tbuckley/cabot-search huggingface dataset:
Abstract 2574: Outcomes of contralateral prophylactic mastectomy in relation to familial history: a decision analysis
Authors: Kalatu R. Davies, Abenaa Brewster, Isabelle Bedrosian, Patricia Parker, Melissa A. Crosby, Susan K. Peterson, Yu Shen, Robert Volk, Scott B. Cantor
Journal: Cancer Research (2016)

Abstract Purpose Family history of breast cancer is associated with an increased risk of contralateral breast cancer (CBC) even in the absence of mutations in the breast cancer susceptibility genes BRCA1/2. We compared quality-adjusted survival outcomes after contralateral prophylactic mastectomy (CPM) with surveillance only (no CPM) among women with breast cancer in relation to degree of family history. Methods We created a microsimulation model for women with a first-degree, second-degree and no family history treated for a stage I, II, or III estrogen receptor (ER)-positive or -negative breast cancer at the ages of 40, 50, 60, and 70 years. The model incorporated a 10-year post-treatment period for risk of developing CBC and/or dying of the primary cancer or CBC. For each patient profile, we used 100,000 microsimulation trials to estimate the quality-adjusted life expectancy for two clinical strategies: CPM and no CPM. Results CPM had a minimal improvement on quality-adjusted life expectancy among women age 50 to 60 with no or a unilateral first or second-degree family history (range -.06 to 0.31) and was unfavorable for the majority of women age 70 with stage III breast cancer regardless of degree of family history (range -.08 to -.02). Sensitivity analysis showed the highest predicted benefit of CPM with 95% risk reduction was 0.57 QALY for a 40-year-old woman with stage I breast cancer who had a first-degree relative with bilateral breast cancer. Conclusion Women age 40 years with stage I breast cancer and a first-degree relative with bilateral breast cancer have a QALY benefit from CPM similar to that reported for BRCA1/2 mutation carriers. For the majority of women, having a family history does not improve the minimal effect of CPM on quality-adjusted life expectancy. Citation Format: Kalatu R. Davies, Abenaa Brewster, Isabelle Bedrosian, Patricia Parker, Melissa A. Crosby, Susan K. Peterson, Yu Shen, Robert Volk, Scott B. Cantor. Outcomes of contralateral prophylactic mastectomy in relation to familial history: a decision analysis. [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 2574.
Abstract 1387: Application of target enrichment combined with unique molecular identifiers to determine allelic frequencies of human cancers
Authors: Daniel C. Kraushaar, Sarah K. Bowman, Theodore B. Davis, Amy B. Emerman, Noa Henig, Kruti M. Patel, Salvatore Russello, Cynthia L. Hendrickson
Journal: Cancer Research (2016)

Abstract Existing target enrichment and library preparation for next-generation sequencing typically utilize PCR amplification steps that introduce substantial bias and sequencing of duplicate reads, which in turn affect the quantification accuracy of somatic allele frequencies. Unique molecular identifiers (UMIs) are random molecular tags that uniquely label each molecule prior to library amplification and aid in the identification of true PCR duplicates and thereby improve the accuracy in estimating the relative molecular copy number of the original sample. Here, we applied a target enrichment method for hybridization-based capture of regions of interest, combined with unique molecule labeling and next-generation sequencing to determine allelic frequencies of select cancer targets. Target enrichment and library preparation can be performed in just under seven hours, and our UMI method is compatible with sample indexing using separate barcodes. To demonstrate the robustness and accuracy of our method, we present the detection and assessment of allelic frequencies of multiple cancer genes across multiple reference standards. The result is a fast and cost-efficient method that enables the determination of even low allelic frequencies with high confidence. Citation Format: Daniel C. Kraushaar, Sarah K. Bowman, Theodore B. Davis, Amy B. Emerman, Noa Henig, Kruti M. Patel, Salvatore Russello, Cynthia L. Hendrickson. Application of target enrichment combined with unique molecular identifiers to determine allelic frequencies of human cancers. [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 1387.
Abstract 614: Cytotoxic activity of enantia chlorantha, nauclea latifolia, and citrus medica extracts on carcinoma cells
Authors: Chenel M. Alford, Alexandra Onyejiaka, Elbert L. Myles
Journal: Cancer Research (2016)

