tbuckley/cabot-search huggingface dataset:
Abstract 1144: Imaging radiotherapy induced pulmonary fibrogenic changes with integrin-PET
Authors: Azeem Saleem, Yusuf Helo, Graham Searle, Fatjon Dekaj, Jo Cook, Zarni Win, Roger Gunn, Paula Wells
Journal: Cancer Research (2019)

Abstract Integrin αvβ6 plays a key role in the fibrotic pathway by activation of Transforming Growth Factor β. Expression of αvβ6 integrin in alveolar epithelium increases after radiotherapy (RT) before onset of fibrosis and anti- αvβ6 therapy prevents fibrogenesis. Post-RT lung fibrosis, a major barrier to improved cure rate presents as progressive pulmonary injury. The utility of PET imaging with a αvβ6 integrin ligand was evaluated in patients with non-small cell lung cancer following pulmonary RT. Subjects who had received pulmonary RT within 6 months were recruited. PET imaging of the lungs over 60 minutes was performed after administration of a fluorine-18 radiolabelled 20 amino acid αvβ6-specific peptide ligand, [18F]-FBAA20FMDV2 (IMAFIB; Cancer Research Technologies (CRT) patented). PET-CT scans were co-registered with the RT planning (RTP) scans and segmented to regions corresponding to RT doses of &amp;gt; 40 Gy (excluding tumour), 25-40 Gy, 15-25 Gy, 8-15 Gy and &amp;lt; 8 Gy. Time activity curves and the standardised uptake values (SUVs) were calculated and comparisons made between RT dose and PET uptake (SUV). Linear regression between SUV and RT dose was performed for each subject and normalised to an intercept of 1. 6 subjects (3M; 3 F) aged 51-75 years underwent an IMAFIB-PET scan between 6 -22 weeks after RT completion and mean IMAFIB radioactivity of 45.4 (range 8.9 – 122) MBq administered. 5 subjects received conformal external beam RT, while one subject received stereotactic RT (SBRT). A correlation between a higher PET uptake (SUV) and higher RT doses received by the lung was observed in all subjects with a significant relationship (p &amp;lt; 0.05) in 3 of the 6 subjects (table). The averaged normalised SUV across all subjects increased monotonically with RT dose, between 1.05 ± 0.14 at 4 Gy and 1.58 ± 0.31 at 52 Gy. Subject No.111216172021RT dose and fractionation55Gy in 5 fractions. SBRT64 Gy in 32 fractions45 Gy in 15 fractions50 Gy in 20 fractions64 Gy in 32 fractions64 Gy in 32 fractionsTime between completion of RT and PET scan (weeks)822136714Gradient of relationship between PET uptake and RT dose0.0290.0050.0100.0060.0030.008Intercept1.3050.5040.8370.3910.6910.469r20.8410.5390.8360.8790.3100.672p value0.0280.1580.0300.0180.1630.089 A relationship between IMAFIB PET uptake and RT dose is consistent with RT dose-related activation of αvβ6 integrin in the irradiated lung and to the induction of lung fibrosis in subjects receiving pulmonary RT. Citation Format: Azeem Saleem, Yusuf Helo, Graham Searle, Fatjon Dekaj, Jo Cook, Zarni Win, Roger Gunn, Paula Wells. Imaging radiotherapy induced pulmonary fibrogenic changes with integrin-PET [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1144.
The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis
Authors: Zobair M. Younossi, Pegah Golabi, Leyla de Avila, James Minhui Paik, Manirath Srishord, Natsu Fukui, Ying Qiu, Leah Burns, Arian Afendy, Fatema Nader
Journal: Journal of Hepatology (2019)
Care of the Transgender Patient
Authors: Joshua D. Safer, Vin Tangpricha
Journal: Annals of Internal Medicine (2019)

