tbuckley/cabot-search huggingface dataset:
High-Intensity Focused Ultrasound (HIFU) Triggers Immune Sensitization of Refractory Murine Neuroblastoma to Checkpoint Inhibitor Therapy
Authors: Avinash Eranki, Priya Srinivasan, Mario Ries, AeRang Kim, Christopher A. Lazarski, Christopher T. Rossi, Tatiana D. Khokhlova, Emmanuel Wilson, Susan M. Knoblach, Karun V. Sharma, Bradford J. Wood, Chrit Moonen, Anthony D. Sandler, Peter C.W. Kim
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Immunotherapy promises unprecedented benefits to patients with cancer. However, the majority of cancer types, including high-risk neuroblastoma, remain immunologically unresponsive. High-intensity focused ultrasound (HIFU) is a noninvasive technique that can mechanically fractionate tumors, transforming immunologically “cold” tumors into responsive “hot” tumors. Experimental Design: We treated &amp;lt;2% of tumor volume in previously unresponsive, large, refractory murine neuroblastoma tumors with mechanical HIFU and assessed systemic immune response using flow cytometry, ELISA, and gene sequencing. In addition, we combined this treatment with αCTLA-4 and αPD-L1 to study its effect on the immune response and long-term survival. Results: Combining HIFU with αCTLA-4 and αPD-L1 significantly enhances antitumor response, improving survival from 0% to 62.5%. HIFU alone causes upregulation of splenic and lymph node NK cells and circulating IL2, IFNγ, and DAMPs, whereas immune regulators like CD4+Foxp3+, IL10, and VEGF-A are significantly reduced. HIFU combined with checkpoint inhibitors induced significant increases in intratumoral CD4+, CD8α+, and CD8α+CD11c+ cells, CD11c+ in regional lymph nodes, and decrease in circulating IL10 compared with untreated group. We also report significant abscopal effect following unilateral treatment of mice with large, established bilateral tumors using HIFU and checkpoint inhibitors compared with tumors treated with HIFU or checkpoint inhibitors alone (61.1% survival, P &amp;lt; 0.0001). This combination treatment significantly also induces CD4+CD44+hiCD62L+low and CD8α+CD44+hiCD62L+low population and is adoptively transferable, imparting immunity, slowing subsequent de novo tumor engraftment. Conclusions: Mechanical fractionation of tumors using HIFU can effectively induce immune sensitization in a previously unresponsive murine neuroblastoma model and promises a novel yet efficacious immunoadjuvant modality to overcome therapeutic resistance.
On the Relation of food to Work Done by the Body: And its Bearing upon Medical Practice
Authors: S. Haughton
Journal: BMJ (1868)

will be taken beneath your feet."But a position, though airy, may yet be impregnable.There are those present who will recollect how the highest placed forts of that town were never taken, but continued to the last to answer shot for shot, and shell for shell, to the Allies.
Hidden Abnormalities and Novel Classification of t(15;17) APL Based on Genomic Alterations.
Authors: Tadayuki Akagi, Seishi Ogawa, Go Yamamoto, Masashi Sanada, Norihiko Kawamata, Carl W. Miller, Der-Cherng Liang, Lee-Yung Shih, H. Phillip Koeffler
Journal: Blood (2007)
Endogenous T Cell Receptors Drive Non-Specific Suppression by Foxp3 MHC Class I-Restricted T Cell Receptor-Transduced Polyclonal CD4+ T Cells in Models of Graft-Versus-Host Disease.
Authors: Benjamin J Uttenthal, Emma Nicholson, Ben Carpenter, Sara Ghorashian, Graham P Wright, Barry R Flutter, Shao-An Xue, Ronjon Chakraverty, Emma Morris
Journal: Blood (2012)
Abstract 644: Enhancing Lymphangiogenesis Ameliorates Chronic Heart Failure
Authors: Loujin Song, Terri Swanson, Xian Chen, Teresa Cunio, Brianna LaViolette, Shoh Asano, Katherine Hales, Jincheng Pang, Andrew Robertson, Casey Ritenour, Magalie Boucher, Rachel J Roth Flach
Journal: Circulation Research (2019)

