Impact of COVID-19 on the performance of a radiation oncology department at a major comprehensive cancer centre in Poland during the first ten weeks of the epidemic.

The outbreak of SARS-CoV-2 coronavirus rapidly altered radiotherapy service delivery around the world. AIM: The main objective of this study was to assess the impact of precautionary measures implemented in response to the COVID-19 pandemic on the performance of a radiation oncology departments and on mitigation the risk of COVID-19 contagion between and among patients and staff. METHODS: The study period was from March 15 until May 22, 2020. We evaluated total number of patients irradiated and those who initiated treatments, taking into account tumours localisations. We assessed the relationship of potential risk of contagion with patients' domiciles locations in regions with high number of COVID19 case. RESULTS AND CONCLUSIONS: The number of patients treated with radiotherapy during the study period decreased due to precautionary measures. After five weeks, the number of radiotherapy treatments began to increase. Just over half of the radiotherapy patients (53.5%) treated at the GPCC reside in the city of Poznan or in one of the ten surrounding counties where COVID19 incidence was low and reached at the end of the study period cumulative number of cases n = 204. The precautionary measures were effective qRT-PCR tests were performed in 1545 individuals (patients and hospital staff) revealing four staff members and none patient with a positive PCR result. Immunoglobulin testing was performed in 1132 individuals (patients and hospital staff). A total of 63 individuals were positive for antibodies.

Genome-wide co-localization of active EGFR and downstream ERK pathway kinases mirrors mitogen-inducible RNA polymerase 2 genomic occupancy.

Genome-wide mechanisms that coordinate expression of subsets of functionally related genes are largely unknown. Recent studies show that receptor tyrosine kinases and components of signal transduction cascades including the extracellular signal-regulated protein kinase (ERK), once thought to act predominantly in the vicinity of plasma membrane and in the cytoplasm, can be recruited to chromatin encompassing transcribed genes. Genome-wide distribution of these transducers and their relationship to transcribing RNA polymerase II (Pol2) could provide new insights about co-regulation of functionally related gene subsets. Chromatin immunoprecipitations (ChIP) followed by deep sequencing, ChIP-Seq, revealed that genome-wide binding of epidermal growth factor receptor, EGFR and ERK pathway components at EGF-responsive genes was highly correlated with characteristic mitogen-induced Pol2-profile. Endosomes play a role in intracellular trafficking of proteins including their nuclear import. Immunofluorescence revealed that EGF-activated EGFR, MEK1/2 and ERK1/2 co-localize on endosomes. Perturbation of endosome internalization process, through the depletion of AP2M1 protein, resulted in decreased number of the EGFR containing endosomes and inhibition of Pol2, EGFR/ERK recruitment to EGR1 gene. Thus, mitogen-induced co-recruitment of EGFR/ERK components to subsets of genes, a kinase module possibly pre-assembled on endosome to synchronize their nuclear import, could coordinate genome-wide transcriptional events to ensure effective cell proliferation.

Bone mineral density in women with polycystic ovary syndrome.

PURPOSE: PCOS is a complex disorder and various features of this disorder may have great importance for bone metabolism. The aim of the study was to determine the relationship between existing hormonal disorders, and bone mineral density (BMD) in young women with PCOS. METHODS: 69 reproductive-aged PCOS women and 30 age-matched healthy controls were enrolled to the study women. In each individual we assessed the body mass index (BMI). We evaluated the serum concentrations of: gonadotropins, prolactin (PRL), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), testosterone (T), thyroid stimulating hormone (TSH), free thyroxine (fT4). We used the Homeostatic Model Assessment-Insulin Resistance Index (HOMA-IR) to diagnose insulin resistance. Bone mineral density in the lumbar spine was measured by dual-energy X-ray absorptiometry (DXA). RESULTS: The PCOS women had lower BMD values as compared to the controls (1.057 ± 0.1260 vs. 1.210 ± 0.1805 g/cm(2), p < 0.0002). In the analysis of PCOS patients according to BMI, only in the subgroup of the normal weight PCOS we find significantly lower BMD in comparison to controls (p = 0.0049). In patients with PCOS, BMD was positively correlated with insulin concentration and HOMA-IR. In the controls Z-score values were positively correlated with insulin concentration and HOMA-IR. CONCLUSIONS: The deleterious effect of estrogen deficiency on bones in PCOS is not balanced by androgen overproduction. Women with PCOS had significantly lower BMD of the lumbar spine compared to controls. Insulin seems to be one of the most important positive bone growth stimulators.