tbuckley/cabot-search huggingface dataset:
A population-based study of large granular lymphocyte leukemia
Authors: M V Shah, C C Hook, T G Call, R S Go
Journal: Blood Cancer Journal (2016)

Abstract Large granular lymphocyte (LGL) leukemia is a lymphoproliferative disorder of cytotoxic cells. T-cell LGL (T-LGL) leukemia is characterized by accumulation of cytotoxic T cells in blood and infiltration of the bone marrow, liver or spleen. Population-based studies have not been reported in LGL leukemia. We present clinical characteristics, natural history and risk factors for poor survival in patients with LGL leukemia using the Surveillance, Epidemiology, and End Results Program (SEER) and the United States National Cancer Data Base (NCDB). LGL leukemia is an extremely rare disease with the incidence of 0.2 cases per 1 000 000 individuals. The median age at diagnosis was 66.5 years with females likely to be diagnosed at 3 years earlier compared with males. Analysis of patient-level data using NCDB ( n =978) showed that 45% patients with T-LGL leukemia required some form of systemic treatment at the time of diagnosis. T-LGL leukemia patients have reduced survival compared with general population, with a median overall survival of 9 years. Multivariate analysis showed that age &gt;60 years at the time of diagnosis and the presence of significant comorbidities were independent predictors of poor survival.
Impact of Minimal Residual Disease in High and Standard Risk Multiple Myeloma
Authors: Carolina Schinke, Shayu Deshpande, Alan Mitchell, Malek Faham, Purvi Patel, Sharmilan Thanendrarajan, Meera Mohan, Pankaj Mathur, Aasiya Matin, Muthukumar Radhakrishnan, Ruslana Tytarenko, Owen W Stephens, Frits van Rhee, Maurizio Zangari, Yogesh Jethava, Nathan Petty, Daisy V. Alapat, Sarah K. Johnson, Joshua Epstein, Bart Barlogie, Faith E Davies, Christoph Heuck, Antje Hoering, Niels Weinhold, Gareth J Morgan
Journal: Blood (2015)
Effect of age on the pharmacokinetics of polymorphic nimodipine in rats after oral administration
Authors: Wenli Liu, Xiaona Wang, Ruilian Chen, Kaixuan Zhang, Yao Li, Yi Li, Duanyun Si, Junbo Gong, Dianshu Yin, Yongli Wang, Zhenping Wei, Mingshi Yang
Journal: Acta Pharmaceutica Sinica B (2016)

The previous investigation has proved that their existed pharmacokinetic difference between the different crystal forms of the polymorphic drugs after oral administration. However, no systemic investigations have been made on the change of this pharmacokinetic difference, resulted either from the physiological or from the pathological factors. In this paper, we used polymorphic nimodipine (Nim) as a model drug and investigated the effect of age difference (2- and 9-month old) on the pharmacokinetics after oral delivery in rats. As the results shown, for L-form of Nim (L-Nim), the AUC0-24 h in 2-month-old rats was 343.68±47.15 ng·h/mL, which is 23.36% higher than that in 9-month-old rats. For H-form of Nim (H-Nim), the AUC0-24 h in 2-month-old rats was 140.91±19.47 ng·h/mL, which is 54.64% higher than that in 9-month-old rats. The AUC0-24 h ratio between H-Nim and L-Nim was 2.44 in 2-month-old rats and 3.06 in 9-month-old rats. Since age difference could result in unparallelled change of the absorption and bioavailability of the polymorphic drugs, the results in this experiment are of value for further investigation of crystal form selection in clinical trials and rational clinical application of the polymorphic drugs.
U.S. Selected Practice Recommendations for Contraceptive Use, 2016
Authors: Kathryn M. Curtis, Tara C. Jatlaoui, Naomi K. Tepper, Lauren B. Zapata, Leah G. Horton, Denise J. Jamieson, Maura K. Whiteman
Journal: MMWR Recommendations and Reports (2016)

