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The discovery of immune checkpoint proteins such as PD-1/PDL-1 and CTLA-4 represents a significant breakthrough in the field of cancer immunotherapy. Therefore, humanized monoclonal antibodies, targeting these immune checkpoint proteins have been utilized successfully in patients with metastatic melanoma, renal cell carcinoma, head and neck cancers and non-small lung cancer. The US FDA has successfully approved three different categories of immune checkpoint inhibitors (ICIs) such as PD-1 inhibitors (Nivolumab, Pembrolizumab, and Cemiplimab), PDL-1 inhibitors (Atezolimumab, Durvalumab and Avelumab), and CTLA-4 inhibitor (Ipilimumab). Unfortunately, not all patients respond favourably to these drugs, highlighting the role of biomarkers such as Tumour mutation burden (TMB), PDL-1 expression, microbiome, hypoxia, interferon-γ, and ECM in predicting responses to ICIs-based immunotherapy. The current study aims to review the literature and updates on ICIs in cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is believed to be the most widespread carcinoma all over the world and the most frequent type of carcinoma among females in India. Approximately 40% of breast lesions which lead to breast cancer is detectable by breast self-examination (BSE). The identification of the barriers of early detection and the baseline knowledge on breast cancer symptoms, risk factors, BSE method and also the effectiveness of a health education intervention among females in Bangalore, India are the main purposes of this research. Methodology: The study was composed of totally 500 female participants from five different institutions in urban and rural of Bangalore in 2020. Assessing baseline knowledge on breast cancer and BSE using selfadministered questionnaires as well as administering interventional health education in the form of a lecture, pamphlets and illustration of proper method of conducting breast self-examination using video tutorials. Conclusion: The baseline knowledge about breast cancer and BSE practice among participants for early detection was found to be insufficient. However, we witnessed a great progress after immediate and follow up intervention. Periodic interventions are essential to prevent relapsing of certain types of barriers. [ABSTRACT FROM AUTHOR]

Objective(s): Adult T-cell leukemia/lymphoma (ATLL) is an aggressive lymphoid malignancy with low survival rate and distinct geographical distribution. In search for novel chemotherapeutics against ATLL, we investigated the combinatorial effects of parthenolide, a sesquiterpene lactone with valuable pharmaceutical activities, and arsenic trioxide (ATO) in vitro. Materials and Methods: MT2 cells, an ATLL cell line, were treated with increasing concentrations of parthenolide (1.25, 2.5, and 5 μg/ml) and ATO (2, 4, 8, and 16 μM) to determine their IC50. Then, cells were treated with a combination of sub-IC50 concentrations of parthenolide (1 μg/ml) and ATO (2 μM) for 72 hr. Cell viability and cell cycle changes were assessed by Alamar blue and PI staining, respectively. To understand the mechanisms responsible for observed effects, expression of CD44, NF-κB (REL-A), BMI-1, and C-MYC were investigated by real-time PCR. Results: Assessment of cell viability indicated that parthenolide significantly increased the toxicity of ATO, as confirmed by accumulation of MT2 cells in the sub G1 phase of the cell cycle. Moreover, molecular analysis revealed significant down-regulation of CD44, NF-κB (REL-A), BMI-1, and C-MYC upon combinatorial administration of parthenolide and ATO in comparison with relevant controls. Conclusion: Taken together, present results showed that parthenolide significantly enhanced the toxicity of ATO in MT2 cells. Therefore, the future possible clinical impact of our study could be combinatorial use of parthenolide and ATO as a novel and more effective approach for ATLL. [ABSTRACT FROM AUTHOR]