Biomedical subjects

Vincenzo Pagliarulo

Publications and source records attributed to Vincenzo Pagliarulo.

6 recordsLinked to original sources

PubMed2006

Clinically overt venous thromboembolism after urologic cancer surgery: results from the @RISTOS Study.

OBJECTIVE: Incidence of venous thromboembolism (VTE) and need for thromboprophylaxis in urologic surgery have received little attention since only one randomised study has addressed this issue in the last 20 yr. The present prospective observational study evaluated incidence and risk factors for clinically overt VTE in a wide spectrum of consecutive patients undergoing surgery for cancer and compared findings in urologic patients with those in patients undergoing general or gynaecologic surgery. METHODS: Patients having cancer surgery (general surgery, gynaecology, urology) were assessed for clinically overt VTE occurring up to 30+/-5 d after intervention or more if the hospital stay was longer. All suspected VTE events were evaluated by an external independent Adjudication Committee. RESULTS: A total of 2373 patients, 1238 (52%) undergoing general surgery, 685 (29%) urologic, and 450 (19%) gynaecologic surgery were evaluated. In urologic patients, most procedures (61%) were endoscopic, with bladder and prostate cancer being the most frequent tumours. In-hospital thromboprophylaxis was given to 71.7% of patients, whereas 32.5% received prophylaxis after discharge. The incidence of VTE in urologic patients was lower (0.87%) than that in general surgery and gynaecologic patients (2.8% and 2.0%, respectively). VTE consisted of three cases of nonfatal and three cases of fatal pulmonary embolism (PE). In four of the six cases, VTE occurred during prophylaxis. CONCLUSIONS: VTE still represents a severe complication and remains the most common cause of death after urologic cancer surgery. Efforts should be made to optimise prophylactic measures to further reduce such risk.

Aged↗

PubMed2006

Detection of occult lymph node metastases in locally advanced node-negative prostate cancer.

PURPOSE: The purpose of this study was to determine the incidence and clinical significance of occult metastases in the lymph nodes of patients with prostate cancer originally considered node negative by routine histologic evaluation. METHODS: Two hundred seventy four patients with pT3 prostate carcinoma treated by radical prostatectomy and bilateral lymph node dissection were included in this study. One hundred eighty patients were staged node negative (N0), while 94 patients were lymph node positive (N+), based on routine histologic evaluation. All lymph nodes from the 180 N0 patients were evaluated for occult metastases by immunohistochemistry using antibodies to cytokeratins and, if positive, prostate-specific antigen. Recurrence and overall survival were compared among patients with occult tumor cells (OLN+), with patients whose lymph nodes remained negative (OLN-), and with the 94 N+ patients. RESULTS: A total of 3,914 lymph nodes were evaluated from 180 N0 patients (average, 21.7 lymph nodes per patient). Occult tumor cells were found in 24 of 180 patients (13.3%). The presence of OLN+ was significantly associated with increased recurrence and decreased survival compared with OLN- patients (P < .001 and P = .019, respectively; relative risk of recurrence, 2.27; relative risk of death 2.07, respectively). The presence of occult lymph node metastases was an independent predictor of recurrence and death in a multivariable analysis. The outcome for patients with OLN+ disease was similar to that for patients with N+ disease. CONCLUSION: The detection of occult lymph node metastases in patients with pT3N0 prostate cancer identifies those with significantly increased risk of prostate cancer recurrence and death.

Aged↗

PubMed2006

The use of genetic programming in the analysis of quantitative gene expression profiles for identification of nodal status in bladder cancer.

BACKGROUND: Previous studies on bladder cancer have shown nodal involvement to be an independent indicator of prognosis and survival. This study aimed at developing an objective method for detection of nodal metastasis from molecular profiles of primary urothelial carcinoma tissues. METHODS: The study included primary bladder tumor tissues from 60 patients across different stages and 5 control tissues of normal urothelium. The entire cohort was divided into training and validation sets comprised of node positive and node negative subjects. Quantitative expression profiling was performed for a panel of 70 genes using standardized competitive RT-PCR and the expression values of the training set samples were run through an iterative machine learning process called genetic programming that employed an N-fold cross validation technique to generate classifier rules of limited complexity. These were then used in a voting algorithm to classify the validation set samples into those associated with or without nodal metastasis. RESULTS: The generated classifier rules using 70 genes demonstrated 81% accuracy on the validation set when compared to the pathological nodal status. The rules showed a strong predilection for ICAM1, MAP2K6 and KDR resulting in gene expression motifs that cumulatively suggested a pattern ICAM1 > MAP2K6 > KDR for node positive cases. Additionally, the motifs showed CDK8 to be lower relative to ICAM1, and ANXA5 to be relatively high by itself in node positive tumors. Rules generated using only ICAM1, MAP2K6 and KDR were comparably robust, with a single representative rule producing an accuracy of 90% when used by itself on the validation set, suggesting a crucial role for these genes in nodal metastasis. CONCLUSION: Our study demonstrates the use of standardized quantitative gene expression values from primary bladder tumor tissues as inputs in a genetic programming system to generate classifier rules for determining the nodal status. Our method also suggests the involvement of ICAM1, MAP2K6, KDR, CDK8 and ANXA5 in unique mathematical combinations in the progression towards nodal positivity. Further studies are needed to identify more class-specific signatures and confirm the role of these genes in the evolution of nodal metastasis in bladder cancer.