Abstract Over 562,340 Americans are expected to die of cancer, more than 1500 people a day. Cancer is the second most common cause of death in the US, exceeded only by heart disease. In the US, cancer accounts for nearly 1 of every 4 deaths. Our study focuses primarily on three plants never before investigated for antitumor activity. They were chosen based upon native ethno medicinal usages. Indigenous primarily to the southwestern region of Nigeria; Enantia chlorantha, Nauclea latifolia, and Citrus medica have all been traditionally used and studies have proven their noteworthy antibacterial, antimicrobial, and anti parasitical activities. These important characteristics provide the rationale behind studying these plants further for potential antitumor agents. Experimental: Methanolic leaf and bark extracts in a series of concentrations were taken from the previously stated plants and exposed to two breast and two colorectal cancer cells for 24 hours. Growth analysis is determined using a cell viability indicator alamar blue and a florescent plate reader. Results: Enantia chlorantha and Citrus medica demonstrated the most potential for containing novel antitumor compounds. However, E. chlorantha proved to be exceedingly toxic to the cellular proliferation of all four tumors cell lines at all concentrations. In addition to this, Nauclea latifolia extracts illustrated the least potential for antitumor activity. In most cases this extract showed little or no effect in reducing cellular proliferation. Conclusion: We conclude that leaf extracts from E. chlorantha and C. medica should be studied further to characterize their antitumor potential, investigate their main active compounds, and to better understand their mechanisms of action. Citation Format: Chenel M. Alford, Alexandra Onyejiaka, Elbert L. Myles. Cytotoxic activity of enantia chlorantha, nauclea latifolia, and citrus medica extracts on carcinoma 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 614.
Case 39-1981
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Charles B. Carrington, Eugene J. Mark
Journal: New England Journal of Medicine (1981)

Presentation of CaseA 58-year-old man was admitted to the hospital because of a cough, fever, and weight loss.He was well until three months earlier, when he began to experience fatigue, malaise, anorexia, fever, chills, and night sweats, with a dry cough and a nonpruritic rash over the lower portions of the legs and feet. During the next month he lost 6 kg in weight. Fatigue and night sweats persisted. One week before admission facial discomfort and xerostomia occurred; an otolaryngologist made a diagnosis of an infected sinus; no oral lesions were observed. Ampicillin and syrup of hydriotic acid . . .
Daily Alternating of Immunomodulating Agents and Rituximab in Therapy for Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphoma: The THRIL (Thalidomide [TH], Rituximab [RI], and Lenalidomide [L]) Regimen
Authors: Morton Coleman, Peter Martin, Jia Ruan, Ruben Niesvizky, John P. Leonard, Rebecca Elstrom, Richard R. Furman
Journal: Blood (2008)
Radium-223 and concomitant therapies in patients with metastatic castration-resistant prostate cancer: an international, early access, open-label, single-arm phase 3b trial
Authors: Fred Saad, Joan Carles, Silke Gillessen, Axel Heidenreich, Daniel Heinrich, Jeremy Gratt, Jérémy Lévy, Kurt Miller, Sten Nilsson, Oana Petrenciuc, Marcello Tucci, Manfred Wirth, Judith Federhofer, Joe M O'Sullivan
Journal: The Lancet Oncology (2016)
Abstract 4427: Role of Smurf2 in regulation of Smad anchor necessary for receptor activation (SARA) in TGFβ-receptor signaling
Authors: Sanghyun Lee, John M. Di Guglielmo
Journal: Cancer Research (2016)

