Discovery of a Phosphodiesterase 7A Inhibitor of High Isozyme Selectivity Exhibiting Anti-Osteoporotic Effects.

Phosphodiesterases (PDEs) have drawn attention due to their critical roles in physiological and pathological conditions. Many research groups have studied these hydrolytic enzymes to develop new drugs, including apremilast as a PDE4 inhibitor and sildenafil as a PDE5 inhibitor. Targeting PDE7 has also been deemed a rational strategy to ameliorate autoimmune conditions.

The Three-Class Annotation Method Improves the AI Detection of Early-Stage Osteosarcoma on Plain Radiographs: A Novel Approach for Rare Cancer Diagnosis.

: Developing high-performance artificial intelligence (AI) models for rare diseases is challenging owing to limited data availability. This study aimed to evaluate whether a novel three-class annotation method for preparing training data could enhance AI model performance in detecting osteosarcoma on plain radiographs compared to conventional single-class annotation. : We developed two annotation methods for the same dataset of 468 osteosarcoma X-rays and 378 normal radiographs: a conventional single-class annotation (1C model) and a novel three-class annotation method (3C model) that separately labeled intramedullary, cortical, and extramedullary tumor components.

Prostate Cancer Patient With Lymph-node Metastasis Treated Only With Methionine Restriction Has Stable Disease for Two Years Demonstrated With PET/CT and PSMA-PET Scanning and PSA Testing.

Background/aim: Metastatic prostate cancer is a recalcitrant disease. Our laboratory has previously treated prostate-cancer patients with methionine restriction effected by a low methionine diet and oral recombinant methioninase (o-rMETase), both alone and in combination with other agents. The present case is a 66-year-old patient who had a radical prostatectomy in 2019 with a Gleason score 3+3 and 3+4.

Elevated-c-MYC-expressing Fibrosarcoma Cells With Acquired Gemcitabine Resistance Remain Sensitive to Recombinant Methioninase: A Potential Clinical Strategy for a Recalcitrant Disease.

Background/aim: For second-line chemotherapy of soft-tissue sarcoma, gemcitabine is administered in combination with docetaxel. However, more effective treatments are required for advanced soft-tissue sarcoma, where the efficacy is limited. The purpose of the present study was to compare the efficacy of rMETase and gemcitabine against HT1080 human fibrosarcoma cells and Hs27 normal fibroblasts, as well as to identify and effectively treat HT1080 cells that are resistant to gemcitabine associated with elevated c-MYC.

Complete Response (CR) in a Previously-progressing Chronic Lymphocytic Leukemia (CLL) Patient Treated With Methionine Restriction in Combination With First-line Chemotherapy.

Background/aim: Chronic lymphocytic leukemia (CLL) is currently incurable. CLL is characterized by disordered DNA methylation. The aim of the present study was to target methylation with methionine restriction in a patient with progressive CLL.