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G Dalbagni

Publications and source records attributed to G Dalbagni.

At least 19 recordsLinked to original sources
PubMed2006

Joint association of polymorphism of the FGFR4 gene and mutation TP53 gene with bladder cancer prognosis.

The impact of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism on bladder cancer is unknown. We found no clear correlations between the FGFR4 genotype and risk of bladder cancer or pathological parameters. Neither the polymorphism nor TP53 mutation status was an independent predictor of prognosis, but they might act jointly on the disease-specific survival of patients.

Aged↗
PubMed2001

[Arachidonic acid and prostaglandins, inflammation and oncology].

CYCLOOXYGENASE PATHWAY: Among the 3 metabolic pathways leading to oxidation of arachidonic acid, the cyclooxygenase (COX) pathway produces prostaglandin G2 that is rapidly transformed into prostaglandin H2. PROSTAGLANDINS: Prostaglandins are inflammation mediators that are strongly implicated in tumorgenesis. They participate in tumor initiation, promotion and growth. INFLAMMATION AND EPITHELIAL CANCER: Chronic inflammation is a risk factor for epithelial cancer. It induces prostaglandin synthesis via activation of COX-2. There is a cause and effect relationship between chronic inflammation and carcinogeneis via COX-2 expression. It has been demonstrated that COX-2 favors tumor invasion and inhibits apoptosis. Tumor growth is favored by PGE2-induced reduction in immunity; COX-2 inhibitors reinforce the immune response. Finally COX-2 is expressed in tumor neovessels and plays a role in angiogenesis.

Arachidonic Acid↗
PubMed2001

[Cyclooxygenases].

TWO ISOFORMS: There are two isoforms of cyclooxygenase (COX) with similar structure and metabolic activity. COX-1 is a constitutional enzyme. COX-2 is an inductible form. CYCLOOXYGENASE-1: COX-1 is present in most tissues, particularly in the kidney, the digestive tract mucosa, platelets, brain, liver and spleen. CYCLOOXYGENASE-2: COX-2 expression can be induced by an inflammatory process. Implicated in the development of certain cancers, COX-2 is expressed in numerous tumor cell lines and in most epithelial carcinomas. COX-2 favors tumor invasion and inhibits apoptosis. When it is absent, tumor growth is slower or stopped.

Apoptosis↗
PubMed2001

[Cyclooxygenase inhibitors].

DISTINCT EFFECTS: Since the discovery of the two isoforms of COX, the therapeutic effects of nonsteroidal antiinflammatory drugs (NSAID) can be distinguished from their adverse effects linked to the inhibition of the constitutional form via selective inhibition of the inducible form. Non-selective NSAID that inhibit both COX isoforms are difficult to use for long-term regimens. NSAID AND CANCER PREVENTION: Epidemiology studies and animal and in vitro studies have demonstrated that regular use of NSAID reduced the incidence of colorectal cancer and certain precancer lesions. PROMISING PERSPECTIVES: COX-2 specific inhibitors, for example cerecoxib or rofecoxib, are potentially interesting for human therapy for chemoprevention of epithelial cancer or as medical treatment, alone or in combination with other anticancer treatments.

Animals↗
PubMed2001

Cystectomy for bladder cancer: a contemporary series.

PURPOSE: To validate the current TNM staging system, we analyzed our contemporary experience with 300 cystectomies. MATERIALS AND METHODS: The pathological material and medical records of 300 patients treated with cystectomy were reviewed, and the new TNM classification was adopted. RESULTS: The median followup of patients with no evidence of disease was 65 months, and overall survival rate was 45% with a median survival of 50 months. In a Cox regression analysis only patient age, pT stage and neoadjuvant chemotherapy were significant factors for survival. The disease specific survival was 67% with a median survival of 94 months. In a multiple proportional hazards analysis only pT stage and previous chemotherapy were significant factors of disease specific survival. A significant difference was seen in the overall and disease specific survival between patients with organ confined and nonorgan confined tumors. We did not observe a difference in the survival rate among patients with pT4a to pT3 tumors. Significant differences were not seen in survival rates between sexes or among patients of different age groups. Transitional cell carcinoma was the predominant histological type, and no significant difference was found in patient outcome among the different histological subtypes. CONCLUSIONS: Bladder cancer can be categorized into organ confined and nonorgan confined tumors. This dichotomous grouping is better suited for evaluating adjuvant clinical trials. The pT stage of the bladder and prostate should be prospectively analyzed together to better define the clinical implications of prostatic involvement. In our opinion the histological subtypes do not affect outcome.

