tbuckley/cabot-search huggingface dataset:
Abstract 3679: PD-L1 driven excluded phenotype in melanoma
Authors: Carl Morrison, Jeffrey Conroy, Mary Nesline, Sean Glenn, Blake Burgher, Maochun Qin, Jonathan Andreas, Vincent Giamo, Felicia L. Lenzo, Angela Omilian, Wiam Bshara, Antonios Papanicolau-Sengos, Yirong Wang, Marc Ernstoff, Mark Gardner, Sarabjot Pabla
Journal: Cancer Research (2018)

Abstract Background: The excluded phenotype has been previously described by the presence of abundant immune cells that do not penetrate the parenchyma of these tumors but instead are retained in the stroma that surrounds nests of tumor cells. These features support a pre-existing anti-tumor immune-related response, but the details of this mechanism are not well elucidated. Methods: 300 formalin-fixed, paraffin-embedded (FFPE) metastatic cutaneous melanoma samples were evaluated by the RNA-seq component of a comprehensive immune profile panel to measure transcript levels of immune-related genes. Resultant data was QC filtered, normalized and ranked based on an assorted reference population of various tumor types. The expression of PD-L1 on the surface of tumor cells was assessed in tumor samples by means of an automated IHC assay (28-8, Dako). A tumor was considered PD-L1 positive if ≥1% of viable tumor cells exhibited complete circumferential or partial linear plasma membrane staining at any intensity. Excluded pattern of T-cell infiltration was defined by CD8 immunohistochemistry by the following definition: Restriction of more than 95% of all CD8+ T-cells present in a tumor to the periphery or interstitial stromal areas and not actively invading nest or groups of neoplastic cells. Results: The excluded phenotype was identified in 34 of 300 (11%). PD-L1 by IHC was positive (≥1%) in the neoplastic cases in 16 of 34 (47%) cases. Membranous staining in immune cells was identified in only 3 of 34 (9%) cases, but was present in &amp;gt;90% of all cases in a non-membranous pattern. In more than one-half of all cases the non-membranous pattern of PD-L1 IHC staining was restricted to the excluded TILs. Higher expression of PD-L1 by RNA-seq was associated with this excluded PD-L1 pattern of staining. Conclusion: In 300 metastatic cutaneous melanoma cases we demonstrated that the excluded phenotype is frequent and represents ~10% of all cases. Moreover, in a significant number of excluded cases expression of PD-L1 by IHC was distinctly limited to the excluded TILs. This finding would support a unique mechanism of PD-L1 anti-tumor immune-related response that needs further investigation. Citation Format: Carl Morrison, Jeffrey Conroy, Mary Nesline, Sean Glenn, Blake Burgher, Maochun Qin, Jonathan Andreas, Vincent Giamo, Felicia L. Lenzo, Angela Omilian, Wiam Bshara, Antonios Papanicolau-Sengos, Yirong Wang, Marc Ernstoff, Mark Gardner, Sarabjot Pabla. PD-L1 driven excluded phenotype in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3679.
Impact of Controlled Pericardial Drainage on Critical Cardiac Tamponade With Acute Type A Aortic Dissection
Authors: TaroHayashi, TakuroTsukube, TeruoYamashita, TomonoriHaraguchi, RitsuMatsukawa, ShuichiKozawa, KyoichiOgawa, YutakaOkita
Journal: Circulation (2012)

Background—Cardiac tamponade is associated with fatal outcomes for patients with acute type A aortic dissection, and the presence of cardiac tamponade should prompt urgent aortic repair. However, treatment of the patient with critical cardiac tamponade who cannot survive until surgery remains unclear. We analyzed our experience of controlled pericardial drainage (CPD) managing critical cardiac tamponade. Methods and Results—Between September 2003 and May 2011, 175 patients with acute type A aortic dissection were treated surgically, including 43 (24.6%) who presented with cardiac tamponade on arrival. Eighteen patients, who did not respond to intravenous volume resuscitation, underwent CPD in the emergency department. An 8F pigtail drainage catheter was inserted percutaneously, and drainage volume was controlled by means of several cycles of intermittent drainage to maintain blood pressure at ≈90 mm Hg. After CPD, all of the patients were transferred to the operating room, and immediate aortic repair was ...
Abstract 1540: Allogeneic chimeric antigen receptor T cells targeting B cell maturation antigen
Authors: Henia Dar, Daniel Henderson, Zinkal Padalia, Ashley Porras, Dakai Mu, Kyungah Maeng, Seshi Police, Demetrios Kalaitzidis, Jonathan Terrett, Jason Sagert
Journal: Cancer Research (2018)

