjustment. The presence of positive meaning was not enough to prevent the detrimental effects of negative meaning on psychosocial adjustment and quality of life among individuals taking part in this study. Future attention to negative meaning is warranted, as it may be at least as important as positive meaning in predicting psychosocial adjustment and quality of

Farewell to GBM-O: Genomic and transcriptomic profiling of glioblastoma with oligodendroglioma component reveals distinct molecular subgroups.

Science.gov (United States)

Hinrichs, Benjamin H; Newman, Scott; Appin, Christina L; Dunn, William; Cooper, Lee; Pauly, Rini; Kowalski, Jeanne; Rossi, Michael R; Brat, Daniel J

2016-01-13

Glioblastoma with oligodendroglioma component (GBM-O) was recognized as a histologic pattern of glioblastoma (GBM) by the World Health Organization (WHO) in 2007 and is distinguished by the presence of oligodendroglioma-like differentiation. To better understand the genetic underpinnings of this morphologic entity, we performed a genome-wide, integrated copy number, mutational and transcriptomic analysis of eight (seven primary, primary secondary) cases. Three GBM-O samples had IDH1 (p.R132H) mutations; two of these also demonstrated 1p/19q co-deletion and had a proneural transcriptional profile, a molecular signature characteristic of oligodendroglioma. The additional IDH1 mutant tumor lacked 1p/19q co-deletion, harbored a TP53 mutation, and overall, demonstrated features most consistent with IDH mutant (secondary) GBM. Finally, five tumors were IDH wild-type (IDHwt) and had chromosome seven gains, chromosome 10 losses, and homozygous 9p deletions (CDKN2A), alterations typical of IDHwt (primary) GBM. IDHwt GBM-Os also demonstrated EGFR and PDGFRA amplifications, which correlated with classical and proneural expression subtypes, respectively. Our findings demonstrate that GBM-O is composed of three discrete molecular subgroups with characteristic mutations, copy number alterations and gene expression patterns. Despite displaying areas that morphologically resemble oligodendroglioma, the current results indicate that morphologically defined GBM-O does not correspond to a particular genetic signature, but rather represents a collection of genetically dissimilar entities. Ancillary testing, especially for IDH and 1p/19q, should be used for determining these molecular subtypes.

electropherotypes and subgroups of group a rotaviruses circulating ...

African Journals Online (AJOL)

Emmanuel Ameh

diarrhea caused by rotaviruses. The virus is a double stranded RNA (dsRNA) virus with 11 segments. Group A rotaviruses show a characteristic 4-2-3-2 pattern following electrophoresis. The VP6 subgroups, I and II exist. This work was carried out to study the prevalence of rotavirus infection among children 0-5 years with ...

Prognostic value of platelet-to-lymphocyte ratio in oncologic outcomes of esophageal cancer: A systematic review and meta-analysis.

Science.gov (United States)

Zhang, Xiangwei; Wang, Yang; Zhao, Linping; Sang, Shaowei; Zhang, Lin

2018-04-01

The platelet-to-lymphocyte ratio (PLR) is a useful prognostic factor in several cancers. However, the prognostic role of PLR in esophageal cancer remains controversial. The aim of this study is to evaluate the association between PLR and the oncologic outcome of esophageal cancer patients through a meta-analysis. Relevant articles were researched from Embase, PubMed, and Web of Science databases. The meta-analysis was performed using hazard ratio (HR) and 95% confidence intervals (CIs) as effect measures. Finally, 19 articles with 6134 patients were included in our study. The summary results indicated that the elevated PLR was negatively related to overall survival (HR= 1.263; 95% CI 1.094, 1.458). The subgroup analysis revealed that increased PLR was associated with poor overall survival in esophageal cancer patients for Asians (HR=1.252; 95% CI 1.141, 1.373) but not for Caucasians (HR=1.463; 95% CI 0.611, 3.502). When the patients were segregated by pathological type, sample size, and HR estimate method, high PLR was also significantly correlated with poor overall survival. In contrast, elevated PLR was not statistically associated with disease-free survival or cancer-specific survival. High PLR is associated with poor overall survival in patients with esophageal cancer. PLR may be a significant predictive biomarker in patients with esophageal cancer. Further large-cohort studies are needed to confirm these findings.

Discrete neurocognitive subgroups in fully or partially remitted bipolar disorder

DEFF Research Database (Denmark)

Jensen, Johan Høy; Knorr, Ulla; Vinberg, Maj

2016-01-01

BACKGROUND: Neurocognitive impairment in remitted patients with bipolar disorder contributes to functional disabilities. However, the pattern and impact of these deficits are unclear. METHODS: We pooled data from 193 fully or partially remitted patients with bipolar disorder and 110 healthy...... controls. Hierarchical cluster analysis was conducted to determine whether there are discrete neurocognitive subgroups in bipolar disorder. The pattern of the cognitive deficits and the characteristics of patients in these neurocognitive subgroups were examined with analyses of covariance and least...... was cross-sectional which limits inferences regarding the causality of the findings. CONCLUSION: Globally and selectively impaired bipolar disorder patients displayed more functional disabilities than those who were cognitively intact. The present findings highlight a clinical need to systematically screen...

A Low-Complexity Subgroup Formation with QoS-Aware for Enhancing Multicast Services in LTE Networks

Science.gov (United States)

Algharem, M.; Omar, M. H.; Rahmat, R. F.; Budiarto, R.

2018-03-01

The high demand of Multimedia services on in Long Term Evolution (LTE) and beyond networks forces the networks operators to find a solution that can handle the huge traffic. Along with this, subgroup formation techniques are introduced to overcome the limitations of the Conventional Multicast Scheme (CMS) by splitting the multicast users into several subgroups based on the users’ channels quality signal. However, finding the best subgroup configuration with low complexity is need more investigations. In this paper, an efficient and simple subgroup formation mechanisms are proposed. The proposed mechanisms take the transmitter MAC queue in account. The effectiveness of the proposed mechanisms is evaluated and compared with CMS in terms of throughput, fairness, delay, Block Error Rate (BLER).

MicroRNA Related Polymorphisms and Breast Cancer Risk

DEFF Research Database (Denmark)

Khan, Sofia; Greco, Dario; Michailidou, Kyriaki

2014-01-01

Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer....... We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41......,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated...

A comparison of three clustering methods for finding subgroups in MRI, SMS or clinical data

DEFF Research Database (Denmark)

Kent, Peter; Jensen, Rikke K; Kongsted, Alice

2014-01-01

). There is a scarcity of head-to-head comparisons that can inform the choice of which clustering method might be suitable for particular clinical datasets and research questions. Therefore, the aim of this study was to perform a head-to-head comparison of three commonly available methods (SPSS TwoStep CA, Latent Gold...... LCA and SNOB LCA). METHODS: The performance of these three methods was compared: (i) quantitatively using the number of subgroups detected, the classification probability of individuals into subgroups, the reproducibility of results, and (ii) qualitatively using subjective judgments about each program...... classify individuals into those subgroups. CONCLUSIONS: Our subjective judgement was that Latent Gold offered the best balance of sensitivity to subgroups, ease of use and presentation of results with these datasets but we recognise that different clustering methods may suit other types of data...

From bench to bedside: What do we know about hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer?

Science.gov (United States)

Wu, Victoria Shang; Kanaya, Noriko; Lo, Chiao; Mortimer, Joanne; Chen, Shiuan

2015-09-01

Breast cancer is a heterogeneous disease. Thanks to extensive efforts from research scientists and clinicians, treatment for breast cancer has advanced into the era of targeted medicine. With the use of several well-established biomarkers, such as hormone receptors (HRs) (i.e., estrogen receptor [ER] and progesterone receptor [PgR]) and human epidermal growth factor receptor-2 (HER2), breast cancer patients can be categorized into multiple subgroups with specific targeted treatment strategies. Although therapeutic strategies for HR-positive (HR+) HER2-negative (HER2-) breast cancer and HR-negative (HR-) HER2-positive (HER2+) breast cancer are well-defined, HR+ HER2+ breast cancer is still an overlooked subgroup without tailored therapeutic options. In this review, we have summarized the molecular characteristics, etiology, preclinical tools and therapeutic options for HR+ HER2+ breast cancer. We hope to raise the attention of both the research and the medical community on HR+ HER2+ breast cancer, and to advance patient care for this subtype of disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

FDG PET/CT in cancer

DEFF Research Database (Denmark)

Petersen, Henrik; Holdgaard, Paw Christian; Madsen, Poul Henning

2016-01-01

PURPOSE: The Region of Southern Denmark (RSD), covering 1.2 of Denmark's 5.6 million inhabitants, established a task force to (1) retrieve literature evidence for the clinical use of positron emission tomography (PET)/CT and provide consequent recommendations and further to (2) compare the actual...... use of PET/CT in the RSD with these recommendations. This article summarizes the results. METHODS: A Work Group appointed a professional Subgroup which made Clinician Groups conduct literature reviews on six selected cancers responsible for 5,768 (62.6 %) of 9,213 PET/CT scans in the RSD in 2012...... use of PET/CT and literature-based recommendations was high in the first five mentioned cancers in that 96.2 % of scans were made for grade A or B indications versus only 22.2 % in gynaecological cancers. CONCLUSION: Evidence-based usefulness was reported in five of six selected cancers; evidence...

Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer

Directory of Open Access Journals (Sweden)

Chiara Francavilla

2017-03-01

Full Text Available Our understanding of the molecular determinants of cancer is still inadequate because of cancer heterogeneity. Here, using epithelial ovarian cancer (EOC as a model system, we analyzed a minute amount of patient-derived epithelial cells from either healthy or cancerous tissues by single-shot mass-spectrometry-based phosphoproteomics. Using a multi-disciplinary approach, we demonstrated that primary cells recapitulate tissue complexity and represent a valuable source of differentially expressed proteins and phosphorylation sites that discriminate cancer from healthy cells. Furthermore, we uncovered kinase signatures associated with EOC. In particular, CDK7 targets were characterized in both EOC primary cells and ovarian cancer cell lines. We showed that CDK7 controls cell proliferation and that pharmacological inhibition of CDK7 selectively represses EOC cell proliferation. Our approach defines the molecular landscape of EOC, paving the way for efficient therapeutic approaches for patients. Finally, we highlight the potential of phosphoproteomics to identify clinically relevant and druggable pathways in cancer.

Association between CD14 gene polymorphisms and cancer risk: a meta-analysis.

Directory of Open Access Journals (Sweden)

Jun Wang

Full Text Available BACKGROUND: Two polymorphisms, -260C/T and -651C/T, in the CD14 gene have been implicated in susceptibility to cancer. However, the results remain inconclusive. This meta-analysis aimed to investigate the association between the two polymorphisms and risk of cancer. METHODS: All eligible case-control studies published up to March 2014 were identified by searching PubMed, Web of Science, CNKI and WanFang database. Pooled odds ratio (OR with 95% confidence interval (CI were used to access the strength of this association in fixed- or random-effects model. RESULTS: 17 case-control studies from fourteen articles were included. Of those, there were 17 studies (4198 cases and 4194 controls for -260C/T polymorphism and three studies (832 cases and 1190 controls for -651C/T polymorphism. Overall, no significant associations between the two polymorphisms of CD14 gene and cancer risk were found. When stratified by ethnicity, cancer type and source of control, similar results were observed among them. In addition, in further subgroups analysis by Helicobacter pylori (H. pylori infection status and tumor location in gastric cancer subgroup, we found that the CD14 -260C/T polymorphism may increase the risk of gastric cancer in H. pylori-infected individuals. CONCLUSIONS: This meta-analysis suggests that the CD14 -260C/T polymorphism may increase the risk of gastric cancer in H. pylori-infected individuals. However, large and well-designed studies are warranted to validate our findings.

Cross-cancer genome-wide analysis of lung, ovary, breast, prostate and colorectal cancer reveals novel pleiotropic associations

Science.gov (United States)

Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D.; Eeles, Rosalind A.; Chatterjee, Nilanjan; Schumacher, Fred; Schildkraut, Joellen; Lindström, Sara; Brennan, Paul; Bickeböller, Heike; Houlston, Richard S.; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Olama, Ali Amin Al; Berndt, Sonja I; Giovannucci, Edward; Grönberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir; Stevens, Victoria L.; Wiklund, Fredrik; Willett, Walter; Goode, Ellen L.; Permuth, Jennifer; Risch, Harvey A.; Reid, Brett M.; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T.; Chang-Claude, Jenny; Hudson, Thomas J.; Kocarnik, Jonathan K.; Newcomb, Polly A.; Schoen, Robert E.; Slattery, Martha L.; White, Emily; Adank, Muriel A.; Ahsan, Habibul; Aittomäki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; dos-Santos-Silva, Isabel; Eliassen, A. Heather; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M.; Johnson, Nichola; Hall, Per; Hazra, Aditi; Hein, Rebecca; Hofman, Albert; Hopper, John L.; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G.; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Müller-Myhsok, Bertram; Muranen, Taru A.; Nevanlinna, Heli; Peeters, Petra H.; Peto, Julian; Prentice, Ross L.; Rahman, Nazneen; Sanchez, Maria Jose; Schmidt, Daniel F.; Schmutzler, Rita K.; Southey, Melissa C.; Tamimi, Rulla; Travis, Ruth C.; Turnbull, Clare; Uitterlinden, Andre G.; Wang, Zhaoming; Whittemore, Alice S.; Yang, Xiaohong R.; Zheng, Wei; Rafnar, Thorunn; Gudmundsson, Julius; Stacey, Simon N.; Stefansson, Kari; Sulem, Patrick; Chen, Y. Ann; Tyrer, Jonathan P.; Christiani, David C.; Wei, Yongyue; Shen, Hongbing; Hu, Zhibin; Shu, Xiao-Ou; Shiraishi, Kouya; Takahashi, Atsushi; Bossé, Yohan; Obeidat, Ma’en; Nickle, David; Timens, Wim; Freedman, Matthew L.; Li, Qiyuan; Seminara, Daniela; Chanock, Stephen J.; Gong, Jian; Peters, Ulrike; Gruber, Stephen B.; Amos, Christopher I.; Sellers, Thomas A.; Easton, Douglas F.; Hunter, David J.; Haiman, Christopher A.; Henderson, Brian E.; Hung, Rayjean J.

2016-01-01

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-staged approach to conduct genome-wide association studies for lung, ovary, breast, prostate and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. PMID:27197191

A 6-gene signature identifies four molecular subgroups of neuroblastoma

Science.gov (United States)

2011-01-01

Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples). Four distinct clusters were identified by Principal Components Analysis (PCA) in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples) using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p INSS stage 4 and/or dead of disease, p < 0.05, Fisher's exact test). Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group's specific characteristics. PMID:21492432

Identification of early breast cancer patient cohorts who may benefit from lapatinib therapy

DEFF Research Database (Denmark)

Strasser-Weippl, Kathrin; Horick, Nora; Smith, Ian E

2016-01-01

with HER2+ early breast cancer not treated with trastuzumab. We performed subgroup analyses and number-needed-to-treat (NNT) calculations using patient and tumour associated predictors. Hormone receptor negative (HR-) patients on lapatinib had a significantly prolonged disease-free survival (DFS) compared...... 5 years) was between 5.9 (node positive patients trastuzumab for HR unselected patients (e.g. 15.6 for DFS at 4 years in HERA). In a subgroup analysis of the adjuvant TEACH trial, we show...... that anti-HER2 monotherapy with a TKI is beneficial as adjuvant therapy in a subgroup of patients. NNT in HER2+ HR- patients are in range with those reported from up-front adjuvant trastuzumab trials....

On approximation of Lie groups by discrete subgroups

Indian Academy of Sciences (India)

2016-08-26

Aug 26, 2016 ... The notion of approximation of Lie groups by discrete subgroups was introduced by Tôyama in Kodai Math. Sem. Rep. 1 (1949) 36–37 and investigated in detail by Kuranishi in Nagoya Math. J. 2 (1951) 63–71. It is known as a theorem of Tôyama that any connected Lie group approximated by discrete ...

Notes on discrete subgroups of Möbius transformations

Indian Academy of Sciences (India)

Abstract. Jørgensen's inequality gives a necessary condition for a nonelementary two generator subgroup of SL(2, C) to be discrete. By embedding SL(2, C) into. ˆU(1, 1; H), we obtain a new type of Jørgensen's inequality, which is in terms of the coefficients of involved isometries. We provide an example to show that this ...

Non-meagre subgroups of reals disjoint with meagre sets

Czech Academy of Sciences Publication Activity Database

Kostana, Ziemowit

2018-01-01

Roč. 241, June (2018), s. 11-19 ISSN 0166-8641 Institutional support: RVO:67985840 Keywords : algebraic sum * Baire property * non-meaurable subgroup Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 0.377, year: 2016 https://www.sciencedirect.com/science/ article /pii/S0166864118300567

Triple SILAC quantitative proteomic analysis reveals differential abundance of cell signaling proteins between normal and lung cancer-derived exosomes.

