摘要:

Peripheral blood cytopenias and dysplastic hematopoietic progenitors characterize the myelodysplastic syndrome. Patients suffer from the consequences of chronic cytopenias or progression to acute myelogenous leukemia. Although allogeneic hematopoietic stem cell transplantation is a potentially curative option, the standard of care for most patients with myelodysplastic syndrome continues to be supportive care, with blood product transfusion and antibiotics for infectious complications. Many patients with myelodysplastic syndrome are not candidates for allogeneic hematopoietic stem cell transplantation because of advanced age, comorbid illnesses, and lack of a histocompatible donor. Increased rates of apoptosis in hematopoietic progenitors, altered production of inflammatory cytokines, neoangiogenesis, and autoreactive T lymphocytes have all been shown to contribute to the phenotype of myelodysplastic syndrome. These recent insights into the pathophysiology of myelodysplastic syndrome have been translated into therapeutic trials of noncytotoxic agents for this disorder. Although clinical responses have been seen with these novel agents, the critical biologic targets have not yet been clearly defined.

ISSN:1040-8746    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Within the past few years, the introduction of imatinib mesylate (imatinib) has profoundly changed the management of patients with chronic myelogenous leukemia. This review article addresses the recent advances in the treatment of chronic myelogenous leukemia—in particular, maturing data on the use of imatinib in different phases of the disease; the optimal therapy of newly diagnosed patients; the emergence of resistance to imatinib and potential strategies to overcome this problem; and finally, the place of stem cell transplantation in current treatment algorithms.

ISSN:1040-8746    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Recent advances in our understanding of the biology of chronic lymphocytic leukemia have made it possible to stratify patients according to risk. In addition, advances in the therapy of patients have improved responses and have for the first time allowed for a risk adapted approach to patients with chronic lymphocytic leukemia similar to that which has been used for acute leukemia for years. Tumor cell differentiation status and presence of specific somatic and immunoglobulin gene mutations have been shown to be reliable predictors of disease behaviors. This knowledge could provide clinicians with tools to better stratify patients and eventually affect their clinical outcomes. Furthermore, new therapeutic agents and treatment combinations that appear to have increased efficacy have been developed.

ISSN:1040-8746    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Acute leukemia is the most common form of childhood cancer and is the primary cause of cancer-related mortality in children. In the United approximately 3250 cases are diagnosed annually in children and adolescents younger than 20 years, of whom 2400 have acute lymphoblastic leukemia (ALL). Treatment results in childhood ALL continue to improve, and the expected current cure rates approach 75 to 80% of all children with ALL, including T-ALL and mature B-cell ALL, the two variants that, not too long ago, had a considerably poorer prognosis compared with the common form of BpALL. The most significant new development in the past 2 years has been the development of further evidence for fetal origin of childhood leukemias, and additional evidence to support the notion that postnatal events modulating the events of immune-mediated elimination of these leukemic clones play a major role in the eventual development of clinical disease. Other epidemiologic developments include (1) increased appreciation of the role of drug-metabolizing enzymes, both in determining the predisposition to leukemia and response to therapy; and (2) both clinical observations and gene expression studies seeming to identify a new approach to the evaluation and treatment of children with MLL (11q23) rearrangements.A most remarkable new development in the induction therapy of childhood leukemia and lymphoma in the United States is the use of urate oxidase for prevention of tumor lysis syndrome and the associated uric acid nephropathy. Drug resistance, determined either on leukemic blast cellsin vitroor by studies of MRD, is being looked at critically in an effort to improve the treatment results further. Consolidation with HDMTX has gained wider popularity with the realization that effective CNS prophylaxis can be achieved with intrathecal therapy plus HDMTX for consolidation.In contrast to ALL, the progress in the therapy of acute myeloid leukemia (AML) lags behind, with cure rates of approximately 40 to 50%. There is no convincing evidence for substitution of daunorubicin with other anthracyclines, nor evidence for using high-dose cytarabine during induction in childhood AML. Rather, a 3 + 10 regimen with total daunorubicin 180 mg/m2and cytarabine 100 to 200 mg/2for 10 days appears to yield the best results. The most important component of the postremission chemotherapy continues to be several courses of high-dose cytarabine. The results from the MRC 10, LAME 89/91 studies and the recent BFM 93 trial with high-dose cytarabine and mitoxantrone suggest that there may be some benefit to including this combination in the postremission phase of AML. Despite these improvements in chemotherapy, allogeneic BMT from a matched family donor remains the best option for most patients (excluding Down syndrome, APL, and possibly those with inv16). Newer prognostic markers of interest include FLT3/ITD and minimal residual disease at the end of induction therapy.