Algorithms↗

PubMed2005

Correlation between sigma2 receptor protein expression and histopathologic grade in human bladder cancer.

Sigma2 (sigma2) receptor proteins are overexpressed in several tissues and tumour cell lines. Although the biomolecular mechanism of this overexpression must be elucidated, sigma2 receptor was considered a potential biomarker for monitoring solid tumour proliferation. In this study, we verified first sigma2 receptor overexpression by saturation analysis with radioligand in six human bladder cancer specimens, then if a possible correlation could be established between sigma2 overexpression and tumour tissue stage and grade. The results displayed that sigma2 receptor protein was normally expressed in human bladder and overexpressed in the case of high-grade transitional cell carcinomas. Moreover, these receptors were undetected in a low-grade squamous cell carcinoma and in a very rare form of anaplastic, large cells plasmacytoid cancer.

Aged↗

PubMed2004

Sensitivity and reproducibility of standardized-competitive RT-PCR for transcript quantification and its comparison with real time RT-PCR.

BACKGROUND: Probe based detection assays form the mainstay of transcript quantification. Problems with these assays include varying hybridization efficiencies of the probes used for transcript quantification and the expense involved. We examined the ability of a standardized competitive RT-PCR (StaRT PCR) assay to quantify transcripts of 4 cell cycle associated genes (RB, E2F1, CDKN2A and PCNA) in two cell lines (T24 & LD419) and compared its efficacy with the established Taqman real time quantitative RT-PCR assay. We also assessed the sensitivity, reproducibility and consistency of StaRT PCR. StaRT PCR assay is based on the incorporation of competitive templates (CT) in precisely standardized quantities along with the native template (NT) in a PCR reaction. This enables transcript quantification by comparing the NT and CT band intensities at the end of the PCR amplification. The CT serves as an ideal internal control. The transcript numbers are expressed as copies per million transcripts of a control gene such as beta-actin (ACTB). RESULTS: The NT and CT were amplified at remarkably similar rates throughout the StaRT PCR amplification cycles, and the coefficient of variation was least (<3.8%) when the NT/CT ratio was kept as close to 1:1 as possible. The variability between the rates of amplification in different tubes subjected to the same StaRT PCR reaction was very low and within the range of experimental noise. Further, StaRT PCR was sensitive enough to detect variations as low as 10% in endogenous actin transcript quantity (p < 0.01 by the paired student's t-test). StaRT PCR correlated well with Taqman real time RT-PCR assay in terms of transcript quantification efficacy (p < 0.01 for all 4 genes by the Spearman Rank correlation method) and the ability to discriminate between cell types and confluence patterns. CONCLUSION: StaRT PCR is thus a reliable and sensitive technique that can be applied to medium-high throughput quantitative transcript measurement. Further, it correlates well with Taqman real time PCR in terms of quantitative and discriminatory ability. This label-free, inexpensive technique may provide the ability to generate prognostically important molecular signatures unique to individual tumors and may enable identification of novel therapeutic targets.

Binding, Competitive↗

PubMed2002

Role of genetic and expression profiling in pharmacogenomics: the changing face of patient management.

As the determination of gene sequences and their function gains speed at the dawn of the third millennium, biomedical research efforts are oriented towards definition of the genetic and molecular expression patterns that may drive different disease. A major part of these efforts is addressed to the definition of inter-individual variations that are expected to become integral for treatment planning, in terms of efficacy and adverse effects of drugs. It is this thrust on genome-based 'rational therapeutics' that is hoped to progressively lead to the era of 'personalized medicine'. This approach uses the technological expertise from genomics and functional genomics to define, predict and monitor the nature of the response of an individual to drugs, and to rationally design newer drugs. In the present review we will conduct our readers through an understanding of the fundamentals of pharmacogenomics and of the technologies currently available that are advancing this relatively new science. Conversely, there are issues raised that concern how medical practice is preparing itself to implement new alternatives for therapeutical interventions and finally, how to respect patient confidentiality and rights.

Antimetabolites, Antineoplastic↗