tbuckley/cabot-search huggingface dataset:
Genetic counseling and cancer risk perception in Brazilian patients at-risk for hereditary breast and ovarian cancer
Authors: E. I. Palmero, M. Caleffi, F. R. Vargas, J. C. C. Rocha, R. Giugliani, L. Kalakun, L. Schuler-Faccini, P. Ashton-Prolla
Journal: Journal of Clinical Oncology (2004)

9698 Background: In Brazil, breast cancer (BC) is the first cause of cancer-related deaths in women of all ages; in Southern Brazil it is the first cause of all deaths in women ages 30–49 years. Only a few cancer genetic services exist in Brazil and studies on hereditary breast and ovarian cancer (HBOC) knowledge, cancer risk perception and impact of genetic counseling in Brazilian patients at-risk for these syndromes have not been published. This study was conducted to evaluate all of these aspects in patients of three major Brazilian capitals. Methods: Patients responded to a specific questionnaire before their first genetic consultation that included questions about demographic data; BC, ovarian cancer (OC) and HBOC knowledge; frequency and compliance to BC/OC age-specific screening guidelines; BC risk factors; cancer risk perception and knowledge and motivation for genetic predisposition testing. For all patients, complete personal and family histories were obtained. Cancer risk was estimated using the Gail model, Claus tables and BRCAPro software whenever appropriate. Results: Two-hundred and seventy patients were included in the study over a period of 2 years; there was an equal distribution of patients with cancer (symptomatic) and without cancer but with a BC/OC family history (asymptomatic). The average age at evaluation was 46 years, being 10 years higher in the symptomatic group of patients. HBOC knowledge was very poor and approximately 30% did not comply to age-specific BC screening guidelines. Most patients perceived their lifetime BC risk as being > 50% and for most, the estimated BC risk was significantly lower (most patients overestimated their BC risk in as much as 8 times, especially in the asymptomatic group). Patients responded to the same questionnaire 12 months later and 60% of them estimated their risk correctly as compared to 22% before genetic counseling. Conclusions: Most patients had a low-moderate lifetime risk of cancer, but significantly overestimated their risk before genetic counseling. Risk perception was reduced and became more consistent with the estimated risk after genetic counseling. No significant financial relationships to disclose.
Satellite-Based Spatiotemporal Trends in PM <sub>2.5</sub> Concentrations: China, 2004–2013
Authors: Zongwei Ma, Xuefei Hu, Andrew M. Sayer, Robert Levy, Qiang Zhang, Yingang Xue, Shilu Tong, Jun Bi, Lei Huang, Yang Liu
Journal: Environmental Health Perspectives (2015)

