Clinical and research issues in breast cancer genetics

Breast cancer is the most common form of cancer in women in the U.S. The risk factors for developing breast cancer include increasing age, a family history of breast cancer, and the lack of a child by age 30. A substantial fraction of breast cancer, however, occurs in women who have no identifiable risk factors. The diagnosis, pathology, treatment, and presymptomatic testing of cancer susceptibility genes are reviewed. Syndromes with an associated risk of breast cancer are described, such as hereditary breast-ovarian cancer syndrome, Li-Fraumeni syndrome, ataxia telangiectasia, and Cowden's disease. With the localization of the BRCA1 gene to chromosome 17q21 and the BRCA2 gene to chromosome 13q12, issues surrounding breast cancer susceptibility genetic testing are assuming an ever greater measure of importance. The sensitivity and specificity for molecular testing of cancer susceptibility genes, however, have not been well defined. The progress in presymptomatic genetic testing is further hampered by various factors such as the technical difficulty in distinguishing mutations from polymorphisms, the number of different mutations identified thus far and the possibility of false positive and false negative results. Laboratory quality assurance/quality control issues are of paramount importance to avoid misleading interpretations. Many issues surrounding genetic screening and testing, such as insurance and employment discrimination, privacy, and informed consent, are under active debate, and guidelines and standards are under active development. It is therefore important to proceed with caution, so that irreversible harm resulting from data misinterpretation can be avoided.     

Professional liability in the managed-care setting

The multiple functions of the phenol moiety that are widely present in disparate sources such as drugs, pesticides, teas, fuel additives and surfactants have not been clearly delineated. The differences in behavior of phenols, which run the gamut from aberrations in DNA/chromosomes to suppression of genotoxic activity of carcinogenic compounds, merit further attention. In this study, a through examination of the growth inhibition patterns of 37, simple 3- and 4-substituted phenols in mouse leukemia cells was carried out and the following quantitative structure-activity relationship (QSAR) was obtained for the 23 electron releasing substituents in X-phenols: log 1/IC50 = -1.58 sigma(+) +0.21 log P + 3.10. In this QSAR, IC50 is the concentration of phenol that induces 50% inhibition of growth. P is a measure of the hydrophobicity of each phenol and Brown's electronic parameter, sigma+, represents the electronic effect of the substituent. The negative dependence on sigma+ is strongly reminiscent of what is observed in the developmental toxicity of phenols on rat embryos as well as for the radical abstraction of a hydrogen atom from phenolic groups. The other 15 electron-attracting substituted X-phenols clearly show a linear dependence on hydrophobicity alone: Log 1/IC50 = 0.62 log P + 2.35. The bifurcation in mechanism of action of this large set of diverse phenols is novel and unusual. It suggests that two distinct processes are operative. In the case of electron releasing substituted phenols, the observations are not inconsistent with a radical mediated process while with electron attracting substituted phenols, non-specific toxicity as modulated by hydrophobicity, appears to predominate.     

The ethical practice of psychology in a managed-care framework.

With the rise of managed healthcare, psychologists face new challenges to their professional ethics. This article examines the dilemmas posed by managed care in 3 areas: client care, the handling of patient data, and issues surrounding membership in a managed-healthcare organization. Case examples of ethical dilemmas and strategies for dealing with these challenges are presented. In an attempt to summarize the strategies used to cope with the ethical dilemmas presented in the case examples, global solutions for the ethical practice of psychology in a managed-care framework are also reviewed. These strategies include understanding managed-care policies, clear communication with the client, additional training, increased advocacy by clinicians, and ultimately, psychologists' involvement in the formation of these organizations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

乳腺癌新辅助化疗的临床研究

目的 评估新辅助化疗对乳腺癌的治疗作用.方法 两组采用不同的方法治疗,进行结果评估.结果 对照组肿瘤控制率42.86%(9/21),治疗组肿瘤控制率61.90%(13/21).结论 新辅助化疗是质量好的治疗方法,值得临床推广.     

Clinical nutrition: opportunity in a changing health care environment

This article summarizes presentations from a satellite symposium, "Clinical Nutrition: Opportunity in a Changing Health Care Environment," held July 26, 1997, at the 37th annual meeting of the American Society for Clinical Nutrition in Montreal. The symposium was cosponsored by the American Society for Clinical Nutrition and the American Society for Parenteral and Enteral Nutrition. The diverse topics served as a practical forum for sharing information on innovative responses, concerns, and impediments in the rapidly evolving practice environment.     

Making research apply: High stakes public policy in a regulatory environment.

