Membrane translocation and activation of GnRH receptor sensitize prostate cancer cells to radiation.

BACKGROUND: GnRH analogs are widely used as neoadjuvant agents for radiotherapy in prostate cancer (PCa) patients, with well-documented effects in reducing tumor bulk and increasing progression-free survival. GnRH analogs act locally in the prostate by triggering apoptosis of PCa cells via activation of the GnRH receptor (GnRHR). During PCa progression, the distribution of GnRHR within the cell is altered, with reduced expression in the cell membrane and remaining sequestered in the endoplasmic reticulum. Pharmacoperone IN3 is able to relocalize GnRHR to the cell membrane. The aim of this study was to evaluate the effect of radiation on PCa cells pretreated with leuprolide, alone or in combination with IN3, as radiosensitizers. MATERIAL AND METHODS: PC3 and human PCa primary cell cultures were treated with IN3 for 24 h, followed by different doses of leuprolide for 48 h and, finally, single doses of radiation (3, 6, and 9 Gy). After radiation, cell survival, apoptosis, cell cycle distribution, and colony growth were evaluated. RESULTS: Radiation reduced cell survival and increased apoptosis in a dose-dependent manner. This effect was also directly related to leuprolide concentration. Pretreatment with IN3 enhanced apoptosis and decreased cell survival, also observing a higher proportion of cells arrested in G2. CONCLUSION: Neoadjuvant leuprolide increases radiation-mediated apoptosis of PCa cells. This effect was enhanced by pretreatment with pharmacoperone IN3. Clinical use of IN3 as a radiosensitizer combined with androgen deprivation therapy to improve survival of patients with PCa remains to be evaluated.

Consideraciones radiológicas del cáncer de pulmón y Covid-19: una mirada oncológica / Radiological considerations of lung cancer and Covid-19: a oncology look

Patients with SARS-Cov-2 infection and lung cancer have an unfavorable prognosis, characterized by higher rates of respiratory failure, use of invasive mechanical ventilation and higher mortality rates. Due to similarities in affected organs in Covid-19 and lung cancer, the radiological accurate diagnosis has become a challenge for physicians. Radiologic findings of lung cancer, such as parenchymal consolidation, spiculation and microlobulations are not specific. Imaging findings of Covid-19 in patients with lung cancer consist of multiple patchy multifocal bilateral ground-glass opacities and consolidations, being hardly distinguishable from an underlying lung malignancy. Differential radiological diagnosis in patients with lung cancer and Covid-19 must include pneumonitis and lung toxicity caused by chemotherapy, target therapies and radiotherapy. Follow-up and simulation tomography in radiotherapy have become an unexpected ally in the early detection of Covid-19 in asymptomatic stages in lung cancer patients. Patients with lung cancer should have particular considerations due to their high risk and the adverse effects of systemic therapies and radiotherapy. (AU)