ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Hematopoietic cell transplantation (HCT) is a treatment with curative potential for sickle cell disease (SCD). The experience of HCT for persons with β-thalassemia major has been successfully extended to SCD. Currently, the event-free survival rate after allogeneic-matched sibling HCT for SCD is 82%. However, short-term and long-term transplant-related complications remain substantial barriers to HCT, particularly in older patients with life-long complications of SCD. Novel conditioning regimens that minimize transplant-associated toxicity have been developed and show promise for wider application of HCT. Alternative stem cell sources may also expand the availability of HCT for selected patients with SCD.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Idiopathic myelofibrosis (IMF) is a hematopoietic stem cell disorder characterized by hypercellularity of the bone marrow with an increase in abnormal megakaryocytes, varying degrees of marrow fibrosis, and extramedullary hematopoiesis. The central lesion of the IMF stem cell is not known; however, the marrow fibrosis is a polyclonal reaction to inflammatory mediators generated by the transformed clone. Historical management approaches have centered on improving the patient’s blood counts in a palliative manner. Recent reports of autologous and allogeneic bone marrow transplantation (BMT) in IMF patients indicate that stable engraftment occurs easily, the marrow fibrosis is a reversible process, and a graft-versus-fibrosis effect may exist. The goals of future therapies will target marrow fibrosis and harness the graft-versus-fibrosis effect to safely and effectively treat patients with IMF.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The myeloablative doses of chemotherapy and radiation used with conventional allogeneic hematopoietic cell transplantation produce considerable morbidity and mortality that generally limit this treatment to patients younger than 55 years of age and in good general medical condition. It has become clear that T-cell-mediated graft-versus-tumor effects play an important role in the elimination of malignant disease after allotransplants. Several investigators have sought to reduce regimen-related toxicities while optimizing graft-versus-tumor effects. Strategies can be broadly categorized as reduced-intensity regimens that retain some toxicities and require hospitalization, and minimally myelosuppressive regimens that rely on immunosuppression for allogeneic engraftment and resultant graft-versus-tumor effects. The latter approach can be performed in the ambulatory care setting. Preliminary results are encouraging. If long-term efficacy is demonstrated, such strategies would expand treatment options for patients who would otherwise be excluded from receiving conventional allografts.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Recent biotechnologic knowledge has enabled the discovery of a cornucopia of genetic abnormalities commonly involved not only in cancer but also in other diseases ranging from the plague to arteriosclerosis. The wealth of possibilities uncovered by this knowledge inspires the hope that today’s dream of a unified concept of common treatment for multiple diseases could become a future reality. This review arbitrarily categorizes recent findings into five major areas. First, cisplatin resistance associated with the nucleotide excision repair pathway can help clinical oncologists to choose between cisplatin and noncisplatin combinations. Second, the relevant role of nuclear factor-κB as a predictor of chemosensitivity can lead to the development of new drugs abrogating nuclear factor-κB expression. Third, the presence of tubulin mutations, which are directly involved in resistance to microtubule-interactive drugs, can guide chemotherapy based on taxane or nontaxane combinations. In addition, certain chromosomal deletions affect genes involved in deoxyribonucleotide synthesis, like ribonucleotide reductase, that intervene in gemcitabine metabolism; this raises interest in investigating deletion at chromosome 11p15.5 as a potential mechanism of gemcitabine resistance. Finally, an overwhelming number of publications have analyzed genes involved in cell cycle regulation and development as predictive markers of survival; however, where these pieces fit into the puzzle of cancer management is still unclear.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

There have been important recent advances in the management of inoperable non–small cell lung cancer. Concurrent cisplatinum-or carboplatin-based chemotherapy and 60 to 64 Gy of thoracic radiation therapy has replaced sequential therapy as the new standard therapy for good-risk patients. New agents such as docetaxel, gemcitabine, and irinotecan are being tested to replace the standard chemotherapy given during thoracic radiation. Phase II studies of induction or consolidation chemotherapy have also shown promise but these agents have not yet been proven to improve outcome in a prospective randomized study. New strategies for optimizing thoracic radiation, primarily by dose escalation with three-dimensional conformal technique, have also led to an improved therapeutic ratio. Alternative strategies may be required for poor-risk, elderly patients.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Cancer is generally viewed as the result of disrupted intra-and intercellular homeostatic regulation. Once the homeostatic balance is lost and malignant transformation has occurred, microenvironmental factors such as degradation of matrix components and host-tumor interactions are essential for survival and growth of malignant cells. Within the previous year, cadherins and matrixins (matrix metalloproteinases) have emerged as key factors in these processes. The pathways involved are interconnected and detailed knowledge about the biologic significance of each member in a given pathway is essential for our understanding of oncogenesis. Restoration of E-cadherin-mediated control over melanoma cells and modulation of the involved regulation pathways are promising novel therapeutic strategies. Another approach is the rational design of inhibitors that perturb matrix metalloproteinases in a particular cell type and interrupt tumor-specific proteinase activation cascades. Advances in these fields will lead to the development of better tools for prevention, diagnosis, and therapy.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

In the past decade, the discovery of tumor antigens recognized by T cells has revolutionized the tumor vaccine field. The appreciation that peptides are bound to and restricted by major histocompatibility class I and II molecules for immune recognition has encouraged a number of early-phase clinical trials of peptide vaccines. I summarize herein the rationale for and the results of a number of clinical trials of peptide vaccines for melanoma, suggesting that immune and clinical responses can be seen in those with metastatic and resected disease using a variety of surrogate assays. The challenge for the future is to correlate the results of immunologic assays with clinical benefit in patients with advanced cancer.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Melanoma is the most common fatal malignancy among young adults, and its incidence and mortality continue to increase at an alarming rate. Epidemiologic studies have clearly demonstrated roles for genetic predisposition and sun exposure in melanoma development. In the past few years, substantial information has been added to the body of evidence suggesting that inherited and somatic genetic events contribute to the pathogenesis of melanoma. This review focuses on recent advances in the understanding of the genetic events, particularly aberration of cell cycle control and transcriptional control mechanisms, implicated in the pathogenesis of melanoma.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID