Resistance to 2-Hydroxy-Flutamide in Prostate Cancer Cells Is Associated with the Downregulation of Phosphatidylcholine Biosynthesis and Epigenetic Modifications.

In this study, we examined the metabolic adaptations of a chemoresistant prostate cancer cell line in comparison to a sensitive cell line. We utilized prostate cancer LNCaP cells and subjected them to a stepwise increase in the antiandrogen 2-hydroxy-flutamide (FLU) concentration to generate a FLU-resistant cell line (LN-FLU). These LN-FLU cells displayed characteristics of cancer stem cells, exhibited drug resistance, and showed a significantly reduced expression of Cyclin D1, along with the overexpression of p16, pointing to a proliferation arrest. In comparing the cancer stem-like LN-FLU cells to the LNCaP cells, we observed a decrease in the expression of CTP-choline cytidylyl transferase α (CCTα), as well as a decline in choline kinase, suggesting altogether a downregulation of the phosphatidylcholine biosynthetic pathway. In addition, we found decreased levels of the protein methyl transferase PRMT2 and the upregulation of the histone deacetylase Sirtuin1 (Sirt1). Analysis of the human prostate cancer samples revealed similar results in a population with high expressions of the stem cell markers Oct4 and ABCB1A1. Our findings suggest that the adaptation of prostate cancer cells to antiandrogens could induce reprogramming into stem cells that survive in a low phosphocholine metabolism and cell cycle arrest and display drug resistance.

Assessment of the needs for palliative care in advanced chronic patients on discharge. / Valoración de la necesidad de atención paliativa de pacientes crónicos avanzados en el momento del alta hospitalaria.

OBJECTIVES: To describe the advanced chronic patients admitted to an internal medicine department and to identify whether they meet the criteria for the need for palliative care at the time of hospital discharge according to the NECPAL-CCOMS.ICO® instrument. MATERIAL AND METHODS: Observational, descriptive and cross-sectional study performed on patients admitted to the internal medicine department of the Hospital Clínico Universitario Lozano Blesa (Saragossa), with a diagnosis of advanced progressive chronic diseases, from May 1, 2017 to September 1, 2017 Variables: sex, age, advanced chronic disease, reason for admission, primary caregiver, origin (residence, address, etc.), number of readmissions in the previous year, existence of advance directives, disability of the patient, existence of order not to resuscitate, Charlson Index and all the variables contained in the NECPAL Instrument CCOMS-ICO ® VERSION 3.0 2016. The data collection was done when the patient was scheduled to be discharged, having resolved the acute circumstance that led to the admission. RESULTS: the sample size was 142 patients who met the inclusion criteria: diagnosis of disease advanced evolutionary chronic ages, Charlson Index ≥3 at the time the patient was scheduled to be discharged and signed their informed consent. The average age was 85.80 years and 50.7% were men. The average age of the women was higher than that of the men. The most prevalent advanced chronic disease was chronic heart disease. None of the patients had advance care directives in place.. Nutritional, functional, cognitive and severe dependence was determined in more than 50%. In more than 90% there was the presence of geriatric syndromes and persistent symptoms. The presence of emotional distress was also evident, as was the use of resources. CONCLUSIONS: A palliative approach in the care of chronicity would have a very positive impact on the quality of life of the patient and family, would positively influence health systems and would result in cost savings. Implementing the NECPAL CCOMS-ICO® instrument in the health services that serve high proportions of chronically ill patients, accompanied by training measures for health personnel and adaptation of resources, can introduce a qualitative and quantitative change that is very relevant in our the health system.