tbuckley/cabot-search huggingface dataset:
Abstract P4-21-33: HER2 activity regulates the pro-trastuzumab immune tumor microenvironment
Authors: E Tagliabue, L Forte, V Regondi, C Ghirelli, P Aiello, T Triulzi
Journal: Cancer Research (2017)

Abstract It is well know that trastuzumab activity against HER2-positive breast carcinomas (BCs) depends also on immune cells. Our genomic analysis of 53 HER2-positive BCs indicated that those exquisitely sensitive to treatment are addicted to this oncoprotein and are enriched in immune pathways and T-cells infiltration, raising the hypothesis that HER2 regulates immune cells recruitment. The aim of this study was to investigate how HER2 activity contributes to mold tumor microenvironment. Gene expression profile analysis of 53 HER2-pos BCs showed that trastuzumab-sensitive tumors express significantly higher levels of chemokines involved in immune cells recruitment (IFNγ-related CXCLs and CCLs) and higher levels of immune checkpoint ligands (PD-L1, PD-L2) than tumors that do not benefit from trastuzumab. Immunohistochemistry analysis on FFPE tumor specimens showed a significant positive association between tumor cell positivity for CXCL9, CXCL10 and CCL2 and trastuzumab sensitivity. In vitro analysis in HER2-positive BC cell lines revealed that while IFNγ-related chemokines (CXCL9 and CXCL10) are not directly regulated by HER2 signaling, CCL2 was significantly up-regulated both at mRNA and protein levels by HER2 stimulation with EGF/HRG and down-modulated by HER2 inhibition with trastuzumab. The EGF-induced increase in CCL2 expression was abrogated by the concomitant treatment with PI3K inhibitor but not with MEK inhibitor, indicating that HER2 regulates CCL2 expression via the PI3K pathway. HER2 signals derived from cell stimulation with EGF/HRG caused also the upmodulation of PD-L1/PD-L2 both at mRNA and protein levels while their inhibition with trastuzumab reduced their levels. Overall, our results support the notion that the activated HER2 oncogene concomitantly induces the expression of CCL2 and PD-L1/PD-L2 regulating infiltration of pro-trastuzumab immune cells and their suppression. Thus, it is likely that activity of trastuzumab in therapy-responsive tumors derives from its ability in relieving suppression of recruited antitumor effector immunity. Supported by Italian Association for Cancer Research (AIRC). Citation Format: Tagliabue E, Forte L, Regondi V, Ghirelli C, Aiello P, Triulzi T. HER2 activity regulates the pro-trastuzumab immune tumor microenvironment [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-33.
Large Scale Selective Ex Vivo Expansion of CD4+CD25+FOXP3+ Regulatory T Cells from Peripheral Blood.
Authors: Tokiko Nagamura-Inoue, Kazuo Ogami, Kazuaki Yokoyama, Kiyoko Izawa, Seiichiro Kobayashi, Shin Nakayama, Ikuo Ishige, Yusuke Inoue, Jun Ooi, Kaoru Uchimaru, Satoshi Takahashi, Arinobu Tojo
Journal: Blood (2008)
Therapeutic targeting of polycomb and BET bromodomain proteins in diffuse intrinsic pontine gliomas
Authors: Andrea Piunti, Rintaro Hashizume, Marc A Morgan, Elizabeth T Bartom, Craig M Horbinski, Stacy A Marshall, Emily J Rendleman, Quanhong Ma, Yoh-hei Takahashi, Ashley R Woodfin, Alexander V Misharin, Nebiyu A Abshiru, Rishi R Lulla, Amanda M Saratsis, Neil L Kelleher, C David James, Ali Shilatifard
Journal: Nature Medicine (2017)
Reducing Exposure to Mouse Allergen Among Children and Adolescents With Asthma Is Achievable, but Is It Enough?
Authors: Leonard B. Bacharier
Journal: JAMA (2017)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Prevalence of FACTOR IX-R338L (FACTOR IX PADUA) IN A COHORT of PATIENTS with Venous Thromboembolism and Mild Elevation of FACTOR IX LEVELS.
Authors: Bruna de Moraes Mazetto, Fernanda A. Orsi, Lúcia Helena Siqueira, Erich Vinicius de Paula, Tayana B Mello, Joyce Maria Annichino-Bizzacchi
Journal: Blood (2009)
Tailored Therapy In Hodgkin Lymphoma, Based on Predefined Risk Factors and Early Interim PET/CT, Can Lead to Modification and Safe Reduction In Therapy: Results of 134 Patients on the Israel National Hodgkin Study.
Authors: Eldad J. Dann, Osnat Bairey, Rachel Bar-Shalom, Marina Izak, Abraham Korenberg, Luiza Akria, Dina Attias, Kalman Filanovsky, Liana Abdach, Neta Goldschmidt, Ron Epelbaum, Jacob M. Rowe, Dina Ben Yehuda, Ofer Shpilberg, Ora B. Paltiel
Journal: Blood (2010)
Abstract P1-03-05: A comprehensive molecular analysis of medullary breast carcinoma: A model of immunomodulatory triple negative breast cancer subtype
Authors: P Romero, G Deniziaut, V Benhamo, L Fuhrmann, F Berger, J Bhalshankar, N Gruel, G MacGrogan, T Popova, E Manié, M-H Stern, D Stoppa-Lyonnet, R Rouzier, O Delattre, I Bieche, A Vincent-Salomon
Journal: Cancer Research (2017)