Previous studies have indicated that cardiac lymphatics are involved in the pathogenesis of acute cardiac injuries. However, the role of cardiac lymphatics in the pathogenesis of chronic heart failure remains unclear. The goal of this study is to investigate the role of cardiac lymphatics in the development of chronic heart failure, and to test the hypothesis that improving lymphatic vascular function will have therapeutic benefits in chronic heart failure. First, we characterized lymphatic endothelial marker expression in human hearts from normal or heart failure patients, and a trend towards reduced lymphatic marker expression was observed. These data suggested that lymphatic vessels may be impaired in chronic heart failure. To test this hypothesis further, angiotensin II infusion was used to induce cardiac dysfunction and hypertrophy in mice. Using lymphangiography, we discovered impaired lymphatic transport in angiotensin II-infused mouse hearts compared with control mouse hearts, suggesting impairments in cardiac lymphatic function. Interestingly, when the angiotensin II infused mice were co-administered VEGFCc156s protein to enhance lymphangiogenesis and improve lymphatic vascular function, the VEGFCc156s-treated mice demonstrated improved cardiac function and reduced cardiac hypertrophy compared with angiotensin II infused mice, indicating a potential beneficial effect of VEGFCc156s treatment on angiotensin II-induced cardiac dysfunction and hypertrophy. Overall, these results demonstrate that cardiac lymphatic vessels were impaired in chronic heart failure, and improving lymphatic vascular function may have therapeutic effects on chronic heart failure. The outcome of the study may provide new insights into developing new therapeutics for chronic heart failure.
Activation of a Mir-181-Targeting HOXA-PBX3 Homeobox Gene Signature Is Associated with Adverse Prognosis of Cytogenetically Abnormal Acute Myeloid Leukemia
Authors: Zejuan Li, Hao Huang, Yuanyuan Li, Xi Jiang, Ping Chen, Stephen Arnovitz, Michael D. Radmacher, Kati Maharry, Abdel Elkahloun, Xinan Yang, Chunjiang He, Colles O. Price, Konstanze Dohner, Zhiyu Zhang, Chen Shen, Mary Beth Neilly, Yves A Lussier, Yanming Zhang, Richard A. Larson, Michelle M. Le Beau, Michael A Caligiuri, Lars Bullinger, Peter Valk, Ruud Delwel, Bob Lowenberg, Paul P. Liu, Guido Marcucci, Clara D. Bloomfield, Janet D. Rowley, Jianjun Chen
Journal: Blood (2011)
Evaluating a 20-gene multiplex assay to identify gene expression signatures of breast cancer progression
Authors: Mervin Gutierrez, Yong Wu, Anna Ivshina, Cynthia Boardman, Lance Miller, Jane Luo
Journal: Cancer Research (2008)

1651  Gene expression profiling has been used to stratify disease progression by elucidating molecular differences between early and later stage cancer. The ability to assess gene expression signatures from a smaller number of genes (10 to 30) allows for higher sample throughout and more practical implementation in a routine testing environment. A multiplex assay targeting 20 genes integrated with a universal priming strategy was developed for this study. This multiplex assay contains primers for 11 genes associated with tumorigenesis, apoptosis, cell-cycle regulation and cell proliferation. In addition, the multiplex assay contains primers for nine reference genes and an internal control gene. RNA amplification was performed using in vitro transcription to produce anti-sense RNA (aRNA), followed by analysis using the 20-gene multiplex assay. The reaction products were separated using capillary electrophoresis technology. The gene expression profiles of normal breast tissue and invasive breast tumors of different pathological stages were characterized from biopsy samples. This study identified distinct gene expression signatures that correlate with tumor progression using a novel quantitative multiplexing methodology.
The effect of medical home enrollment on cardiometabolic medication adherence among Medicaid-insured cancer patients.
Authors: Lisa Spees, Stephanie B. Wheeler, Xi Zhou, Krutika B Amin, Chris Baggett, Jennifer Leigh Lund, Ben Urick, Joel Farley, Katherine Elizabeth Reeder-Hayes, Justin G Trogdon
Journal: Journal of Clinical Oncology (2019)

