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Biomedical subjects

L Cindolo

Publications and source records attributed to L Cindolo.

12 recordsLinked to original sources

Preliminary report of a multicentric study on environmental risk factors in Ta-T1 transitional cell carcinoma of the bladder. A study from Gruppo Studi Tumori Urologici Foundation.

OBJECTIVE: The distribution of potential environmental risk factors among patients affected by superficial transitional cell carcinoma of the bladder (TCCB) has been analyzed. METHODS: Patients affected by superficial TCCB underwent TUR and early intravesical chemotherapy. Detailed data about age, sex, residence, employment, active and passive cigarette smoking, water resource and hair dye use were centralized. Analysis has been conducted on 474 patients affected by Ta-T1 G1-2 TCCB at medium risk for recurrence. Patients with primary single Ta G1-2, Tis or T1G3 tumors were excluded from the present analysis. RESULTS: Over 80% of the patients lived in urban areas, 22% were employed in industries presumed at risk for bladder cancer, 8% used hair dye and 75% were smokers. Bottled water was the only water resource in 42% of the patients. Employment in industry at risk (p = 0.01) and cigarette smoking (p = 0.04) resulted in being statistically related to tumor multiplicity. Moreover, the period of cigarette smoking was significantly longer in patients with recurrent tumors (p = 0.026). The municipal water supply represented the main water source in never-smokers (p = 0.01) rather than in smokers and in patients harboring T1 rather than Ta tumors (p = 0.03). CONCLUSIONS: Employment in industry at risk and cigarette smoking resulted in being related to tumor multiplicity. The length of exposure to cigarette smoking was related to the natural history of the tumor. A drinkable water source emerged as a risk factor in absence of cigarette smoking.

Adult↗

cAMP induced modifications of HOX D gene expression in prostate cells allow the identification of a chromosomal area involved in vivo with neuroendocrine differentiation of human advanced prostate cancers.

The acquisition of epithelial-neuroendocrine differentiation (ND) is a peculiarity of human advanced, androgen-independent, prostate cancers. The HOX genes are a network of transcription factors controlling embryonal development and playing an important role in crucial adult eukaryotic cell functions. The molecular organization of this 39-gene network is unique in the genome and probably acts by regulating phenotype cell identity. The expression patterns of the HOX gene network in human prostate cell phenotypes, representing different stages of prostate physiology and prostate cancer progression, make it possible to discriminate between different human prostate cell lines and to identify loci and paralogous groups harboring the HOX genes mostly involved in prostate organogenesis and cancerogenesis. Exposure of prostate epithelial phenotypes to cAMP alters the expression of lumbo-sacral HOX D genes located on the chromosomal region 2q31-33 where the cAMP effector genes CREB1, CREB2, and cAMP-GEFII are present. Interestingly, this same chromosomal area harbors: (i) a global cis-regulatory DNA control region able to coordinate the expression of HOX D and contiguous phylogenetically unrelated genes; (ii) a prostate specific ncRNA gene associated with high-risk prostate cancer (PCGEM1); (iii) a series of neurogenic-related genes involved with epithelial-neuronal cell conversion. We report the expression of neurexin 1, Neuro D1, dlx1, and dlx2 in untreated and cAMP treated epithelial prostate cells. The in vivo expression of Neuro D1 in human advanced prostate cancers correlate with the state of tumor differentiation as measured by Gleason score. Thus, we suggest that the chromosomal area 2q 31-33 might be involved in the epithelial-ND characteristic of human advanced prostate cancers.

Bucladesine↗

Neuroendocrine differentiation after neoadjuvant hormonal treatment in prostate cancer.

AIM: Neuroendocrine (NE) differentiation occurs in various degree in the majority of prostatic adenocarcinomas and it has been correlated with tumor progression and poor prognosis. There is little knowledge about the impact of NE differentiation on tumor response to neoadjuvant hormonal treatment (NHT). The role of NE differentiation as a marker of recurrence after radical prostatectomy (RP) is also unclear. We evaluated whether there is an increase in NE differentiation during the course of NHT and whether the tumor relapse after radical surgery correlates with the extent of NE differentiation. METHODS: RP specimens from 44 patients submitted to 3 months of NHT and RP specimens from 40 nonpretreated patients were histologically assessed. Staining for NE differentiated prostate tumor cells was carried out using a specific monoclonal antibody against chromogranin A (CgA). RESULTS: CgA positive cells were found in 4 of 40 patients (10%) in the RP group and in 4 of 44 patients (9%) of the NHT+RP group. At follow-up, we had 21 biochemically relapsed patients. Among them, 6 were CgA positive (75% of 8 patients), whereas is were CgA negative (20% of 76 patients). CONCLUSIONS: The NE differentiation doesn't increase after NHT. Although not statistically significant a trend to higher risk of relapse among the chromogranin positive samples was observed. The significance of NE differentiation in the progression of the disease and its relation to other known prognostic factors remains unclear.

