Triple-negative subtype of breast cancer (TNBC) is hallmarked by frequent disease relapse and shows highest mortality rate. Although PD-1/PD-L1 immune checkpoint blockades have recently shown promising clinical benefits, the overall response rate remains largely insufficient. Hence, alternative therapeutic approaches are warranted. Given the immunosuppressive properties of CD73-mediated adenosine release, CD73 blocking approaches are emerging as attractive strategies in cancer immunotherapy. Understanding the precise mechanism regulating the expression of CD73 is required to develop effective anti-CD73-based therapy. Our previous observations demonstrate that the transcription factors driving epithelial-to-mesenchymal transition (EMT-TF) can regulate the expression of several inhibitory immune checkpoints. Here we analyzed the role of the EMT-TF SNAI1 in the regulation of CD73 in TNBC cells. We found that doxycycline-driven SNAI1 expression in the epithelial -like TNBC cell line MDA-MB-468 results in CD73 upregulation by direct binding to the CD73 proximal promoter. SNAI1-dependent upregulation of CD73 leads to increased production and release of extracellular adenosine by TNBC cells and contributes to the enhancement of TNBC immunosuppressive properties. Our data are validated in TNBC samples by showing a positive correlation between the mRNA expression of CD73 and SNAI1. Overall, our results reveal a new CD73 regulation mechanism in TNBC that participates in TNBC-mediated immunosuppression and paves the way for developing new treatment opportunities for CD73-positive TNBC.
Background Colorectal cancer (CRC) is the third leading cause of malignancy in Syria. The aim of our study was to assess the awareness and knowledge of CRC and its screening methods among medical students at the University of Aleppo. Methods A cross-sectional study of medical students at the University of Aleppo was conducted using a self-administered 12-element questionnaire. The questionnaire consisted of demographics, awareness of CRC, knowledge of CRC and its screening methods. Awareness of CRC included three questions asking students if they ever heard of CRC and its screening methods. Knowledge of CRC was evaluated through three sets of questions about CRC risk factors, signs and symptoms, and preventative methods. The students were selected randomly during academic lectures. A χ 2 or Fisher's exact tests for categorical variables were used for statistical analysis, as appropriate. A two-sided p < 0.05 was considered statistically significant. We stratified students based on pre-clinical versus clinical years and average academic score. Results A total of 824 students completed the questionnaire. The majority of students were aware of CRC (98.9%) and CRC screening methods (79.8%). Students had poor knowledge of CRC risk factors (16.5% for non-modifiable factors and 11.7% for modifiable factors), signs and symptoms (52.6%), and protective factors (9.9%). Only 31.7% of students were able to identify the appropriate age to initiate screening for average-risk individuals. Clinical students had better awareness and knowledge of CRC and its screening methods. Clinical students with higher academic score showed better awareness and knowledge in some elements. Conclusion Our study reported high awareness and poor knowledge rates of CRC and its screening methods among medical students at the University of Aleppo. Although clinical students had higher awareness and knowledge of CRC compared to pre-clinical students, the impact of academic score revealed variable results.
Programmed death‐ligand 1 (PD‐L1) expression has long been used as a biomarker to stratify patients with cancer who will benefit from anti‐PD‐1/PD‐L1 immunotherapy. However, the use of PD‐L1 as a biomarker to guide treatment decisions has recently been called into question due to its dynamic and heterogeneous expression within each tumor and among different tumors as well as during tumor cell plasticity. Therefore, understanding the molecular basis of PD‐L1 expression would enable delineating its value as a reliable biomarker in the clinic. Here, we provide our perspective on the involvement of CMTM6 and CMTM7 as new lead candidates for the regulation of PD‐L1 in breast tumors undergoing an epithelial to mesenchymal transition.
Background: Omental alveolar rhabdomyosarcoma in adults is a very hazardous tumor. Its pathogenesis is still under discussion and many studies consider it different from its pediatric counterpart. This tumor can arise from any soft tissue in the body thus it can be found anywhere, but it's found mainly in the head and neck region. Omentum as the primary site was reported only by six studies in the English literature before. In this paper we aim to report the seventh case and perform a review of all paperworks that pertains to this topic. Case Presentation: we present a case of a 52 years old smoker male. His medical record was not significant. He presented with dull pain in the right iliac fossa. He had suffered from generalized abdominal pain in the past several months but this time the pain was unbearable. On examination he had a palpable mass in the region. CT revealed a mass arising from omentum. A laparotomy was performed and biopsies were taken, stained, examined and led to the diagnosis of ARMS. The patient was put on radio and chemo-therapy. He missed some appointments after that. When he was admitted 2 months later he was suffering from neurological symptoms which after performing lumbar puncture turned out to be tumor metastasis. Regrettably the patient died after his second cycle of chemotherapy.Conclusion: Adult rhabdomyosarcomas are rare tumors that can arise from any soft tissue including omentum and should be taken into consideration when we deal with primary tumors originating from that area. The studies and our understanding for this neoplasm is still so limited and should be expanded widely.
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