Abstract Non-small cell lung cancer (NSCLC) is a major form of lung cancer and is the leading cause of cancer mortality in the western world. Transforming growth factor β (TGFβ) deregulation leads to many human diseases: TGFβ is a tumor suppressor in normal lung epithelium; however, it switches roles and promotes lung cancer metastasis in cancer cells. TGFβ induces cell proliferation, migration and invasion in NSCLC cells. The canonical pathway of TGFβ is initiated through binding of TGFβ ligand to transmembrane Ser/Thr kinase receptors, which propagate their signaling via receptor regulated R-Smads; proteins that function as intracellular effectors in the TGFβ pathway. Once activated, R-Smads form a complex with common (Co)-Smads that translocates into the nucleus to regulate transcriptional responses. Access of R-Smads to the activated receptor complex is regulated by an adaptor protein called Smad anchor for receptor activation (SARA). SARA facilitates the activation of Smads and allow efficient Smad signalling. In addition to R-Smads and Co-Smads, inhibitory Smads (I-Smads) regulate TGFβ signalling. I-Smads block the signalling by competing against R-Smads for the association with TβR complex or by targeting receptors for ubiquitin-mediate degradation. I-Smads recruit the E3 ubiquitin ligases, Smad ubiquitination regulatory factors (Smurfs), to catalyze degradation of the receptor complex. The overall aim of the project is to characterize SARA in TGFβ receptor signalling and study the interaction of SARA with different proteins involved in the pathway, such as Smurf2 and Smad7. We first examined how SARA, Smurf2 and Smad7 influence each other by performing a multi-combination transfection study. We also examined the interaction between SARA and Smurf2 through co-immunoprecipitation. We observed that the level of SARA decrease in the presence of Smurf2 and Smad7. In the presence of Smurf2 ligase inactive mutant and Smad7, the level of SARA is somewhat recovered. However, SARA does not directly interact with Smurf2. These data together suggest that SARA and Smurf2 influence each other in a very close manner. It also suggest that it could be a transient interaction. Characterizing SARA in TGFβ receptor signalling will provide us with possible drug targets for NSCLC. Citation Format: Sanghyun Lee, John M. Di Guglielmo. Role of Smurf2 in regulation of Smad anchor necessary for receptor activation (SARA) in TGFβ-receptor signaling. [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 4427.
Laparoscopic anti-reflux surgery for idiopathic pulmonary fibrosis at a single centre
Authors: Ganesh Raghu, Ellen Morrow, Bridget F. Collins, Lawrence A.T. Ho, Marcelo W. Hinojosa, Jennifer M. Hayes, Carolyn A. Spada, Brant Oelschlager, Chenxiang Li, Eric Yow, Kevin J. Anstrom, Dylan Mart, Keliang Xiao, Carlos A. Pellegrini
Journal: European Respiratory Journal (2016)

We sought to assess whether laparoscopic anti-reflux surgery (LARS) is associated with decreased rates of disease progression in patients with idiopathic pulmonary fibrosis (IPF).The study was a retrospective single-centre study of IPF patients with worsening symptoms and pulmonary function despite antacid treatment for abnormal acid gastro-oesophageal reflux. The period of exposure to LARS was September 1998 to December 2012. The primary end-point was a longitudinal change in forced vital capacity (FVC) % predicted in the pre- versus post-surgery periods.27 patients with progressive IPF underwent LARS. At time of surgery, the mean age was 65 years and mean FVC was 71.7% pred. Using a regression model, the estimated benefit of surgery in FVC % pred over 1 year was 5.7% (95% CI -0.9-12.2%, p=0.088) with estimated benefit in FVC of 0.22 L (95% CI -0.06-0.49 L, p=0.12). Mean DeMeester scores decreased from 42 to 4 (p<0.01). There were no deaths in the 90 days following surgery and 81.5% of participants were alive 2 years after surgery.Patients with IPF tolerated the LARS well. There were no statistically significant differences in rates of FVC decline pre- and post-LARS over 1 year; a possible trend toward stabilisation in observed FVC warrants prospective studies. The ongoing prospective randomised controlled trial will hopefully provide further insights regarding the safety and potential efficacy of LARS in IPF.
Abstract 2796: Regulation of HIF-1α by hnRNP A18 contributes to tumor promotion under hypoxic conditions
Authors: Elizabeth T. Chang, Palak Parekh, Qingyuan Yang, France Carrier
Journal: Cancer Research (2016)

