ISSN:1173-8804    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

During the last decade, increased understanding of the molecular mechanisms responsible for immune activation to protect against challenges by tumor cells has revolutionized the field of immunotherapy research. It has been demonstrated that the dysfunction of the host's immune system represents one of the major mechanisms by which tumors evade immunosurveillance. This is due, for example, to T cell anergy, the existence of regulatory T cells, and systemic defects of dendritic cells derived from tumor patients. In addition, escape from immunosurveillance can also be linked to tumor-related factors, including secretion of immunosuppressive cytokines, resistance to apoptosis, and deficient expression of immunomodulatory molecules and major histocompatibility complex (MHC) class I antigens possibly due to immunoselection. Both host- and tumor-related mechanisms can lead to a failure to mount a proper anti-tumor-specific immune response, and these are frequently key factors in limiting the success of cancer immunotherapy.

ISSN:1173-8804    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

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.

ISSN:1173-8804    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Cutaneous wounds inevitably heal with scars, which can be disfiguring and compromise function. In general, the greater the insult, the worse the scarring, although genetic make up, regional variations and age can influence the final result. Excessive scarring manifests as hypertrophic and keloid scars. At the other end of the spectrum are poorly healing chronic wounds, such as foot ulcers in diabetic patients and pressure sores. Current therapies to minimize scarring and accelerate wound healing rely on the optimization of systemic conditions, early wound coverage and closure of lacerations, and surgical incisions with minimal trauma to the surrounding skin. The possible benefits of topical therapies have also been assessed. Further major improvements in wound healing and scarring require an understanding of the molecular basis of this process. Promising strategies for modulating healing include the local administration of platelet derived growth factor (PDGF)-BB to accelerate the healing of chronic ulcers, and increasing the relative ratio of transforming growth factor (TGF)β-3 to TGFβ-1 and TGFβ-2 in order to minimize scarring.

ISSN:1173-8804    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Scintillation proximity assay (SPA), characterized by its speed, sensitivity, reliability, and the fact that no separation step is required, has become an important technique in high-throughput screening (HTS) for new drugs, and for investigating their biological interactions. The SPA technique now plays a key role in HTS, in that it can be used in many assay formats including radioimmunoassays (RIAs), ligand-receptor binding assays, and enzyme assays. The SPA-based enzyme assay is usually designed in three formats corresponding to different enzymes: signal removal format for hydrolytic enzymes, signal addition format for polymerase and transferase enzymes, and product capture format for antibodies, DNA probes, receptors or other specific binding proteins. The use of SPA in RIAs has been facilitated by new carriers, such as membranes that can be configured in various shapes and sizes, allowing the assay to be performed on samples from many sources including tissue, serum, plasma or cells. This review presents the principles of SPA, discusses supporting materials and quenching effects, as well as detailed examples of the latest advances.

ISSN:1173-8804    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

BackgroundAtopic eczema/dermatitis syndrome (AEDS) is a chronic inflammatory skin disease, affecting 10–20% of children and 1–3% of adults. The purpose of this pilot study was to assess the clinical and anti-inflammatory effect of bacterial and ribosomal immunotherapy with Immucytal®(Pierre Fabre Médicament, France) in children with AEDS.MethodsSeventeen children with allergic and non-allergic forms of AEDS (AAEDS and NAAEDS, respectively), graded moderate to severe (Severity Scoring of Atopic Dermatitis [SCORAD] index of >25), received ribosomal immunotherapy (Immucytal®) once daily according to the standard treatment regimen (4 consecutive days a week for 3 weeks, and then 4 consecutive days a month for 4 months). We assessed the clinical status of AEDS using the SCORAD index at baseline, and after 8 and 20 weeks of treatment. Furthermore, peripheral blood from patients was examined for the frequencies of CD4+ cells expressing interferon (IFN)-γ and interleukin (IL)-4 using flow cytometry.ResultsThere was a progressive and significant clinical improvement of AEDS, confirmed by a reduction of the SCORAD index over time in both AEDS forms (p < 0.01). Pooled data from the two groups showed that the mean baseline index of 43 was reduced to 17 after treatment. Overall, these data indicate a marked improvement in total clinical severity of AEDS (–62%). Flow cytometry analysis showed that frequencies of the two CD4+ T cell subsets did not differ significantly from the beginning to the end of the study in both forms of AEDS. However, the percentage of CD4+ cells expressing IL-4 in children with AAEDS tended to decrease by the end of treatment with ribosomal immunotherapy. Clinical and laboratory data confirmed that immunotherapy was well tolerated.ConclusionsThe results of this pilot investigation suggest that ribosomal immunotherapy may be beneficial in the management of AEDS in children, and that this could be at least partially explained by a role in restoring the type 2 helper-T cell imbalance seen in allergic patients. Placebo-controlled, randomized clinical trials are recommended in order to confirm these findings.

ISSN:1173-8804    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Etanercept (Enbrel®), a tumor necrosis factor (TNF)-α antagonist produced by recombinant technology, is approved for use in the US as subcutaneous monotherapy in adults with moderate-to-severe psoriasis who are candidates for systemic therapy or phototherapy. The drug is also indicated in patients with psoriatic arthritis, in whom it may be used in combination with methotrexate.In well designed trials in patients with moderate-to-severe psoriasis, short-term etanercept therapy (typically 25 or 50mg twice weekly) significantly increased the proportion of patients achieving a 75% reduction in the Psoriasis Area and Severity Index score compared with placebo. Similarly, in well designed trials in patients with psoriatic arthritis, treatment with short-term etanercept 25mg twice weekly, alone or in combination with methotrexate, improved clinical features of the disease, while radiographic progression of joint damage appeared to be significantly slowed in a nonblind 1-year extension. Short-term etanercept therapy was well tolerated in patients with psoriasis or psoriatic arthritis. Etanercept is thus a valuable new option for the treatment of patients with chronic moderate-to-severe plaque psoriasis (who are candidates for systemic therapy or phototherapy or have failed other systemic therapies) or with psoriatic arthritis.

ISSN:1173-8804    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Pegfilgrastim (Neulasta®), the sustained-duration form of filgrastim (recombinant human granulocyte colony-stimulating factor [G-CSF]), is created by the addition of a polyethylene glycol (PEG) moiety to filgrastim. Its approved indication in the US is to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive chemotherapy.A single subcutaneous injection of pegfilgrastim once per chemotherapy cycle was more effective than placebo as an adjunct to moderately myelosuppressive chemotherapy for breast cancer, no less effective than daily injections of filgrastim as an adjunct to highly myelosuppressive chemotherapy for breast cancer, and as effective as daily filgrastim as an adjunct to chemotherapy for lymphoma (predominantly non-Hodgkin lymphoma [NHL]) and acute myeloid leukemia. Pegfilgrastim has also successfully supported delivery of dose-dense chemotherapy, stem cell mobilization, and stem cell transplantation after high-dose chemotherapy in patients with non-myeloid or myeloid malignancies. By offering a convenient alternative to daily filgrastim, once-per-cycle administration of pegfilgrastim has the potential to simplify the management of chemotherapy-induced neutropenia, further improve patient health-related quality of life, and reduce total treatment costs in breast cancer and NHL, and possibly other cancer settings. Pegfilgrastim should, likewise, permit simplification of G-CSF–based stem cell mobilization and transplantation procedures.

ISSN:1173-8804    

出版商:ADIS    

年代:2005

数据来源: ADIS