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J R Masters

Publications and source records attributed to J R Masters.

At least 91 records · Page 5Linked to original sources
PubMed1986

Intravesical chemotherapy: studies on the relationship between osmolality and cytotoxicity.

The effectiveness of intravesical chemotherapy for the treatment of superficial bladder cancer may be influenced by the conditions of administration, such as the osmotic strength of the instillate. Urine from patients with bladder cancer before treatment had osmolalities in the range 187 to 852 mOsm./kg. and these had decreased by an average of 135 mOsm./kg. at the completion of intravesical chemotherapy. Clinical preparations of drugs used for intravesical chemotherapy had osmotic strengths ranging from 65 to 1,038 mOsm./kg. The antitumor activities of the drugs most frequently used intravesically (doxorubicin, epodyl, mitomycin C and thiotepa), and of cisplatin and epirubicin in media of 6 different osmolalities were measured with a human bladder cancer cell line by inhibition of colony-forming ability. Reducing osmotic strength from 590 to 125 mOsm./kg. significantly increased the in vitro cytotoxicities of thiotepa, mitomycin C, cisplatin and epirubicin but not those of doxorubicin and epodyl. We conclude that the use of an instillate at the lowest achievable osmotic strength probably will be optimal for the intravesical administration of chemotherapeutic drugs.

Antineoplastic Agents↗
PubMed1986

Tissue culture model of transitional cell carcinoma: characterization of twenty-two human urothelial cell lines.

Twenty-two continuous cell lines derived from normal and neoplastic urothelium, maintained under identical culture conditions, were characterized in terms of isozyme phenotype, tumorigenicity, and xenograft morphology following xenotransplantation to nude mice, cytological appearance, in vitro growth rate, labelling index, and colony-forming efficiency, in parallel with separate studies of in vitro drug sensitivities and monoclonal antibody reactivities. Three groups were identified: (a) distinct lines with differing isozyme patterns, a broad spectrum of growth characteristics, and xenograft morphologies similar to the histopathology of the parent tumors after periods of up to 17 yr following establishment in vitro; (b) cross-contaminated sublines (maintained separately in different laboratories for periods of up to 10 yr), with identical isozyme patterns and similar growth characteristics, but differing markedly in tumorigenicity and xenograft morphology; and (c) lines derived from normal urothelium which were nontumorigenic and had an isozyme pattern usually only encountered in untransformed cells. These data indicate that cell lines representative of human transitional cell carcinomas can be selected on the basis of xenograft morphology and isozyme patterns, and that a panel of lines derived from normal and neoplastic urothelium could provide a model system to study the biology and treatment of this disease.

Carcinoma, Transitional Cell↗
PubMed1985

Comparison of the cytotoxic activities of chemotherapeutic drugs using a human bladder cancer cell line.

Many chemotherapeutic drugs have been used to treat patients with advanced bladder cancer, but few of these have been evaluated adequately in phase II clinical trials. Continuous cell lines provide one means for comparing the in vitro cytotoxicities of anticancer agents. In this study, a continuous cell line derived from a transitional cell cancer of the human bladder, which still produces tumours histologically similar to the tumour of origin on xenotransplantation, was used to measure the in vitro cytotoxicities of twelve chemotherapeutic drugs by clonogenic assay. The most cytotoxic agents tested were methotrexate, mitoxantrone, adriamycin, mitomycin C and cisplatin. These in vitro findings are compatible with the activity of these drugs given systemically as single agents in phase II clinical trials in patients with advanced bladder cancer.

Animals↗
PubMed1985

Monoclonal antibodies to human urothelial cell lines and hybrids: production and characterization.

Eleven independent monoclonal antibodies, the LBS series, were isolated after immunization of mice with RT112 cells, a continuous cell line derived from a transitional cell carcinoma of the human bladder. These antibodies were tested by indirect immunofluorescence on a panel of 28 human cell lines, of which 17 were urothelial carcinoma-derived, 4 of non-urothelial carcinoma origin, 3 fibroblast cell lines, 4 lymphoblastoid lines and 7 murine cell lines. Also tested were 7 somatic cell hybrid clones derived by fusion of human RT112 cells with murine bladder carcinoma MB63T/H cells. None of the LBS antibodies reacted with mesenchyme-derived cells, although all reacted with RT112 cells. On the basis of reactivity with the cell line panel, the antibodies were divided into 3 groups. Group I (LBS-1 and 19) reacted with all human epithelium-derived cell lines. Group II (LBS-2, 8, 15 and 17) reacted only with human urothelium-derived cells, tending to recognise the least anaplastic types. Group III antibodies (LBS-10, 20A, 20B, 21 and 34) were urothelium-specific on the human continuous cell line panel, but additionally reacted with murine urothelial and epithelial cell lines. The 6 human-specific antibodies (Group I and II) were used for preliminary analysis of human gene expression in a series of 7 mouse X human urothelial somatic cell hybrids. Each hybrid reacted with at least 1 LBS antibody, although there were changes in gene expression with time in culture, indicating both loss and unmasking of human genes. These data suggest the LBS-series antibodies recognise different determinants associated with epithelial and urothelial cell differentiation, and thus may be valuable probes in the study of normal differentiation and malignant transformation in human urothelial cells.

