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Biomedical subjects

M S Soloway

Publications and source records attributed to M S Soloway.

At least 235 records · Page 13Linked to original sources
PubMed1982

Growth characteristics of N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT)-induced mouse bladder tumor lines in a human tumor stem cell assay.

Four N-[4-(5-nitro-2-furyl)-2-thiazolyl]-Formamide (FANFT)-induced mouse bladder tumor (MBT) lines were tested for their ability to form colonies in a tumor stem cell assay. Anticancer drug testing was done using this assay to determine whether reproducible colony survival curves could be be produced. All four cell lines produced colonies at 10--14 days, whether taken from culture or murine tumor. Cloning efficiencies ranged from 0.29% to 1.93% from culture and from 0.005% to 0.05% from the murine source. Growth characteristics were described. Cells from colonies were histologically similar to the original cells plated. A linear relationship existed between the number of cells plated and the number of colonies produced. In vitro drug studies were reproducible and correlated with in vivo data. Therefore, MBT lines can be used for in vitro drug testing in a tumor stem cell assay and may be useful in selecting active chemotherapeutic agents in the murine tumor model.

Animals↗
PubMed1982

Single and sequential combination intravesical chemotherapy of murine bladder cancer.

We investigated the effectiveness of intravesically administered drugs on the tumor incidence and tumor size in a FANFT-induced animal model for bladder cancer. In the first experiment 106 C3H/He mice were divided into a control and three treatment groups. Therapy consisted of either cis-diamminedichloroplatinum (II) (DDP), mitomycin C, or thio-tepa. There was a reduction in the tumor incidence in all treated groups; this was statistically significant for those receiving mitomycin C (p less than 0.04) and DDP (p less than 0.001). No significant difference in the mean or median tumor weight (an index of tumor volume) between the treated and control groups was found. In a second experiment intravesical combination chemotherapy was compared to single-agent therapy. Animals received either doxorubicin hydrochloride (Adriamycin), mitomycin C, thio-tepa, mitomycin C + doxorubicin, or mitomycin C + thio-tepa. Although there was no significant difference in tumor incidence among the groups with the exception of mice receiving thio-tepa, animals receiving sequential combination chemotherapy had lower mean and median bladder weights suggesting an improved therapeutic effect.

Animals↗
PubMed1982

Effect of media and growth promoters on in vitro cultivation of normal murine urinary bladder epithelium.

Growth potential of normal murine epithelium was investigated by means of 3 culture media: RPMI 1640 with fetal calf serum, Dulbecco's with fetal calf serum and McCoy's with horse serum. The effect of 3 growth promoters was tested separately with each of the 3 media. A total of 886 explants were cultured from 29 murine bladders and epithelial outgrowth was obtained in 35.2 per cent. The growth medium 1640 with 20 per cent fetal calf serum and epithelial growth factor produced the most abundant outgrowth of explants. McCoy's medium containing 15 per cent horse serum produced significantly lower outgrowth compared to the medium containing fetal calf serum (p less than 0.001). Epidermal growth factor has a stimulating effect and horse serum has an inhibitory effect on growth of normal murine epithelial cells.

Animals↗
PubMed1982

The clonogenic growth of cells derived from bladder barbotage in patients with transitional cell carcinoma of the bladder: a preliminary report.

Tumor cells obtained from bladder washings in 41 patients with transitional cell carcinoma of the bladder and 15 control subjects were analyzed for their ability to produce cluster and/or colony formation in a tumor stem cell assay. In vitro cell growth was correlated with the presence of tumor at the time of bladder washing, tumor grade and treatment status. Of 34 bladder washings from patients with biopsy-proved transitional cell carcinoma 88 per cent produced cluster and/or colony formation. Specimens from patients not currently receiving intravesical chemotherapy at the time of bladder barbotage produced colonies in 54 per cent of the cases, compared to 25 per cent from patients receiving therapeutic or maintenance therapy. Higher grade tumors produced more viable cells at bladder barbotage but clonal growth rates were independent of histologic grade. We conclude that bladder barbotage may serve as a source of cells for chemotherapeutic drug testing in patients with transitional cell carcinoma of the bladder. Bladder washings also may be useful as a source of tumor cells for monitoring the in vivo growth potential of bladder cancer in the tumor stem cell assay.

