Biomedical subjects

Stephen P Kantrow

Publications and source records attributed to Stephen P Kantrow.

3 recordsLinked to original sources

PubMed2004

Stable transgene expression in tumors and metastases after transduction with lentiviral vectors based on human immunodeficiency virus type 1.

The relatively low efficiency of target cell transduction and variations in the stability of transgene expression by retroviral vectors based on the Moloney murine leukemia virus (MoMLV) are major impediments to the use of such vectors in cancer gene therapy approaches. The present study was designed to investigate the stability and efficiency of transgene expression in human lung and breast cancer cell lines transduced with vectors based on human immunodeficiency virus type 1 (HIV-1) in vitro and in vivo in nude mouse models of metastasis. H460 lung carcinoma cells and MDA-MB-231 breast carcinoma cells were transduced with lentiviral vectors encoding enhanced green fluorescent protein (EGFP) and beta-galactosidase (beta-Gal), respectively. Transduced H460 cells were administered to nude mice by either intravenous or subcutaneous injection and MDA-MB-231 cells were implanted orthotopically into the mammary fat pad of such mice to induce primary tumor and metastatic lung tumor formation. High-level EGFP expression was maintained in transduced H460 cells in metastatic lung nodules for up to 6 weeks and transgene expression in vitro persisted for at least 23 days after retrieval of EGFP-positive H460 cells from the lungs of tumor-bearing mice and subsequent cultivation in vitro. Likewise, beta-Gal expression levels in metastatic MDA-MB-231 cells in lungs remained high for up to 11 weeks. Southern blot analyses carried out with DNA from lung nodules showed that proviral DNAs in H460 cells were maintained stably over many cell generations and during subsequent reimplantation in vivo. However, molecular analyses revealed variations in transgene copy numbers and expression levels among individual lung clones. These results demonstrate the usefulness of HIV-1-based lentiviral vectors for sustained and stable transgene expression in human lung and breast cancer cell lines in vitro and in vivo.

Animals↗

PubMed2004

Coagulation in sepsis.

Activation of the coagulation cascade during invasive infection can result in purpura fulminans, with rapid progression of tissue ischemia, or may manifest as abnormal clotting indices alone. Although severe derangements in coagulation are associated with organ dysfunction and increased mortality, the contribution of coagulopathy to the pathophysiology of sepsis remains incompletely understood. Over the past decade, investigators have evaluated several therapeutic anticoagulant strategies in sepsis, and manipulation of the coagulation system has emerged as a key concept in the current management of this disease. Clinical observations during treatment of septic patients with the endogenous anticoagulant activated protein C have stimulated additional study of interactions between endothelial injury, coagulation, and inflammation. This review describes clotting abnormalities during sepsis and discusses the clinical experience with therapeutic strategies intended to oppose excessive coagulation.

Animals↗

PubMed2002

Success of lung transplantation without surveillance bronchoscopy.

BACKGROUND: No current evidence demonstrates improved survival or decreased rate of bronchiolitis obliterans syndrome (BOS) despite regularly scheduled fiberoptic bronchoscopy (FOB) with transbronchial biopsy and bronchoalveolar lavage (TBB/BAL) after lung transplantation. Reduced lung function detected with spirometry or oximetry in symptomatic and asymptomatic lung allograft recipients (LARs) may be a more appropriate indication for bronchoscopic sampling. HYPOTHESIS: Clinically indicated TBB/BAL without routine invasive surveillance sampling of the transplanted lung does not decrease survival or increase the rate of BOS in LARs. METHODS: We reviewed 91 consecutive LARs transplanted at Ochsner Clinic between January 1995 and December 1999. Clinical indications for FOB with TBB/BAL include 10% decline in forced expiratory volume in 1 second below baseline; 20% decrease in forced expiratory flow rate between 25% and 75% of the forced vital capacity; or unexplained respiratory symptoms, signs, or fever. Along with demographic and clinical data, 1-year and 3-year survival rates for these 91 LARs were compared with 5,430 LARs from the International Society for Heart and Lung Transplantation (ISHLT) Registry transplanted during the same 60-month period. Ten of the 91 patients did not survive to hospital discharge after transplantation. We divided the remaining 81 LARs into 2 subsets: Group A patients (n = 43) underwent zero to 1 TBB/BAL and Group B patients (n = 38) required more than 1 procedure. Demographic data, rejection, infection, and incidence of BOS were compared between groups. RESULTS: The 1-year and 3-year survival rates in the Ochsner LAR cohort were 85% and 73%, respectively, vs 72% and 57% in the ISHLT cohort p < 0.01. The relative risks of death in the Ochsner group at 1- and 3-years were 0.56 (0.35-0.91) and 0.66 (0.48-0.92), respectively, p < 0.05. The median (range) follow-up was 910 days (60-1,886) for Group A and 961 days (105-1,883) for Group B, p = not significant. We observed twice as many patients with cystic fibrosis and twice as many pneumonia episodes in Group B. The rate of acute rejection in each group was not statistically different. The cumulative incidence of BOS was increased in Group B at 1 year and at 3 years (5% and 56%) when compared with Group A (3% and 13%), p < 0.01. CONCLUSIONS: Based on the findings from this observational, single-institution study, clinically indicated TBB/BAL without routine surveillance sampling of the lung allograft is unlikely to pose greater risk than does regularly scheduled bronchoscopy after lung transplantation.

Adult↗