The activated partial thromboplastin time.
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Biomedical subjects
Publications and source records attributed to J L Chin.
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OBJECTIVE: Several new minimally invasive therapies have recently been popularized for both malignant and benign prostate disorders, including interstitial implantation of radioactive seeds and high-radiofrequency wires, cryoablation, transurethral thermotherapy, and laser prostatectomy. Complications can be incurred during the various procedures, often as a result of injury to adjacent anatomic structures. Some of the complications are inadvertent, whereas others are inherent in the particular treatment process. We hope to increase awareness and understanding of some of the potential complications. METHODS AND MATERIALS: Magnetic resonance (MR) and three-dimensional transrectal ultrasonography (TRUS) imaging were utilized to illustrate the relevant pelvic anatomy in, respectively, a healthy volunteer and four patients undergoing evaluation for prostate symptoms. In addition, data from the Visible Human dataset (the Visible Human Project is part of the National Library of Medicine 1986 Long-Range Plan) were used. RESULTS: The potential complications relating to urinary sphincter and anal sphincter control, sexual function, pelvic musculature, and pelvic nerve physiology could be explained on the basis of the MR and TRUS findings using cryoablation for illustrative purposes. CONCLUSION: A clear understanding of the relevant anatomy and physiology is essential for the physician to provide patient counseling preoperatively regarding anticipated sequelae and to avoid preventable intraoperative complications related to minimally invasive therapeutic procedures for the prostate.
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We previously reported that the murine fibroblast cell line LTA is tumorigenic but non-metastatic, and is non-responsive to a transfected H-ras oncogene. In contrast, NIH 3T3 cells are non-tumorigenic but are ras-responsive and become metastatic when transfected with ras. Somatic cell hybrids between LTA and NIH 3T3 cells are tumorigenic, metastatic and ras-responsive. Here we examined expression of type IV collagenases in parental LTA and NIH 3T3 cells (with and without ras) and four metastatic LTA x NIH 3T3 hybrids (also with and without ras). Parental NIH 3T3-derived cells had both 72 kDa and 92 kDa gelatinase activities, and LTA-derived cells had either aberrantly sized approximately 90 kDa activity alone or neither enzyme activity. All four metastatic hybrids expressed 60-72 kDa gelatinase activity, while three of them also had 92 kDa activity and one had only minimal 92 kDa activity. Thus the metastatic phenotype of the hybrids was associated with expression of 72 kDa gelatinase. Levels of RNA for tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2) were relatively constant, suggesting independent regulation of type IV collagenases and their inhibitors. Southern blotting and probing with PCR-synthesized cDNA fragments of the mouse 72 kDa type IV collagenase gene showed that this gene was present in all cells although the structure of this gene in one of the three LTA cell lines differed from that of the other cells. Our results suggest that a key change in the metastatic hybrids, relative to non-metastatic parental LTA cells, is induction of expression of 72 kDa type IV collagenase.
We previously showed that tumorigenic, non-metastatic LTA cells can be converted to a metastatic phenotype either by cell fusion with non-malignant NIH 3T3 cells, or by transfection with genomic DNA from metastatic murine B16F1 or human 1GR37 melanoma cells. In order to identify a gene present in NIH 3T3 cells that is responsible for this conversion, we transferred DNA from an NIH 3T3 genomic library into LTA cells and tested for changes in metastatic properties, assessed in the chick embryo. We found that 3 of 4 pools of transfectant clones showed significantly increased metastatic ability over the vector-only control transfectants. All three metastatic transfectant pools showed significantly increased RNA levels of the 72 kDa type IV gelatinase (MMP-2). To test whether increased expression of MMP-2 was sufficient to convert LTA cells to metastatic ability, we transfected full length MMP-2 cDNA, in a CMV-promoter expression construct, into LTA cells. Stable transfectants with elevated MMP-2 RNA and enzymatic activity were obtained. The highest MMP-2 expressing clone was assayed for experimental metastatic ability in the chick embryo, and found to be no more metastatic than LTA parental cells. We conclude that increased MMP-2 expression accompanies the malignant conversion of LTA cells, but MMP-2 expression alone is not sufficient to bring about this change. The inability of LTA cells to metastasize thus appears to be due to a more complex defect than insufficient MMP-2. This study supports the idea that malignant conversion may require the concerted activation of multiple genes, which are in turn controlled by regulatory genes, whose identification will be important in understanding and controlling metastasis.