miRNA-7 and miRNA-324-5p regulate alpha9-Integrin expression and exert anti-oncogenic effects in rhabdomyosarcoma.

The prognosis of patients with metastatic rhabdomyosarcoma (RMS), the most common type of soft tissue sarcoma in children, is poor and no strategies have been identified to improve their dismal prognosis. Alpha-9 integrin (ITGA9) plays a particularly crucial role in cancer progression and invasiveness. Despite the consensus on the remarkable pro-oncogenic potential of this protein, the miRNA-mediated regulation of ITGA9 has barely been studied to date. In the present study, miR-7 and miR-324-5p were selected as the best candidates after a screening to find ITGA9 regulators, and their effects on cell proliferation and invasion in RMS are described and characterized for the first time. Interestingly, the overexpression of both miRNA produced a clear impairment of cell proliferation, while miR-7 also induced a remarkable drop in cell invasion. Furthermore, the stable overexpression of both miRNA was found to reduce tumor growth in orthotopic RMS models and miR-7 was able to impair metastatic lung colonization. Consequently, we conclude that miR-7 and miR-324-5p show anti-oncogenic and anti-metastatic potential, thereby opening up the possibility of being used as novel therapeutic tools to avoid RMS progression.

Ligand-dependent Hedgehog pathway activation in Rhabdomyosarcoma: the oncogenic role of the ligands.

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children. The Hedgehog (HH) pathway is known to develop an oncogenic role in RMS. However, the molecular mechanism that drives activation of the pathway in RMS is not well understood. METHODS: The expression of HH ligands was studied by qPCR, western blot and immunohistochemistry. Functional and animal model studies were carried out with cells transduced with shRNAs against HH ligands or treated with HH-specific inhibitors (Vismodegib and MEDI-5304). Finally, the molecular characterisation of an off-target effect of Vismodegib was also made. RESULTS: The results showed a prominent expression of HH ligands supporting an autocrine ligand-dependent activation of the pathway. A comparison of pharmacologic Smoothened inhibition (Vismodegib) and HH ligand blocking (MEDI-5304) is also provided. Interestingly, a first description of pernicious off-target effect of Vismodegib is also reported. CONCLUSIONS: The clarification of the HH pathway activation mechanism in RMS opens a door for targeted therapies against HH ligands as a possible alternative in the future development of better treatment protocols. Moreover, the description of a pernicious off-target effect of Vismodegib, via unfolded protein response activation, may mechanistically explain its previously reported inefficiency in several ligand-dependent cancers.

Patient-derived xenografts for childhood solid tumors: a valuable tool to test new drugs and personalize treatments

The use of preclinical models is essential in translational cancer research and especially important in pediatric cancer given the low incidence of each particular type of cancer. Cell line cultures have led to significant advances in cancer biology. However, cell lines have adapted to growth in artificial culture conditions, thereby undergoing genetic and phenotypic changes which may hinder the translational application. Tumor grafts developed in mice from patient tumor tissues, generally known as patient-derived xenografts (PDXs), are interesting alternative approaches to reproducing the biology of the original tumor. This review is focused on highlighting the interest of PDX models in pediatric cancer research and supporting strategies of personalized medicine. This review provides: (1) a description of the background of PDX in cancer, (2) the particular case of PDX in pediatric cancer, (3) how PDX can improve personalized medicine strategies, (4) new methods to increase engraftment, and, finally, (5) concluding remarks (AU)

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Patient-derived xenografts for childhood solid tumors: a valuable tool to test new drugs and personalize treatments.

The use of preclinical models is essential in translational cancer research and especially important in pediatric cancer given the low incidence of each particular type of cancer. Cell line cultures have led to significant advances in cancer biology. However, cell lines have adapted to growth in artificial culture conditions, thereby undergoing genetic and phenotypic changes which may hinder the translational application. Tumor grafts developed in mice from patient tumor tissues, generally known as patient-derived xenografts (PDXs), are interesting alternative approaches to reproducing the biology of the original tumor. This review is focused on highlighting the interest of PDX models in pediatric cancer research and supporting strategies of personalized medicine. This review provides: (1) a description of the background of PDX in cancer, (2) the particular case of PDX in pediatric cancer, (3) how PDX can improve personalized medicine strategies, (4) new methods to increase engraftment, and, finally, (5) concluding remarks.

Protocolo de atención al niño inmigrante y a los hijos de inmigrantes / No disponible

En los últimos años, un porcentaje considerable de consultas de Atención Primaria (AP)está dedicado a niños procedentes de países de renta baja.El protocolo que presentamos se ha hecho con el objetivo de mejorar la atención al niñoinmigrante, lo que incluye la detección de factores de riesgo, el tratamiento de los problemasmédicos y su seguimiento.Además, y como parte de la labor del pediatra de AP, se destaca la necesidad de favorecerla integración de la población infantil inmigrante. Conocer la procedencia, la cultura, loshábitos alimentarios y la situación socioeconómica de estos niños es un requisito necesariopara individualizar la atención de manera adecuada, detectar patologías presentes y futurasy poner en marcha las actividades preventivas y terapéuticas más eficaces. Entre ellasdestacamos la prevención de la mutilación genital femenina

In recent years, a considerable amount of Primary Care (PC) visits are devoted to childrencoming from low income countries.We present some guidelines elaborated with the objective of improving the healthcarefor immigrant children. They include risk factors’ detection, treatment of medical conditionsand follow up.Besides, being a part of PC paediatrician’s task, we underline the need of helping the integrationof the immigrant children. It is compulsory to know the origin, culture, food habitsand socio-economic situation of these children in order to implement individualized and correctcare, to detect present and future diseases and to start more efficient preventive ant therapeuticactivities. We emphasize prevention of female genital mutilation among them

Migration pathways of hypodermically injected technetium-99m in dogs.

Hypodermic injection of technetium-99m (99mTc-pertechnetate) at points of low electrical resistance give rise to rapid, longitudinal, and progressive diffusion of the radioactive tracer. We assessed the effect of cutaneous incisions that did not intersect the migration trajectory of 99mTc-pertechnetate and the re-establishment of pathways after the suture of incisions that intersected the migration trajectory. Linear and rapid migration of 99mTc-pertechnetate was not altered or prevented by incisions that did not intersect the migration pathway. Different patterns of 99mTc-pertechnetate spread were found when incisions intersected the radioactive pathways until restoration of the normal migration pathway observed in undamaged skin occurred. In all experiments in which migration of 99mTc-pertechnetate was observed, lavage of surgical wounds was followed by disappearance of the 99mTc-pertechnetate migration observed around the suture. Linear migration of the tracer was not observed when the incision was left uncovered, filled with petroleum jelly, or with a solid silicone sheet, but it was seen when non-sutured incisions were filled with transonic or silicone gel or covered with a solid silicone sheet parallel to the cutaneous plane. These data show that after a cutaneous incision that intersected the diffusion trajectory of the radioactive tracer, linear migration of 99mTc-pertechnetate hypodermically injected at points of low electrical resistance was restored before healing of the cutaneous incision and was independent of incisions made on the skin not overlying the radioactive pathway. A mechanism similar to that of capillary electrophoresis is suggested to explain the hypodermic diffusion of inert particles through specific and constant linear pathways.