ISSN:1040-8746    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Complete remission can be achieved in the majority of children and adults with acute leukemia but relapses are frequent due to persistent disease below the level of detectability of light microscopy Recently more sensitive molecular biologic and immunologic approaches have been developed for monitoring of leukemia-specific or -associated markers. Methods are now available for follow-up studies in all leukemic entities. New insights have already been gained into the efficiency of therapeutic strategies; persistence of a leukemic marker is a common finding in patients shortly after induction treatment and does not necessarily predict relapse, and increase of positive signals or reappearance of a leukemic marker in complete remission often precedes relapse. However, not all methods are standardized, and levels of sensitivity differ. Conclusions for stratification of postremission therapy can only be drawn after evaluation of ongoing, prospective studies.

ISSN:1040-8746    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Increasing understanding of the processes regulating cell growth, differentiation, and the process of malignant transformation as well as the identification of immunologic defense mechanisms against leukemic cells and a better knowledge of the pharmacokinetics of cytostatic drugs, provide the basis for novel therapeutic approaches being explored in preclinical investigations and early clinical trials. These approaches include antileukemic therapy at the molecular level by attempts to block the translation of central oncogenes by antisense oligonucleotides or the interference with abnormal signal transduction by modulation of key enzyme systems, eg, tyrosine kinases or protein kinase C. Reversion of the neoplastic phenotype may be obtained by transfection of tumor cells with wild-type tumor-suppressor genes or restoration of cellular differentiation, ie, by retinoic acid in acute promyelocytic leukemia. Antisense oligonucleotides may also be applied to abrogate abnormal expression of hematopoietic growth factors. Growth factors are also being used clinically to sensitize leukemic cells prior to cytostatic treatment or for a more rapid recovery of normal hematopoiesis after intensive chemotherapy. Immunologic approaches against leukemic cells are based on the identification of disease-specific markers, providing the target for antibody therapy with monoclonal antibodies coupled to immunotoxins or allowing the augmentation of cell-mediated immunity by cytokine stimulation, ie, with interleukin-2 or retroviral transfer of genes, eg, the tumor necrosis factor-α gene into effector cells. New perspectives also arise from a more detailed knowledge of cytostatic drug pharmacokinetics and the detection of metabolic differences between leukemic cells and their normal hematopoietic counterparts, allowing the design of more specific and tumor-directed drug scheduling. This review highlights some examples of recent preclinical findings that may translate into a better understanding of leukemia biology and ultimately improved therapy for these diseases.

ISSN:1040-8746    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

New clinical and epidemiologic studies provide information about the possible causes of human leukemia. Evidence for a viral etiology continues to appear, and the relationship between myelodysplastic syndrome and the leukemias is now linked through molecular genetic studies. Molecular mechanisms of leukemogenesis are being understood through evaluation of preleukemic conditions and predisposing medical illnesses. Epipodophyllotoxins and, to a lesser extent, cisplatin are being linked causally to secondary leukemia. Potential environmental causes of leukemia are being intensively investigated with both positive and negative results. The literature on the epidemiology of leukemia is growing rapidly, and important leads toward a more complete understanding of its etiology are emerging.

ISSN:1040-8746    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

A consistent stimulus to increase interest in malignant disease is the discovery of new successful treatments. The dramatic activity of the nucleoside analogues, 2-deoxycoformycin, fludarabine, and 2-chlorodeoxyadenosine, in indolent lymphoproliferative diseases has caused a reawakening of interest in the biology and treatment of chronic lymphocytic leukemia and hairy-cell leukemia. The high response rate has led to a reevaluation of criteria for response in these diseases as well as indications for treatment and prognostic factors.

ISSN:1040-8746    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Recent advances in therapy for childhood acute lymphoblastic leukemia have come primarily from the intensive laboratory study of patient's lymphoblasts. DNA-ploidy determination, the analysis of specific chromosomal translocations, andin vitrochemosensitivity studies now facilitate the stratification of risk groups and the prediction of treatment outcome. More is known about the heterogeneity of molecular defects involved in leukemogenesis, and this information is being exploited to devise sensitive tests for minimal residual disease. Conventional chemotherapy of childhood acute lymphoblastic leukemia is associated with adverse neuropsychological sequelae and second malignancies when intensive epipodophyllotoxin therapy is used. Treatment of relapsed acute lymphoblastic leukemia remains problematic. The development of alternative donor marrow sources will expand the role of bone marrow transplantation, which has provided better outcomes for a limited number of patients. We are still waiting to spawn novel therapeutic agents that are more effective and less toxic than present chemotherapy.

ISSN:1040-8746    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The treatment of acute myeloid leukemia has made steady rather than spectacular progress in the past few years, principally because of improved supportive care. The use of hematopoietic growth factors may contribute to the speed of normal bone marrow recovery following treatment; however, their potential role as modifiers of drug pharmacokinetics may be equally valuable in overcoming drug resistance. The full range of expression of the phenomenon of resistance is being intensively explored, and therapeutic opportunities for overcoming the P-glycoprotein pump are now being introduced. Gene therapy and exciting immunologic manipulations are also developing rapidly, and the role of suppressor genes has reached a fascinating point in research and clinical applications.

ISSN:1040-8746    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:1040-8746    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Familial neuroendocrine tumors are reviewed. The most dramatic advances have been the application of molecular genetic techniques to define the etiologies and develop predictive testing for patients with multiple endocrine neoplasia type 1 and type 2 syndromes. All three neoplastic lesions involved in multiple endocrine neoplasia type 1 (parathyroid, pituitary, and pancreatic islet) have shown loss of heterozygosity at chromosome 11. By contrast, the most consistent occurrence of loss of heterozygosity in tumors from multiple endocrine neoplasia type 2 patients was not at chromosome 10 but at chromosome 1 p. Molecular genetic testing of multiple endocrine neoplasia type 1 and type 2 family members at risk provides a powerful tool for early identification and treatment of susceptible individuals. Efforts to clarify familial neuroendocrine tumors without associated multiple endocrine neoplasia syndromes continue. The best characterized tumor of this type is familial medullary thyroid carcinoma. Familial paraganglioma, neuroblastoma, and carcinoid also are reviewed. Potential barriers to genetic screening for familial neuroendocrine tumors are discussed.

ISSN:1040-8746    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Neuroendocrine tumors are a group of malignancies that arise from primitive neuroectodermal cells. There is, however, considerable variation in the location and clinical behavior of these tumors. They are often difficult to distinguish from other malignancies and difficult to classify. Recent advances in molecular genetics have attempted to resolve some issues regarding accurate diagnosis, classification into prognostic subgroups, and understanding of basic common mechanisms underlying the development of these tumors. Correlation of morphologic changes with molecular changes induced by some potential therapeutic differentiating agents may lead to more rational therapy for these malignancies.

ISSN:1040-8746    

出版商:OVID    

年代:1993

数据来源: OVID