BackgroundThree decades of rapid economic development is causing severe and widespread PM2.5 (particulate matter ≤ 2.5 μm) pollution in China. However, research on the health impacts of PM2.5 exposure has been hindered by limited historical PM2.5 concentration data.ObjectivesWe estimated ambient PM2.5 concentrations from 2004 to 2013 in China at 0.1° resolution using the most recent satellite data and evaluated model performance with available ground observations.MethodsWe developed a two-stage spatial statistical model using the Moderate Resolution Imaging Spectroradiometer (MODIS) Collection 6 aerosol optical depth (AOD) and assimilated meteorology, land use data, and PM2.5 concentrations from China’s recently established ground monitoring network. An inverse variance weighting (IVW) approach was developed to combine MODIS Dark Target and Deep Blue AOD to optimize data coverage. We evaluated model-predicted PM2.5 concentrations from 2004 to early 2014 using ground observations.ResultsThe overall model cross-validation R2 and relative prediction error were 0.79 and 35.6%, respectively. Validation beyond the model year (2013) indicated that it accurately predicted PM2.5 concentrations with little bias at the monthly (R2 = 0.73, regression slope = 0.91) and seasonal (R2 = 0.79, regression slope = 0.92) levels. Seasonal variations revealed that winter was the most polluted season and that summer was the cleanest season. Analysis of predicted PM2.5 levels showed a mean annual increase of 1.97 μg/m3 between 2004 and 2007 and a decrease of 0.46 μg/m3 between 2008 and 2013.ConclusionsOur satellite-driven model can provide reliable historical PM2.5 estimates in China at a resolution comparable to those used in epidemiologic studies on the health effects of long-term PM2.5 exposure in North America. This data source can potentially advance research on PM2.5 health effects in China.CitationMa Z, Hu X, Sayer AM, Levy R, Zhang Q, Xue Y, Tong S, Bi J, Huang L, Liu Y. 2016. Satellite-based spatiotemporal trends in PM2.5 concentrations: China, 2004–2013. Environ Health Perspect 124:184–192; http://dx.doi.org/10.1289/ehp.1409481
DOT1L Inhibitor EPZ-5676 Displays Synergistic Antiproliferative Activity in Combination with Standard of Care Drugs or DNA Hypomethylating Agents in MLL-Rearranged Leukemia Cells
Authors: Christine R Klaus, Scott R. Daigle, Dorothy Iwanowics, L. Danielle Johnston, Carly A Therkelsen, Jesse J Smith, Mikel P Moyer, Robert A. Copeland, Edward J Olhava, Margaret Porter Scott, Roy M. Pollock, Alejandra Raimondi
Journal: Blood (2013)
PAGE-B predicts the risk of developing hepatocellular carcinoma in Caucasians with chronic hepatitis B on 5-year antiviral therapy
Authors: George Papatheodoridis, George Dalekos, Vana Sypsa, Cihan Yurdaydin, Maria Buti, John Goulis, Jose Luis Calleja, Heng Chi, Spilios Manolakopoulos, Giampaolo Mangia, Nikolaos Gatselis, Onur Keskin, Savvoula Savvidou, Juan de la Revilla, Bettina E. Hansen, Ioannis Vlachogiannakos, Kostantinos Galanis, Ramazan Idilman, Massimo Colombo, Rafael Esteban, Harry L.A. Janssen, Pietro Lampertico
Journal: Journal of Hepatology (2015)
Brief Communication: Attenuation of Herpesvirus saimiri for Marmosets After Successive Passage in Cell Culture at 39° C2
Authors: Priscilla A. Schaffer, Lawrence A. Falk, Friedrich Deinhardt
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Brief Communication: Attenuation of Herpesvirus saimiri for Marmosets After Successive Passage in Cell Culture at 39° C Get access Priscilla A. Schaffer, Priscilla A. Schaffer Search for other works by this author on: Oxford Academic PubMed Google Scholar Lawrence A. Falk, Lawrence A. Falk Search for other works by this author on: Oxford Academic PubMed Google Scholar Friedrich Deinhardt Friedrich Deinhardt Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 55, Issue 5, November 1975, Pages 1243–1246, https://doi.org/10.1093/jnci/55.5.1243 Published: 01 November 1975 Article history Received: 21 April 1975 Accepted: 27 June 1975 Published: 01 November 1975
Analysis of the prognostic value of the shed antigen of HER2/neu in premenopausal breast cancer patiens in the TABLE study
Authors: D. Luftner, K. Pechlivanis, R. Geppert, A. Stroux, K. Possinger
Journal: Journal of Clinical Oncology (2007)

11007 Background: The HER-2/neu oncoprotein is a transmembrane tyrosine kinase that belongs to the family of epidermal growth factor receptors. It is known to be overexpressed in 20–40% of breast cancers. Increased serum HER-2/neu (sHER-2/neu) concentrations at the beginning of adjuvant breast cancer therapy have been shown to be of prognostic importance (Mehta et al, 1998). Using the sera from the Takeda® Adjuvant Breast Cancer Study with Leuprorelin (TABLE study), we tested for the prognostic value of sHER-2/neu. Methods: A total of 133 premenopausal, node-positive, hormone-receptor positive patients received either 11.25 mg of leuprorelin s.c. every 3 months over 2 years or CMF chemotherapy for 6 cycles. Blood samples were collected at baseline and at 3, 6, 12, 18, 24 and 30 mo. The primary endpoint of the study was to determine the relapse-free survival (RFS) after 2 years. sHER-2/neu was measured using a standardized ELISA (upper limit of normal 15 ng/ml). As the baseline sHER-2/neu concentrations ranged from 3.8–14.0 ng/ml, results were grouped in terciles. Data were analyzed using Kaplan-Meier and Cox Proportional Hazards survival analysis. Results: Material was available from 80 patients in leuprorelin arm and 53 patients in CMF arm. 65 of 133 patients had relapsed during the follow-up time of up 7 years after treatment. The median RFS was 62.9 mo. The RFS time depended on the concentrations of sHER-2/neu at baseline: RFS was significantly shorter in patients of the third tercile with sHER-2/neu levels &gt;8.8 ng/ml than in patients of the first tercile with levels &lt;7.2 ng/ml (p=0.0232). Five years after initial therapy, we found that 73% of patients in the first tercile group of baseline sHER-2/neu had no relapse. In the second tercile, 63.3% of patients were relapse-free, while in the third tercile only 47.2% of patients had not suffered from a relapse. Conclusions: Higher sHER-2/neu concentrations at the beginning of adjuvant therapy in the TABLE-Study have a prognostic importance for RFS. This observation was evaluated irrespective of the HER-2/neu tissue status and could be of clinically importance for adjuvant therapy with the monoclonal anti-HER-2/neu antibody trastuzumab or other anti-HER-2/neu targeted therapies. No significant financial relationships to disclose.
Dispersed repeats and structural reorganization in subclover chloroplast DNA.
Authors: B G Milligan, J N Hampton, J D Palmer
Journal: Molecular Biology and Evolution (1989)

