Biomedical subjects

Robert J Kruklitis

Publications and source records attributed to Robert J Kruklitis.

3 recordsLinked to original sources

PubMed2006

Transbronchial needle injection: a systematic review of a new diagnostic and therapeutic paradigm.

BACKGROUND AND OBJECTIVE: Transbronchial needle catheters are commonly used during flexible and rigid bronchoscopy for needle aspiration. The use of these catheters can be expanded by employing the technique of transbronchial needle injection. METHODS AND RESULTS: By injecting lesions in the airways, peribronchial structures, mediastinum, or lung parenchyma, transbronchial needle injection has been applied to the treatment of lung cancer, inflammatory disorders of the airways, recurrent respiratory papillomatosis, as well as bronchopleural fistulas. Diagnostic applications have included the localization of peripheral lung nodules as well as sentinel lymph nodes. CONCLUSIONS: Our review defines this bronchoscopic technique and summarizes its various reported applications.

Bronchoscopy↗

PubMed2004

Immuno-gene therapy with interferon-beta before surgical debulking delays recurrence and improves survival in a murine model of malignant mesothelioma.

OBJECTIVES: Immuno-gene therapy of mesothelioma with an adenovirus encoding interferon-beta mediated strong antitumor responses in murine models with low but not high tumor burden. Our goals were to determine the mechanisms responsible for this loss of efficacy and to test the hypothesis that the combination of preoperative adenovirus encoding interferon-beta and surgical resection would be effective in treating bulky tumors. METHODS: Flank tumors of a mouse mesothelioma cell line were treated with adenovirus encoding interferon-beta or adenoviral vector encoding the bacterial protein beta-galactosidase. Cytotoxic T lymphocytes and tumor infiltration by T lymphocytes were measured. Tumors were surgically excised 72 hours later and tumor cells were injected in the contralateral flank to create a model of a metastatic focus. Tumor-free survival and distant metastatic disease were assessed. RESULTS: Immuno-gene therapy effectively treated small tumors (<200 mm(3)) but did not reduce the size of large (>800 mm(3)) flank tumors. Although treatment with adenovirus encoding interferon-beta resulted in the generation of tumor-neutralizing splenocytes in large tumors, the number of T cells visualized within the tumors was minimal. Tumors treated with adenovirus encoding interferon-beta (versus adenoviral vector encoding the bacterial protein beta-galactosidase or phosphate-buffered saline solution) prior to debulking increased long-term tumor-free survival and resulted in two- to sixfold smaller foci of implanted tumor cells at 2 weeks postoperatively. CONCLUSIONS: The use of adenovirus encoding interferon-beta or surgical debulking alone is ineffective in treating large tumors, but combining preoperative adenovirus encoding interferon-beta and surgical debulking significantly reduces tumor recurrence and improves long-term tumor-free survival. We postulate that adenovirus encoding interferon-beta amplifies the cytotoxic T-lymphocyte antitumor response, allowing elimination of residual tumor cells.

Adenoviridae↗

PubMed2004

Endobronchial gene therapy.

Gene therapy for pulmonary disease, a field still in the experimental stage, has nonetheless progressed considerably in the past decade. There have been significant advances in pre-clinical studies, as well as important developments resulting from multiple early-phase human clinical trials for a variety of respiratory disorders. Although there are several ways of delivering therapeutic genes to the lungs, the primary delivery modality remains flexible bronchoscopy. The flexible bronchoscope, because of its unique access to both large and small airways, serves as an ideal instrument to deliver therapeutic genes to the tracheobronchial tree, even to small airways and alveoli that are beyond the reach of the bronchoscope. In addition, bronchoscopic gene delivery has the capacity to treat pulmonary vascular disorders because delivery of marker and therapeutic genes via the airways has been demonstrated to successfully transduce the pulmonary vascular endothelium. This article describes the various methods and disease targets of bronchoscopically mediated gene therapy, focusing in particular on the results of clinical studies and providing a glimpse into the future of the field.

Journal Article↗