MAP17 (PDZK1IP1) and pH2AX are potential predictive biomarkers for rectal cancer treatment efficacy

Rectal cancer represents approximately 10% of cancers worldwide. Preoperative chemoradiotherapy increases complete pathologic response and local control, although it offers a poor advantage in survivorship and sphincter saving compared with that of radiotherapy alone. After preoperative chemoradiotherapy, approximately 20% of patients with rectal cancer achieve a pathologic complete response to the removed surgical specimen; this response may be related to a better prognosis and an improvement in disease-free survival. However, better biomarkers to predict response and new targets are needed to stratify patients and obtain better response rates. MAP17 (PDZK1IP1) is a small, 17 kDa non-glycosylated membrane protein located in the plasma membrane and Golgi apparatus and is overexpressed in a wide variety of human carcinomas. MAP17 has been proposed as a predictive biomarker for reactive oxygen species, ROS, inducing treatments in cervical tumors or laryngeal carcinoma. Due to the increase in ROS, MAP17 is also associated with the marker of DNA damage, phosphoH2AX (pH2AX). In the present manuscript, we examined the values of MAP17 and pH2AX as surrogate biomarkers of the response in rectal tumors. MAP17 expression after preoperative chemoradiotherapy is able to predict the response to chemoradiotherapy, similar to the increase in pH2AX. Furthermore, we explored whether we can identify molecular targeted therapies that could help improve the response of these tumors to radiotherapy. In this sense, we found that the inhibition of DNA damage with olaparib increased the response to radio- and chemotherapy, specifically in tumors with high levels of pH2AX and MAP17.Spanish Ministry of Economy and Competitivity, Plan Estatal de I+D+I 2013–2016, ISCIII (Fis: PI15/00045) and CIBER de Cáncer (CB16/12/00275)co-funded by FEDER from Regional Development European Funds (European Union), Consejería de Ciencia e Innovación (CTS-1848)Consejería de Salud of the Junta de Andalucía (PI-0096–2014)

Cuaderno de prácticas de dibujo para la presentación de diseños de producto

Departament d'Enginyeria de Sistemes Industrials i Disseny. Codi assignatura: DI 100

Preliminary Study on the Effect of an Early Physical Therapy Intervention after Sentinel Lymph Node Biopsy: A Multicenter Non-Randomized Controlled Trial

Selective sentinel lymph node biopsy (SLNB) represents a minimally invasive surgery in patients with breast cancer. The purpose of this study was to explore the possible effect of an early physiotherapy intervention for the recovery of the upper limb and the surgical scars after SLNB in comparison with usual care. A total of 40 patients were enrolled in either the control group (n = 20) or the experimental group (n = 20). The intervention group performed an early physiotherapy program based on functional exercises, scar manual therapy, and educational tips. The control group received usual care. Shoulder range of motion (ROM), grip strength, upper limb pain and disability (SPADI), scar recovery (POSAS), myofascial adhesions (MAP-BC), quality of life (EORTCQLA-BR-23) and the presence of axillary web syndrome (AWS) and lymphoedema were assessed at baseline and immediately after intervention. A follow-up period of 6 months was performed for lymphoedema surveillance. Between groups significant differences in favor of the intervention were found for ROM (r = 0.43), grip strength (r = 0.32), SPADI (d = 0.45), POSAS (d = 1.28), MAP-BC (d = 1.82) and EORTCQLQ-BR 23 general function subscale (d = 0.37) (p < 0.05 for all variables). Our results suggest that an early physical therapy program seems to be more effective than usual care in women after SLNB. However, results should be interpreted with caution and future randomized trial with a larger sample size is neededThis research was partially supported by ICPFA. Grant number 04722/19P/MA. The funder had no role in the design of the study and collection, analysis, and interpretation of data, and in writing the manuscript. Partial funding for open access charge: Universidad de Málag

Peer actions for a service learning project to prevent drug-facilitated sexual assaults

