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Publicaciones Sobre Temas de Interés
CELULAS MADRE/CANCER
Estudios publicados recientemente, en Nature (2) y en Science (1), exponen la teoría de la moderna investigación oncológica que sostiene que los tumores, al igual que los órganos y tejidos, se forman a partir de pequeñas colonias de células madre:
- Nature. 2012 Aug 1. doi: 10.1038/nature11287. [Epub ahead of print]
A restricted cell population propagates glioblastoma growth after chemotherapy.
Chen J, Li Y, Yu TS, McKay RM, Burns DK, Kernie SG, Parada LF.
Source
Department of Developmental Biology & Kent Waldrep Center for Basic Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9133, USA.
Abstract
“Glioblastoma multiforme is the most common primary malignant brain tumour, with a median survival of about one year. This poor prognosis is due to therapeutic resistance and tumour recurrence after surgical removal. Precisely how recurrence occurs is unknown. Using a genetically engineered mouse model of glioma, here we identify a subset of endogenous tumour cells that are the source of new tumour cells after the drug temozolomide (TMZ) is administered to transiently arrest tumour growth. A nestin-?TK-IRES-GFP (Nes-?TK-GFP) transgene that labels quiescent subventricular zone adult neural stem cells also labels a subset of endogenous glioma tumour cells. On arrest of tumour cell proliferation with TMZ, pulse-chase experiments demonstrate a tumour re-growth cell hierarchy originating with the Nes-?TK-GFP transgene subpopulation. Ablation of the GFP(+) cells with chronic ganciclovir administration significantly arrested tumour growth, and combined TMZ and ganciclovir treatment impeded tumour development. Thus, a relatively quiescent subset of endogenous glioma cells, with properties similar to those proposed for cancer stem cells, is responsible for sustaining long-term tumour growth through the production of transient populations of highly proliferative cells.”
- Nature. 2012 Aug 1. doi: 10.1038/nature11344. [Epub ahead of print]
Defining the mode of tumour growth by clonal analysis.
Driessens G, Beck B, Caauwe A, Simons BD, Blanpain C.
Source
Université Libre de Bruxelles, IRIBHM, Brussels B-1070, Belgium.
Abstract
“Recent studies using the isolation of a subpopulation of tumour cells followed by their transplantation into immunodeficient mice provide evidence that certain tumours, including squamous skin tumours, contain cells with high clonogenic potential that have been referred to as cancer stem cells (CSCs). Until now, CSC properties have only been investigated by transplantation assays, and their existence in unperturbed tumour growth is unproven. Here we make use of clonal analysis of squamous skin tumours using genetic lineage tracing to unravel the mode of tumour growth in vivo in its native environment. To this end, we used a genetic labelling strategy that allows individual tumour cells to be marked and traced over time at different stages of tumour progression. Surprisingly, we found that the majority of labelled tumour cells in benign papilloma have only limited proliferative potential, whereas a fraction has the capacity to persist long term, giving rise to progeny that occupy a significant part of the tumour. As well as confirming the presence of two distinct proliferative cell compartments within the papilloma, mirroring the composition, hierarchy and fate behaviour of normal tissue, quantitative analysis of clonal fate data indicates that the more persistent population has stem-cell-like characteristics and cycles twice per day, whereas the second represents a slower cycling transient population that gives rise to terminally differentiated tumour cells. Such behaviour is shown to be consistent with double-labelling experiments and detailed clonal fate characteristics. By contrast, measurements of clone size and proliferative potential in invasive squamous cell carcinoma show a different pattern of behaviour, consistent with geometric expansion of a single CSC population with limited potential for terminal differentiation. This study presents the first experimental evidence for the existence of CSCs during unperturbed solid tumour growth.”
- Science. 2012 Aug 10; 337(6095):730-5. Epub 2012 Aug 1.
Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas.
Schepers AG, Snippert HJ, Stange DE, van den Born M, van Es JH, van de Wetering M, Clevers H.
Source
Hubrecht Institute, Koninklijke Nederlandse Akademie van Wetenschappen, and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, Netherlands.
Abstract
“The concept that tumors are maintained by dedicated stem cells, the so-called cancer stem cell hypothesis, has attracted great interest but remains controversial. Studying mouse models, we provide direct, functional evidence for the presence of stem cell activity within primary intestinal adenomas, a precursor to intestinal cancer. By "lineage retracing" using the multicolor Cre-reporter R26R-Confetti, we demonstrate that the crypt stem cell marker Lgr5 (leucine-rich repeat-containing heterotrimeric guanine nucleotide-binding protein-coupled receptor 5) also marks a subpopulation of adenoma cells that fuel the growth of established intestinal adenomas. These Lgr5(+) cells, which represent about 5 to 10% of the cells in the adenomas, generate additional Lgr5(+) cells as well as all other adenoma cell types. The Lgr5(+) cells are intermingled with Paneth cells near the adenoma base, a pattern reminiscent of the architecture of the normal crypt niche.”
Nota: Para obtener el texto completo de los referidos artículos comunicarse con el CDIC.
EORTC/HISTORIA
Commentary: Fifty Years of the European Organisation for Research and Treatment of Cancer (EORTC) – Making the Difference for the European Oncology Community
Françoise Meunier, Mark Lawler and H.M. Pinedoc
“Standing on the Shoulders of Giants: The Origins of the EORTC
“The year 1962 marks a watershed for cancer care and cancer research in Europe. The previous November, a group of 20 individuals had met in Paris to discuss the establishment of a group that might work together and share expertise in the burgeoning field of cancer chemotherapy. A subsequent follow-up meeting in Milan in 1962 led to the formation of the Groupe Européen de Chimiothérapie Anticancéreuse (GECA). Its co-founders were Belgian clinician Henri Tagnon, French clinician George Mathé, Italian Director of the Mario Negri Institute Silvio Garattini, and Dutch scientist Dirk van Beckum (the first four Presidents of GECA/EORTC). Tagnon had returned from Memorial Sloan-Kettering in the U.S. and recognized the complementary value of treatment and research in the care of the cancer patient. These four like-minded individuals also realized that breaking down national boundaries and creating a transnational collective of selected clinicians and researchers with a common goal would be of critical importance in advancing the discipline of clinical oncology in Europe. They proposed that the “continental” rather than the “national” approach would result in the “cross fertilization of minds and elimination of parochial types of planning and working” and result in “training in clinical medicine and research [that] is more successful when carried out in a broader environment” [1]. Tagnon created a coordinating office in Brussels that recognized the critical importance of the multidisciplinary approach and the added value of international cooperation for cancer research and treatment in Europe. In 1968, this cooperative initiative became the European Organization for Research and Treatment of Cancer (EORTC), which this year celebrates its 50th Anniversary...”
Fuente: The Oncologist. June 2012; 17(6): e6-e7
Ver artículo completo:
http://theoncologist.alphamedpress.org/content/17/6/e6.full.pdf+html
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