Associations Between Social Cognitive Determinants and Movement-Related Behaviors in Studies Using Ecological Momentary Assessment Methods: Systematic Review.

Background: The social cognitive framework is a long-standing framework within physical activity promotion literature to explain and predict movement-related behaviors. However, applications of the social cognitive framework to explain and predict movement-related behaviors have typically examined the relationships between determinants and behavior across macrotimescales (eg, weeks and months). There is more recent evidence suggesting that movement-related behaviors and their social cognitive determinants (eg, self-efficacy and intentions) change across microtimescales (eg, hours and days).

Digital genomic quantification of tumor-infiltrating lymphocytes.

Infiltrating T lymphocytes are frequently found in malignant tumors and are suggestive of a host cancer immune response. Multiple independent studies have documented that the presence and quantity of tumor-infiltrating lymphocytes (TILs) are strongly correlated with increased survival. However, because of methodological factors, the exact effect of TILs on prognosis has remained enigmatic, and inclusion of TILs in standard prognostic panels has been limited.

Longitudinal screening algorithm that incorporates change over time in CA125 levels identifies ovarian cancer earlier than a single-threshold rule.

Purpose: Longitudinal algorithms incorporate change over time in biomarker levels to individualize screening decision rules. Compared with a single-threshold (ST) rule, smaller deviations from baseline biomarker levels are required to signal disease. We demonstrated improvement in ovarian cancer early detection by using a longitudinal algorithm to monitor annual CA125 levels.

An integrative genomic approach identifies p73 and p63 as activators of miR-200 microRNA family transcription.

Although microRNAs (miRNAs) are important regulators of gene expression, the transcriptional regulation of miRNAs themselves is not well understood. We employed an integrative computational pipeline to dissect the transcription factors (TFs) responsible for altered miRNA expression in ovarian carcinoma. Using experimental data and computational predictions to define miRNA promoters across the human genome, we identified TFs with binding sites significantly overrepresented among miRNA genes overexpressed in ovarian carcinoma.

Potential role of HE4 in multimodal screening for epithelial ovarian cancer.

In screening for epithelial ovarian cancer, unnecessary surgery can be reduced by limiting use of transvaginal ultrasound (TVU) to women with increasing CA125 serum levels. Replacing or augmenting TVU with measurement of a serum marker specific for malignancy might further improve screening performance. Serum samples from 112 invasive ovarian cancer patients and 706 matched control subjects from the Prostate, Lung, Colorectal, and Ovarian trial were used to evaluate human epididymis protein 4 (HE4), mesothelin, matrix metalloproteinase 7 (MMP7), SLPI, Spondin2, and insulin-like growth factor binding protein 2 (IGFBP2) for their potential use in screening.

Activation of the MEK-S6 pathway in high-grade ovarian cancers.

The primary objective of this study is to show the activation and analyze the regulation of the MEK- S6 kinase pathway in high-grade ovarian cancer. Phospho-ERK (pERK), a direct substrate of MEK and 2 phosphorylation sites on the ribosomal protein, S6, Ser235/236, and Ser240/244, which are both targeted by the MEK and PI3-kinase/AKT pathways, were analyzed in 13 cell lines, 28 primary cancers and 8 cases of cancer cells from ascites. In primary cancers, ERK and S6 phosphorylation was measured by immunohistochemistry (IHC).

Integrative proteomic analysis of serum and peritoneal fluids helps identify proteins that are up-regulated in serum of women with ovarian cancer.

Background: We used intensive modern proteomics approaches to identify predictive proteins in ovary cancer. We identify up-regulated proteins in both serum and peritoneal fluid. To evaluate the overall performance of the approach we track the behavior of 20 validated markers across these experiments.

Assessing lead time of selected ovarian cancer biomarkers: a nested case-control study.

Background: CA125, human epididymis protein 4 (HE4), mesothelin, B7-H4, decoy receptor 3 (DcR3), and spondin-2 have been identified as potential ovarian cancer biomarkers. Except for CA125, their behavior in the prediagnostic period has not been evaluated.