Adult↗
PubMed2001

Genetic alterations in tp53 in recurrent urothelial cancer: a longitudinal study.

PURPOSE: Because bladder cancer has a recurrence rate that can be as high as 90% at 2 years, we sought to clarify whether these metachronous tumors are polyclonal or monoclonal in origin. We have examined the genetic alterations of the TP53 gene in a cohort of patients with urothelial cancer who underwent multiple biopsies at different times and sites because of tumor recurrence and/or progression. We postulated that if tumor cells at different points in the natural history of the disease contain an identical mutation in the TP53 gene, this pattern could provide evidence for the monoclonality of the recurrent bladder tumors. EXPERIMENTAL DESIGN: Fifty-three biopsy specimens from 13 patients at different times and sites were selected for this study. Microdissection was used to ensure the purity of tumor cells. DNA extraction, PCR, and direct sequencing of exons 5 through 8 of the TP53 gene were conducted following protocols optimized in our laboratory. RESULTS: We found that specimens from seven patients carried tumor-specific TP53 mutations. The number of lesions in these patients ranged from two to seven, extending from 2 to 4 years. All of the seven patients displayed identical mutations in the different microdissected tumors. CONCLUSIONS: On the basis of these data, it appears that the recurrent bladder tumors originate from the same clone.

DNA Mutational Analysis↗
PubMed2001

Results of high dose rate brachytherapy, anterior pelvic exenteration and external beam radiotherapy for carcinoma of the female urethra.

PURPOSE: We evaluated a multimodality approach to locally advanced urethral carcinoma in women. MATERIALS AND METHODS: Between August 1996 and July 1999, 6 women were treated for locally advanced carcinoma of the urethra with anterior pelvic exenteration followed by high dose 192iridium intraoperative radiation therapy. Four of the 6 patients were also treated with neoadjuvant or concomitant platinum based chemotherapy. RESULTS: Two patients had no evidence of disease, 3 had distant metastasis and 2 had local recurrence at a mean followup of 21 months (range 12 to 47). Radiation was relatively well tolerated with no major adverse events. CONCLUSIONS: High dose intraoperative brachytherapy followed by external beam radiation is relatively well tolerated. Local control seems to have improved. We must evaluate a larger cohort of patients to determine this impact of the combined modality on local control and patient survival.

Adult↗
PubMed2000

Current use and questions concerning intravesical bladder cancer group for superficial bladder cancer.

Bacille Calmette-Guerin (BCG) is the most effective therapy for CIS of the bladder. Although several series have shown a decrease in recurrence and progression of T1 tumor, this effect is temporary. More than one half of patients with T1 tumors treated with BCG will progress over the longterm. A second course of BCG is indicated after an initial complete response. There is no definitive answer regarding the efficacy of maintenance therapy or the optimum dose of BCG. Randomized trials are needed to address these issues in a more conclusive manner. Phase III trials have shown that mitomycin C can be as effective as BCG in the management of papillary tumors; however, BCG is more effective in patients with CIS and high-risk superficial tumors.

Administration, Intravesical↗
PubMed1999

Prognostic significance of transcription factor E2F-1 in bladder cancer: genotypic and phenotypic characterization.

