tbuckley/cabot-search huggingface dataset:
Community platinum use in neoadjuvant or adjuvant HER2- breast cancer.
Authors: Laura Rose Bobolts, Melissa Armitage, Mary Michelle Tamayo, William J. Hrushesky, Jurgen Kogler, Anna E. Schorer, Kenneth Wurtz, Charles L. Bennett, William S. Shimp, Anmol Baranwal, Dinah Faith Q. Huff, Carol Anthony, Robert Walton, Marc L. Fishman
Journal: Journal of Clinical Oncology (2015)

e12029 Background: There is increasing evidence that platinum-based chemotherapy (PBC) is beneficial in breast cancer. Utilization of platinum agents are on the rise in potentially curable HER2-negative (HER2-) disease. This trend is particularly evident in triple negative breast cancer (TNBC), which lacks a specific molecular therapeutic target. Few data defines the optimal PBC regimen or candidates for these regimens. The aim of this study was to determine the frequency of PBC regimens selected in the community for HER2- non-metastatic breast cancer. Methods: This retrospective chart review tabulated PBC drug authorization requests across the US, from January 2014 to January 2015 for stages I-III HER2- breast cancer patients. We included 47 patients and recorded the following variables: age, stage, ER/PR, HER2, and BRCA status, planned chemotherapy and neoadjuvant versus adjuvant. Results: Carboplatin was the only platinum requested. The majority of PBC authorization requests were for triple negative breast (TNBC) patients (85%) age less than 60 (74%). Stage II disease predominated (43%), as did neoadjuvant PBC use (83%). Only 6% of cases were documented BRCA+, while 83% had no documented BRCA testing. Fifteen percent were ER/PR+ and HER2-. Neoadjuvant PBC was requested for stage I disease in two of these seven ER/PR+ patients. Paclitaxel qwk plus carboplatin q3wk with sequential ddAC was requested in 68%, with 94% in the neoadjuvant setting. Conclusions: Carboplatin is used with increasing frequency for the neoadjuvant therapy of early stage HER2- breast cancer, even in hormone receptor positive stage I disease. Further investigation is needed to determine whether this strategy prolongs overall survival and diminishes breast cancer-related mortality. PBC Regimen Stage I ER/PR+ TNBC Neoadj Paclitaxel qwk-Carboplatin q3wk - > ddAC (n = 32) 16% 16% 84% 94% Docetaxel-Carboplatin (n = 5) 60% 0% 100% 40% Paclitaxel-Carboplatin (n = 4) 25% 0% 100% 75% Paclitaxel or Docetaxel-Carboplatin - > FAC (n = 2) 0% 50% 50% 100% Paclitaxel or Docetaxel q3wk-Carboplatin - > AC (n = 2) 0% 0% 100% 100% Cyclophopshamide-Carboplatin (n = 1) 100% 0% 100% 0% AC - > Paclitaxel - > Docetaxel-Carboplatin (n = 1) 0% 100% 0% 0%
Primary Central Nervous System (PCNS) Post-Transplant Lymphoproliferative Disease (PTLD): An International Report of 65 Cases in the Modern Era
Authors: Andrew M. Evens, Sylvain Choquet, Aimee Kroll, Sonali M. Smith, Véronique Leblond, Rupali Roy, Bruce Barton, Daan Dierickx, David Schiff, Thomas M. Habermann, Ralf Trappe
Journal: Blood (2011)
Platelet Endothelial Aggregation Receptor-1 is a Critical Determinant of Endothelial Cell Function
Authors: Christophe Vandenbriele, Alexandre Kauskot, Aernout Luttun, Stefan Janssens, Marc Hoylaerts, Peter Verhamme
Journal: Circulation (2012)

Background: Platelet endothelial aggregation receptor-1 (PEAR1), a type I transmembrane receptor, is expressed on platelets and endothelial cells (ECs) but its contribution to EC function is unknown. We aim to unravel its (patho)physiological role in ECs.

Methods and results: PEAR1 expression was analyzed in cultured human endothelial progenitors (blood outgrowth endothelial cells or BOECs), in ECs from human umbilical cord and in ECs freshly isolated from multiple vascular beds (qPCR). mRNA expression was heterogeneous, with the lowest expression in BOECs and the highest in macrovascular and microvascular ECs from heart and liver. Umbilical cord ECs showed intermediate PEAR1 levels. Stainings of human hemangiomas (pyogenic granuloma) revealed low expression of PEAR1 in the young, rapidly proliferating ECs of the granuloma compared to normal subcutaneous ECs.