Abstract Medullary breast carcinoma (MBC) is a rare subtype of triple negative breast cancer (TNBC)with specific genomic features within the spectrum of basal-like carcinoma. The frequent association between BRCA constitutive mutation and MBC phenotype has been reported previously. In this study including 19 MBC and 36 non-MMB basal-like carcinoma (BLC), we refine the genomic and transcriptomic knowledge about this entity. Using pan genomic Affymetrix genome-wide human SNP6.0 array, we show that i/ MBC harbour more copy number alterations and losses of heterozygocity than BLC and that ii/ the high frequency of BRCAness genomic trait among MBC. Unsupervised and supervised analysis of GeneChip Uman Genome U133 Plus 2.0 Array transcriptomic generated data confirmed that MBC clearly differ from BLC in terms of gene expression level, with 92 genes overexpressed and 154 genes underexpressed in MBC over BLC. Immune response and inflammatory response are the most differentially represented pathways in MBC over BLC. Pro apoptotic gene BCLG is by far the more overexpressed gene in MBC. A validation study conducted with RT-QPCR among 526 breast tumors form all molecular subtype confirmed the specificity of BCLG overexpression in MBC, which was confirmed at protein level using immunohistochemisytry. Moreover, we show that a vast majority of MBC belong o the immunomodulatory TNBC subtype according to Lehman et al. Finally, we confirm the better prognosis of MBC toward BLC. Our observations epitomize the importance of developing DNA repair targeting drugs and immunotherapy based trials in order to improve the outcome of such a specific entity. Citation Format: Romero P, Deniziaut G, Benhamo V, Fuhrmann L, Berger F, Bhalshankar J, Gruel N, MacGrogan G, Popova T, Manié E, Stern M-H, Stoppa-Lyonnet D, Rouzier R, Delattre O, Bieche I, Vincent-Salomon A. A comprehensive molecular analysis of medullary breast carcinoma: A model of immunomodulatory triple negative breast cancer subtype [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-03-05.
Abstract B20: Development of metastatic patient-derived xenografts (PDXs) for accurate assessment of anti-metastatic therapeutics in pre-clinical settings
Authors: Ryan Ice, Anna Kiseleva, Yuriy Loskutov, Matthew Smolkin, Adham Salkeni, Hannah Hazard, Ginger Layne, Elena Pugacheva
Journal: Clinical Cancer Research (2016)

