[Show abstract][Hide abstract] ABSTRACT: Benign prostatic hyperplasia (BPH) represents a pattern of non-malignant growth of prostatic fibromuscular stroma. Metabolic disturbances such us pre-diabetes and metabolic syndrome may have a role in BPH pathophysiology. A potential explanation for the above relationship involves the insulin-like growth factor (IGF) axis as well as IGF binding proteins, (IGFBPs) of which the most abundant form is IGFBP-3. Therefore, the aim of the present study was to investigate the association between intra-prostatic levels of IGF-1, IGF-2 as well as to evaluate the role of locally expressed IGFBP-3 in BPH development in pre-diabetes. A total of 49 patients admitted to the Urology department of a tertiary urban Greek hospital, for transurethral prostate resection, or prostatectomy and with pre-diabetes [impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) or both] were finally included. The majority of the sample consisted of subjects with IGT (51.0%), followed by IFG and IGT (32.7%) and isolated IFG (16.3%). For all participants a clinical examination was performed and blood samples were collected. In addition, total prostate (TP) volume or transitional zone (TZ) volume were estimated by transrectal ultrasonography. The results of the multivariate analysis regarding TP volume showed that higher PSA (p<0.001), larger waist circumference (p=0.007) and higher IGFBP-3 expression levels (p<0.001) independently predicted higher TP volume. The results regarding the volume of the TZ showed that higher PSA (p<0.001), larger waist circumference (p<0.001) and higher IGFBP-3 expression levels (p=0.024) were independently associated with higher TZ volume. Our findings show that intra-prostatic levels of IGFBP-3, PSA and waist circumference, but not overall obesity, are positively associated with prostate volume. IGFBP-3 seems to be a multifunctional protein, which can potentiate or inhibit IGF activity.
PLoS ONE 01/2013; 8(12):e81411. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The field of the potential applications of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) beyond their unambiguous cardiovascular beneficial effects is steadily increasing. In this regard, statins have also been shown to possess anti-inflammatory, immunomodulatory, antioxidant and growth inhibitory properties. Regarding their role in carcinogenesis, both preclinical and clinical studies report conflicting results. Intriguingly, accumulating evidence suggests that statins may relate to decreased prostate cancer incidence and recurrence risk. However, data from clinical studies seem to be still weak and are confounded by several factors. Nonetheless, preclinical data suggest that statins might exert a chemopreventive role against prostate cancer by inhibiting the proliferation and inducing apoptosis of prostate cancer cells and also inhibiting angiogenesis, inflammation and metastasis. Cholesterol lowering as well as statin pleiotropy through inhibition of the synthesis of isoprenoids have both been implicated in their anticancer properties. In this review, we discuss the preclinical and clinical evidence supporting the preventive or potentially harmful effects of statins on prostate tumourigenesis and conclude that statins should not be recommended for the prevention of prostate cancer development or progression based on the current data.
European journal of cancer (Oxford, England: 1990) 02/2011; 47(6):819-30. · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the diagnostic value of an initial 24-sample transrectal ultrasound guided (TRUS) prostate biopsy protocol compared to the 10-core technique.
We retrospectively reviewed the prostate biopsy database of consecutive men undergoing prostate biopsies under local anesthesia by using the 10 (Group A) and 24 (Group B) protocols. Men were stratified according to biopsy protocol and PSA levels. Exclusion criteria were age ≥ 75 years and PSA > 20 ng/mL. The Mann-Whitney U and Fisher's exact test were used for statistical analysis.
Between April 2007 and August 2009, 869 men underwent TRUS prostate biopsies of which 379 were eligible for the study. Group A (10-cores) consisted of 243 (64.11%) men and group B (24-cores) included 139 (35.89%) men. The overall prostate cancer detection rate was 39.09% and 34.55% in Group A and B, respectively (p = 0.43). An overall 9.8% increase in Gleason 7 detection rate was found in Group B (p = 0.24). The high-grade prostatic intraepithelial neoplasia (HGPIN) detection rate in men with negative initial biopsies was 15.54% and 35.55% in Group A and B, respectively (p < 0.001). In patients with PSA < 10 ng/mL, the 24-core technique increased Gleason 7 detection rate by 13.4% (p = 0.16) and HGPIN by 23.4% (p = 0.0008), compared to the 10 core technique. The 24-core technique increased the concordance between needle biopsy and prostatectomy specimen compared to 10-core technique (p < 0.002).
The initial 24-core prostate biopsy protocol did not show any benefit in the detection of prostate cancer compared to the 10-core technique. However, it improved the HGPIN detection and the correlation between biopsy results and radical prostatectomy Gleason score in men with lower PSA levels.
International braz j urol: official journal of the Brazilian Society of Urology 02/2011; 37(1):87-93; discussion 93.
[Show abstract][Hide abstract] ABSTRACT: Cell cycle regulation, which is important for normal cellular proliferation, is controlled by a complex network of intracellular proteins, with cyclins, cyclin-dependent kinases (CDKs) and cyclin-dependent kinase inhibitors (CD-KIs) playing a central role. This equilibrium is interrupted in cancer cells, resulting in uncontrolled cellular proliferation.
In the present study we examined, by means of semi-quantitative RT-PCR, the expression of G(1)-phase cell cycle regulators MDM2, E2F1, Cyclin D1 (CCND1), CDK4, p19(INK4D), p21(WAF1/CIP1) and p27(KIP1) in a series of 32 bladder cancer specimens paired with adjacent normal tissues.
Cyclin D1 was overexpressed in 10/32 (31.2%) and downregulated in 8/32 (25.0%) bladder cancer specimens. Additionally, p21 was overexpressed in 9/32 (28.1%) and downregulated in 10/32 (31.3%) cancer samples. On the contrary, MDM2, E2F1, CDK4, p19 and p27 expression was normal in the majority of malignant specimens. Further statistical analysis revealed significant associations between increased p21 levels and bladder cancer patients with no exposure to chemicals (p=0.048), as well as with patients with no artificial sweetener intake (p=0.012), and between increased Cyclin D1 levels and study subjects with no artificial sweetener intake (p=0.012).
Based on these results, we conclude that Cyclin D1 and p21 mRNA deregulation seems to be an important event in bladder carcinogenesis. However, further studies are needed, in order to determine whether these two cell cycle regulators can be used as markers for the early detection of bladder cancer and to monitor its progression and recurrence.
Journal of B.U.ON.: official journal of the Balkan Union of Oncology 01/2011; 16(2):323-30. · 0.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Urinary bladder cancer accounts for approximately 5% of all newly diagnosed malignancies in the developed world. Smoking, occupational exposure and dietary factors constitute the most important exogenous risk factors for bladder carcinogenesis. Yet, individuals with seemingly equal exposure to environmental carcinogens develop bladder cancer in an unpredictable manner. This is probably attributed to the fact that DNA repair capacity varies in human populations, pointing the role of genetic susceptibility in human cancer. Numerous studies demonstrated that certain genetic and epigenetic alterations are fairly constant. Loss of heterozygosity (LOH) at chromosome 9 is an aberration found in urothelial cell carcinoma (UCC) of all stages and grades as well as in dysplastic urothelium, possibly representing an early event in urinary bladder carcinogenesis. On the contrary, gains of 3p can only be found in tumors demonstrating highly malignant behavior. Microsatellite instability (MSI) is another frequent finding in urinary bladder cancer. This has led many investigator groups to employ the analysis for MSI for early diagnosis of UCC with promising results. The silencing of certain genes such as p16(INK4A) and DAPK by aberrant methylation of their promoter region also represents an important mechanism in carcinogenesis. Similarly, alterations in certain tumor suppressor genes and proto-oncogenes result in uncontrolled cell proliferation, reduced apoptosis and have been associated with more aggressive UCC phenotypes. Undoubtedly, the application of these observations in clinical practice will make a breakthrough in the management of bladder cancer.
Journal of B.U.ON.: official journal of the Balkan Union of Oncology 01/2011; 16(4):589-601. · 0.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A real-time PCR targeting IS6110 was employed for the detection of Mycobacterium tuberculosis DNA in specimens collected from 10 patients treated with intravesical M. bovis bacillus Galmette-Guérin (BCG) immunotherapy for bladder malignancy. BCG DNA was detected in all urine specimens taken 24 h after the instillations, as well as in 24% of the specimens collected 7 days after the instillations; it was also detected in a single specimen taken 6 weeks after the last instillation. BCG DNA was detected in 8.3% of the blood specimens taken 1 day after instillation, and its amplification was associated with cases of self-limiting fever. These findings give indications that this real-time PCR is helpful to recognize BCG bacteremic cases, which may lead to mycobacterial infection.
Journal of clinical microbiology 01/2011; 49(4):1206-8. · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In 2004, the WHO recognized the plasmacytoid subtype as a distinct variant of vesical malignancy. We present a case of plasmacytoid urothelial carcinoma of the bladder treated with radical surgery and adjuvant chemotherapy, thus achieving long-term survival. A 70-year-old woman presented with persistent dysuria and underwent cystoscopy which revealed the presence of diffuse deformity, involving the right lateral vesical wall. Histology revealed the presence of muscle-invasive urothelial carcinoma of the plasmacytoid variant. The patient subsequently underwent radical cystectomy and orthotopic ileal neobladder substitution, as well as adjuvant chemotherapy. At 36 months of follow-up, the patient is free of local recurrence and metastases, while her voiding function is well preserved. Bladder plasmacytoid urothelial carcinoma is considered a rare tumor, with unique microscopic and immunohistochemical features. The ideal therapeutic approach is debatable, but the combination of radical surgery and chemotherapy should constitute the mainstay of management.
Urologia Internationalis 01/2011; 86(3):370-372. · 1.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cancer is one of the leading fatal diseases in the western world and many approaches have been proposed for both its treatment and prevention. Several of these approaches are dealing with the use of chemicals or with the use of signaling molecules that interfere with critical pathways in cancer progression. Yet, there is still a lot to be learned for the biology and mechanisms of oncogenesis, tumor progression, and tumor biology in general. What that has been neglected throughout the years is the understanding of biological systems from the physical perspective and the understanding of their mechanisms from the physical point of view. Since living systems could be considered as physical systems, there exists the possibility of examining biological phenomena under this perspective. In the present work we use computational and physical approaches to study and model the tolerance limits and mechanics of cell membranes. Our scope is to gain a better understanding of these phenomena and potentially use them for therapeutic purposes, since we are referring to tumor cells.
Biomedical Engineering, 2011 10th International Workshop on; 01/2011
[Show abstract][Hide abstract] ABSTRACT: To investigate the expression of RhoA, RhoB, RhoC, Rac1 and Cdc42 kinases in urothelial cell carcinoma (UCC) of the urinary bladder and determine the expression profile of 107 Rho-associated genes, including GTPases, GDIs, GAPs and GEFs.
Rho expression was investigated using microarrays, qPCR and Western blotting in 77 UCC specimens with paired normal urothelium. Computational analysis was also performed on Gene Expression Omnibus datasets. Further microarray analysis was carried out for the expression profiling of the Rho-associated genes.
RhoB mRNA and protein levels were significantly lower in UCC, suggesting a tumour-suppressor role. On the contrary, mRNA of RhoC and protein levels of RhoA, RhoC and Cdc42, respectively, were significantly higher in UCC vs. normal tissue. High Cdc42 mRNA levels correlated with worse overall survival (p=0.027), whereas high RhoB mRNA levels correlated both with better overall (p=0.0258) and cancer-specific (p=0.0272) survival. Computational analysis verified the expression profile of Rho kinases among superficial UCCs, muscle-invasive UCCs and normal tissues.
The majority of the Rho-related genes showed over-expression in UCC vs. normal tissue. Alterations in RhoA, RhoB, RhoC, Rac1 and Cdc42 expression play a significant role in the genesis and progression of UCC of the urinary bladder.
Journal of B.U.ON.: official journal of the Balkan Union of Oncology 01/2011; 16(3):511-21. · 0.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cancer of the urinary bladder is the second most common malignancy of the genitourinary tract, currently accounting for up to 5% of all newly diagnosed tumours in the western world. Urinary bladder carcinogenesis seems to develop from the interaction of environmental exposure and genetic susceptibility. Smoking, specific industrial chemicals, dietary nitrates and arsenic represent the most important exogenous risk factors. Chromosomal abnormalities, silencing of certain genes by abnormal methylation of their promoter region, alterations in tumour suppressor genes and proto-oncogenes that induce uncontrolled cell proliferation and reduced apoptosis, are molecular mechanisms that have been reported in bladder carcinogenesis. In this article, we discuss the environmental risk factors of bladder cancer and we review the genetic and epigenetic alterations, including aberrant DNA methylation and deregulation of microRNAs expression. We also discuss the role of p53 and retinoblastoma suppressor genes in disease progression. Finally, we present recent reports on the use of molecular profiling to predict disease stage and grade and direct targeted therapy.