279 Background: Medical homes, developed to increase care coordination among vulnerable patient populations, have been successful in improving outcomes of patients with multiple chronic comorbidities, but have not been evaluated among cancer survivors. We determined the impact of medical home enrollment on adherence to anti-diabetics, anti-lipidemics, and anti-hypertensives among Medicaid patients diagnosed with non-metastatic breast, colorectal, or lung cancer. Methods: Using linked cancer registry and claims data from North Carolina, we included Medicaid-insured adults diagnosed from 2004-2012 with breast, colorectal, or lung cancer who had at least one cardiometabolic condition (i.e., hyperlipidemia, hypertension, and diabetes mellitus). For each cardiometabolic condition, we measured medication adherence using ambulatory proportion of days covered (PDC). We examined the impact of medical home enrollment on PDC across the phases of cancer care (i.e., pre-cancer diagnosis, treatment, and survivorship phases) using a differences-in-differences model. All models adjusted for age, sex, race/ethnicity, dual enrollment, cancer type, comorbidity index, and number of cardiometabolic conditions. Results: We included, respectively, 765, 1079, and 1634 cancer patients with diabetes, hyperlipidemia, and hypertension. Overall, adherence to anti-lipidemics was lower than adherence to anti-diabetics and anti-hypertensives. In the pre-diagnosis phase, mean PDC across all cardiometabolic conditions was slightly lower for cancer patients enrolled in a medical home than those not enrolled in a medical home. However, medication adherence improved 3-5% in the treatment phase and 7% in the survivorship phase for cancer patients in a medical home compared to cancer patients not in a medical home during the pre-diagnosis phase. Conclusions: These results provide evidence that enrollment in a medical home can improve medication adherence, even among vulnerable cancer patients with complex health needs. The medical home model is an effective healthcare system intervention through which to provide better care coordination and improve patient outcomes.
Impact of an oncology acute care clinic (ACC) in a comprehensive cancer care setting to reduce emergency visits and subsequent hospitalizations: A pilot study.
Authors: Anamika Chaudhuri, Andrew J. Wagner, Craig A. Bunnell, Anne Gross, Emma Green, Danielle Bowers, Belen Fraile
Journal: Journal of Clinical Oncology (2019)

110 Background: Emergency Department (ED) visits and subsequent hospitalizations are a major source of healthcare resource utilization and costs among cancer patients, compromising quality of care and patient satisfaction. Emerging evidence, including OCM and other alternative payment models suggest many of these visits may be preventable and effectively managed in oncology-specific urgent care clinics. Little is known about such care delivery models in the comprehensive cancer care arena. Methods: As part of larger effort to provide better, efficient, timely care to patients, an acute care clinic (ACC), appropriately staffed to provide ancillary services, was set up in an academic hospital outpatient setting with hours of operations 10:30- 8:00 pm to effectively manage patients with cancer-related symptoms. The objective was to change the site of care for patients who would otherwise be seen in the ED and discharged home as well as to potentially decrease the frequency of hospitalization following ED evaluation by providing oncology subspecialized care. A retrospective analysis of 4 months pre- and post-intervention was performed with emergency visits per 1000 visits per month as the primary outcome and subsequent hospitalizations as a secondary outcome. Results: A total of 1593 patients (821 pre-intervention and 772 post-intervention) were included. Preliminary analysis revealed a 7% observed reduction in ED visits (0.25 vs 0.23 visits per month per 1000 visits; p = 0.85) for oncology patients which otherwise would have seen a 12% increase, following the historical trend. Data also suggest more effective avoidance of acute care settings with discharge disposition for patients from ED pre-intervention versus ACC post-intervention being 32% vs 72% home, 67% vs 13% inpatient, 1% vs 6% ED respectively. Conclusions: The creation of an ACC to manage urgent patient visits in an ambulatory setting decreased ED visits and the likelihood of patient admission. Although initial findings suggest improved preliminary outcomes, further analysis is required to make any causal inference on the true impact of ACC intervention for reduction of ED and hospitalizations.
Cowden Syndrome as an indication for bilateral prophyllactic mastectomy: A series of two cases
Authors: M. Loewen, A. Ashikari, P. Kelemen, A. Salzberg, J. Savino, R. Ashikari
Journal: Journal of Clinical Oncology (2006)

10761 Background: Multiple hamartoma syndrome, or Cowden Syndrome, is an autosomal dominant disorder which predisposes toward neoplasms in the thyroid, colon, and breast. Chemoprevention in women with a genetic predisposition toward breast cancer has not yet been shown to be beneficial in prospective data. Bilateral prophylactic mastectomy (BMP) has emerged as a viable option for women with suspected genetic predispositions toward breast cancer, with an estimated risk reduction of around 90 percent. Our search of the literature has not detected any case series of BMP in the Cowden Syndrome patients. Methods: We present two women presenting with historical and physical evidence for this Cowden Syndrome with desire to undergoing PBM. Results: Both women successfully underwent subcutaneous bilateral mastectomy with immediate reconstruction. (See table ) They are both alive without evidence of breast cancer to date. Conclusions: Cowden Syndrome can be added to other genetic syndromes with clear predispositions toward breast cancer, and presents an option for prophylactic bilateral mastectomy in women who desire a risk reduction for breast cancer. [Table: see text] No significant financial relationships to disclose.
Repeat Infusion of CD19-Specific Chimeric Antigen Receptor T-Cell Could Improve the Efficacy with Consistent Safety in Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Authors: Jianda Hu, Ting Yang, Xiaozhu Yang, Na Xian, Yanxin Chen, Peifang Jiang, Gangxiong Huang
Journal: Blood (2018)
Abstract 846: The Effects and Mechanisms of Pyridostigmine on Cell Proliferation and Fibrosis of Human Cardiac Fibroblasts
Authors: Li-Shui Shen
Journal: Circulation Research (2019)

