Relationship of DNA content to conventional prognostic factors in clinically localised carcinoma of the prostate.

One hundred and nine patients treated by total prostatectomy for apparently localised carcinoma were analysed to investigate the prognostic significance of capsular invasion and penetration, seminal vesicle invasion, lymph node metastases, grade as assessed by the Gleason and MD Anderson Hospital (MDAH) systems and DNA content measured by flow cytometry of nuclear material extracted from paraffin embedded tumour. Comparison of DNA content was made with 36 benign prostates. Mean follow-up/survival was 60.7 months, at which time 21 patients had evidence of recurrence or had died. Only 5 patients had local recurrence. Tumour grade, as assessed by both the Gleason Sum Score and the MDAH system, correlated with anatomical extent and was the most important determinant of time to recurrence. Fifty-nine tumours were diploid, 44 tetraploid and 6 aneuploid. One of 36 benign prostates showed aneuploidy. Ploidy did not correlate with the anatomical extent of the tumour or with grade. Tetraploid tumours recurred earlier than diploid tumours. None of 6 aneuploid tumours have recurred, although only 3 have been followed beyond 5 years. Multivariate analysis showed that after accounting for grade, none of the other variables, including ploidy, contributed any additional significant prognostic information. Although the results must be regarded as preliminary, in view of the small number of patients with recurrence, they suggest that DNA content offers limited prognostic information in clinically localised prostate cancer.

The in vitro and in vivo effects of extracorporeal shock waves on malignant cells.

The in vitro cytotoxic effect of extracorporeal shock waves (ESW) on renal cell carcinoma (RCC) cells was compared to the effect on normal human embryonic kidney (NHEK) cells. In the in vitro studies cell samples were brought into the second focal point and exposed to different numbers of shock wave impulses. The four parameters of RCC tumor cell injury which were measured, i.e., cell viability, cell growth, cell attachment and electron microscopic evidence of damage, were augmented with increasing SW levels. At 2,000 shock waves (SW) a significant decrease in RCC viability, cell growth and cell attachment was seen compared to the NHEK cells. In the in vivo experiment a FANFT induced bladder tumor was transplanted into the right hind legs of C3H/He mice and the tumors were exposed to 1,400 SW. Preliminary data showed that 1,400 SW at day 12 post transplant significantly inhibited tumor growth. Combining 1,400 SW with cis-diamminedichloroplatinum (4 mg/kg) did not enhance the tumor inhibitory effect of each individually. Doxorubicin (5 mg/kg) and 1,400 SW produced a significant synergistic tumor inhibitory effect.

Quantitative measurements of humoral immune response in mice to a FANFT induced bladder tumor.

Using unfixed mouse bladder tumor cells (MBT) as target cells and a modified avidin-biotin-complex (ABC) method made it possible to detect a humoral immune response in C3H mice with growing MBT tumors. The rise of the serum levels is significant (p less than 0.005) when compared to control animals and correlates with the tumor size. Mice with recurrences after surgical removal of the primary tumor had significantly (p less than 0.05) higher serum values than animals without recurrence. Purulent or granulomatous inflammatory changes, muscle necrosis, growth of a lymphoma or an ovarian carcinoma did not significantly change the results (p less than 0.05). Injection of myeloma cells from a different strain of mice caused a minimal, but significant increase in the values when compared to controls (p less than 0.0001). However, the slope of the curve differed significantly (p less than 0.05) from that in mice with MBT tumors. Irradiated MBT cells or Corynebacterium parvum used as immunomodulators significantly increased the serum values (p less than 0.001). In the presence of a growing MBT tumor, however, the immunomodulation did not substantially falsify the results. The serum values were related to the corresponding tumor sizes.

Automated differential cell counting of viable cells.

A rapid, automated method of differentially counting viable cells by ethidium bromide-acridine orange cytofluorography is described (Takasugi 1971). The method is shown to have comparability, equal precision, and sensitivity to the standard trypan blue, visual method. The method is applicable to microcytotoxicity testing.