Transgender persons are a diverse group whose gender identity differs from their sex recorded at birth. Some choose to undergo medical treatment to align their physical appearance with their gender identity. Barriers to accessing appropriate and culturally competent care contribute to health disparities in transgender persons, such as increased rates of certain types of cancer, substance abuse, mental health conditions, infections, and chronic diseases. Thus, it is important that clinicians understand the specific medical issues that are relevant to this population.
Abstract 12711: Long Term Outcomes After Acute Myocardial Infarction Requiring Mechanical Support Devices: A J-Minuet Substudy
Authors: Takashi Morita, Masatake Fukunami, Takahisa Yamada, Koichi Nakao, Yukio Ozaki, Kazuo Kimura, Junya Ako, Teruo Noguchi, Satoshi Yasuda, Satoru Suwa, Kazuteru Fujimoto, Yasuharu Nakama, Wataru Shimizu, Yoshihiko Saito, Atsushi Hirohata, Yasuhiro Morita, Teruo Inoue, Atsunori Okamura, Toshiaki Mano, Kunihiro Nishimura, Yoshihiro Miyamoto, Hisao Ogawa, Masaharu Ishihara
Journal: Circulation (2018)

Introduction: Mechanical support (MS) devices such as intra-aortic balloon pumping (IABP) and veno-arterial extra corporeal membrane oxygenation (VA-ECMO) are essential for AMI patients complicated...
Abstract P088: The Association of Religious Affiliation With Cholesterol Levels Among South Asians: The Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study
Authors: Grishma Hirode, Nazleen Bharmal, Namratha Kandula, Alka M Kanaya
Journal: Circulation (2017)

Background: South Asians have disproportionately high rates of cardiovascular disease. Dyslipidemia is a common and contributing factor. Objective: We hypothesized that lifestyle behaviors are influenced by religious beliefs and may be associated with cholesterol levels. We determined the associations between religious affiliation and LDL-cholesterol, HDL-cholesterol, and triglycerides among South Asians in the U.S. Methods: We performed cross-sectional analyses of the 2010-2013 baseline data from the MASALA study (n=906). Using multivariate linear regression models, we examined the associations between self-reported religious affiliation (Hinduism/Jainism, Sikhism, Islam, Other and None) and lipid levels after controlling for age, sex, and cholesterol medication use. We determined whether smoking, alcohol use, physical activity, and dietary pattern would explain the association. Results: The mean age was 55±9 years, 46% were women, and 29% were taking cholesterol medications. The majority of respondents were Hindu and/or Jain (74%), followed by 8% Sikh, 7% Islamic, 6% no religious affiliation, and 5% other (Christian, Buddhist, Zoroastrian, and multiple religious affiliations). The mean LDL was 111±32 mg/dl, median HDL was 48 mg/dl (IQR: 40-57), and median triglycerides was 119 mg/dl (IQR: 88-157). The table shows the associations of religious affiliation with lipid levels in serially adjusted models. The majority of the effect of religious affiliation was attenuated by physical activity for LDL; by alcohol use, physical activity and smoking for HDL; and by alcohol use and physical activity for triglycerides. Conclusions: Islamic religious affiliation was associated with higher LDL, triglycerides and lower HDL, and Hinduism was associated with lower HDL. However, lifestyle behaviors completely explained these associations. Thus, religion-specific tailoring of interventions designed to promote healthy lifestyle changes to reduce cholesterol levels among South Asians may be useful.
Abstract 2827: Identification of chemotherapeutic resistant microbiota profile in colorectal cancer
Authors: Shuyun Rao, Charles Hadley King, Raja Mazumder, Shoujun Gu, Richard Amdur, Bibhuti Mishra, Lopa Mishra
Journal: Cancer Research (2019)