Abstract B cell maturation antigen (BCMA) is a tumor necrosis factor family cell surface receptor that binds B cell activating factor (BAFF) and a proliferation inducing ligand (APRIL) and is involved in the long-term survival of B cells. BCMA has been shown to be expressed broadly on monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) cells and for this reason has been pursued as a potential antigen for the treatment of MM. Indeed, clinical studies evaluating autologous chimeric antigen receptor T cells (CAR-T cells) targeting BCMA for the treatment of MM have shown promising efficacy with &amp;gt;80% response rates. However, logistical challenges will potentially limit the number of patients that have access to autologous therapies. Using the CRISPR/CAS9 system, we generated allogeneic CAR-T cells targeting BCMA by disrupting the beta-2-microglobulin (B2M) and T cell receptor alpha constant (TRAC) genes and inserting an anti-BCMA CAR into the TRAC locus. This results in allogeneic CAR-T cells lacking the major histocompatibility complex (MHC) and endogenous T cell receptor (TCR) expression while being potently cytotoxic towards cells expressing BCMA. These data show proof-of-concept for an “off the shelf” CAR-T therapy targeting BCMA. Citation Format: Henia Dar, Daniel Henderson, Zinkal Padalia, Ashley Porras, Dakai Mu, Kyungah Maeng, Seshi Police, Demetrios Kalaitzidis, Jonathan Terrett, Jason Sagert. Allogeneic chimeric antigen receptor T cells targeting B cell maturation antigen [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1540.
High Performance Flexible Organic Electrochemical Transistors for Monitoring Cardiac Action Potential
Authors: Yuanying Liang, Mathis Ernst, Fabian Brings, Dmitry Kireev, Vanessa Maybeck, Andreas Offenhäusser, Dirk Mayer
Journal: Advanced Healthcare Materials (2018)

Abstract Flexible and transparent electronic devices possess crucial advantages over conventional silicon based systems for bioelectronic applications since they are able to adapt to nonplanar surfaces, cause less chronic immunoreactivity, and facilitate easy optical inspection. Here, organic electrochemical transistors (OECTs) are embedded in a flexible matrix of polyimide to record cardiac action potentials. The wafer‐scale fabricated devices exhibit transconductances (12 mS V −1 ) and drain–source on‐to‐off current ratios (≈10 5 ) comparable to state of the art nonflexible and superior to other reported flexible OECTs. The transfer characteristics of the devices are preserved even after experiencing extremely high bending strain and harsh crumpling. A sub‐micrometer poly(3,4‐ethylenedioxythiophene) doped with poly(styrenesulfonate) layer results in a fast transport of ions between the electrolyte and the polymer channel characterized by a cut‐off frequency of 1200 Hz. Excellent device performance is proved by mapping the propagation of cardiac action potentials with high signal‐to‐noise ratio. These results demonstrate that the electrical performance of flexible OECTs can compete with hard‐material‐based OECTs and thus potentially be used for in vivo applications.
Abstract 21036: Subablative Therapeutic Ultrasound Reduces Mitral and Tricuspid Annular Dimension: Preclinical Evaluation of the ReCor Device
Authors: Hasan Jilaihawi, Anita Asgar, Renu Virmani, Anique Ducharme, Hiroshi Nakagawa, Yan-Fen Shi, Naima Carter-Monroe, Elena Ladich, Atsushi Ikeda, Raoul Bonan
Journal: Circulation (2010)

Background: We hypothesized that Therapeutic Ultrasound(TU) from the ReCor device could result in a reduction in mitral annular(MA) and tricuspid annular(TA) dimension with potential application in...
Explanation for the Decline in Coronary Heart Disease Mortality Rates in Auckland, New Zealand, Between 1982 and 1993
Authors: SimonCapewell, RobertBeaglehole, MarySeddon, JohnMcMurray
Journal: Circulation (2000)

