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Biomedical subjects

J Lehr

Publications and source records attributed to J Lehr.

21 records · Page 2Linked to original sources

Establishment and characterization of a new human prostatic cancer cell line: DuCaP.

BACKGROUND: The lack of appropriate, clinically relevant, cell-based model systems has limited prostate cancer research and the development of new therapeutic modalities. Here we report the isolation and characterization of a new adherent prostate cancer cell line, derived from the dura mater of a cancer patient. METHODS: Prostate cancer tissue was harvested at autopsy from a metastatic lesion to the dura mater of a patient with hormone refractory prostate cancer. This tissue was xenografted into SCID mice and later harvested and plated on tissue culture dishes. For characterization, soft agar clonegenic assay, in vivo xenograft growth, in vitro doubling time, karyotype analysis, immunocytochemistry for cytokeratin-18, androgen receptor, and PAP (prostatic acid phosphatase) expression, RT PCR for PAP, PSMA (prostate specific membrane antigen), expression and northern and western blot analysis to determine expression of Rb and p53, were performed. RESULTS: DuCap grows in vitro (passage 55), forms colonies in soft agar, produces tumors in SCID mice (xenograft passage 12), and is androgen sensitive. DNA content was hypertriploid. PSA was detected in mouse serum and media. Cells were AR, PAP and cytokeratin-18 positive by immunocytochemistry. PSMA and PAP were detected by RT-PCR. AR, P53, and Rb were expressed in Northern blot analysis. P53 protein was detected in Western blot analysis but Rb protein was not. CONCLUSIONS: This cell line exhibits many phenotypic characteristics of clinical prostate carcinoma, including expression of PSA, PSMA, PAP and AR.

Androgens↗

High-frequency ventilation: a promising new approach to mechanical ventilation.

Adequate pulmonary ventilation can be achieved in experimental animals and in humans using tidal volumes on the order of the anatomic dead space volume applied at very high ventilatory frequencies (3-30 Hz). Classical mechanism of gas exchange cannot account for these paradoxical observations, but theories based on the concept of augmented diffusion may provide an adequate explanation for this phenomenon. Even though the exact mechanisms accounting for gas exchange are not well understood, a number of successful ventilators have been designed and tested based on the concept of small volume/high frequency ventilation. The differences among these various ventilators are compared and contrasted and possible clinical uses of the technique are discussed.

Animals↗

Oral cyclophosphamide and oral hydroxyurea in the treatment of hormone refractory prostate cancer in rats.

Hormone refractory prostate cancer is a fatal disease and currently no standard cytotoxic chemotherapy exists for prostate cancer. The recent use of prostate specific antigen as an endpoint for clinical trial has resulted in the ability to test the activity of chemotherapy agents in a quick manner. The aim of this study was to investigate the activity of the oral combination of two familiar agents, cyclophosphamide and hydroxyurea, against hormone refractory prostate cancer. In vitro studies demonstrated that hydroxyurea was more active than cyclophosphamide against the anaplastic Dunning rat prostate cancer cell line, Mat-LyLu. In vivo experiments, however, demonstrated cyclophosphamide to be superior to hydroxyurea. The combination of both agents failed to enhance inhibition of subcutaneously implanted Mat-LyLu cells. A human trial of oral cyclophosphamide using prostate specific antigen as an intermediate endpoint may be warranted.

Adenocarcinoma↗