Abstract Background: Emerging data shows a rise in CRC incidence in men and women under 55 years of age, with a potential new risk factors including alterations in the microbiome. While recent advances have significantly reduced CRC morbidity and mortality, such as screening and new therapeutic strategies, how the microbiome modulates CRC chemotherapy response remains understudied. This alarming trend presents an urgent need for further understanding of the molecular mechanisms and “signatures” of the gut microbiome in CRC patients. Key driving pathways in CRC include WNT, RAS, RAF, APC and TGF-β signaling. Modulating the gut immune response includes multiple mechanisms, including sensors through carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) that serve as receptors to microbes, and crosstalk with signaling pathways such as TGF-β signaling pathway. Interestingly, disruption of TGF-β leads to increased sensitivity to cisplatin and other DNA cross-linking agents. Hypothesis and Aims: Our hypothesis is that the gut microbiome plays a key role in modulating the TGF-β pathway by CEACAMs binding to specific microbial species, thereby impeding the TGF-β pathway and altering chemotherapy response. Our aims are to explore TCGA genomics, and functional interactions between gut microbiota, CEACAMs, and TGF-β signaling in processing chemotherapy response. Methods and Results: We first analyzed microbiome signatures in normal and CRC patients, and identified a signature pattern. TCGA analyses in 9,125 human cancers reveal alterations of TGF-β with CEACAM members in over 40% of CRC and correlate with a cancer stem cell signature. Mechanistic studies reveal that CEACAMs inhibit TGF-β tumor suppressor signaling by blocking TGFBR1, and promoting invasive CRC. Likewise, our TGF-β signaling-deficient mouse models spontaneously develop CRC, as well as metastases, likely modulated in part by the microbiome. Furthermore, key defects in the TGF-β pathway alter sensitivity to 5-FU and DNA cross-linking agents, such as cisplatin, through disruption of DNA repair pathways. Conclusion: The TGF-β pathway is important in maintaining colon epithelial cell homeostasis potentially through interactions with CEACAMs and gut microbiota. When the pathway is disrupted, epithelial cells are more susceptible to transformation and invasion, potentially identifying specific populations that are more sensitive to chemotherapy such as cisplatin and 5FU. Citation Format: Shuyun Rao, Charles Hadley King, Raja Mazumder, Shoujun Gu, Richard Amdur, Bibhuti Mishra, Lopa Mishra. Identification of chemotherapeutic resistant microbiota profile in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2827.
Abstract 2477: CopyCat: estimating genomic copy number profiles from high-throughput single cell RNA seq data
Authors: Ruli Gao, Nicholas Navin
Journal: Cancer Research (2019)

Abstract CopyCat is a computational approach for estimate genomic-copy number profiles from high-throughput single cell RNAseq data that is generated by technologies, such as Drop-Seq, 10X genomics or Nanowells. CopyCat involves first normalizing and transforming unique molecular index (UMI) count data matrices to calculate single cell copy number states from low-coverage datasets using gene-bin windows across the human genome, and does not require a reference normal cell control. The resulting binned data is normalized and used for segmentation to reduce noise from individual genes that can contribute to gene dosage effects along chromosomes. We show that this methods is highly effective at distinguishing diploid and aneuploid cells in human tumors or cancer cell lines, and can efficiently detect major (&amp;gt;10mb) chromosomal amplifications and deletions compared to copy number data generated by DNA sequencing of match samples. We further show that this method can resolve some clonal substructure within individual tumors, when subpopulations are distinguished by large chromosomal events. Our method outputs segmented copy number profiles and predicted classifications of normal (diploid) and tumor (aneuploid) cell states for individual single cells. It is implemented in R and is available on Github. Citation Format: Ruli Gao, Nicholas Navin. CopyCat: estimating genomic copy number profiles from high-throughput single cell RNA seq data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2477.
Abstract 17916: Untreated Iron Deficiency is Associated With an Increased Risk for Thrombotic Complications in Patients With Left Ventricular Assist Devices
Authors: Ruth Tamrat, Rahat Muslem, P. Elliot Miller, Glenn Whitman, Chris Sciortino, Nisha A Gilotra, Stuart D Russell, Ryan J Tedford, Brian A Houston
Journal: Circulation (2016)

Introduction: Thrombotic complications are a major cause of morbidity and mortality in LVAD patients. In non-LVAD patients, iron deficiency (ID) is associated with increased risk of thrombotic even...
Heterogeneous antiretroviral drug distribution and HIV/SHIV detection in the gut of three species
Authors: Corbin G. Thompson, Elias P. Rosen, Heather M. A. Prince, Nicole White, Craig Sykes, Gabriela de la Cruz, Michelle Mathews, Claire Deleage, Jacob D. Estes, Paige Charlins, Leila R. Mulder, Martina Kovarova, Lourdes Adamson, Shifali Arora, Evan S. Dellon, Anne F. Peery, Nicholas J. Shaheen, Cynthia Gay, David C. Muddiman, Ramesh Akkina, J. Victor Garcia, Paul Luciw, Angela D. M. Kashuba
Journal: Science Translational Medicine (2019)

