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Query: UMLS:C0019621 (Langerhans cell histiocytosis)
 3,250 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes insipidus and anterior pituitary dysfunction, are familiar central nervous system (CNS) complications of Langerhans cell histiocytosis (LCH) but the pathophysiology and biological behaviour of other forms of CNS involvement in LCH are poorly understood. In an attempt to improve our understanding of these rare complications, we studied 23 patients with LCH in whom neuroradiological abnormalities, with or without neurological dysfunction other than diabetes insipidus, developed during the course of disease. Neuroradiological abnormalities were of three basic types (a) poorly-defined changes in white matter, (b) well-defined changes in white and grey matter and (c) extra-parenchymal "tumoural" masses. There was a profusion of associated neurological signs and symptoms in most cases but some patients were asymptomatic. The neuropathological features were complex but infiltration of the CNS by histiocytes with xanthomatous change, particularly prominent in mass lesions, was common in the 13 cases in which biopsies were done. Patients with lytic lesions of the skull and diabetes insipidus are evidently most at risk of developing these rare manifestations of LCH. Therapeutic questions could not be answered from this study because no standard treatment had been given and outcome varied widely.
Br J Cancer Suppl 1994 Sep
PMID:Central nervous system disease in Langerhans cell histiocytosis. 807 2

As a rare, sporadic disease Langerhans cell histiocytosis (LCH) presents a difficult problem in defining a likely etiology. Epidemiological data would not a priori lead one to choose a viral etiology. However, there are rare tumours which occur as sequelae of common infections from Epstein-Barr virus or human papilloma viruses. Likewise some viruses can cause cells to elaborate cytokines which could ultimately stimulate Langerhans cell growth. There is only a small amount of experimental data testing the hypothesis that viruses might be associated with LCH. The theoretical constructs surrounding this question and new data refuting the association are summarised.
Br J Cancer Suppl 1994 Sep
PMID:Viruses and Langerhans cell histiocytosis: is there a link? 807 3

Langerhans cell histiocytosis (LCH) is characterised by an accumulation of cells ('LCH cells') with the same phenotypic features as normal Langerhans cells found in skin and other organs. The pathogenesis of LCH is unknown but there is increasing evidence to implicate the involvement of lymphokines and proinflammatory cytokines in the tissue damage seen in this disorder. Apart from histiocytes, the lesions contain giant cells, macrophages, neutrophils, eosinophils, lymphocytes, plasma cells and occasional mast cells that are the hallmark of an inflammatory process. The role of cytokines in the recruitment of haemopoietic cells within inflammatory lesions has only recently been recognised. In this article, we review the possible role of cytokines in the pathogenesis of LCH, and provide an overview of the methods currently used to detect and quantitate them. An appreciation of the type, distribution and amount of different cytokines released within lesions can provide clues to the possible aetiology of LCH. Using immunoassays, in situ hybridisation and RT-PCR, increased amounts of IL-1, IL-3, IL-4, IL-8, GM-CSF, TNF alpha, TGF beta and LIF have been demonstrated in LCH lesions. Lymphocytes constitutively produce GM-CSF and IL-3 and, to a lesser degree, IL-1, IL-4 and LIF whilst histiocytes produce TNF alpha, IL-1 beta and GM-CSF.
Br J Cancer Suppl 1994 Sep
PMID:The role of cytokines in the pathogenesis of Langerhans cell histiocytosis. 807 4

Optimal treatment of Langerhans cell histiocytosis remains problematic. The absence of controlled studies and the lack of standard diagnostic and evaluation criteria have impeded therapeutic progress even though knowledge of basic aspects of LCH have advanced. Historical analysis of outcome suggests little improvement until very recently, but marked differences in outcome according to extent of disease. Consequently, major and now successful efforts have been made to stratify LCH patients into different 'risk groups'. Recent findings suggest that combination chemotherapy for multisystem disease is beneficial and that VP-16 is a useful new agent for treating LCH, despite controversies regarding its side effects. The first randomised international treatment study, LCH-1, being conducted by the Histiocyte Society, should resolve some of these controversies. Other experimental therapies may be considered for children with severe, unresponsive LCH.
Br J Cancer Suppl 1994 Sep
PMID:Treatment of Langerhans cell histiocytosis--evolution and current approaches. 807 5

The successful use of cytotoxic agents in the clinical management of LCH depends upon the selective targeting of cells participating in the disease process. The topoisomerase 'poisons', currently used extensively in the treatment of aggressive malignancies, represent an intriguing class of cytotoxic agents exerting their cytostatic and cytotoxic effects at multiple levels according to cell type. The non-DNA intercalating topoisomerase II poison, etoposide (VP-16), is the "drug of first choice" in the treatment of LCH by cytotoxic chemotherapy. This major anticancer agent traps the nuclear enzyme DNA topoisomerase II on DNA in a sequence-specific manner, the processing of trapped complexes giving rise to a plethora of cellular effects not least the potential activation of pathways leading to cell cycle arrest and apoptosis. This short review describes the principles of topoisomerase inhibition, the multiplicity of cellular effects and the concept of cellular targeting in LCH. The successful treatment of LCH by cytotoxic chemotherapy will depend on both the identity of the target tissues and a clear view of therapeutic intent, given the potential for induction of haematological neoplasia.
Br J Cancer Suppl 1994 Sep
PMID:Multilevel therapeutic targeting by topoisomerase inhibitors. 807 6

Since the Langerhans Cell (LC) is of haemopoietic origin it may be possible to cure Langerhans cell histiocytosis (LCH) by ablating the patient's own haemopoietic system and replacing it with donor bone marrow--a process termed bone marrow transplantation (BMT). This assumes that the LC itself is the fundamentally abnormal cell though BMT is also a logical therapy even if other cells of haemopoietic origin are eventually shown to be the primary cause of LCH. Marrow ablation/BMT has an appreciable morbidity and mortality and has therefore been reserved for the few LCH patients with a very poor prognosis. The results in these patients engenders cautious optimism that myeloablation/BMT in LCH may have a limited role. Myeloablative chemotherapy or radiotherapy followed by autologous bone marrow 'rescue' is also feasible but risks the return of 'untreated' LCH cells, or their precursors, causing exacerbation of disease.
Br J Cancer Suppl 1994 Sep
PMID:Myeloablative therapy and bone marrow transplantation for Langerhans' cell histiocytosis. 807 7

Many recent studies have demonstrated the range of disorders in which monoclonal antibodies have a clinical role. The monoclonal antibody NA1/34, directed against a surface antigen present on lesional cells ('LCH cells'), has been found to localise in vivo to sites of disease. This review explores the possible applications and limitations of monoclonal antibody based-therapy in Langerhans cell histiocytosis.
Br J Cancer Suppl 1994 Sep
PMID:Monoclonal antibody therapy in Langerhans cell histiocytosis--feasible and reasonable? 807 8

A number of recent studies have shown that it is possible to obtain significant levels of gene transfer and expression in marrow progenitor cells and their progeny by using retroviral vectors. The data obtained from these studies and the possible applications to Langerhans cell histiocytosis (LCH) are reviewed.
Br J Cancer Suppl 1994 Sep
PMID:Current status of gene transfer into haemopoietic progenitor cells: application to Langerhans cell histiocytosis. 807 9

Although effective treatments are available for many children with LCH, there are many others for whom no definitive therapy yet exists. These patients include those with 1) multisystem disease and associated organ dysfunction, 2) chronic, relapsing disease, 3) new onset pituitary involvement associated with diabetes insipidus and 4) long-term complications such as pulmonary fibrosis, liver fibrosis or CNS involvement. This introductory paper discusses these clinical problem areas and then reviews several new therapeutic approaches including novel chemotherapeutic agents, immunosuppressive strategies, bone marrow transplantation and gene therapy.
Br J Cancer Suppl 1994 Sep
PMID:Treatment options--commentary. 807 10

Langerhans cell histiocytosis is difficult to study because of its rarity. Although recent studies indicate that it may be a clonal proliferation this does not prove that it is a malignant tumour. New methods for culturing dendritic cells and their precursors provide the opportunity to resolve issues relating to clonality, underlying genetic lesions and functional abnormalities in LCH or other lesional cells. The expression of the CD1a antigen on LCH cells provides a target for therapy.
Br J Cancer Suppl 1994 Sep
PMID:The scientific challenge of Langerhans cell histiocytosis. 807 11


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