The service-learning methodology combines active learning processes and community service. This service-learning experience was performed using an interdisciplinary and cross plan. The teachers made a horizontal coordination in the courses, and a vertical coordination in subjects of the Degrees involved. This allowed working together in the students’ curricular training process. It also permitted covering various specific skills, as corresponds to the different subjects, whilst optimizing the students’ workload. The service addressed the problem of drug-facilitated sexual assaults (DFSA) in the youth leisure nightlife. DFSA is the temporary disability of a person caused by a decrease in her/his volitional and cognitive abilities due to the voluntary or involuntary consumption of a psychoactive substance. An active learning about the problem was encouraged in the classroom, focused on recognizing myths, attitudes, and risk situations. The service-learning actions to the community was based on an anonymous survey conducted among the students, which dealt with the problem. The Service Learning was stimulated through the design, planning and development of activities aimed at gaining social awareness of the existing problem while favouring peer learning processes. The students undertook awareness actions at different levels, spreading their message by means of social networks, high school workshops, and information stands on the street.Teaching Innovation projects UAH / EV951 and UAH / EV1024 of the University of Alcalá; Research project MSCBS-PNSD-2018I032 of the Ministry of Health Consumption and Social Welfare, National Drug Plan; IUICP2019 /06 Research project of the University Institute of Police Science Research. P. Prego-Meleiro and F. Zapata thank the UAH for their scholarships.Quintanilla, G.; Ortega-Ojeda, F.; García-Ruiz, C.; Prego-Meleiro, P.; Figueroa Navarro, C.; Bravo-Serrano, B.; García-Pernía, MR.... (2020). Peer actions for a service learning project to prevent drug-facilitated sexual assaults. En 6th International Conference on Higher Education Advances (HEAd'20). Editorial Universitat Politècnica de València. (30-05-2020):1425-1433. https://doi.org/10.4995/HEAd20.2020.11313OCS1425143330-05-202

PAI1 is a Marker of Bad Prognosis in Rectal Cancer but Predicts a Better Response to Treatment with PIM Inhibitor AZD1208

Colorectal cancer (CRC) is the third most common cancer worldwide. The standard treatment in locally advanced rectal cancer is preoperative radiation alone or in combination with chemotherapy, followed by adjuvant chemotherapy. Rectal cancer is highly lethal, with only 20% of patients showing a complete remission (by RECIST) after standard treatment, although they commonly show local or systemic relapse likely due to its late detection and high chemotherapy resistance, among other reasons. Here, we explored the role of PAI1 (Serpin E1) in rectal cancer through the analyses of public patient databases, our own cohort of locally advanced rectal cancer patients and a panel of CRC cell lines. We showed that PAI1 expression is upregulated in rectal tumors, which is associated with decreased overall survival and increased metastasis and invasion in advanced rectal tumors. Accordingly, PAI1 expression is correlated with the expression of (Epithelial-to-Mesenchymal Transition) EMT-associated genes and genes encoding drug targets, including the tyrosine kinases PDGFRb, PDGFRa and FYN, the serine/threonine kinase PIM1 and BRAF. In addition, we demonstrate that cells expressing PAI1 protein are more sensitive to the PIM inhibitor AZD1208, suggesting that PAI1 could be used to predict response to treatment with PIM inhibitors and to complement radiotherapy in rectal tumors.España Consejería de Salud of the Junta de Andalucía (PI-0397-2017)España , Consejeria of Economía, Conocimiento, Empresas y Universidad of the Junta de Andalucia (P18-RT-2501

Competencias para el empleo: comunicación y emprendimiento

Depto. de Investigación y Psicología en EducaciónFac. de EducaciónFALSEsubmitte

Identification of hereditary breast and ovarian cancer germline variants in Granada (Spain): NGS perspective

Funding for open access charge: Universidad de Granada/CBUA. Maria Molina-Zayas has been a recipient of the 2018 AEFA Post-residency Grant (Spanish Association of Clinical Laboratory) and Dr. Carmen Garrido-Navas holds a postdoctoral fellowship from the Ministry of Economy, Competitiveness, Enterprises and Universities (DOC_01682).The aim of this study was to assess the prevalence of germline variants in cancer-predisposing genes by either targeted (BRCA1/2) or multigene NGS panel in a high-risk Hereditary Breast and Ovarian Cancer (HBOC) cohort. Samples from 824 Caucasian probands were retrospectively collected and the impact of genetic diagnosis and genetic variants epidemiology in this cohort was evaluated. Performance of risk-reducing prophylactic measures, such as prophylactic mastectomy and/or prophylactic oophorectomy, was assessed through clinical follow-up of patients with a positive genetic result. Pathogenic variants predisposing to HBOC were identified in 11.9% (98/824) individuals at BRCA2 (47/98), BRCA1 (24/98), PALB2 (8/51), ATM (7/51), CHEK2 (6/51) MSH6, (2/51), RAD51C (2/51) and TP53 (2/386). Of them, 11 novel pathogenic variants and 12 VUS were identified, characterized, and submitted to ClinVar. Regarding clinical impact, the risk of developing basal or Her2 breast cancer was increased 15.7 times or 37.5 times for BRCA1 and MSH6 pathogenic variants respectively. On the contrary, the risk of developing basal or luminal A breast cancer was reduced to 81% or 77% for BRCA2 and BRCA1 pathogenic variants, respectively. Finally, 53.2% of individuals testing positive for class IV/V variants underwent prophylactic surgery (mastectomy, oophorectomy or both) being significantly younger at the cancer diagnosis than those undertaking prophylactic measures (p = 0.008). Of them, 8 carried a pathogenic/likely pathogenic variant in other genes different from BRCA1 and BRCA2, and the remaining (46.7%) decided to continue with clinical follow-up. No differences in pathogenicity or risk of developing cancer were found for BRCA1/2 between targeted and multigene sequencing strategies; however, NGS was able to resolve a greater proportion of high-risk patients.Universidad de Granada/CBUA2018 AEFA Post-residency Grant (Spanish Association of Clinical Laboratory)Ministry of Economy, Competitiveness, Enterprises and Universities DOC_0168