Antineoplastic Agents, Hormonal↗

Tension-free transobturator approach for female stress urinary incontinence.

AIM: UraTape is a new sling for female stress urinary incontinence (SUI) inserted via a transobturator percutaneous approach. We report the safety, feasibility and short-term results of this new surgical procedure. METHODS: UraTape (Porgès-Mentor) is a non-elastic polypropylene tape, with a silicone coated central part. The sling is placed tension-free under the mid-urethra and extended through the obturator foramen bypassing the posterior face of the ischiopubic ramus. From September 2002 to May 2003, 80 females affected by SUI associated with urethral hypermobility and without severe uro-genital prolapse (with cystocele 1st grade) received UraTape. Mean age was 56 (39-79) years. Sixty-two out of 80 had a positive Q tip test; 16/80 had recurrent incontinence after Burch or colpoplasty according to Kelly; 22/60 had mixed incontinence. Preoperative evaluations included: complete history and physical examination, urinalysis, urodynamic investigations, abdominal and pelvic ultrasound. Quality of life assessment was carried out pre- and postoperatively. RESULTS: Mean operative time was 16 (11-36) minutes. No major intraoperative complications were observed. One bladder neck laceration occurred and was treated intraoperatively. No cystoscopy was performed. Mean hospital postoperative stay time was 1.1 (1-6) days. All patients were examined periodically at 7, 30 and 90 days from intervention (mean follow-up 4 months, 1-8). There was no urethral erosion. One vaginal erosion with inguinal abscess was diagnosed and treated without removing the sling. Two de novo urge incontinence was observed. The objective and subjective cure rates were 92% and 97%; 96% expressed good quality of life (satisfied/very satisfied). CONCLUSION: This procedure is a safe, effective new technique for the treatment of female SUI. The easy technique, the short learning curve and the very high grade of satisfaction of the patients show that this approach is based upon effective anatomical and physiological criteria. Further follow-up is necessary in order to evaluate urodynamic changes and overall satisfaction.

Adult↗

In vivo expression of the whole HOX gene network in human breast cancer.

The HOX network contains 39 genes that act as transcriptional regulators and control crucial cellular functions during both embryonic development and adult life. Inside the network, this is achieved according to the rules of temporal and spatial co-linearity with 3' HOX genes acting on the anterior part of the body, central HOX genes on the thoracic part and lumbo-sacral HOX genes on the caudal region. We analysed HOX gene expression in normal breast tissue and in primary breast cancers by reverse-transcriptase-polymerase chain reaction (RT-PCR). 17 out of 39 HOX genes were expressed in the normal breast tissue. The expression of thoracic HOX genes tended to be similar in normal and neoplastic breast tissues suggesting that these genes are involved in breast organogenesis. In contrast, cervical and lumbo-sacral HOX gene expression was altered in the primary breast cancers with respect to normal breast tissue. This supports their involvement in breast cancer evolution and suggests they could be targets for future cancer therapies.

Adult↗

A preoperative clinical prognostic model for non-metastatic renal cell carcinoma.

OBJECTIVE: To develop a model to predict the outcome before surgery for non-metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: The records of 660 patients with non-metastatic RCC, operated at three European medical institutes, were reviewed. Univariate and multivariate analyses were used to assess the clinical and pathological variables affecting disease-free survival. RESULTS: The median (range) follow-up was 42 (2-180) months; the disease recurred in 110 patients (16%). The 2- and 5-year overall survival was 87% and 54%, respectively. Five variables were significant in the univariate analysis, i.e. clinical presentation, clinical and pathological size, tumour grade and stage (P < 0.05). The preoperative variables, e.g. clinical presentation and clinical tumour size, were retained from the multivariate model. A recurrence risk formula (RRF) was constructed from this model, as (1.28 x presentation (asymptomatic = 0; symptomatic = 1) + (0.13 x clinical size)). Using this equation, the 2- and 5-year disease-free survival was 96% and 93% for an RRF of < or = 1.2 and 83% and 68% for an RRF of > 1.2. CONCLUSION: A formula was developed which, independent of stage, can be used to predict the rate of treatment failure in patients who undergo nephrectomy for non-metastatic RCC. The RRF might be useful for more accurate sub-grouping of good-prognosis patients, and for counselling patients before surgery, their personalized follow-up or adjuvant treatment once available.

