Purpose: This study aimed to investigate radiation-induced lesions on the skin in an experimental animal model. Methods and Materials: Cutaneous wounds were induced in Wistar rats by 4 MeV energy electron beam irradiation, using a dose rate of 240 cGy/min, for 3 different doses (10 Gy, 40 Gy, and 60 Gy). The skin was observed 5, 10, and 25 days (D) after ionizing radiation exposition. Results: Infiltrate inflammatory process was observed in D5 and D10, for the 40 Gy and 60 Gy groups, and a progressive increase of transforming growth factor β1 is associated with this process. It could also be noted a mischaracterization of collagen fibers at the high-dose groups. Conclusion: It was observed that the lesions caused by ionizing radiation in rats were very similar to radiodermatitis in patients under radiotherapy treatment. Advances in Knowledge: This study is important to develop strategies to prevent radiation-induced skin reactions.
5 May 2021 in International Journal of Radiation Biology
Purpose: Technological advancement in the treatment of cancer together with early detection and diagnosis have considerably improved the survival of breast cancer patients. On the other hand, the potential of patients developing side effects from cancer treatment are not negligible. Despite the progress that has been made in terms of early diagnosis, therapy, and survival, including improvements in the chemotherapeutic agents, radiation and molecular targeted therapies, cardiotoxicity of cancer therapy is still cause for concern. Radiation therapy for breast cancer is associated with increased risk of heart disease and myocardial infarction. Furthermore, the association of radiation therapy to chemotherapy is an important aspect to be considered in the development of cardiac disease, as this could play an additional role as a risk factor. Besides the heart effect, other side effects can be observed in the bone, ovary, uteri, and other organs. This paper aims to review the recent literature to present the current understanding of side effects associated with breast cancer treatment. The focus is on recent preclinical studies that have assessed potential changes in different organs that may be injured after breast cancer treatment, both due to both radiation and chemotherapy agents. Conclusion: Radiation-induced heart disease is one important side effect that must be considered during the treatment planning and patient follow-up. The cardiac damage can be potentialized when chemotherapy is associated to radiotherapy, and the literature findings indicate that heart fibrosis plays an important role at the radio-chemotherapy induced cardiac damage. Literature findings also showed important side effects at the bone, that can lead to ospeoporosis, due to the decrease of calcium, after radio or chemotherapy treatments. This decrease could be explained by the ovarian failure observed at rats after chemotherapy treatment. It is of great importance to acknowledge the complications originating from the treatment, so that new strategies can be developed. In this way, it will be possible to minimize side effects and improve the patients’ quality of life.
Assisted reproductive technologies (ART) may increase risk for abnormal placental development, preterm delivery and low birthweight. We investigated placental morphology, transporter expression and paired maternal/umbilical fasting blood nutrient levels in human term pregnancies conceived naturally (n = 10) or by intracytoplasmic sperm injection (ICSI; n = 11). Maternal and umbilical vein blood from singleton term (>37 weeks) C-section pregnancies were assessed for levels of free amino acids, glucose, free fatty acids (FFA), cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low-density lipoprotein (VLDL) and triglycerides. We quantified placental expression of GLUT1 (glucose), SNAT2 (amino acids), P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) (drug) transporters, and placental morphology and pathology. Following ICSI, placental SNAT2 protein expression was downregulated and umbilical cord blood levels of citrulline were increased, while FFA levels were decreased at term (p < 0.05). Placental proliferation and apoptotic rates were increased in ICSI placentae (p < 0.05). No changes in maternal blood nutrient levels, placental GLUT1, P-gp and BCRP expression, or placental histopathology were observed. In term pregnancies, ICSI impairs placental SNAT2 transporter expression and cell turnover, and alters umbilical vein levels of specific nutrients without changing placental morphology. These may represent mechanisms through which ICSI impacts pregnancy outcomes and programs disease risk trajectories in offspring across the life course.
1 February 2023 in Molecular and Cellular Endocrinology
Background: The placenta undergoes morphological and functional adaptations to adverse exposures during pregnancy. The effects ofsuboptimal maternal body mass index (BMI), preterm birth, and infection on placental histopathological phenotypes are not yet well understood, despite the association between these conditions and poor offspring outcomes. We hypothesized that suboptimal maternal prepregnancy BMI and preterm birth (with and without infection) would associate with altered placental maturity and morphometry, and that altered placental maturity would associate with poor birth outcomes. Methods: Clinical data and human placentae were collected from 96 pregnancies where mothers were underweight, normal weight, overweight, or obese, without other major complications. Placental histopathological characteristics were scored by an anatomical pathologist. Associations between maternal BMI, placental pathology (immaturity and hypermaturity), placental morphometry, and infant outcomes were investigated for term and preterm births with and without infection. Results: Fetal capillary volumetric proportion was decreased, whereas the villous stromal volumetric proportion was increased in placentae from preterm pregnancies with chorioamnionitis compared to preterm placentae without chorioamnionitis. At term and preterm, pregnancies with maternal overweight and obesity had a high percentage increase in proportion of immature placentae compared to normal weight. Placental maturity did not associate with infant birth outcomes. We observed placental hypermaturity and altered placental morphometry among preterm pregnancies with chorioamnionitis, suggestive of altered placental development, which may inform about pregnancies susceptible to preterm birth and infection. Conclusions: Our data increase our understanding of how common metabolic exposures and preterm birth, in the absence of other comorbidities or complications, potentially contribute to poor pregnancy outcomes and developmental programming.