Background—We sought to determine how much of the recent, substantial fall in coronary heart disease (CHD) mortality rates in New Zealand can be attributed to “evidence-based” medical and surgical treatments and how much can be attributed to cardiovascular risk factor reductions. Methods and Results—A cell-based mortality model was developed and refined. This model combined (1) the published effectiveness of cardiological treatments and risk factor reductions with (2) data on all medical and surgical treatments administered to all CHD patients and (3) trends in population cardiovascular risk factors (principally smoking, cholesterol, and hypertension) from 1982 to 1993 in Auckland, New Zealand (population 996 000). Between 1982 and 1993, CHD mortality rates fell by 23.6%, with 671 fewer CHD deaths than expected from baseline mortality rates in 1982. Forty-six percent of this fall was attributed to treatments (acute myocardial infarction 12%, secondary prevention 12%, hypertension 7%, heart failure 6%, and...
Abstract 609: Neutrophils play a critical role in mediating antitumor activity of a combination therapy of radiation and immunotherapy
Authors: Mi-Hua Tao, Chia-Jen Wu, Yi-Ting Tsai, Ping-Yi Wu
Journal: Cancer Research (2018)

Abstract The goal of cancer immunotherapy is to elicit robust tumor-specific immune responses that can generate durable tumor regression and/or eradication. Recent clinical trials using immune checkpoint blockades specific to programmed cell death-1/ligand-1 (PD-1/PD-L1) have shown durable clinical responses in various cancer types but benefit only a small portion of patients. We previously demonstrated that combination of radiation and immunotherapy of interleukin 12 (IL-12) and granulocyte macrophage colony-stimulator factor (GM-CSF) greatly improved the therapeutic efficacy than either single therapy alone. In analysis of the tumor-infiltrating leukocytes post combination therapy, we found that the number of CD11b+F4/80-/Ly6G+ neutrophils were greatly increased. In this study, we characterized these tumor-associated neutrophils (TANs) before and after treatment and investigated their role in mediating the antitumor activity of the combination therapy. We isolated TANs from the regressing tumors and demonstrated that these TANs were impaired in their immunosuppressive activities. Flowcytometric analysis revealed that several co-stimulatory molecules, including class II major histocompatibility complex, CD40 and CD86, were increased on these TANs. Accordingly, these TANs gained the ability to stimulate T cell proliferation. Antibody-depletion experiments showed that TANs were required for tumor regression in RT/12GM combination therapy. Together, our data demonstrate that combination of radiotherapy and IL-12/GM-CSF improved antitumor immunity through enhancing antigen presentation activity and reduced immunosuppressive functions of TANs. Citation Format: Mi-Hua Tao, Chia-Jen Wu, Yi-Ting Tsai, Ping-Yi Wu. Neutrophils play a critical role in mediating antitumor activity of a combination therapy of radiation and immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 609.
Abstract 5776: Pharmacologic and PK/PD study of D-0502: An orally bioavailable SERD with potent antitumor activity in ER-positive breast cancer cell lines and xenograft models
Authors: Yaolin Wang, Zhe Shi, Yueheng Jiang, Xing Dai
Journal: Cancer Research (2018)

Abstract Breast cancer is the most common form of cancer in women in the developed world, with estrogen receptor-positive (ER+) breast cancer accounting for 70-80% of all breast cancers. Endocrine therapy such as selective estrogen receptor degrader (SERD) fulvestrant has been used effectively to extend the life of ER+ breast cancer patients, either alone or in combination with CDK4/6 inhibitor (palbociclib or abemaciclib). However, due to poor pharmacokinetic property, fulvestrant has to be given via intramuscular injection. In addition, patients relapsed after prolonged endocrine therapy with aromatase inhibitors such as letrozole and anastrozole due to emergence of ER mutations. Here, we report the discovery of D-0502, an orally bioavailable SERD with potent activity in various ER+ breast cancer cell lines and xenograft models. In addition, combination of our SERD candidates and palbociclib in both MCF-7 xenograft model and ESR-1 mutated (Y537S) patient-derived breast cancer xenograft model resulted in further tumor growth inhibition or regression. Comparison of various SERD molecules showed our candidate has more potent antitumor activity in MCF-7 xenograft model than GDC-0810, AZD9496 and fulvestrant. More importantly, drug metabolism and pharmacokinetic (PK) studies both in vitro and in vivo demonstrated that our SERD molecule D-0502 exhibits superior PK profiles suitable for clinical development. Citation Format: Yaolin Wang, Zhe Shi, Yueheng Jiang, Xing Dai. Pharmacologic and PK/PD study of D-0502: An orally bioavailable SERD with potent antitumor activity in ER-positive breast cancer cell lines and xenograft models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5776.
Contribution of SPECT/CT to Evaluate Urinary Leakage Suspicion in Renal Transplant Patients
Authors: Bulent Yazici, Aylin Oral, Aysegül Akgün
Journal: Clinical Nuclear Medicine (2018)

