tbuckley/cabot-search huggingface dataset:
Impact of Neoatherosclerosis after Stent Implantation Assessed by Optical Coherence Tomography on Cardiac Troponin Elevation After Elective Percutaneous Coronary Intervention
Authors: Lee Tetsumin, Kakuta Tsunekazu, Murai Tadashi, Iwai Toshiyuki, Takagi Takamitsu, Masuda Ryo, Uchiyama Takashi, Kusa Shigeki, Nakamura Hiroaki, Miyazaki Shinsuke, Taniguchi Hiroshi, Hachiya Hitoshi, Fujiwara Hideomi, Iesaka Yoshito, Isobe Mitsuaki
Journal: Circulation (2013)
68Ga-DOTATATE PET/CT in Pituitary Carcinoma
Authors: Gursan Kaya, Basak Soydas Turan, Selcuk Dagdelen, Mustafa Berker, Murat Tuncel
Journal: Clinical Nuclear Medicine (2021)

Abstract A 47-year-old woman with atypical pituitary adenoma was referred to the neurosurgery department due to recent back pain. She had multiple transsphenoidal surgery, stereotactic body radiation, and 177 Lu-DOTATATE therapy. Her spinal MRI showed multiple spinal masses. The patient underwent 68 Ga-DOTATATE PET/CT to confirm the metastatic spread of the disease. PET/CT images showed increased uptake at the local recurrent tumor site and spinal metastases confirmed by biopsy to pituitary carcinoma. Our case presents the role of 68 Ga-DOTATATE PET/CT in patients with pituitary carcinoma.
Persistent Gender Pay Gaps in Medicine
Authors: Rita F. Redberg, Anna L. Parks, Jessica Beth Rubin
Journal: JAMA Internal Medicine (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Abstract 1541: Incorporation of an IgG4-derived spacer improves the activity of nanobody-based CAR T cells targeting a membrane-distal epitope of glypican 1 in pancreatic cancer
Authors: Nan Li, Dan Li, Jiajia Pan, Mitchell Ho
Journal: Cancer Research (2021)

Abstract Background &amp; Aims: Epitope recognition and antigen density have emerged as major parameters affecting the anti-tumor activity of chimeric antigen receptor (CAR) T cells. Glypican 1 (GPC1) is a cell surface proteoglycan that is expressed in pancreatic cancer. Here, we investigate how the choice of an epitope and an extracellular spacer in CAR design can determine T cell activation in high- or low- GPC1-expressing tumors. Methods: We use mouse hybridoma and phage display technologies to isolate GPC1-specific antibodies or nanobodies with distinct epitopes, and analyze GPC1 protein expression in pancreatic cancer. We construct CARs with different extracellular spacers and test them in GPC1-positive cell and mouse models. We use droplet digital PCR and genomic sequencing methods to analyze persistent CAR T cells in mice. Results: We isolate a camel nanobody D4 and a mouse monoclonal antibody HM2 recognizing the membrane-distal and membrane-proximal epitopes of GPC1, respectively, with similar high affinity. GPC1 protein was frequently detected in pancreatic tumor tissues and normal pancreas adjacent to tumors. Both D4 and HM2 CAR T cells with the hinge and transmembrane domain (TM) from CD8 regressed high GPC1-expressing xenograft tumors. Interestingly, D4 CAR containing a short IgG4 hinge spacer and CD28 TM outperformed the initial D4 CAR against low GPC1-expressing tumors in vitro and in vivo. Conclusion: By optimizing spacer and TM designs, the activity of nanobody D4-based CAR T cell targeting a membrane-distal epitope of GPC1 is significantly enhanced against low GPC1-expressing tumors, suggesting it might improve the efficacy of GPC1-targeted CAR T cell therapy in pancreatic cancer. Citation Format: Nan Li, Dan Li, Jiajia Pan, Mitchell Ho. Incorporation of an IgG4-derived spacer improves the activity of nanobody-based CAR T cells targeting a membrane-distal epitope of glypican 1 in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1541.
Abstract 2545: A novel tool for the accurate and affordable early diagnosis of pancreatic cancer via machine learning and bioinformatics
Authors: Siya Goel, Jean Honorio
Journal: Cancer Research (2021)

