Biomedical subjects

Luca Cindolo

Publications and source records attributed to Luca Cindolo.

At least 19 recordsLinked to original sources

PubMed2006

Renal cell carcinoma with nodal metastases in the absence of distant metastatic disease: prognostic indicators of disease-specific survival.

OBJECTIVES: Outcome of patients with exclusive renal cell carcinoma (RCC) nodal metastases without distant metastases is not extensively described. We explored the ability of standard risk factors such as tumour size, Fuhrman grade, histologic subtype and symptom classification to predict renal cell carcinoma-specific survival (RCC-SS). METHODS: Analyses targeted 171 patients with RCC nodal metastases and absence of distant metastases. Univariable, multivariable, and predictive accuracy analyses addressed RCC-SS with the intent of identifying independent and most informative predictors of RCC-SS in this cohort of patients. RESULTS: Median RCC-SS was 2.3 yr. Symptom classification (61.3%, p<0.001) demonstrated the highest univariable accuracy. In multivariable analyses, symptom classification contributed the most to the combined predictive accuracy of all variables (+4.2%, p<0.001), followed by Fuhrman grade (+2.3%) and histologic subtype (+1.0%). CONCLUSIONS: Renal cell carcinoma-specific survival of patients with exclusive nodal metastases may show important variability. In presence of systemic symptoms, survival is extremely poor. Substantially better survival may be expected in patients with local or no symptoms. This observation has important implications when adjuvant therapies are considered.

Adolescent↗

PubMed2006

Relationship between age at diagnosis and clinicopathologic features of renal cell carcinoma.

OBJECTIVES: To analyse the influence of age at diagnosis on tumour characteristics and cancer-specific survival in renal cell carcinoma (RCC). METHODS: Data on age, tumour characteristics, and survival for 4774 patients from 12 European RCC databases were recorded. Patients were divided into four groups according to age at diagnosis: < or =40, >40 and <60, > or =60 and <80, and > or =80 yr. The following variables were analysed: TNM stage, Fuhrman grade, tumour size, symptoms at diagnosis, ECOG performance status (PS), and cancer-specific survival. The groups were compared for usual clinical and pathologic variables, and cancer-specific survival. RESULTS: The four groups accounted for 288 (6%), 1839 (38.5%), 2499 (52.3%), and 148 cases (3.2%), respectively. Differences were found among groups for tumour stage, symptoms at diagnosis, ECOG PS, Fuhrman grade (p<0.001), tumour size, M stage, and histologic subtype (p: 0.02). Patients < or =40 yr were more likely to have papillary or chromophobe RCCs and less likely to have clear-cell RCCs. No significant difference was found among groups for N stage (p: 0.15). The 5-yr cancer-specific survival rates for the four age categories were 85%, 74%, 70%, and 69%, respectively. In multivariate analysis age category remained an independent prognostic parameter (p<0.001). CONCLUSIONS: Renal tumours diagnosed in younger age are characterized by lower tumour stages and grades as well as favourable histologic patterns compared with tumours in older patients. Basic research is required for explaining such a relationship between age, tumour aggressiveness, and therefore tumour biology.

Adult↗

PubMed2006

NeuroD1 expression in human prostate cancer: can it contribute to neuroendocrine differentiation comprehension?

