PubMed Health⌕ Search

Biomedical subjects

J R Masters

Publications and source records attributed to J R Masters.

At least 73 records · Page 4Linked to original sources
PubMed1989

The incidence and influence upon fertility of antisperm antibodies in seminal fluid following vasectomy reversal.

Seminal plasma samples from men undergoing vasovasostomy were analysed for antisperm antibodies using the indirect immunobead test. A pre-operative assessment showed antisperm antibodies of either IgA or IgG class to be present in 9/27 (33.3%) men. A significant increase (P less than 0.05) in the post-operative incidence of the antibodies was seen in the men who achieved patency (27/45, 60%) but not in those men for whom no sperm were seen in the ejaculate (4/10, 40%). After follow-up for a minimum of 1 year, conception rates for couples in which the male partner had achieved patency were similar in the groups with no antibodies detected post-operatively (12/18, 66.7%) or with IgA alone (2/3, 66.7%), but was reduced significantly in the presence of IgG (1/9, 11.1%; P less than 0.05) or IgA + IgG (3/15, 20.0%; P less than 0.01).

Autoantibodies↗
PubMed1989

DNA ploidy and the prognosis of stage pT1 bladder cancer.

The histopathological grade, proportion of "S"-phase nuclei and DNA ploidy values were linked and of prognostic significance in a retrospective series of stage pT1 bladder cancers. Nuclei were extracted from paraffin sections of 75 biopsies (56 patients). DNA ploidy and the proportion of "S"-phase nuclei were measured using flow cytometry. Progressive disease (pT2 or greater) developed within 3 years in 35% (6/17) of patients with poorly differentiated tumours, 35% (8/23) with aneuploid tumours and 35% (7/20) of those with a high proportion of "S"-phase nuclei. Of 8 tumours with all 3 features, progressive disease developed in 6 cases (75%). Of 9 patients who developed progressive disease, 8 (89%) had aneuploid tumours. Progressive disease did not develop in 11 patients with well differentiated tumours, compared with 4% (1/24) in diploid/tetraploid tumours and 7% (2/27) in those with a low/medium percentage of "S"-phase nuclei. In contrast to muscle-invasive disease, recurrent superficial tumours developed with a high incidence in all groups. Only 6/56 patients (11%) remained alive and disease-free for 3 years. It is concluded that these 3 features are of similar prognostic significance and accuracy in identifying patients requiring more aggressive therapy.

Adult↗
PubMed1988

Differential repair of platinum-DNA adducts in human bladder and testicular tumor continuous cell lines.

The formation and removal of four platinum-DNA adducts were immunochemically quantitated in cultured cells derived from a human bladder carcinoma cell line (RT112) and from two lines derived from germ cell tumors of the testis (833K and SUSA), following exposure in vitro to 16.7 microM (5 micrograms/ml) cisplatin. RT112 cells were least sensitive to the drug and were proficient in the repair of all four adducts, whereas SUSA cells, which were 5-fold more sensitive, were deficient in the repair of DNA-DNA intrastrand cross-links in the sequences pApG and pGpG. Despite expressing a similar sensitivity to SUSA cells, 833K cells were proficient in the repair of all four adducts, although less so than the RT112 bladder tumor cells. In addition, SUSA cells were unable to repair DNA-DNA interstrand cross-links whereas 50-85% of these lesions were removed in RT112 and 833K cells 24 h following drug exposure. It is possible that the inability of SuSa cells to repair platinated DNA may account for their hypersensitivity to cisplatin.

Cell Line↗
PubMed1988

c-myc oncoprotein levels in bladder cancer.

The protein coded by the oncogene c-myc, p62c-myc, was measured using monoclonal antibodies and flow cytometry in nuclei derived from paraffin-wax sections of transitional cell carcinomas of the human bladder. Superficial disease (stages pTa and pT1) which did not recur within 5 years of diagnosis had significantly higher oncoprotein levels than those which did recur or were muscle-invasive (stage pT2 or greater) at presentation (P less than 0.01). These preliminary findings indicate that oncoprotein levels might have prognostic significance for bladder cancer.

Antibodies, Monoclonal↗
PubMed1988

Intravesical chemotherapy: combination with dimethyl sulfoxide does not enhance cytotoxicity in vitro.

There is evidence that dimethyl sulfoxide (DMSO) can increase the anticancer activity of chemotherapeutic drugs. As DMSO is instilled into the bladder for interstitial cystitis, it could be readily adopted in clinical practice if it was found to enhance the effectiveness of the drugs used for intravesical chemotherapy. The purpose of this study was to investigate, using a human bladder cancer cell line, the hypothesis that DMSO enhances the activity of these agents. However, the addition of 4% DMSO to the four drugs most frequently used for intravesical chemotherapy (adriamycin, epodyl, mitomycin-c, thiotepa) did not increase tumour cell kill in vitro.