Science.gov (United States)

Clark, David J; Fondrie, William E; Yang, Austin; Mao, Li

2016-02-05

Exosomes are 30-100 nm sized membrane vesicles released by cells into the extracellular space that mediate intercellular communication via transfer of proteins and other biological molecules. To better understand the role of these microvesicles in lung carcinogenesis, we employed a Triple SILAC quantitative proteomic strategy to examine the differential protein abundance between exosomes derived from an immortalized normal bronchial epithelial cell line and two non-small cell lung cancer (NSCLC) cell lines harboring distinct activating mutations in the cell signaling molecules: Kirsten rat sarcoma viral oncogene homolog (KRAS) or epidermal growth factor receptor (EGFR). In total, we were able to quantify 721 exosomal proteins derived from the three cell lines. Proteins associated with signal transduction, including EGFR, GRB2 and SRC, were enriched in NSCLC exosomes, and could actively regulate cell proliferation in recipient cells. This study's investigation of the NSCLC exosomal proteome has identified enriched protein cargo that can contribute to lung cancer progression, which may have potential clinical implications in biomarker development for patients with NSCLC. The high mortality associated with lung cancer is a result of late-stage diagnosis of the disease. Current screening techniques used for early detection of lung cancer lack the specificity for accurate diagnosis. Exosomes are nano-sized extracellular vesicles, and the increased abundance of select protein cargo in exosomes derived from cancer cells may be used for diagnostic purposes. In this paper, we applied quantitative proteomic analysis to elucidate abundance differences in exosomal protein cargo between two NSCLC cell lines with distinctive oncogene mutations and an immortalized normal bronchial epithelial cell line. This study revealed proteins associated with cell adhesion, the extracellular matrix, and a variety of signaling molecules were enriched in NSCLC exosomes. The present data reveals

Integrated analysis of DNA methylation and gene expression reveals specific signaling pathways associated with platinum resistance in ovarian cancer

Directory of Open Access Journals (Sweden)

Chung Jae

2009-06-01

Full Text Available Abstract Background Cisplatin and carboplatin are the primary first-line therapies for the treatment of ovarian cancer. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, resulting in fully chemoresistant, fatal disease. Although the precise mechanism(s underlying the development of platinum resistance in late-stage ovarian cancer patients currently remains unknown, CpG-island (CGI methylation, a phenomenon strongly associated with aberrant gene silencing and ovarian tumorigenesis, may contribute to this devastating condition. Methods To model the onset of drug resistance, and investigate DNA methylation and gene expression alterations associated with platinum resistance, we treated clonally derived, drug-sensitive A2780 epithelial ovarian cancer cells with increasing concentrations of cisplatin. After several cycles of drug selection, the isogenic drug-sensitive and -resistant pairs were subjected to global CGI methylation and mRNA expression microarray analyses. To identify chemoresistance-associated, biological pathways likely impacted by DNA methylation, promoter CGI methylation and mRNA expression profiles were integrated and subjected to pathway enrichment analysis. Results Promoter CGI methylation revealed a positive association (Spearman correlation of 0.99 between the total number of hypermethylated CGIs and GI50 values (i.e., increased drug resistance following successive cisplatin treatment cycles. In accord with that result, chemoresistance was reversible by DNA methylation inhibitors. Pathway enrichment analysis revealed hypermethylation-mediated repression of cell adhesion and tight junction pathways and hypomethylation-mediated activation of the cell growth-promoting pathways PI3K/Akt, TGF-beta, and cell cycle progression, which may contribute to the onset of chemoresistance in ovarian cancer cells. Conclusion Selective epigenetic disruption of distinct biological

Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer.

Science.gov (United States)

Francavilla, Chiara; Lupia, Michela; Tsafou, Kalliopi; Villa, Alessandra; Kowalczyk, Katarzyna; Rakownikow Jersie-Christensen, Rosa; Bertalot, Giovanni; Confalonieri, Stefano; Brunak, Søren; Jensen, Lars J; Cavallaro, Ugo; Olsen, Jesper V

2017-03-28

Our understanding of the molecular determinants of cancer is still inadequate because of cancer heterogeneity. Here, using epithelial ovarian cancer (EOC) as a model system, we analyzed a minute amount of patient-derived epithelial cells from either healthy or cancerous tissues by single-shot mass-spectrometry-based phosphoproteomics. Using a multi-disciplinary approach, we demonstrated that primary cells recapitulate tissue complexity and represent a valuable source of differentially expressed proteins and phosphorylation sites that discriminate cancer from healthy cells. Furthermore, we uncovered kinase signatures associated with EOC. In particular, CDK7 targets were characterized in both EOC primary cells and ovarian cancer cell lines. We showed that CDK7 controls cell proliferation and that pharmacological inhibition of CDK7 selectively represses EOC cell proliferation. Our approach defines the molecular landscape of EOC, paving the way for efficient therapeutic approaches for patients. Finally, we highlight the potential of phosphoproteomics to identify clinically relevant and druggable pathways in cancer. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

1842676957299765Latent class cluster analysis to understand heterogeneity in prostate cancer treatment utilities

Directory of Open Access Journals (Sweden)

Meghani Salimah

2009-01-01

Full Text Available Abstract Background Men with prostate cancer are often challenged to choose between conservative management and a range of available treatment options each carrying varying risks and benefits. The trade-offs are between an improved life-expectancy with treatment accompanied by important risks such as urinary incontinence and erectile dysfunction. Previous studies of preference elicitation for prostate cancer treatment have found considerable heterogeneity in individuals' preferences for health states given similar treatments and clinical risks. Methods Using latent class mixture model (LCA, we first sought to understand if there are unique patterns of heterogeneity or subgroups of individuals based on their prostate cancer treatment utilities (calculated time trade-off utilities for various health states and if such unique subgroups exist, what demographic and urological variables may predict membership in these subgroups. Results The sample (N = 244 included men with prostate cancer (n = 188 and men at-risk for disease (n = 56. The sample was predominantly white (77%, with mean age of 60 years (SD ± 9.5. Most (85.9% were married or living with a significant other. Using LCA, a three class solution yielded the best model evidenced by the smallest Bayesian Information Criterion (BIC, substantial reduction in BIC from a 2-class solution, and Lo-Mendell-Rubin significance of < .001. The three identified clusters were named high-traders (n = 31, low-traders (n = 116, and no-traders (n = 97. High-traders were more likely to trade survival time associated with treatment to avoid potential risks of treatment. Low-traders were less likely to trade survival time and accepted risks of treatment. The no-traders were likely to make no trade-offs in any direction favouring the status quo. There was significant difference among the clusters in the importance of sexual activity (Pearson's χ2 = 16.55, P = 0.002; Goodman and Kruskal tau = 0.039, P < 0.001. In

Transcriptome classification reveals molecular subtypes in psoriasis

Directory of Open Access Journals (Sweden)

Ainali Chrysanthi

2012-09-01

Full Text Available Abstract Background Psoriasis is an immune-mediated disease characterised by chronically elevated pro-inflammatory cytokine levels, leading to aberrant keratinocyte proliferation and differentiation. Although certain clinical phenotypes, such as plaque psoriasis, are well defined, it is currently unclear whether there are molecular subtypes that might impact on prognosis or treatment outcomes. Results We present a pipeline for patient stratification through a comprehensive analysis of gene expression in paired lesional and non-lesional psoriatic tissue samples, compared with controls, to establish differences in RNA expression patterns across all tissue types. Ensembles of decision tree predictors were employed to cluster psoriatic samples on the basis of gene expression patterns and reveal gene expression signatures that best discriminate molecular disease subtypes. This multi-stage procedure was applied to several published psoriasis studies and a comparison of gene expression patterns across datasets was performed. Conclusion Overall, classification of psoriasis gene expression patterns revealed distinct molecular sub-groups within the clinical phenotype of plaque psoriasis. Enrichment for TGFb and ErbB signaling pathways, noted in one of the two psoriasis subgroups, suggested that this group may be more amenable to therapies targeting these pathways. Our study highlights the potential biological relevance of using ensemble decision tree predictors to determine molecular disease subtypes, in what may initially appear to be a homogenous clinical group. The R code used in this paper is available upon request.

The impact of national cancer awareness campaigns for bowel and lung cancer symptoms on sociodemographic inequalities in immediate key symptom awareness and GP attendances

Science.gov (United States)

Moffat, J; Bentley, A; Ironmonger, L; Boughey, A; Radford, G; Duffy, S

2015-01-01

Background: National campaigns focusing on key symptoms of bowel and lung cancer ran in England in 2012, targeting men and women over the age of 50 years, from lower socioeconomic groups. Methods: Data from awareness surveys undertaken with samples of the target audience (n=1245/1140 pre-/post-bowel campaign and n=1412/1246 pre-/post-lung campaign) and Read-code data extracted from a selection general practitioner (GP) practices (n=355 for bowel and n=486 for lung) were analysed by population subgroups. Results: Unprompted symptom awareness: There were no significant differences in the magnitude of shift in ABC1 vs C2DE groups for either campaign. For the bowel campaign, there was a significantly greater increase in awareness of blood in stools in the age group 75+ years compared with the 55–74 age group, and of looser stools in men compared with women. Prompted symptom awareness: Endorsement of ‘blood in poo' remained stable, overall and across different population subgroups. Men showed a significantly greater increase in endorsement of ‘looser poo' as a definite warning sign of bowel cancer than women. There were no significant differences across subgroups in endorsement of a 3-week cough as a definite warning sign of lung cancer. GP attendances: Overall, there were significant increases in attendances for symptoms directly linked to the campaigns, with the largest percentage increase seen in the 50–59 age group. For the bowel campaign, the increase was significantly greater for men and for practices in the most-deprived quintile, whereas for lung the increase was significantly greater for practices in the least-deprived quintile. Conclusions: The national bowel and lung campaigns reached their target audience and have also influenced younger and more affluent groups. Differences in impact within the target audience were also seen. There would seem to be no unduly concerning widening in inequalities, but further analyses of the equality of impact across

Differences in feedforward trunk muscle activity in subgroups of patients with mechanical low back pain.

