RESUMO
A phase I gene transfer clinical study was undertaken to examine the ability to introduce a potential anti-human immunodeficiency virus (HIV) gene therapeutic into hematopoietic progenitor cells (HPC), thereby contributing to multilineage engraftment. The potential therapeutic effect of genetically modifying HPC with protective genes in HIV-infected adults depends in part on the presence of adult thymic activity and myeloid capacity in the setting of HIV replication. Herein we report the presence and expression of a retroviral vector encoding an anti-HIV-1 ribozyme in mature hematopoietic cells of different lineages, and de novo T-lymphocyte development ensuing from genetically engineered CD34(+) HPC. Sustained output of vector-containing mature myeloid and T-lymphoid cells was detected even in patients with multidrug-resistant infection. In addition, the study showed that the degree of persistence of gene-containing cells was dependent on transduced HPC dose. These novel findings support the concept of gene therapy as a modality to effect immune reconstitution with cells engineered to inhibit HIV replication and this report represents the first demonstration of long-term maintenance of a potential therapeutic transgene in HIV disease.
Assuntos
Fármacos Anti-HIV , Terapia Genética/métodos , Infecções por HIV/imunologia , HIV-1 , Transplante de Células-Tronco Hematopoéticas , RNA Catalítico/genética , Adulto , Antígenos CD34/análise , Linfócitos T CD4-Positivos/metabolismo , Feminino , Expressão Gênica , Técnicas de Transferência de Genes , Vetores Genéticos , Infecções por HIV/terapia , HIV-1/genética , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/enzimologia , Humanos , Linfócitos/citologia , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Células Mieloides/citologia , Reação em Cadeia da Polimerase , Retroviridae/genéticaRESUMO
PURPOSE/OBJECTIVES: To review the clinical significance, methods of testing, and outcomes of trastuzumab (Herceptin) treatment for HER2 gene amplification and HER2 protein overexpression in breast cancer. DATA SOURCES: Published articles and abstracts, online resources, a clinical handbook, and product information. DATA SYNTHESIS: HER2 gene amplification or HER2 protein overexpression can be found in 20%-25% of breast cancers and is important pathogenic and prognostic information. HER2 also predicts patient response to trastuzumab. Patients with HER2-positive metastatic breast cancer benefit from trastuzumab whether selected by immunohistochemistry, which measures the HER2 protein, or fluorescence in situ hybridization (FISH), which measures the HER2 oncogene. However, patients who are identified accurately as HER2 gene-amplified by FISH derive the greatest benefit. CONCLUSIONS: Accurate testing is crucial for appropriate identification of patients for trastuzumab therapy. FISH is the most reproducible and accurate method. IMPLICATIONS FOR NURSING: Education regarding HER2 testing and trastuzumab helps patients to make informed decisions and facilitates active participation in their care as well as enhances dialogue with physicians.