Metastatic osteosarcoma at diagnosis: prognostic factors and long-term outcome--the French pediatric experience

BACKGROUND: The objective of this report was to estimate long-term outcome and prognostic factors in children and adolescents who presented with metastatic osteosarcoma at diagnosis. Patients were treated in six French pediatric oncology centers with surgery and multiagent chemotherapy, mainly with high-dose methotrexate. Their medical records were reviewed retrospectively. METHODS: The medical records of patients who were treated for metastatic osteosarcoma from 1987 to 2000 were reviewed. Patients were treated with the chemotherapy regimens recommended for nonmetastatic disease in children (the French Society of Pediatric Oncology OS 87 and OS 94 protocols) or, in a few patients, with other chemotherapy regimens. Surgical excision of the primary tumor and, when possible, of all metastatic sites was performed based on a personalized assessment of each patient's situation. RESULTS: Seventy-eight patients age < 20 years were treated. Forty-six patients (59%) had only 1 metastatic site (35 to the lungs and 11 to bone). Twenty-eight patients (36%) achieved a complete remission after combination chemotherapy and surgery. The event-free survival and overall survival rates at 5 years were 14% and 19%, respectively. To date, 14 patients (18%) have remained alive with a median follow-up of 112 months. Pretreatment features associated with a shorter event-free survival in the multivariate analysis were metastasis to at least two organs and high alkaline phosphatase level. Patients with at least 1 of these poor prognostic factors had a 2.6% event-free survival rate at 5 years despite treatment. CONCLUSIONS: The survival of patients with metastatic osteosarcoma were treated with conventional chemotherapy and surgery remained very poor. Patients should be classified into different prognostic groups and treated accordingly. New therapeutic approaches are warranted to improve the prognosis for patients with the most severe disease.     

Disclosure of diagnosis of Alzheimer's disease in French general practice

Most practitioners find disclosing the diagnosis of Alzheimer s disease (AD) to an individual with dementia very difficult. Literature results show a wide variability in attitudes and clinicalpractice, and diagnosis seems to be more often disclosed to caregivers than to patients. The objective of this study was to examine whether and how diagnosis of AD is disclosed in French general practice and which issues are addressed with the patient. A questionnaire was sent via mail to 1,629 general practitioners (GPs), 1,105 belonging to the Sentinel's network and 524 specially recruited doctors practicing in the Rh?ne-Alpes region. A total of 631 questionnaires were returned (response rate, 39 percent), of which 616 were eligible for analysis. Twenty-eight percent of GPs reported having disclosed diagnosis to the patient (25 percent mentioned "Alzheimer's disease"), whereas 88 percent considered it their role to announce the diagnosis to the patient. Regarding the type of information provided to the patient, only 25 percent discussed the nature of the illness, 23 percent behavioral problems, and 47 percent depression, mainly for psychological reasons (63 percent). Stress was discussed with 79 percent of the caregivers. We concluded that GPs do not discuss the consquences of AD and symptoms (e.g., behavioral disorders) with patients, mainly for psychological reasons, whereas they have a less-reluctant attitude toward caregivers. As the GP has the weighty task of providing ropriate community care and psychological support to the patient, it is of utmost importance to reflect on how disclosure of diagnosis can be facilitated.     

A probable case of alveolar echinococcosis in Normandy, France

Echinococcus multilocularis induced liver infection was diagnosed in a Moroccan patient. Diagnosis was based on CT scan results and Western Blot test. Contamination probably occurred in France, in the Cherbourg area where the patient travelled frequently and ate wild berries. This case and other recently reported cases outside the usual endemic areas (Besan?on and the Massif Central) suggest that the Echinococcus multilocularis epidemic has moved towards the west of France. French gastroenterologists should be aware of this parasitic disease.     

The adenine nucleotide translocator: a new potential chemotherapeutic target

Identification of new targets is of utmost importance for the development of efficient apoptosis-modulating drugs. This has become possible from the unraveling of the basic apoptosis mechanisms and notably, from the demonstration of the mitochondrial membrane permeabilization as a central rate-limiting step of numerous models of cell death. Indeed, molecular and pharmacological studies revealed that the adenine nucleotide translocator (ANT) could be a therapeutic target. First, ANT is a bi-functional protein. It mediates the exchange of cytosolic ADP and mitochondrial ATP, and contributes to apoptosis via its capacity to become a lethal pore. Second, both ANT functions are under the control of the (anti)-oncogenes from the Bax/Bcl-2 family, and third, agents as diverse as proteins, lipids, ions, pro-oxidants or chemotherapeutic agents directly modulate the pore-forming activity of ANT. Here, we will review the mode of apoptosis induction by various classes of chemotherapeutic agents, which all influence directly ANT pro-apoptotic function. Hopefully, this will yield several clues to the modulation of apoptosis from a therapeutic perspective.     

Caffeic acid phenethyl ester (CAPE) prevents inflammatory stress in organotypic hippocampal slice cultures

Caffeic acid phenethyl ester (CAPE) is an antioxidant component of propolis, a natural product secreted by honeybee. Recent literature shows that CAPE inhibits nuclear factor kappa B (NFkappaB) activation in cell lines. Since NFkappaB was shown to be a crucial factor in neuroinflammation and to be associated with some neuropathologies, CAPE might reduce these disorders in brain too and have therapeutic applications. To test this hypothesis we used a model of endotoxic insult (interferon-gamma, followed by lipopolysaccharide) on rat organotypic hippocampal cultures. Cerebral inflammatory responses were strongly inhibited by CAPE (100 microM): reductions of NFkappaB nuclear activity, tumor necrosis factor alpha and nitric oxide productions were observed. At the dose of maximal effects (100 microM), an increase of cAMP-responsive element binding protein (CREB) activity, which anti-inflammatory role is well known, was seen. We compared CAPE effects with those of other drugs: anti-inflammatory as acetyl-salicylate and dexamethasone (glucocorticoid), antioxidant as pyrrolidine dithiocarbamate, or selective permeant inhibitor of NFkappaB as SN 50 peptide. These studies lead us to conclude that CAPE presents an interesting and original neuropharmacological profile compared to these drugs and might be helpful in the prevention of neurotoxic events due to excessive inflammatory reaction in brain. CAPE interferes with several effectors of neuroinflammation that might have complementary and synergic effects and allows a rather durable control since an acute treatment at the time of endotoxin exposure allows to control inflammatory factors for over 48 h.     

Applying peptide antigens onto bare skin: induction of humoral and cellular immune responses and potential for vaccination.

The development of non-invasive immunisation procedures is a top priority for public health agencies when it is realised that the current immunisation practices are unsafe, particularly in developing countries due to the widespread reuse of non-sterile syringes. There is a risk of abscess formation resulting in impairment of meat quality or the value of the hide, and the risk of transmission of infectious diseases when vaccines are administered to food animals by injection. Recently, the skin has emerged as an alternative route for non-invasive delivery of vaccines. Topical application of various types of antigens (mainly proteins and toxoids) with an adjuvant resulted in the induction of systemic and mucosal immune responses. However, due to skin barrier constraints and the physicochemical properties of large molecular weight proteins, the immune responses are variable and require further optimisation. Small molecular size synthetic peptides when applied onto bare skin with an adjuvant are effective immunogens, inducing both humoral and cellular immune responses. Their use as vaccines offers considerable advantages over conventional preparations in terms of safety, purity, stability, availability and cost. Therefore, they could be the most suitable candidate immunogens for skin immunisation. This review describes our recent observations on the immunogenicity of synthetic peptides applied onto bare skin in relation to vaccination.