OBJECTIVES: Neuroendocrine differentiation is a common feature of prostate cancer (pCA). NeuroD1 is a neuronal transcription factor able to convert epithelial cells into neurons. The aim of the study is to investigate NeuroD1 expression and compare it with chromogranin-A, synaptophysin, and CD56 staining in human prostate cell lines and surgical specimens. METHODS: We detected NeuroD1 gene expression, by duplex reverse transcriptase-polymerase chain reaction, in primary human prostate fibroblasts, in EPN, LNCaP, DU145, and PC3 cell lines before and after cAMP exposure, in 6 BPH and 11 pCA samples. Thereafter 166 paraffin sections from normal and neoplastic prostates were stained with NeuroD1, chromogranin-A, synaptophysin, and CD56 antibodies. The relationships between chromogranin-A and NeuroD1 and clinicopathologic parameters were evaluated by multivariate logistic regression analysis. RESULTS: NeuroD1 is inactive in baseline prostate cell lines and BPHs, whereas it is actively expressed in cAMP-treated EPN, PC3, and DU145 cells. In our surgical series, positive chromogranin-A, synaptophysin, CD56, and NeuroD1 staining was detected in 26.5%, 4.3%, 3.1%, and 35.5%, respectively (difference between chromogranin-A and NeuroD1: p<0.05). The multivariate analysis showed a strong association between chromogranin-A and microscopic perineural invasion (OR: 2.49; 95%CI, 0.85-7.32; p=0.097) and a high primary Gleason score (OR: 1.96; 95%CI, 1.14-3.39; p=0.015), whereas NeuroD1 expression strictly correlated to microscopic perineural invasion (OR: 2.97; 95%CI, 1.05-8.41; p=0.04). CONCLUSIONS: Expression of NeuroD1 versus chromogranin-A is more frequent in pCA, and correlates to increased indicators of malignancy in moderately to poorly differentiated pCA, and could be involved in the pathophysiology of the neuroendocrine differentiation of pCA.

Adenocarcinoma↗

PubMed2006

Tumor size improves the accuracy of TNM predictions in patients with renal cancer.

OBJECTIVES: Current staging for renal cancer (RC) does not directly rely on tumor size. We examined the increment in accuracy related to inclusion of pathologically determined tumor size in prediction of nodal metastases (N+), distant metastases (M+), and cancer-specific survival (CSS). METHODS: Partial or radical nephrectomy was performed in 2245 patients with clear cell histology. Pathologic stages were T1a in 566, T1b in 490, T2 in 303, T3 in 831, and T4 in 55 patients. Tumor size was 0.5-25 cm (mean, 6.8). Multivariate models relied on 1997 and 2002 TNM variables and addressed N+, M+ disease, and CCS. Their accuracy was compared according to either the presence or absence of tumor size. RESULTS: In all univariate and multivariate models, tumor size was a statistically significant predictor of all outcomes (p< or =0.001). In all multivariate models, tumor size added between 3.7% and 0.8% to predictive accuracy of either 1997 or 2002 TNM categories. CONCLUSIONS: Tumor size represents a highly significant, multivariate, and informative predictor of RC outcomes and may warrant inclusion in future TNM revisions.

Carcinoma, Renal Cell↗

PubMed2005

Proposal for revision of the TNM classification system for renal cell carcinoma.

BACKGROUND: The current study defined an optimal tumor size breakpoint to stratify localized renal cell carcinoma (RCC) into groups with significantly different cancer-related outcomes and proposed a revision of the TNM classification system. METHODS: The authors analyzed the data from 1138 patients who had undergone partial or radical nephrectomy for localized RCC at 7 European urologic centers. The optimal pathologic size breakpoint was calculated using the martingale residuals from a Cox proportional hazards regression model. RESULTS: The mean follow-up time was 87 months. The scatterplot of tumor size versus expected risk of death per patient suggested that an interval of 5-6 cm was appropriate. A total of 720 (63.3%) and 418 (36.7%) patients had tumors measuring < or = 5.5-cm and tumors measuring > 5.5-cm, respectively. Significant cancer-specific survival differences between the two groups of patients were reported in the series by all the centers participating in the study. On univariate analysis, the other variables found to be associated with cancer-specific survival were the patient's age, symptomatic tumor presentation, and the Fuhrman nuclear grade. On multivariate analysis, the pathologic stage of the primary tumor defined according to the 5.5-cm breakpoint was found to be an independent predictor of cancer-specific survival, as well as age, mode of presentation, and nuclear grade. According to the multivariate analysis, the authors clustered patients into 3 groups with statistically significant outcome differences: 1) patients with < or = 5.5-cm incidentally detected RCC; 2) patients with < or = 5.5-cm symptomatic RCC; and 3) patients with > 5.5-cm RCC. This cancer-related outcome stratification was valid regardless of the patient's age. CONCLUSIONS: The 5.5-cm breakpoint was found to be the optimal tumor size breakpoint with which to stratify patients with organ-confined RCC. The study supported the upgrade of the TNM classification system according to this breakpoint.

