ABSTRACT
This review focuses on the main oncogenes studied in transitional cell carcinoma (TCC) in order to describe their mechanisms of action and investigate their possible prognostic value. Each oncogene family is reported following the order through which the proliferative signal is transduced from the extracellular space via a growth factor to the nucleus where transcription factors are switched on. Oncogenic activation at any level of the pathway will cause an increased transcription of genes enhancing the cell cycle, and proliferation will therefore be amplified. The main molecular or immunohistochemical studies from the literature on the aberrant expression of these genes are examined and compared with the aid of tables. Conclusions suggest that, although some may initially appear promising, no oncogene, has thus far been found to have a definite prognostic value superior to conventional grading and staging.
Subject(s)
Carcinoma, Transitional Cell/genetics , Gene Expression Regulation, Neoplastic , Oncogenes/genetics , Urinary Bladder Neoplasms/genetics , Carcinoma, Transitional Cell/diagnosis , Humans , Predictive Value of Tests , Prognosis , Urinary Bladder Neoplasms/diagnosisABSTRACT
OBJECTIVES: To explain the overall survival (OS) and disease free survival (DFS) in relation to nm23-H1 protein, DNA-ploidy and S-phase fraction (SPF) in transitional cell carcinoma of the bladder. PATIENTS AND METHODS: Ninety-four samples were obtained from patients with transitional cell carcinoma of the bladder examined between 1994 and 1996. The patients were underwent cistectomy or surgical biopsy and the material was histologically evaluated according to World Health Organization classification. Nm23-H1 protein expression in immunohistological staining and DNA ploidy, S-phase fraction by flow cytometric were performed. RESULTS: The correlation between OS and staging, grading, DNA-ploidy and S-phase was significant; whereas the overall survival and nm23-H1 protein, was not significant. The relationship between DFS and stage, DNA-ploidy and S-phase had a significant value. The correlation between DFS and age, sex, grading and nm23-H1 protein was not significant. There was no significant difference in age, sex, stage, grading, DNA-ploidy and SPF distribution between patients with nm23-H1 positive bladder cancer and those with nm23-H1 negative tumours. CONCLUSION: In our study, multivariate analysis showed that stage, ploidy and SPF were the strongest prognostic factors in predicting disease-free survival and prolonged survival, while nm23-H1 expression was not related to disease progression and/or prolonged survival. This expression, therefore, does not appear to be an independent prognostic factor in bladder cancer, although a still larger number of patients and a longer follow-up period are now needed for a definitive assessment of the prognostic significance of nm23-H1 expression.
Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Transitional Cell/pathology , Monomeric GTP-Binding Proteins , Nucleoside-Diphosphate Kinase , Ploidies , Transcription Factors/analysis , Urinary Bladder Neoplasms/pathology , Adult , Age Factors , Aged , Aneuploidy , Biopsy , Carcinoma, Transitional Cell/genetics , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/surgery , Cystectomy , Diploidy , Disease-Free Survival , Female , Humans , Male , Middle Aged , NM23 Nucleoside Diphosphate Kinases , Neoplasm Staging , Polyploidy , S Phase , Sex Factors , Survival Rate , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/surgeryABSTRACT
OBJECTIVES: To study the ablative activity of intravesical mitomycin C followed by intravesical bacillus Calmette-Guérin (BCG) on a papillary marker tumour and to determine the incidence of side effects. METHODS: Thirty-five patients with multiple pTa or pT1 bladder tumours were treated with 4 instillations of mitomycin C at weekly intervals followed by 6 instillations at weekly intervals of BCG-RIVM. All visible tumours were resected before starting intravesical instillations except one marker tumour. Response was determined 2 weeks after the last instillation. RESULTS: The incidence of adverse effects was similar to previously reported toxicity of either mitomycin C or BCG alone. Complete response, histologically proven, was observed in 16 of 35 patients and in 3 patients without histological confirmation. One patient showed progression. CONCLUSION: The sequential combination of mitomycin C and BCG is an efficacious treatment. The measurement of response to a marker tumour is a safe and efficient method to test new drugs or combinations of drugs.
Subject(s)
Adjuvants, Immunologic/therapeutic use , Antibiotics, Antineoplastic/therapeutic use , BCG Vaccine/therapeutic use , Carcinoma, Transitional Cell/therapy , Mitomycin/therapeutic use , Neoplasms, Multiple Primary/therapy , Urinary Bladder Neoplasms/therapy , Administration, Intravesical , Aged , Aged, 80 and over , Antibiotics, Antineoplastic/administration & dosage , BCG Vaccine/immunology , Biomarkers, Tumor/metabolism , Carcinoma, Transitional Cell/pathology , Colony-Forming Units Assay , Combined Modality Therapy , Female , Humans , Immunotherapy , Longitudinal Studies , Male , Middle Aged , Mitomycin/administration & dosage , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Neoplasms, Multiple Primary/pathology , Urinary Bladder Neoplasms/pathologyABSTRACT
Between March 1986 and March 1987, 48 patients with stage D prostate carcinoma were entered into a multicentric pilot study using the pure nonsteroidal antiandrogen nilutamide (Anandron--RU 23908) at the dose of 100 mg t.i.d. as the only therapy until disease progression or the occurrence of toxicity. Minimum follow-up was 15 months. Median age of patients was 72 (56 to 83) and median initial Performance Status (PS) was 1 (0 to 3). Of the 48 patients, 29 were untreated, while 19 patients were progressing following treatment by orchiectomy, LHRH analogs, or other endocrine therapies. According to the National Prostatic Cancer Project (NPCP) criteria, 43 patients were evaluable for response. Overall best response in untreated patients was partial response (PR), 41.6%; stationary disease (SD), 54.1%; 73.6% of pretreated patients achieved SD. Median progression-free survival and overall survival in untreated patients were 325 and 696 days, respectively, and 174 and 447 days, respectively, in pretreated patients. The more common side effects were G.I. toxicity (65%), hemeralopia (27%), and alcohol intolerance (6.2%). Results of this study suggest that Anandron may be a safe and effective treatment for patients with advanced prostatic cancer.
Subject(s)
Antineoplastic Agents/therapeutic use , Imidazoles/therapeutic use , Imidazolidines , Prostatic Neoplasms/drug therapy , Aged , Aged, 80 and over , Androgen Antagonists/adverse effects , Androgen Antagonists/therapeutic use , Antineoplastic Agents/adverse effects , Humans , Imidazoles/adverse effects , Male , Middle Aged , Neoplasm Staging , Vision Disorders/chemically inducedSubject(s)
Cyproterone/therapeutic use , Diethylstilbestrol/therapeutic use , Estramustine/therapeutic use , Medroxyprogesterone/therapeutic use , Nitrogen Mustard Compounds/therapeutic use , Prostatic Neoplasms/drug therapy , Castration , Clinical Trials as Topic , Cyproterone/administration & dosage , Diethylstilbestrol/administration & dosage , Estramustine/administration & dosage , Humans , Male , Medroxyprogesterone/administration & dosage , Neoplasm Metastasis , Prostatic Neoplasms/pathology , Random AllocationABSTRACT
52 patients with advanced bladder cancer, no longer controlled by conventional therapy, have been treated by combination chemotherapy with Adriamycin and 5-fluorouracil. The objective remission rate has been 40%. The morbidity of the chemotherapy has not been excessive. The response has not been related to the histological grade of the primary tumour and previous treatment. Patients with a good performance status (Karnofsky index) have responded better than those with a poor performance status.