Methods: Immunoassays were used to determine concentrations of CA125, HE4, mesothelin, B7-H4, DcR3, and spondin-2 proteins in prediagnostic serum specimens (1-11 samples per participant) that were contributed 0-18 years before ovarian cancer diagnosis from 34 patients with ovarian cancer (15 with advanced-stage serous carcinoma) and during a comparable time interval before the reference date from 70 matched control subjects who were participating in the Carotene and Retinol Efficacy Trial.

Regulation of miR-200 family microRNAs and ZEB transcription factors in ovarian cancer: evidence supporting a mesothelial-to-epithelial transition.

Objective: Our objective was to characterize the expression and function of the miR-200 family of microRNAs (miRNA) in ovarian carcinogenesis.

Methods: We used qRT-PCR to examine expression of the miR-200 miRNA family and its predicted targets, the ZEB1 and ZEB2 transcriptional repressors, in primary cultures of normal cells from the surface of the ovary and in a panel of 70 ovarian cancer tissues and 15 ovarian cancer cell lines. We studied the mechanisms of regulation of miR-200 miRNAs and ZEB transcription factors in ovarian cells using 3' UTR luciferase reporters, promoter luciferase reporters and siRNAs.

Repertoire of microRNAs in epithelial ovarian cancer as determined by next generation sequencing of small RNA cDNA libraries.

Background: MicroRNAs (miRNAs) are small regulatory RNAs that are implicated in cancer pathogenesis and have recently shown promise as blood-based biomarkers for cancer detection. Epithelial ovarian cancer is a deadly disease for which improved outcomes could be achieved by successful early detection and enhanced understanding of molecular pathogenesis that leads to improved therapies. A critical step toward these goals is to establish a comprehensive view of miRNAs expressed in epithelial ovarian cancer tissues as well as in normal ovarian surface epithelial cells.

Circulating microRNAs as stable blood-based markers for cancer detection.

Improved approaches for the detection of common epithelial malignancies are urgently needed to reduce the worldwide morbidity and mortality caused by cancer. MicroRNAs (miRNAs) are small ( approximately 22 nt) regulatory RNAs that are frequently dysregulated in cancer and have shown promise as tissue-based markers for cancer classification and prognostication. We show here that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity.

Proteomic analysis of ovarian cancer cells reveals dynamic processes of protein secretion and shedding of extra-cellular domains.

Background: Elucidation of the repertoire of secreted and cell surface proteins of tumor cells is relevant to molecular diagnostics, tumor imaging and targeted therapies. We have characterized the cell surface proteome and the proteins released into the extra-cellular milieu of three ovarian cancer cell lines, CaOV3, OVCAR3 and ES2 and of ovarian tumor cells enriched from ascites fluid.

Methodology And Findings: To differentiate proteins released into the media from protein constituents of media utilized for culture, cells were grown in the presence of [(13)C]-labeled lysine.

Bead-based ELISA for validation of ovarian cancer early detection markers.

Purpose: Efforts to validate ovarian cancer early detection biomarkers with immunoassays are challenged by the limited specimen volumes available. We sought to develop a specimen-efficient assay to measure CA125 in serum, assess its reproducibility, validity, and performance, and test its potential for multiplexing and combining with human epididymis protein 4 (HE4), a promising novel ovarian cancer marker.

Experimental Design: Four pairs of commercially available anti-CA125 antibodies and one pair of anti-HE4 antibodies were evaluated for accuracy in measuring known concentrations of antigen on a bead-based platform.

Serologic analysis of ovarian tumor antigens reveals a bias toward antigens encoded on 17q.

We utilized SEREX immunoscreening to identify a set of novel tumor antigens that are associated with human serous ovarian cancer and may prove useful for the early detection and treatment of this disease. Extensive screening with a panel of sera from 25 late-stage ovarian cancer patients against 3 independent cDNA libraries identified a set of 9 antigens that were immunogenic in more than 1 patient and not in a panel of 20-45 normal female serum donors. These antigens include p53, NY-ESO-1, UBQLN1, HOXB6, TOP2A, putative helicase-RUVBL (RUVBL), HMBA-inducible (HEXIM1), DDX5 and HDCMA.

Evidence of a founder effect and refinement of the hereditary neuralgic amyotrophy (HNA) locus on 17q25 in American families.

Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder that is associated with episodic recurrent brachial plexus neuropathy. A mutation for HNA maps to chromosome 17q25. To refine the HNA locus further, we carried out genetic linkage studies in seven pedigrees with a high density set of DNA markers from chromosome 17q25.

