281. [Neural stem cells and Notch signalling].
Development and repair of the nervous system are based on the existence of neural stem cells (NSCs) able to generate neurons and glial cells. Among the mechanisms that are involved in the control of embryo or adult NSCs, the Notch signalling plays a major role. In embryo, the pathway participates in the maintenance of NSCs during all steps of development of the central nervous system which starts with the production of neurons also called neurogenesis and continues with gliogenesis giving rise to astrocytes and oligodendrocytes. During the postnatal and adult period, Notch signalling is still present in the major neurogenic areas, the subventricular zone of the lateral ventricles and the subgranular zone of the hippocampus. In these regions, Notch maintains NSC quiescence, contributes to the heterogeneity of these cells and displays pleiotropic effects during the regeneration process occurring after a lesion.
282. [The use and storage of stem cells and cord blood: French and English law comparative approach].283. [Ovarian failure: New treatments in perspective?].
The premature loss of ovarian function may have physical and psychological consequences. A better understanding of its mechanism is therefore needed. Because they are affecting the oocyte quality, the decline of the ovarian reserve and high maternal age are implicated in many defects leading to chromosomal defects, modifications of gene expression or alterations of the mitochondrial pattern of the oocyte. However, cellular therapies such as ovarian follicle activation or isolation of ovarian stem cells are promising treatments of ovarian failure.
285. [Functional results and treatment of functional dysfunctions after radical prostatectomy].
To describe the functional results and treatment of functional dysfunctions after radical prostatectomy for localized prostate cancer.
288. [Miscellaneous medical news stories, July 2015].289. [Mesenchymal stem cell therapy, a new hope for eye disease].
Mesenchymal stem cells (MSC) are adult stem cells, first identified in skeletal tissues and then found in the entire body. MSC are able to not only differentiate into specialized cells within skeletal tissue - chondrocytes, osteocytes, adipocytes and fibroblasts - but also secrete a large range of soluble mediators defining their secretome and allowing their interaction with a number of cell protagonists. Thus, in a general sense, MSC are involved in tissue homeostasis through their secretome and are specifically responsible for cell turn-over in skeletal tissues. For a decade and a half, safety and efficiency of MSC has led to the development of many clinical trials in various fields. However, results were often disappointing, probably because of difficulties in methods and evaluation. At a time when the first clinical trials using MSC are emerging in ophthalmology, the goal of this literature review is to gather and put into perspective preclinical and clinical results in order to better predict the future of this innovative therapeutic pathway.
290. [Early human transplants: 60th anniversary of the first successful kidney transplants].
First kidney transplant attempts begin with the 20th century: improving vascular sutures, understanding the phenomena of rejection or tolerance, then progress in HLA groups enable early success in the second half of the century. Definition of brain death, use of corticosteroids, radiotherapy and prime immunosuppressors promote the development of transplants. Discover of cyclosporine in the 1980s, and legislative developments augur a new era. Many advances are arising: use of stem cells from the donor, enhancement of Maastricht 3 donor or living donation. Finally organ transplantation remains an immense human adventure, but also scientific and ethic.
291. [Ethical problems raised by new reproductive biotechnologies and stem cells].
Research about the hormonal mechanisms controlling reproduction in mammals has soared during the first half of the 20th century. It has produced a series of discoveries with important outcomes, not only scientific, but also impacting the ways of life. Besides the advent of the contraceptive pill, it has permitted to isolate and cultivate in vitro the female gamete, to fertilize it, thus obtaining a zygote that continues to develop until the blastocyst stage outside the maternal organism. The embryo, transferred into a foster-mother, develops normally until term: the first "test-tube baby" was born in this way in 1978. But the only fact of being able to cultivate the human egg in vitro was to open other possibilities and allow further biological advances: embryonic stem cells (ES cells) obtained from blastocysts and, more recently, from induced Pluripotent Stem cells (iPS), which can potentially be derived from all types of differentiated cell types obtained from adult individuals. From then on, the advent of a new medicine could be anticipated, regenerative because able to replace deficient or absent cells within the organism. As each of these steps was reached, scientists have encountered vigorous opposition from the people: the new potentials disturbed the conceptions that man had of his relationship to nature, in particular in two sensitive domains: sexuality and reproduction. The progress of science has however been accepted by most as soon as it was understood that humanity could anticipate advantages from these advances.
292. [Paroxysmal nocturnal hemoglobinuria: An unknown cause of thrombosis?].
作者: C Doutrelon.;S Skopinski.;C Boulon.;J Constans.;J-F Viallard.;R Peffault de Latour.
来源: J Mal Vasc. 2015年40卷6期384-90页
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder of hematopoietic stem cells. Somatic mutation in the phosphatidylinositol glycan class A (PIG-A), X-linked gene, is responsible for a deficiency in glycosphosphatidylinositol-anchored proteins (GPI-AP). The lack of one of the GPI-AP complement regulatory proteins (CD55, CD59) leads to hemolysis. The disease is diagnosed with hemolytic anemia, marrow failure and thrombosis. Thromboembolic complication occurs in 30% of patient after 10 years of follow-up and is the first event in one out of 10 patients. The two most common sites are hepatic and cerebral veins. These locations are correlated with high risk of death. Currently, these data are balanced with the use of a monoclonal antibody (Eculizumab), which has significantly improved the prognosis with a survival similar to general population after 36 months of follow-up. Anticoagulant treatment is recommended after a thromboembolic event but has no place in primary prophylaxis.
293. [Cellular therapy and leg ulcers: Future approaches].
The prevalence of leg ulcers, which are most commonly caused by venous insufficiency, is high in Europe. Current treatments are fairly unsatisfactory, with long healing times in many cases, as well as a high risk of relapse. Over the last 15 years, improved understanding of the cellular and molecular mechanisms at work in delayed wound healing has contributed to the development of cellular therapy in this field. The use of keratinocytes or cultured fibroblasts, whether autogenic or allogenic, has been of little value in terms of either healing times or rates of complete healing. For the moment, there are very few allogenic skin substitutes available; they are expensive and have been insufficiently studied in the indication of leg ulcers. Pluripotent mesenchymal adult stem cells have proved capable of accelerating wound healing in animal models and their study in chronic wounds in humans is currently awaited.
294. [Sequential grafts of cutaneous cells: First results of a new procedure and review of the literature].
作者: Gabriel Sabeh.;Michel Sabé.;Salah Ishak.;Rodrigue Sweid.;Mohamad Ayoubi.;Abdel Majid Chahal.
来源: J Med Liban. 2015年63卷2期47-58页
A new choice for major burn wounds is presented. An alternative method for skin grafting and cutaneous substitute for bum victims and chronic non healing wounds. The new method of skin grafting is applied repetitively and non-invasively until healing is achieved. PATIENTS AND PROCEDURE: 39 patients including 33 burns victims and six with chronic wounds were treated between February and September 2012. One to four square centimeters of autologous skin graft were transformed with biodegradation of cellular peptic bonds with the goal of obtaining a rich solution of cutaneous cells (1.5 million skin cells/cm2). The process duration averaged 100 minutes. Part of the solution was sprayed immediately on the recipient skin zones. The remaining solution was divided up and kept in cryotubes inside a container of liquid nitrogen. Successive sprays were performed at each dressing.
295. [The return of germline gene therapy].
The recent development of a powerful and flexible genome editing technique (the CRISP-cas9 method) accelerates tremendously the production of animal models and will significantly enhance the perspectives of (somatic) gene therapy. However, it also raises a real possibility of germline modifications in humans, with therapeutic aims or for "improvement": this raises thorny ethical questions that are no longer theoretical (as in the 1990s) but will have to be faced in the very near future.
299. ["Artificial" spermatozoa: next step in assisted reproduction?].300. [Radioresistance parameters in head and neck cancers and methods to radiosensitize].
作者: J Biau.;E Chautard.;J Miroir.;M Lapeyre.
来源: Cancer Radiother. 2015年19卷5期337-46; quiz 360-1, 363页
Head and neck cancers have been widely studied concerning their sensitivity to radiation therapy. Several parameters affect tumour response to radiation therapy. Some parameters are linked to the tumour. Large or invasive tumours, localization, such as oral cavity or adenopathy, are factors of radioresistance. Others parameters are linked to the patients themselves. Tobacco intoxication during radiotherapy and a low hemoglobin level contribute to radioresistance. More recently, a positive human papilloma virus (HPV) status has been reported to positively affect radiosensitivity. Finally, other parameters are related to tumour biology. Hypoxia, intrinsic radiosensitivity of tumour cells, tumour differentiation and repopulation (provided by Ki-67 index or EGFR level) are components of radiosensitivity. Currently, concurrent chemoradiotherapy is one of the gold standard treatments to overcome clinical outcome of locally advanced head and neck cancer. This combination increases locoregional control and survival. Taxane-based induction chemotherapy can also be an alternative. Another validated approach is the association of radiotherapy with cetuximab (EGFR targeting) but only one randomized study has been published. Fractionation modifications, especially hyperfractionation, have given positive results on both tumour control and survival. Strategies targeting hypoxia improve locoregional control but have less clinical impact.
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