This study examined the initial behaviour of 48 human oral squamous cell carcinomas (SCC) in cell culture. The early outcome of these cultures (contamination, absence of cell growth, epithelial cell senescence/fibroblast overgrowth, extended keratinocyte growth) did not reflect the clinical characteristics of the tumours of origin. Four new human oral SCC cell lines were characterized more extensively. Each cell line was immortal, 3T3-independent, and expressed low degrees of anchorage independence (CFE less than 4 per cent). Two of the four cell lines were tumorigenic in athymic mice. All of the cell lines expressed keratin intermediate filaments and two showed weak co-expression of vimentin. A wide range of keratins were expressed by the tumour xenografts; cornified keratins (K1, K10) were only expressed in the absence of K19 and vimentin, and vice versa. The nuclear:cytoplasmic ratio and the degree of serum independence correlated with each other and with the STNMP clinical grading of the tumours of origin.
Endoureterotomy and endopyelotomy usually involve an endoscopic antegrade approach. In an effort to simplify this technique, we designed an 8-mm balloon catheter with a 100-microns electrocautery cutting wire (Acucise) for retrograde incision of the ureter under fluoroscopic control. Twenty-eight patients with ureteral or ureteropelvic junction obstruction of 3.5 cm or less underwent Acucise endoureterotomy or endopyelotomy. The average operating time was 100 minutes, and the average hospital stay was 2.6 days. Follow-up was obtained with a subjective symptom score, intravenous urography, diuretic renal scan, a Whitaker test, or various combinations thereof. All patients had a minimum of 3 months of follow-up (mean 3.8 months; range 3-9 months). Overall, of the 21 patients who had symptoms of upper tract urinary obstruction, 14 (67%) had complete resolution, and another 4 (19%) had partial resolution, of their symptoms. Postoperative studies demonstrated normal upper tracts in 71% and improvement in another 14% of the patients. In our experience, the Acucise ureteral cutting balloon device provides an effective and efficient means for performing a retrograde endoureterotomy or endopyelotomy.
This study examined the response of human keratinocytes in different stages of transformation to exogenous TGF-beta 1 and EGF as well as their receptor and growth-factor expression. Cells of the spontaneously immortalized HaCaT cell line and c-Ha-ras transfected clones (I-6, I-7, II-3, II-4) exhibited different tumorigenic potentials when transplanted to athymic mice. HaCaT- and I-6 cells were non-tumorigenic, I-7 cells formed persisting epidermal cysts (benign tumours) and II-3 and II-4 cells developed into invasive squamous-cell carcinomas. TGF-beta 1 inhibited thymidine uptake in a dose-dependent manner, a progressive decrease in response being associated with an increasing malignant potential (HaCaT greater than I-6 greater than I-7 = II-4). HaCaT-cells and ras-clones expressed TGF-beta 1 mRNA at similar levels, but cells of increasing malignant potential secreted markedly less receptor-binding TGF-beta (HaCaT greater than I-6 = I-7 greater than II-3 greater than II-4) into the culture medium. Whilst ras-transfected cells expressed fewer TGF-beta receptors than HaCaT cells, there was little difference between TGF-beta receptor number or affinity between the 4 transfected cell clones. The same was true for the TGF-beta receptor types, but Type-II receptors were expressed at lower levels by the malignant clones II-3 and II-4. When HaCaT and ras-transfected cells were investigated for their response to exogenous EGF, cells were refractory (I-7, II-4), partially stimulated (I-6) or fully stimulated (HaCaT). Cells with increasing malignant potential produced increasing amounts of endogenous TGF-alpha (II-4 = II-3 greater than I-7 = I-6 greater than HaCaT). All tumorigenic ras clones expressed higher mRNA levels than HaCaT-cells. Ras-transfected clones expressed fewer high- and low-affinity EGF receptors than HaCaT cells with a tendency toward increased numbers of high-affinity EGF receptors associated with increasing malignant potential (II-4 = II-3 greater than I-7 greater than I-6) but these changes were associated with a progressive decrease in receptor affinity. The results indicate that tumour progression in human epidermal keratinocytes transfected with c-Ha-ras is associated with a progressive abrogation of TGF-beta 1 and EGF growth control. They suggest that the increased autonomous growth potential associated with advanced stages of epithelial tumour progression can be defined more closely using a cellular profile of TGF-beta and EGF.
In an effort to further evaluate the potential application of laparoscopy to urologic surgery, we explored the feasibility of using this minimally invasive approach for performing a partial nephrectomy. Nine female pigs underwent laparoscopic partial nephrectomy (LPN) utilizing a plastic cable tie (15 mm. x 4 mm. x 1 mm.) to achieve renal ischemia and an Argon Beam Coagulator probe (ABC) (Birtcher Medical Systems) to fulgurate the transected surface. Six weeks after LPN, 6 pigs underwent creatinine clearance, renin level, arteriography, BP samples and were then killed. The renal remnants were weighed and sectioned for histological studies. These studies revealed excellent function of the renal remnant, no AV fistula, and no evidence of renovascular hypertension. LPN is a feasible, repeatable procedure in the pig. Control of the renal hilum, transient parenchymal compression with a plastic cable, and use of the argon beam coagulator are key elements in performing this procedure.
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