Background: Heart failure (HF) is a common, costly, and potentially fatal condition. Cardiac fibrosis plays a key role in the process of HF. Pyridostigmine (PYR) could improve the cardiac function by inhibiting collagen deposition in cardiac tissue, but the molecular mechanisms are unknown. Objective: To investigate the effects and mechanisms of Pyridostigmine on cell proliferation and fibrosis in human cardiac fibroblasts (HCFs). Methods: The model of fibrosis in HCFs was induced by transforming growth factor beta. After the intervention of PYR, the content of collagen I(COL1) was observed by measuring the hydroxyproline concentration. The cell cycle of HCFs was screened by Flow cytometry. The mRNA levels of Connective tissue growth factor (CTGF) and Smad3 were examined by real-time qPCR analysis. The expressions of CTGF, Smad3, pSmad3 were examined by Western blot. Results: Compared with the TGF-β group, the TGF-β+PYR group had significantly lower proportion of S/G2 phased cells[(30.8±1.4) % vs (48.6±3.5)%], less synthesis of COL1 [(0.95±0.15) vs (1.25±0.18)]and fewer expressions of CTGF mRNA [(1.73±0.10) vs (2.92±0.12)]and CTGF protein[(1.23±0.42) vs (2.36±0.62)]. However, the expressions of Smad3 mRNA [(1.50±0.06) vs (1.55±0.08)], Smad3 protein [(2.85±0.45) vs (2.98±0.47)] and pSmad3 protein [(2.39±0.32) vs (2.51±0.52)] between these two groups showed no difference (P&gt;0.05). Conclusion: Pyridostigmine significantly alleviated cell proliferation and collagen synthesis in HCFs induced by TGF-β, and its mechanism was related to the inhibition of CTGF expression rather than blocking the TGF-β/Smads signaling pathway.
Abstract 259: Resistin Accelerates Fibroblast-Myofibroblast Differentiation and Induces Myocardial Fibrosis
Authors: Rajvir Singh, Ravinder K Kaundal, Baoyin Zhao, Rihab Bouchareb, Roger Hajjar, Djamel Lebeche
Journal: Circulation Research (2019)

Background: Cardiac fibrosis (CF) is a major cause of heart failure in patients with ischemic insult, obesity, and diabetes. CF, characterized by excessive deposition of extracellular matrix proteins and myofibroblast differentiation, leads to profound changes in ventricular architecture and geometry, and thereby reduces cardiac function. Resistin, an adipokine has been linked to obesity, insulin resistance and diabetes. Our previous findings have implicated resistin in CF, however the molecular mechanisms underlying this process are still unclear. In this study, we investigated whether resistin regulates the transdifferentiation of fibroblasts into myofibroblasts as well as the molecular pathways leading to resistin-induced fibrotic response. Methods: Fibroblast-to-myofibroblast differentiation was induced with resistin, TGFβ1 or FBS for 48hours in isolated cardiac fibroblasts from adult mouse and mouse embryonic fibroblasts (NIH3T3 cells). Resistin knockout mice were challenged with high fat diet for 16 weeks to stimulate cardiac lipotoxicity. Fibrotic response and markers were determined in harvested hearts. Results: Adult cardiac fibroblasts stimulated with resistin displayed increased fibroblast-to-myofibroblast differentiation, with significantly increased levels of collagen, fibronectin, and connective tissue growth factor. Mechanistically, we demonstrated that resistin promotes fibrogenesis via Jak-Stat and c-Jun signaling pathways, independently of TGFβ1. In-vivo study confirmed the role of resistin in cardiac fibrosis. Resistin knockout mice, when challenged with high fat diet to stimulate cardiac lipotoxicity, showed a decrease in fibrosis paralleled with reduced mRNA levels of various markers of fibrosis such as collagen, fibronectin and connective tissue growth factor compered to wild type hearts. A significant improvement in heart function was also observed in resistin knockout mice. Conclusions: To our knowledge, these findings are the first to demonstrate a role of resistin in the process of cardiac fibroblast-to-myofibroblast conversion through Jak-Stat and c-Jun signaling. These results bring new insights into the mechanisms by which resistin may contribute to cardiac fibrosis.
KIR Expression on inVitro-Derived Natural Killer Cells Does Not Regulate Killing of Allogeneic Targets
Authors: Yunzu Michele Wang, Huang Zhu, Alessa Ruiz-Cisneros, Naveen Heragu, Eivind Heggernes Ask, Hanna Julie Hoel, Karl-Johan Malmberg, Dan S Kaufman
Journal: Blood (2018)
“It’s important to me”: A qualitative analysis of shared decision-making and patient preferences in early-stage breast cancer patients.
Authors: Valerie Lawhon, Rebecca England, Audrey S. Wallace, Courtney Williams, Stacey A. Ingram, Aidan Gilbert, Gabrielle Betty Rocque
Journal: Journal of Clinical Oncology (2019)