Adolescent↗

PubMed2005

Comparison of predictive accuracy of four prognostic models for nonmetastatic renal cell carcinoma after nephrectomy: a multicenter European study.

BACKGROUND: The objective of the current study was to compare, in a large multicenter study, the discriminating accuracy of four prognostic models developed to predict the survival of patients undergoing nephrectomy for nonmetastatic renal cell carcinoma (RCC). METHODS: A total of 2404 records of patients from 6 European centers were retrospectively reviewed. For each patient, prognostic scores were calculated according to four models: the Kattan model, the University of California at Los Angeles integrated staging system (UISS) model, the Yaycioglu model, and the Cindolo model. Survival curves were estimated by the Kaplan-Meier method and compared by the log-rank test. Discriminating ability was assessed by the Harrell c-index for censored data. The primary end point was overall survival (OS), and the secondary end points were cancer-specific survival (CSS) and disease recurrence-free survival (RFS). RESULTS: At last follow-up, 541 subjects had died of any causes, with a 5-year OS rate of 80%. The 5-year CSS and RFS rates were 85% and 78%, respectively. All models discriminated well (P < 0.0001). The c-indexes for OS were 0.706 for the Kattan nomogram, 0.683 for the UISS model, and 0.589 and 0.615 for the Yaycioglu and Cindolo models, respectively. The Kattan nomogram was found to improve discrimination substantially in the UISS intermediate-risk patients. CONCLUSIONS: The current study appears to better define the general applicability of prognostic models for predicting survival in patients with nonmetastatic RCC treated with nephrectomy. The results suggest that postoperative models discriminate substantially better than preoperative ones. The Kattan model was consistently found to be the most accurate, although the UISS model was only slightly less well performing. The Kattan model can be useful in the UISS intermediate-risk patients.

Adolescent↗

PubMed2005

Multiinstitutional European validation of the 2002 TNM staging system in conventional and papillary localized renal cell carcinoma.

BACKGROUND: The current study validated the 2002 edition of the TNM staging system in a multicenter, multinational European series of localized renal cell carcinoma (RCC). METHODS: The authors analyzed the clinical data of 2217 patients who had undergone radical or partial nephrectomy for localized RCC in 7 urologic centers. RESULTS: In the current study, 1065 patients (48%) were classified as having pT1a disease, 771 (34.8%) were classified as having pT1b disease, and 381 (17.2%) were classified as having pT2 disease. Tumor histotype was conventional RCC in 1886 patients (85%), papillary in 182 (8.2%) patients, chromophobe in 64 (2.9%) patients, and unclassified in 85 (3.8%) patients. The mean follow-up time was 65.36 +/- 52.09 months. The 5 and 10-year disease-specific survival probabilities were 95.3% and 91.4% in patients with pT1a disease, 91.4% and 83.4% in patients with pT1b disease, and 81.6% and 75.2% in patients with pT2 disease (log-rank test P value = 0.0000). The disease-specific survival rates of patients with pT1a RCC were significantly higher than those recorded in patients with pT1b and pT2 RCC. Similarly, the disease-specific survival probabilities of patients with pT1b RCC were significantly better than those of patients with pT2 RCC. Analyzing the seven series individually, the 2002 TNM staging system provided appropriate stratification for only one series. The 2002 TNM staging system allowed significant stratification of the cancer-related outcomes in the subgroup of patients with conventional RCC but not in those with papillary carcinomas. CONCLUSIONS: The application of the 2002 TNM staging system in the current multicenter series enabled the authors to demonstrate optimal stratification of patients with localized RCC. Stratifying by tumor histotype, the data coming from the whole group analysis were reconfirmed for clear cell RCC only.

Adolescent↗

PubMed2005

Prognostic value of histologic subtypes in renal cell carcinoma: a multicenter experience.

PURPOSE: To analyze to what extent histologic subtype is of prognostic importance in renal cell carcinoma based on a large, international, multicenter experience. PATIENTS AND METHODS: Four thousand sixty-three patients from eight international centers were included in this retrospective study. Histologic subtype (1997 International Union Against Cancer [UICC] criteria of tumor response), age, sex, TNM stage, Fuhrman grade, tumor size, Eastern Cooperative Oncology Goup performance status (ECOG PS), and overall survival were determined in all cases. The prognostic values of clear cell, papillary, and chromophobe histologic features were assessed by uni- and multivariate analysis using the Kaplan-Meier method and Cox model, respectively. RESULTS: Clear cell, papillary, and chromophobe carcinomas accounted for 3,564 (87.7%), 396 (9.7%) and 103 (2.5%) cases, respectively. In univariate analysis, a trend toward a better survival was observed when clear cell, papillary, and chromophobe histologies were considered prognostic categories (log-rank P = .0007). However, in multivariate analysis, TNM stage, Fuhrman grade and ECOG PS, but not histology, were retained as independent prognostic variables (P < .001). CONCLUSION: The stratification in three main renal cell carcinoma histologic subtypes as defined by the 1997 UICC-American Joint Committee on Cancer consensus should not be considered a major prognostic variable comparable to TNM stage, Fuhrman grade and ECOG PS.

Adolescent↗

PubMed2005

Chromophobe renal cell carcinoma: comprehensive analysis of 104 cases from multicenter European database.

OBJECTIVES: To analyze the clinical behavior of chromophobe renal cell carcinoma (CRCC), we retrospectively evaluated the data from six European centers. In 1985, CRCC was identified as a new RCC histologic subtype. Because of its low frequency, only few large CRCC series are available. METHODS: We created a renal cancer database including 3228 patients who underwent surgery between 1986 and 2002 in six European centers. The relevant clinical and pathologic data were extracted from the clinical charts at each institution and collected into a unique database. RESULTS: Of the 3228 patients, 104 (3.2%) affected by CRCC were identified. The mean age at diagnosis was 57.6 years (range 22 to 83). Of the 104 patients, 51 (49%) were men and 53 (51%) were women. The mean tumor size was 6.4 +/- 3.6 cm. An incidental diagnosis accounted for 61.5% of the cases. Radical nephrectomy was performed in 88 patients (85%). After a median follow-up of 38 months (mean 44, range 1 to 153), no local recurrence was observed. The 5-year overall survival rate for CRCC was 81%. Of the 104 patients, 5 (4.8%) and 9 (8.6%) died of unrelated causes and renal cancer, respectively. CONCLUSIONS: Our series confirmed a favorable outcome for the CRCC subtype with little local aggressiveness and a low propensity for progression and death from cancer.

Adult↗

PubMed2005

How to decrease pain during transrectal ultrasound guided prostate biopsy: a look at the literature.

PURPOSE: There is growing interest among urologists on the need for decreasing pain during transrectal ultrasound (TRUS) guided prostate biopsy. MATERIALS AND METHODS: We performed a systematic MEDLINE search of clinical trials of any kind of anesthesia, analgesia or sedation during TRUS guided prostate biopsy published since 2000. We critically analyzed the impact of pain and discomfort associated with the procedure, the described methods for evaluating it and the different techniques that have been described. RESULTS: There is strong evidence in the current literature that patient tolerance and comfort during TRUS guided prostate biopsy can be improved by anesthesia/analgesia. What remains is the need to urge all urologists to introduce it in clinical practice as a routine part of the procedure, whatever the biopsy scheme. CONCLUSIONS: Of the various options periprostatic anesthetic infiltration has been shown to be safe, easy to perform and highly effective. It should be considered the gold standard at the moment, even if the optimal technique remains to be established. Further studies addressing this issue are warranted.

Anesthetics↗

PubMed2004

Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: an international multicenter study.