This report from CDCâs Morbidity and Mortality Weekly Report (MMWR) addresses a select group of common, yet sometimes controversial or complex, issues regarding initiation and use of specific contraceptive methods.
Abstract 3323: Breast cancer stem cell culture and enrichment using poly(ϵ-caprolactone) 3D scaffolds
Authors: Marc Rabionet, Sonia Palomeras, Ines Ferrer, Ariadna Sarrats, Ariadna Giro-Perafita, Maria Luisa Garcia-Romeu, Joaquim Ciurana, Teresa Puig
Journal: Cancer Research (2016)

Abstract Introduction: Cancer stem cell (CSC) population displays self-renewal capabilities, resistance to conventional therapies and a tendency for post-treatment recurrence. Increasing knowledge about CSCs phenotype and functions is needed to investigate new therapeutic strategies against CSC population. Poly(ϵ-CaproLactone) (PCL) as biocompatible and free toxic dye polymer, have been used to manufacture scaffolds, solid structures suitable for 3D cancer cell culture. It has been described that scaffold cell culture enhances the CSCs population. Experimental procedures: A RepRap BCN3D+ printer and 3.5 mm PCL wire were used to fabricate circular scaffolds. PCL design and fabrication parameters were first determined and then optimized considering several product features of the resulting scaffolds. MCF7 breast carcinoma cell line was used to assess scaffolds adequacy for 3D cell culture. To evaluate CSC enrichment the Mammosphere Forming Index (MFI) was performed in 2D and 3D MCF7 cultures. Summary of the new, unpublished data: Results shown that the 60º scaffolds were more suitable for 3D culture than the 45º and 90º ones. Moreover, 3D culture experiments both, in adherent and non-adherent conditions, showed a significant increase on MFI compared to 2D cultures (control). Thus, 3D cell culture with PCL scaffolds could be useful to improve cancer cell culture and to enrich the CSCs population. Basically cells population growth with a 3D culture better and higher in value as it is demonstrated within the work. Conclusions: Thus, 3D cell culture with PCL scaffolds could be useful to improve cancer cell culture and to enrich the CSCs population for further pre-clinical studies on CSC molecular characterization and treatment. Citation Format: Marc Rabionet, Sonia Palomeras, Ines Ferrer, Ariadna Sarrats, Ariadna Giro-Perafita, Maria Luisa Garcia-Romeu, Joaquim Ciurana, Teresa Puig. Breast cancer stem cell culture and enrichment using poly(ϵ-caprolactone) 3D scaffolds. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3323.
Case 15-1975
Authors: Norman Geschwind, Edward P. Richardson
Journal: New England Journal of Medicine (1975)

Presentation of CaseA 77-year-old woman was admitted to the hospital because of a gait disturbance.She was well until 10 years previously, when a mild tremor developed in the hands; it became more pronounced in subsequent years. She was otherwise in vigorous health. During the prolonged terminal illness of her husband she took effective charge of his care and managed all his needs at home. Six months before admission her husband died, and on the day of his death she awoke from a nap disoriented and unable to plan the evening's activities. On the following day her speech was . . .
Heme Oxygenase-1 Controls an HDAC4-miR-206 Pathway of Oxidative Stress in Rhabdomyosarcoma
Authors: Maciej Ciesla, Paulina Marona, Magdalena Kozakowska, Mateusz Jez, Marta Seczynska, Agnieszka Loboda, Karolina Bukowska-Strakova, Agata Szade, Magdalena Walawender, Magdalena Kusior, Jacek Stepniewski, Krzysztof Szade, Bart Krist, Oleksandr Yagensky, Aleksandra Urbanik, Bernarda Kazanowska, Jozef Dulak, Alicja Jozkowicz
Journal: Cancer Research (2016)

