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At least 919 records · Page 51Linked to original sources
PubMed2005

Molecularly targeted therapies for breast cancer.

BACKGROUND: The management of patients with localized and advanced breast cancer continues to evolve. Chemotherapy, endocrine therapy, and trastuzumab are effective therapies but leave considerable room for improvement. As the cellular aberrations inherent to cancer cells in general and breast cancer cells specifically are better understood, therapies to target specific cellular pathways continue to be developed with the goal of expanding available effective therapy through better patient selection. METHODS: We conducted a computerized search of the medical literature as well as a manual search of selected meeting abstracts. RESULTS: Several targeted therapies are in phase III clinical trials testing their promise in the treatment of breast cancer. Many other agents are completing phase I and II testing. An overview of the most promising agents in clinical development is discussed herein. CONCLUSIONS: Targeted therapy for breast cancer is a reality at this time, and several new agents hold promise for expanding and refining the pool of patients likely to further benefit from this approach in the near future.

Antibodies, Monoclonal↗
PubMed2006

The role of the IGF system in cancer growth and metastasis: overview and recent insights.

IGF-I receptor (IGF-IR) signaling and functions are mediated through the activities of a complex molecular network of positive (e.g., type I IGF) and negative (e.g., the type II IGF receptor, IGF-IIR) effectors. Under normal physiological conditions, the balance between the expression and activities of these molecules is tightly controlled. Changes in this delicate balance (e.g., overexpression of one effector) may trigger a cascade of molecular events that can ultimately lead to malignancy. In recent years, evidence has been mounting that the IGF axis may be involved in human cancer progression and can be targeted for therapeutic intervention. Here we review old and more recent evidence on the role the IGF system in malignancy and highlight experimental and clinical studies that provide novel insights into the complex mechanisms that contribute to its oncogenic potential. Controversies arising from conflicting evidence on the relevance of IGF-IR and its ligands to human cancer are discussed. Our review highlights the importance of viewing the IGF axis as a complex multifactorial system and shows that changes in the expression levels of any one component of the axis, in a given malignancy, should be interpreted with caution and viewed in a wider context that takes into account the expression levels, state of activation, accessibility, and functionality of other interacting components. Because IGF targeting for anticancer therapy is rapidly becoming a clinical reality, an understanding of this complexity is timely because it is likely to have an impact on the design, mode of action, and clinical outcomes of newly developed drugs.

Animals↗
PubMedDate not supplied

How effective is reality orientation for elderly, confused patients?

Nurses still use reality orientation as a form of therapy, with care plans still discussing orientation in terms of time, place and person. This article aims to explore and review selected studies in an attempt to quantify the effects, if any, and concludes with relevant ethical considerations inherent within the technique.

Age Factors↗
PubMed2005

Experiences in K and -K.

In this paper the author explores and expands Bion's concepts of K and -K and delineates the nature of the relationship between the two. While Bion views envy as a principal motivating force for -K, his conception of -K goes considerably beyond this. The author explores manifestations of -K not driven by envy and, consequently, not necessarily pathological or pathogenic. -K is viewed by the author as a psychological process, which may serve many functions, including the communication of the patient's fear that knowing will bring on psychological catastrophe. -K, under circumstances that he describes, may serve to protect the individual's sense of continuity of being. The need to know the truth (K) may be at odds with the need to survive psychically, for example, when a person fears that the truth will kill him, or those he loves and depends upon. This idea is explored in two ways: first, by means of a discussion of the Oedipus myth in which Oedipus attempts to evade knowing for fear of recognizing that a prophesied catastrophe has already occurred; and, second, by means of a clinical exploration of the conflict between the need to know and the need to survive. The author discusses his analytic work with a severely disturbed patient for whom not knowing was felt to be essential to her psychic survival. Her need not to know reached a point where she psychically obliterated the analyst through the use of negative hallucination.

Adult↗
PubMed2001

Sarcoma.

ASCO 2001 was a banner year for innovative systemic therapy for sarcomas. Imatinib mesylate (STI571, Gleevec) shows clear activity not only in chronic myelogenous leukemia, for which the drug received Food and Drug Administration approval, but also in gastrointestinal stromal tumors as well, by virtue of imatinib mesylate binding to the abl, kit, and platelet-derived growth factor receptor tyrosine kinases. Ecteinascidin-743 (ET-743) demonstrates activity against a fraction of other soft-tissue sarcomas. Gemcitabine-based regimens show at least some activity against a subset of soft-tissue sarcomas. Given the lack of new agents for sarcoma therapy since the development of ifosfamide, these studies give hope that the term "effective systemic therapy for sarcoma" might become a reality.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Recent advances in the development of an inhaled insulin product.

Inhaled insulin first entered clinical human testing in the mid 1990s. Since then, the commercial potential and technical challenges of an inhaled insulin product have grown increasingly clear, with several pharmaceutical partnerships now targeting treatment of diabetes mellitus through inhalation products in clinical development. While clinical results to date show the therapy to be generally promising, recent data have raised questions related to human safety and slowed progress toward a commercial product. Answering these questions positively in the coming years will be critical to making inhalation therapy a practical diabetes-care reality.

Administration, Inhalation↗
PubMed2005

Novel biological approaches to the intra-articular treatment of osteoarthritis.

Osteoarthritis is common, incurable and difficult to treat. Because osteoarthritis is symptomatic only in a limited number of weight-bearing joints and lacks obvious extra-articular manifestations, it is well suited to local therapy administered by intra-articular injection. Several biologically based, local therapies of this type are either in clinical use or in development. Intra-articular injections of hyaluronic acid are widely used, but are highly controversial because their mode of action is unclear and clinical trials have provided contradictory results. The conclusions of meta-analyses are also discordant. An alternative therapy, based on the intra-articular injection of autologous conditioned serum, is used in Europe. This product, known as Orthokine, is generated by incubating venous blood with etched glass beads. In this way, peripheral blood leukocytes produce elevated amounts of the interleukin-1 receptor antagonist and other anti-inflammatory mediators that are recovered in the serum. Considerable symptomatic relief has been reported in clinical trials of this product. Alternatively, instead of injecting a heterogeneous, incompletely characterized mixture of native molecules into the joint, it is possible to inject recombinant growth factors and cytokine antagonists. None of these are in routine clinical use, but promising preliminary human trials have been performed with insulin-like growth factor-1 and the interleukin-1 receptor antagonist. It is possible that sustained intra-articular production of such factors could be achieved by gene transfer. Although gene therapy for osteoarthritis is not yet a clinical reality, the first human trial should begin next year.

Adjuvants, Immunologic↗
PubMedDate not supplied

[Myocardial regeneration: future at reach].

The last few years have witnessed a growing interest in regenerative therapy of the failing heart by cell transplantation. Initial studies with skeletal myoblasts were conducted more than 10 years ago. However, the potential of bone marrow derived cells has more recently led to a flurry of experimental studies generating overall positive but occasionally conflicting results. The ethics of initiating clinical trials with stem cells in patients with heart failure has been questioned. Although laboratory research attempts to overcome a number of questions surrounding the usefulness and safety of cell therapy, the accumulated body of evidence warrants implementation of clinical trials. The earliest of these have now documented the feasibility of cell therapy. It is now appropriate to conduct safety and efficacy studies which, if carefully done, should allow assessment of the extent to which this concept of regenerative therapy can be made a clinical reality.

Clinical Trials as Topic↗
PubMed1988

[Inpatient psychoanalytic treatment of patients with structural ego disorders].