PURPOSE: To evaluate ability of the University of California Los Angeles Integrated Staging System (UISS) to stratify patients with localized and metastatic renal cell carcinoma (RCC) into risk groups in an international multicenter study. PATIENTS AND METHODS: 4,202 patients from eight international academic centers were classified according to the UISS, which combines TNM stage, Fuhrman grade, and Eastern Cooperative Oncology Group performance status. Distribution of the UISS categories was assessed in the overall population and in each center. RESULTS: The UISS stratified both localized and metastatic RCC into three different risk groups (P <.001). For localized RCC, the 5-year survival rates were 92%, 67%, and 44% for low-, intermediate-, and high-risk groups, respectively. A trend toward a higher risk of death was observed in all centers for increasing UISS risk category. For metastatic RCC, the 3-year survival rates were 37%, 23%, and 12% for low-, intermediate-, and high-risk groups, respectively; in 6 of 8 centers, a trend toward a higher risk of death was observed for increasing UISS risk category. A greater variability in survival rates among centers was observed for high-risk patients. CONCLUSION: This study defines the general applicability of the UISS for predicting survival in patients with RCC. The UISS is an accurate predictor of survival for patients with localized RCC applicable to external databases. Although the UISS may be useful for patients with metastatic RCC, it may be less accurate in this subset of patients due to the heterogeneity of patients and treatments.

Adult↗

PubMed2004

Frequency, clinical presentation and evolution of renal oncocytomas: multicentric experience from a European database.

OBJECTIVES: To understand the clinical behavior of renal oncocytoma in a retrospective analysis of a European multicentric nephrectomies database. METHODS: The records of 891 patients who underwent surgical resection of renal neoplasm were reviewed. Relevant clinical and pathological data for each patient were retrieved in a database. RESULTS: Thirty-two (3.6%) cases of renal oncocytoma were identified. Twenty patients (62.5%) were asymptomatic. No case of lymphatic invasion or metastatic disease, nor any evidence of vascular or fat tissue invasion was found. Thirty-one cases (96%) exhibited low mitotic activity. In one case the presence of renal clear cell carcinoma (diameter: 1.5cm) was found. After a median follow-up of 42 months, 87.5% of patients were alive with no evidence of tumor, while 9.3% of patients had died for non-malignant causes. One patient had not treated the tumor surgically and was disease-free at a 27-month follow-up. CONCLUSIONS: Renal oncocytoma is a benign neoplasm, characterized by slow growth and excellent prognosis after surgery. Nephron sparing techniques may be adequate for tumor removal.

Adenocarcinoma, Clear Cell↗

PubMed2004

Safety and efficacy of partial nephrectomy for all T1 tumors based on an international multicenter experience.

PURPOSE: We compared cancer specific survival of patients undergoing partial and radical nephrectomies for T1N0M0 renal tumors according to tumor size in a large multicenter series. MATERIALS AND METHODS: A retrospective analysis of 1454 patients undergoing partial or radical nephrectomy for T1N0M0 renal tumors from 7 international academic centers was performed. Data were obtained for each patient including TNM stage (determined according to the 2002 TNM criteria), tumor size, type of surgery (partial versus radical nephrectomy) and cancer specific survival. Recurrence events were recorded when available. RESULTS: Partial and radical nephrectomies were performed in 379 (26.1%) and 1075 (73.9%) cases, respectively. Mean followup +/- SD was 62.5 +/- 51.8 months. Recurrence data were available on 544 patients. There were no significant differences in local or distant recurrence rates between patients undergoing partial or radical nephrectomy for either T1a (p = 0.6) or T1b tumors (p = 0.5). For patients with T1a tumors, there was no significant difference in the rate of cancer specific deaths between the partial (314) and radical (499) nephrectomy groups (2.2% versus 2.6%, respectively, p = 0.8). For patients with T1b tumors there was also no significant difference in the rate of cancer specific deaths between patients undergoing partial (65) and patients undergoing radical (576) nephrectomy (6.2% versus 9%, respectively, p = 0.6). CONCLUSIONS: Partial nephrectomy is becoming the gold standard for renal tumors less than 4 cm but this treatment is much more controversial for larger T1 tumors. This large multicenter study suggests that it is safe to expand the indications of partial nephrectomy to include patients with T1N0M0 tumors up to 7 cm. However, careful patient selection remains necessary.

Carcinoma, Renal Cell↗

PubMed2004

Multi-institutional validation of a symptom based classification for renal cell carcinoma.

