Radiotherapy is commonly used for treating various types of cancer. In addition, adipose tissue is not routinely spared during typical radiation treatment. Although radiation is known to induce metabolic effects in patients, the effects of radiation therapy on adipose tissue have not been elucidated. Currently, few studies have investigated the impact of radiation exposure on adipose tissue, and these have primarily involved whole-body irradiation. This study aimed to understand the acutely persistent damage caused by clinically relevant radiation doses in adipocytes. Specifically, in vitro and in vivo, irradiated adipocytes increased reactive oxygen species (ROS) and lipid peroxidation levels and elevated lipolytic activity compared to unirradiated adipocytes. RNA sequencing also revealed the upregulation of senescence and inflammation pathways. We observed an increase in macrophage and T-cell accumulation at both 1 and 6 months after radiation exposure using in vivo models. Many of the changes observed in irradiated adipose tissue, including oxidative stress, metabolic dysfunction, inflammation, and senescence, are consistent with those observed in adipose tissue from obese patients, in which obesity is a known driver of many cancers. As adipose tissue damage is maintained chronically, protecting adipose tissue from the harmful effects of radiation exposure may improve radiation-induced toxicity and reduce cancer recurrence and progression.

Obesity is a common risk factor in multiple tumor types, including prostate cancer. Obesity has been associated with driving metastasis, therapeutic resistance, and increased mortality. The effect of adipose tissue on the tumor microenvironment is still poorly understood. This review aims to highlight the work conducted in the field of obesity and prostate cancer and bring attention to areas where more research is needed. In this review, we have described key differences between healthy adipose tissues and obese adipose tissues, as they relate to the tumor microenvironment, focusing on mechanisms related to metabolic changes, abnormal adipokine secretion, altered immune cell presence, and heightened oxidative stress as drivers of prostate cancer formation and progression. Interestingly, common treatment options for prostate cancer ignore the adipose tissue located near the site of the tumor. Because of this, we have outlined how excess adipose tissue potentially affects therapeutics’ efficacy, such as androgen deprivation, chemotherapy, and radiation treatment, and identified possible drug targets to increase prostate cancer responsiveness to clinical treatments. Understanding how obesity affects the tumor microenvironment will pave the way for understanding why some prostate cancers become metastatic or treatment-resistant, and why patients experience recurrence.

Acute radiation syndrome (ARS) occurs when hematopoietic or gastrointestinal cells are damaged by radiation exposure causing DNA damage to the bone marrow and gastrointestinal epithelial stem cell populations. In these highly proliferative cell types, DNA damage inhibits stem cell repopulation. In humans and animals, this inability to regenerate stem cells is lethal. Within this manuscript, several compounds, Amifostine, Captopril, Ciprofloxacin, PrC-210, 5-AED (5-androstene-3β,17β-diol), and 5-AET (5-androstene-3β,7β,17B-triol), are assessed for their ability to protect against ARS in an in vitro and/or in vivo setting. ARS was accomplished by irradiating mouse bone marrow cells or rat intestinal epithelial (IEC-6) cells in vitro with 4–8 Gy and in vivo by exposing Mus musculus to 7.3 Gy of whole-body irradiation. The primary endpoints of this study include cellular viability, DNA damage via γ-H2AX, colony formation, and overall survival at 30-days post-irradiation. In addition to evaluating the radioprotective performance of each compound, this study establishes a distinct set of in vitro assays to predict the overall efficacy of potential radioprotectors in an in vivo model of ARS. Furthermore, these results highlight the need for FDA-approved medical intervention to protect against ARS.

Large-scale radiation catastrophes and localized exposure incidents remain major threats to public health. Effective treatment following radiation exposure is challenging because radiation dose, timing, and affected tissues can vary widely between individuals. To better understand the biological response to radiation injury, we employed a multi-omics approach integrating transcriptomics, proteomics, and metabolomics. In this study, mouse bone marrow was analyzed at 1, 6, and 24 h after whole-body irradiation and compared with bone marrow from non-irradiated mice. Multivariate and univariate analyses revealed time-dependent changes across transcriptomic, proteomic, and metabolomic profiles. We further applied machine learning-based integrative analysis and biomarker discovery approaches to identify key molecular responses associated with radiation exposure. Integrated analysis showed that the acute radiation response in bone marrow included immune-related processes, followed by intermediate metabolic reprogramming, and later disruptions in cell cycle regulation. Biomarker analysis identified several promising candidates, including the transcripts Sapcd2 and Cd28, proteins FRIL1 and CDK1, and the metabolites 3-hydroxyisobutyrate and taurine. Overall, our findings demonstrate that bone marrow from irradiated mice undergoes dynamic and coordinated molecular changes over time. These responses include activation of ferroptosis defense mechanisms, mitotic dysfunction, and pathways associated with programmed cell death.