Abstract Rhabdomyosarcoma (RMS) is an aggressive soft tissue cancer characterized by disturbed myogenic differentiation. Here we report a role for the oxidative stress response factor HO-1 in progression of RMS. We found that HO-1 was elevated and its effector target miR-206 decreased in RMS cell lines and clinical primary tumors of the more aggressive alveolar phenotype (aRMS). In embryonal RMS (eRMS), HO-1 expression was induced by Pax3/7-FoxO1, an aRMS hallmark oncogene, followed by a drop in miR-206 levels. Inhibition of HO-1 by tin protoporphyrin (SnPP) or siRNA downregulated Pax3/7-FoxO1 target genes and induced a myogenic program in RMS. These effects were not mediated by altered myoD expression; instead, cells with elevated HO-1 produced less reactive oxygen species, resulting in nuclear localization of HDAC4 and miR-206 repression. HO-1 inhibition by SnPP reduced growth and vascularization of RMS tumors in vivo accompanied by induction of miR-206. Effects of SnPP on miR-206 expression and RMS tumor growth were mimicked by pharmacologic inhibition of HDAC. Thus, HO-1 inhibition activates an miR-206–dependent myogenic program in RMS, offering a novel therapeutic strategy for treatment of this malignancy. Cancer Res; 76(19); 5707–18. ©2016 AACR.
Abstract 475: NTF2 regulates nuclear size in mammalian cells and may contribute to altered nuclear size in melanoma
Authors: Lidija D. Vukovic, Bradley A. Stohr, Dan L. Levy
Journal: Cancer Research (2016)

Abstract Nuclear size and morphology are distinct cancer features that pathologists use for diagnostic purposes. Proteins that regulate nuclear size have been identified in Xenopus, where nuclear import rates correlate with nuclear size. The levels of two nuclear import factors, importin α and NTF2, were shown to be particularly important in nuclear size regulation. It has also been shown that importin α2 is a potential biomarker in non-small cell lung cancer, as well as importin α1 in breast cancer. Our data implicate that NTF2 is a possible cancer biomarker. Our main goal is to analyze how these nuclear scaling factors affect nuclear size during carcinogenesis and to test how nuclear size impacts cancer growth characteristics. We find that manipulating the levels of importin α2 and NTF2 in HeLa and MRC-5 cells leads to altered nuclear size, demonstrating a conserved function for these factors in nuclear size regulation. To place these results in a cancer context, we are focusing on melanoma cell lines, including radial and vertical growth primary melanomas and metastatic melanomas. We find that, compared to normal melanocytes, the nuclear-to-cytoplasmic (N/C) volume ratio is increased in the cancer cell lines. Western blot analysis revealed an inverse correlation between NTF2 protein levels and nuclear size. We confirmed these results using a melanoma tissue microarray, finding similar differences in nuclear size and NTF2 expression levels between benign nevi and melanomas. We next performed transient transfection experiments with our melanoma cell lines. Importin α2 knock down led to smaller nuclear size, while knocking down the levels of NTF2 increased nuclear size, consistent with our Xenopus results. We also observed reduced nuclear size when NTF2 was ectopically expressed. Currently we are generating stable, inducible melanoma cell lines where we can precisely alter NTF2 and importin α expression levels using doxycycline. We will use these inducible cell lines to examine how altering nuclear size impacts cell proliferation rates, invasiveness, and apoptosis. We will also investigate how nuclear size affects gene positioning using FISH, focusing on genes involved in melanoma formation and metastasis. In the long term, we plan to move these studies into a mouse model where we can test how nuclear size affects in vivo metastatic capacity. Citation Format: Lidija D. Vukovic, Bradley A. Stohr, Dan L. Levy. NTF2 regulates nuclear size in mammalian cells and may contribute to altered nuclear size in melanoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 475.
Definitions for Sepsis and Septic Shock
Authors: Charles L. Sprung, Konrad Reinhart
Journal: JAMA (2016)

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Backtracking Leukemia Clonal Evolution from Post-Transplantation Relapse to Initial Diagnosis to Identify Founder Mutations and Mechanisms of Immune Evasion
Authors: Luca Vago, Davide Cittaro, Cristina Toffalori, Dejan Lazarevic, Chiara Brambati, Giacomo Oliveira, Gabriele Bucci, Lara Crucitti, Nicoletta Cieri, Lorenza Chiesa, Benedetta Mazzi, Cristina Tresoldi, Bernhard Gentner, Matteo G Carrabba, Massimo Bernardi, Jacopo Peccatori, Chiara Bonini, Vito Lampasona, Katharina Fleischhauer, Fabio Ciceri, Elia Stupka
Journal: Blood (2014)
Evaluation of the potential clinical utility of risk models incorporating genomic risk information.
Authors: E. A. Comen, L. Balistreri, T. Kirchhoff, M. Gaudet, A. V. Dutra-Clarke, K. Offit, M. E. Robson
Journal: Journal of Clinical Oncology (2010)