Science.gov (United States)

Silfies, Sheri P; Mehta, Rupal; Smith, Sue S; Karduna, Andrew R

2009-07-01

To investigate alterations in trunk muscle timing patterns in subgroups of patients with mechanical low back pain (MLBP). Our hypothesis was that subjects with MLBP would demonstrate delayed muscle onset and have fewer muscles functioning in a feedforward manner than the control group. We further hypothesized that we would find differences between subgroups of our patients with MLBP, grouped according to diagnosis (segmental instability and noninstability). Case-control. Laboratory. Forty-three patients with chronic MLBP (25 instability, 18 noninstability) and 39 asymptomatic controls. Not applicable. Surface electromyography was used to measure onset time of 10 trunk muscles during a self-perturbation task. Trunk muscle onset latency relative to the anterior deltoid was calculated and the number of muscles functioning in feedforward determined. Activation timing patterns (Pfeedforward (P=.02; eta=.30; 1-beta=.83) were statistically different between patients with MLBP and controls. The control group activated the external oblique, lumbar multifidus, and erector spinae muscles in a feedforward manner. The heterogeneous MLBP group did not activate the trunk musculature in feedforward, but responded with significantly delayed activations. MLBP subgroups demonstrated significantly different timing patterns. The noninstability MLBP subgroup activated trunk extensors in a feedforward manner, similar to the control group, but significantly earlier than the instability subgroup. Lack of feedforward activation of selected trunk musculature in patients with MLBP may result in a period of inefficient muscular stabilization. Activation timing was more impaired in the instability than the noninstability MLBP subgroup. Training specifically for recruitment timing may be an important component of the rehabilitation program.

Tailored radiotherapeutic strategies for disseminated uterine cervical cancer patients

International Nuclear Information System (INIS)

Im, Jung Ho; Yoon, Hong In; Kim, Sunghoon; Nam, Eun Ji; Kim, Sang Wun; Yim, Ga Won; Keum, Ki Chang; Kim, Young Tae; Kim, Gwi Eon; Kim, Yong Bae

2015-01-01

To investigate the role of radiotherapy (RT) in and to suggest radiotherapeutic strategies for patients presenting with disseminated cervical cancer. We retrospectively analyzed 50 patients diagnosed as the disseminated cervical cancer with distant lymph nodal or visceral organ metastasis between September 1980 and August 2012. Patients were divided into two subgroups according to visceral organ metastasis: 35 patients diagnosed with distant lymph node metastasis only (group A) and 15 patients with visceral organ metastasis (group B). All patients received external beam RT to the pelvis (median dose 45 Gy) and high-dose rate intracavitary RT (median dose 30 Gy). Thirty-nine patients (78%) received chemotherapy. Median follow-up time was 74 months. The 5-year pelvic control rate (PCR) was 85.8%, and the progression-free survival (PFS), and overall survival (OS) rates were 28.7%, and 36.2%, respectively. The major treatment failure was systemic progression (32 patients, 64%). The 5-year PCRs in groups A and B were 87.4% and 74.7%, respectively (p > 0.05). Meanwhile, PFS and OS rates for group A were significantly better than those for group B (35.3% vs. 13.3%, p = 0.010; and 46.3% vs. 13.3%, p = 0.009, respectively). Our data revealed considerable prognostic heterogeneity in disseminated cervical cancer. Even though a high PCR was achieved in patients treated with definitive RT, survival outcomes were dependent on progression of visceral organ metastasis. Therefore, personalized RT and chemotherapy treatment strategies according to the presence of visceral organ metastasis in disseminated cervical cancer patients may help improve clinical outcomes

Identification of subgroups of inflammatory and degenerative MRI findings in the spine and sacroiliac joints

DEFF Research Database (Denmark)

Arnbak, Bodil Al-Mashhadi; Jensen, Rikke Krüger; Manniche, Claus

and the clinical presentation of back pain. The objectives of this explorative study were: 1) Investigate subgroups of MRI findings of the spine and sacroiliac joints (SIJs) using Latent Class Analysis (LCA) and 2) Investigate whether these subgroups differ in their demographic and clinical characteristics...

A Preclinical Model of Chronic Alcohol Consumption Reveals Increased Metastatic Seeding of Colon Cancer Cells in the Liver.

Science.gov (United States)

Im, Hwi-Jin; Kim, Hyeong-Geug; Lee, Jin-Seok; Kim, Hyo-Seon; Cho, Jung-Hyo; Jo, Il-Joo; Park, Sung-Joo; Son, Chang-Gue

2016-04-01

Liver metastasis is the main cause of death from colorectal cancer. Alcohol consumption impacts liver function and is suggested to be an independent risk factor for liver metastasis of colorectal cancer, but no experimental evidence supporting this hypothesis has been demonstrated to date. In this study, we investigated the effect of alcohol intake on liver metastasis. We examined colon cancer cell spread from the spleen in mice provided with water (control group), alcohol for 4 weeks before tumor injection (prealcohol), alcohol for 3 weeks after tumor injection (postalcohol), or alcohol throughout the 7-week study (alcohol). Alcohol intake significantly increased hepatic metastatic burden in the prealcohol (2.4-fold, P < 0.001), postalcohol (2.0-fold, P < 0.01), and alcohol groups (2.2-fold, P < 0.001). A fluorescence-based metastasis tracking assay also confirmed an alcohol-induced increase in the abundance of tumor cells in the liver (2.5-fold, P < 0.001). Investigation of the host microenvironment revealed an alcohol-induced inflammatory response marked by elevated TNFα, IL1β, IL6, and IFNγ protein levels, as well as increased expression of intercellular molecule-1 (ICAM1) in hepatic tissues after 4 weeks of alcohol consumption. Moreover, the peripheral blood of mice provided with alcohol for 4 weeks exhibited reduced natural killer and CD8(+) T-cell counts. Collectively, our findings suggest that chronic alcohol consumption accelerates liver metastasis of colorectal cancer cells through alterations to the liver microenvironment and inactivation of immune surveillance. Cancer Res; 76(7); 1698-704. ©2016 AACR. ©2016 American Association for Cancer Research.

Conclusions from the engineering subgroup of the SSC liquid argon calorimeter working group

International Nuclear Information System (INIS)

Bederede, D.; Cooper, W.; Mulholland, G.; Kroon, P.; Guryn, W.; Lobkowicz, F.; Mason, I.; Pohlen, J.; Schindler, R.H.; Scholle, E.A.; Watanabe, Y.; Watt, R.

1990-01-01

The SSC Calorimeter Workshop was organized to explore the feasibility of each calorimeter technology for use in a 4π detector at the SSC. The Liquid Argon Calorimeter group further subdivided into four subgroups; Hermeticity, Engineering, Module Details, and Electronics. This is the report of the Engineering Subgroup whose charge was to evaluate the cost, schedule, manpower, safety, and facilities requirements for the construction of a large liquid argon calorimeter for the SSC

Subgroup differences in the lexical tone mismatch negativity (MMN) among Mandarin speakers with congenital amusia.

Science.gov (United States)

Nan, Yun; Huang, Wan-ting; Wang, Wen-jing; Liu, Chang; Dong, Qi

2016-01-01

The association/dissociation of pitch processing between music and language is a long lasting debate. We examined this music-language relationship by investigating to what extent pitch deficits in these two domains were dissociable. We focused on a special neurodevelopmental pitch disorder - congenital amusia, which primarily affects musical pitch processing. Recent research has also revealed lexical tone deficits in speech among amusics. Approximately one-third of Mandarin amusics exhibits behavioural difficulties in lexical tone perception, which is known as tone agnosia. Using mismatch negativities (MMNs), our current work probed lexical tone encoding at the pre-attentive level among the Mandarin amusics with (tone agnosics) and without (pure amusics) behavioural lexical tone deficits compared with age- and IQ-matched controls. Relative to the controls and the pure amusics, the tone agnosics exhibited reduced MMNs specifically in response to lexical tone changes. Their tone-consonant MMNs were intact and similar to those of the other two groups. Moreover, the tone MMN reduction over the left hemisphere was tightly linked to behavioural insensitivity to lexical tone changes. The current study thus provides the first psychophysiological evidence of subgroup differences in lexical tone processing among Mandarin amusics and links amusics' behavioural tone deficits to impaired pre-attentive tone processing. Despite the overall music pitch deficits, the subgroup differences in lexical tone processing in Mandarin-speaking amusics suggest dissociation of pitch deficits between music and speech. Copyright © 2015 Elsevier B.V. All rights reserved.

Identifying Changes in Youth's Subgroup Membership over Time Based on Their Targeted Communication about Substance Use with Parents and Friends

Science.gov (United States)

Kam, Jennifer A.

2011-01-01

Using latent class/transition analyses, this study: (a) identified subgroups of youth based on their targeted communication about substance use with parents and friends, (b) examined subgroup differences in substance use, and (c) considered changes in subgroup membership over four years. Among 5,874 youth, five subgroups emerged, with parents-only…

Incidence of female breast cancer among atomic bomb survivors, 1950-1985

International Nuclear Information System (INIS)

Tokunaga, Masayoshi; Land, C.E.; Tokuoka, Shoji; Akiba, Suminori; Nishimori, Issei; Soda, Midori

1994-01-01

An incidence survey among atomic bomb survivors identified 807 breast cancer cases, and 20 second breast cancers. As in earlier surveys of the Life Span Study population, a strongly linear radiation dose response was found, with the highest dose-specific excess relative risk (ERR) among survivors under 20 years old at the time of the bombings. Sixty-eight of the cases were under 10 years old at exposure, strengthening earlier reports of a marked excess risk associated with exposure during infancy and childhood. A much lower, but marginally significant, dose response was seen among women exposed at 40 years and older. It was not possible, however to discriminate statistically between age at exposure and age at observation for risk as the more important determinant of ERR per unit dose. A 13-fold ERR at 1 Sv was found for breast cancer occurring before age 35, compared to a 2-fold excess after age 35, among survivors exposed before age 20. This a posteriori finding, based on 27 exposed, known-dose, early-onset cases, suggests the possible existence of a susceptible genetics subgroup. Further studies, involving family histories of cancer and investigations at the molecular level, are suggested to determine whether such a subgroup exists. 41 refs., 5 figs., 10 tabs

A protein and mRNA expression-based classification of gastric cancer.