Abstract Background: Although advances in treating early stage breast cancers have increased the overall survival rate, once the disease has metastasized treatment options subside to palliative care. The limited access to metastatic biopsies and disease-relevant pre-clinical models to test new therapeutics targeted against advanced metastatic cancers limits progress and translation of investigational therapeutics to the clinic. Methods: To address this deficiency we developed a collection of metastatic patient derived xenograft models via direct transplantation of metastatic biopsy or residual surgical material in immunocompromised mice. We successfully collected and established triple negative as well as ER/PR positive patient xenografts which are available for collaborative research. We further characterized and utilized the PDXs to assess the efficacy of new combination therapy to treat distant metastases. Results: The efficacy of Aurora A kinase inhibition by small molecule inhibitor MLN8237 (Alisertib) as monotherapy and in combination with microtubule targeting drug, eribulin, on different stages of metastasis and potential mechanisms of its action was defined. Our work using PDX models indicates that Alisertib does not limit growth of the primary tumor. These findings are similar to the results of clinical trials with Alisertib in breast cancer. Importantly, we found that Alisertib dramatically decreases growth of the established metastases and prevents further dissemination via inactivation of AKT and activation of cytotoxic autophagy. Combination of Alisertib with eribulin led to a synergistic decrease in metastases to distant organs and provided additional local control of mammary tumor growth. Conclusion: Metastatic PDX models provide new, accurate assessment of anti-metastatic regiment's efficacy. MLN8237 plus eribulin combination shows synergistic inhibition of metastatic spread, growth of established metastases and prolongs overall survival. Future clinical trials are needed to further test this regiment in clinic to improve survival of metastatic cancer patients. Citation Format: Ryan Ice, Anna Kiseleva, Yuriy Loskutov, Matthew Smolkin, Adham Salkeni, Hannah Hazard, Ginger Layne, Elena Pugacheva{Authors}. Development of metastatic patient-derived xenografts (PDXs) for accurate assessment of anti-metastatic therapeutics in pre-clinical settings. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr B20.
Abstract ES1-2: Paracrine signaling and intratumoral heterogeneity
Authors: JM Rosen
Journal: Cancer Research (2017)

Abstract Breast cancer is no longer considered a single disease, but instead comprises multiple subtypes with genetically and most likely epigenetically heterogeneous tumors composed of numerous clones. Both the hierarchical cancer stem cell (CSC) and clonal evolution models have been invoked to help explain this intratumoral heterogeneity. Several recent studies have helped define the functional interactions among the different cellular subpopulations necessary for the evolution of this complex ecosystem. These interactions involve paracrine interactions that include locally acting Wnt family members, reminiscent of the signaling pathways important for normal mammary gland development and stem cell self-renewal. In addition, they involve interactions between breast cancer cells and the immune microenvironment. In this presentation, we will discuss the interactions among various cell populations in both normal and tumor tissues. A better understanding of these interactions, especially in the metastatic setting, will be important for the development of improved combinatorial therapies designed to prevent relapse and to ultimately decrease mortality. Citation Format: Rosen JM. Paracrine signaling and intratumoral heterogeneity [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr ES1-2.
Anti-Leukemia and Multiple Myeloma Selective Activity of CXCR4 Antagonist 4F-Benzoyl-TN14003 Involves Apoptotic Death Pathway.
Authors: Katia Beider, Michal Begin, Michal Abraham, Hanna Wald, Ido Weiss, Ori Wald, Eli Pikarsky, Evelyne Zeira, Orly Eizenberg, Eithan Galun, Arnon Nagler, Amnon Peled
Journal: Blood (2009)
Impact of Age and Treatment Group in Childhood High Hyperdiploid Low Risk B-Cell Acute Lymphoblastic Leukemia (ALL): Results of the CLG-EORTC 58951 Study
Authors: Laura Clement, Stefan Suciu, Isabelle Luquet, Alina Ferster, Karima Yakouben, Anne Uytterbroeck, Catherine Paillard, Nicolas Sirvent, Vitor Costa, Barbara De Moerloose, Francoise Mazingue, Emmanuel Plouvier, Martine Munzer, Maryline Poirée, Odile Minckes, Frédéric Millot, Dominique Plantaz, Caroline Piette, Frank Speleman, Hélène Cavé, Jutte VanderWerff-tenBossch, Pierre Simon Rohrlich, Yves Bertrand, Yves Benoit, Geneviève Plat
Journal: Blood (2016)
Allogeneic dendritic cell (DC) vaccination as an “off the shelf” treatment to prevent or delay relapse in elderly acute myeloid leukemia patients: Results of phase I study.
Authors: Arjan A van den Loosdrecht, Saskia Santegoets, Sandra van Wetering, Satwinder Kaugh Singh, Malika Koppes, Anthony Hall, Tanja D. de Gruijl, Gert J. Ossenkoppele, Ada M Kruisbeek
Journal: Journal of Clinical Oncology (2013)