It is known that renal scintigraphy is the best imaging modality in the diagnosis of urinary leakage. Usually, only planar images are diagnostic but sometimes they are unclear when urinoma is small and adjacent to kidney or bladder. In other respects, planar images can be false-positive in the case of increased blood flow of abdominal wall. We suggested using SPECT/CT in differential diagnosis. An atlas of SPECT/CT is presented, which includes 3 cases that urinoma was diagnosed by SPECT/CT, which were unclear on planar images, and one case that urinary leakage suspicion on planar image was ruled out by SPECT/CT.
Abstract 1568: Advancing convergence and innovation in cancer research: National Cancer Institute Center for Strategic Scientific Initiatives (CSSI)
Authors: Sarah G. Elder, Jerry S. Lee, Michelle A. Berny-Lang, Sean E. Hanlon
Journal: Cancer Research (2018)

Abstract Since 2003, the National Cancer Institute's Center for Strategic Scientific Initiatives (CSSI) has worked to develop the resources and infrastructures investigators need to surmount roadblocks in cancer research. To this end, CSSI manages programs that promote technology development and cross-disciplinary collaboration and provide support for investigators in nascent and challenging research fields. This support includes funding opportunities, shared reagent and database resources, and assistance in the development of standards and protocols. CSSI also provides a network of partners in industry and government that can help NCI-funded researchers advance their technologies toward commercialization and translation. This presentation will highlight technologies including single-cell isolation and analysis techniques that have been supported through various CSSI mechanisms from proof of concept to translation into the clinic. Citation Format: Sarah G. Elder, Jerry S. Lee, Michelle A. Berny-Lang, Sean E. Hanlon. Advancing convergence and innovation in cancer research: National Cancer Institute Center for Strategic Scientific Initiatives (CSSI) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1568.
Abstract 2486: PTEN fusion gene promotes growth in cancer
Authors: Yanping Yu, Silvia Chang, Baoguo Ren, George Michalopoulos, George Tseng, Jianhua Luo
Journal: Cancer Research (2018)

Abstract Deletion or mutation of PTEN is frequent in a variety of human cancers and is an underlying mechanism for cancer development. Here, we report a PTEN-involved fusion gene and the corresponding genome breakpoint in human cancers. Pten fusion is highly recurrent in cancers and their matched lymph nodes and is located nucleoli. Targeted knockout of this fusion gene in Du145 and MCF7 cells impeded tumor cell growths, retarded S phase entry, and reduced invasiveness, and was prone to the UV- induced apoptosis. Knockout of PTEN-fusion blocked xenografted-tumor growth in mice, while forced-expression of PTEN -fusion through hydrodynamic injection into mice led to hepatocellular carcinoma. These findings indicate that the genome rearrangement of PTEN-fusion results in an oncogenic fusion protein in addition to the loss of Pten as an underlying mechanism in driving cancer development. Citation Format: Yanping Yu, Silvia Chang, Baoguo Ren, George Michalopoulos, George Tseng, Jianhua Luo. PTEN fusion gene promotes growth in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2486.
Abstract 65: Impact of tumor-infiltrating dendritic cells in esophageal squamous cell carcinoma treated with neoadjuvant chemotherapy
Authors: Junya Nishimura, Hiroaki Tanaka, Yoshihito Yamakoshi, Soichiro Hiramatsu, Tatsuro Tamura, Takahiro Toyokawa, Kazuya Muguruma, Kosei Hirakawa, Masaichi Ohira
Journal: Cancer Research (2018)

