Adv Exp Med Biol
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The growing success of immune checkpoint inhibitors (ICIs) has led to effectively treating several types of cancers. Even though their use has been associated with the development of cardiac adverse effects, which may decrease the overall survival in cancer patients. ⋯ Although cardiotoxicities related to immunotherapy are reportedly rare, they can be severe and associated with life-threatening conditions such as fulminant myocarditis, hemodynamic instability, and cardiac arrest. We will review the most commonly reported cardiovascular toxicities associated with ICIs and their management.
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Myeloid-derived suppressor cells (MDSCs) represent a heterogenous population of immature myeloid cells capable of modulating immune responses. In the context of cancer, MDSCs are abnormally produced and recruited to the tumor microenvironment (TME) to aid in the establishment of an immunosuppressive TME that facilitates tumor escape. ⋯ In this chapter, we review MDSC characterization, development, expansion, and mechanisms that facilitate immunosuppression and tumor progression. Furthermore, we highlight studies demonstrating the clinical significance of MDSCs in various disease states in addition to strategies that modulate various aspects of MDSC biology for therapeutic gain.
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Chronic obstructive pulmonary disease (COPD) is a lung disease affected by both genetic and environmental factors. Therefore, the role of epigenetics in the pathogenesis of COPD has attracted much attention. ⋯ The present review aims at overviewing the effect of DNA methylation on etiology, pathogenesis, pathophysiological changes, and complications of COPD. The clarification of aberrant methylation of target genes, which play important roles in the initiation and progression of COPD, will provide new disease-specific biomarker and targets for early diagnosis and therapy.
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The interactions between tumor cells and the non-malignant stromal and immune cells that make up the tumor microenvironment (TME) are critical to the pathophysiology of cancer. Mesenchymal stem cells (MSCs) are multipotent stromal stem cells found within most cancers and play a critical role influencing the formation and function of the TME. MSCs have been reported to support tumor growth through a variety of mechanisms including (i) differentiation into other pro-tumorigenic stromal components, (ii) suppression of the immune response, (iii) promotion of angiogenesis, (iv) enhancement of an epithelial-mesenchymal transition (EMT), (v) enrichment of cancer stem-like cells (CSC), (vi) increase in tumor cell survival, and (vii) promotion of tumor metastasis. ⋯ Tumor-suppressive effects are observed when MSCs are used in higher ratios to tumor cells. Additionally, MSC function appears to be tissue type dependent and may rely on cancer education to reprogram a naïve MSC with antitumor effects into a cancer-educated or cancer-associated MSC (CA-MSC) which develops pro-tumorigenic function. Further work is required to delineate the complex crosstalk between MSCs and other components of the TME to accurately assess the impact of MSCs on cancer initiation, growth, and spread.
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Breast cancer diagnosed during pregnancy or lactation up to 1 year post-partum is often referred to as pregnancy-associated breast cancer (PABC) , although the definition varies with length of post-partum period. The incidence rate has been reported to range from 17.5 to 39.9 per 100,000 births, but the rate is substantially lower during pregnancy (ranging from 3.0 to 7.7) than during the post-partum period (ranging from 13.8 to 32.2). ⋯ In studies comparing outcomes in women with PABC to other young breast cancer patients, it is crucial to adjust for age, since the age distribution of PABC depends both on age at pregnancy and age at breast cancer. Large studies have shown similar prognosis for women with PABC compared to other young women with breast cancer, when accounting for differences in age, stage and other tumour characteristics.