Administration, Intravesical↗
PubMed1988

Differential sensitivities to gamma radiation of human bladder and testicular tumour cell lines.

Gamma radiation sensitivities of continuous cell lines from nine human tumours were measured, comparing four derived from transitional cell carcinomas of the bladder with five from non-seminomatous germ cell tumours of the testis. The testicular cells were significantly more radiosensitive than the bladder cells, corresponding to the response to therapy of these tumour types in patients. These observations indicate that radiosensitivity is retained in vitro and is an inherent property of the testicular tumour cells. These gamma radiation sensitivities were compared with those of SV40-transformed fibroblasts derived from a normal individual and one with the heritable disease, ataxia-telangiectasia (A-T). The bladder cells had gamma radiation sensitivities similar to that of the SV40-transformed normal line. The testicular cells were hypersensitive to gamma radiation, although not as sensitive as the SV40-transformed A-T line. A-T cells, unlike those derived from normal individuals, continue to synthesize DNA at a normal rate following radiation exposure, prompting a comparison of the kinetics of DNA synthesis in three bladder and three testicular tumour cell lines. One of the bladder and two testicular lines showed a reduced inhibition when compared to the other tumour cell lines and the SV40-transformed normal line. Thus there was no clear association between DNA synthesis inhibition and radiosensitivity.

Carcinoma, Transitional Cell↗
PubMed1987

Differential expression of collateral sensitivity or resistance to cisplatin in human bladder carcinoma cell lines pre-exposed in vitro to either X-irradiation or cisplatin.

Two sublines were derived from a human bladder carcinoma continuous cell line (RT112-P), one by exposure to fractionated X-irradiation (RT112-DXR8) and the other by continuous exposure to cisplatin (RT112-CP). RT112-DXR8 cells were 1.6- to 2-fold more sensitive to cisplatin and 2 analogues, carboplatin and iproplatin, compared with the parental line, whereas RT112-CP cells were 1.6- to 2.8-fold more resistant to these agents. Uptake of 195mcisplatin was elevated 1.4-fold in RT112-DXR8 cells compared with RT112-P cells whereas uptake into RT112-CP cells was similar to that of the parental line. Binding of 195mcisplatin to DNA was similar in all 3 lines. Levels of reduced glutathione were significantly elevated in RT112-CP cells and significantly reduced in RT112-DXR8 cells compared with the parental cells. In addition, activities of glutathione reductase and glutathione peroxidase were higher in RT112-CP cells than in the parental cells whereas the activity of glutathione-S-transferase was similar in all 3 cell lines. A 2.5-fold greater induction of DNA-DNA interstrand crosslinks occurred in RT112-DXR8 cells compared with the parental line, whereas crosslinking in RT112-CP cells, whilst initially similar to that seen in RT112-P cells, was significantly elevated at later times. These findings suggest that mechanisms associated with the expression of resistance and collateral sensitivity to cisplatin may differ.

Cell Line↗
PubMed1987

Intravesical chemotherapy: combination with Tween 80 increases cytotoxicity in vitro.

Tween 80 was shown to enhance significantly the cytotoxic activities of the four drugs (adriamycin, epodyl, mitomycin-c, thiotepa) most frequently administered intravesically to treat superficial bladder cancer. The colony forming ability of a human bladder cancer cell line, RT112, was measured following a 1 h exposure to each of the four drugs both alone and in combination with 0.1% and 0.3% Tween 80. Cell survival was not reduced by 0.1% Tween 80 alone. We conclude that the combination of Tween 80 with these drugs might increase the therapeutic index of intravesical chemotherapy.

Administration, Intravesical↗
PubMed1987

Factors influencing the sensitivity of two human bladder carcinoma cell lines to cis-diamminedichloroplatinum(II).

A two-fold difference in sensitivity to cis-diamminedichloroplatinum(II) (cisplatin), as judged by colony forming assays, has been demonstrated in two human bladder carcinoma continuous cell lines. Approximately twice as many DNA-DNA interstrand cross-links (ISL) and a 2-fold greater inhibition of DNA synthesis occurred in the more sensitive T24 cell line than in the RT112 cell line after exposure to the same concentrations of cisplatin. Equitoxic concentrations of cisplatin resulted in similar extents of ISL and inhibition of DNA synthesis in both cell lines. Although drug uptake was identical, twice as much cisplatin was bound to the DNA of T24 cells than RT112 cells. However after equitoxic concentrations of cisplatin the DNA from both cell lines was platinated to a similar extent. In addition, levels of glutathione (GSH), glutathione reductase (GR) and total glutathione-S-transferases (GST) were higher in the less sensitive RT112 cell line.