Imaging reveals that antiretroviral drugs are not distributed evenly in the mammalian gut, with potential implications for HIV replication.
Correlation between values of specific biomarkers and outcome in metastatic colorectal cancer patients treated with regorafenib
Authors: V. Ricci, A. Falletta, C. Granetto, M. Paccagnella, A. Abbona, E. Fea, T. Fabozzi, C. Lo Nigro, M. Merlano
Journal: Annals of Oncology (2019)
Mechanisms underlying skeletal muscle’s resistance to metastases.
Authors: Eva Vertes, Hilary Coller, Sean Scully, Nandor Garamszegi
Journal: Cancer Research (2006)

5139   Metastases to skeletal muscle (SM) are extremely rare. SM is highly perfused and the lack of hematogenous metastases to SM suggests that SM-derived factors may exert anti-tumorogenic and/or antimetastatic activity. To test this hypothesis, mouse C2C12 pre-myoblasts were cultured and differentiated into skeletal myotubes. Conditioned medium (CM) was collected and examined for its effects on mouse breast cancer cell proliferation and invasive/migratory potential. CM from C2C12 cells maintained in an undifferentiated, myoblastic state with TGF-β and C2C12 cells induced to differentiate into osteoblasts with BMP-2 were collected as controls. CM was heat inactivated and its effects on tumor cell proliferation and metastatic potential tested. Preliminary data suggest that myotube-conditioned medium inhibits breast cancer cell proliferation whereas myoblast-conditioned medium stimulates cell proliferation in a time-dependent manner. We also performed a matrigel migration assay as an  in vitro  model of metastases. In preliminary experiments, myotube-CM exhibited an inhibitory effect on the metastatic potential of breast cancer cells. This effect was partially relieved by heat inactivation, suggesting that a heat-labile factor may be partially responsible for this inhibitory activity. Anti-tumorogenic and anti-metastatic compounds in SM could potentially represent promising reagents for the treatment of metastatic tumors.
Palliative Inotrope Therapy
Authors: Sarah Chuzi, Larry A. Allen, Shannon M. Dunlay, Haider J. Warraich
Journal: JAMA Cardiology (2019)

<h3>Importance</h3> The number of patients living with end-stage heart failure is steadily growing, and ambulatory intravenous inotropic support is increasingly offered as a palliative therapy. However, the optimal ways to initiate, manage, and discuss the risks and benefits of palliative inotropes in the current era of heart failure care are unclear. <h3>Observations</h3> The initiation of palliative inotropes requires an understanding of clinical, psychosocial, and economic factors, as well as the changing risk-to-benefit calculus. While earlier studies suggested that outpatient inotrope therapy provided symptomatic benefit at the expense of reduced survival, recent data suggest that the survival of patients receiving chronic inotropes may be improving over time, perhaps owing to the use of implantable cardioverter defibrillators, concurrent guideline-directed medical therapy, or lower doses of inotropes. The use of heart failure therapies, such as β-blockade, among patients receiving palliative inotropes is controversial but may be appropriate in select situations. <h3>Conclusions and Relevance</h3> The role of palliative inotropes is changing in tandem with advances in chronic heart failure care. However, there remains a profound lack of data and guidance on the effect of palliative inotropes on quality of life and mortality and little consensus on how this therapy can be optimally used in contemporary practice. This review provides a framework for the prescription and management of palliative inotropes, including a discussion of potential risks and benefits and a roadmap for how to initiate, maintain, and wean them.
Abstract 17166: Homocysteine Modulates the Density and Composition of Myoendothelial Junctions
Authors: Cheng-Hung Chen, Richard S. Beard, Adam C. Straub, Katie Heberlein, Brant E. Isakson, Shawn E. Bearden
Journal: Circulation (2010)

Hyperhomocysteinemia (HHcy) is a risk factor for macrovascular and neurovascular disease. HHcy also impairs the vasomotor function of microvessels though little is known of how homocysteine affects...
Abstract 2754: Affinity-based probe reveal Bim negatively regulates the chaperone functions of Hsp70, a non-Bcl-2 BH3 receptor
Authors: Ziqian Wang, Zhichao Zhang, Ting Song, Zongwei Guo
Journal: Cancer Research (2019)