Science.gov (United States)

Setia, Namrata; Agoston, Agoston T; Han, Hye S; Mullen, John T; Duda, Dan G; Clark, Jeffrey W; Deshpande, Vikram; Mino-Kenudson, Mari; Srivastava, Amitabh; Lennerz, Jochen K; Hong, Theodore S; Kwak, Eunice L; Lauwers, Gregory Y

2016-07-01

The overall survival of gastric carcinoma patients remains poor despite improved control over known risk factors and surveillance. This highlights the need for new classifications, driven towards identification of potential therapeutic targets. Using sophisticated molecular technologies and analysis, three groups recently provided genetic and epigenetic molecular classifications of gastric cancer (The Cancer Genome Atlas, 'Singapore-Duke' study, and Asian Cancer Research Group). Suggested by these classifications, here, we examined the expression of 14 biomarkers in a cohort of 146 gastric adenocarcinomas and performed unsupervised hierarchical clustering analysis using less expensive and widely available immunohistochemistry and in situ hybridization. Ultimately, we identified five groups of gastric cancers based on Epstein-Barr virus (EBV) positivity, microsatellite instability, aberrant E-cadherin, and p53 expression; the remaining cases constituted a group characterized by normal p53 expression. In addition, the five categories correspond to the reported molecular subgroups by virtue of clinicopathologic features. Furthermore, evaluation between these clusters and survival using the Cox proportional hazards model showed a trend for superior survival in the EBV and microsatellite-instable related adenocarcinomas. In conclusion, we offer as a proposal a simplified algorithm that is able to reproduce the recently proposed molecular subgroups of gastric adenocarcinoma, using immunohistochemical and in situ hybridization techniques.

Non-meagre subgroups of reals disjoint with meagre sets

Czech Academy of Sciences Publication Activity Database

Kostana, Ziemowit

2018-01-01

Roč. 241, June (2018), s. 11-19 ISSN 0166-8641 Institutional support: RVO:67985840 Keywords : algebraic sum * Baire property * non-meaurable subgroup Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 0.377, year: 2016 https://www. science direct.com/ science /article/pii/S0166864118300567

Consumption and direct costs of dental care for patients with head and neck cancer: A 16-year cohort study.

Science.gov (United States)

Lexomboon, Duangjai; Karlsson, Pär; Adolfsson, Jan; Ekbom, Anders; Naimi-Akbar, Aron; Bahmanyar, Shahram; Montgomery, Scott; Sandborgh-Englund, Gunilla

2017-01-01

Patients with head and neck (H&N) cancer are commonly treated with surgery and/or radiotherapy, which can increase the risk of oral infection, dental caries, and periodontal disease. The present study investigated dental care consumption and costs in patient with H&N cancer before and after the cancer diagnosis. Data from Swedish regional and national registers were used to follow up dental care utilization and dental procedure costs. The analysis included 2,754 patients who had been diagnosed with H&N cancer (exposed cohort) in Stockholm County, Sweden, during 2000-2012 and 13,036 matched persons without cancer (unexposed cohort). The exposed cohort was sub-grouped into irradiated and non-irradiated patients for analysis. The exposed cohort underwent a moderately higher number of dental procedures per year than the unexposed cohort in both the year of the cancer diagnosis and the year after cancer diagnosis; in addition, these numbers were higher in the irradiated than in the non-irradiated subgroup of the exposed cohort. Dental care consumption and costs in the exposed cohort declined over time but remained at a slightly higher level than in the unexposed cohort over the long term (more than two years). Examinations and preventive procedures accounted for most of the higher consumption in the short term (2 years) and at the longer term follow-up. Swedish national insurance subsidized costs for dental treatment, which were highest in the irradiated subgroup and lowest in the unexposed cohort. Direct costs to the patient, however, were similar among the groups. Swedish national health insurance protects patients with H&N cancer from high dental expenditures. Further studies on the cost-effectiveness of preventive dental care for patients are needed.

Deep sequencing reveals distinct patterns of DNA methylation in prostate cancer.

Science.gov (United States)

Kim, Jung H; Dhanasekaran, Saravana M; Prensner, John R; Cao, Xuhong; Robinson, Daniel; Kalyana-Sundaram, Shanker; Huang, Christina; Shankar, Sunita; Jing, Xiaojun; Iyer, Matthew; Hu, Ming; Sam, Lee; Grasso, Catherine; Maher, Christopher A; Palanisamy, Nallasivam; Mehra, Rohit; Kominsky, Hal D; Siddiqui, Javed; Yu, Jindan; Qin, Zhaohui S; Chinnaiyan, Arul M

2011-07-01

Beginning with precursor lesions, aberrant DNA methylation marks the entire spectrum of prostate cancer progression. We mapped the global DNA methylation patterns in select prostate tissues and cell lines using MethylPlex-next-generation sequencing (M-NGS). Hidden Markov model-based next-generation sequence analysis identified ∼68,000 methylated regions per sample. While global CpG island (CGI) methylation was not differential between benign adjacent and cancer samples, overall promoter CGI methylation significantly increased from ~12.6% in benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues, respectively (P-value prostate tissues, 2481 differentially methylated regions (DMRs) are cancer-specific, including numerous novel DMRs. A novel cancer-specific DMR in the WFDC2 promoter showed frequent methylation in cancer (17/22 tissues, 6/6 cell lines), but not in the benign tissues (0/10) and normal PrEC cells. Integration of LNCaP DNA methylation and H3K4me3 data suggested an epigenetic mechanism for alternate transcription start site utilization, and these modifications segregated into distinct regions when present on the same promoter. Finally, we observed differences in repeat element methylation, particularly LINE-1, between ERG gene fusion-positive and -negative cancers, and we confirmed this observation using pyrosequencing on a tissue panel. This comprehensive methylome map will further our understanding of epigenetic regulation in prostate cancer progression.

Cohesive subgroup formation : enabling and constraining effects of social capital in strategic technology alliance networks

NARCIS (Netherlands)

Duysters, G.M.; Lemmens, C.E.A.V.

2002-01-01

In this paper we will examine the role of embeddedness and social capital in the process of cohesive subgroup formation in strategic technology alliance networks. More in particular, we will investigate the social mechanisms that enable and enforce cohesive subgroup formation. We will argue that the

Guide-line of the radio-iodine (131I) therapy in Graves' disease and thyroid cancer

International Nuclear Information System (INIS)

Mori, Yutaka; Ikekubo, Katsuji

2005-01-01

Radio-iodine ( 131 I) therapy has been using in Graves' disease and well differentiated thyroid cancer. The rules of control in the discharge from radio-isotope hospital were notified in 1999 in Japan. Guideline of the 131 I therapy in Graves' disease and thyroid cancer were prepared by sub-group of Japanese Society of Nuclear Medicine. (author)

Effectiveness of Acupuncture for Early Recovery of Bowel Function in Cancer: A Systematic Review and Meta-Analysis.

Science.gov (United States)

Liu, Yi-Hua; Dong, Guang-Tong; Ye, Yang; Zheng, Jia-Bin; Zhang, Ying; Lin, Hong-Sheng; Wang, Xue-Qian

2017-01-01

The aim of this study was to evaluate the effects of acupuncture therapy to reduce the duration of postoperative ileus (POI) and to enhance bowel function in cancer patients. A systematic search of electronic databases for studies published from inception until January 2017 was carried out from six databases. Randomized controlled trials (RCTs) involving the use of acupuncture and acupressure for POI and bowel function in cancer patients were identified. Outcomes were extracted from each study and pooled to determine the risk ratio and standardized mean difference. 10 RCTs involving 776 cancer patients were included. Compared with control groups (no acupuncture, sham acupuncture, and other active therapies), acupuncture was associated with shorter time to first flatus and time to first defecation. A subgroup analysis revealed that manual acupuncture was more effective on the time to first flatus and the time to first defecation; electroacupuncture was better in reducing the length of hospital stay. Compared with control groups (sham or no acupressure), acupressure was associated with shorter time to first flatus. However, GRADE approach indicated a low quality of evidence. Acupuncture and acupressure showed large effect size with significantly poor or inferior quality of included trials for enhancing bowel function in cancer patients after surgery. Further well-powered evidence is needed.

The effect of XPD polymorphisms on digestive tract cancers risk: a meta-analysis.

Science.gov (United States)

Du, Haina; Guo, Nannan; Shi, Bin; Zhang, Qian; Chen, Zhipeng; Lu, Kai; Shu, Yongqian; Chen, Tao; Zhu, Lingjun

2014-01-01

The Xeroderma pigmento-sum group D gene (XPD) plays a key role in nucleotide excision repair. Single nucleotide polymorphisms (SNP) located in its functional region may alter DNA repair capacity phenotype and cancer risk. Many studies have demonstrated that XPD polymorphisms are significantly associated with digestive tract cancers risk, but the results are inconsistent. We conducted a comprehensive meta-analysis to assess the association between XPD Lys751Gln polymorphism and digestive tract cancers risk. The digestive tract cancers that our study referred to, includes oral cancer, esophageal cancer, gastric cancer and colorectal cancer. We searched PubMed and EmBase up to December 31, 2012 to identify eligible studies. A total of 37 case-control studies including 9027 cases and 16072 controls were involved in this meta-analysis. Statistical analyses were performed with Stata software (version 11.0, USA). Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. The results showed that XPD Lys751Gln polymorphism was associated with the increased risk of digestive tract cancers (homozygote comparison (GlnGln vs. LysLys): OR = 1.12, 95% CI = 1.01-1.24, P = 0.029, P heterogeneity = 0.133). We found no statistical evidence for a significantly increased digestive tract cancers risk in the other genetic models. In the subgroup analysis, we also found the homozygote comparison increased the susceptibility of Asian population (OR = 1.28, 95% CI = 1.01-1.63, P = 0.045, P heterogeneity = 0.287). Stratified by cancer type and source of control, no significantly increased cancer risk was found in these subgroups. Additionally, risk estimates from hospital-based studies and esophageal studies were heterogeneous. Our meta-analysis suggested that the XPD 751Gln/Gln genotype was a low-penetrate risk factor for developing digestive tract cancers, especially in Asian populations.

Oligometastases in prostate cancer: restaging stage IV cancers and new radiotherapy options

International Nuclear Information System (INIS)

Moreno, Antonio José Conde; Albiach, Carlos Ferrer; Soria, Rodrigo Muelas; Vidal, Verónica González; Gómez, Raquel García; Antequera, María Albert

2014-01-01

There are various subgroups of patients with metastatic prostate cancer: polymetastatic, oligometastatic, or oligo-recurrent cancers whose progression follows different courses and for whom there are different treatment options. Knowledge of tumor dissemination pathways and different genetic and epigenetic tumor profiles, as well as their evolution during disease progression, along with new diagnostic and therapeutic advances has allowed us to address these situations with local ablative treatments such as stereotactic body radiation therapy or stereotactic radiosurgery. These treatments provide high rates of local control with low toxicity in metastatic spread for primary cancers including those of pulmonary, digestive, and renal origin, while these types of treatments are still emerging for cancers of prostatic origin. There are several retrospective studies showing the effectiveness of such treatments in prostate cancer metastases, which has led to the emergence of prospective studies on the issue and even some phase II studies intended to prevent or delay systemic treatments such as chemotherapy. Here we collect together and review these past experiences and the studies currently underway. These types of radiotherapy treatments redefine how we approach extracranial metastatic disease and open up new possibilities for combination therapy with new systemic treatment agents

The association between subgroups of MRI findings identified with latent class analysis and low back pain in 40-year-old Danes

DEFF Research Database (Denmark)

Jensen, Rikke K; Kent, Peter; Jensen, Tue S

2018-01-01

for identifying latent classes (subgroups) of MRI findings within multivariable datasets. The purpose of this study was to investigate the association between subgroups of MRI findings and the presence of LBP in people from the general population. METHODS: To identify subgroups of lumbar MRI findings...... regression. RESULTS: Six subgroups were identified in the clinical dataset and the data from the general population cohort fitted the subgroups well, with a median posterior probability of 93%-100%. These six subgroups described two pathways of increasing degeneration on upper (L1-L3) and lower (L4-L5......) lumbar levels. An association with LBP was found for the subgroups describing severe and multiple degenerative MRI findings at the lower lumbar levels but none of the other subgroups were associated with LBP. CONCLUSION: Although MRI findings are common in asymptomatic people and the association between...

Integrative genome-wide expression profiling identifies three distinct molecular subgroups of renal cell carcinoma with different patient outcome

Directory of Open Access Journals (Sweden)

Beleut Manfred

2012-07-01

Full Text Available Abstract Background Renal cell carcinoma (RCC is characterized by a number of diverse molecular aberrations that differ among individuals. Recent approaches to molecularly classify RCC were based on clinical, pathological as well as on single molecular parameters. As a consequence, gene expression patterns reflecting the sum of genetic aberrations in individual tumors may not have been recognized. In an attempt to uncover such molecular features in RCC, we used a novel, unbiased and integrative approach. Methods We integrated gene expression data from 97 primary RCC of different pathologic parameters, 15 RCC metastases as well as 34 cancer cell lines for two-way nonsupervised hierarchical clustering using gene groups suggested by the PANTHER Classification System. We depicted the genomic landscape of the resulted tumor groups by means of Single Nuclear Polymorphism (SNP technology. Finally, the achieved results were immunohistochemically analyzed using a tissue microarray (TMA composed of 254 RCC. Results We found robust, genome wide expression signatures, which split RCC into three distinct molecular subgroups. These groups remained stable even if randomly selected gene sets were clustered. Notably, the pattern obtained from RCC cell lines was clearly distinguishable from that of primary tumors. SNP array analysis demonstrated differing frequencies of chromosomal copy number alterations among RCC subgroups. TMA analysis with group-specific markers showed a prognostic significance of the different groups. Conclusion We propose the existence of characteristic and histologically independent genome-wide expression outputs in RCC with potential biological and clinical relevance.

High Spicy Food Intake and Risk of Cancer: A Meta-analysis of Case-control Studies.

Science.gov (United States)

Chen, Yu-Heng; Zou, Xiao-Nong; Zheng, Tong-Zhang; Zhou, Qi; Qiu, Hui; Chen, Yuan-Li; He, Mei; Du, Jia; Lei, Hai-Ke; Zhao, Ping

2017-09-20

Studies on the association between spicy food intake and cancer risk have reported inconsistent results. We quantitatively assessed this association by conducting a meta-analysis based on evidence from case-control studies. PubMed, EMBASE, and the Cochrane Library were searched for eligible publications. Combined odds ratios (OR s) with their 95% confidence interval (CI) were calculated using a random- or fixed-effects model. The methodological quality of the included articles was assessed using the Newcastle-Ottawa scale (NOS). All data were analyzed using STATA 11.0 software (version 11.0; StataCorp., College Station, TX, USA). Subgroup analyses were also performed with stratification by region, sex, number of cases, cancer subtype, source of the control group, and NOS score. A total 39 studies from 28 articles fulfilled the inclusion criteria for the meta-analysis (7884 patients with cancer and 10,142 controls). Comparison of the highest versus lowest exposure category in each study revealed a significant OR of 1.76 (95% CI = 1.35-2.29) in spite of significant heterogeneity (P cases, different sources of the control group, and high-quality articles (NOS score of ≥ 7). However, no statistically significant association was observed for women, esophageal cancer, gallbladder cancer, or low-quality articles (NOS score of case-control studies suggested that a higher level of spicy food intake may be associated with an increased incidence of cancer despite significant heterogeneity. More studies are warranted to clarify our understanding of the association between high spicy food intake and the risk of cancer.

Single-Phase Mail Survey Design for Rare Population Subgroups

Science.gov (United States)

Brick, J. Michael; Andrews, William R.; Mathiowetz, Nancy A.

2016-01-01

Although using random digit dialing (RDD) telephone samples was the preferred method for conducting surveys of households for many years, declining response and coverage rates have led researchers to explore alternative approaches. The use of address-based sampling (ABS) has been examined for sampling the general population and subgroups, most…

The ergodic theory of lattice subgroups

CERN Document Server

Gorodnik, Alexander

2010-01-01

The results established in this book constitute a new departure in ergodic theory and a significant expansion of its scope. Traditional ergodic theorems focused on amenable groups, and relied on the existence of an asymptotically invariant sequence in the group, the resulting maximal inequalities based on covering arguments, and the transference principle. Here, Alexander Gorodnik and Amos Nevo develop a systematic general approach to the proof of ergodic theorems for a large class of non-amenable locally compact groups and their lattice subgroups. Simple general conditions on the spectral theory of the group and the regularity of the averaging sets are formulated, which suffice to guarantee convergence to the ergodic mean

Mineralogy and Petrography of MIL 090001, a Highly Altered CV Chondrite from the Reduced Sub-Group

Science.gov (United States)

Keller, Lindsay P.

2011-01-01

MIL 090001 is a large (greater than 6 kg) CV chondrite from the reduced subgroup (CV(sub red)) that was recovered during the 2009-2010 ANSMET field season [1]. The CV(sub red) subgroup meteorites retain primitive characteristics and have escaped the Na and Fe meta-somatism that affected the oxidized (CV(sub ox)) subgroups. MIL 090001 is, however, reported to be altered [1], and thus a major objective of this study is to characterize its mineralogy and petrography and the extent of the alteration.

Petrography and geochemistry of iron formations of the Paleoproterozoic Koegas Subgroup, Transvaal Supergroup, Griqualand West, South Africa

OpenAIRE

2013-01-01

M.Sc. (Geology) Nel, B.P. (2013). Petrography and geochemistry of iron formations of the Paleoproterozoic Koegas Subgroup, Transvaal Supergroup, Griqualand West, South Africa. MSc thesis (unpublished), University of Johannesburg, Aucklandpark, pp. 133. The Early Paleoproterozoic Koegas Subgroup comprises a succession of siltstone, mudstone, iron-­‐formation, chert and carbonate rocks that overlies the iron-­‐formations of the Asbestos Hills Subgroup with sharp contact. It is overlain with ...

Interaction of phosphorus pentachloride with trichlorides of metals of the second half of lanthanide series and scandium subgroup

International Nuclear Information System (INIS)

Salyulev, A.B.; Vovkotrub, Eh.G.; Strekalovskij, V.N.

1999-01-01

With the use of Raman laser spectroscopy a study is made into interactions of molten TbCl 3 , ErCl 3 , YbCl 3 , YCl 3 and ScCl 3 with phosphorus pentachloride vapors at elevated pressure (up to 30-35 atm) as well as solid REM trichlorides with molten PCl 5 . It is revealed for first time that the interaction can be accompanied by reactions resulting in formation of complex chloride cations [PCl 4 ] + and anions [MCl 6 ] 3- of trivalent metals. The prediction is made about the possibility of chemical interaction of phosphorus pentachloride with trichlorides of all yttrium subgroup lanthanides under similar conditions

Epigenetic subgroups of esophageal and gastric adenocarcinoma with differential GATA5 DNA methylation associated with clinical and lifestyle factors.

Directory of Open Access Journals (Sweden)

Xinhui Wang

Full Text Available BACKGROUND: Adenocarcinomas located near the gastroesophageal junction have unclear etiology and are difficult to classify. We used DNA methylation analysis to identify subtype-specific markers and new subgroups of gastroesophageal adenocarcinomas, and studied their association with epidemiological risk factors and clinical outcomes. METHODOLOGY/PRINCIPAL FINDINGS: We used logistic regression models and unsupervised hierarchical cluster analysis of 74 DNA methylation markers on 45 tumor samples (44 patients of esophageal and gastric adenocarcinomas obtained from a population-based case-control study to uncover epigenetic markers and cluster groups of gastroesophageal adenocarcinomas. No distinct epigenetic differences were evident between subtypes of gastric and esophageal cancers. However, we identified two gastroesophageal adenocarcinoma subclusters based on DNA methylation profiles. Group membership was best predicted by GATA5 DNA methylation status. We analyzed the associations between these two epigenetic groups and exposure using logistic regression, and the associations with survival time using Cox regression in a larger set of 317 tumor samples (278 patients. There were more males with esophageal and gastric cardia cancers in Cluster Group 1 characterized by higher GATA5 DNA methylation values (all p<0.05. This group also showed associations of borderline statistical significance with having ever smoked (p-value = 0.07, high body mass index (p-value = 0.06, and symptoms of gastroesophageal reflux (p-value = 0.07. Subjects in cluster Group 1 showed better survival than those in Group 2 after adjusting for tumor differentiation grade, but this was not found to be independent of tumor stage. CONCLUSIONS/SIGNIFICANCE: DNA methylation profiling can be used in population-based studies to identify epigenetic subclasses of gastroesophageal adenocarcinomas and class-specific DNA methylation markers that can be linked to

Familial risks and estrogen receptor-positive breast cancer in Hong Kong Chinese women.

Science.gov (United States)

Tse, Lap Ah; Li, Mengjie; Chan, Wing-cheong; Kwok, Chi-hei; Leung, Siu-lan; Wu, Cherry; Yu, Ignatius Tak-sun; Yu, Wai-cho; Lao, Xiangqian; Wang, Xiaorong; Wong, Carmen Ka-man; Lee, Priscilla Ming-yi; Wang, Feng; Yang, Xiaohong Rose

2015-01-01

The role of family history to the risk of breast cancer was analyzed by incorporating menopausal status in Hong Kong Chinese women, with a particular respect to the estrogen receptor-positive (ER+) type. Seven hundred and forty seven breast cancer incident cases and 781 hospital controls who had completed information on family cancer history in first-degree relatives (nature father, mother, and siblings) were recruited. Odds ratio for breast cancer were calculated by unconditional multiple logistic regression, stratified by menopausal status (a surrogate of endogenous female sex hormone level and age) and type of relative affected with the disease. Further subgroup analysis by tumor type according to ER status was investigated. Altogether 52 (6.96%) breast cancer cases and 23 (2.95%) controls was found that the patients' one or more first-degree relatives had a history of breast cancer, showing an adjusted odds ratio (OR) of 2.41 (95%CI: 1.45-4.02). An excess risk of breast cancer was restricted to the ER+ tumor (OR = 2.43, 95% CI: 1.38-4.28), with a relatively higher risk associated with an affected mother (OR = 3.97, 95%CI: 1.46-10.79) than an affected sister (OR = 2.06, 95%CI: 1.07-3.97), while the relative risk was more prominent in the subgroup of pre-menopausal women. Compared with the breast cancer overall, the familial risks to the ER+ tumor increased progressively with the number of affected first-degree relatives. This study provides new insights on a relationship between family breast cancer history, menopausal status, and the ER+ breast cancer. A separate risk prediction model for ER+ tumor in Asian population is desired.

Empirically derived pain-patient MMPI subgroups: prediction of treatment outcome.

Science.gov (United States)

Moore, J E; Armentrout, D P; Parker, J C; Kivlahan, D R

1986-02-01

Fifty-seven male chronic pain patients admitted to an inpatient multimodal pain treatment program at a Midwestern Veterans Administration hospital completed the MMPI, Profile of Mood States (POMS), Tennessee Self-Concept Scale (TSCS), Rathus Assertiveness Schedule (RAS), activity diaries, and an extensive pain questionnaire. All patients were assessed both before and after treatment, and most also were assessed 2-5 months prior to treatment. No significant changes occurred during the baseline period, but significant improvements were evident at posttreatment on most variables: MMPI, POMS, TSCS, RAS, pain severity, sexual functioning, and activity diaries. MMPI subgroup membership, based on a hierarchical cluster analysis in a larger sample, was not predictive of differential treatment outcome. Possible reasons for comparable treatment gains among these subgroups, which previously have been shown to differ on many psychological and behavioral factors, are discussed.

Subgroup effects in a randomised trial of different types and doses of exercise during breast cancer chemotherapy.

Science.gov (United States)

Courneya, K S; McKenzie, D C; Mackey, J R; Gelmon, K; Friedenreich, C M; Yasui, Y; Reid, R D; Vallerand, J R; Adams, S C; Proulx, C; Dolan, L B; Wooding, E; Segal, R J

2014-10-28

The Combined Aerobic and Resistance Exercise Trial tested different types and doses of exercise in breast cancer patients receiving chemotherapy. Here, we explore potential moderators of the exercise training responses. Breast cancer patients initiating chemotherapy (N=301) were randomly assigned to three times a week, supervised exercise of a standard dose of 25-30 min of aerobic exercise, a higher dose of 50-60 min of aerobic exercise, or a higher dose of 50-60 min of combined aerobic and resistance exercise. Outcomes were patient-reported symptoms and health-related fitness. Moderators were baseline demographic, exercise/fitness, and cancer variables. Body mass index moderated the effects of the exercise interventions on bodily pain (P for interaction=0.038), endocrine symptoms (P for interaction=0.029), taxane/neuropathy symptoms (P for interaction=0.013), aerobic fitness (P for interaction=0.041), muscular strength (P for interaction=0.007), and fat mass (P for interaction=0.005). In general, healthy weight patients responded better to the higher-dose exercise interventions than overweight/obese patients. Menopausal status, age, and baseline fitness moderated the effects on patient-reported symptoms. Premenopausal, younger, and fitter patients achieved greater benefits from the higher-dose exercise interventions. Healthy weight, fitter, and premenopausal/younger breast cancer patients receiving chemotherapy are more likely to benefit from higher-dose exercise interventions.

Density character of subgroups of topological groups

OpenAIRE

Leiderman, Arkady; Morris, Sidney A.; Tkachenko, Mikhail G.

2015-01-01

A subspace Y of a separable metrizable space X is separable, but without X metrizable this is not true even If Y is a closed linear subspace of a topological vector space X. K.H. Hofmann and S.A. Morris introduced the class of pro-Lie groups which consists of projective limits of finite-dimensional Lie groups and proved that it contains all compact groups, locally compact abelian groups and connected locally compact groups and is closed under products and closed subgroups. A topological group...

Debate: Subgroup analyses in clinical trials: fun to look at - but don't believe them!

Directory of Open Access Journals (Sweden)

Sleight Peter

2000-07-01

Full Text Available Abstract Analysis of subgroup results in a clinical trial is surprisingly unreliable, even in a large trial. This is the result of a combination of reduced statistical power, increased variance and the play of chance. Reliance on such analyses is likely to be more erroneous, and hence harmful, than application of the overall proportional (or relative result in the whole trial to the estimate of absolute risk in that subgroup. Plausible explanations can usually be found for effects that are, in reality, simply due to the play of chance. When clinicians believe such subgroup analyses, there is a real danger of harm to the individual patient.

Global Expression Profiling and Pathway Analysis of Mouse Mammary Tumor Reveals Strain and Stage Specific Dysregulated Pathways in Breast Cancer Progression.

