Emerging Therapeutic Implications of <i>STK11</i> Mutation: Case Series

Abstract STK11 was first recognized as a tumor suppressor gene in the late 1990s based on linkage analysis of patients with Peutz-Jeghers syndrome. STK11 encodes LKB1, an intracellular serine-threonine kinase involved in cellular metabolism, cell polarization, regulation of apoptosis, and DNA damage response. Recurrent somatic loss-of-function mutations occur in multiple cancer types, most notably in 13% of lung adenocarcinomas. Recent reports indicate that KRAS-mutant non-small cell lung cancers harboring co-mutations in STK11 do not respond to PD-1 axis inhibitors. We present three patients with STK11-mutated tumors and discuss the proposed mechanisms by which germline and somatic alterations in STK11 promote carcinogenesis, potential approaches for therapeutic targeting, and the new data on resistance to immune checkpoint inhibitors. Key Points STK11 is a tumor suppressor gene, and loss-of-function mutations are oncogenic, due at least in part to loss of AMPK regulation of mTOR and HIF-1-α. Clinical trials are under way, offering hope to patients whose STK11-mutated tumors are refractory and/or have progressed on chemotherapeutic regimens. Whether gastrointestinal cancers with STK11 loss of function will show the same outcome and potential refractoriness to immune therapy that were reported for lung cancer is unknown. However, physicians managing such patients should consider the experience in lung cancer, particularly outside the context of a clinical trial. In the CheckMate-057 trial lung tumors harboring co-mutations in KRAS and STK11 had an inferior response to PD-1 axis inhibitors. Coupled with the observation that STK11-mutated tumors were found to have a cold immune microenvironment regardless of KRAS status, the conclusion could extend to KRAS wild-type tumors with STK11 mutation. Current data suggest that the use of PD-1 axis inhibitors may be ill advised in the presence of STK11 mutation. </jats:sec

Evaluation of sacral bone parameters in Sex determination by three – dimensional CT images

Introduction: Gender determination in forensic medicine plays an important role in determining the identity which is very important for both the present time and in the future. (Aim)Background: To improve sex determination using skeletal remains, morphometrical study of some bones can be helpful. The aim of this study is to assess the application of five parameters of sacral bone by means of Three – Dimensional (3D) images reconstructed by multi-slice Computed Tomography (CT) in sex determination of Iranian individuals. &nbsp;Materials and Methods: This cross-sectional study was conducted on one hundred of Iranian people with equal number of men and women who have undergone Pelvic CT in radiology department of Hazrat Rasoul-Akram Hospital were included. Five anthropometric indices including S1 Perimeter, S1 Area, Anterior-posterior diameter (APD), Maximum transverse diameter (MTD) and Maximum breadth of sacral alae (MBA) of their sacral bone were measured using computed tomography (CT) three dimensional images with an accuracy of 0.01º and 0.01 mm and then the association of the measurements with the gender of individuals was studied. Conclusion:&nbsp; No significant difference was observed between two gender groups in terms of age (P=0.678).&nbsp