The role of PEAR1 in EC proliferation was evaluated in the hybrid cell line EA.hy926. PEAR1 knockdown by lentiviral transduction (short-hairpin anti-PEAR1 construct; shPEAR1) doubled the EC proliferation rate, as compared to control lentiviral-transduced cells. This was associated with significantly increased baseline Akt-P levels (PI3K-activity) in shPEAR1 cells and significantly decreased levels of the phosphatase PTEN (PI3K-antagonist). Expression of the proliferation suppressor p21/CIP1 in shPEAR1 ECs was reduced by 60±2% (mean±SEM, qPCR), whereas the band intensity for CDC2 significantly rose on western blots, consistent with increased mitosis. In in vitro matrigel tube formation assays, using human umbilical artery endothelial cells (HUAECs), PEAR1 knockdown significantly (p<0.005) increased total tube length and number of tube branching points compared to control HUAEC tubes. PEAR1 expression rose 5-fold during tube formation. This was associated with a 3-fold increase of PTEN whereas PTEN-levels dropped 1,5-fold during tube formation of PEAR1-knockdown HUAECs, compatible with increased phosphorylation of Akt in shPEAR1 ECs.

Anti-PEAR1 antibodies behaved as a pseudo-ligand in EA.hy926 ECs and HUAECs and triggered PEAR1- and Akt-phosphorylation. In turn, this resulted in PEAR1/Akt-mediated phosphorylation of eNOS (activating site P1177 on western blot) and in anti-PEAR1 pseudoligand stimulated tube formation.

Conclusions: We provide the first evidence that PEAR1 is expressed in ECs from multiple vascular beds and that PEAR1 plays a suppressive role on proliferation, eNOS-activation and tube formation through the PI3K/Akt/PTEN pathway. The upregulation of PEAR1 during EC maturation is compatible with this suppressive role.
Dynamic serial monitoring of EGFR mutations in plasma DNA samples in EGFR mutant NSCLC patients treated with EGFR TKI.
Authors: Myung-Ju Ahn, Ji Yun Lee, Sung Hee Lim, Min-Young Lee, Haesu Kim, Hee Kyung Kim, Seonggyu Byeon, Jun soo Ham, Bai Yali, Wei Xiumin, Ho Yun Lee, Jong-Mu Sun, Jin Seok Ahn, Eun Kyung Cho, Hye Ryun Kim, Young Joo Min, Dong-Wan Kim, Keunchil Park, Xu Qing, Mao Mao
Journal: Journal of Clinical Oncology (2015)

8078 Background: Detection of epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer (NSCLC) patients is mainly based on tissue biopsy, which is invasive and time consuming. Furthermore, there is still a need for serial monitoring of EGFR mutations and detection of EGFR tyrosine kinase inhibitors (TKIs) resistance. We hypothesized that plasma-based EGFR mutation analysis may be feasible for monitoring response to EGFR TKIs and could be used to predict the resistance. Methods: From February 2012 through April 2014, 200 EGFR mutant NSCLC patients were enrolled and treated with EGFR TKIs (141 patients for gefitinib, 46 patients for erlotinib, and 13 patients for afatinib). Plasma samples were prospectively obtained every 2 months from baseline until disease progression. The longitudinally collected plasma samples (n = 277) from 61 patients who progressed were analyzed using droplet digital PCR (ddPCR). We identified an association between serial EGFR mutant titers in plasma cell-free DNA (cfDNA) samples and the patient’s clinical response to EGFR TKIs. Results: Of a total 60 baseline cfDNA samples available for ddPCR, 40 (67%) samples demonstrated same mutation in the matched tumors (i.e. sensitivity: 65% (13/20) for L858R vs 68% (27/40) for exon 19 deletions). The concordance rate of plasma with tissue results of EGFR mutation was 88% for L858R and 78% for exon 19 deletion, respectively. All the samples showing EGFR mutations in plasma showed a dramatic decrease of mutant copies (greater than 50%) in blood in the first 2 months after treatment. We also found the secondary mutation (T790M) emerged in 15 patients around 3~13 months after treatment and can be detected before disease progression as determined by CT scan. Correlation between the tumor volume and the level of cfDNA EGFR mutations will be updated. Conclusions: These results suggest that ddPCR is an appropriate method for determining plasma-based EGFR mutation status and may aid in monitoring response to EGFR TKIs and early detection of EGFR TKIs resistance. Concordance between EGFR mutation status assessed by ddPCR and clinical tissue result. prior treatment N=60 ddPCR L858R + L858R- E19 + E19 - Tissue + 13 7 27 13 Tissue - 0 40 0 20
Combined modality therapy of locally advanced adenocarcinoma of the rectum: Update of a phase I trial of preoperative radiation (RT) with concurrent capecitabine (Cap) and irinotecan (Ir)
Authors: E. P. Mitchell, P. Anne, S. Goldstein, G. Isenberg, J. Fitzgerald, J. Palazzo, W. Hauck, J. Lavarino, J. Sanson, W. J. Curran
Journal: Journal of Clinical Oncology (2006)