BACKGROUND: We sought to identify and characterize potential alterations in E2F-1, a transcription factor that binds to the retinoblastoma protein (pRB), in bladder neoplasms and to elucidate a possible role for E2F-1 as an oncogene or a tumor suppressor gene. METHODS: Tumor samples from 133 evaluable patients with bladder cancer were analyzed for E2F-1 gene mutations by use of polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis and DNA sequencing. In addition, tumors were studied for E2F-1 and pRB protein expression by use of immunohistochemistry. Results from the above analyses were correlated with clinicopathologic parameters and outcome. All P values are two-sided. RESULTS: A polymorphism, consisting of a nucleotide change at amino acid codon 393 in exon 7 (GGC-->AGC [Gly-->Ser]), was identified in seven of 133 case patients, being present in both tumor and corresponding normal tissues. No bandshifts were identified in the nuclear-localization or DNA-binding domains on PCR-SSCP analysis. On immunohistochemical analysis, E2F-1 nuclear reactivity was observed in less than 5% of the cells from 53 tumors and in 5%-75% of the cells from the remaining 80 tumors. The pattern of E2F-1 protein expression was not altered in relation to the identified polymorphism. pRB nuclear reactivity greater than 20% (of tumor cells stained) was present in 66% of the samples. E2F-1 nuclear reactivity correlated inversely with the percentage of cells showing pRB reactivity (Kendall tau(b) = -0.18; P = .019). On multivariate analysis, patients with lower E2F-1 reactivity had statistically significantly increased risks of progression to metastases (P = .001) and death (P = .02). CONCLUSIONS: E2F-1 alterations occur at the phenotypic level, rather than at the genotypic level, in bladder cancer. The adverse outcome for patients whose tumors exhibit low E2F-1 nuclear expression suggests a possible tumor suppressor role for E2F-1 in bladder cancer.

Carcinoma↗
PubMed1999

Male urethral carcinoma: analysis of treatment outcome.

OBJECTIVES: To evaluate our experience with primary carcinomas of the male urethra and to analyze the impact of tumor variables and treatment on overall, disease-specific, local recurrence-free, and metastasis-free survival. METHODS: Between 1958 and 1996, we identified 46 men with primary carcinoma of the bulbar and anterior urethra. The median follow-up was 125 months (1 to 336). The patients were stratified by stage, nodal status, histologic type, treatment, type of surgery, site of disease, year at diagnosis, and smoking status. RESULTS: The overall survival and disease-specific survival rates at 5 years were 42% and 50%, respectively. The recurrence-free survival and metastasis-free survival rates at 5 years were 51% and 56%, respectively. The overall survival rate was 83% for superficial disease versus 36% for invasive tumors. The overall survival rate was 26% for tumors of the bulbar urethra versus 69% for tumors of the anterior urethra. CONCLUSIONS: Current modalities of treatment are ineffective for local control and survival. New treatment strategies are needed for urethral cancer.

Adult↗
PubMed1999

Is transurethral biopsy of the bladder necessary after 3 months to evaluate response to bacillus Calmette-Guerin therapy?

PURPOSE: We assessed the need for transurethral biopsy of the bladder at the 3-month evaluation in patients who have received intravesical bacillus Calmette-Guerin (BCG). MATERIALS AND METHODS: A total of 81 patients collectively received 83, 6-week courses of BCG between 1995 and 1997, and underwent transurethral bladder biopsies 3 months after initiation of immunotherapy. The pretreatment and posttreatment bladder biopsy results, urinary cytology and posttreatment cystoscopic findings were correlated. RESULTS: Transitional cell carcinoma was demonstrated in 5 of 11 patients with erythematous bladder mucosa and a positive cytology compared to none of 37 with an erythematous lesion and a negative cytology. Of 12 patients with a papillary lesion on cystoscopy and a positive biopsy 10 had a negative cytology, and only 1 of 13 patients with a negative cystoscopy had a positive biopsy. CONCLUSIONS: Bladder biopsy is not necessary in patients 3 months after receiving BCG who have a normal office cystoscopy or an erythematous bladder and normal urine cytology.

Adjuvants, Immunologic↗
PubMed1999

Toxicology and pharmacokinetics of intravesical gemcitabine: a preclinical study in dogs.

More active and well-tolerated agents are needed for the treatment of superficial bladder cancer. This study investigated intravesical gemcitabine to establish the toxicology and pharmacokinetics necessary for clinical trials. Beagle dogs (in groups of 2; n = 6) received 100 mg, 350 mg, or 1 g of drug by intravesical administration on alternate days three times/week for 4 weeks. Animals were observed for clinical signs of toxicity; gemcitabine levels and peripheral blood counts were taken three times weekly. The dogs were euthanized, and a full necropsy was performed at days 1 and 14 after the last dose. Intravesical gemcitabine was given at 100 mg (n = 2), 350 mg (equivalent to the 1000 mg/m2 human dose; n = 3), and 3.5 g (n = 1). i.v. gemcitabine was given at 350 mg (n = 2). Plasma samples drawn at time points up to 8 h were analyzed for systemic absorption and clearance of drug. Doses of 100 and 350 mg were well tolerated with no clinical side effects. Necropsies revealed normal bone marrow cellularity and normal bladder histology. At 1 g, signs of severe clinical toxicity were evident, and after only three doses, necropsies demonstrated severe bone marrow hypoplasia, cystitis, and intestinal necrosis. At all intravesical doses, significant systemic absorption was seen. The T1/2 (+/- SD) for intravesical and i.v. administration of 350 mg was 328 (+/-6.8) min and 99.3 (+/-5.2) min, respectively (P<0.001). Intravesical gemcitabine is well tolerated and has no direct bladder toxicity at doses up to 1000 mg/m2. Higher doses result in gastrointestinal, bladder, and bone marrow toxicity.