The plastid genome from subclover, Trifolium subterraneum, is unusual in a variety of respects, compared with other land-plant chloroplast DNAs. Gene mapping of subclover chloroplast DNA reveals major structural reorganization of the genome. Ten clusters of genes are rearranged in both order and orientation. Eight large inversions are sufficient to explain this reorganization; however, the actual evolutionary changes may have been more complex. For example, a fine-scale analysis of a set of ribosomal protein genes reveals the occurrence of insertions, deletions, and transpositions. Associated with this unusually unstable genome are two structural features potentially involved in the rearrangements. A dispersed family of repeats, with each element about 1 kb in length, is present in at least six copies. A survey of a wide taxonomic range of species indicates that these elements are unique to the chloroplast DNAs of subclover and two closely related species. Several of the repeated elements are associated with genomic rearrangements, and one repeat is inserted within a normally highly conserved series of genes. This set of dispersed repeats may be the first family of transposable elements found in any organelle genome. In addition, the subclover genome is much larger than those in other closely related legumes, even when one takes into account the presence of the repeated elements. Some of the extra DNA has no sequence similarity to other chloroplast genomes and may represent insertion of DNA from another genome. These unusual features are not found in the structurally stable chloroplast genomes of other vascular plants and may, therefore, be implicated in the rapid and major reorganization of the chloroplast DNA in subclover.
Retrospective Comparison Of Survival and Leukemic Transformation In Myelofibrosis Patients Treated With Ruxolitinib Versus Momelotinib Versus Fedratinib Versus Pomalidomide
Authors: Animesh Pardanani, Ramy A. Abdelrahman, Kebede Begna, Darci Zblewski, Aref Al-Kali, Mrinal M. Patnaik, William Hogan, Curtis A. Hanson, Mark R. Litzow, Ayalew Tefferi
Journal: Blood (2013)
Immune monitoring technology primer: immunoprofiling of antigen-stimulated blood
Authors: Laura Rosa Brunet, Samuel LaBrie, Thorsten Hagemann
Journal: Journal for ImmunoTherapy of Cancer (2016)

TruCulture® Whole Blood Collection and Culture system is a whole blood collection and stimulation platform from Myriad RBM (Austin, USA). Compelling evidence from several studies on the immune contexture of the tumor has revealed that infiltration by specific leukocyte cell subsets with specific
Expression of epithelial cell adhesion molecule in carcinoma cells present in blood and primary and metastatic tumors
Authors: G. V. Doyle, C. G. Rao, D. Chianese, M. C. Miller, R. A. Sanders, S. Braun, L. W. M. M. Terstappen
Journal: Journal of Clinical Oncology (2004)

9541 Background: The Epithelial Cell Adhesion Molecule (EpCAM) is involved in homophillic cell-cell adhesion and proliferation in normal epithelia and is frequently over-expressed in primary and metastatic adenocarcinomas. However, it has been postulated that during detachment and dissemination of tumor cells, the antigen may of necessity be down-regulated. Circulating tumor cells (CTC) by definition, may demonstrate this phenomenon as they have successfully escaped their local microenvironment and entered the circulation. The objective of this study was to investigate this paradox. Methods: EpCAM expression of CTC was compared to tumor cells in paraffin embedded tissue micro-arrays containing various benign diseases and carcinomas. EpCAM expression on CTC was determined by flowcytometry (FCM) and in paraffin embedded tissue by immunohistochemistry (IHC). To permit comparison of FCM results to those derived by IHC, EpCAM was quantified on cancer cell lines by FCM and then paraffin embedded cell-blocks of these lines were used as staining guides for IHC analysis of tissue micro-arrays. Results: By IHC, 97% (384/397) of solid tissues analyzed had detectable EpCAM, with 72% of tissues showing antigen expression levels of 400,000 molecules / cell. FCM analysis of CTC from 100 metastatic carcinoma patients with >2 CTC / 90μL blood showed EpCAM expression ranging from 9,900 to 246,000 (mean 49,700) antigens per cell. Conclusions: The ten fold lower expression of EpCAM on CTC compared to primary and metastatic tissues indicates that EpCAM expression is transient, and dependent upon the local microenvironment. This supports the hypothesis that the EpCAM molecule is down-regulated on a subset of carcinoma cells potentially to facilitate entry into and survival during transit through the circulation. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Immunicon Corp. Immunicon Corp. Immunicon Corp. Veridex Immunicon Corp.
Phase II trial of single-agent cetuximab in patients with persistent or recurrent epithelial ovarian or primary peritoneal carcinoma with the potential for dose escalation to rash
Authors: R. J. Schilder, A. E. Lokshin, R. W. Holloway, R. D. Alvarez, H. Pathak, C. Aghajanian, C. W. Drescher, A. K. Godwin
Journal: Journal of Clinical Oncology (2007)

