tbuckley/cabot-search huggingface dataset:
An Optimized Full-Length FLT3/CD3 Bispecific Antibody Demonstrates Potent Anti-leukemia Activity and Reversible Hematological Toxicity
Authors: Yik Andy Yeung, Veena Krishnamoorthy, Danielle Dettling, Cesar Sommer, Kris Poulsen, Irene Ni, Amber Pham, Wei Chen, Sindy Liao-Chan, Kevin Lindquist, S. Michael Chin, Allison Given Chunyk, Wenyue Hu, Barbra Sasu, Javier Chaparro-Riggers, Ivana Djuretic
Journal: Molecular Therapy (2020)

FLT3 (FMS-like tyrosine kinase 3), expressed on the surface of acute myeloid leukemia (AML) blasts, is a promising AML target, given its role in the development and progression of leukemia, and its limited expression in tissues outside the hematopoietic system. Small molecule FLT3 kinase inhibitors have been developed, but despite having clinical efficacy, they are effective only on a subset of patients and associated with high risk of relapse. A durable therapy that can target a wider population of AML patients is needed. Here, we developed an anti-FLT3-CD3 immunoglobulin G (IgG)-based bispecific antibody (7370) with a high affinity for FLT3 and a long half-life, to target FLT3-expressing AML blasts, irrespective of FLT3 mutational status. We demonstrated that 7370 has picomolar potency against AML cell lines in vitro and in vivo. 7370 was also capable of activating T cells from AML patients, redirecting their cytotoxic activity against autologous blasts at low effector-to-target (E:T) ratio. Additionally, under our dosing regimen, 7370 was well tolerated and exhibited potent efficacy in cynomolgus monkeys by inducing complete but reversible depletion of peripheral FLT3+ dendritic cells (DCs) and bone marrow FLT3+ stem cells and progenitors. Overall, our results support further clinical development of 7370 to broadly target AML patients. FLT3 (FMS-like tyrosine kinase 3), expressed on the surface of acute myeloid leukemia (AML) blasts, is a promising AML target, given its role in the development and progression of leukemia, and its limited expression in tissues outside the hematopoietic system. Small molecule FLT3 kinase inhibitors have been developed, but despite having clinical efficacy, they are effective only on a subset of patients and associated with high risk of relapse. A durable therapy that can target a wider population of AML patients is needed. Here, we developed an anti-FLT3-CD3 immunoglobulin G (IgG)-based bispecific antibody (7370) with a high affinity for FLT3 and a long half-life, to target FLT3-expressing AML blasts, irrespective of FLT3 mutational status. We demonstrated that 7370 has picomolar potency against AML cell lines in vitro and in vivo. 7370 was also capable of activating T cells from AML patients, redirecting their cytotoxic activity against autologous blasts at low effector-to-target (E:T) ratio. Additionally, under our dosing regimen, 7370 was well tolerated and exhibited potent efficacy in cynomolgus monkeys by inducing complete but reversible depletion of peripheral FLT3+ dendritic cells (DCs) and bone marrow FLT3+ stem cells and progenitors. Overall, our results support further clinical development of 7370 to broadly target AML patients.
Neonicotinoid Insecticides: Molecular Targets, Resistance, and Toxicity
Authors: Kazuhiko Matsuda, Makoto Ihara, David B. Sattelle
Journal: The Annual Review of Pharmacology and Toxicology (2020)

Neonicotinoids have been used to protect crops and animals from insect pests since the 1990s, but there are concerns regarding their adverse effects on nontarget organisms, notably on bees. Enhanced resistance to neonicotinoids in pests is becoming well documented. We address the current understanding of neonicotinoid target site interactions, selectivity, and metabolism not only in pests but also in beneficial insects such as bees. The findings are relevant to the management of both neonicotinoids and the new generation of pesticides targeting insect nicotinic acetylcholine receptors.
Final Results of a Japanese Phase 1 Trial Evaluating A C-Met Inhibitor Tivantinib in Combination with an EGFR Inhibitor Erlotinib in Advanced/Metastatic Non-Small Cell Lung Cancer (ARQ 197-003/005 Study)
Authors: N. Yamamoto, H. Murakami, T. Takahashi, H. Hayashi, Y. Fujisaka, T. Hirashima, K. Takeda, M. Satouchi, K. Nakagawa
Journal: Annals of Oncology (2012)
Bone marrow niche-derived extracellular matrix-degrading enzymes influence the progression of B-cell acute lymphoblastic leukemia
Authors: Divij Verma, Costanza Zanetti, Parimala Sonika Godavarthy, Rahul Kumar, Valentina R. Minciacchi, Jakob Pfeiffer, Markus Metzler, Sylvain Lefort, Véronique Maguer-Satta, Franck E. Nicolini, Barbara Burroni, Michaela Fontenay, Daniela S. Krause
Journal: Leukemia (2020)

