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At least 289 records · Page 16Linked to original sources
PubMed2005

DNA methylation and cancer therapy: new developments and expectations.

PURPOSE OF REVIEW: In addition to having genetic causes, cancer can also be considered an epigenetic disease. The main epigenetic modification is DNA methylation, and patterns of aberrant DNA methylation are now recognized to be a common hallmark of human tumors. One of the most characteristic features is the inactivation of tumor-suppressor genes by CpG-island hypermethylation of the CpG islands located in their promoter regions. These sites, among others, are the targets of DNA-demethylating agents, the promising chemotherapeutic drugs that are the focus of this article. RECENT FINDINGS: Four exciting aspects have recently arisen at the forefront of the advancements in this field: first, the development of new compounds with DNA-demethylating capacity that are less toxic (for example, procaine) and may be administered orally (for example, zebularine); second, a better knowledge of the molecular mechanisms underlying the action of these drugs for particular genes and throughout the genome; third, the establishment of more reliable techniques to measure the effects of these drugs in clinical samples, such as high-performance capillary electrophoresis; and fourth, a decisive effort in the clinical trials that has merited the approval of 5-azacytidine by the U.S. Food and Drug Administration for the treatment of myelodysplastic syndrome. SUMMARY: We are at the dawn of an era when epigenetic drugs will be an important weapon in our arsenal in the war against cancer. Hematological malignancies have provided a promising starting point, but studies will surely extend to all solid tumors. However, we need to continue our research to develop more specific DNA-demethylating agents, to understand their biologic effects, and to determine whether they may be successfully combined with other epigenetic drugs, such as the inhibitors of histone deacetylases, and classic chemotherapy compounds.

Antineoplastic Agents↗
PubMed2005

Subversion of the Bcl-2 life/death switch in cancer development and therapy.

The Bcl-2 protein family, which largely determines commitment to apoptosis, has central roles in tumorigenesis and chemoresistance. Its three factions of interacting proteins include the BH3-only proteins (e.g., Bim, Puma, Bad, Noxa), which transduce diverse cytotoxic signals to the mammalian pro-survival proteins (Bcl-2, Bcl-x(L), Bcl-w, Mcl-1, A-1), whereas Bax and Bak, when freed from pro-survival constraint, provoke the mitochondrial permeabilization that triggers apoptosis. We have discovered unexpected specificity in their interactions. Only Bim and Puma, which mediate multiple cytotoxic signals, engage all the pro-survival proteins. Noxa and Bad instead bind subsets and cooperate in killing, indicating that apoptosis requires neutralization of different pro-survival subsets. Furthermore, Mcl-1 and Bcl-x(L), but not Bcl-2, directly sequester Bak in healthy cells, and Bak is freed only when BH3-only proteins neutralize both its guards. BH3-only proteins such as Bim are tumor suppressors and mediate many of the cytotoxic signals from anticancer agents. Hence, compounds mimicking them may prove valuable for therapy. Indeed, the recently described ABT-737 is a promising "BH3 mimetic" of Bad. We find that, like Bad, ABT-737 kills cells efficiently only if Mcl-1 is absent or down-regulated. Thus, manipulation of apoptosis by targeting the Bcl-2 family has exciting potential for cancer treatment.

Animals↗
PubMed1987

[Alternatives and further development of therapy of acute myeloid leukemia in adults. Update of West German multicenter studies].

The 1982 randomized, multicenter trial on adult-AML in West Germany revealed a superiority of remission duration (p = 0.004) and survival (p = 0.06) for patients receiving monthly myelosuppressive maintenance chemotherapy after TAD9-induction and consolidation as compared to patients without maintenance. In the 1985 pilot study double induction as a new approach followed by consolidation and monthly maintenance in patients up to 60 years of age was found well practicable, with 77% complete remissions and 12% early deaths in 81 patients. In addition preliminary remission duration and survival at 1 1/2 years appear favorable.

Adolescent↗
PubMedDate not supplied

Interventions for confusion and dementia. 4: Alternative approaches.