1528 Background: For women at increased risk of breast cancer (BC), MRI is recommended at a >20% lifetime risk and tamoxifen at >1.67% 5-year risk. Risk may be estimated by use of models such as Gail, Claus, and BRCAPro. Several SNPs are associated with modest elevations (relative risk < 2) of BC risk. We have shown that the combined genomic risk (CGR) derived from SNP genotyping is independent of risk calculated from empiric models (abstract 901, SABCS 2009). Here, we investigated whether adjusting empiric model estimates by a CGR term would significantly change MRI and tamoxifen recommendations. Methods: Subjects were 475 unaffected, BRCA mutation- negative women who underwent BC risk assessment because of a family history of breast or ovarian cancer. Absolute BC risks were calculated by Gail, Claus, and BRCAPro models. Subjects were genotyped at 15 loci known to be associated with increased risk. For each subject, CGR was calculated using a log-additive model. Monte Carlo simulation using published allele frequencies and odds ratios was performed to calculate the average CGR (avCGR) for the population. Risk estimates for each individual were adjusted by multiplying the calculated absolute risk by the adjusted CGR (CGR/avCGR). Results: Median age at testing was 46 years (range 24-83). Median BC risk by Gail was 1.8% (5 yr) and 18.5% (lifetime, LT); Claus: 1.5% (5 yr) and 11.8% (LT); BRCAPro 1.1% (5 yr) and 11.6% (LT). The Table below illustrates the proportion of subjects who would have recommendations for tamoxifen or MRI changed by genomic adjustment of the original model-derived risk estimate. Conclusions: The use of genomic information to adjust risk estimates could reclassify a significant proportion of women with respect to recommendations for breast cancer screening and prevention interventions. The proportion reclassified varies depending upon which empiric model is used. The clinical validity of this approach requires further study to determine the calibration of adjusted estimates. Reclassification Model for original estimate Gail Claus BRCAPro No Tam to Tam 24 (10.7%) 28 (11.2%) 44 (12.6%) Tam to no Tam 32 (12.6%) 31 (19.4%) 35 (27.3%) No MRI to MRI 66 (22.4%) 27 (8.2%) 48 (10.1%) MRI to no MRI 55 (29.4%) 17 (25%) 2 (66.7%) No significant financial relationships to disclose.
Electroretinograms in autism: a pilot study of b-wave amplitudes
Authors: E R Ritvo, D Creel, G Realmuto, A S Crandall, B J Freeman, J B Bateman, R Barr, C Pingree, M Coleman, R Purple
Journal: American Journal of Psychiatry (1988)

The authors recorded electroretinograms for 27 autistic patients and 20 age- and sex-matched healthy volunteers. Thirteen (48%) of the autistic patients demonstrated subnormal b-wave amplitudes, which may indicate abnormal retinal function. One patient was tested serially at two sites; his low b-wave amplitude did not vary over time or between the two sites. If this retinal finding can be confirmed at other laboratories and in larger samples of autistic patients, it might provide a marker for a specific subtype of autism.
Abstract 2733: Novel function of the RAI2 protein in genomic integrity of breast cancer cells
Authors: Stefan Werner, Kerstin Borgmann, Klaus Pantel, Harriet Wikman
Journal: Cancer Research (2016)

