Identification of the BRAF V600E mutation in a patient with sclerosing pneumocytoma: A case report
LUNG CANCER
Authors: Jiang, Guanming; Zhang, Min; Tan, Qinquan; Lin, Shunhuan; Zeng, Yihong; Liu, Chun; Chen, Rongrong; Zhou, Jianping
Abstract
Objectives: Sclerosing pneumocytoma (sclerosing hemangioma, SP) is a rare benign tumor of the lung with a low risk of recurrence. The genomic profile of SP is not well-known. Here we report gene mutation findings in a 17year-old girl with SP. Materials and methods: Immunohistochemistry (IHC), next-generation sequencing (NGS), and sanger sequencing were performed on the tumor tissue of this patient for pathological diagnosis and gene mutation analysis. Results and conclusion: Two mutations were identified in the tumor tissue by NGS and sanger sequencing: AKT1 E17K and BRAF (B-Raf proto-oncogene, serine/threonine kinase) V600E. This is the first case report of a BRAF V600E mutation in a patient with SP. This discovery extends our understanding of the pathogenesis of SP, and suggests the need for future testing of BRAF V600E in this rare tumor type.
In silicodrug design and molecular docking studies targeting Akt1 (RAC-alpha serine/threonine-protein kinase) and Akt2 (RAC-beta serine/threonine-protein kinase) proteins and investigation of CYP (cytochrome P450) inhibitors against MAOB (monoamine oxidase B) for OSCC (oral squamous cell carcinoma) treatment
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
Authors: Sharif Siam, Mohammad Kawsar; Sarker, Anusree; Sayeem, Mohammad Manzur Sharif
Abstract
The overexpression of Akt1 (RAC-alpha serine/threonine-protein Kinase) and Akt2 (RAC-beta serine/threonine-protein Kinase) is a hallmark of Oral Squamous Cell Carcinoma (OSCC). Because of the elevated frequency of OSCC occurrence in South Asian countries, novel therapeutic approaches are indispensable. Drugs that inhibit the overexpression of Akt1 and Akt2 proteins in Akt pathway and do not cause reduced expression of MAOB can be leads for OSCC treatment. In this study, Akt1, Akt2 and MAOB were targeted and 100 CYP inhibitors were screened through severalin silicoapproaches and Galuteolin and Linarin were identified as potential leads for OSCC treatment as they inhibited Akt1 proteins with strong binding affinities of -12.3 and -11.5 kcal/mol respectively and also Akt2 proteins with strong binding affinities of -11.4 and -11.1 kcal/mol respectively, but they did not inhibit MAOB. Decreased expression of MAOB in tissues causes OSCC but overexpression is also responsible for other types of diseases and cancers. From the investigation of CYP inhibitors against MAOB, five CYP inhibitors- Diosmetin, Acacetin, Epicatechin, Eriodictyol and Capillin have expressed inhibitory action against MAOB without any interference with Akt1 and Akt2. This study mainly represents that Galuteolin and Linarin in the Akt pathway can be perceived for OSCC treatment and other five CYP inhibitors - Diosmetin, Acacetin, Epicatechin, Eriodictyol and Capillin for the treatment of other diseases and cancers caused by overexpression of MAOB. ADMET properties of CYP inhibitors obtained from admetSAR 2.0 and were compared with reference drugs for validation. Communicated by Ramaswamy H. Sarma.