ISSN:1040-8746    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The leukemias are complex diseases with a wide range of clinical, morphologic, biologic, molecular, and clinical features and a consequent array of possible responses to any given intervention. Although progress has been made in the management of the leukemias, most patients who fail to respond to front-line therapies or who relapse after an initial response die from progressive disease. The balance between efficacy and toxicity of traditional cytotoxic therapies is increasingly unacceptable. As a consequence, the search for therapeutic advances is more focused on affecting the critical steps involved in the development, propagation, and mutation of malignant clones. This article briefly reviews current data on some agents being developed for the treatment of patients with leukemia, with an emphasis on modulators of angiogenesis, inhibitors of the ubiquitin-proteasome pathway, novel nucleoside analogues, and gene hypomethylation agents.

ISSN:1040-8746    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Over the past several years, the application of a spectrum of cytogenetic and molecular diagnostic techniques has dramatically improved our understanding of the pathophysiology of leukemia. These techniques include chromosomal translocations visualized by G-banding techniques, fluorescence in-situ hybridization, spectral karyotyping, comparative genomic hybridization, loss of heterozygosity analysis, and characterization of point mutations by DNA sequence analysis. We will review the application of these techniques, update novel findings utilizing these techniques over the past year as they apply to specific leukemias, and review the clinical and therapeutic implications of these findings.

ISSN:1040-8746    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

For most of the 20th century, subclassification of acute myeloid leukemia (AML) was based on the resemblance of blasts to normal hematopoiesis. This approach was standardized by the French-American-British (FAB) group. Because of limited clinical relevance, clinicians resorted to other patient characteristics to determine treatment and predict outcome in AML. A different approach based on the relationship of a case to myelodysplastic syndrome (MDS) has been proposed. The new World Health Organization (WHO) subclassification of AML includes elements of this new proposal but retains as a major category the historical subclassification. The WHO group has also proposed modifications of the FAB subclassification of MDS. These MDS proposals have generated discussion of diagnostic criteria for MDS and a philosophical discussion of whether MDS should still be considered a syndrome, or rather a specific set of diseases characterized by genetic instability and poor outcome.

ISSN:1040-8746    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Acute myeloid leukemia is a disease predominantly affecting older adults, with a median age at diagnosis of 65 years. Compared with younger adults or children with AML, older adults have a poor prognosis and represent a discrete population in terms of disease features, treatment-related complications, and overall outcome. Management of AML in this population often includes intensive, anthracycline-based chemotherapy, which can effect a 1.5- to 4-month survival advantage compared with nonintensive therapy but at a cost of early deaths, long length of hospital stay, and substantial transfusional support. Nonintensive therapy or palliative care remains an important option for many patients. Aggressive postremission therapy or the use of hematopoietic growth factor support does not appear to improve survival. Future directions include therapies targeted at immunomodulation, at angiogenesis, and in particular against intracellular signals that promote proliferation at the expense of differentiation.

ISSN:1040-8746    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Multiple myeloma is a clonal B-cell tumor of slowly proliferating plasma cells within the bone marrow. Among hematologic malignancies, it constitutes 10% of the cancers and ranks as the second most frequently occurring hematologic cancer in the United States, after non-Hodgkin lymphoma. Interleukin-6 is an important cytokine in myeloma cell growth and proliferation. Close cell-to-cell contact between myeloma cells and the bone marrow stromal cells triggers a large amount of interleukin-6 production, which supports the growth of these cells, as well as protecting them from apoptosis induced by dexamethasone and other chemotherapeutic agents. Therapies modulating the tumor and its microenvironment are being actively pursued with the goal of converting multiple myeloma to a chronic disease with the patients maintaining a normal lifestyle.

ISSN:1040-8746    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:1040-8746    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Carcinoid tumors are rare neoplasms which, by tradition, have been divided into foregut, midgut, and hindgut tumors. Although they share many features, they seem to have different molecular backgrounds. Foregut tumors very often show involvement of theMEN1gene with deletions and mutations, whereas midgut carcinoids display genetic changes on chromosome 18. Hindgut tumors in general show rather low proliferation capacity, and transforming growth factor-&agr;/epidermal growth factor receptor autocrine mechanism may play a role in the tumor development. Sometimes it might be a problem to delineate the location of the primary carcinoid tumor, but analyzing thyroid transcription factor-1 can be of help, because this factor is only expressed in foregut carcinoid and not in midgut or hindgut tumors. Chromogranin A is an important general tumor marker for all types of carcinoid tumors. Somatostatin receptor scintigraphy is a cornerstone in staging and localization of carcinoid tumors, but newer techniques such as positron emission tomography will challenge its position in the future. Although surgical cure is not obtainable, a more aggressive surgery has emerged during the last decade. Debulking and other cytoreductive procedures are quite common today. Somatostatin analogues have been the treatment of choice in symptomatic patients with carcinoid tumors, but more recent studies have indicated a cytostatic effect of somatostatin analogues. Tumor-targeted radioactive treatment based on somatostatin analogues is now under clinical evaluation. Preliminary data indicate interesting clinical potentials.

ISSN:1040-8746    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Less than 1% of all cancers are present in the thyroid, yet thyroid nodules are found in 4 to 10% of the adult population. Because thyroid nodules are relatively common, the diagnostic dilemma is to distinguish between a more common benign nodule, which usually does not require specific treatment, and a malignant nodule, which requires thyroidectomy and further treatment. Thyroid nodules usually are an incidental finding on a routine examination by a primary care physician. When patients seek treatment for symptomatic nodules, a more serious problem may be indicated, and thyroid cancer is suggested. However, additional studies have demonstrated the use of genetic markers and immunohistochemistry in the diagnosis of thyroid nodules, which may lead to a more rational approach to the treatment. This article reviews literature published in the last 12 months pertaining to the pathogenesis, diagnosis, and treatment of thyroid nodules.

ISSN:1040-8746    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Somatostatin and its octapeptide analogues exert their effects through interaction with somatostatin receptor (sst) subtypes 1 through 5 (sst1–5). Somatostatin binds with high affinity to all sst subtypes, whereas the currently commercially available octapeptide analogues bind only with a high affinity to sst2and sst5. Pituitary tumors, endocrine pancreatic tumors, and carcinoid tumors express multiple sst subtypes, but sst2predominance is found in 90% of carcinoids and 80% of endocrine pancreatic tumors. Sst2and sst5predominance is found in growth hormone–secreting pituitary tumors. In patients harboring sst2- or sst5-positive neuroendocrine tumors, clinical symptomatology can be controlled by the chronic administration of one of the currently commercially available octapeptide somatostatin analogues. Tumors and metastases that bear sst2or sst5can be visualized in vivo after injection of radiolabeled octapeptide analogues. Radiolabeled octapeptide analogues can also be used for radiotherapy of sst2- and sst5-positive advanced or metastatic neuroendocrine tumors.

ISSN:1040-8746    

出版商:OVID    

年代:2002

数据来源: OVID