Science.gov (United States)

Mei, Yan; Yang, Jun-Ping; Lang, Yan-Hong; Peng, Li-Xia; Yang, Ming-Ming; Liu, Qin; Meng, Dong-Fang; Zheng, Li-Sheng; Qiang, Yuan-Yuan; Xu, Liang; Li, Chang-Zhi; Wei, Wen-Wen; Niu, Ting; Peng, Xing-Si; Yang, Qin; Lin, Fen; Hu, Hao; Xu, Hong-Fa; Huang, Bi-Jun; Wang, Li-Jing; Qian, Chao-Nan

2018-05-01

It is believed that the alteration of tissue microenvironment would affect cancer initiation and progression. However, little is known in terms of the underlying molecular mechanisms that would affect the initiation and progression of breast cancer. In the present study, we use two murine mammary tumor models with different speeds of tumor initiation and progression for whole genome expression profiling to reveal the involved genes and signaling pathways. The pathways regulating PI3K-Akt signaling and Ras signaling were activated in Fvb mice and promoted tumor progression. Contrastingly, the pathways regulating apoptosis and cellular senescence were activated in Fvb.B6 mice and suppressed tumor progression. We identified distinct patterns of oncogenic pathways activation at different stages of breast cancer, and uncovered five oncogenic pathways that were activated in both human and mouse breast cancers. The genes and pathways discovered in our study would be useful information for other researchers and drug development.

Unsupervised Analysis of Array Comparative Genomic Hybridization Data from Early-Onset Colorectal Cancer Reveals Equivalence with Molecular Classification and Phenotypes

Directory of Open Access Journals (Sweden)

María Arriba

2017-01-01

Full Text Available AIM: To investigate whether chromosomal instability (CIN is associated with tumor phenotypes and/or with global genomic status based on MSI (microsatellite instability and CIMP (CpG island methylator phenotype in early-onset colorectal cancer (EOCRC. METHODS: Taking as a starting point our previous work in which tumors from 60 EOCRC cases (≤45 years at the time of diagnosis were analyzed by array comparative genomic hybridization (aCGH, in the present study we performed an unsupervised hierarchical clustering analysis of those aCGH data in order to unveil possible associations between the CIN profile and the clinical features of the tumors. In addition, we evaluated the MSI and the CIMP statuses of the samples with the aim of investigating a possible relationship between copy number alterations (CNAs and the MSI/CIMP condition in EOCRC. RESULTS: Based on the similarity of the CNAs detected, the unsupervised analysis stratified samples into two main clusters (A, B and four secondary clusters (A1, A2, B3, B4. The different subgroups showed a certain correspondence with the molecular classification of colorectal cancer (CRC, which enabled us to outline an algorithm to categorize tumors according to their CIMP status. Interestingly, each subcluster showed some distinctive clinicopathological features. But more interestingly, the CIN of each subcluster mainly affected particular chromosomes, allowing us to define chromosomal regions more specifically affected depending on the CIMP/MSI status of the samples. CONCLUSIONS: Our findings may provide a basis for a new form of classifying EOCRC according to the genomic status of the tumors.

Lung cancer exosomes as drivers of epithelial mesenchymal transition.

Science.gov (United States)

Rahman, Mohammad A; Barger, Jennifer F; Lovat, Francesca; Gao, Min; Otterson, Gregory A; Nana-Sinkam, Patrick

2016-08-23

Exosomes, a subgroup of extracellular vesicles (EVs), have been shown to serve as a conduit for the exchange of genetic information between cells. Exosomes are released from all types of cells but in abundance from cancer cells. The contents of exosomes consist of proteins and genetic material (mRNA, DNA and miRNA) from the cell of origin. In this study, we examined the effects of exosomes derived from human lung cancer serum and both highly metastatic and non-metastatic cells on recipient human bronchial epithelial cells (HBECs). We found that exosomes derived from highly metastatic lung cancer cells and human late stage lung cancer serum induced vimentin expression, and epithelial to mesenchymal transition (EMT) in HBECs. Exosomes derived from highly metastatic cancer cells as well as late stage lung cancer serum induce migration, invasion and proliferation in non-cancerous recipient cells. Our results suggest that cancer derived exosomes could be a potential mediator of EMT in the recipient cells.

Computer tomography, magnetic resonance imaging, and positron emission tomography or positron emission tomography/computer tomography for detection of metastatic lymph nodes in patients with ovarian cancer: A meta-analysis

International Nuclear Information System (INIS)

Yuan Ying; Gu Zhaoxiang; Tao Xiaofeng; Liu Shiyuan

2012-01-01

Objectives: To compare the diagnostic performances of computed tomography (CT), magnetic resonance (MR) imaging, and positron emission tomography (PET or PET/CT) for detection of metastatic lymph nodes in patients with ovarian cancer. Methods: Relevant studies were identified with MEDLINE and EMBASE from January 1990 to July 2010. We estimated the weighted summary sensitivities, specificities, OR (odds ratio), and summary receiver operating characteristic (sROC) curves of each imaging technique and conducted pair-wise comparisons using the two-sample Z-test. Meta-regression, subgroup analysis, and funnel plots were also performed to explain the between-study heterogeneity. Results: Eighteen eligible studies were included, with a total of 882 patients. PET or PET/CT was a more accurate modality (sensitivity, 73.2%; specificity, 96.7%; OR [odds ratio], 90.32). No significant difference was detected between CT (sensitivity, 42.6%; specificity, 95.0%; OR, 19.87) and MR imaging (sensitivity, 54.7%; specificity, 88.3%; OR, 12.38). Meta-regression analyses and subgroup analyses revealed no statistical difference. Funnel plots with marked asymmetry suggested a publication bias. Conclusion: FDG-PET or FDG-PET/CT is more accurate than CT and MR imaging in the detection of lymph node metastasis in patients with ovarian cancer.

Two subgroups of antipsychotic-naive, first-episode schizophrenia patients identified with a Gaussian mixture model on cognition and electrophysiology

DEFF Research Database (Denmark)

Bak, N.; Ebdrup, B.H.; Oranje, B

2017-01-01

Deficits in information processing and cognition are among the most robust findings in schizophrenia patients. Previous efforts to translate group-level deficits into clinically relevant and individualized information have, however, been non-successful, which is possibly explained by biologically...... different disease subgroups. We applied machine learning algorithms on measures of electrophysiology and cognition to identify potential subgroups of schizophrenia. Next, we explored subgroup differences regarding treatment response. Sixty-six antipsychotic-naive first-episode schizophrenia patients...... be used to classify subgroups of schizophrenia patients. The two distinct subgroups, which we identified, were psychopathologically inseparable before treatment, yet their response to dopaminergic blockade was predicted with significant accuracy. This proof of principle encourages further endeavors...

Distinct trajectories of positive and negative affect after colorectal cancer diagnosis

NARCIS (Netherlands)

Ciere, Yvette; Janse, Moniek; Almansa, Josué; Visser, Annemieke; Sanderman, Robbert; Sprangers, Mirjam A.G.; Ranchor, Adelita V.; Fleer, Joke

2017-01-01

Objective: Insight into trajectories of positive affect (PA) and negative affect (NA) across the cancer continuum may improve understanding of the nature of adjustment problems. The primary aim of this study was to identify subgroups of patients with distinct trajectories of PA and NA following

Distinct Trajectories of Positive and Negative Affect After Colorectal Cancer Diagnosis

NARCIS (Netherlands)

Ciere, Yvette; Janse, Moniek; Almansa, Josué; Visser, Annemieke; Sanderman, Robbert; Sprangers, Mirjam A G; Ranchor, Adelita V; Fleer, Joke

OBJECTIVE: Insight into trajectories of positive affect (PA) and negative affect (NA) across the cancer continuum may improve understanding of the nature of adjustment problems. The primary aim of this study was to identify subgroups of patients with distinct trajectories of PA and NA following

Changes in body mass index in long-term childhood cancer survivors

NARCIS (Netherlands)

van Santen, HM; Geskus, Ronald B; Raemaekers, Steven; van Trotsenburg, A S Paul; Vulsma, Thomas; van der Pal, Helena J H; Caron, Hubert N; Kremer, Leontien C M

2015-01-01

BACKGROUND: Previous studies have reported changes in the body mass index (BMI) with time in childhood cancer survivors (CCSs) during follow-up. The limitations of these studies include that they described only a subgroup of survivors or used questionnaires with self-reported heights and weights.

A note on TI-subgroups of finite groups

Indian Academy of Sciences (India)

A kernel and a complement of a quasi-Frobenius group G are the preimages of a kernel and a complement of the Frobenius group G/Z(G), respectively. Lemma 1.2 [1]. A group G is quasi-Frobenius if and only if G possesses a noncentral subgroup H such that H ∩ Hg ≤ Z(G) for all g ∈ G − H. In this case, H is a comple-.

Irreducible almost simple subgroups of classical algebraic groups

CERN Document Server

Burness, Timothy C; Marion, Claude; Testerman, Donna M

2015-01-01

Let G be a simple classical algebraic group over an algebraically closed field K of characteristic p\\geq 0 with natural module W. Let H be a closed subgroup of G and let V be a nontrivial p-restricted irreducible tensor indecomposable rational KG-module such that the restriction of V to H is irreducible. In this paper the authors classify the triples (G,H,V) of this form, where V \

Integrated analysis of breast cancer cell lines reveals unique signaling pathways