13547 Background: We previously reported the combination of preoperative radiation (RT) with concurrent Irinotecan and 5-FU in locally advanced rectal cancer, was well tolerated and had an excellent pathologic complete response rate (CR) of 25%, but with catheter related infections and thromboses as major toxicities (Proc Am Soc Clin Onc 22: 2003). With the potential benefits of capecitabine (Cap) and no need for an implanted catheter, a phase I study was initiated to determine the toxicity and maximum tolerated dose (MTD) of Cap with concurrent Ir and RT. Methods: Eligible patients (pts) had primary or recurrent Stage II or III rectal adenocarcinoma, without a history of prior RT or chemotherapy. The treatment regimen was as follows: external beam RT at 1.8Gy daily M-F, to a total dose of 50.4 or 54 Gy; Ir 50 mg/m 2 IV, d 1, 8, 15, 22; dose escalating Cap starting at 825 mg/m 2 PO divided in 2 doses, Q 12h. Surgical resection occurred at 6–10 weeks. Dose limiting toxicity is defined as Gr4 heme or non-heme Gr3. Results: A total of 16 pts have enrolled on the study, 10 male and 6 female;the median age was 57 (range 44–77). All are evaluable for toxicity. The Table reviews the maximum toxicities. Grade three diarrhea is the only dose-limiting toxicity to date. There has also been 3 pts with Gr 3 hematologic toxicity. There has been no Gr 4 toxicity. Patients are currently accruing on the 4 th dose level of capecitabine. A total of 13 pts have completed the preoperative phase and three are currently on treatment. Eleven pts have had surgical resection. One pt refused surgery due to a biopsy proven CR to chemoradiation. One pt refused surgery and died of disease. Of the 11 pts undergoing surgical resection, there have been 3 pathologic CR. Conclusions: The preoperative combination of capecitabine, irinotecan and radiation in locally advanced rectal cancer pts is feasible and well tolerated. The study continues to accrue, and the MTD has not been achieved. [Table: see text] [Table: see text]
Executive Summary of the American Heart Association and American Thoracic Society Joint Guidelines for Pediatric Pulmonary Hypertension
Authors: Steven H. Abman, D. Dunbar Ivy, Stephen L. Archer, Kevin Wilson
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Although pulmonary hypertension (PH) contributes significantly to poor outcomes in diverse pediatric diseases, approaches toward the care of children with PH have been limited by the lack of consensus guidelines from experts in the field. In a joint effort from the American Heart Association and American Thoracic Society, a committee of experienced clinicians was formed to systematically identify, synthesize, and appraise relevant evidence and then to formulate evidence-based recommendations regarding the diagnosis and management of pediatric PH. This brief report is an executive summary of the officially approved guidelines developed by the committee, highlighting a few key recommendations regarding the care of children with PH. Guidelines and the rationale for grading the strength of each recommendation are included in the online supplement.
Phase II trial of high-dose interleukin-2 (IL-2) with priming and concomitant sargramostim (GM-CSF) in patients with advanced melanoma.
Authors: J. Lutzky, D. H. Lawson, Y. Enriquez-Nunez, D. Gabrilovich
Journal: Journal of Clinical Oncology (2010)