Abstract Specific and reciprocal interactions with the bone marrow microenvironment (BMM) govern the course of hematological malignancies. Matrix metalloproteinase-9 (MMP-9), secreted by leukemia cells, facilitates tumor progression via remodeling of the extracellular matrix (ECM) of the BMM. Hypothesizing that leukemias may instruct the BMM to degrade the ECM, we show, that MMP-9-deficiency in the BMM prolongs survival of mice with BCR-ABL1-induced B-cell acute lymphoblastic leukemia (B-ALL) compared with controls and reduces leukemia-initiating cells. MMP-9-deficiency in the BMM leads to reduced degradation of proteins of the ECM and reduced invasion of B-ALL. Using various in vivo and in vitro assays, as well as recipient mice deficient for the receptor for tumor necrosis factor (TNF) α (TNFR1) we demonstrate that B-ALL cells induce MMP-9-expression in mesenchymal stem cells (MSC) and possibly other cells of the BMM via a release of TNFα. MMP-9-expression in MSC is mediated by activation of nuclear factor kappa B (NF-κB) downstream of TNFR1. Consistently, knockdown of TNF-α in B-ALL-initiating cells or pharmacological inhibition of MMP-9 led to significant prolongation of survival in mice with B-ALL. In summary, leukemia cell-derived Tnf α induced MMP-9-expression by the BMM promoting B-ALL progression. Inhibition of MMP-9 may act as an adjunct to existing therapies.
Serum Concentration of Estrone (E1), not Estradiol (E2), is the Independent Predictive Factor of Response to Neo-Adjuvant Exemestane Treatment in Postmenopausal Breast Cancer Patients: JFMC 34-0601 TR
Authors: S. Saji, M. Takada, N. Honma, N. Masuda, Y. Yamamoto, K. Kuroi, H. Yamashita, S. Ohno, T. Ueno, M. Toi
Journal: Annals of Oncology (2012)
Four-Year Survival Update for Metastatic Melanoma (MM) Patients (PTS) Treated with Ipilimumab (IPI) + Dacarbazine (DTIC) on Phase 3 Study CA184-024
Authors: M. Maio, I. Bondarenko, C. Robert, L. Thomas, C. Garbe, A. Testori, S. Francis, K. Chin, J. Wolchok
Journal: Annals of Oncology (2012)
Overcoming Neurophobia With the Help of Peruvian Talking Bears
Authors: Brian Dewar, Gregory S. Day, Michel C. F. Shamy
Journal: JAMA Neurology (2020)

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 Neurology 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 Neurology journal
Impact of lower chemotherapy dose on treatment outcome and survival of patients with advanced Hodgkin lymphoma: Single institution experience.
Authors: Zoran Tomasevic, Zorica Tomasevic
Journal: Journal of Clinical Oncology (2012)