5577 Background: Data in other tumor types showed a correlation between severity of acneiform rash and cetuximab (Cet) response. This study evaluated if Cet dose escalation to cause Grade 2 rash correlated with anti-tumor activity and if sera-based markers could predict likelihood of response. Methods: A 2-stage design was used with 50 patients (pts) planned. Eligibility: persistent/recurrent ovarian or primary peritoneal carcinoma; up to 2 prior regimens, including 1 platinum/taxane-based regimen; ECOG PS = 2; measurable EGFR-positive tumors. Pts received an initial dose of Cet 400 mg/m 2 , then 250 mg/m 2 weekly for two 3-week cycles. Pts who had SD and &lt; Grade 2 rash were dose escalated in 75 mg/m 2 increments every 3 weeks until Grade 2 rash or maximum 400 mg/m 2 . Blood, pre- and/or post-treatment, was obtained from 13 of 25 pts with measurable response and the sera evaluated for potential predictive markers of response. Results: The study was stopped due to inadequate number of responders among the first 25 pts. Median age: 58 years (range: 31–79); median number of cycles: 2 (range: 1–11). At first assessment, 4 pts remained at 250 mg/m 2 ; 8 pts were dose-escalated to 325 mg/m 2 ; of these, 4 were increased to 400 mg/m 2 . One pt achieved PR; 9 pts had best response of SD. Median PFS: 2.1 months; 4-month PFS rate: 25%; 1-year survival rate: 54.8%. Rash (96%) was the most common drug-related adverse event (2 pts with Grade 3); 1 pt had Cet-induced Grade 4 hypersensitivity. Serologic markers including cytokines, chemokines, and growth and angiogenic factors were analyzed in sera from 9 pts exhibiting PD and 4 pts with SD. In pre-treatment samples, the average values of 9 of these markers were significantly reduced in pts exhibiting SD vs PD (P=0.052 to 0.00018, t-test). Changes in marker levels after Cet treatment were not significant indicators of SD. Conclusions: Single-agent Cet showed minimal activity in these previously treated pts. However, the low number of dose-escalated pts limits complete evaluation of the hypothesis regarding response and dose escalation to rash. We did identify that pts with reduced levels of 9 serologic markers at baseline were more likely to have disease control on Cet treatment. No significant financial relationships to disclose.
The US Food and Drug Administration’s Proposed Rule to Increase Regulation of Indoor Tanning Devices
Authors: Elliot J. Coups, Alan C. Geller, Sherry L. Pagoto
Journal: JAMA Dermatology (2016)

This Viewpoint discusses potential implications of the age and risk certification restrictions proposed by the US Food and Drug Administration in response to the US Surgeon General’s 2014 call to action to prevent skin cancer.
Increased mortality with elevated plasma endothelin‐1 in acute heart failure: an ASCEND‐HF biomarker substudy
Authors: Antonio L. Perez, Justin L. Grodin, Yuping Wu, Adrian F. Hernandez, Javed Butler, Marco Metra, G. Michael Felker, Adriaan A. Voors, John J. McMurray, Paul W. Armstrong, Randall C. Starling, Christopher M. O'Connor, W. H. Wilson Tang
Journal: European Journal of Heart Failure (2015)
Reduced Proteolytic Shedding of Receptor Tyrosine Kinases Is a Post-Translational Mechanism of Kinase Inhibitor Resistance
Authors: Miles A. Miller, Madeleine J. Oudin, Ryan J. Sullivan, Stephanie J. Wang, Aaron S. Meyer, Hyungsoon Im, Dennie T. Frederick, Jenny Tadros, Linda G. Griffith, Hakho Lee, Ralph Weissleder, Keith T. Flaherty, Frank B. Gertler, Douglas A. Lauffenburger
Journal: Cancer Discovery (2016)