Application of topical interferon alpha 2b in corneal-conjunctival intraepithelial neoplasia: monitoring of four cases

Introducción: El tratamiento convencional del carcinoma in situ conjuntival es la escisión quirúrgica. Sin embargo esta forma de tratamiento presenta una tasa de recurrencia del 30% y conlleva un alto riesgo de insuficiencia límbica. Esto ha motivado a distintos autores a la utilización de antimetabolitos como terapia adyuvante e incluso como tratamiento primario, tales como la mitomicina C o el interferón alfa 2b. Material y métodos: Presentamos cuatro pacientes, que consultan en nuestra unidad por lesión en conjuntiva. La evaluación clínica fue llevada a cabo mediante biomicroscopía y el análisis microscópico fue desarrollado por anatomía patológica y citología de impresión. De esta formalos cuatro casos fueron diagnosticados de Neoplasia intraepitelial (NI) “carcinoma in situ". Los pacientes fueron tratados con interferón alfa 2b a una concentración de un millón de unidades repartidos 4 veces al día. Resultados, discusión y conclusiones: Se resolvieron con éxito los cuatro casos. El tiempo medio de curación de las lesiones fue de un mes, solo un paciente presento efectos adversos (una queratitis punctata) y no requirió suspender el tratamiento. En nuestra muestra, por tanto, se demuestra la eficacia y seguridad del tratamiento en la NI con interferón alfa 2b. Por último, planteamos si el interferón alfa 2b podría ser goldstandard en el tratamiento de la NI en nuestra área.Introduction: The conventional treatment of conjunctival carcinoma in situ is surgical excision. Nevertheless this form of treatment has a recurrence rate of 30% and carries a high risk of limbic insufficiency. This has motivated several authors to use antimetabolites as adjunctive therapy and even as primary treatment, as with mitomycin C or interferon alpha 2b. Materials and methods: We present four patients, who consulting in our unit for conjunctival lesion. Clinical evaluation was performed using biomcroscopy and the microscopic analysis was obtained by pathology and impression cytology. In this way the four cases were diagnosed ofintraepithelial neoplasia (IN) “carcinoma in situ”. The patients are treated with interferon alpha 2b at a concentration of one million units scheduled four times a day. Results, discussion and conclusions: We successfully resolved four cases. The average healing time of the lesions was one month, with only one patient presenting adverse effects (one punctate keratitis), but did not require discontinuation of therapy. In our sample, we demonstrate the effectiveness and safety of this therapy in IN. We wonder whether interferon should be the gold standard for the treatment of intraepithelial neoplasia in this area

Induction of Lysosome Membrane Permeabilization as a Therapeutic Strategy to Target Pancreatic Cancer Stem Cells

Despite significant efforts to improve pancreatic ductal adenocarcinoma (PDAC) clinical outcomes, overall survival remains dismal. The poor response to current therapies is partly due to the existence of pancreatic cancer stem cells (PaCSCs), which are efficient drivers of PDAC tumorigenesis, metastasis and relapse. To find new therapeutic agents that could efficiently kill PaCSCs, we screened a chemical library of 680 compounds for candidate small molecules with anti-CSC activity, and identified two compounds of a specific chemical series with potent activity in vitro and in vivo against patient-derived xenograft (PDX) cultures. The anti-CSC mechanism of action of this specific chemical series was found to rely on induction of lysosomal membrane permeabilization (LMP), which is likely associated with the increased lysosomal mass observed in PaCSCs. Using the well characterized LMP-inducer siramesine as a tool molecule, we show elimination of the PaCSC population in mice implanted with tumors from two PDX models. Collectively, our approach identified lysosomal disruption as a promising anti-CSC therapeutic strategy for PDAC

Nutrição enteral domiciliaria: descrição das características clínicas dos pacientes atendidos na consulta telefônica de enfermagem

Home enteral nutrition&nbsp;(HEN) is an alternative for patients who&nbsp;are unable to feed orally because of their clinical situation and who do not need to&nbsp;be hospitalized.La nutrición enteral domiciliaria (NED) es una alternativa para&nbsp;aquellos pacientes que presentan incapacidad de alimentarse naturalmente&nbsp;a causa de su situación clínica y que no&nbsp;necesitan estar en un medio hospitalario.A nutrição enteral domiciliaria (NED) é uma alternativa para os&nbsp;pacientes que não conseguem se alimentar naturalmente, devido à sua situação&nbsp;clínica e que não precisam de estar em&nbsp;ambiente hospitalar