Abstract Pancreatic cancer (PC) is the fourth leading cause of cancer death in the United States due to its five-year survival rate of 8.9%. Late diagnosis, affiliated with the asymptomatic nature in early stages and the location of the cancer with respect to the pancreas, makes current widely-accepted screening methods unavailable. Prior studies have achieved low (70-75%) diagnostic accuracy, possibly because 80.1% of PC cases are associated with diabetes, leading to misdiagnosis. To address the problems of frequent late diagnosis and misdiagnosis, an accessible, accurate, and affordable diagnostic tool was developed by analyzing the expression of nineteen genes in PC and diabetes. First, machine learning algorithms were trained on four groups of subjects, depending on the occurrence of PC and Diabetes. The models were analyzed with 400 PC subjects at varying stages to ensure validity. Naive Bayes, Neural Network, and K-Nearest Neighbors models achieved the highest testing accuracy of around 92.6%. Second, a novel user interface, PanCan Diagnosis, was designed to test an individual's occurrence of PC where the average likelihood of PC was displayed. Third, the biological implication of the nineteen genes was investigated using bioinformatics tools. It was found that these genes were significantly involved in regulating the cytoplasm, cytoskeleton and nuclear receptor activity in the pancreas, specifically in acinar and ductal cells. This novel tool is the first in the literature that achieves a PC diagnostic accuracy of above 90%, potentially increasing the five-year survival rate to 36%. Citation Format: Siya Goel, Jean Honorio. A novel tool for the accurate and affordable early diagnosis of pancreatic cancer via machine learning and bioinformatics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2545.
Abstract 1401: MYC mediates retinoic acid resistance by suppressing cellular retinoic acid-binding protein (CRABP2) transcription in HER2-enriched breast cancers
Authors: Won-Shik Choi, Rong-Zong Liu, Roseline Godbout
Journal: Cancer Research (2021)

Abstract Introduction: HER2-positive (HER2+) breast cancers express high levels of the growth-promoting HER2 protein. The development of a targeted drug, trastuzumab, has greatly improved clinical outcome for HER2+ patients. However, intrinsic and acquired resistance to trastuzumab are common. Clearly, additional therapeutic interventions are required for the clinical management of HER2-enriched breast cancers. Retinoic acid (RA) is a vital signaling molecule that regulates multiple biological processes, including cell proliferation, differentiation, and death. RA has been successfully used in the treatment of acute promyelocytic leukemia. RA also holds promise for the treatment of solid cancers like breast cancer. RA action is mediated through transcription factor RARα and the RA binding protein CRABP2, which deliver RA to RARα in the nucleus. The HER2 gene (ERBB2) is frequently co-amplified with the gene encoding RARα, a key determinant of RA sensitivity. It seems surprising, therefore, that HER2+ breast cancers are refractory to RA treatment. MYC is an oncogene that inhibits RARα activity in leukemia cells. Importantly, MYC is preferentially amplified and overexpressed in HER2+ breast cancers. My research aims to elucidate the mechanism underlying RA resistance in HER2+ breast cancers, with a special focus on the role of MYC. Hypothesis: MYC attenuates RA action by inhibiting the CRABP2-RARα pathway. Results: RNA levels of MYC are negatively correlated with CRABP2 RNA levels. Depletion of MYC upregulates CRABP2 at both the RNA and protein levels. Furthermore, we found that MYC binds to the CRABP2 promoter region suggesting that MYC may directly suppress CRABP2 gene transcription activity. Our results show that ectopic expression of MYC inhibits, whereas depletion of MYC activates RAR activity. Consistently, ectopic expression of MYC increases RA resistance, whereas depletion of MYC sensitizes cells to RA treatment. When CRABP2 is depleted along with MYC-knockdown, cell proliferation is rescued, suggesting that MYC mediates RA resistance, at least partially through downregulation of CRABP2. We also found that RA treatment enhances trastuzumab responsiveness in HER2+ breast cancer cells. Significance: This study sheds light on the role and mechanism of MYC in governing RA resistance in HER2+ breast cancer cells. Our results support the use of RA and trastuzumab for the treatment of subsets of patients with HER2+/low MYC breast cancers. Citation Format: Won-Shik Choi, Rong-Zong Liu, Roseline Godbout. MYC mediates retinoic acid resistance by suppressing cellular retinoic acid-binding protein (CRABP2) transcription in HER2-enriched breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1401.
Association between previous negative biopsies and lower rates of disease progression during active surveillance for prostate cancer
Authors: M.L. Piccinelli, S. Luzzago, L. Jannello, M. Malfatto, F.A. Mistretta, R. Bianchi, E. Di Trapani, M. Catellani, G. Cozzi, A. Cioffi, G. Marvaso, D. Bottero, M. Ferro, D.V. Matei, G. Renne, B.A. Jereczek Fossa, G. Musi, O. De Cobelli
Journal: European Urology (2021)
European monitoring of notifications of hepatitis C virus infection in the general population and among injecting drug users (IDUs) – the need to improve quality and comparability
Authors: L Wiessing, B Guarita, I Giraudon, H Brummer-Korvenkontio, M Salminen, S  A Cowan
Journal: Eurosurveillance (2008)