Carcinoma, Transitional Cell↗
PubMed1982

Circadian and day-to-day variation of prostatic acid phosphatase.

The circadian and day-to-day variation of serum levels of prostatic acid phosphatase determined by radioimmunoassay was investigated in 10 men with a normal prostate, 8 with benign prostatic hyperplasia and 10 with prostate cancer. Serum samples were obtained on 1 day at 8 a.m., 12:00 noon and 4:30 pm. in 23 patients, and on 3 consecutive days at 8 a.m. in an additional 5 patients. There was a variability in enzyme level throughout the day but without any distinct pattern. Prostate cancer patients with elevated levels of prostatic acid phosphatase did demonstrate a greater variability throughout the day than patients with a normal prostate or with benign prostatic hyperplasia. The day-to-day serum prostatic acid phosphatase in patients with a normal prostate varied little and remained within the normal range.

Acid Phosphatase↗
PubMed1982

In vitro characterization of four N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) induced mouse bladder tumors.

Four longterm murine bladder tumor cell lines were established in vitro. The 4 lines were initiated from primary N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) induced murine bladder tumors arising in C3H/He mice. Each was maintained as a solid tumor in syngeneic mice for at least 30 generations before initiation in tissue culture. The cell lines MBT-2, MBT-8, MBT-409 and MBT-683, have been subcultured over 75 times in vitro for 18 months. They are all epithelial, grow in islands on plastic Petri dishes before confluent growth and form colonies in soft agar suspension culture. Morphologic studies indicate that all 4 lines have epithelial characteristics and karyotypic studies indicate that all lines have polyploidy and marker chromosomes. Population doubling times range from 10 to 26 hours and are consistent for each line.

Animals↗
PubMed1982

Platinum kinetics in patients treated with cis-dichlorodiammine platinum (II).

The pharmacokinetics of platinum have been studied in six patients following treatment with cis-dichlorodiammine platinum (CDDP) for metastatic bladder cancer. Each patient received CDDP by 15 min intravenous infusion with total doses ranging from 90 to 120 mg (360 to 480 mg/h). Platinum disposition was biexponential with a relatively rapid distribution and slow elimination. Individual patient elimination half-lives varied from 16.1 to 53.3 h. Although normalized for body weight, individual distribution parameters, V1 and V area, varied from 0.17 to 0.70 L/kg and 0.67 to 1.47 L/kg, respectively. Total body clearance (TBC) also revealed considerable interpatient differences (7 to 40 ml/kg/h). Observed parameter variations could not be explained in terms of existing clinical data. These findings suggest that the pharmacokinetics of platinum in the individual patient might be difficult to predict, and thus serum platinum concentrations should be monitored during cis-dichlorodiammine platinum (II) therapy.

Aged↗
PubMed1982

Time- and concentration-dependent inhibition of the clonogenic growth of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide-induced murine bladder tumor cell lines by cis-diamminedichloroplatinum(II).

The influence of the concentration and time of exposure to cis-diamminedichloroplatinum on the inhibition of the clonogenic growth of three N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide mouse bladder tumor cell lines was evaluated in a tumor colony assay. Drug testing was performed in the murine model, and tumor cells were removed from the animals for in vitro testing. Murine drug testing revealed marked cis-diamminedichloroplatinum sensitivity of all three mouse bladder tumor lines. One-hr incubation in cis-diamminedichloroplatinum was an adequate time of drug exposure to produce in vitro colony survival curves predictive of in vivo sensitivity to the drug. Furthermore, it was found that 6- to greater than 24-hr exposure to the drug was required to produce colony survival curves in the tumor colony assay predictive of tumor sensitivity. High drug concentrations using 1-hr drug incubation or continuous incubation in drug both produced colony survival curves predictive of tumor sensitivity. Both methods, however, would require higher products of the drug concentration multiplied by time curves than could theoretically be clinically achievable in the murine model. Until pharmacokinetic data on cis-diamminedichloroplatinum are available in this murine model, higher drug sensitivity boundaries than are presently being used for other chemotherapeutic agents will have to be utilized when testing these mouse bladder tumor cell lines for their sensitivity to cis-diamminedichloroplatinum in a tumor colony assay.