Abstract Kinase inhibitor resistance often involves upregulation of poorly understood “bypass” signaling pathways. Here, we show that extracellular proteomic adaptation is one path to bypass signaling and drug resistance. Proteolytic shedding of surface receptors, which can provide negative feedback on signaling activity, is blocked by kinase inhibitor treatment and enhances bypass signaling. In particular, MEK inhibition broadly decreases shedding of multiple receptor tyrosine kinases (RTK), including HER4, MET, and most prominently AXL, an ADAM10 and ADAM17 substrate, thus increasing surface RTK levels and mitogenic signaling. Progression-free survival of patients with melanoma treated with clinical BRAF/MEK inhibitors inversely correlates with RTK shedding reduction following treatment, as measured noninvasively in blood plasma. Disrupting protease inhibition by neutralizing TIMP1 improves MAPK inhibitor efficacy, and combined MAPK/AXL inhibition synergistically reduces tumor growth and metastasis in xenograft models. Altogether, extracellular proteomic rewiring through reduced RTK shedding represents a surprising mechanism for bypass signaling in cancer drug resistance. Significance: Genetic, epigenetic, and gene expression alterations often fail to explain adaptive drug resistance in cancer. This work presents a novel post-translational mechanism of such resistance: Kinase inhibitors, particularly targeting MAPK signaling, increase tumor cell surface receptor levels due to widely reduced proteolysis, allowing tumor signaling to circumvent intended drug action. Cancer Discov; 6(4); 382–99. ©2016 AACR. This article is highlighted in the In This Issue feature, p. 331
A Case Study of Statistics in the Regulatory Process: The FD&amp;amp;C Red No. 40 Experiment&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: S Lagakos, F Mosteller
Journal: JNCI Journal of the National Cancer Institute (1981)

Unexpected findings in a mouse study in which the safety of FD&C No. 40 (Red 40) was examined led to additional experimentation and to new statistical analyses and models. The possibility of acceleration of tumors raised questions about an operational definition of acceleration and of appropriate statistical methods for assessing acceleration, especially in the face of data dredging. The evaluation of Red 40 was further complicated by cage and litter effects and the multigenerational design. In this report the investigations of these studies are reviewed and are used to illustrate how new scientific work can emerge through the regulatory process. A number of issues in animal experimentation that need to be examind are indicated.
Expression of Lewis&lt;sup&gt;X&lt;/sup&gt; and Sialylated Lewis&lt;sup&gt;X&lt;/sup&gt; Antigens in Human Colorectal Polyps&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M Yuan, S H Itzkowitz, L D Ferrell, Y Fukushi, A Palekar, S Hakomori, Y S Kim
Journal: JNCI Journal of the National Cancer Institute (1987)

The LewisX (LeX) antigen [characterized by trisaccharide Gal beta 1----4 (Fuc alpha 1----3)N-acetylglucosamine] is an oncodevelopmental antigen in the human colon. Monoclonal antibodies (MoAbs), anti-SSEA-1 and AH8-183, which recognize LeX antigen either on short oligosaccharide side chains or as a terminal immunodeterminant on longer carbohydrate side chains of glycoconjugates, bind to most colon cancer tissues but also to some normal colon mucosae. However, the monoclonal antibodies FH1, FH4, FH6, and IB9, which recognize extended difucosylated and trifucosylated LeX structures or their sialylated derivatives, are more cancer-associated because they rarely bind to normal colon mucosa. In the present study, these MoAbs were used to compare the expression of various LeX-related antigens in premalignant (adenomatous) and nonpremalignant (hyperplastic) colorectal polyps. Antigen expression in polyps was also compared to antigen expressions of normal colon mucosa and colon cancer tissues. The four MoAbs recognizing extended LeX antigens bound to adenomatous polyps (APs) significantly more than to hyperplastic polyps (HPs). In contrast, anti-SSEA-1 and AH8-183 recognizing monofucosyl LeX were less able to distinguish between APs and HPs. In APs, staining with the four MoAbs recognizing extended LeX antigens correlated with the premalignant parameters of larger polyp size, more severe dysplasia, and increased villose component. However, staining with AH8-183 correlated only with polyp size, and anti-SSEA-1 correlated only with polyp size and degree of dysplasia. In general, the staining frequency of HPs was similar to that of normal colon mucosa, although FH6, which did not stain any specimens of normal mucosa, stained a few HPs. The staining frequency of APs was less than that of colon cancer tissues, but these differences were generally not statistically significant. In conclusion, extended LeX antigens and their sialylated derivatives are cancer-associated antigens that are expressed preferentially in premalignant colon polyps, that tend to correlate with malignant potential in these polyps, and that may eventually help to define mechanisms involved in the polyp-to-cancer sequence.