ALTHOUGH Maisin and Picard (1924) induced cancer of the bladder by implanting pellets containing tar into the bladders of rats, Bonser, Clayson and Jull (1951) developed the technique of bladder implantation in mice, which as modified by Allen, Boyland, Dukes, Horning and Watson (1957) Onie of the difficulties of the method is the choice of a suitable medium with which to mix the substances to be tested. Most apparently inert materials induce tumours in a proportion of mice and even the most active carcinogens do not induce cancer in all the mice treated. For this reason a few substances which would be expected to be biologically inert have been tried.
METHODS AND MATERIALSThe technique used was the same as that described by Allen et al. (1957). With practice it is possible to expose the bladder and insert the pellet through a small incision in the skin. The incision may be so small that it can be closed with a single stitch. The probability that the incidence of tumours was due to chance was calculated by the x2 test. Stock mice bred in the Chester Beatty Research Institute were used.Cholesterol (Roche Products), and stearic acid (B.D.H.) were recrystallised from ethanol. Hexadeconal (cetyl alcohol) and octadecanol were purchased from British Drug Houses Ltd.
RESULTS AND DISCUSSIONTurmour Induction with " Inert " VehiclesThe incidence of tumours with inert substances some of which might be used in place of paraffin wax or cholesterol are given in Table I. Magnesium stearate gave a low incidence of tumours but it has the disadvantage that in the presence of chelating agents (e.g. ortho aminophenols and 8-hydroxyquinoline) the magnesium forms chelates. If such agents are being tested they would therefore be present as chelates.
One hundred and seventeen patients with advanced squamous cell carcinoma of the head and neck were randomised between two combination schedules, one with and the other without adramycin. Responses (more than 50% tumor regression) were 67% overall with 63% responding to the combination without adriamycin and 82% responding to the schedule containing it. The increase in response rate seen with the addition of adriamycin is not statistically significant. Prior radiotherapy reduced the likelihood of response to chemotherapy.
During the past two decades, understanding of the general nature and control of the closely integrated process of wound healing has been expanded (1-4). The role of native collagen synthesized de novo in the process of healing cutaneous wounds has been referenced by many workers in the past decade 4 Murrell Farms; Fort Worth, TX. 5 Microcrystalline collagen wound pad ; Avicon, 6 Curity gauze sponges ; Kendall Hospital Products 7 3 M Co., Minneapolis, MN. Inc., Fort Worth, TX. Div. ; Chicago, IL. Sta-tite, Cheeseborough-Pond ; New York, New York.
INTRODUCTION: Widespread use of PSA screening has raised concerns of overdiagnosis of low risk and underdiagnosis of high grade cancer. This is primarily due to the low sensitivity and specificity of PSA. PCA3, a non-coding large chain ribonucleic acid, is significantly over-expressed in cancer tissue and quantitatively measured by a novel urinary assay. The objective of this NCI EDRN trial was to conduct a comprehensive, independent validation of the PROGENSA PCA3 Assay for the detection of prostate cancer. METHODS: A prospective, PROBE-compliant NCI validation trial was undertaken at 11 clinical sites to evaluate PCA3 positive predictive value (PPV, PCA3 score >60) in the initial biopsy setting and negative predictive value (NPV, PCA3 score <20) in the repeat biopsy setting. PCA3 was obtained prior to biopsy but following an attentive DRE. We hypothesized that PPV for an initial prostate biopsy to be at least 55% and that NPV for a repeat biopsy to be at least 75%. The accuracy of PCA3 in detecting any prostate cancer and secondarily, high grade cancer (Gleason > 7), was compared to PCPT risk calculator through ROC curve analysis. RESULTS: 880 eligible men (mean age 62 years) were enrolled; 305 had a prior negative prostate biopsy. 99% had an informative PCA3 test. For the detection of any cancer, PPV was 80% (95% CI: 0.72 - 0.86) in the initial biopsy group while NPV was 88% (95% CI: 0.81 - 0.93) in the repeat biopsy group. PCA3 performance was superior to PCPT risk estimation and improved upon the detection of any cancer (p<0.006) and high grade cancer (p<0.02) when combined with the PCPT risk model. CONCLUSIONS: PCA3 ability to detect prostate cancer was superior to PCPT risk calculator in both the initial (p < 0.0001) and repeat biopsy setting (p=0.001)Independent validation of PCA3 demonstrated a high PPV in the initial biopsy setting and a high NPV in the repeat biopsy setting. Given the significant improvements in risk estimation over PCPT, PCA3 is expected to greatly enhance clinical decision making.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4451. doi:1538-7445.AM2012-4451
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