While reality orientation and reminiscence are useful therapies, recent years have been a growing awareness of other approaches to caring for people with dementia. This article discusses some of the less established, but potentially valuable, approaches--validation therapy, resolution therapy and multisensory environments. Validation therapy seeks to help care givers understand the thoughts and feelings of care receivers. In contrast to the confrontational approach of reality orientation, it encourages empathy between giver and receiver. Resolution therapy develops aspects of validation therapy, adopting a less structured, more psychodynamic and individualistic approach. Multisensory environments use sensory stimulation to achieve pleasure for the individual. All three approaches have a limited knowledge base, but share a humanistic philosophy that enables them to contribute to a person's quality of life.

Confusion↗
PubMed2002

Therapies in development for community-acquired pneumonia.

The current use of antimicrobials has become more complex due to the extensive emergence of antibiotic resistance. The single most important approach in resistance control is probably the judicious use of chemotherapeutic agents. New agents that may be of use in the treatment of community-acquired pneumonia are currently in development. Antimicrobials can be grouped according to their mechanism of action. These include protein synthesis inhibitors (ketolides, oxazolidinones, streptogramins and glycylcyclines), nucleic acid synthesis inhibitors (fluoroquinolones), peptidoglycan synthesis inhibitors (beta-lactams and glycopeptides) and agents interfering with membrane function (cationic peptides and lipopeptides). Among those agents under development, only the oxazolidinones, the cationic peptides and the lipopeptide antibiotics can be truly regarded as structurally novel inhibitors as the other agents are analogues of existing compounds which have been in clinical use for many years.

Anti-Bacterial Agents↗
PubMed2002

Rheumatoid arthritis: developing pharmacological therapies.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that, despite recent advances in therapy, still results in significant morbidity, mortality and disability. The aetiology remains unknown and past therapies, although helpful for the majority of patients, have been suboptimal. The recent introduction of newer agents has changed the treatment paradigm of RA. COX-2 inhibitors, anti-TNF agents and interleukin-1 antagonists have allowed us to treat RA more effectively with relatively low risk of side effects. Investigations of other possible treatment pathways, such as inhibition of angiogenesis, may produce still better treatment and rapid unraveling of the immune system and how it relates to RA greatly enhances the opportunities for improved therapeutics in RA.

Adalimumab↗
PubMed1994

Issues in the selection and development of therapies in alcoholism treatment matching research.

There are a large number of possible approaches to the treatment of alcohol abuse and dependence. From a practical and methodological standpoint, however, only a limited number of interventions can realistically be included in research studies of treatment matching. A key question in planning studies of matching is what treatments to include. The recent book by Beutler and Clarkin on systematic treatment selection in general psychotherapy provides a framework within which to discuss alcoholism treatment matching and the criteria applied to decisions concerning (1) modes of treatment, (2) treatment format, (3) specific therapeutic strategies and the (4) treatment setting. The methodological and practical issues raised and the decisions reached in Project MATCH are presented in each of these areas. The therapies chosen for Project MATCH, based on these criteria, are described.

Alcoholism↗
PubMed2005

Involvement of PI3K/Akt pathway in prostate cancer--potential strategies for developing targeted therapies.

This review presents some therapeutic interventions actually considered in prostate cancer therapy to compensate constitutive activation of the PI3K/Akt signalling pathway induced, particularly, by mutations of PTEN gene. Special emphasis is placed on applicability of EGF-R tyrosine kinase, COX-2, PDK-1, mTOR and farnesyltransferase inhibitors.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMedDate not supplied

Influence of antihypertensive therapy on development and progression of diabetic glomerulopathy.

Capillary hypertension is suggested to be the underlying cause of microvascular disease affecting the kidney, the retina, and other organs and tissues in diabetic patients and animals. Hyperglycemia causes an expansion of extracellular volume, which induces a vasodilatory response. Hemodynamic adaptation to vasodilation leads to an increase in intracapillary hydraulic pressure, which subsequently causes vascular damage. In experimental animals, restoration of capillary pressure to normal levels by ingestion of a low-protein diet or administration of an angiotensin I-converting enzyme inhibitor has been shown to prevent microvascular damage in the kidney, and dietary protein restriction limits injury in the retina as well. Atrial natriuretic peptide, which is secreted by atrial myocytes in response to volume expansion, may be involved in mediation of the hemodynamic adaptation (vasodilatory response) that results in diabetic microvascular disease.

Animals↗