Hepatitis C virus (HCV) infection is a serious public health problem in Europe, and it is estimated that a large number of people are unaware of their infection [1-3]. HCV infection may lead to symptomatic chronic liver disease after many years of asymptomatic infection. Effective treatment is available for HCV infection; however, the efficacy for many genotypes remains low and therapy is prolonged, involving both weekly injections and daily oral medication, and can be associated with significant adverse effects [4,5]. Where documented, injecting drug use is a major transmission route for HCV infections [1,6,7]. In many European countries, national surveillance of HCV infections has been established relatively recently.
Clinical and immunologic implications of COVID-19 in patients with melanoma and renal cell carcinoma receiving immune checkpoint inhibitors
Authors: Benjamin Switzer, John Haanen, Paul C Lorigan, Igor Puzanov, Samra Turajlic
Journal: Journal for ImmunoTherapy of Cancer (2021)

The clinical and immunologic implications of the SARS-CoV-2 pandemic for patients with cancer receiving systemic anticancer therapy have introduced a multitude of clinical challenges and academic controversies. This review summarizes the current evidence, discussion points, and recommendations regarding the use of immune checkpoint inhibitors (ICIs) in patients with cancer during the SARS-CoV-2 pandemic, with a focus on patients with melanoma and renal cell carcinoma (RCC). More specifically, we summarize the theoretical concepts and available objective data regarding the relationships between ICIs and the antiviral immune response, along with recommended clinical approaches to the management of melanoma and RCC patient cohorts receiving ICIs throughout the course of the COVID-19 pandemic. Additional insights regarding the use of ICIs in the setting of current and upcoming COVID-19 vaccines and broader implications toward future pandemics are also discussed.
Abstract 1203: ZL-1211 exhibits broad anti-tumor activity in CLDN18.2 high- and low-expressing models
Authors: Hiroyasu Konno, Yong Li, Xinchuan Dai, Bee Sun, Wenhua Shi, Min Chen, Wenying Li, Shou Li, Lishan Kang, Holly Li, Frank Tao, Sophia Yin, Bingbing Wang, Lishen Shan, Bing Wan, Petter Veiby, James Yan, Karl Hsu, David Bellovin, Omar Kabbarah
Journal: Cancer Research (2021)

Abstract Targeting the lineage marker CLDN18.2 with ADCC-eliciting monoclonal antibody therapeutics has shown promising clinical activity in the gastric, esophageal, and pancreatic cancer indications. However, clinical efficacy was mainly observed in tumors that expressed very high levels of CLDN18.2, which represented only ~30% of cases, and was much less pronounced in tumors with low levels of CLDN18.2. Here we present ZL-1211, a novel CLDN18.2-targeting monoclonal antibody that was engineered to promote enhanced ADCC and to drive efficacy in tumors that exhibit a broad range of CLDN18.2 expression levels. We demonstrate that ZL-1211 can robustly inhibit the growth of tumor cells that express not only high but also low levels of CLDN18.2 in vitro as well as a variety of in vivo models. ZL-1211 strongly induced ADCC, ADCP, and CDC and inhibited the growth of a series of in vitro models more potently than the leading clinical benchmark, including cell lines engineered to exogenously express varying levels of CLDN18.2 as well as gastric and pancreatic cancer cell lines that endogenously express low, medium, and high target levels. Consistent with our in vitro findings, ZL-1211 also exhibited greater anti-tumor efficacy than the leading clinical benchmark in CLDN18.2-positive patient-derived xenograft and syngeneic models in vivo. Together, our data suggest that ZL-1211 might provide therapeutic benefit for a wider spectrum of low- and high-CLDN18.2 expressing tumors than the leading clinical benchmark. A Ph1 dose escalation study to assess the safety and preliminary efficacy of ZL-1211 is planned. Citation Format: Hiroyasu Konno, Yong Li, Xinchuan Dai, Bee Sun, Wenhua Shi, Min Chen, Wenying Li, Shou Li, Lishan Kang, Holly Li, Frank Tao, Sophia Yin, Bingbing Wang, Lishen Shan, Bing Wan, Petter Veiby, James Yan, Karl Hsu, David Bellovin, Omar Kabbarah. ZL-1211 exhibits broad anti-tumor activity in CLDN18.2 high- and low-expressing models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1203.
Abstract 84: Characterization of oncogenic KRAS A59 alleles and their cooperation with the MAPK signaling pathway
Authors: Christian W. Johnson, Elizabeth M. Terrell, Christin E. Burd, Deborah Morrison, Kevin M. Haigis
Journal: Cancer Research (2021)