Psychoneurotic and psychosomatic patients with severe personality disorders suffer from structural defects of their ego-functions and are in need of specific treatment techniques which can be supplied by the differentiated strategies of inpatient psychoanalysis. The experiences of a specific inpatient ward of the Psychosomatic department at the Central Institute of Mental Health in Mannheim are summarized whereby the use of the inward setting to initiate long term psychotherapeutic processes is emphasized. According to an integrative treatment concept various verbal and non-verbal modalities of experience and working through represented by different members of the therapeutic team co-operate within their well defined functions. The main task of the team is to identify the various splitting mechanisms of the patients with personality disorders and to combine all the walled off ways of experiencing and social behavior into a complete picture of his person. To this end close attention is payed to the dynamics within the group of the patients as well as with the group of the therapists. As a precondition the setting of the ward and its rules of conduct for inpatient group life have closely to be watched and the respective behavior of the patients and the team has to be monitored. We describe our setting, the time phases of treatment, the tasks of the different therapists, and explicitely emphasize sociotherapeutic aspects for the final therapy phase. At last, we mention special emotional difficulties waiting for therapists who work in this setting.

Adult↗
PubMed1986

Identification and its vicissitudes as observed in psychosis.

I have described the mechanisms that operate in psychotic identification. One mechanism is psychotic introjection, characterized by a refusion of 'all good' self and object representations. This re-fusion threatens the destruction of the self as a consequence of the defensive blurring of these self and object representations. The second operative mechanism is projective identification, which I have defined in comparison with and in contrast to projection. Projective identification threatens the destruction of the relation with the object. The case I have described in detail illustrates these psychotic identifications, the development of psychotic transferences wherein the patient cannot differentiate herself and her thinking from the therapist and his thinking, and the struggle around a sense of personal identity at a point of resolution of the psychotic transference. This case also illustrates that an integrated self includes two types of self-representations: those centred on self differentiation and those which reflect the observing functions of the parental images internalized into the self.

Adult↗
PubMedDate not supplied

Notes on the potential differentiation of borderline conditions.

It is argued that the borderline personality organization as now conceived embraces a spectrum of differentiable diagnostic groupings. Lumping these diagnostic clusters under a single descriptive heading contributes to continuing conceptual ambiguities and theoretical confusion in the understanding of borderline psychopathology. A potential differentiation of borderline entities on clinical grounds is suggested. The bases for discrimination of higher-order borderline conditions versus lower-order conditions are explored. Current accounts of borderline pathology tend to focus on lower-order pathology as characteristic, but do not account for the full range of the borderline spectrum. Other potential discriminations between an hysterical continuum and an obsessional-schizoid continuum are explored. Differential diagnoses suggested include pseudoschizophrenia, psychotic character, borderline personality, and primitive hysteric in the hysterical continuum; schizoid personality, false-self organization, and as-if personality in the schizoid continuum. The syndrome of identity diffusion is also suggested as part of the borderline spectrum.

Borderline Personality Disorder↗
PubMed1981

[Fundamental problems of therapeutic teamwork in psychiatry (author's transl)].

Certain institutional and organizational prerequisites are fundamental in present-day translation into reality of essential concepts of psychiatric therapy and rehabilitation. These include, for example, the basic structure of therapeutic co-operation and the form of such co-operation as practices by a multiprofessional team. The creation and shaping of facilities based on the principle of mutual therapeutic co-operation and joint working of team members engaged in therapy, are innovations and are representative of a development by which a specific style in psychiatry gradually takes shape and by which it becomes adequately conscious of its social tasks. As with all innovatory developments there is an inherent danger that individual elements of such innovations assume of life of their own and undergo mystification. The concept "team" in psychiatry form of co-operation can solve many more problems than it can cope with. Hence it is definitely useful to investigate critically into the structure of teamwork in psychiatry, into its possibilities and prerequisites and into the extent to which teams are superior to conventional forms of organization in meeting the specific demands made by treating the mentally diseased. It becomes evident that among the basic conditions of teamwork are significant attitudes to therapy and that the therapeutic approaches derived therefrom can be successful only on teamwork basis. At the same time, however, limitations become apparent beyond which teamwork - now no longer understood as a problem-related principle of co-operation, but as an ideology - threatens to become dysfunctional and anti-therapeutic, creating compulsions which are diametrically opposed to the very essence of therapy and also to the needs of the therapist group.

Humans↗