Animals↗
PubMed1985

The biological and clinical significance of HCG-containing cells in seminoma.

The morphological appearance, incidence and prognostic significance of human chorionic gonadotrophin (HCG)-containing cells in seminomas were examined in a retrospective series of 228 orchidectomy specimens, obtained between 1958 and 1972. Sections from each tumour were stained with haematoxylin and eosin (H & E) and immunocytochemically for HCG. In 33 (14.5%) of the tumours HCG-containing cells were observed, but in only 12 were these recognised in an initial study of the H & E stained sections. HCG staining was seen predominantly in syncytiotrophoblastic giant cells and rarely in "mulberry" cells and mononuclear seminoma cells. Of the patients whose tumours included HCG-containing cells 23% died of their disease within 2 years of orchidectomy, compared with only 8% of the patients whose tumours lacked this feature. It is concluded that immunocytochemical staining for HCG should form part of the routine histological assessment of seminomas, and that the presence of HCG-containing cells indicates a more aggressive disease.

Adult↗
PubMed1985

Serum and tissue tumour markers in seminomas.

The serum expression of the tumour markers hydroxybutyric dehydrogenase (HBD), beta human chorionic gonadotrophin (beta HCG), alphafetoprotein (alpha FP) and placental alkaline phosphatase (PLAP) has been assessed in a consecutive series of 50 patients with pure seminoma. In pre-orchiectomy sera from 15 patients with stage I disease, HBD was elevated in 5, beta HCG in 3, alpha FP in 1 and PLAP in 1 (of 3 only). In 27 patients with stage 2 or 3 disease, prior to chemotherapy, serum HBD was elevated in 19, beta HCG in 11, alpha FP in 2 and PLAP in 10 (of 18). The presence of beta HCG was investigated immunocytochemically in primary tumour tissue from 39 patients. It was demonstrated in 6 of 21 tumours from patients with stage I disease and 5 of 18 with stage 2 or 3 disease.

Alkaline Phosphatase↗
PubMed1985

Immunocytochemical localisation of prostate-specific antigen: specificity and application to clinical practice.

An immunocytochemical method to localise prostate-specific antigen (PSA) in paraffin sections was used to establish the prostatic origin of both primary and metastatic tumours. The specificity of the technique was confirmed in 65 known primary (63 PSA-positive) and 17 metastatic prostatic carcinomas (16 PSA-positive). Thirteen non-prostatic primary carcinomas and a series of benign proliferative and malignant conditions which might be considered in the morphological differential diagnosis of prostatic adenocarcinoma were PSA-negative. The technique has now been applied diagnostically to tumour tissue resected from 21 patients. These neoplasms of the base and neck of the bladder could not be categorised as prostatic or urothelial in origin by clinical and endoscopic assessment or by conventional histopathology. In 11 patients such tumours were PSA-positive, indicating a prostatic origin. In two further patients, the prostatic origin of lymph node secondaries was confirmed in the absence of a clinically apparent primary. The technique is a valuable adjunct to conventional histopathology.

Adenocarcinoma↗
PubMed1984

Identification of synergistic combinations of spirogermanium with 5-fluorouracil or cisplatin using a range of human tumour cell lines in vitro.

A series of continuous human tumour cell lines, derived from various tumour types, were used to establish whether the combination of spirogermanium (SP) with other 'standard' antitumour drugs proved superior to these as single agents in reducing cell survival in vitro. A non-cytotoxic concentration of SP was selected and when combined with a range of concentrations of cisplatin or 5-fluorouracil (5-FU), definite synergistic cell kill was noted in all lines tested. In contrast, the combination of SP with various other antitumor drugs, including adriamycin, methotrexate and the vinca alkaloids and with X-irradiation did not enhance cytotoxicity. These pre-clinical in vitro studies suggest that benefit may accrue from combining SP with either 5-FU or cisplatin and provide a basis for their clinical evaluation in colo-rectal tumours or transitional cell cancer of the bladder, respectively.

Antineoplastic Agents↗
PubMed1984

Association between infertility following reversal of vasectomy and the presence of sperm agglutinating activity in semen.

A statistically significant association between infertility, following reversal of vasectomy, and the presence of sperm agglutinating activity in post-operative semen samples has been demonstrated in a retrospective study. Sperm agglutinating activity was measured using a microtitration assay, and the number of positive samples rose from 3/78 (4%) pre-operatively, to 34/134 (25%) post-operatively. High titres (greater than or equal to 1:32) of agglutinating activity were observed only when viable sperm were present in the ejaculate. Positive semen titres were obtained only when parallel serum samples were positive at titres of greater than or equal to 1:256. Conception only occurred in the partner of one man whose seminal plasma contained agglutinating activity, but 22/34 (65%) of the men whose semen lacked such activity were fertile.

