ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Within the past year, the draft sequence of the human genome was completed and made available to researchers worldwide. Recent advances in technology along with the vast amount of sequence data on the human genome now provide a previously unimagined means of defining the genetic architecture of cancer cells. Implicit in this approach is the ability to describe the evolution of that architecture as normal breast cells progress toward the malignant phenotype. Ongoing experiments involving the simultaneous analysis of the entire genome in a high-throughput manner are expected to reveal those genes and regulatory mechanisms that are critical at each step of progression toward malignancy, including (1) providing a growth advantage over normal cells, (2) maintaining the malignant state, (3) modulating response to therapy, and (4) developing metastatic potential. Once these data are available, the ability to design preventive, diagnostic, prognostic, and therapeutic tools directed at those targets will be within reach.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Breast cancer remains a worldwide public health concern despite the fact that mortality rates have been declining in some countries as a result of improvements in adjuvant therapy and screening for breast cancer. In the prevention arena, advances in our understanding of the effects of tamoxifen have led to the investigations of newer agents that may provide extended options for breast cancer prevention in high-risk women. For women who are carriers of a mutation in the breast cancer susceptibility genes BRCA1 or BRCA2, prophylactic oophorectomy and bilateral mastectomy have emerged as preventative surgical options that can significantly impact breast cancer risk. In addition, the identification of potentially modifiable risk factors for breast cancer such as dietary folate intake, alcohol consumption, physical activity, and certain anthropometric factors provides opportunities for intervening in breast cancer prevention both among women at average and high risk. The challenge remains in overcoming the limitations of mammography and clinical breast examination by developing and evaluating new technologies for breast cancer screening such as digital mammogram and breast magnetic resonance imaging.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

We review recent reports on breast cancer and its predictors, emphasizing the clinical utility of tissue samples from patients. We highlight indicators of increased cancer risk and lesions without metastatic capacity at time of detection, but of sufficient risk of attaining metastatic capacity that treatment is mandated (ie,ductal carcinomain situ). Emphasized are histologic features of importance in stratification of ductal carcinomain situ.We also review invasive lesions with little capacity for metastatic behavior and indicators of low malignant potential. Included are several papers reviewing the usefulness of histologic grading, emphasizing mitotic counts. Also, the continuing utility of recognizing some special and unusual types of breast cancer is detailed. Sentinel lymph node evaluation by histology is included because some minimal or artifactual findings in lymph nodes can mimic true metastases.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Radiation oncology is essential in the management of breast cancer. Each year the scientific literature is replete with evidence of radiation's role in the treatment of this disease. The goal of this article is to motivate the reader to discuss and critically review some of these publications. The authors have made a subjective selection of clinical publications addressing radiation and breast cancer from the past 13 months. Articles were chosen on the basis of their ability to influence both current and future therapy. Some readers will no doubt disagree with our choices; however, if this disappointment generates discussion and review of these and other articles, we have achieved our goal.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

A large body of data on systemic therapy has been presented and published in the past year, including new information on primary risk reduction, patient selection for adjuvant systemic therapy, and anthracycline-analogs. New data on ongoing adjuvant trials (including taxane studies), unpublished updates from the fourth Oxford Overview in September 2000, and provocative data on ovarian ablation were important features of the November 2000 National Institutes of Health Consensus Development Conference on Adjuvant Therapy for Breast Cancer. Important new data on anti-estrogen therapy, including aromatase inhibitors and pure antiestrogens, further expand the role of the oldest targeted breast cancer therapy. Trastuzumab and other novel compounds are being investigated as single-agents and in combination with conventional systemic approaches. Discussions on the long-term effects of adjuvant therapy have taken center stage also. These and other important ongoing developments since 2000 are examined in this review article.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Apoptosis is a distinctive form of cell death that reflects cleavage of a subset of intracellular polypeptides by proteases known as caspases. Two major intracellular caspase cascades, one activated predominately by death receptor ligands and the other triggered by various cellular stresses, including DNA damage and microtubule disruption, have been delineated. Activation of these protease cascades is tightly regulated by a number of polypeptides, including Bcl-2 family members, inhibitor of apoptosis proteins, and several protein kinases. The demonstration that many antineoplastic agents induce apoptosis in susceptible cells raises the possibility that factors affecting caspase activation and activity might be important determinants of anticancer drug sensitivity. Here, we review recent studies describing the regulation of apoptotic pathways and identify potential implications of these findings for resistance to antineoplastic agents.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Drug resistance eventually occurs in most hematologic malignancies treated with chemotherapy. The mechanisms responsible for drug resistance include expression of transporters of xenobiotics of the adenosine triphosphate-binding cassette protein superfamily (P-glycoprotein, multidrug resistance associated proteins, breast cancer resistance protein), modifications of enzymes like deoxycytidine kinase, and defects in chemotherapy-induced apoptosis. The efforts to overcome this drug resistance have been focused, thus far, on modulation of P-glycoprotein. Several compounds were manufactured for this purpose, and phase III trials of PSC833, one of the most potent P-glycoprotein inhibitors, are completed. The emergence of modulators with several adenosine triphosphate-binding cassette protein targets, like GG120918 (inhibiting P-glycoprotein and breast cancer resistance protein) and VX710 (inhibiting P-glycoprotein and multidrug resistance associated protein 1), are of clinical interest in malignancies often expressing several efflux pumps simultaneously. Another approach is the use of “furtive” drugs like liposomal or nanoparticular anthracyclines.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Farnesyltransferase inhibitors represent a new class of agents that target signal transduction pathways responsible for the proliferation and survival of diverse malignant cell types. Although these agents were developed to prevent a processing step necessary for membrane attachment and maturation of Ras proteins, recent studies suggest that farnesyltransferase inhibitors block the farnesylation of additional cellular polypeptides, thereby exerting antitumor effects independent of the presence of activatingrasgene mutations. Clinical trials of two farnesyltransferase inhibitors–the tricyclic SCH66336 and the methylquinolone R115777–as single agents have demonstrated disease stabilization or objective responses in 10 to 15% of patients with refractory malignancies. Combinations of farnesyltransferase inhibitors with cytotoxic chemotherapies are yielding complete and partial responses in patients with advanced solid tumors. A phase I trial of R115777 in refractory and relapsed acute leukemias induced responses in 8 (32%) of 25 patients with acute myelogenous leukemia (including two complete remissions) and in two of three with chronic myelogenous leukemia in blast crisis. In patients with solid tumors, accessible normal tissues such as peripheral blood lymphocytes or, perhaps more germane to epithelial malignancies, buccal mucosa have provided surrogate tissues that allow confirmation that farnesyltransferase is inhibitedin vivoat clinically achievable drug doses. In conjunction with the R115777 acute leukemia trial, serial measurements provided evidence of farnesyltransferase enzyme inhibition, interference with farnesyltransferase function (ie, protein processing), and blockade of signal transduction pathways in leukemic bone marrow cells. Preclinical studies of farnesyltransferase inhibitor resistance and clinical trials of farnesyltransferase inhibitors in combination with other agents currently are in progress.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID