Bulletin et memoires de l'Academie royale de medecine de Belgique最新文献

Osteonecrosis of the femoral head is a rare disease that affects young patients and is characterized by the occurrence of a necrotic lesion in the femoral head, loss of mechanical resistance of dead bone and collapse of the femoral head. Patients complain of hip pain and loss of function that could lead to total hip replacement. So far, osteonecrosis was considered as a vascular disease due to vascular section or compression leading to bone necrosis. We studied the physiopathology of the osteonecrosis considering it as a bone disease. We demonstrated as well as other teams that the number of mesenchymal stem cells, precursors of bone cells and osteoblastic cells, were reduced in patients with osteonecrosis. We initiated a controlled double blind trial to study the efficacy of stem cells implantation--obtained from concentrated bone marrow--in the osteonecrosis zone. This study showed that bone marrow implantation could delay disease progression to the fractural stage and improve hip pain and joint symptoms. We then tried to improve this treatment by developing a bone cell therapy product formed of osteoblastic cells. A novel cell therapy product formed ofosteoblastic cells, PREOB was developed. PREOB was tested in a randomized, controlled phase II trial in osteonecrosis of the femoral head and showed its superiority compared to concentrated bone marrow. Today, this cellular therapy product is developed by Bone Therapeutics, a spin-offcompany of the "Université libre de Bruxelles". Other bone diseases are characterized by reduced activities of stem cells that are unable to meet the need of bone remodelling due to a non-union fracture, for example. Clinical studies also showed that concentrated bone marrow could be implanted into the non-union. However, its efficacy was dependent on the number of implanted stem cells. The cellular therapy product is currently tested in a phase I trial with promising preliminary results. Cellular therapy for bone diseases is a novel therapeutic approach that evolves from stem cells to the use of the differentiated cells of interest.

The emotional power of music opens novel prospects in the field of affective neurosciences. To clarify the neurobiological substrate of emotions brought by music, we adopted an integrative approach, which combines neuropsychology, brain imaging and electrophysiology (intracranial depth electrode recordings). The results of a series of studies carried out in patients with focal brain lesions allow to describe the involvement of different temporal lobe regions and, in particular, of the amygdala in these emotional judgments before discussing the therapeutic benefits of music to handle Alzheimer's disease.

In tumours, a significant fraction of neoplastic cells are engaged in the cell cycle (growth fraction) and are therefore targets for radiation therapy and chemotherapy. Unfortunately, in most disseminated cancers, such treatments cannot lead to complete cure. Many different mechanisms have been described to explain this resistance. The hypothesis of the existence of "cancer stem cells "has been recently proposed. Indeed, the tumour would contain a small subpopulation of cancer cells displaying the phenotypical characteristics of multipotential stem cells. Since such cells display different signalling pathways compared with more differentiated cells, this might explain at least partially the resistance to treatments. Chronic myeloid leukaemia is a good model in favour of cancer stem cells, but the presence of such cells in all types of cancers is still a matter of debate. Several questions emerge: is the multipotential stem cell, the cell of origin of cancer? What is the relevance of the cancer stem cell paradigm for understanding cancer cell biology and to envision new therapeutic, hopefully curative, therapies? The case of chronic myeloid leukaemia is used to discuss these questions.

Breast cancer remains by far the most frequent cancer in women, for that matter it is the most frequent cancer in Belgium affecting both men and women. At the moment, more than 9000 cases are detected annually. The development of screening allows us, fortunately, to detect lesions and stages earlier, in that way locoregional treatmenthas considerably evolved. Since the seventies, radical mastectomy, which consists of the removal ofthe mammary gland, the axillary glands (lymph nodes) and sometimes the pectoral muscle, has been progressively replaced by conservatory treatment. This consists of a wide excision of the tumour with a safety resection margin, followed by a complete removal of the axillary glands (lymph nodes) then followed by a course of external radiotherapy testing treated six weeks daily on a five days week basis. During the nineties, in cases with certain precise indications, the complete axillary gland removal has been replaced by the removal of the first gland chain (lymph node chain) called "sentinel nodes". This technique avoids all morbidity associated to the complete lymph node removal. Finally, very recently, the classic external radiotherapy has been replaced by partial radiotherapy delivered exclusively in a few minutes during the surgical operation. Therefore, we can offer patients with early stage lesions a locoregional treatment carried out in one to two hours with an in-stay hospitalisation of two nights. This new technique manifestly offers a better locoregional control of the illness and very likely enhances (improves) their chances of recovery.

Trypanosoma cruzi, the protozoan agent of Chagas disease infects ten million people in Latin America where it is the main cause of cardiac failure. It is transmitted by insect vectors in endemic areas, and also congenitally, by transfusion of infected blood, transplantation of infected organs and oral route in both endemic and non-endemic areas. Since the 1990s, a constant decrease of incidence of infection is observed in Latin America, where vector control programmes and improvement of blood banks have been implemented. However, the important migration flows in the last decades for economic reasons have brought considerable numbers of Latin American subjects infected with T. cruzi, in US, Europe, Japan and Australia. Such globalization of T. cruzi infection/Chagas disease has been confirmed in an WHO historical meeting in 2007, emphasizing the importance of a wise management of such patients and the need of implementing control measures in blood banks, transplantation centres and maternities of involved countries in non-endemic areas. This paper considers these elements and the present situation of Chagas disease in Europe and Belgium.

Immunogenic cell death, characterized by calreticulin exposure on the surface of the dying cell, release of the nuclear protein high mobility group box 1 (HMGB1), and release of ATP, enables stimulation of the immune system. We outlined the importance of this kind of cell death for the success of some anticancer chemotherapies. However, defects in the immunogenic cell death signalling pathway can lead to therapeutic failure, apparently because anticancer immune responses must contribute to the efficacy of chemotherapeutic regimens. These defects can be related to the therapy, the tumour cell, the host or the tumour-host interface. It is necessary to characterize these defects to restore and improve the efficacy of anticancer chemotherapies.

The discovery of the dynamic electrical properties of bone is at the origin of the therapeutical application of the electromagnetic fields in Orthopaedics and Traumatology. The first empirical treatment of non-union, fresh fractures and osteonecroses allowed the observation of several effects which, without justifying a systematic clinical application, encouraged further fundamental research. The results of this work realized during 35 years are summarized in the present article. After exposure to specific electromagnetic fields, we observed a modification of the DNA activity and an increased production of RNA. During enchondral ossification, the amount of acid GAGS increased faster and the ossification of the primary ossification point is accelerated. On fresh fractures, the rigidity of the callus increased faster. Finally, the microarrays analyses show an upregulation of mRNA involved in cellular differentiation and proliferation. The mRNA responsible of the production of BMP-2 is significantly increased, explaining the main results observed after the expense of experimental models of the bond tissues. All the observed results are in favour of an acceleration of the cellular differentiation at the expense of the proliferation.

Squamous cell cancer of the uterine cervix is associated with a high morbidity and mortality worldwide and in Belgium. The link between cervical cancer and HPV has generated, in recent years, a great interest for studies aiming to better understand the role of the immune system in the control of these infections and for the development of prophylactic anti-HPV vaccines. The purpose of this work was to analyse the immune co-factors implicated in the promotion of the neoplastic process. We have shown that both virus-induced immune alterations and squamous metaplasia in the transformation zone of the uterine cervix play a role to create an immunotolerogenic microenvironment during the cervical carcinogenesis.