A rare polyadenylation signal mutation of the FOXP3 gene (AAUAAA-->AAUGAA) leads to the IPEX syndrome.

The mouse scurfy gene, Foxp3, and its human orthologue, FOXP3, which maps to Xp11.23-Xq13.3, were recently identified by positional cloning.

Rater agreement and utility of the mutagen-induced chromosome damage assay.

Chromosomal damage in peripheral blood lymphocytes induced by short-term in vitro exposure to the cytotoxic antibiotic bleomycin was first described in 1983 and proposed as a phenotypic assay for chromosome instability. This assay was subsequently described as potentially useful in assessing an individual's risk to environmental carcinogens in 1989. Since 1995 numerous published studies have used this assay to assess risk for cancer in the aerodigestive tract, particularly lung cancer, in various ethnic populations.

Evidence for genetic heterogeneity in hereditary neuralgic amyotrophy.

Hereditary neuralgic amyotrophy (HNA) is a rare autosomal dominant disorder characterized by recurrent episodes of severe arm and shoulder pain with weakness, atrophy, and sensory impairment in a brachial plexus distribution. Recent studies mapped the HNA locus to chromosome 17q25. Two pedigrees with clinically typical HNA in which markers from chromosome 17q25 do not cosegregate with the disease and in which lod scores do not support linkage to chromosome 17q25 were identified.

Maximizing the motivational impact of feedback of lung cancer susceptibility on smokers' desire to quit.

This two-by-two factorially designed study evaluate approaches for communicating feedback of lung cancer susceptibility to smokers as a method for motivating smoking cessation. The study factors were: method of communicating feedback (by mail with telephone follow-up or in-person) and carbon monoxide feedback (yes or no). One-hundred-forty-four smokers were stratified on race and randomized to one of four conditions.

Synergistic interaction between anti-p185HER-2 ricin A chain immunotoxins and radionuclide conjugates for inhibiting growth of ovarian and breast cancer cells that overexpress HER-2.

Radionuclide conjugates or ricin A chain (RTA) immunotoxins that target pl85HER-2 have partially inhibited the growth of human ovarian cancer xenografts in athymic mice but generally have not cured mice bearing human tumor transplants. The present study was undertaken to explore whether a combination of ionizing radiation and an immunotoxin could exert additive or synergistic cytotoxicity in culture and in vivo against cancer cells that overexpress p185HER-2. In cell culture, treatment with 200-2000 cGy external beam irradiation followed by incubation with TA1-anti-pl85mHER2-RTA immunotoxin (TA1-RTA) produced synergistic inhibition of clonogenic growth of ovarian and breast cancer cells that expressed > 10(6) pl85HER-2 receptors/cell.

SSA/RO52gene and expressed sequence tags in an 85 kb region of chromosome segment 11p15.5.

Frequent allelic loss in lung cancer has been described in a region on chromosome segment 11p15.5 (LOH11A). The region is approximately 650 kb in size and flanked by the markers D11S988 centromeric and D11S860 telomeric.

Lung cancer and the human gene for ribonucleotide reductase subunit M1 (RRM1).

LOH11A is a region of Chromosome (Chr) 11p15.5 where 75% of lung cancers show loss of heterozygosity (LOH). Clinical and cell biological studies suggest that LOH11A contains a tumor/metastasis suppressor gene.

Relative cytotoxic activity of immunotoxins reactive with different epitopes on the extracellular domain of the c-erbB-2 (HER-2/neu) gene product p185.

Different epitopes on the extracellular domain of the HER-2 receptor can serve as distinct targets for immunotoxins. To determine the optimal epitope target for immunotoxin therapy, 7 anti-HER-2 ricin A chain murine monoclonal immunotoxins, each reactive with different epitopes of HER-2 receptor, were tested for cytotoxic activity. The immunotoxins produced 1.

A 1.4-Mb high-resolution physical map and contig of chromosome segment 11p15.5 and genes in the LOH11A metastasis suppressor region.

The centromeric part of chromosome segment 11p15.5 contains a region of frequent allele loss in many adult solid malignancies. This region, called LOH11A, is lost in 75% of lung cancers and is thought to contain a gene that may function as a metastasis suppressor.