e18531 Background: Combined chemotherapy regimen, although highly effective, still fail to cure about one third of patients with advanced Hodgkin lymphoma (aHL). On the other hand, similar proportions of patients are probably over treated and cure might be obtained with less intensive doses. The aim of this retrospective analysis is to evaluate chemotherapy dose intensity and cumulative dose in aHL, in the context of treatment outcome and survival. Methods: At the Institute for Oncology and Radiology of Serbia, during 1991-1993 all consecutive aHL patients have been treated with MOPP (M; 41 pts) and afterwards (1994-1996) with MOPP/ABVD (M/A; 40 pts). In accordance to previous local practice, chemotherapy was given in projected, absolute doses, calculated on average body surface area of 1.7 m 2 . Characteristics of patients in both regimens were well balanced for age, gender, PS, B symptoms, histology, stage, laboratory prognostic parameters (International Prognostic Score- IPS). Approximately 50% pts in both groups were in high/intermediate risk IPS. Relative dose intensity (RDI), defined as given/scheduled dose ratio per week and relative cumulative dose (RCD), defined as given/projected dose ratio, were retrospectively analyzed whether there is potential negative impact on response, time to relapse and survival. Results: The average RCD and RDI for both regimens were 85% and 58%. Complete remission (CR) was achieved in 60% (M/A 67% vs. M 54%) (p=NS); 90% of pts with CR in both groups had no relapse during follow up. Different cumulative doses and dose intensity had no significant impact on time to relapse and overall survival. However, trend for better overall survival for patients receiving RDI over 60% was observed (p=0.09). Hemoglobin level ≤10.5 g/dl had significant adverse effect on outcome regardless of treatment dosage (p=0.02). No second malignancy has been registered during follow up. Conclusions: Although this retrospective analysis does not pretend to recommend lower chemotherapy dose regimen for routine treatment, it seems that selected aHL patients could still be effectively treated with less chemotherapy dose intensity, because 90% of pts with CR are cured.
P2.06 Exploiting The Mutanome for Tumor Vaccination
Authors: J. Castle, S. Kreiter, J. Diekmann, M. Löwer, N. van der Roemer, J. de Graaf, S. Selmi, M. Diken, S. Boegel, C. Paret, M. Koslowski, A.N. Kuhn, C.M. Britten, C. Huber, Ö. Türeci, U. Sahin
Journal: Annals of Oncology (2012)
The Feasibility of Blood Pressure Control with Autonomic- Assisted Hypertension Therapy versus JNC 8 Therapy
Authors: Gary L. Murray, Joseph Colombo
Journal: Clinical Cardiology and Cardiovascular Interventions (2020)

Background: Over one billion people have Hypertension (HTN); mortality and morbidity are increasing. The Parasympathetic and Sympathetic (P&amp;S) nervous systems prominently affect the onset and progression of HTN, yet P&amp;S measures are not used to assist in management. Our objective was to determine the feasibility of HTN control using P&amp;S-guided to JNC 8 HTN therapy. Methods: 46 uncontrolled HTN patients were randomized prospectively to P&amp;S-assisted management, adjusting JNC 8 therapy using the ANX 3.0 Autonomic Monitor and adding (r) Alpha Lipoic Acid (Group 1) vs. JNC 8 (Group 2). Results: The two Groups were similar in: 1) age (mean 66 vs. 70 y/o for Groups 1 and 2, respectively; 2) initial resting home Blood Pressure (BP, Group 1 mean=162/90 mmHg vs. Group 2 mean=166/87 mmHg, 3) initial resting office BP Group 1 mean=151/75 mmHg vs. Group 2 mean=155/73 mmHg, and 4) ethnicity. Upon follow-up (mean=8.35 mo.): 1) mean resting home BPs were 145/77 mmHg (Group 1, 74% of patients at JNC 8 goal) vs. 155/83.5 mmHg (Group 2, 30.4% at JNC 8 goal), and 2) mean resting office BPs were 138/71 mmHg (Group 1) vs. 146/65 mmHg (Group 2). At the study’s conclusion, Group 1 Sympathetic tone was lower than that for Group 2 both at rest and upon standing, and Group 1 Parasympathetic tone was higher than that for Group 2 both at rest and upon standing. Conclusion: P&amp;S-assisted HTN therapy is feasible, resulting in improved BP control, through healthier P&amp;S tone on fewer prescription medications.
Concomitant Polypharmacy is Associated with Irinotecan-Induced Adverse Drug Reactions in Patients with Cancer
Authors: K. Fujita, T. Sasaki, Y. Sunakawa, H. Ishida, K. Yamashita, K. Miwa, S. Saji, Y. Kato, Y. Sasaki
Journal: Annals of Oncology (2012)
Paclitaxel as Third-Line Chemotherapy for Refractory Small-Cell Lung Cancer to both Etoposide- and Camptothecin-Based Chemotherapy
Authors: M.-J. Kim, J.-O. Lee, Y.J. Kim, K.-W. Lee, J.H. Kim, S.-M. Bang, J.S. Lee
Journal: Annals of Oncology (2012)
Natural products, PGC-1 , and Duchenne muscular dystrophy
Authors: Ipek Suntar, Antoni Sureda, Tarun Belwal, Ana Sanches Silva, Rosa Anna Vacca, Devesh Tewari, Eduardo Sobarzo-Sánchez, Seyed Fazel Nabavi, Samira Shirooie, Ahmad Reza Dehpour, Suowen Xu, Bahman Yousefi, Maryam Majidinia, Maria Daglia, Giuseppe D'Antona, Seyed Mohammad Nabavi
Journal: Acta Pharmaceutica Sinica B (2020)