PURPOSE: We validate the prognostic value of a symptom based classification (S classification) in a multi-institutional study. MATERIALS AND METHODS: A total of 2,242 patients from 5 European centers were included in this study. Based on symptoms at diagnosis, patients were stratified into 3 groups of S1-asymptomatic tumors, S2-tumors with local symptoms and S3-tumors with systemic symptoms. Variables such as age, gender, tumor size, TNM stage, Fuhrman grade, Eastern Cooperative Oncology Group (ECOG) performance status, perinephric fat, renal vein and adrenal invasion were also considered for prognostic value. The end point of the study was cancer specific survival. Survival assessment was made with univariate and multivariate analyses using the Kaplan-Meier method and Cox regression analysis. RESULTS: Of the patients 1,018 (45.4%) were classified as S1, 865 (38.6%) S2 and 339 (16.0%) S3. The S classification correlated to tumor stage, grade and ECOG (p <0.001). On univariate analysis ECOG performance status, S classification, tumor size, TNM stage, Fuhrman grade, and adrenal, perinephric fat or vein invasion were significant prognostic factors (p <0.001). The S classification provided a significant prognostic stratification in the aggregate as well at each of the 5 centers. On multivariate analysis the S classification, TNM stage, Fuhrman grade, and perinephric fat and renal vein invasion remained independent prognostic factors (p <0.001). CONCLUSIONS: This study confirms that it is possible to graduate symptoms for a prognostic purpose. The proposed symptom score should be evaluated for its integration in prognostic algorithms.

Adolescent↗

PubMed2004

Symptoms as well as tumor size provide prognostic information on patients with localized renal tumors.

PURPOSE: T stage stratification of organ confined renal tumors is based only on tumor size. Currently T1a and T1b are defined as tumors less or greater than 4 cm. However, to our knowledge the validity of this stratification has not been determined. We determined whether symptoms could add additional prognostic information when integrated with tumor size into the TNM classification. MATERIALS AND METHODS: Patients with T1-T2N0M0 renal tumors at 6 academic centers in Europe and the United States were included in this study. T stage was defined according to the 2002 TNM classification. Age, gender, T stage, tumor size, symptoms at presentation, Fuhrman grade and cancer specific survival were determined in all cases. Survival estimates were compared using the Kaplan-Meier method and multivariate analysis of the data were performed with the Cox model. RESULTS: A total of 1,771 patients with pT1-T2N0M0 renal tumors were included in this study. There were 1,148 males and 623 females. Mean age was 59.6 years. Median tumor size was 5 cm. Of the tumors 781 (44.1%), 616 (34.8%) and 374 (21.1%) were stages T1a, T1b and T2, respectively. In 825 patients (46.6%) symptoms were related to renal cancer. T stage and symptoms strongly correlated, in that 67%, 51% and 29% of patients with T1a, T1b and T2 tumors, respectively, were asymptomatic. Symptoms increased the risk of cause specific death for each T stage level. On multivariate analysis Fuhrman grade (HR 1.46), T stage (HR 1.81) and symptoms (HR 2.98) were independent predictors of survival. Based on these results 4 groups resulting from combinations of 2002 TNM stage and symptoms with significantly different risks of death were defined, namely 1) T1a-4 cm or less without symptoms, 2) T1b-4 cm or less with symptoms and greater than 4 cm without symptoms, 3) T2a-greater than 4 cm and 7 cm or less with symptoms, and 4) T2b-greater than 7 cm with symptoms CONCLUSIONS: In this study we noted that a system combining tumor size and symptoms can accurately stratify patients for predicting survival in those with organ confined renal tumors. Our data support the idea that symptoms should be integrated in further modifications of the TNM system.

Adolescent↗

PubMed2004

Standard versus hydrophilic catheterization in the adjuvant treatment of patients with superficial bladder cancer.

