Disease prognosis and therapeutic strategies in patients with advanced non-small cell lung cancer (NSCLC): a 6-year epidemiological study between 2015-2021.

Background: Lung cancer is the top cause of mortality in males and the second largest cause of cancer-related fatalities in women worldwide. Non-small cell lung cancer (NSCLC) cases are discovered at an advanced stage, raising major challenges in disease management and survival outcomes. This study aimed to investigate the clinical findings and management of stage IIIB and IV NSCLC patients for better decision-making, disease management, and understanding of this fatal disease. Methods: In this cohort study of 340 patients, a total of 140 (41.2%) were diagnosed with advanced-stage NSCLC at a mean age of 64 years. The electronic data of patients from 2015 to 2021 who met the inclusion criteria were retrieved from two tertiary hospitals in Riyadh, Saudi Arabia, and an Excel sheet was used to record the variables. Patients' data including all categorical variables such as gender, stage, metastasis, ALK, EGFR, and ROS, etc., and continuous variables such as age and body mass index (BMI) were retrieved and analyzed. Results: The multivariate Cox-regression model indicated that smoking was the significant risk factor of death for two-thirds of male smokers (37.9%), with a median survival time of 123 days. Disease progression was higher with pleural and brain metastasis, and localized metastasis was the highest in 75% of patients. The intent of treatment was mainly palliative, however, a statistically significant association was found with the simultaneous use of chemotherapy and immunotherapy. Patients' response to first-line treatment revealed a significant improvement if chemotherapy treatment was maintained at the same dose without interruption of dosage. Conclusions: The overall cure and survival rates for NSCLC remain low, particularly in metastatic disease. Therefore, continued research into new drugs and combination therapies is required for better decision-making to expand the clinical benefit to a broader patient population and to improve outcomes in NSCLC.

Evolutionary analysis of LMP-1 genetic diversity in EBV-associated nasopharyngeal carcinoma: Bioinformatic insights into oncogenic potential.

EBV latent membrane protein 1 (LMP-1) is an important oncogene involved in the induction and maintenance of EBV infection and the activation of several cell survival and proliferative pathways. The genetic diversity of LMP-1 has an important role in immunogenicity and tumorigenicity allowing escape from host cell immunity and more metastatic potential of LMP-1 variants. This study explored the evolutionary of LMP-1 in EBV-infected patients at an advanced stage of nasopharyngeal carcinoma (NPC). Detection of genetic variability in LMP-1 genes was carried out using Sanger sequencing. Bioinformatic analysis was conducted for translation and nucleotide alignment. Phylogenetic analysis was used to construct a Bayesian tree for a deeper understanding of the genetic relationships, evolutionary connections, and variations between sequences. Genetic characterization of LMP-1 in NPC patients revealed the detection of polymorphism in LMP-1 Sequences. Motifs were identified within three critical LMP-1 domains, such as PQQAT within CTAR1 and YYD within CTAR2. The presence of the JACK3 region at specific sites within CTAR3, as well as repeat regions at positions (122-132) and (133-143) within CTAR3, was also annotated. Additionally, several mutations were detected including 30 and 69 bp deletions, 33 bp repeats, and 15 bp insertion. Although LMP-1 strains appear to be genetically diverse, they are closely related to 3 reference strains: prototype B95.8, Med- 30 bp deletion, and Med + 30 bp deletion. In our study, one of the strains harboring the 30 bp deletion had both bone and bone marrow metastasis which could be attributed to the fact that LMP-1 is involved in tumor metastasis, evasion and migration of NPC cells. This study provided valuable insights into genetic variability in LMP-1 sequences of EBV in NPC patients. Further functional studies would provide a more comprehensive understanding of the molecular characteristics, epidemiology, and clinical implications of LMP-1 polymorphisms in EBV-related malignancies.

Revisiting macrophages in ovarian cancer microenvironment: development, function and interaction.

Tumor-associated macrophages (TAMs) are an important component of the tumor microenvironment (TME) and have been linked to immunosuppression and poor prognosis. TAMs have been shown to be harmful in ovarian cancer (OC), with a positive correlation between their high levels of tumors and poor overall patient survival. These cells are crucial in the progression and chemoresistance of OC. The primary pro-tumoral role of TAMs is the release of cytokines, chemokines, enzymes, and exosomes that directly enhance the invasion potential and chemoresistance of OC by activating their pro-survival signalling pathways. TAMs play a crucial role in the metastasis of OC in the peritoneum and ascities by assisting in spheroid formation and cancer cell adhesion to the metastatic regions. Furthermore, TAMs interact with tumor protein p53 (TP53), exosomes, and other immune cells, such as stem cells and cancer-associated fibroblasts (CAFs) to support the progression and metastasis of OC. In this review we revisit development, functions and interactions of TAMs in the TME of OC patients to highlight and shed light on challenges and excitement down the road.