Absorption↗
PubMed1998

Results of laparoscopic pelvic lymphadenectomy in patients at high risk for nodal metastases from prostate cancer.

BACKGROUND: Laparoscopic pelvic lymphadenectomy (LPLND) can be performed safely and with minimal morbidity in the staging of prostate cancer. Its utility in evaluating patients at high risk for metastatic disease before primarily nonsurgical treatment modalities was evaluated. METHODS: Twenty-four consecutive patients who underwent LPLND between June 1993 and July 1996 were studied. These patients were considered poor surgical candidates based on several risk factors, as follows: elevation of serum PSA >20 in 19 patients (79%); elevation of serum acid phosphatase in 4 patients (17%); digital rectal examination findings indicative of extraprostatic extension or seminal vesical involvement in 14 patients (58%); and poorly differentiated tumors on prostate biopsy in 19 patients (79%). Nineteen patients (79%) had two or more of these risk factors. Median PSA for the entire series of patients was 35.2 ng/mL (range 7.9 to 133 ng/mL), and median Gleason score was 7 (range 5 to 9). Preoperative CT or MRI was negative for pelvic lymph node metastases in 17 of 23 patients (79%), and bone scan was negative in all 24 patients. RESULTS: Unilateral (n = 2) or bilateral (n = 22) LPLND was performed in all patients. Six patients (25%) had lymph node metastases detected laparoscopically. Five of the six patients had palpable extraprostatic extension (T3a/b) or invasion of a seminal vesical (T3c), and in four of these patients the site of the metastatic lymph nodes was ipsilateral to the palpable prostate abnormality. None of the risk factors was independently predictive of lymph node metastases within this series of patients. An average of 10.8 +/- 6.5 lymph nodes was removed at a mean operative time of 174 +/- 10 minutes for patients undergoing bilateral LPLND. Estimated blood loss was minimal for 20 of 22 patients (92%) undergoing LPLND alone, and there were no complications requiring open exploration. Mean postoperative hospital stay was 1.2 +/- 0.5 days for patients undergoing LPLND alone. CONCLUSIONS: LPLND can be used efficiently to identify patients with nodal metastases from select high-risk patients. This, in turn, can exclude such patients from noncurative local and regional therapy.

Acid Phosphatase↗
PubMed1998

Female urethral carcinoma: an analysis of treatment outcome and a plea for a standardized management strategy.

OBJECTIVE: To evaluate our experience with primary carcinomas of the female urethra, by analysing the impact of tumour variables and treatment on overall, disease-specific, local recurrence- and metastasis-free survival. PATIENTS AND METHODS: Between 1958 and 1994, 72 women (median age 60 years, mean 59, range 21-84) with primary urethral carcinoma were identified. They were followed for a median (range) of 85 (0-384) months. The patients were stratified by stage, nodal status, histology, treatment, type of surgery, site of disease, year of diagnosis and smoking habit. RESULTS: In a univariate analysis, stage, nodal status, type of surgery and site of the disease were important factors for survival and recurrence. In a multivariate analysis, primary stage, nodal status and site of disease were independent predictors of survival. CONCLUSION: Current modalities of treatment are ineffective for local control and survival; new treatment strategies are needed for female urethral cancers.

Adult↗
PubMed1997

Chromosome 16 in primary prostate cancer: a microsatellite analysis.