227 Background: Shared decision-making (SDM) occurs when both patient and provider are involved in the treatment decision-making process. SDM allows patients to understand the pros and cons of different treatments while also helping them select the one that aligns with their care goals when multiple options are available. This qualitative study sought to understand different factors that influence early-stage breast cancer (EBC) patients’ approach in selecting treatment. Methods: This cross-sectional study included women with stage I-III EBC receiving treatment at the University of Alabama at Birmingham from 2017-2018. To understand SDM preferences, patients completed the Control Preferences Scale and a short demographic questionnaire. To understand patient’s values when choosing treatment, semi-structured interviews were conducted to capture patient preferences for making treatment decisions, including surgery, radiation, or systemic treatments. Interviews were audio-recorded, transcribed, and analyzed using NVivo. Two coders analyzed transcripts using a constant comparative method to identify major themes related to decision-making preferences. Results: Amongst the 33 women, the majority of patients (52%) desired shared responsibility in treatment decisions. 52% of patients were age 75+ and 48% of patients were age 65-74, with an average age of 74 (4.2 SD). 21% of patients were African American and 79% were Caucasian. Interviews revealed 19 recurrent treatment decision-making themes, including effectiveness, disease prognosis, physician and others’ opinions, side effects, logistics, personal responsibilites, ability to accomplish daily activities or larger goals, and spirituality. EBC patient preferences varied widely in regards to treatment decision-making. Conclusions: The variety of themes identified in the analysis indicate that there is a large amount of variability to what preferences are most crucial to patients. Providers should consider individual patient needs and desires rather than using a “one size fits all” approach when making treatment decisions. Findings from this study could aid in future SDM implementations.
Relative Abundance Analysis of the Oral and Gastrointestinal Microbiome during Autologous Transplantation for Multiple Myeloma: Results of a Prospective Pilot Study and Association with Transplant Outcomes
Authors: Najla H El Jurdi, Ali Filali, Iman Salem, Mauricio Retuerto, Nina Dambrosio, Hillard M Lazarus, Richard Creger, Paolo F Caimi, Brenda Cooper, Ben Tomlinson, Leland Metheny, Ehsan Malek, Folashade Otegbeye, Rafick-Pierre Sekaly, Mahmoud Ghannoum, Marcos de Lima
Journal: Blood (2018)
A Prospective Evaluation of Vitamin B1 (thiamine) Level in Myeloproliferative Neoplasms: Clinical Correlations and Impact of JAK2 Inhibitor Therapy
Authors: Naseema Gangat, Amy Phelps, Terra L. Lasho, Christy Finke, Curtis A. Hanson, Rhett P. Ketterling, Mrinal M. Patnaik, Animesh Pardanani, Ayalew Tefferi
Journal: Blood (2018)
Comparable Outcome After Single-Antigen Mismatched Versus Matched Unrelated Donor Hematopoietic Cell Transplantation,
Authors: Christian Pfrepper, Anja Büttner, Thoralf Lange, Haifa K. Al-Ali, Christian Niederwieser, Gerhard Behre, Michael Cross, Dietger Niederwieser
Journal: Blood (2011)
A Single Autologous Stem Cell Transplant (ASCT) Followed By Two Years of Post-Transplant Therapy in Recently Diagnosed Elderly Multiple Myeloma (MM) Patients. Safety and Response Results from the Prospective Phase II Trial (NCT01849783)
Authors: Kalyan Nadiminti, Christopher Strouse, Praveen Vikas, Lindsay Dozeman, Allyson Schultz, Gabrielle Berns, Jillna Claus, Sarah L Mott, Umar Farooq, Margarida Silverman, Michael Tomasson, Fenghuang Zhan, Yogesh Jethava
Journal: Blood (2018)