NCAPH drives breast cancer progression and identifies a gene signature that predicts luminal a tumour recurrence.

BACKGROUND: Luminal A tumours generally have a favourable prognosis but possess the highest 10-year recurrence risk among breast cancers. Additionally, a quarter of the recurrence cases occur within 5 years post-diagnosis. Identifying such patients is crucial as long-term relapsers could benefit from extended hormone therapy, while early relapsers might require more aggressive treatment. METHODS: We conducted a study to explore non-structural chromosome maintenance condensin I complex subunit H's (NCAPH) role in luminal A breast cancer pathogenesis, both in vitro and in vivo, aiming to identify an intratumoural gene expression signature, with a focus on elevated NCAPH levels, as a potential marker for unfavourable progression. Our analysis included transgenic mouse models overexpressing NCAPH and a genetically diverse mouse cohort generated by backcrossing. A least absolute shrinkage and selection operator (LASSO) multivariate regression analysis was performed on transcripts associated with elevated intratumoural NCAPH levels. RESULTS: We found that NCAPH contributes to adverse luminal A breast cancer progression. The intratumoural gene expression signature associated with elevated NCAPH levels emerged as a potential risk identifier. Transgenic mice overexpressing NCAPH developed breast tumours with extended latency, and in Mouse Mammary Tumor Virus (MMTV)-NCAPHErbB2 double-transgenic mice, luminal tumours showed increased aggressiveness. High intratumoural Ncaph levels correlated with worse breast cancer outcome and subpar chemotherapy response. A 10-gene risk score, termed Gene Signature for Luminal A 10 (GSLA10), was derived from the LASSO analysis, correlating with adverse luminal A breast cancer progression. CONCLUSIONS: The GSLA10 signature outperformed the Oncotype DX signature in discerning tumours with unfavourable outcomes, previously categorised as luminal A by Prediction Analysis of Microarray 50 (PAM50) across three independent human cohorts. This new signature holds promise for identifying luminal A tumour patients with adverse prognosis, aiding in the development of personalised treatment strategies to significantly improve patient outcomes.

Value of PD-L1, PD-1, and CTLA-4 Expression in the Clinical Practice as Predictors of Response to Nivolumab and Ipilimumab in Monotherapy in Patients With Advanced Stage Melanoma.

BACKGROUND: The introduction of immune checkpoint inhibitors (ICI) has improved the survival outcomes of patients with advanced melanoma. To date, only a few studies have evaluated the immunohistochemical (IHC) expression of PD-1 and CTLA-4 in tumor-infiltrating lymphocytes (TILs) as predictive markers of response to ICI, most of them in the context of clinical trials. Moreover, the predictive value of PD-L1 in melanoma cells in the response to immunotherapy is unclear. The aim of our study was to assess the IHC expression of PD-L1, PD-1, and CTLA-4 in samples of patients with advanced melanoma and to establish their prognostic value as predictors of ICI response in a university hospital. METHODS: The expression of PD-L1, PD-1, and CTLA-4 was evaluated in pretreatment tumor samples in a series of 35 patients, 21 patients treated with nivolumab and 14 patients with ipilimumab in monotherapy. RESULTS: In the nivolumab group, 4 tumors (19%) were positive for PD-L1 and all of them showed a partial response to the treatment. However, 4 patients whose tumors did not express PD-L1 also responded to nivolumab. PD-1 expression was not associated with better progression-free survival (PFS). In the ipilimumab group, 5 patients (35.7%) showed expression of CTLA-4. Positive cases showed a better PFS; however, one negative case responded to ipilimumab. CONCLUSIONS: Nivolumab produces a better response compared with ipilimumab in patients with melanoma. The IHC expression of PD-L1 and CTLA-4 are associated with a higher response rate to nivolumab and ipilimumab, respectively, and better PFS, but the existence of responder patients with negative expression suggests that they are not adequate biomarkers to select candidate patients for ICI in the clinical practice.