Female↗
PubMed1983

In vitro responses of human prostate tumour cell lines to a range of antitumour agents.

Four human prostate tumour continuous cell lines were employed for in vitro drug sensitivity testing of nine cytotoxic drugs, X-irradiation and two hormonal preparations. Responses were assessed by measuring cell survival as judged by colony formation in agarose. A marked heterogeneity of responses was noted to many of the agents studied, including X-irradiation. However, in terms of ID70 values for 24-h drug exposures, comparable responses in all the cell lines tested, with values falling within a 1.4- to 2.9-fold range, were noted with actinomycin D, adriamycin, m-AMSA, dibromodulcitol, 5-fluorouracil, hydroxyurea and ICRF-159. In contrast, mixed responses to cis-platinum and methotrexate were particularly marked, with ID70 values differing by factors of 3.8 and 7.5 respectively. In addition, when higher drug concentrations of m-AMSA, cis-platinum, dibromodulcitol and ICRF-159 were employed, significant deviations in the four survival curves became apparent. Continuous exposure to diethylstilboestrol and medroxyprogesterone acetate caused negligible cell kill. Due to these variable responses it was not possible to predict that any agent tested might have specific value in the treatment of prostate cancer. However, preliminary in vitro screening with such a panel of cell lines may complement in vivo studies with models of prostatic cancer and prove useful in investigations of mechanisms of drug resistance.

Cell Line↗
PubMed1983

Human benign prostatic hyperplasia in organ culture: studies on iododeoxyuridine uptake.

Prostate tissue architecture and function may be retained in vitro using organ culture. However, the application of the technique is limited due to the lack of simple means for measuring tissue response, for instance to factors controlling cell growth. It is confirmed in this study that measuring the uptake of the radioactive precursor of DNA, 5-[125I]-iodo-2'-deoxyuridine, is simple, rapid, and reproducible provided the heterogeneity of benign prostatic hyperplasia (BPH) is taken into account. Factors affecting the reproducibility (numbers of replicate explants and dishes), specificity (removal of unbound radioactivity and uptake into killed tissue), and sensitivity (radioactive concentration and exposure period) of this technique were investigated. A particular advantage of this approach is that histological assessments are made on the same tissue used for biochemical measurements. Furthermore, the method is sufficiently simple to permit serial investigations chronologically concerning factors, such as hormones, controlling BPH cell growth.

DNA↗
PubMed1983

Androgen metabolism by human prostatic tumours in organ culture.

Metabolism of testosterone and 5 alpha-dihydrotestosterone were investigated in benign and malignant human prostatic tumours maintained for 48 hr in organ culture. When tritiated testosterone was used as substrate there were significant differences between the metabolic pathways of the two types of tumour. Whilst the benign tumour had a predominantly reductive pathway leading to the formation of 5 alpha-reduced metabolites of testosterone, an oxidative pathway producing androstenedione was found to be the major pathway operative in the intermediate and poorly differentiated malignant specimens studied. In contrast to these differences observed in the metabolic pathway of testosterone when tritiated 5 alpha-dihydrotestosterone was used as substrate, no significant differences in the pattern of radiometabolites were observed.

Androstenedione↗
PubMed1981

Altered androgen metabolism in carcinoma of the prostate.

Testosterone metabolism was investigated in benign hypertrophied and malignant prostates using a tissue culture technique. The results demonstrated a distinct difference between the two types of tumour. The benign tissue was found to metabolize testosterone via a reductive pathway. The main radiometabolites were found to be dihydrotestosterone and androstanediols. On the other hand, the malignant tumours showed less ability to metabolize testosterone and the metabolism by these tumours was found to be an oxidative one, with the main metabolite being androstenedione.

Androstenediols↗
PubMed1980

Factors influencing the outcome of vasectomy reversal.

Fifty-six vasectomy reversals performed during the period 1976 to 1978 have been reviewed with reference to factors which might influence the outcome. Spermatozoa appeared in the ejaculate in 51 (91%) and remained in numbers greater than 10 million per ejaculate in 35 (63%). The wives of 14 men conceived. The following factors have been shown to be associated with a favourable result: a short delay between vasectomy and its reversal, a short previously resected segment, opalescent fluid from the cut lower end of the vas and the absence of circulating antisperm antibodies. A substantially higher conception rate was achieved when the husband had remained with his original partner. Sixty-two testicular biopsies obtained at the time of vasectomy reversal were examined by light microscopy and showed no gross impairment of spermatogenesis. Immunofluorescent techniques failed to show the presence of antigen antibody complexes in 36 testicular biopsies and in 12 vasal stumps.

Adult↗