TNF-α/IL-1/NF-κB transduction pathway in human cancer prostate

TNFα exerts apoptosis throughout an intracellular transduction pathway that involves the kinase proteins TRAF-2 (integration point of apoptotic and survival signals), ASK1 (pro-apoptotic protein), MEK-4 (p38 activator and metastasis suppressor gene), JNK (stress mitogen activated protein kinase) and the transcription factor AP-1. TNFα also exerts proliferation by p38 activation, or when TRAF-2 simultaneously induces the transcription factor NF-κB by NIK. NIK and p38 may also be activated by IL-1. P38 activated several transcription factors such as Elk-1, ATF-2 and NF-κB. NIK also may activate NF-κB. The aim of the present article was to evaluate the different components of this TNFα/IL-1 transduction pathway in human prostate carcinoma (PC) in comparison with normal human prostate. In prostate cancer, pro-apoptotic TNFα/AP-1 pathway is probably inactivated by different factors such as p21 (at ASK-1 level) and bcl-2 (at JNK level), or diverted towards p38 or NIK activation. IL-1α enhances proliferation through IL-1RI that activates either NIK or p38 transduction pathway. P38 and NIK activate different transcription factors related with cell proliferation and survival such as ATF-2, Elk-1 or NF-κB. In order to search a possible target to cancer prostate treatment we proposed that inhibition of several proinflamatory cytokines such as IL-1 and TNFα might be a possible target for PC treatment, because decrease the activity of all transduction pathway members that activate transcription factors as NF-κB, Elk-1 or ATF-2.Ministerio de Educación y Cienci

Prognostic value of inhibitors of apoptosis proteins (IAPs) and caspases in prostate cancer: caspase-3 forms and XIAP predict biochemical progression after radical prostatectomy

Background: The expression status of apoptotic regulators, such as caspases and inhibitors of apoptosis proteins (IAPs), could reflect the aggressiveness of tumors and, therefore, could be useful as prognostic markers. We explored the associations between tumor expression of caspases and IAPs and clinicopathological features of prostate cancer – clinical and pathological T stage, Gleason score, preoperative serum PSA levels, perineural invasion, lymph node involvement, surgical margin status and overall survival – and evaluated its capability to predict biochemical progression after radical prostatectomy. Methods: Protein expression of caspases (procaspase-8, cleaved caspase-8, procaspase-3, cleaved caspase-3, caspase-7 and procaspase-9) and IAPs (cIAP1/2, cIAP2, NAIP, Survivin and XIAP) was analyzed by immunohistochemistry in radical prostatectomy samples from 84 prostate cancer patients. Spearman’s test, Kaplan-Meier curves, and univariate and multivariate Cox proportional hazard regression analysis were performed. Results: cIAP1/2, cIAP2, Survivin, procaspase-8, cleaved caspase-8, procaspase-3 and caspase-7 expression correlated with at least one clinicopathological feature of the disease. Patients negative for XIAP, procaspase-3 or cleaved caspase-3 had a significantly worse prognosis. Of note, XIAP, procaspase-3 and cleaved caspase-3 were predictors of biochemical progression independent of Gleason score and pathological T stage. Conclusions: Our results indicate that alterations in the expression of IAPs and caspases contribute to the malignant behavior of prostate tumors and suggest that tumor expression of XIAP, procaspase-3 and cleaved caspase-3 may help to identify prostate cancer patients at risk of progression

GH/IGF Axis gene expression profile in developing atlantic bluefin tuna (Thunnus thynnus)

Resumen del trabajo presentado en el XIII Congreso de la Asociación Ibérica de Endocrinología Comparada - AIEC, celebrado online los días 16 y 17 de septiembre de 2021Atlantic bluefin tuna (ABFT), Thunnus thynnus (Linnaeus, 1758), is a large migratory oceanic top predator, considered as an important worldwide fishery source and a key species in pelagic ecosystems. Survival during the early life stages is crucial for future recruitment success, with larval growth being a determining process. Fish growth and development are mainly controlled by the GH/IGF axis, being involved in skeletal and soft tissue growth, as well as in immune function, appetite control, behavior (including foraging, aggression, and predator avoidance). To characterize the ontogenetic development profile of the GH/IGF axis at the level of gene expression, an ABFT larval rearing experiment (under controlled feeding conditions) was performed in the aquaculture facilities of the Spanish Institute of Oceanography (IEO), in Mazarrón during June 2019. Eggs and larvae from 3 replicates were collected regularly every 2-3 days from 0 until 30 days post-hatching (dph). In a total of 14 sampling points (n = 6-12 larvae) along the ontogeny, growth hormone (gh) and two forms of insulin growth factor (igf1 and igf2) were analyzed by real-time RT-PCR. A sigmoidal gh expression profile was observed, with higher values at 5 and 23 (maximum) dph, and lower values at 0 (minimum), 12 and 30 dph. Nevertheless, igf1 and igf2 showed a gradual increase from early days, also with lower values at 0 and 12 dph, but with maximum levels at 30 dph. Results are discussed considering growing rates and transition from larvae to juvenile, underlining the importance of gh/ igf axis during the ABFT early development and growthResearch funded by ECOLATUN CTM2015-68473-R (MINECO/FEDER). The authors wish to thank the technicians from the culture facilities of the Aquaculture Experimental plant in Mazarrón, Murcia (IEO-CSIC)

Best practices during COVID-19 pandemic in solid organ transplant programs in Spain

Clinical management of transplant patients abruptly changed during the first months of COVID-19 pandemic (March to May 2020). The new situation led to very significant challenges, such as new forms of relationship between healthcare providers and patients and other professionals, design of protocols to prevent disease transmission and treatment of infected patients, management of waiting lists and of transplant programs during state/city lockdown, relevant reduction of medical training and educational activities, halt or delays of ongoing research, etc. The two main objectives of the current report are: 1) to promote a project of best practices in transplantation taking advantage of the knowledge and experience acquired by professionals during the evolving situation of the COVID-19 pandemic, both in performing their usual care activity, as well as in the adjustments taken to adapt to the clinical context, and 2) to create a document that collects these best practices, thus allowing the creation of a useful compendium for the exchange of knowledge between different Transplant Units. The scientific committee and expert panel finally standardized 30 best practices, including for the pretransplant period (n = 9), peritransplant period (n = 7), postransplant period (n = 8) and training and communication (n = 6). Many aspects of hospitals and units networking, telematic approaches, patient care, value-based medicine, hospitalization, and outpatient visit strategies, training for novelties and communication skills were covered. Massive vaccination has greatly improved the outcomes of the pandemic, with a decrease in severe cases requiring intensive care and a reduction in mortality. However, suboptimal responses to vaccines have been observed in transplant recipients, and health care strategic plans are necessary in these vulnerable populations. The best practices contained in this expert panel report may aid to their broader implementation.Funding: This Project was funded by an unrestricted grant from Chiesi Pharmaceuticals. Ampersand Consulting was also involved as a methodological adviso