8560 Background: GM-CSF is a multifunctional cytokine that augments T-cell proliferation in the presence of antigen presenting cells (APC) and up-regulates the IL-2 receptor on T lymphocytes and monocytes.Studies have suggested that adding GM-CSF to IL-2 is synergistic, but no data is available on the clinical outcomes of a combination of GM-CSF with the standard HD-IL-2 regimen. Methods: Eligibility criteria included stageIII/IV melanoma, ECOG PS 0-1, and adequate organ function. Patients with > 2 chemotherapy regimens or active CNS metastases were excluded. GM-CSF 125 mg/m2 was injected subcutaneously 7 days before day 1 of HD- IL-2 and continued for 4 weeks, encompassing two cycles of HD-IL-2. IL-2 was administered intravenously at the standard 600,000 U/kg, as published. Immunologic assessments including dendritic cells (DC), IL-2 receptor (IL-2R) and regulatory T-cell (Treg) frequencies were performed at predetermined intervals. A two-stage design targeted a response rate (RR) of ≥ 15%. If ≥ 1 response were seen in 19 patients, accrual would proceed to 30 evaluable patients. Study endpoints included one-year survival, RR, progression-free survival (PFS) and safety. Results: Thirty-six patients were accrued. Six patients were not evaluable because they were either not treated or did not complete at least one course of therapy. Treatment toxicity was comparable to the known toxicity of HD-IL-2 alone. One sudden unexpected death occurred in one patient during IL-2 administration. The median follow-up is 16.2 months. In the 30 evaluable patients there were no complete responses, 4 (13%) partial responses, 8 (27%) with stable disease and 18 (60%) with disease progression. The median overall survival was 10.7 months and PFS was 2.4 months. One-year survival and PFS rates were 32.5% and 7.5%, respectively. Treatment increased DC, IL-2R and Treg in most patients tested. Conclusions: While treatment of advanced melanoma with HD-IL-2 with priming and concomitant sargramostim appears safe, the clinical outcomes are similar to what has been reported for HD-IL-2 alone. Further analyses of the immunologic parameters and clinical correlations will be conducted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer, Genzyme, Novartis Bayer Bayer, Berlex, Genzyme, Novartis
A Thousand Fly Genomes: An Expanded<i>Drosophila</i>Genome Nexus
Authors: Justin B. Lack, Jeremy D. Lange, Alison D. Tang, Russell B. Corbett-Detig, John E. Pool
Journal: Molecular Biology and Evolution (2016)

The Drosophila Genome Nexus is a population genomic resource that provides D. melanogaster genomes from multiple sources. To facilitate comparisons across data sets, genomes are aligned using a common reference alignment pipeline which involves two rounds of mapping. Regions of residual heterozygosity, identity-by-descent, and recent population admixture are annotated to enable data filtering based on the user’s needs. Here, we present a significant expansion of the Drosophila Genome Nexus, which brings the current data object to a total of 1,121 wild-derived genomes. New additions include 305 previously unpublished genomes from inbred lines representing six population samples in Egypt, Ethiopia, France, and South Africa, along with another 193 genomes added from recently-published data sets. We also provide an aligned D. simulans genome to facilitate divergence comparisons. This improved resource will broaden the range of population genomic questions that can addressed from multi-population allele frequencies and haplotypes in this model species. The larger set of genomes will also enhance the discovery of functionally relevant natural variation that exists within and between populations.
Midline for apheresis of peripheral blood stem cells
Authors: F. Oleari, P. Mordenti, D. Vallisa, M. Moretto, C. Arbasi, S. Bontini, S. Carini, S. Castellani, C. Gozzo, O. Grassi, M. Muroni, M.R. Cordani, L. Cappucciati, L. Cavanna
Journal: Annals of Oncology (2015)
Myeloma XI Trial for Newly Diagnosed Multiple Myeloma (NDMM); A Report of Second Primary Malignancy (SPM) Rates and the Importance of Review of Reported Cases
Authors: John R Jones, David A Cairns, Rachel Sigsworth, Corinne Collett, Charlotte Pawlyn, Alina Striha, Lorenzo Melchor, Martin F Kaiser, Mark T Drayson, Faith E Davies, Walter M Gregory, Kevin Boyd, Roger G Owen, Graham H Jackson, Gareth J Morgan
Journal: Blood (2015)
The T(14;20)(q32;q12) : A Rare Cytogenetic Change in Multiple Myeloma Associated with Poor Outcome
Authors: Marie-Christiane Vekemans, Heidi Lemmens, Chantal Doyen, Greet Bries, HIlde Demuynck, Pascal Pierre, Jan Lemmens, Peter Meeus, Michel Delforge, Deborah Bauwens, Iwona Wlodarska, Peter Vandenberghe, Lucienne Michaux
Journal: Blood (2008)
A randomized phase III trial of myeloablative autologous peripheral blood stem cell (PBSC) transplant (ASCT) for high-risk neuroblastoma (HR-NB) employing immunomagnetic purged (P) versus unpurged (UP) PBSC: A Children’s Oncology Group study
Authors: S. G. Kreissman, J. G. Villablanca, R. C. Seeger, S. A. Grupp, W. B. London, J. M. Maris, J. R. Park, S. L. Cohn, K. K. Matthay, C. P. Reynolds
Journal: Journal of Clinical Oncology (2008)