Adult↗

[Erectile dysfunction in kidney transplanted patients].

BACKGROUND: Erectile dysfunction (ED) is the inability to achieve and/or maintain an erection for satisfactory sexual performance or intercourse. ED profoundly affects the quality of life. While the effects of dialysis on ED are documented, the benefits of renal transplantation are unknown. METHODS: This study evaluates the prevalence of ED and the effects of transplantation on ED in kidney transplanted patients. Erectile function was assessed using the self-administered International Index of Erectile Function (IIEF). The domains investigated by IIEF are: (1) erectile function, (2) orgasmic function, (3) sexual desire, (4) intercourse satisfaction, (5) overall satisfaction. At the entry patients underwent clinical examination by urologist and neurologist; blood was collected for biochemical analysis. One-hundred-fifteen (89%) patients filled in the questionnaire. RESULTS: Fifty-two (45%) patients did not complain about ED, which was reported by sixty-three patients (55%). No clinical and/or biochemical difference was found between patients with and without ED. Hypertension was equally present among patients; administration of beta-blockers was significantly more frequent among patients without ED. ED was already present during dialysis in 40 patients. After transplantation ED disappeared in 8 (20%), ameliorated in 13 (32,5%), worsened in 2 (5%), remained unchanged in 17 (42,5%) and appeared "ex novo" in 27 (43%) patients. ED is significantly correlated (p<0.01) to the age of subjects. CONCLUSIONS: The data of the present study indicate that: 1) ED is still present in many transplanted men; 2) renal transplantation cures ED in only few cases; 3) ED may appear "ex novo" after transplantation.

Adult↗

Not traditional prognostic factors in human conventional renal carcinoma.

The evaluation of know prognostic factors is an essential step of the assessment of the patients affected by primary renal carcinoma. As long as the major biological mechanisms of renal carcinomas remain unknown, it will be impossible to achieve an accurate prognostic judgement. The TNM classification has always been the main source of information. Nevertheless, recently several investigations evaluated the prognostic power of serum and cellular markers. The aim of this study is to identify those markers which show statistical reliability and can be used in the clinical practice. A literature search was performed on MEDLINE to identify potential not traditional prognostic factors for patients with renal cell carcinoma edited from January 1997 through April 2000 using prognosis and clear cell carcinoma and kidney as keywords. We considered also articles cited in references of first selected manuscript. The analysis of serum and cellular prognostic markers does not allow the identification of specific factors, reliable, independent, easy to dose, widely useful and whose informations are repeatable. Currently classical prognostic factors (staging, grading, hystologic type, patient clinical conditions, anaemia, presentation modalities, etc.) represent the only useful elements after surgical time in RCC patients. Among serum prognostic factors, CRP and ferritin play a crucial role. These proteins appear ideal in monitoring the disease over time, due to simple test execution and specimens repeatability. Among RCC molecular markers, proliferation index result promising for their reliability and reproducibility, the easy dosage and high series number tested. Literature data suggest that the ideal marker for renal carcinomas has not been identified yet. However, C-reactive protein, ferritin and the proliferative activity indexes (Ki67 and AgNOR) appear to be, at present, the best prognostic tools. To confirm obtained results and to use biomolecolar markers on a routinary base further studies on wide surgical series will be required. The improvement of technical tool and costs reduction represent also a necessary step toward the identification of efficient prognostic markers in RCC.

Biomarkers↗

galectin-1 and galectin-3 expression in human bladder transitional-cell carcinomas.