3029 Background: Vaccines against tumor-associated antigens represent an appealing strategy for preventing tumor recurrence. A novel immunotherapy platform is represented by the DCOne cell line, which originates from a human myeloid leukemia cell line, endogenously expresses a range of tumor associated antigens and can be differentiated into mature dendritic cells. Methods: A phase I study enrolled 12 AML patients (age range 58-71) who were either in CR1/CR2 (n=5) or had smouldering disease (n=7), at high risk of relapse and ineligible for available post-remission therapies, in a 3+3 design, starting with 4 bi-weekly intradermal DCOne DC vaccinations of 10E6 cells (n=3), 25E6 (n=3) or 50E6 (n=6). Patients were monitored for clinical and immunological responses for 126 days and surviving patients were followed up after study completion. Results: Treatment was well tolerated in all patients, with expected toxicities of injection site reactions (&lt; grade 2). During the study 3 patients died: 2 from infections and 1 from leukemia. Patients who survived more than 6 months post-vaccination showed remarkable survival (22 mo after the first patient was recruited, 3 patients have been alive for 22, 20 and 16 months respectively). One patient with smouldering AML at entry achieved CR2 after vaccination; one patient who was in CR2 at entry, relapsed 8 mo after vaccination and entered CR3 following a single low dose of 5-AZA. Remarkably, 1/5 patients that were evaluable by IFNg ELIPOTs showed vaccination-induced specific T cell responses to WT-1 and PRAME, antigens present in DCOne DC. In addition, increased post vaccination delayed type hypersensitivity reactions were observed in all cohorts. Furthermore, induction of systemic immune responses, with increases in CD4+ and CD8+ T cell proliferative responses and/or seroconversion to DCOne DC and/or AML blasts was seen in 5 out of 9 patients. Conclusions: Vaccination with DCOne derived DC is feasible in AML, generated cellular and humoral immune responses, and interesting clinical responses. The hypothesis that immune responses correlate with clinical benefit will be investigated in a randomised phase II trial. Clinical trial information: NCT01373515.
Acute Monoblastic Leukemia and Myeloproliferative Neoplasm Observed in an Elderly Man Had the Same Clonal Origin
Authors: Shinya Sato, Yasushi Miyazaki, Hidehiro Itonaga, Masataka Taguchi, Yasushi Sawayama, Daisuke Imanishi, Tomoko Hata, Yukiyoshi Moriuchi, Hiroyuki Mishima, Kohichiro Yoshiura
Journal: Blood (2015)
Phase Ib Study of Oral Panobinostat In Combination with 5-Azacitidine (5-aza) In Patients with Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), or Acute Myeloid Leukemia (AML)
Authors: Pierre Fenaux, Daniel J DeAngelo, Guillermo Garcia-Manero, Michael Lübbert, Anand P. Jillella, Mikkael A. Sekeres, Ivo J. Winiger, Margaret Squier, Xiaodong Li, Oliver G. Ottmann
Journal: Blood (2010)
Abstract P1-05-02: Genomic, transcriptomic and immune features of breast cancer according to the patient's body mass index at diagnosis
Authors: C Desmedt, M Fornili, V Detours, G van den Eynden, R Salgado, M Maetens, D Brown, S Nik-Zainal, C Sotiriou, E Biganzoli
Journal: Cancer Research (2017)

Abstract This abstract was withdrawn by the authors.
Vitamin D supplementation in pregnancy, prenatal 25(OH)D levels, race, and subsequent asthma or recurrent wheeze in offspring: Secondary analyses from the Vitamin D Antenatal Asthma Reduction Trial
Authors: Helene M. Wolsk, Benjamin J. Harshfield, Nancy Laranjo, Vincent J. Carey, George O'Connor, Megan Sandel, Robert C. Strunk, Leonard B. Bacharier, Robert S. Zeiger, Michael Schatz, Bruce W. Hollis, Scott T. Weiss, Augusto A. Litonjua
Journal: Journal of Allergy and Clinical Immunology (2017)
Advanced imaging assessment of gout: comparison of dual-energy CT and MRI with anatomical pathology
Authors: Ashika Chhana, Anthony Doyle, Amy Sevao, Satya Amirapu, Peter Riordan, Michael Dray, Sue McGlashan, Jillian Cornish, Nicola Dalbeth
Journal: Annals of the Rheumatic Diseases (2017)

Dual-energy CT (DECT) and MRI are advanced imaging methods used to visualise gout pathology. DECT can identify monosodium urate (MSU) crystals in people with gout,1 ,2 and also has conventional CT properties, allowing assessment of tophus and bone pathology.3 ,4 MRI is used to assess inflammation, bone erosion and cartilage damage in gout.5–7 This study aimed to compare DECT and MRI with corresponding anatomical pathology in the assessment of gout.

