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Computational-aided rational mutation design of pertuzumab to overcome active HER2 mutation S310F through antibody-drug conjugates.
Proc Natl Acad Sci U S A
January 2025
Laboratory of Precision Medicine and Biopharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.
View Article and Find Full Text PDFLong-Term Clinical Outcomes for Bone-Anchored Hearing Implants: 3-Year Comparison Between Minimally Invasive Ponto Surgery and the Linear Incision Technique With Tissue Preservation.
Otol Neurotol
February 2025
Department of Otorhinolaryngology-Head and Neck Surgery, Donders Center for Neuroscience, Radboud University Medical Center, Radboud University, Nijmegen, the Netherlands.
Objective: To compare the 3-year outcomes of the modified minimally invasive Ponto surgery (m-MIPS) to both the original MIPS (o-MIPS) and linear incision technique with soft tissue preservation (LIT-TP) for inserting bone-anchored hearing implants (BAHIs).
Study Design: Prospective study with three patient groups: m-MIPS, o-MIPS, and LIT-TP.
Setting: Tertiary referral center.
Differentiation of antigen-activated B cells into pro-proliferative germinal center (GC) B cells depends on the activity of the transcription factors MYC and BCL6, and the epigenetic writers DOT1L and EZH2. GCB-like Diffuse Large B Cell Lymphomas (GCB-DLBCLs) arise from GCB cells and closely resemble their cell of origin. Given the dependency of GCB cells on DOT1L and EZH2, we investigated the role of these epigenetic regulators in GCB-DLBCLs and observed that GCB-DLBCLs synergistically depend on the combined activity of DOT1L and EZH2.
View Article and Find Full Text PDFAnesthetic management for upper arm amputation in a patient with acute rapid atrial fibrillation and a large thyroid goiter: A case report.
Medicine (Baltimore)
January 2025
Department of Anesthesiology, Yanbian University Hospital, Yanji, Jilin, P.R. China.
Rationale: Patients with atrial fibrillation and a large goiter have high perioperative risks and often cannot tolerate general anesthesia, making it necessary for us to explore new safe and effective anesthesia methods.
Patient Concerns: The patient presented with atrial fibrillation accompanied by rapid ventricular rate, a thrombus attached to the left atrial appendage, and a massive thyroid goiter compressing the airway.
Diagnosis: After the left humerus fracture surgery, the patient's internal fixation loosened and fractured, accompanied by infection, formation of sinus tracts, and suppuration.
Tunneled Pleural Catheters: An Effective Nonsurgical Alternative for Nonexpandable Lung in Chronic Pleural Infection.
J Bronchology Interv Pulmonol
January 2025
Division of Thoracic Surgery and Interventional Pulmonology, Beth Israel Deaconess Medical Center, Harvard Medical School.
Background: Open window thoracostomy (OTW) is the standard of care for debilitated patients with chronic pleural infection and nonexpandable lungs (NEL) who are not candidates for major surgical intervention. Tunneled pleural catheters (TPC) offer tremendous treatment potential in this setting based on their efficacy in malignant pleural effusion and NEL. We aim to assess the efficacy, safety, and health care utilization of TPC in this setting.
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