Animals↗
PubMed1981

The morphologic effects of mitomycin C in mammalian urinary bladder.

This investigation was intended to determine the morphologic changes of mitomycin C. It is part of a series of experiments designed to evaluate the cytologic and histologic effects of topical chemotherapeutic agents using the FANFT experimental model system in mice. The results for mitomycin C are very similar to those previously reported for thio-tepa. The indicate that these chemicals produce few, if any, drug-specific light microscopic alterations. Rather, mitomycin C and thio-tepa apparently act as toxic substances, causing increased exfoliation, degeneration, and necrosis of urothelial cells. The implications of these findings and suggestions for future investigations are discussed.

Administration, Topical↗
PubMed1981

Cis-diamminedichloroplatinum (II) in locally advanced and metastatic urothelial cancer.

Twenty-seven consecutive patients with locally extensive or metastatic urothelial cancer, primarily bladder, were given cis-diamminedichloroplatinum (II) (DDP) at a dose of 70 mg/m2 every three weeks. All patients had hydration and mannitol-induced diuresis initiated before administration of DDP. Nine patients (33%) had a partial response; 12 (45%) remained stable for an average duration of six months. Responders had a significantly greater survival than nonresponders. Although severe nephrotoxicity did not occur, patients with either a solitary or obstructed kidney were at greater risk of an increase in the serum creatinine during therapy.

Adult↗
PubMed1981

Comparison between a purified and standard diet on FANFT-induced murine bladder cancer.

We investigated the effect of two diets containing equal amounts of the carcinogen FANFT on the incidence and induction time of murine bladder carcinoma in mice. At each time interval, the tumor incidence in the mice ingesting a purified, high-calorie diet, was equal or greater than the tumor incidence in the animals fed standard mouse chow. The mean animal weight of the mice ingesting the purified diet was consistently higher than that of the mice fed the standard diet. The bladder weights (an index of tumor volume) showed no significant difference between the mice receiving the two diets. Since mice eat to fulfill their caloric requirements, the animals ate less of the purified diet and the cost per year was lower.

Animal Feed↗
PubMed1981

Evaluation of cystography for detection of bladder carcinoma in mice: comparison with urinary cytology.

Cystography was compared to urinary cytology in an effort to determine whether or not this modality might be useful in the detection of FANFT-induced bladder tumors in mice. Compared to gross examination of the bladders in 24 mice, cystography had the same degree of accuracy as urinary cytology--79.2 per cent. Comparison of the cystographic and cytologic diagnoses with histology revealed that cytology was more accurate, 79.2 vs 66.6 per cent. Cystography was especially helpful in detecting papillary tumors while cytology was more accurate in the detection of high-grade, high-stage tumors or carcinoma in situ (CIS). Cystography in mice can complement cytology as an additional useful technique for detection of bladder carcinoma.

Animals↗
PubMed1981

The diagnostic value of urine versus bladder washing in patients with bladder cancer.

In a prospective, critical appraisal of simultaneously collected cystoscopic urine and bladder cancer washing for the evaluation of patients with bladder cancer little consistent difference in cellular yield or preservation could be documented between the 2 techniques. Diagnostic cells usually occurred in both types of specimens but in 20 to 30 per cent of the cases they could be identified only in cystoscopic urine. Over-all, 13.1 per cent of the cancers would have been missed had cystoscopic urine not been examined cytologically. Although bladder washing alone has a greater diagnostic yield than cystoscopic urine alone urine remains a valuable source of diagnostic information and should be evaluated, even when simultaneously collected bladder washings are available.

Cystoscopy↗
PubMed1981

Pathological changes associated with topical chemotherapy for superficial bladder cancer.

With use of previous observations in experimental animals as a basis for comparison the cytologic and histologic changes in human patients who underwent topical chemotherapy for superficial bladder cancer were documented. Despite the potential for inhibition of deoxyribonucleic acid replication these drugs apparently act in vivo as toxic substances, causing increased exfoliation with denudation of papillary and/or flat urothelium. Multinucleation was common but confined to superficial cells. Atypical cells, such as those observed after systemic chemotherapy with cyclophosphamide, rarely were present and could be distinguished readily from neoplastic elements. Although topical chemotherapy may suppress tumor growth and progression it apparently does not eradicate the neoplastic process.

Administration, Topical↗