Abstract The Kirsten rat sarcoma (KRAS) proto-oncogene regulates signaling pathways that control proliferation (e.g. MAPK pathway), metabolism and survival (e.g. AKT pathway), and apoptosis (e.g. Hippo pathway). Mutations in KRAS are found in 40% of colorectal cancers (CRC). However, there are no FDA-approved drugs for CRC that target this oncogene. One reason why developing drugs against KRAS is difficult is because a number of different oncogenic alleles have been identified. Thus, an allele-specific approach to target KRAS is necessary. In turn, this approach requires a detailed understanding of their structure and function to drive cell transformation and tissue dysregulation. Our goal is to characterize the function of KRAS A59T in CRC. These alleles are interesting for a number of reasons. First, A59T discriminates retroviral homologues of mammalian RAS from their cellular counterparts. Second, unlike other oncogenic alleles, the KRAS A59T protein undergoes autophosphorylation, the biological function of which is unknown. Third, patient data show that A59 alleles of KRAS frequently co-occur with other genetic alterations in the MAPK signaling pathway, which is uncommon for other KRAS alleles. We hypothesize that KRAS autophosphorylation promotes CRC in a manner that is independent, but cooperative, with the MAPK signaling pathway. To test this hypothesis, we first characterized the function of KRAS A59T and its phosphomimetic A59E using in silico and biochemical techniques, along with classic assays of cell transformation. Next, we generated a new genetically engineered mouse model, K-Ras+/LSL-A59E, in order to test how KRAS autophosphorylation cooperates with other oncogenic mechanisms of MAPK pathway activation to alter colon homeostasis and model colon tumorigenesis. Consistent with our hypothesis, KRAS autophosphorylation and A59E inhibit KRAS-effector interactions that activate the MAPK, AKT, and Hippo signaling pathways. How this change in function alters the ability of K-RasA59E, versus K-RasG12D, to promote hyperproliferation and tumor development in combination with N-RasQ61K and Apc loss in the mouse colon, is currently underway. Ultimately, these studies bring us closer to discovering allele-specific vulnerabilities of KRAS and provide a means to test less understood aspects of oncogenic KRAS signaling. Citation Format: Christian W. Johnson, Elizabeth M. Terrell, Christin E. Burd, Deborah Morrison, Kevin M. Haigis. Characterization of oncogenic KRAS A59 alleles and their cooperation with the MAPK signaling pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 84.
Contemporary management of male anterior urethral strictures by reconstructive urology experts. Results from EAU-YAU survey among ESGURS members
Authors: F. Campos Juanatey, E.A. Fes Ascanio, C. Rosenbaum, J. Adamowicz, F. Castiglione, M. Waterloos, L. Kluth
Journal: European Urology (2021)
Abstracts From the NCCN 2021 Virtual Annual Conference
Authors: Prasanna Ananth, Sophia Mun, Noora Reffat, ; Soo, Jung Kang, Sarah Pitafi, Xiaomei Ma, Cary Gross, Joanne Wolfe, Amye Tevaarwerk, Travis Osterman, Waddah Arafat, Jeffrey Smerage, Fernanda Polubriaginof, Tricia Heinrichs, Jessica Sugalski, Daniel Martin, Anupam Rishi, Jordan Mcdonald, Sabrina Saeed, Rutika Mehta, David Pointer, Jessica Frakes, Sarah Hoffe, Jacques Fontaine, Jose Pimiento
Journal: Journal of the National Comprehensive Cancer Network (2021)

