RESUMO
Since its development in 1943, lidocaine has been one of the most commonly used local anesthesia agents for surgical procedures. Lidocaine alters neuronal signal transmission by prolonging the inactivation of fast voltage-gated sodium channels in the cell membrane of neurons, which are responsible for action potential propagation. Recently, it has attracted attention due to emerging evidence suggesting its potential antitumor properties, particularly in the in vitro setting. Further, local administration of lidocaine around the tumor immediately prior to surgical removal has been shown to improve overall survival in breast cancer patients. However, the exact mechanisms driving these antitumor effects remain largely unclear. In this article, we will review the existing literature on the mechanism of lidocaine as a local anesthetic, its effects on the cancer cells and the tumor microenvironment, involved pathways, and cancer progression. Additionally, we will explore recent reports highlighting its impact on clinical outcomes in cancer patients. Taken together, there remains significant ambiguity surrounding lidocaine's functions and roles in cancer biology, particularly in perioperative setting.
Assuntos
Anestésicos Locais , Progressão da Doença , Lidocaína , Neoplasias , Humanos , Lidocaína/uso terapêutico , Lidocaína/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Anestésicos Locais/uso terapêutico , Anestésicos Locais/farmacologia , Anestésicos Locais/administração & dosagem , Animais , Microambiente Tumoral/efeitos dos fármacos , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologiaRESUMO
Gastric cancer (GC) remains a lethal disease, with over 26,000 new cases and more than 11,000 deaths annually in the US. Thus, a deeper understanding of GC biology is critical to improve survival. Myogenesis is the formation of muscle fibers, which is a mesodermal tissue. In cancer, epithelial-to-mesenchymal transition (EMT) is a known phenomenon that promotes metastasis and poor survival. Given that myogenesis produces mesenchymal cells, we hypothesized that GC with increased myogenesis is linked to aggressive tumor behaviors and less favorable outcomes. In this study, three GC patient cohorts: TCGA (n=375), GSE26253 (n=432), and GSE84437 (n=482), were analyzed. The "MYOGENESIS" set in the Hallmark collection which comprises 200 myogenesis-related genes was analyzed to perform gene set variation analysis to create a score to quantify the myogenesis activity. Our results showed that T category of AJCC cancer staging that reflects the tumor invasion to stomach wall consistently correlated with myogenesis activity in two GC cohorts. High myogenesis GC was associated with lower cell proliferation, evidenced by reduced proliferation scores, decreased Ki67 gene expression, and less enrichment of E2F Targets, G2M checkpoint, MYC Targets V1, and V2 gene sets. High myogenesis tumors showed increased stromal cells (fibroblasts and adipocytes) infiltration within the tumor microenvironment, as well as less silent and non-silent mutation rates and copy number alterations. Higher lymphocyte infiltration, leukocyte fraction, T-cell receptor richness, and B-cell receptor richness were associated with high myogenesis GC. However, infiltration of CD4 cells, T helper type 1 and 2 cells, Natural Killer cells, regulatory T cells, and plasma cells was lower, with increased infiltration of dendritic cells in high myogenesis GC. High myogenesis GC enriched EMT, Hedgehog, TGF-ß, and KRAS gene sets. Furthermore, it was associated with enhanced angiogenesis, evidenced by enrichment of Angiogenesis, Coagulation, and Hypoxia gene sets, and increased infiltration of microvascular and lymphatic endothelial cells and pericytes. High myogenesis GC consistently correlated with worse overall survival in all three cohorts, and worse disease-specific and progression-free survival in the TCGA cohort. Hence, our findings suggest that GC with enhanced myogenesis is associated with decreased cell proliferation, increased EMT and angiogenesis, and worse prognosis.
RESUMO
BACKGROUND: Traumatic brain injury (TBI) due to single-level falls (SLF) are frequent and often require interhospital transfer. This retrospective cohort study aimed to assess the safety of a criteria for non-transfer among a subset of TBI patients who could be observed at their local hospital, vs mandatory transfer to a level 1 trauma center (L1TC). METHODS: We conducted a 7-year review of patients with TBI due to SLF at a rural L1TC. Patients were classified as transfer/non-transfer according to the Brain Injuries in Greater East Texas (BIGTEX) criteria. The primary outcome measure was the occurrence of a critical event defined as deteriorating repeat head computed tomography (CT) scan or neurological status, neurosurgical intervention, or death. RESULTS: Of the 689 included patients, 63 (9.1%) were classified as non-transfer. Although there were 4 cases with a neurological change and one with a head CT change among the non-transfer group, there were no neurosurgical procedures or deaths. The Cox Proportional Hazard model showed a near 3-fold increased risk of experiencing a critical event if classified as a non-transfer. The multivariable regression model showed patients with an Abbreviated Injury Scale (AIS) of 3 was twice as likely to experience a critical event, with an AIS of 4, three times, and 3 times more likely to be classified to transfer. DISCUSSION: The BIGTEX criteria identify a subset of patients who can safely be observed at their local hospital. To confirm the safety and efficacy of this transfer criteria recommendation, a prospective study is warranted.