Desempenho zootécnico e custos de alimentação de juvenis de tainha submetidos à restrição alimentar

O objetivo deste trabalho foi avaliar o efeito de restrição alimentar sobre o desempenho zootécnico e custo de alimentação em juvenis de tainha (Mugil liza). Foram avaliados cinco taxas de alimentação - 100, 80, 60, 40 e 20% da saciedade, denominados F100%, F80%, F60%, F40% e F20% -, em triplicata. Juvenis com 0,21±0,03 g (n=30) foram distribuídos em 15 tanques de 200 L. A estimativa do custo foi feita quanto à produção de mil juvenis de tainha. A sobrevivência foi superior a 93%, e não houve influência dos tratamentos. A taxa de crescimento específico no tratamento F100% foi de 5,96±0,18% por dia, e o peso final foi aproximadamente seis vezes maior que o inicial. Tainhas do tratamento F20% apresentaram menor índice hepatossomático, hepatócitos e núcleos menores e menor reserva de glicogênio hepático em relação aos demais tratamentos. A redução da taxa de alimentação influenciou negativamente o crescimento de juvenis de tainha. No entanto, uma taxa de alimentação em torno de 72% da saciedade é capaz de promover o melhor aproveitamento do alimento consumido, com 28% de redução do custo da ração.

Identification of Multiple Mechanisms of Resistance to Vemurafenib in a Patient with BRAFV600E-Mutated Cutaneous Melanoma Successfully Rechallenged after Progression.

PURPOSE: To investigate the mechanism(s) of resistance to the RAF-inhibitor vemurafenib, we conducted a comprehensive analysis of the genetic alterations occurring in metastatic lesions from a patient with a BRAF(V600E)-mutant cutaneous melanoma who, after a first response, underwent subsequent rechallenge with this drug. EXPERIMENTAL DESIGN: We obtained blood and tissue samples from a patient diagnosed with a BRAF(V600E)-mutant cutaneous melanoma that was treated with vemurafenib and achieved a near-complete response. At progression, he received additional lines of chemo/immunotherapy and was successfully rechallenged with vemurafenib. Exome and RNA sequencing were conducted on a pretreatment tumor and two subcutaneous resistant metastases, one that was present at baseline and previously responded to vemurafenib (PV1) and one that occurred de novo after reintroduction of the drug (PV2). A culture established from PV1 was also analyzed. RESULTS: We identified two NRAS-activating somatic mutations, Q61R and Q61K, affecting two main subpopulations in the metastasis PV1 and a BRAF alternative splicing, involving exons 4-10, in the metastasis PV2. These alterations, known to confer resistance to RAF inhibitors, were tumor-specific, mutually exclusive, and were not detected in pretreatment tumor samples. In addition, the oncogenic PIK3CA(H1047R) mutation was detected in a subpopulation of PV1, but this mutation did not seem to play a major role in vemurafenib resistance in this metastasis. CONCLUSIONS: This work describes the coexistence within the same patient of different molecular mechanisms of resistance to vemurafenib affecting different metastatic sites. These findings have direct implications for the clinical management of BRAF-mutant melanoma. Clin Cancer Res; 19(20); 5749-57. ©2013 AACR.

Nouvelles armes thérapeutiques contre le mélanome de stade IV [New therapeutic weapons in stage IV melanoma].

The treatment of stage IV melanoma has been revolutionized over the last years with the development of immunotherapies that, for the first time, have shown a significant benefit in overall survival, as well as with extremely effective targeted therapies, that also led to improved survival. These results are the fruits of an important translational research effort that allowed a rational approach with a very fast clinical development. The treatment of metastatic melanoma is, therefore, an illustration of the new paradigms of modern molecular research in oncology. In this review, we will present the various agents that have made the proof of their clinical benefit, as well as the scientific discoveries that allowed their development. Some of the remaining questions will be touched upon with the ongoing clinical trials. Inclusion of patients in these studies remains the top priority to improve on the clinical care.

Los inicios de la conquista romana de Iberia: los campamentos de campaña del curso inferior del río Ebro

La investigación arqueológica de los campamentos de campaña romano-republicanos localizados en el curso inferior del río Ebro permite una nueva perspectiva de estudio sobre los inicios de la conquista romana en la península ibérica.

Successes and limitations of targeted cancer therapy in melanoma.

The treatment of stage IV melanoma has witnessed a very impressive pace of innovation in recent years, to a point where the management of these patients has very little in common to what was standard practice 5 years ago. If the gain in overall survival, the high response rates or the induction of a significant fraction of long survivors are all very exciting news for our patients and their families, the path that led to these discoveries is as important. Rather than empirical, the development of these new strategies has been extremely rational, based on state-of-the-art basic biology and immunology, exemplary translational research and, finally, hypothesis-driven targeted trials that led to rapid approval. In this review, we will cover all the new targeted therapies that have emerged as the results of these translational programs, focusing mainly on signaling pathway- and immune checkpoint-targeted therapies. Taken collectively, these new developments set the bar for a new paradigm in future translational and clinical research in both melanoma as well as other tumor types.