Drenaje linfático subcutáneo (linfocentesis) de la extremidad superior en el linfedema relacionado con el cáncer de mama. A propósito de un caso / Subcutaneous lymphatic drainage (lymphocentesis) of the upper limb in breast cancer - related lymphedema. A propose of a case

El edema es el resultado de un desequilibrio entre la filtración capilar y el drenaje linfático del espacio intersticial; el edema no linfático se produce como resultado de un cambio en la permeabilidad de las paredes capilares y, como consecuencia, se origina un cambio de gradiente entre las presiones hidrostáticas de los vasos sanguíneos y los tejidos; en cambio, el linfedema se refiere a que el edema es causado por daño linfático, en todos los casos de edema crónico habrá alguna alteración del drenaje linfático, ya sea por una anormalidad subyacente (primaria o secundaria), ya sea por “falla linfática” debido a sobrecarga linfática. El grado de daño linfático influye en la presentación clínica del edema; con el tiempo, el componente líquido del edema puede ser sustituido por fibrosis y/o tejido adiposo. El linfedema de las extremidades es una de las enfermedades más difíciles de manejar en medicina paliativa. Un estudio retrospectivo reciente reveló que el 46 % de los edemas eran de tipo mixto (linfático y no linfático), el 29 % eran linfedema y el 10 % eran edemas no relacionados con el sistema linfático. En la mayoría de los casos es una consecuencia de las enfermedades malignas y sus tratamientos, y supone una enorme pérdida de calidad de vida. Cuando fallan las técnicas de drenaje por compresión y la compresión con medias, se puede intentar el drenaje subcutáneo. Hay pocos informes con diversas técnicas de drenaje subcutáneo, con inserción de catéteres simples o múltiples, diferentes modos de recogida de líquido, sobre todo en las extremidades inferiores con variación en la tasa de éxito. (AU)

Edema is the result of an imbalance between capillary filtration and lymphatic drainage of the interstitial space; non-lymphatic edema occurs as a result of change in the permeability of capillary walls, resulting in change in the gradient between the hydrostatic pressures of the blood vessels and tissues, whereas lymphedema refers to edema being caused by lymphatic damage; in all cases of chronic edema there will be some impairment of lymphatic drainage, either by an underlying abnormality (primary or secondary) or by “lymphatic failure” due to lymphatic overload. The degree of lymphatic damage influences the clinical presentation of edema; over time, the fluid component of edema may be replaced with fibrosis and/or adipose tissue. Lymphedema of the extremities is one of the most difficult diseases to manage in palliative medicine. A recent retrospective study revealed that 46 % of edema cases were of mixed type (lymphatic and non-lymphatic), 29 % were lymphedema cases, and 10 % were non-lymphatic edema cases. In most cases it is a consequence of malignant diseases and their treatments, and represents an enormous loss of quality of life. When compression drainage and compression stocking techniques fail, subcutaneous drainage may be attempted. There are few reports with various subcutaneous drainage techniques, with insertion of single or multiple catheters, different modes of fluid collection, especially in the lower extremities, with variation in success rate. (AU)

Computational repurposing of therapeutic small molecules from cancer to pulmonary hypertension.

Cancer therapies are being considered for treating rare noncancerous diseases like pulmonary hypertension (PH), but effective computational screening is lacking. Via transcriptomic differential dependency analyses leveraging parallels between cancer and PH, we mapped a landscape of cancer drug functions dependent upon rewiring of PH gene clusters. Bromodomain and extra-terminal motif (BET) protein inhibitors were predicted to rely upon several gene clusters inclusive of galectin-8 (LGALS8). Correspondingly, LGALS8 was found to mediate the BET inhibitor­dependent control of endothelial apoptosis, an essential role for PH in vivo. Separately, a piperlongumine analog's actions were predicted to depend upon the iron-sulfur biogenesis gene ISCU. Correspondingly, the analog was found to inhibit ISCU glutathionylation, rescuing oxidative metabolism, decreasing endothelial apoptosis, and improving PH. Thus, we identified crucial drug-gene axes central to endothelial dysfunction and therapeutic priorities for PH. These results establish a wide-ranging, network dependency platform to redefine cancer drugs for use in noncancerous conditions.

Characterization of Engineered L1 Retrotransposition Events: The Recovery Method.

Long Interspersed Element class 1 retrotransposons (LINE-1 or L1) are abundant Transposable Elements in mammalian genomes and their mobility continues to impact the human genome. The development of engineered retrotransposition assays has been instrumental to understand how these elements are regulated and to identify domains involved in the process of retrotransposition. Additionally, the modification of a retrotransposition indicator cassette has allowed developing straightforward approaches to characterize the site of new L1 insertions in cultured cells. In this chapter, we describe a method termed "L1-recovery" that has been used to characterize the site of insertion on engineered L1 retrotransposition events in cultured mammalian cells. Notably, the recovery assay is based on a genetic strategy and avoids the use of PCR and thus reduces to a minimum the appearance of false positives/artifacts.

Expression profile of telomere-associated genes in multiple myeloma.

To further contribute to the understanding of multiple myeloma, we have focused our research interests on the mechanisms by which tumour plasma cells have a higher survival rate than normal plasma cells. In this article, we study the expression profile of genes involved in the regulation and protection of telomere length, telomerase activity and apoptosis in samples from patients with monoclonal gammopathy of undetermined significance, smouldering multiple myeloma, multiple myeloma (MM) and plasma cell leukaemia (PCL), as well as several human myeloma cell lines (HMCLs). Using conventional cytogenetic and fluorescence in situ hybridization studies, we identified a high number of telomeric associations (TAs). Moreover, telomere length measurements by terminal restriction fragment (TRF) assay showed a shorter mean TRF peak value, with a consistent correlation with the number of TAs. Using gene expression arrays and quantitative PCR we identified the hTERT gene together with 16 other genes directly involved in telomere length maintenance: HSPA9, KRAS, RB1, members of the Small nucleolar ribonucleoproteins family, A/B subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins, and 14-3-3 family. The expression levels of these genes were even higher than those in human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), which have unlimited proliferation capacity. In conclusion, the gene signature suggests that MM tumour cells are able to maintain stable short telomere lengths without exceeding the short critical length, allowing cell divisions to continue. We propose that this could be a mechanism contributing to MM tumour cells expansion in the bone marrow (BM).