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Biomedical subjects

M J Droller

Publications and source records attributed to M J Droller.

At least 37 records · Page 2Linked to original sources
PubMed1998

Detecting human bladder carcinoma cells in voided urine samples by assaying for the presence of telomerase activity.

BACKGROUND: In an attempt to find a more sensitive and specific noninvasive assay for the detection of bladder carcinoma, the authors assayed exfoliated cells from patients' voided urine for the presence of telomerase, an enzyme that maintains a cell's chromosomal length and is thought to be active in the transformation of normal somatic cells into immortal human tumor cells. METHODS: The authors used a polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assay to determine the presence of telomerase activity in voided urine samples from patients with known but yet untreated bladder carcinoma (n = 104) and from patients with hematuria of benign causes (n = 47). For 88 of the patients with bladder carcinoma, cytology was determined independently of the telomerase results or the pathology findings. RESULTS: Of the 104 bladder carcinoma specimens, 88 (85%) tested positive for the presence of telomerase. Seventy-nine percent (23 of 29) of the Grade 1 tumors, 84% (32 of 38) of the Grade 2 tumors, and 87.5% (28 of 32) of the Grade 3 tumors were positive for telomerase activity. Five patients with carcinoma in situ (100%) were also positive. Telomerase activity was not found in 31 of 47 patients with bladder calculi, benign urethral stricture, benign prostatic hyperplasia, or inflammation. In the 16 patients (34%) who did have a false-positive result when tested for telomerase, all had either chronic or severe inflammation, including 1 patient with an inverted papilloma, 1 patient with cystitis cystica, and 1 patient with cystitis glandularis. However, for 35 normal, healthy volunteers whose voided urine samples were also assayed for the presence of telomerase activity, none was found. By comparison, only 51% (45 of 88) of the cytology samples from patients with bladder carcinoma yielded positive findings, whereas 49% (43 of 88) resulted in false-negative readings for tumors. Only 13% (3 of 23) of the Grade 1 tumors, 44% (14 of 32) of the Grade 2 tumors, and 82% (23 of 28) of the Grade 3 tumors were diagnosed by cytology. All five patients with carcinoma in situ were positive for cytology as well as for telomerase activity. When cytology was compared with the PCR-based telomerase assay in determining the presence of bladder carcinoma, the difference in the overall detection rates (85% for telomerase vs. 51% for cytology) was significant (P < 0.001). Furthermore, when telomerase activity was compared with cytology for low grade lesions (Grades 1 and 2), the difference in the detection rates (82% for telomerase vs. 31% for cytology) was also significant (P < 0.001). CONCLUSIONS: Urinary cytology yields poor results for low grade tumors. This study shows the possible application of the telomerase assay in detecting bladder carcinoma, in particular low grade tumors, in voided urine samples.

Adult↗
PubMed1998

Sensitivity and specificity of NMP-22, telomerase, and BTA in the detection of human bladder cancer.

OBJECTIVES: The recent introduction of novel molecular markers into clinical urology has created a need to evaluate the efficacy and utility of these potential markers. The ideal assay for bladder cancer should be noninvasive, sensitive, specific, and cost-effective. We compared the Matritech nuclear maxtrix protein (NMP)-22 assay, telomerase activity, and the Bard bladder tumor antigen (BTA) assay for the detection of human bladder cancer. METHODS: A single voided urine sample was obtained from patients with hematuria without bladder cancer and from patients with known bladder cancer before any treatment. Approximately 50 to 100 mL of voided urine sample was collected and aliquotted for the various assays. The results were compared to single cytologic results and ultimately to pathologic findings. RESULTS: In 47 patients with bladder cancer, the overall sensitivity was 81% for NMP-22, 80% for telomerase, 40% for BTA, and 40% for cytology. For Ta tumors (n = 31), sensitivity was 81% for NMP-22, 70% for telomerase, 32% for BTA, and 26% for cytology. For T1 or higher stage tumors (n = 13), sensitivity was 82% for NMP-22, 91% for telomerase, 64% for BTA, and 64% for cytology. The remaining 3 patients had carcinoma in situ (CIS). When tumors were stratified by tumor grade, grade I tumors (n = 16) were detected at 69% with NMP-22, 65% with telomerase, 13% with BTA, and 6% with cytology. Grade II tumors (n = 14) were detected at 86% with NMP-22, 72% with telomerase, 36% with BTA, and 36% with cytology. Grade III tumors (n = 14) were detected at 93% with NMP-22, 93% with telomerase, 79% with BTA, and 79% with cytology. Patients with CIS (n = 3) were detected at 67% with NMP-22, 100% with telomerase, 33% with BTA, and 67% with cytology. In 30 patients with hematuria but without bladder cancer, the overall specificity of the assays was 77% for NMP-22, 80% for telomerase, 73% for BTA, and 94% for cytology. CONCLUSIONS: In the population tested, NMP-22 and the telomerase assays gave similar sensitivity and specificity for the detection of bladder cancer, and appear to offer a greater sensitivity than the BTA assay and/or conventional cytology.

Aged↗
PubMed1998

Urinary telomerase and its possible role as a marker for bladder cancer.

