Malignant pleural mesothelioma (MPM) is an aggressive cancer with dismal prognosis, largely due to poor response rates to and rapid relapse after first-line pemetrexed (MTA)/cisplatin chemotherapy. A better understanding of the molecular mechanisms underlying chemotherapy sensitivity and duration represents a significant but still unmet clinical need. In this study, we reported on a kinome CRISPR/Cas9 knockout screen that identified several G-M checkpoint kinases, including WEE1, whose loss of function sensitizes MPM cells to standard chemotherapy. We further showed that deregulation of the G-M checkpoint contributes to chemotherapy resistance, and that WEE1 inhibition synergizes with cisplatin/MTA, leading to enhanced MPM cell death and potent antitumor effects Mechanistically, WEE1 blockage overrides chemotherapy-induced G-M cell-cycle arrest and promotes premature mitotic entry, which causes DNA damage accumulation and ultimately apoptosis. Our results suggest a new therapeutic combination for MPM, and support the application of CRISPR/Cas9-based functional genomics in identifying novel therapeutic targets to potentiate existing cancer therapies.
Introduction: Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by rapidly enlarging, painful ulcers with undermined borders. The management of PG is challenging due to the lack of standardized evidence-based treatments.
Areas Covered: This review examines recent efforts to establish standardized outcomes for clinical trials to facilitate the drug development process for PG.
Introduction: Duchenne muscular dystrophy (DMD) is a severe X-linked disorder characterized by progressive muscle weakness and eventual death due to cardiomyopathy or respiratory complications. Currently, there is no cure for DMD, with standard treatments primarily focusing on symptom management. Using immunosuppressive measures and optimized vector designs allow for gene therapies to better address the underlying genetic cause of the disease.
Objectives: This study aimed to evaluate the efficacy of low-dose interleukin (IL-2) treatment for bullous pemphigoid (BP) caused by anti-programmed cell death protein 1/ligand 1 (PD-1/PD-L1) inhibitors.
Methods: Low-dose IL-2 treatment was standardized for BP. The Bullous Pemphigoid Disease Area Index (BPDAI), 5D-Itch Scale (5D-IS), and Dermatology Life Quality Index (DLQI) were recorded before and after treatment, and hexachromatic lymphocytes, regulatory T cells (Treg cells), and cytokines were measured.
Background And Objectives: The standard of care for patients with metastatic hormone-sensitive prostate cancer (mHSPC) includes androgen deprivation therapy (ADT), novel antihormonal therapies (NHT) and/or chemotherapy. Patients with newly diagnosed oligometastatic prostate cancer (omPCa) represent a distinct subgroup of mHSPC, for which the optimal treatment, particularly the role of radical prostatectomy (RP) and metastasis-directed therapy (MDT), is currently under debate.
Materials And Methods: In this single center, retrospective analysis, 43 patients with newly diagnosed omPCa were included.
With no effective treatments for functional recovery after injury, spinal cord injury (SCI) remains one of the unresolved healthcare challenges. Human induced pluripotent stem cell (hiPSC) transplantation is a versatile patient-specific regenerative approach for functional recovery after SCI. Injectable electroconductive hydrogel (ECH) can further enhance the cell transplantation efficacy through a minimally invasive manner as well as recapitulate the native bioelectrical microenvironment of neural tissue.