Abstract We have recently identified the RAI2 protein as putative metastasis-suppressor related to dedifferentiation, early occurring bone metastasis formation, and survival of hormone dependent breast carcinomas. Nevertheless, low RAI2 expression is also predictive for poor patient outcome in hormone independent tumors and is furthermore associated with mutation of p53 in primary breast tumors. Thus, besides sustaining luminal differentiation, RAI2 might possess a general function as tumor suppressor that is, as indicated by association with p53 status, possibly related to maintenance of genomic stability. In order to characterize its potential role in genomic integrity, we screened lysates from RAI2 depleted MCF-7 and KPL-1 breast cancer cell lines with phosphorylation-specific antibody arrays. Additionally, we analyzed changes in expression of cell cycle related genes and proteins by qPCR and Western Blot analysis. We also conducted cytogenetic assays to investigate whether RAI2 depletion affects chromosomal stability and mitotic progression. Finally, we evaluated a possible association of RAI2 expression with aneuploidy in published expression data sets from breast cancer patients. As revealed by antibody array analysis, RAI2 depletion causes activation of p53 protein in MCF-7 and KPL-1 breast cancer cells, which was accompanied by a significant increase of senescent cells in the corresponding cell populations. Furthermore RAI2 depletion causes downregulation of several key factors of G2/M transition, like Aurora kinases A and B as well as Cyclins A2, B1 and B2. Concomitantly, we found in RAI2-depleted cell cultures reduction of mitotic index, increase of unattached chromosomes in metaphase and lagging chromosomes and during anaphase. This finding was further approved by an increase of numerical aberrations in RAI2 knockdown cells. Finally, we could show an association between low RAI2 expression and higher level of chromosomal instability in primary tumors from breast cancer patients. In conclusion, we found that loss of RAI2 function is associated with decreased mitotic fidelity. Thus, besides sustaining differentiation in hormone dependent breast tumor, RAI2 also acts as general tumor suppressor that maintains genomic integrity. Reference: Werner S et al., Cancer Discovery. 2015 May;5(5):506-19 Citation Format: Stefan Werner, Kerstin Borgmann, Klaus Pantel, Harriet Wikman. Novel function of the RAI2 protein in genomic integrity of breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2733.
Abstract 2382: Novel integration of genomic and morphological information reveals tumor tissue heterogeneity
Authors: Chen-Chung Lee, Paul Predki, Christopher Raub, Darryl Shibata, Clive Taylor, Emil Kartalov, Kenna Anderes
Journal: Cancer Research (2016)

Abstract Cancer treatment decisions today are predominantly based upon decades-old histological methods, which more recently have been combined with simple phenotypic or molecular tests. To advance this paradigm, we have developed a digital molecular morphology platform that integrates histological images with next-generation sequencing (NGS) or PCR data. This allows us to visualize DNA mutations and RNA expression levels across a histological image, and to correlate mutational or expression status to cell morphological features. Thus, providing a novel approach to mapping tumor heterogeneity. The basic approach is to overlay a microstructure on top of H&amp;E-stained FFPE slides to create a large number of tissue-bottomed micro-wells, which can be as small as a single cell or contain clusters of cells. Reagents are added to the micro-wells and biochemical reactions are carried out and analyzed in place (PCR) or partially offline (NGS). In the case of NGS, barcodes are used to reference the resulting sequence back to the tissue image. Software is then used to analyze and visualize the resulting genetic information in the context of the original histological image. Our initial work has focused on FFPE cancer biopsies using targeted cancer genes and gene panels. Here we demonstrate the use of this approach to measure and visualize KRAS G12V mutational status in colorectal cancer tissues, using both PCR and NGS detection modalities. We show that with this method we are able to efficiently extract DNA from the tissue while maintaining a leak-proof physical integrity from one micro-well to another. Further, we are able to PCR-amplify DNA in the micro-wells for direct fluorescence detection, or to create libraries for sequencing. Detection of KRAS G12V correlates well with malignant morphological features in the H&amp;E stained tissue, and appears to present a more sensitive way to detect mutations than PCR or NGS from bulk FFPE tissue alone. We are currently applying this technology to a variety of research and clinical applications, ranging from assessment of tumor heterogeneity and evolution, to prediction of patient outcome, to post-operative NGS-based characterization of surgical margins. This integration of cellular and molecular data promises to more fully enable precision medicine to guide the course of treatment and improve individual patient outcomes. Citation Format: Chen-Chung Lee, Paul Predki, Christopher Raub, Darryl Shibata, Clive Taylor, Emil Kartalov, Kenna Anderes. Novel integration of genomic and morphological information reveals tumor tissue heterogeneity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2382.