Abstract Background: Tumor-infiltrating CD8+T cells have been found to be associated with favorable outcome of patients in many cancers including esophageal squamous cell carcinoma (ESCC). Dendritic cells (DCs) are the most potent antigen-presenting cells to induce CD8+T cells. Several investigators have shown that tumor infiltrating mature DCs (mDCs) were associated with favorable prognosis of cancer patients. We showed that mDCs were associated with favorable prognosis of ESCC patients who had not received preoperative treatment. Neoadjuvant chemotherapy (NAC) is the standard treatment for Stage II/ III thoracic esophageal carcinoma in Japan. The effect of chemotherapy on tumor infiltrating DCs remains unclear. Purpose: The aim of this study was to examine the correlation of efficacy of NAC and locally infiltrating DCs in ESCC patients. Object and Methods: Formalin-fixed, paraffin-embedded blocks of primary lesions were collected from 50 patients with ESCC who underwent surgical treatment after NAC at Osaka City University Hospital. Immunohistochemical analysis using anti-LAMP-3 antibody and CD8 antibody was used to evaluate tumor infiltrating DCs and CD8+T cells. The number of LAMP-3+DCs and CD8+T cells were counted at ×400 magnification. We divided the 50 cases into two groups according to the median number of tumor infiltrating DCs and CD8+T cells to examine the correlation of efficacy of NAC and locally infiltrating DCs. Results: LAMP-3+DCs were predominantly observed in peritumoral area and sparsely found in intratumoral area, whereas CD8+T cells distributed between both peritumoral and intratumoral areas. LAMP-3+DCs infiltrated the peritumoral space from 0 to 19.0 (median 6.0) and the intratumoral space from 0 to 3.8 (median 0.0). Patients with histological effect (≧Grade 1a) had higher infiltration of mDCs than Grade 0. Patients with high infiltration of mDCs had better prognosis than those with low. The number of mDCs had positive correlation with the number of tumor infiltrating CD8+T cells. Conclusions: Our results suggested that increase of tumor infiltrating mDCs was associated with histological effect of NAC and favorable prognosis in ESCC. Citation Format: Junya Nishimura, Hiroaki Tanaka, Yoshihito Yamakoshi, Soichiro Hiramatsu, Tatsuro Tamura, Takahiro Toyokawa, Kazuya Muguruma, Kosei Hirakawa, Masaichi Ohira. Impact of tumor-infiltrating dendritic cells in esophageal squamous cell carcinoma treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 65.
Abstract 14574: Peripartum Cardiomyopathy and Hypertensive Pregnancy Subtypes Among 1.6 Million Pregnancies in California Independently Predict Subsequent Incident Myocardial Infarction, Heart Failure, and Stroke
Authors: Rima Arnaout, Gregory Nah, Gregory M Marcus, Zian H Tseng, Elyse Foster, Ian Harris, Punag Divanji, Jeffrey Olgin, Liviu Klein, Juan Gonzalez, Nisha I Parikh
Journal: Circulation (2016)

Introduction: Cardiovascular complications from the hemodynamic challenge of pregnancy and childbirth present an opportunity to assess risk for later cardiovascular disease (CVD) in many women. Peripartum cardiomyopathy (PPCM) and hypertensive pregnancy (HP) are interrelated and are each individually associated with CVD. However, prior studies have not assessed PPCM and specific subtypes of HP as predictors of subsequent myocardial infarction (MI), heart failure (HF), and stroke (ischemic, hemorrhagic and embolic). Methods: The Healthcare Cost and Utilization Project was used to identify unique admissions for PPCM and HP in California hospitals between 1/1/2002 and 12/31/2005 with ICD9 codes. We employed multivariable Cox proportional hazards models to determine the association of PPCM and HP (with subtypes defined as chronic HTN + gestational HTN, chronic HTN + preeclampsia, de novo gestational HTN, and de novo preeclampsia) with subsequent admissions for MI, HF and stroke through 12/31/2011. Results: Am...
Germline duplication of ATG2B and GSKIP genes is not required for the familial myeloid malignancy syndrome associated with the duplication of chromosome 14q32
Authors: Daria V. Babushok, Natasha L. Stanley, Jennifer J. D. Morrissette, David B. Lieberman, Timothy S. Olson, Stella T. Chou, Elizabeth O. Hexner
Journal: Leukemia (2018)
Effects of Barium on Mature and Embryonic Heart Cells
Authors: MorrisKleinfeld, EdwardStein, ClemTionaytis
Journal: Circulation Research (1966)

Barium chloride was administered to isolated preparations of dog heart and rat atrium and to trypsinized embryonic chick heart cells cultured in vitro. Transmembrane action potentials recorded from pacemaker, specialized conductive and contractile fibers of the dog heart, and atrial fibers of rat heart showed a slowing in the rising and falling phases of the action potential and a prominent negative after-potential. The action potential of the Purkinje fiber of the dog heart showed in addition a depolarization during diastole. A decrease in resting potential was observed later. The isometric tension developed by the rat atrium showed a significant increase which was greater at the higher concentractions (greater than 3.5 x 10-4M) of barium chloride. The cultured embryonic heart cells were appreciably more sensitive to barium than the mature heart cells. An increase in rate of beat of the embryonic heart cells was observed at concentrations of 10-6M whereas a change in heart rate was first observed in the ...