Cadaveric joint specimens were obtained from two donors; a donor aged 82 years with crystal-proven tophaceous gout and a control donor aged 89 years without gout (12 joints from each).

All joints were scanned by DECT (SOMATOM Definition Flash, Siemens Medical, Erlangen, Germany) and MRI (3T MAGNETOM Skyra, Siemens Medical), and then processed for histology, including digital photography of sectioned digits (sagittal plane) for macroscopic analysis, and preparation of histology slides from each individual joint for microscopic analysis. Slides were stained with H&E or 1% toluidine blue. Collection and use of cadaveric tissue was in accordance with the New Zealand Human Tissue Act 2008.

All images and histology data were systematically assessed for gout pathology by experienced readers who were blinded to diagnosis and each other's scores. …
Multi-Institutional Assessment of Adverse Health Outcomes Among North American Testicular Cancer Survivors After Modern Cisplatin-Based Chemotherapy
Authors: Chunkit Fung, Howard D. Sesso, Annalynn M. Williams, Sarah L. Kerns, Patrick Monahan, Mohammad Abu Zaid, Darren R. Feldman, Robert J. Hamilton, David J. Vaughn, Clair J. Beard, Christian K. Kollmannsberger, Ryan Cook, Sandra Althouse, Shirin Ardeshir-Rouhani-Fard, Steve E. Lipshultz, Lawrence H. Einhorn, Sophie D. Fossa, Lois B. Travis
Journal: Journal of Clinical Oncology (2017)

Purpose To provide new information on adverse health outcomes (AHOs) in testicular cancer survivors (TCSs) after four cycles of etoposide and cisplatin (EPX4) or three or four cycles of bleomycin, etoposide, cisplatin (BEPX3/BEPX4). Methods Nine hundred fifty-two TCSs &gt; 1 year postchemotherapy underwent physical examination and completed a questionnaire. Multinomial logistic regression estimated AHOs odds ratios (ORs) in relation to age, cumulative cisplatin and/or bleomycin dose, time since chemotherapy, sociodemographic factors, and health behaviors. Results Median age at evaluation was 37 years; median time since chemotherapy was 4.3 years. Chemotherapy consisted largely of BEPX3 (38.2%), EPX4 (30.9%), and BEPX4 (17.9%). None, one to two, three to four, or five or more AHOs were reported by 20.4%, 42.0%, 25.1%, and 12.5% of TCSs, respectively. Median number after EPX4 or BEPX3 was two (range, zero to nine and zero to 11, respectively; P &gt; .05) and two (range, zero to 10) after BEPX4. When comparing individual AHOs for EPX4 versus BEPX3, Raynaud phenomenon (11.6% v 21.4%; P &lt; .01), peripheral neuropathy (29.2% v 21.4%; P = .02), and obesity (25.5% v 33.0%; P = .04) differed. Larger cumulative bleomycin doses (OR, 1.44 per 90,000 IU) were significantly associated with five or more AHOs. Increasing age was a significant risk factor for one to two, three to four, or five or more AHOs versus zero AHOs (OR, 1.22, 1.50, and 1.87 per 5 years, respectively; P &lt; .01); vigorous physical activity was protective (OR, 0.62, 0.51, and 0.41, respectively; P &lt; .05). Significant risk factors for three to four and five or more AHOs included current (OR, 3.05 and 3.73) or former (OR, 1.61 and 1.76) smoking ( P &lt; .05). Self-reported health was excellent/very good in 59.9% of TCSs but decreased as AHOs increased ( P &lt; .001). Conclusion Numbers of AHOs after EPX4 or BEPX3 appear similar, with median follow-up of 4.3 years. A healthy lifestyle was associated with reduced number of AHOs.
GATA2 Mutations in Pediatric Acute Myeloid Leukemia: A Study of the Japanese Childhood AML Cooperative Study Group.
Authors: Norio Shiba, Kentarou Ohki, Myoung-ja Park, Souichi Adachi, Masao Kobayashi, Akitoshi Kinoshita, Manabu Sotomatsu, Hirokazu Arakawa, Akio Tawa, Keizo Horibe, Ichiro Tsukimoto, Yasuhide Hayashi
Journal: Blood (2012)