The experiences of 3 social psychologists asked to evaluate (and improve) a series of large-scale programs designed to change energy-related attitudes and behavior are described. The research generated significant change but also substantial conflict involving both the utility companies being evaluated and the state agency that commissioned the evaluation. This experience is reviewed with an eye to maximizing the usefulness of future efforts to apply social psychology in complex and potentially conflicted public policy arenas. The difference between influence and power models of applied research is discussed, and possible remedies are examined for social psychologists undertaking future research similar in scale, policy consequences, or potential controversy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral research in cancer as a model for health psychology.

Comments on the meta-analysis of psychosocial interventions with adult cancer patients by T. J. Meyer and M. M. Mark (see record 1995-22645-001) and argues that Meyer and Mark's analysis points to the need to identify conditions and problems that are best suited to particular psychosocial interventions. These interventions must also retain clinical relevance to cancer prevention and cure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Immunoprevention of cancer poses a challenge to pharmacological research

The evolving understanding of the molecular mechanisms of carcinogenesis establishes that the long latency period would offer numerous opportunities for intervention before the final step of fully developed malignancy has been reached. Immunoprevention of cancer may be a new approach to cancer control, by eliminating the cellular minimal deviations that are seen in the early phases of carcinogenesis. Available results of immunotherapy of preneoplastic lesions and data on anticarcinogenesis with immunoregulators in experimental models are in good accordance with theoretical expectations. However, clinical research on immunoregulators still focuses on the treatment of advanced cancer. The major problem hampering a wider application of immunoregulators in cancer prevention is the possibility of potential adverse effects, which are largely unknown. The promotion of future research in this area is essential. Moreover, the ethical issues of intervention trials in cancer must be discussed, by considering the potential psychological and social consequences.     

New directions in breast cancer research

Research in breast cancer extends in many directions, stimulated by concerns related to the high incidence of the disease and the relative unpredictability of its clinical course. Examples of work in several directions are presented here arranged by four levels of analysis. 1) Molecular, intracellular events (molecular genetics). Recent identification of genes that predispose to breast cancer, and the isolation of those genes and their protein products, permit investigations of the most critical issues: the roles of these genes in normal development and breast differentiation, and how their alteration permits or contributes to tumor initiation. Thus, we expect that understanding the functions of the genes involved in inherited susceptibility to breast cancer will also be informative for sporadic breast cancers. 2) Cellular biology (cellular models for preneoplastic disease). We examine models of breast cancer development and ask how they help to validate a morphologic sequence for human breast neoplasia and whether they permit investigation of how to modify disease progression. Two useful models, one in transgenic mice and the other using human breast stem cells capable of culture and xenograft growth, are now available. 3) Tissue and organ (the tumor and its local environment). We look at the relationship of the tumor cell population to its local environment (stroma, blood vessels, etc.). This leads naturally to questions of how neighboring tissues and cytokines may modify tumor growth. 4) The individual as an organism and member of a population (hormonal rise and chemoprevention). We address identification of the primarily hormonal risk factors and a possible related mode of cancer prevention.     

Artificial neural networks in cancer research

Current therapy does not cure the majority of patients with B cell non-Hodgkin's lymphoma (NHL) and further intensification does not benefit the patient. Therefore, new approaches are necessary. Immunotherapy has become again a major interest as a new treatment modality for B cell lymphoma since the discovery that the lymphoma specific Id can be presented to antigen-specific T cells. Vaccination of the tumour-bearing host is one of the major strategies to induce a T cell mediated anti-tumour immunity in vivo. For B cell lymphomas the lymphoma specific Id can be used as a tumour-specific antigen to stimulate T cells. Alternatively, the malignant B cells can be modified to become efficient antigen presenting cells (APCs) and present peptides from their own tumour-specific antigens to the autologous T cells. Currently explored and future vaccination strategies for B cell lymphoma will be discussed here.     

Hyperthermia in cancer research: current status

There are critical maximum temperatures above which irreversible damage occurs in cells and tissues. Exposure to high temperature, referred to as hyperthermia (HT), can result in cell death, tissue damage or even death of the organism. Clinical application of HT as a primary treatment or as an adjuvant to radio-/chemo- therapy of cancer is based on its ability to cause localized tumor tissue damage. Experimental data provide HT with a strong biological rationale. Early clinical experience suggested that HT will become an important modality as an adjuvant to radiotherapy in the treatment of human malignancies, but its application is currently limited to mainly superficial tumors. Its full realization as a treatment modality for cancer therapy awaits further laboratory investigations as well as controlled clinical trials. A better understanding of the biological mechanisms of its action, interaction with chemotherapeutic drugs and radiation damage, role of tumor microenvironment such as oxygen status and pH of tumors, and kinetics of thermotolerance can lead to refinement in its clinical implementation. The present review attempts to analyse the published literature during the last one and half decades.