Galectin-1 and galectin-3 are galactoside-binding proteins involved in different steps of tumor progression and potential targets for therapy. We have investigated the expression of these galectins in 38 human bladder transitional-cell carcinomas of different histological grade and clinical stage and in 5 normal urothelium samples. Galectin-1 mRNA levels were highly increased in most high-grade tumors compared with normal bladder or low-grade tumors. Western blot and immuno-histochemical analysis of normal and neoplastic tissues revealed a higher content of galectin-1 in tumors. Galectin-3 mRNA levels were also increased in most tumors compared with normal urothelium, but levels were comparable among tumors of different histological grade.

Adult↗

["Classic" vs autolubricant catheterization for endovesicular chemotherapy. Preliminary experience].

AIM: The aim of this study was to evaluate the frequency of urinary tract infections (UTI) after catheterisation for instillation comparing two systems: the "classic" method and the catheterisation using a new autolubricant device: EasiCath Coloplast. METHODS: During the period of endovesical chemotherapy (between 4 and 48 weeks), 22 patients (6 females and 18 males) were studied, aged between 53 and 78 years old. We have performed 139 instillations using Nelaton Ch 14 or 12 type catheters lubricated with gel based on lidocaine, neomicyn and fluocinolone ("classic" method). Instead 135 patients have been treated with autolubricant devices according to the manufacturer's instructions. After 48 hours from instillation, a total of 274 catheterisation have been examined using urine tests and urine culture with antibiogram. We administered a 5-point visual analogic score to the patients weighing the post-instillation dysuria. RESULTS: With "classic" method UTI frequency is 7.19% (10/139). The most common pathogen has been E. coli (7/10). With autolubricant catheters UTI frequency is 2.96 (4/135). Klebsiella, Enterobacter, as well as E. coli (2/4) have been identified as pathogen. All patients with infections have been treated with targeted antibiotics based on the antibiogram. CONCLUSIONS: We have observed the people with autolubricant catheters left more comfort then those undergoing to the "classic" catheterisation. The frequency of post-catheterisation, dysuria was also reduced. Our data show that the new method is safer and easier to handle then the "classic" one. Moreover, common anaesthetic/antibiotic lubricant have important bacteriostatic effects that reduce the BCG viability.

Aged↗

Cell-specific transcriptional regulation and reactivation of galectin-1 gene expression are controlled by DNA methylation of the promoter region.

The galectin-1 gene is developmentally regulated gene whose activity is strongly modulated during cell differentiation and transformation. We have previously shown that galectin-1 promoter constructs are highly active when transiently transfected in cells both expressing and not expressing the endogenous gene and that the basal activity is determined by a small region encompassing the transcription start site (from positions -50 to +50). We have now investigated the role of DNA methylation in galectin-1 gene expression. Southern blot analysis with HpaII and MspI endonucleases and sodium bisulfite analysis of genomic DNA from expressing and nonexpressing cell lines and cell hybrids showed a close correlation between gene activity and demethylation of the 5' region of the galectin-1 gene. We found that the galectin-1 promoter region is fully methylated, at every CpG site on both strands, in nonexpressing differentiated rat liver (FAO) and thyroid (PC C13) cells and unmethylated in the expressing undifferentiated liver (BRL3A) and thyroid transformed (PC myc/raf) cell lines. In addition, reactivation of the silent FAO alleles in FAO-human osteosarcoma (143tk-) hybrid cells is accompanied by a complete demethylation of the promoter region. Finally, when galectin-1 chloramphenicol acetyltransferase (CAT) promoter constructs were methylated in vitro by SssI methylase at every cytosine residue of the CpG doublets and transfected into mouse fibroblasts, the transcription of the CAT reporter gene was strongly inhibited.

Animals↗

Prevalence of silent prostatic adenocarcinoma in 165 patients undergone cystoprostatectomy: a retrospective study.

The reported prevalence of prostatic adenocarcinoma (PCa) in adults represents only the . The present retrospective study was carried out to estimate the prevalence of the silent PCa in 165 subjects (median age: 69 years; range: 40-82) undergone radical cystoprostatectomy for bladder cancer. To this aim, 38 subjects had routinely prostatic sampling by histology (group A), whereas 127 had systematic pathological sampling of the gland (group B). Silent PCa was diagnosed in 17 subjects (9.7%): 1 subject was in the group A (0.7%) and 16 were in the group B (9%). The data suggest that systematic examination of the prostatic specimens should be performed in order to approach the real prevalence of silent PCa in adult population.

Adenocarcinoma↗