Peroxisome proliferator-activated receptor γ (PPARγ) is a transcriptional coactivator that binds to a diverse range of transcription factors. PPARγ coactivator 1 (PGC-1) coactivators possess an extensive range of biological effects in different tissues, and play a key part in the regulation of the oxidative metabolism, consequently modulating the production of reactive oxygen species, autophagy, and mitochondrial biogenesis. Owing to these findings, a large body of studies, aiming to establish the role of PGC-1 in the neuromuscular system, has shown that PGC-1 could be a promising target for therapies targeting neuromuscular diseases. Among these, some evidence has shown that various signaling pathways linked to PGC-1α are deregulated in muscular dystrophy, leading to a reduced capacity for mitochondrial oxidative phosphorylation and increased reactive oxygen species (ROS) production. In the light of these results, any intervention aimed at activating PGC-1 could contribute towards ameliorating the progression of muscular dystrophies. PGC-1α is influenced by different patho-physiological/pharmacological stimuli. Natural products have been reported to display modulatory effects on PPARγ activation with fewer side effects in comparison to synthetic drugs. Taken together, this review summarizes the current knowledge on Duchenne muscular dystrophy, focusing on the potential effects of natural compounds, acting as regulators of PGC-1α.
The 8.1 Ancestral Haplotype is Strongly Associated with the Risk of Small Cell Lung Cancer
Authors: J. Kocsis, L. Graf, A. Szilagyi, B. Dome, L. Tamasi, G. Galffy, Z. Orosz, Z. Prohaszka, G. Fust, Z. Bartfai
Journal: Annals of Oncology (2012)
Is there a Benefit on Survival of Tyrosine-Kinase Inhibitors Versus Chemotherapy in First Line in Mutated EGFR Patients with Advanced Non-Small Cell Cancer (NSCLC)? A Meta-Analysis
Authors: G. Des Guetz, B. Uzzan, K. Chouahnia, P. Nicolas, L. Zelek, M. Pailler, J. Morère
Journal: Annals of Oncology (2012)
Association of Baseline Prostate-Specific Antigen Level With Long-term Diagnosis of Clinically Significant Prostate Cancer Among Patients Aged 55 to 60 Years
Authors: Evan Kovac, Sigrid V. Carlsson, Hans Lilja, Jonas Hugosson, Michael W. Kattan, Erik Holmberg, Andrew J. Stephenson
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The use of prostate-specific antigen (PSA) screening for prostate cancer is controversial because of the risk of overdiagnosis and overtreatment of indolent cancers. Optimal screening strategies are highly sought. <h3>Objective</h3> To estimate the long-term risk of any prostate cancer and clinically significant prostate cancer based on baseline PSA levels among men aged 55 to 60 years. <h3>Design, Setting, and Participants</h3> This secondary analysis of a cohort in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial uses actuarial analysis to analyze the association of baseline PSA levels with long-term risk of any prostate cancer and of clinically significant prostate cancer among men aged 55 to 60 years enrolled in the screening group of the trial between 1993 and 2001. <h3>Exposure</h3> Single PSA measurement at study entry. <h3>Main Outcomes and Measures</h3> Long-term risk of any prostate cancer and clinically significant prostate cancer diagnoses. <h3>Results</h3> There were 10 968 men aged 55 to 60 years (median [interquartile range] age, 57 [55-58] years) at study enrollment in the screening group of the PLCO Cancer Screening Trial who had long-term follow-up. Actuarial 13-year incidences of clinically significant prostate cancer diagnosis among participants with a baseline PSA of 0.49 ng/mL or less was 0.4% (95% CI, 0%-0.8%); 0.50-0.99 ng/mL, 1.5% (95% CI, 1.1%-1.9%); 1.00-1.99 ng/mL, 5.4% (95% CI, 4.4%-6.4%); 2.00-2.99 ng/mL, 10.6% (95% CI, 8.3%-12.9%); 3.00-3.99 ng/mL, 15.3% (95% CI, 11.4%-19.2%); and 4.00 ng/mL and greater, 29.5% (95% CI, 24.2%-34.8%) (all pairwise log-rank<i>P</i> ≤ .004). Only 15 prostate cancer–specific deaths occurred during 13 years of follow-up, and 9 (60.0%) were among men with a baseline PSA level of 2.00 ng/mL or higher. <h3>Conclusions and Relevance</h3> In this secondary analysis of a cohort from the PLCO Cancer Screening Trial, baseline PSA levels among men aged 55 to 60 years were associated with long-term risk of clinically significant prostate cancer. These findings suggest that repeated screening can be less frequent among men aged 55 to 60 years with a low baseline PSA level (ie, &lt;2.00 ng/mL) and possibly discontinued among those with baseline PSA levels of less than 1.00 ng/mL.
A multicentre, randomized, double‐masked, parallel group, vehicle‐controlled phase IIb study to evaluate the safety and efficacy of 1% and 3% topical minocycline gel in patients with papulopustular rosacea
Authors: G. Webster, Z.D. Draelos, E. Graber, M.S. Lee, S. Dhawan, M. Salman, G.N. Magrath
Journal: British Journal of Dermatology (2020)