Abstract The identification of novel non-Bcl-2 BH3 receptors is still challenge owing to frequently weak, transient and reversible binding character of the PPIs mediated by them. Herein, we designed and synthesized an affinity-based probe (AfBP), S1b-probe, by introducing a photo-crosslinker to an artificial BH3 mimetic. Hsp70 proteins were identified as novel BH3 receptors in situ. The PPIs between Bcl-2 proteins and Hsp70 proteins were further validated by fluorescent polarization (FP), isothermal titration calorimetry (ITC) and Co-immunoprecipitation (Co-IP) experiments. Structural and functional analysis by photo-crosslinking/LC-MS/MS sequencing, 1H-15N transverse relaxation optimized spectroscopy (TROSY-HSQC), trypsin proteolysis, single-turnover ATPase rates and denatured rhodanese aggregation measurement demonstrated that BimBH3 bind in the NBD domain of Hsp70 proteins to act as a co-chaperone that negatively regulates the ATPase activity and chaperone functions. S1g, derived from BH3 mimetics, was screened as a specific Hsp70 inhibitor in native physiological context by using S1b-probe. Citation Format: Ziqian Wang, Zhichao Zhang, Ting Song, Zongwei Guo. Affinity-based probe reveal Bim negatively regulates the chaperone functions of Hsp70, a non-Bcl-2 BH3 receptor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2754.
Abstract 1503: Effect of immune cell depletion on the responses to PD1 treatment in syngeneic models
Authors: Ying Jin, Yongli Shan, Annie Xiaoyu An, Henry Qixiang Li, Davy Xuesong Ouyang
Journal: Cancer Research (2019)

Abstract Immunological checkpoint inhibitors, i.e., PD1 or PD-L1 antibodies, reverse cancer immunosuppression and promote antitumor immune responses in several cancer types. However, targeting PD-1/PD-L1 axis is only effective in ~20% of cancer patients, while some of the initial responders also develop resistance to the treatment. It is critical to fully understand which lineages of immune cells play major roles mediating PD1 responses in a given tumor microenvironment. While it’s well-known that PD1 antibody works through activating cytotoxic T cells, the contributions of other immune cell populations in PD1 treatment are not well defined. To understand how different lineages of immune cells impact PD1 efficacy, we removed various immune cell subpopulations in MC38 and Hepa 1-6 murine models when treated with PD1 antibody. In this study, mice inoculated with MC38 or Hepa1-6 tumors were treated with PD1 antibody or a combination of PD1 with depletion antibodies. The effectiveness of immune cell depletion was assessed by flow cytometry. CD4-, CD8- T cells, NK cells, MDSC and macrophages were depleted with anti-CD4 (GK1.5), anti-CD8 (2.43), anti-NK1.1 (PK136), anti-GR1 (RB6-8C5) antibodies and clodronate liposomes, respectively. As expected, depletion of CD8 T cells completely abrogated the antitumor effect of PD1 treatment, confirmed the crucial roles for CD8 T cells in tumor killing. Surprisingly, depletion of CD4 T cells and macrophages showed quite opposite effects in MC38 and Hepa1-6 lines - while significantly sensitizing MC38 tumors to PD1 treatment, PD1 efficacy is deteriorated in Hepa1-6. Depletion of NK cells enhanced the tumor inhibition effect in Hepa1-6 with 4 tumors showed complete or partial regression, without significant impact on MC38 tumors. Taken together, our studies have shown an unequivocal role of CD8 T cells in PD1 induced tumor growth inhibition. However, other lineages of immune cells may act differently upon PD1 blockade release, presumably depending on specific tumor microenvironment. Additional study is needed to differentiate the effects of Treg depletion vs. non-Treg CD4 T cell depletion. Citation Format: Ying Jin, Yongli Shan, Annie Xiaoyu An, Henry Qixiang Li, Davy Xuesong Ouyang. Effect of immune cell depletion on the responses to PD1 treatment in syngeneic models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1503.