Purpose: Metaplastic carcinoma of the breast (MCB) is a rare cancer characterized by the histologic presence of two or more histological cell types originating from epithelial and mesenchymal stem cells. Patients with metastatic MCB have a low response rate to conventional chemotherapy and poor survival. Optimal treatment strategies for metastatic MCB are urgently needed.
Methods: We retrospectively reviewed a patient who had enrolled in the phase II/III seamless study, BELLE-4 (NCT01572727). The patient's response to the study drug assessed by an investigator per protocol and clinical course were examined and compared with those of the main cohorts in the BELLE-4 study.
Results: Our patient exhibited metastatic MCB and received systemic chemotherapy, paclitaxel (70 mg/m/week) and buparlisib (80 mg/day), a pan-class I phosphatidylinositol-3 kinase (PI3K) inhibitor. The optimal response was a confirmed partial response for 17 months in total. During the compassionated use program period, the tumor regrew when buparlisib was stop because of toxicity, and responded to the treatment again after resumed the buparlisib treatment. The overall survival of the patient after the development of metastatic MCB was 42 months. She experienced grade 3 hyperglycemia similar to that observed in the main cohort.
Conclusion: Buparlisib plus weekly paclitaxel might be a new treatment option for patients with metastatic MCB harboring a PIK3CA mutation. Additional prospective studies for investigating the efficacy of the proposed combination are warranted.
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http://dx.doi.org/10.1016/j.jfma.2018.12.004 | DOI Listing |
Nat Commun
January 2025
Department of Chemistry, New York University, New York, NY, USA.
Advancements in cryo-EM have stimulated a revolution in structural biology. Yet, for membrane proteins near the cryo-EM size threshold of approximately 40 kDa, including transporters and G-protein coupled receptors, the absence of distinguishable structural features makes image alignment and structure determination a significant challenge. Furthermore, resolving more than one protein conformation within a sample, a major advantage of cryo-EM, represents an even greater degree of difficulty.
View Article and Find Full Text PDFCirc Arrhythm Electrophysiol
December 2024
Department of Cardiology, Amsterdam UMC Location University of Amsterdam, Heart Center, Amsterdam Cardiovascular Sciences Heart failure and Arrhythmias, the Netherlands (L.R.A.O.N., S.P., L.V.A.B., T.F.B., A.-F.B.E.Q., W.v.d.S., L.S., J.A.d.V., J.G.P.T., N.R.B., J.R.d.G., K.M.K., A.d.W., A.A.M.W., R.E.K.).
Circ Cardiovasc Qual Outcomes
November 2024
Department of Cardiology, Amsterdam Cardiovascular Sciences Heart Failure and Arrhythmias, Amsterdam University Medical Centers Location University of Amsterdam, Heart Center, the Netherlands (R.E.K., J.A.d.V., L.V.A.B., T.F.B., S.P., A.-F.B.E.Q., L.S., W.v.d.S., A.d.W., J.R.d.G., K.M.K., J.G.P.T., A.A.M.W., L.R.A.O.N.).
N Engl J Med
November 2024
From the Section of Endocrinology and Metabolism, Department of Medicine, and Section of Pediatric Endocrinology, Department of Pediatrics, Yale Obesity Research Center (Y-Weight), Yale School of Medicine, New Haven, CT (A.M.J.); Diabetes Complications Research Centre, University College Dublin, Dublin (C.W.R.); Eli Lilly, Indianapolis (A.S., S.Z., R.B., M.C.B., N.N.A., I.J.); Comprehensive Weight Control Center, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine, New York (L.J.A.); Hospital 9 de Julho, São Paulo (B.H.); University of Toronto and Wharton Weight Management Clinic - both in Toronto (S.W.); the Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, United Kingdom (J.P.H.W.); and University of Colorado School of Medicine, Aurora (L.P.).
Background: Obesity is chronic disease and causal precursor to myriad other conditions, including type 2 diabetes. In an earlier analysis of the SURMOUNT-1 trial, tirzepatide was shown to provide substantial and sustained reductions in body weight in persons with obesity over a 72-week period. Here, we report the 3-year safety outcomes with tirzepatide and its efficacy in reducing weight and delaying progression to type 2 diabetes in persons with both obesity and prediabetes.
View Article and Find Full Text PDFPediatr Nephrol
November 2024
Inmunova SA, Ciudad Autónoma de Buenos Aires, Argentina.
Background: Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is a severe condition mainly affecting children. It is one of the leading causes of acute kidney injury in the pediatric population. There is no established therapy for this disease.
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