Background: There are no existing quality measures to define optimal end-of-life care (EOLC) for children with cancer, contributing to high healthcare utilization and variable palliative care provision.In a preceding study, we developed a set of 26 measures of EOLC quality.Our objective in the current study was to reach stakeholder consensus on which of these candidate quality measures to prioritize.Methods: We conducted an iterative crosssectional electronic survey, using a modified Delphi method.We convened a stakeholder panel, including interdisciplinary healthcare professionals, bereaved parents, and family advocates.In each of two rounds of surveys, participants were asked to rate quality measures on a 9-point Likert scale, based on perceived importance.Healthcare professionals were additionally asked to rate each measure on perceived feasibility.After each round, we computed median ratings on importance and feasibility of measurement.Open-ended responses following Round 1 were summarized to identify new quality measures to include in Round 2. We retained quality measures that received a median score of $8 in importance.Results: Twenty-five participants completed both rounds of the survey.In Round 1, participants were asked to rate 26 candidate EOLC quality measures.Following Round 1, 9 quality measures were removed due to median importance scores ,8.Six of the eliminated measures pertained to healthcare resource use.Two measures on
Comparing the Performance of Two Recommended Criteria for Establishing a Diagnosis for Hypersensitivity Pneumonitis
Authors: Ivette Buendia-Roldan, Hiram Aguilar-Duran, Kerri A. Johannson, Moisés Selman
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Comparing the Performance of Two Recommended Criteria for Establishing a Diagnosis for Hypersensitivity Pneumonitis." American Journal of Respiratory and Critical Care Medicine, 204(7), pp. 865–868
Abstract 738: Targeting metabolic vulnerabilities of endocrine resistant breast cancers using XPO1 and NAMPT inhibition
Authors: Qianying Zuo, Ayca Mogol, Ozan Imir, Yosef Landesman, Zeynep Madak Erdogan
Journal: Cancer Research (2021)

Abstract Introduction: Approximately 70% of human breast cancers express estrogen receptor alpha (ERα), providing the potential for targeted endocrine therapy for patients. Unfortunately, 30-40% of ER+ patients still experience recurrence and metastasis with a 5-year relative overall survival rate of just 24%. Previously, we described metabolic changes in metastatic breast cancer cells that are driven by single therapies and the metastatic organ microenvironment. Combining selinexor (SEL), a small molecule inhibitor of exportin 1 (XPO1) approved by the FDA for treatment of some hematologic malignancies, with the current therapies used for advanced breast cancers (e.g. tamoxifen) decreased metabolic adaptations in response to individual drug treatments and prevented colony formation in hydrogels and tumor growth in xenograft models. Since we observed a reliance on NAD+ metabolism in cancer cells that are treated with single therapies, in the current study we investigated co-targeting metabolic alterations using SEL and the NAMPT inhibitor KPT-9274. Methods: We established 3D cell culture systems in novel hydrogels derived from decellularized bone, lung, and liver tissues - the major sites of metastasis of ER+ breast cancers, and compared with standard Matrigel culture. Endocrine responsive (MCF7 and T47D) and resistant (MCF7 and T47D cells with ESR1 Y537S or D538G mutations) breast cancer cell lines were treated with SEL or KPT-9274. Tumorigenicity was assessed using in vitro cell viability and colony formation assays and in vivo breast cancer cell line xenografts in athymic mice. Metabolic changes were assessed using whole metabolite profiling by GC-MS and a Seahorse XF analyzer. Results: Combining an FDA-approved XPO1 small molecule inhibitor, Selinexor (SEL) with the NAMPT inhibitors decreased metabolic adaptations in response to individual drug treatments, and prevented colony formation in hydrogels and tumor growth in xenograft models. Conclusions: Targeting drug and metastatic-site induced adaptations to regenerate new vulnerabilities in endocrine-resistant breast tumors are novel. Given the need for better strategies for improving therapy response of metastatic ER+ tumors, our findings show uncovering the role XPO1-NAMPT crosstalk plays in metastatic breast cancer could lead to new combined therapies that reduce mortality. Citation Format: Qianying Zuo, Ayca Mogol, Ozan Imir, Yosef Landesman, Zeynep Madak Erdogan. Targeting metabolic vulnerabilities of endocrine resistant breast cancers using XPO1 and NAMPT inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 738.