Voided urine from patients with bladder cancer and from control patients with either hematuria or with no urologic conditions were examined for telomerase activity in order to explore the possibility that this activity could be used as a marker for the detection of bladder cancer. This assay was found to have an overall sensitivity in detecting bladder cancer of 85% (88/104) with 79% (23/29) grade 1 tumors, 84% (32/38) grade 2 tumors, 87.5% (28/32) grade 3 tumors, and 100% (5/5) carcinoma in situ testing positive. This compared favorably with urinary cytology which had an overall sensitivity of 51% and sensitivities of 13%, 44%, 82%, and 100% for grades 1, 2, 3 tumors and carcinoma in situ, respectively. The specificity of telomerase in patients with benign causes of hematuria was 66%, and in normal volunteers without urologic conditions, it was 100%. Assessment of nuclear matrix protein suggested comparable sensitivity and specificity. Evaluation of bladder tumor antigen showed less sensitivity for low-grade disease and less specificity, as it was influenced by inflammation and instrumentation. Telomerase thus seems to be a means whereby low-grade tumors may be detected in examination of voided urine and may offer an advantage in monitoring for recurrent disease.

Biomarkers, Tumor↗
PubMed1998

Risk factors in clonal development from superficial to invasive bladder cancer.

Bladder cancer has classically been associated with exogenous risk factors, and a large literature has identified risk factors associated with the genesis of transitional cell carcinoma. Only recently have efforts been made to identify host factors and to evaluate possible changes in tumour presentation and biology, including grade and stage, in association with these risk factors. The available literature appears to demonstrate alterations in tumour biology associated with environmental carcinogens. Various studies have suggested a consistent upgrading of bladder cancer stage and grade as a result of cigarette smoking and high risk occupational exposures. It is important, however, that all factors associated with increased risk for bladder cancer be more extensively evaluated in assessing the validity of this concept.

Humans↗
PubMed1997

Applications of telomerase in urologic oncology.

Vertebrates have special structures at the ends of their chromosomes, known as telomeres, which are composed of 5- to 15-kb pairs of a guanine-rich hexameric repeat (TTAGGG)n. In normal somatic cells there is a progressive degradation of telomeres with aging. The cell can afford to lose only a finite number of these telomeres before significant sequences of the parent DNA are lost, resulting in chromosomal instability and cell death. However, germ-cell telomeres are maintained despite multiple rounds of replication. This suggests that they produce an enzyme that maintains their telomere length. This enzyme, a ribonucleoprotein, is called telomerase. In this review, we discuss the presence of telomerase activity in various human cancers and, in particular, in urologic tumors. We describe the potential clinical utility of detection of the presence of telomerase activity in cells from voided urine samples of patients with bladder cancer.

Enzyme Inhibitors↗
PubMed1997

Bladder cancer.

Explore the source record for details and available documents.

Carcinoma, Transitional Cell↗
PubMed1996

Environment and the genitourinary tract.

A variety of environmental factors have been associated with conditions that affect the genitourinary system. Chronic lead exposure and halogenated hydrocarbons have been found to affect sperm production and fertility. Heavy metals such as mercury and cadmium have been associated with renal tubular toxicity and kidney failure. Aromatic amines, used in a number of industrial processes and most commonly found in the dye industry, have been associated with development of bladder cancer. The same substances that are metabolites in cigarette smoke have been found to explain the strong association between bladder cancer and cigarette smoking. Chlorination and fluoridation have recently been associated with bladder cancer. In each of these associations, host factors may contribute to the toxicity of these substances either by detoxifying them or by converting them to more active agents. Education and regulation are needed to decrease the environmental risk they create.

Cocarcinogenesis↗
PubMed1995

LAK cell mediated apoptosis of human bladder cancer cells involves a pH-dependent endonuclease system in the cancer cell: possible mechanism of BCG therapy.

Intravesical bacillus Calmette-Guerin (BCG) is an effective treatment for superficial bladder cancer. However, its mechanism has been only partially elucidated. We studied whether LAK cell killing of human bladder cancer cells occurs via apoptosis (programmed cell death) or necrosis. Fluorescent dye labeled T24 cells were observed to undergo morphologic changes associated with apoptosis in the presence of LAK cells when analyzed under a fluorescence microscope. Furthermore, analysis of the DNA isolated from the cytotoxic assay confirmed that the LAK cell induced death of the T24 cells occurred via apoptosis. By pretreating the LAK cells with antifibronectin antibodies, we were able to significantly inhibit the LAK cell killing of the T24 cells. The percentage of cytotoxicity was reduced from 50% to 13% (p = 0.001), and the apoptotic pattern seen on agarose gel electrophoresis was significantly diminished. There was no significant change in the viability of the LAK cells following treatment with the antibodies. Endonuclease isolation from human bladder cancer T24 cells demonstrated that these cells express a pH-dependent and not a Ca++/Mg++ dependent endonuclease. Significant degradation of a target DNA was observed only in pH 4 to pH 5.6 buffers containing endonuclease from T24 cells and not in pH 6 to pH 8 buffers containing endonuclease from T24 cells. The presence or absence of Ca++/Mg++ in the various pH buffers did not alter the endonuclease activity. Finally, we demonstrated that death of T24 cells can be induced by altering the intracellular pH of the cells to 5.6 or lower with the proton ionophore nigericin. We conclude that LAK cells induce T24 cells to undergo apoptosis and that this process involves the fibronectin molecule present on the LAK cell membrane. Furthermore, the cleavage postulate that, in vivo, LAK cells activated by IL-2 produced by BCG activated CD4+ cells may induce bladder cancer cells to undergo apoptosis. This may partially explain the mechanism whereby BCG achieves its therapeutic effect.

Antibodies↗