Abstract The RNA-binding protein heterogenous ribonucleoprotein A18 (hnRNP A18) is a new protein translation regulator found to be elevated in many cancers. Previous work from our lab has shown that hnRNP A18 is able to bind and regulate the translation of a group of mRNAs under stress conditions, including hypoxia. Hypoxia has largely been recognized as an innate characteristic of solid tumors and plays numerous cellular and physiologic roles such as cell proliferation, invasion, migration, metastasis, and angiogenesis. Given its extensive function in solid tumors, combined with computational results showing a possible hnRNP A18 signature motif in the 3’UTR of HIF-1α, we sought to determine if hnRNP A18 binds HIF-1α mRNA and how this affects tumor promotion and growth. Results: Our data indicates that hnRNP A18 protein is able to bind HIF-1α mRNA. Under hypoxic conditions, down-regulation of hnRNP A18 significantly decreases HIF-1α mRNA stability, leading to reduced amounts of HIF-1α protein levels in melanoma cells. Treatment with CoCl2 increases hnRNP A18 protein levels in melanoma cells, but not in normal melanocytes. Additionally, colony survival assay demonstrates that down-regulation of hnRNP A18 decreases cells’ survival rates under a hypoxic environment. The functional significance of this effect was observed in a mouse xenograft model where down-regulation of hnRNP A18 significantly reduced melanoma and breast tumor growth. Immunohistochemistry staining of xenograft specimens showed overlapping localization of hnRNP A18 to the tumor hypoxic regions. Lastly, proteome profiling of the xenograft tumors showed a significant decrease of key angiogenic-related factors (e.g., angiogenin, endoglin, VEGF) when hnRNP A18 is reduced. Conclusion: Heterogenous ribonucleoprotein A18 is able to regulate HIF-1α mRNA and modulate its protein levels under hypoxic conditions. The oxygen-deprived regions generated in the central core of a solid tumor leads to up-regulation of hnRNP A18 and consequently HIF-1α, resulting in tumor growth and promotion. New therapeutics targeting hnRNP A18 would therefore be a logical next-step in developing a novel mechanism-based therapy for cancer treatment. Citation Format: Elizabeth T. Chang, Palak Parekh, Qingyuan Yang, France Carrier. Regulation of HIF-1α by hnRNP A18 contributes to tumor promotion under hypoxic conditions. [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 2796.
Abstract LB-006: Macrophage-dependent activation of Notch1 signaling regulates breast tumor cell intravasation
Authors: Jeanine Pignatelli, Jose Javier Bravo-Cordero, Minna Roh-Johnson, Saumil Gandhi, Yarong Wang, Robert Singer, Louis Hodgson, Maja Oktay, John Condeelis
Journal: Cancer Research (2016)

Abstract The process of intravasation, a key component to the metastatic cascade, remains poorly understood. How the multi-cell type tumor microenvironment facilitates tumor cell intravasation is largely unknown. Intravital imaging of rodent mammary tumors has shown that direct contact between a Mena expressing tumor cell, a perivascular macrophage and an endothelial cell forms a microanatomical structure named TMEM (Tumor Microenvironment of Metastasis) which is the site where intravasation occurs in mammary tumors. Clinical studies have shown that the number of TMEM is correlated with increased risk of developing distant metastasis in breast cancer patients. While TMEM is an excellent prognostic marker for predicting metastasis, the mechanisms of TMEM assembly and function are not well understood. Recently, we showed that heterotypic cell contact between tumor cells and macrophages induces the formation of invadopodia in tumor cells, invasive structures necessary for matrix degradation and required for tumor cell intravasation. In further work we found that Notch1, a known receptor involved in heterotypic cell contact signaling, is involved. In the absence of Notch1 signaling, macrophage-induced invadopodium formation and tumor cell intravasation are abolished. This heterotypic tumor cell - macrophage interaction regulates the expression profile of Mena in the tumor cell. Upon touching, the transcription of Mena shows a rapid kinetic response, with detectable changes in single transcriptome activity within 1 hour. Inhibition of Notch1 in vivo results in decreased intravasation of mammary tumor cells. Our findings indicate that Notch1 signaling regulates heterotypic cell contact mediated invadopodium formation, transendothelial migration and intravasation and reveals a novel Notch1/Mena pathway as a molecular target to prevent TMEM function and therefore metastasis. Citation Format: Jeanine Pignatelli, Jose Javier Bravo-Cordero, Minna Roh-Johnson, Saumil Gandhi, Yarong Wang, Robert Singer, Louis Hodgson, Maja Oktay, John Condeelis. Macrophage-dependent activation of Notch1 signaling regulates breast tumor cell intravasation. [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 LB-006.
Abstract 4180: Rewiring the cytokine network in melanoma
Authors: Raghavendar Nagaraju, Christopher Dee, Helen Young, Jorge Barriuso, Christopher Secombes, Adam Hurlstone
Journal: Cancer Research (2016)

