CCR7 as a novel therapeutic target in t-cell PROLYMPHOCYTIC leukemia

T-cell prolymphocytic leukemia (T-PLL) is a poor prognostic disease with very limited options of efficient therapies. Most patients are refractory to chemotherapies and despite high response rates after alemtuzumab, virtually all patients relapse. Therefore, there is an unmet medical need for novel therapies in T-PLL. As the chemokine receptor CCR7 is a molecule expressed in a wide range of malignancies and relevant in many tumor processes, the present study addressed the biologic role of this receptor in T-PLL. Furthermore, we elucidated the mechanisms of action mediated by an anti-CCR7 monoclonal antibody (mAb) and evaluated whether its anti-tumor activity would warrant development towards clinical applications in T-PLL. Our results demonstrate that CCR7 is a prognostic biomarker for overall survival in T-PLL patients and a functional receptor involved in the migration, invasion, and survival of leukemic cells. Targeting CCR7 with a mAb inhibited ligand-mediated signaling pathways and induced tumor cell killing in primary samples. In addition, directing antibodies against CCR7 was highly effective in T-cell leukemia xenograft models. Together, these findings make CCR7 an attractive molecule for novel mAb-based therapeutic applications in T-PLL, a disease where recent drug screen efforts and studies addressing new compounds have focused on chemotherapy or small molecules.Peer reviewe

Parallel Implementations Assessment of a Spatial-Spectral Classifier for Hyperspectral Clinical Applications

Hyperspectral (HS) imaging presents itself as a non-contact, non-ionizing and non-invasive technique, proven to be suitable for medical diagnosis. However, the volume of information contained in these images makes difficult providing the surgeon with information about the boundaries in real-time. To that end, High-Performance-Computing (HPC) platforms become necessary. This paper presents a comparison between the performances provided by five different HPC platforms while processing a spatial-spectral approach to classify HS images, assessing their main benefits and drawbacks. To provide a complete study, two different medical applications, with two different requirements, have been analyzed. The first application consists of HS images taken from neurosurgical operations; the second one presents HS images taken from dermatological interventions. While the main constraint for neurosurgical applications is the processing time, in other environments, as the dermatological one, other requirements can be considered. In that sense, energy efficiency is becoming a major challenge, since this kind of applications are usually developed as hand-held devices, thus depending on the battery capacity. These requirements have been considered to choose the target platforms: on the one hand, three of the most powerful Graphic Processing Units (GPUs) available in the market; and, on the other hand, a low-power GPU and a manycore architecture, both specifically thought for being used in battery-dependent environments

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field