Cytogenetic and molecular genetic analyses of prostate cancer specimens have revealed nonrandom chromosomal deletions, affecting chromosomes 7q, 8p, 10q and 16q. Based on these data, we designed this study to further characterize the altered region(s) on chromosome 16 by evaluating 16 microsatellite markers on a population composed of 32 paired normal and primary prostatic tumor samples. The 16 microsatellites selected mapped to 11 distinct loci on 16q and 5 loci on 16p. No alterations were identified affecting 16p. However, 16 of 31 (51%) informative cases showed molecular alterations in at least one of the loci analyzed on 16q, consisting of 18 deletions and 11 bandshifts. Moreover, most of the deletions clustered at 6 microsatellite loci, mapping to the 16q22.1-23.1 region. Our results suggest that microsatellite alterations on the long arm of chromosome 16 are frequent events in prostate cancer, and that the 16q22.1-23.1 region might harbor a tumor suppressor gene involved in prostate cancer.

Adenocarcinoma↗
PubMed1997

Cooperative effects of p53 and pRB alterations in primary superficial bladder tumors.

Altered patterns of p53 and pRB expression have been reported to be frequent events and to have prognostic significance in bladder cancer. To assess the potential adverse consequences of having altered patterns of both p53 and pRB proteins in patients with bladder neoplasms compared with having one or neither abnormality, we have studied a cohort of superficial transitional cell carcinomas of the urinary bladder by immunohistochemical analysis. The present study included 59 well-characterized superficial transitional cell carcinomas (Ta, n = 28; T1, n = 31) for which clinicopathological variables were available. Nuclear overexpression of p53 was identified in 22 cases (37%). A statistically significant association was observed between the p53-positive phenotype and disease progression (P < 0.001), as well as reduced survival (P < 0.001). Undetectable levels of pRB were observed in 11 cases (19%). Patients with a pRB-negative phenotype had a more frequent disease progression (P = 0.014) and decreased overall survival (P = 0.014). We also observed a significant association between altered p53 and undetectable pRB expression patterns (P = 0.001). Nine tumors showed both a p53-positive and a pRB-negative phenotype. There was an even more marked increase in progression (P = 0.00005) and decreased overall survival (P = 0.0004) in patients whose tumors had both alterations after controlling for tumor stage, tumor grade, and suspicion of vascular invasion. These data suggest that alterations of p53 and pRB have a cooperative negative effect on both progression and survival in primary bladder cancer. It may be postulated that aberrant p53 and pRB expression deregulates cell cycle control at the G1 checkpoint and engenders tumor cells with reduced response to programmed cell death. The imbalance produced by an enhanced proliferative activity and a decreased apoptotic rate may determine the aggressive clinical course of the bladder tumors harboring both p53 and pRB alterations.

Carcinoma, Transitional Cell↗
PubMed1997

Pathological staging and biochemical recurrence after neoadjuvant androgen deprivation therapy in combination with radical prostatectomy in clinically localized prostate cancer: results of a phase II study.

OBJECTIVES: To assess the pathological staging and biochemical progression-free survival (assessed using serum prostate-specific antigen level) of patients with clinically localized prostate cancer using neoadjuvant androgen deprivation therapy (ADT) in combination with radical retropubic prostatectomy (RRP). PATIENTS AND METHODS: A prospective study was carried out on 69 patients with localized prostate cancer who were enrolled in a trial of 3 months of ADT followed by RRP (group 1). These patients were compared with 72 patients matched for age and clinical stage who declined ADT therapy and had RRP concurrently (group 2). Assignment to the individual treatment groups was thus determined by the patient's preference and not the physician's selection. Pathological staging and biochemical progression-free recurrence were compared between the groups. RESULTS: The rate of organ-confined (pT2) tumours was 74% in group 1 and 49% in group 2 (P < 0.01), and the rate of margin-negative tumours was 87% in group 1 and 64% in group 2 (P < 0.01). Within a median follow-up of 35 months, there was no significant difference in biochemical failure between the groups (P = 0.37). Patients with pT2 disease, regardless of treatment, had similar biochemical failure rates. In the patients with margin-positive disease, there was a significantly higher biochemical failure rate in group 1 (P = 0.02). CONCLUSIONS: The rates of organ- and specimen-confined disease were higher among the patients treated with ADT. The preliminary follow-up suggested that patients with pT2 disease after ADT have a biochemical progression-free recurrence rate similar to pT2 patients treated with RRP alone. Additionally, high biochemical failure rates in patients with margin-positive disease after ADT may identify a subset of more biologically aggressive tumours in need of early adjuvant treatment.

Aged↗