Alteraciones genéticas del cáncer colorrectal: implicaciones en el pronóstico y en el tratamiento de la enfermedad / No disponible

En los últimos años se ha avanzado de forma notable en el conocimiento de las distintas alteraciones genéticas presentes en el cáncer colorrectal (CCR) y su asociación con la ontogenia y la progresión tumoral. Así, mientras que la presencia de mutaciones en los genes APC y KRAS, se asocia con el proceso de transformación neoplásica, las mutaciones en SMAD y DCC alteraciones a nivel de los cromosomas 7, 17p y 18q y los cariotipos complejos constituirían habitualmente alteraciones genéticas asociadas con la progresión tumoral. Desde el punto de vista pronóstico, la presencia de inestabilidad de microsatélites (IMS) se asocia con menores tasas de recaída y mayor supervivencia global, así como con la resistencia a tratamiento adyuvante con fluoropirimidinas, mientras que las mutaciones en el gen BRAF se han asociado con recaídas precoces. A nivel molecular, los estudios sobre la heterogeneidad genética intratumoral asociada al proceso metastásico del CCR se han centrado en analizar mutaciones de genes involucrados en el tratamiento de la enfermedad, observándose la existencia de distintos perfiles mutacionales entre tumores primarios, metástasis ganglionares y metástasis hepáticas de un mismo paciente. En este sentido, la heterogeneidad genética del CCR a nivel intratumoral podría explicar las altas tasas de recaída y los tumores refractarios tratados con anticuerpos monoclonales

No disponible

Riesgo cardiovascular presente en estudiantes de una universidad de México / Cardiovascular risk in a Mexican university students

Introducción: Las enfermedades cardiovasculares son la primera causa de muerte en el mundo, dichas enfermedades se pueden prevenir mediante el control de los factores de riesgo, donde destacan la obesidad, hipertensión, tabaquismo, sedentarismo y antecedentes familiares. Objetivo: Identificar el factor de riesgo cardiovascular más frecuente en los estudiantes universitarios. Material y métodos: Estudio comparativo, observacional, prospectivo y transversal; se realizó en 8 facultades de la Universidad Veracruzana Región Veracruz, divididas en dos grupos, el primero del área de Ciencias de la Salud y el Segundo de áreas mixtas; de cada facultad se estudiaron 43 alumnos, dando una muestra total de 344; se registraron los siguientes datos: antecedentes familiares, tabaquismo, actividad física y se obtuvieron valores como peso, talla, presión arterial y glucemia capilar. Resultados: En el grupo 1 se encontró que el 50,6% de los estudiantes presentaban sobrepeso, 10,5% obesidad, 22,1% hipertensión arterial, 1,2% hiperglucemia, 19,2% fumadores, 70,9% sedentarios y en cuanto a los antecedentes familiares de diabetes, hipertensión arterial y obesidad poseen valores similares (22-23%). En cuanto al grupo 2, se obtuvieron 29,7% estudiantes con sobrepeso, 9,3% obesidad, 11,6% hipertensión arterial, 4,7% hiperglucemia, 15,7% fumadores, 41,3% sedentarios, en cuanto a los antecedentes familiares destacaba la diabetes con 58,1% como principal. Conclusiones: El sedentarismo es el factor de riesgo cardiovascular más frecuente en los estudiantes, el segundo factor de riesgo más frecuente es el sobrepeso los antecedentes heredofamiliares de diabetes y obesidad se ubican en tercer lugar, el menos frecuente en ambos grupos fue la hiperglucemia.

Introduction: Cardiovascular disease is the leading cause of death world wide. Such diseases can be prevented by controlling cardiovascular risk factors, among which include obesity, hypertension, smoking, sedentary life style and family history. Objectives: identify the most frequent cardiovascular risk factor in university students. Material and methods: This was a comparative, observational, prospective and cross- sectional study; It was performed in 8 different faculties of the Universidad Veracruzana Region Veracruz Boca del Rio, divided into two groups, the first in the area of Health Sciences and the second of mixed areas; each school 43 students were studied, giving a total sample of 344 students; data of family history, smoking, physical activity were recorded and values such as weight, height, blood pressure and blood glucose were obtained. Results: In group 1, it was found that 50.6% of students were overweight, 10.5% were obese, 22.1% hypertension, 1.2% hyperglycemia, 19.2% were smokers, 70.9% were sedentary and as a family history of diabetes, hypertension and obesity have similar values (22-23%). As group 2, 29.7% students were obtainedoverweight,9.3%wereobese,11.6% hypertension,4.7%hyperglycemia,15.7%were smokers, 41.3% were sedentary, as the family history included diabetes with 58.1% as principal. Conclusions: Physical inactivity is the cardiovascular risk factor more prevalent in students, the second most common risk factor is overweight, a family history of diabetes and obesity are located in third place, less frequent in both groups was Hyperglycemia.