Papulopustular rosacea is characterized by chronic facial erythema and inflammatory facial lesions. Minocycline has anti-inflammatory properties which may be effective in the treatment of rosacea inflammatory lesions.To assess the safety and efficacy of once-daily topical minocycline gel 1% and 3% in patients with papulopustular rosacea.This was a prospective, 12-week, double-blinded study conducted at 26 sites in the United States; 270 patients with papulopustular rosacea and 12-40 inflammatory lesions were randomized to minocycline 1%, minocycline 3% or vehicle. The primary endpoint was the mean change in inflammatory lesions at week 12. Key secondary endpoints included success on an Investigator's Global Assessment (IGA).Baseline mean lesion counts were 24·6, 25·1 and 24·3 in the minocycline 1%, minocycline 3% and vehicle groups, respectively; at week 12, the counts had decreased by 12·6, 13·1 and 7·9, respectively. Minocycline significantly decreased lesions, compared with the vehicle [P = 0·01, 95% confidence interval (CI) 7·9 to 0·9, for minocycline 1%; P = 0·007, 95% CI 8·3 to 1·3, for minocycline 3%]. The proportion of patients achieving IGA success was 39% in the minocycline 1% arm [P = 0·34, odds ratio (OR) 1·396 and OR 95% CI 0·71 to 2·75 vs. vehicle], 46% in the minocycline 3% arm (P = 0·04, OR 2·03 and OR 95% CI 1·04 to 3·95 vs. vehicle) and 31% in the vehicle arm.Minocycline topical gel appears to be safe and tolerable at concentrations of 1% and 3%, and both concentrations significantly decreased inflammatory lesion counts, with a significantly larger proportion of patients achieving IGA success at week 12 in the minocycline 3% arm. These findings support further evaluation of minocycline gel for treating inflammatory lesions associated with papulopustular rosacea. Linked Comment: Hampton. Br J Dermatol 2020; 183:412-413.
Osteoporosis Screening in Younger Postmenopausal Women
Authors: Carolyn J. Crandall, Kristine E. Ensrud
Journal: JAMA (2020)

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
Maintenance Pemetrexed (PEM) Plus Best Supportive Care (BSC) Versus Placebo Plus BSC after PEM Plus Cisplatin for Advanced Nonsquamous NSCLC
Authors: C.K. Obasaju, L.G. Paz-Ares, F. De Marinis, M. Dediu, M. Thomas, J.L. Pujol, P. Bidoli, O. Molinier, T.P. Sahoo, E. Laack, M. Reck, J. Corral, S.A. Melemed, W.J. John, N. Chouaki, A. Zimmermann, C.M. Visseren-Grul, C. Gridelli
Journal: Annals of Oncology (2012)