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Biomedical subjects

Masanobu Uchiyama

Publications and source records attributed to Masanobu Uchiyama.

2 recordsLinked to original sources

[A Case of Stage Ⅳ Lung Adenocarcinoma with Bilateral Breast Metastases Mimicking Inflammatory Breast Cancer].

Breast metastases from primary lung cancers with inflammatory breast cancer (IBC)-like features are rare. Here, we report a patient with bilateral breast metastases from an advanced lung adenocarcinoma that mimicked IBC. A 67-year-old woman was diagnosed with right middle lobe lung adenocarcinoma with pleural and peritoneal dissemination (cT2aN2M1c, cStage ⅣB) and received systemic therapy. Twenty-nine months later, skin erythema and edema appeared in both breasts, suggesting bilateral IBC. Core needle biopsies of both breasts revealed atypical carcinomas without intraductal or lobular in situ components. Immunohistochemistry showed thyroid transcription factor-1 and Napsin A positivity and GATA3 negativity, supporting the diagnosis of metastatic lung adenocarcinoma of the breasts. Comprehensive genomic profiling of the breast specimen revealed an EGFR exon 19 deletion, and osimertinib achieved disease control within 1 year. This report highlights a diagnostic pitfall in which lung adenocarcinoma metastasis to the breast mimics IBC and underscores the importance of biopsy, an appropriate immunohistochemical panel, and molecular testing to establish a correct diagnosis and guide optimal systemic therapy.

Humans

Vinigrol Tricyclic Scaffold Biosynthesis Employs an Atypical Terpene Cyclase and a Multipotent Cyclization Cascade.

Vinigrol (1) is a fungal diterpenoid consisting of a decahydro-1,5-butanonaphthalene ring system with no analogs in nature. Despite immense efforts in synthetic studies, the vinigrol biosynthesis pathway remains largely unknown. Herein, we identified a biosynthetic gene cluster for 1 and fully elucidated the biosynthetic pathway. By employing an AlphaFold-generated model structure, we identified the possible catalytic residues of the noncanonical terpene cyclase and analyzed their function by site-directed mutagenesis. We found that the G340A mutation opened a cryptic pathway for an unprecedented tetracyclic diterpene, defined here as virgarene. Retro-biosynthetic theoretical analysis provided a solid foundation for the complex cyclization pathway for the vinigrol scaffold, its chemical transformation to a structurally distinct bonnadiene, and redirection of the enzymatic cyclization cascade to virgarene. Close inspection of the terpene cyclization pathway via integrated experimental and theoretical approaches would allow efficient exploration of novel terpenoid chemistries.

Cyclization