INTRODUCTION: The aim of the present study is to compare a hydrophilic catheter to the standard polyvinyl chloride catheter with regard to bacteriological safety and overall comfort in patients undergoing intravesical immuno- or chemotherapy for bladder cancer. MATERIALS AND METHODS: One hundred patients (80 males, 20 females; median age 65.8 years, range 48-79 years) eligible for intravesical prophylaxis of superficial bladder cancer recurrences were randomized to receive intravesical therapy using a standard catheter (group A, n = 50) or a hydrophilic catheter (group B, n = 50). Urinalysis and urine culture were performed 2 days after catheterization. Comfort during catheterization was assessed by a 5-point visual analogue scale at the end of the first four instillations. RESULTS: Urinary tract infection (UTI) was detected in 7.4% of catheterizations in group A, whereas it occurred in 3.5% of catheterizations in group B (p < 0.01). Escherichia coli was the most frequent pathogen regardless of the device used. At the end of each of the first four instillations, the mean score for discomfort was significantly higher in group A than in group B (p < 0.001), although catheterization was progressively better tolerated regardless of the device used (both p < 0.005). None of the patients were found to be suffering from orchitis, epididymitis or gross haematuria. CONCLUSION: Hydrophilic catheters may be used safely and are well tolerated by patients undergoing intravesical immuno- or chemotherapy. The hydrophilic catheter was associated with a significantly lower occurrence of UTI and higher acceptability compared to the standard device. These data should be considered with regard to patient compliance with intravesical therapy.

Aged↗

PubMed2003

Hyperexpression of locus C genes in the HOX network is strongly associated in vivo with human bladder transitional cell carcinomas.

Bladder carcinogenesis remains unclear despite the identification of chemical, environmental and genetic factors. It has recently been reported that the chromosomal region 12q13-q15, containing crucial cancer genes such as MDM2, CDK4 and GLI, is amplified in bladder cancer. In the same region are also located the genes of the locus HOX C, flanked by keratin genes whose protein product may be a prognostic marker of bladder cancer. The HOX genes constitute a network of transcription factors controlling embryonal development and play 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 phenotypical cell identity. We have analysed the expression of the whole HOX gene network in pairs of normal-tumour bladder and in tumoral biopsies. Comparison between normal urothelium and bladder tumour has identified dramatic variations of expression in a block of three genes (HOX C4, HOX C5 and HOX C6) localized in the HOX C locus on the chromosome 12q13 and in the paralogous group 11 HOX genes, involved during normal development in the formation of the urogenital system. These data suggest a key involvement of the HOX gene network, and especially the locus C, in bladder cancer.

Aged↗

PubMed2003

HOX gene network is involved in the transcriptional regulation of in vivo human adipogenesis.

Adipogenesis is regulated by the sequential activation of a series of transcription factors: the C/EBP proteins of type beta and delta trigger the process while PPARgamma and C/EBPalpha induce the differentiation from pre-adipocyte to adipocyte, followed by adipo-specific gene expression. A number of observations suggest the involvement of genes controlling embryonal development in adipogenesis. In human thyroid follicular carcinoma, it has been recently identified an oncogenetic fusion protein resulting from the interaction between the isoform PPARgamma1 of PPARgamma and the homeoprotein encoded by the PAX-8 gene. Recent observations have pointed out that gene expression associated with adipocyte differentiation in vivo and in vitro, although partially overlapping, is actually different. HOX genes make up a network of transcription factors (homeoproteins) controlling embryonal development as well as crucial functions of adult eukaryotic cells. The molecular organization of this network of 39 genes appears to be unique in the genome and probably acts regulating phenotypic cell identity. In the present study we have analyzed the expression of the complete HOX gene network, in vivo, in different deposits of human white adipose tissue and in embryonal brown adipose tissues. Most of the genes in the HOX network are active in white as well as brown adipose tissue. Furthermore HOX genes display a deposit-specific expression in white adipose tissue. Moreover, expression of the paralogous group 4 genes (HOX A4, HOX B4, HOX C4, and HOX D4), together with that of isolated genes in the network, appears to discriminate between white and brown adipose tissue. This data allows us to postulate the involvement of the HOX network in transcriptional regulation of human adipogenesis and to hypothesize on the molecular mechanisms that could be implicated.

Adipocytes↗