Abstract Malignant melanoma is one of the most aggressive types of malignancies in humans resulting in 50,000 deaths worldwide annually. Fortuitously, malignant melanoma is highly immunogenic and it is now well established that the host immune system can detect and kill melanoma. T helper type-1 lymphocytes (TH1) play a pivotal role in inducing and maintaining anti-tumour immune responses. In melanoma patients, it has been observed that higher number of TH1 cells in the tumour micro-environment lead to better prognosis. In this study, using an autochthonous zebrafish melanoma model, when we forced the expression of interferon gamma (IFNg) locally in the tumour microenvironment, thereby potentially enhancing TH1 differentiation, we observed an inflammatory response against melanoma that eventually lead to complete tumour regression. Using transposon mediated BAC transgenesis, we have generated a Tg(cd4:mcherry) reporter line labelling CD4+ cells in zebrafish. By driving Human NRASQ61L in zebrafish melanocytes we have modelled melanoma in zebrafish and later when these fish developed tumours we forced the expression of IFNg in melanoma cells using a tamoxifen inducible LSL/CreERT2 system driven by mitfa minimal promoter. Experiments were performed using animals with and without CreERT2. Following tamoxifen administration, we observed a loss of pigmentation in all the IFNg induced tumours (n = 12) by 2 weeks post induction which gradually increased over the study period. Whereas no loss of pigmentation was observed in control tumours (n = 12) throughout the study period. At 9 weeks post induction, the study was terminated and tumours were analysed using histology. In tumours were IFNg was induced, we observed that the tumour tissue was now replaced with fibrotic tissue accompanied by a marked lymphocyte infiltration and patches of necrosis. However, new tumour nodules were also observed to develop in the vicinity of regressing nodules which are unpigmented and potentially hypo-immunogenic. We observed no signs of tumour regression in control tumours. Although preliminary, our data is very exciting and promising as it will open new avenues for developing combinatorial therapies in melanoma. Using a high throughput in-vivo model system such as zebrafish, it is an exciting proposition to test the impact of combining anti-PD1/PDL1 inhibitors with various cytokines/chemokines in inducing effective and sustained tumour regression in melanoma. Citation Format: Raghavendar Nagaraju, Christopher Dee, Helen Young, Jorge Barriuso, Christopher Secombes, Adam Hurlstone. Rewiring the cytokine network 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 4180.
Cell-Free Hemoglobin, HMOX1 and APOL1 in Sickle Cell Nephropathy
Authors: Santosh L. Saraf, Xu Zhang, Binal Shah, Krishnamurthy P. Gudehithlu, Rick Kittles, Michel Gowhari, Jose Arruda, Roberto F. Machado, Mark T Gladwin, Ashok Singh, Victor R. Gordeuk
Journal: Blood (2014)
Impaired Shedding of TNF Receptor 1 Aggravates High Fat Diet Induced Non-Alcoholic Fatty Liver Disease But Does Not Cause Insulin Resistance in Mice
Authors: Pascal Hommelberg, Marcela Aparicio-Vergara, Marijke Schreurs, Nanda Gruben, Rinke Stienstra, Ronit Shiri-Sverdlov, Niels Kloosterhuis, Alain de Bruin, Bart van de Sluis, Debby Koonen, Marten H. Hofker
Journal: Hepatology (2012)
HuMax-CD20, a novel fully human anti-CD20 monoclonal antibody
Authors: A Hagenbeek, T Plesner, P Johnson, L Pedersen, J Walewski, A Hellmann, B Link, T Robak, M Wojtukiewicz, M Pfreundschuh, M Kneba, A Engert, P Sonneveld, J Petersen, J Radford
Journal: Blood (2005)