10011 Background: ASCT improves outcome for HR-NB, but potential risk of reinfusion of viable tumor in PBSC could affect event-free survival (EFS). We assessed the impact of ASCT with immunomagnetic purging of PBSC, compared to UP product, on EFS, PBSC tumor content, engraftment, and ASCT toxicity. Methods: Between 2/2001 and 3/2006, 489 eligible newly diagnosed HR-NB pts were randomized at study entry to have P or UP PBSC obtained and cryopreserved after 2 cycles of induction chemotherapy. Purging was performed centrally using carbonyl iron depletion of phagocytes followed by 2 cycles of magnetic beads with 5 anti-NB monoclonal antibodies. After 6 chemotherapy cycles, pts received melphalan (180–210 mg/m2), carboplatin (AUC 4.1 to max 1700 mg/m2), and etoposide (800–1352 mg/m2) based on GFR followed by PBSC support. Post-ASCT pts had radiation to primary and MIBG+ sites, then 6 cycles of 13-cis-retinoic acid. EFS and overall survival (OS) from enrollment [primary endpoint] were analyzed as intent-to- treat. Results: Median age at study entry was 3.1 yrs (range 91 days-29 years), 44% of 392 tumors tested had MYCN amplification and 424 were INSS stage 4. There were 368 pts transplanted (178 P and 190 UP). Crossover from P to UP arm occurred in 30 pts and from UP to P arm in 5 pts. Only 5 pts (1 P and 4 UP) had NB detected in PBSC by immunocytology at collection, none after purging. RT- PCR analysis of tumor in PBSC products is ongoing. The median time to ANC>500 was 13 days for P and 11 days for UP (p= 0.0001). Toxic death following ASCT was 3.2%, (8 P, 4 UP) mainly due to infection. There was no difference in toxicities between arms. Conclusions: Centralized immunomagnetic purging of PBSC in the context of dose-intensive chemoradiotherapy and biologic therapy in first response did not impact EFS or OS at 2 years. RT-PCR analyses of PBSC products will determine if purging of rare tumor cells occurred. Cohorts N 2 yr EFS ± SE (%) 2-sided p-value 2 yr OS ±SE (%) 2-sided p-value Purged 244 47 ± 3 0.7881 69 ± 3 0.2920 Unpurged 245 49 ± 3 73 ± 3 No significant financial relationships to disclose.
High Expression Levels of Iaps Predict Poor Overall Survival in Childhood De Novo Acute Myeloid Leukemia.
Authors: Ingo Tamm, Stephan Richter, Doreen Oltersdorf, Ursula Creutzig, Jochen Harbott, Frank Scholz, Leonid Karawajew, Wolf-Dieter Ludwig, Wuchter Christian
Journal: Blood (2004)
Use of Projection Analyses and Obesity Trends—Reply
Authors: Katherine M. Flegal, Cynthia L. Ogden
Journal: JAMA (2016)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Optimal Generation of Tissue-Resident but Not Circulating Memory T Cells during Viral Infection Requires Crosspriming by DNGR-1 + Dendritic Cells
Authors: Salvador Iborra, María Martínez-López, Sofía C. Khouili, Michel Enamorado, Francisco J. Cueto, Ruth Conde-Garrosa, Carlos del Fresno, David Sancho
Journal: Immunity (2016)
Utilization of Next Generation Sequencing Identifies Potentially Actionable Mutations with Prognostic Significance in Chronic Lymphocytic Leukemia
Authors: Jie Wang, Jennifer J.D. Morrissette, E. Paul Wileyto, Stephen J. Schuster, Alexandra Vandegrift, Allison Rago, Colleen Dorsey, David Porter, Daniel J. Landsburg, Prioty Islam, Sunita Dwivedy Nasta, Jakub Svoboda, Alison Loren, Scott Weber, Edward A. Stadtmauer, Anthony Mato
Journal: Blood (2015)
Lung cancer probability in subjects with CT-detected pulmonary nodules
Authors: Nanda Horeweg, Joost Van Rosmalen, Marjolein Heuvelmans, Carlijn M Van der Aalst, Rozemarijn Vliegenthart, Ernst T Scholten, Kevin Ten Haaf, Kristiaan Nackaerts, Jan-Willem Lammers, Harry J. M Groen, Carla Weenink, Erik Thunnissen, Peter Van Ooijen, Pim A De Jongh, Truuske De Bock, Willem Mali, Harry J De Koning, Matthijs Oudkerk
Journal: Journal of Thoracic Oncology (2013)