Biological Transport↗
PubMed1987

Histological grade, elastosis, DNA ploidy and the response to chemotherapy of breast cancer.

The relationships between response to chemotherapy of advanced breast cancer and the histological type, grade, elastosis content and DNA ploidy of the primary tumours were examined using paraffin-embedded tissue derived from 125 patients. Higher response rates were seen amongst tumours with a high elastosis content and those that were diploid. However, selection of patients with advanced breast cancer for chemotherapy will not be assisted significantly by an assessment of these features in the primary tumour.

Aneuploidy↗
PubMed1987

Differential sensitivities of human testicular and bladder tumor cell lines to chemotherapeutic drugs.

The in vitro drug sensitivities of 5 human testicular tumor cell lines (Tera II, SuSa, NEC-8, 833K, T3B1) and 5 human bladder carcinoma cell lines (RT4, RT112, T24, HT1197, HT1376) were compared. Cytotoxicities of cisplatin and doxorubicin were assessed by inhibition of colony-forming ability during continuous exposure to a range of drug concentrations. The ranges of the drug concentrations required to kill 70% of clonogenic cells obtained against the testicular cell lines were 1-7 ng/ml and 21-161 ng/ml for doxorubicin and cisplatin, respectively, compared with 4-19 ng/ml and 112-431 ng/ml for the bladder cell lines. This study shows that continuous cell lines retain the relative clinical chemosensitivities of their tumors of origin. The results also indicate that testicular tumor cells are inherently more sensitive to the cytotoxic effects of chemotherapeutic drugs than are bladder cancer cells.

Cell Line↗
PubMed1986

Intravesical chemotherapy. Studies on the relationship between pH and cytotoxicity.

The influence of pH on the antitumor activity of drugs used for intravesical chemotherapy was studied. A human continuous cell line derived from a transitional cell carcinoma of the bladder was exposed to 6 drugs (Adriamycin [doxorubicin], cisplatin, epirubicin, epodyl, mitomycin C, and thiotepa) for 1 hour at 11 pH values ranging from 5.2 to 9.7, and cytotoxicity was measured by inhibition of colony formation. pH had a marked influence on drug activity: cisplatin, mitomycin C, and thiotepa were most cytotoxic in acid media, Adriamycin, and epirubicin in alkaline media, while epodyl was the only drug whose cytotoxicity was unaffected by pH. In addition to these in vitro studies, comparisons were made of the pH of urine samples obtained from patients immediately before and at the completion of intravesical chemotherapy. Changes in pH up to a maximum of +/- 1.6 units were observed, although in most cases, values were similar before and after therapy. All the drugs used were acidic in solution, with the exception of thiotepa. It is concluded that by adjusting solvent and urine pH to the optimum value for each drug, the effectiveness of intravesical chemotherapy might be enhanced.

Antineoplastic Agents↗
PubMed1986

Influence of clonogenic assay methodology on measurement of drug sensitivities in vitro.

To assess the influence of clonogenic assay methodology on measurement of reproductive cell kill, the in vitro sensitivities of a human bladder cancer cell line, RT112, to methotrexate and adriamycin were determined using ten different procedures. Marked differences in dose-response to methotrexate, but not adriamycin, were observed.

Antineoplastic Agents↗
PubMed1986

Intravesical chemotherapy: in vitro studies on the relationship between dose and cytotoxicity.

The relative importance of two variables, drug concentration and period of exposure, in relation to the therapeutic potential of intravesical chemotherapy was examined in an experimental system. A human bladder cancer cell line was exposed to a range of concentrations of the four drugs commonly used to treat superficial bladder cancer (adriamycin, epodyl, mitomycin-c, thiotepa) for periods of 30, 60 and 120 min. An exponential relationship was observed between clonogenic cell kill and both drug concentration and period of exposure. Thus, under the experimental conditions employed, cytotoxicity is proportional to dose (i.e. concentration X period of exposure). These two variables are of equal importance in relation to tumor cell kill, indicating that maximum therapeutic benefit may be obtained by using the highest concentration achievable for as long as the patient can retain the instillate, bearing in mind the potential increase in toxicity to the patient and the cost.

Antineoplastic Agents↗
PubMed1986

Response to endocrine therapy and breast cancer differentiation.

The purpose of this study was to determine whether aspects of tumour differentiation are associated with response to endocrine therapy in patients with advanced breast cancer. The features studied were the histological type, grade, and elastosis content of the primary tumours, and the disease-free interval. Statistically significant associations were observed between response to endocrine therapy and histological grade and disease-free interval. In addition, statistically significant associations were observed between histological grade and elastosis and disease-free interval. It is concluded that tumours which are more highly differentiated have a better chance of responding to endocrine therapy.

Androgens↗