ISSN:1040-8746    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Since the discovery of the first oncogene 26 years ago, a large body of research has convincingly demonstrated that the initiation and progression of cancers involve the accumulation of genetic aberrations in the cell. Many techniques have been developed to identify these genetic abnormalities. The recent completion of human genome sequencing and advances in DNA microarray technology allow rapid genetic analysis to take place on a genome-wide scale and have revolutionized the way cancers are studied. This groundbreaking approach of studying cancer promises to provide a better understanding of the underlying mechanism for tumorigenesis, more accurate diagnosis, more comprehensive prognosis, and more effective therapeutic interventions.

ISSN:1040-8746    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Serial analysis of gene expression has been widely used to characterize gene expression patterns associated with tumor formation. These studies resulted in the identification of tumor-specific markers, transcriptional pathways, or therapeutic targets. In this review, recent applications and developments of serial analysis of gene expression and their impact on the diagnosis and treatment of cancer are discussed. A combination of serial analysis of gene expression and small-scale microarray analysis represents a strategy that should facilitate the identification and exploitation of tumor-specific gene expression for diagnostic or therapeutic purposes. In addition, cancer diagnosis and treatment may benefit from a complementation between serial analysis of gene expression and quantitative proteomics in the future.

ISSN:1040-8746    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Single nucleotide polymorphisms are the most abundant genetic markers in the human genome whose analyses can be easily conducted on a large scale. Most established methods for high-throughput single nucleotide polymorphism analyses are qualitative and are not suitable for genetic analysis of archived tumor specimens, which have compromised tissue integrity and normal tissue contaminations. Recent studies have focused on the development of quantitative methods for single nucleotide polymorphism analyses that can tolerate such imperfections in archived tissues. These methods have been used to measure the rate of allelic imbalance in small adenocarcinomas and to reveal novel correlations between allelic imbalance and disease progression in colorectal cancer. Therefore, quantitative single nucleotide polymorphism analysis provides a powerful tool for the identification of novel tumor markers and for the characterization of genetic alterations in human tumors.

ISSN:1040-8746    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Many different signaling pathways are involved in deregulation of cell proliferation leading to cancer. Although genomic approaches successfully identified a great variety of molecules associated with cancerogenesis, other strategies must be applied to elucidate complex interactions between these molecules. One promising approach is fluorescence resonance energy transfer, a proximity-dependent fluorescence phenomenon. With the development of spectrally different fluorescent proteins and improved technologies for fluorescence measurements, this approach gains an enormous potential for future research. The fluorescence resonance energy transfer principle can be applied for studying all kinds of interactions or conformational changes, and it can also be used for microscopic visualization and subcellular localization of biochemical reactions, thereby promoting the progress of cancer research. Moreover, it can be exploited to develop sensitive and efficient drug screening systems and to design valuable diagnostic tools.

ISSN:1040-8746    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:1040-8746    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Thyroid nodules are found in 4 to 7% of the population, and with the increased use of radiographic methods, incidental nodules are becoming more prevalent. Only 5% of all nodules will be malignant, and thyroid cancer accounts for only 0.4% of all cancer deaths. The preferred diagnostic approach is early referral, avoidance of numerous radiologic evaluations, and early performance fine-needle aspiration. This article reviews the literature of the last 12 months and discusses some of the new molecular, genetic, and immunostaining techniques in the evaluation of thyroid nodules.

ISSN:1040-8746    

出版商:OVID    

年代:2003

数据来源: OVID