Smile esthetics from odontology students' perspectives.

Objectives: To analyze the perception of smile esthetics and its alterations in dental degree students; to determine whether there are differences in that perception among students in different study years on those courses and between genders; and to determine if the circumstance of having received prior orthodontic treatment could influence that perception.

Material And Methods: Students (n = 192) in different study years of the dental degree course at the University of Valencia, Spain, analyzed two photographs of a patient in which, by means of computer software, midline diastema, upper and lower midlines, crown length of the maxillary right central incisor, occlusal cant, and "gummy" smile were altered. Students assessed the photographs on a scale from 1 to 10.

Analysis of competing risks of causes of death and their variation over different time periods in Hodgkin's disease.

Purpose: Hodgkin's disease is considered a model of curable illness. However, long-term studies show excessive mortality in relation to the general population. We studied the various causes of death by use of competing risks and their evolution over the years.

Implication of polycomb members Bmi-1, Mel-18, and Hpc-2 in the regulation of p16INK4a, p14ARF, h-TERT, and c-Myc expression in primary breast carcinomas.

Purpose: Deregulation of mammalian Polycomb group (PcG) members may contribute to human carcinogenesis. p16INK4a and p14ARF tumor suppressors, human telomerase reverse transcriptase (h-TERT), and oncoprotein c-Myc have been implicated in the regulation of the cell cycle and proliferation mediated by PcG proteins, mainly Bmi-1, in mice and in cell culture experiments. Here, we examine whether these in vitro findings can be extrapolated to the in vivo situation.

Extracellular tumor DNA in plasma and overall survival in breast cancer patients.

In this study, we examined whether free DNA extracted from the plasma of breast cancer patients, characterized as tumor DNA, could predict the overall survival (OS) of breast cancer patients. In total, 147 patients and 35 healthy controls were studied. Plasma DNA was assessed in the same way as tumor DNA, following identification of similar alterations in polymorphic markers and TP53 gene mutations.

The GADD45, ZBRK1 and BRCA1 pathway: quantitative analysis of mRNA expression in colon carcinomas.

GADD45 is a growth arrest-associated gene that is induced in response to DNA damage. This gene is a target for coordinate regulation by both ZBRK1 and BRCA1. A sequence within intron 3 of GADD45 supports specific assembly of the ZBRK1/BRCA1 complex.

Irinotecan combined or alternated with bolus 5-fluorouracil and folinic acid versus the Mayo Clinic regimen in the first-line therapy of advanced colorectal cancer.

The objective of this study was to assess the efficacy and safety of two regimens of irinotecan, combined or alternated with bolus 5-fluorouracil (5-FU) and folinic acid (FA), and the Mayo Clinic regimen as first-line therapy for colorectal cancer (CRC). A total of 152 patients with advanced CRC were randomised, and 149 patients were treated intravenously by irinotecan 125 mg/m2, FA 20 mg/m2 followed by 5-FU 500 mg/m2 bolus, weekly for 4 weeks (arm A, Saltz regimen; n=46), or irinotecan 350 mg/m2 alternating with FA 20 mg/m2/day followed by 5-FU bolus 425 mg/m2/day for 5 days (arm B; n=53), or FA 20 mg/m2/ day followed by 5-FU bolus 425 mg/m2/day over 5 days every 4 weeks (arm C, Mayo Clinic regimen; n=50). Patients were analyzed for tumor response, time to progression, overall survival, safety and quality of life.

Overexpression of p16INK4a correlates with high expression of p73 in breast carcinomas.

The p16-cyclin D-Cdk4(6)-pRB-E2F and p73 pathways are involved in the control of cell-cycle progression, and genetic lesions in both pathways frequently occur in breast carcinomas and other human cancers. The p16INK4a gene is involved in regulation of the G1/S transition, and when overexpressed, the p73 gene activates transcription of p53-responsive genes and promotes apoptosis. These pathways are related, for instance, p73 is also downstream of E2F-1, since E2F-1 induces p73-mediated apoptosis in the absence of p53.

Prognostic factors in Hodgkin's disease.

Hodgkin's disease (HD) is a curable tumoral disease. However, there are groups of patients who suffer relapse and the identification of prognostic factors and the adaptation of treatments to individual risk is one the lines of investigation in this disease. A study was performed on 526 patients diagnosed of HD in our hospital between January 1967 and September 2001.

Promoter methylation of the PTEN gene is a common molecular change in breast cancer.

About 25-50% of women with Cowden disease, a syndrome associated with germ-line mutations of the PTEN gene (at 10q23), develop breast cancer (BC), but PTEN mutations have been found in only 5% of sporadic BCs. However, 29-48% of BCs display loss of heterozygosity in 10q23, and about 40% of BCs show a decrease or absence of PTEN protein levels at the time of diagnosis. Promoter hypermethylation has been identified as an alternative mechanism of tumor-suppressor gene inactivation, but its importance in PTEN silencing in sporadic BC is unknown.

Altered expression of the ZBRK1 gene in human breast carcinomas.

The ZBRK1 protein is a member of the KRAB-ZFP family. It functions as a transcriptional repressor by binding to its recognition sequence within target genes and producing a nucleoprotein complex containing its co-repressor BRCA1 and also probably the co-repressor KAP-1. Alterations that affect the ZBRK1 gene have not been reported in human tumours.

Intronic deletion affecting a negative regulatory region of TP73 is related to breast and colorectal carcinomas.

The TP73 gene encodes a nuclear protein that has high homology with TP53. TP73 is rarely mutated in human cancer. The presence of a 1-kb regulatory fragment within the first intron of TP73 was recently reported.

A multicenter phase II study of irinotecan in patients with advanced colorectal cancer previously treated with 5-fluorouracil.

This multicenter, open-label, phase II study was performed to assess the efficacy and toxicity of irinotecan 350 mg/m2 intravenously every 3 weeks in patients with advanced colorectal cancer (CRC) previously treated with 5-fluorouracil (5-FU). The study enrolled 115 patients and a total of 558 cycles (median, 6 per patient) were administered. The overall objective response rate on an intent-to-treat basis was 18% (with 1 complete response and 20 partial responses), whereas 42 patients (37%) showed stable disease.

Prevalence of aberrant methylation of p14ARF over p16INK4a in some human primary tumors.

The INK4a/ARF locus encodes two unrelated tumor suppressor proteins, p16INK4a and p14ARF, which participate in the two main cell-cycle control pathways, p16-Rb and p14-p53. Methylation of CpG promoter islands has been described as a mechanism of gene silencing. Exon 1 of the p16INK4a gene and the p14ARF promoter gene reside within CpG islands.

Intratumoral heterogeneity in microsatellite alterations in BRCA1 and PTEN regions in sporadic colorectal cancer.

Background: Chromosome regions 17q21 (BRCA1) and 10q23 (PTEN) have been found deleted in colorectal cancer.

Methods: We studied the frequency of loss of heterozygosity (LOH) in these 2 regions in 214 patients with only 1 sample per tumor and in 100 patients with several samples per tumor. Three microsatellite markers of each region were used for the LOH test.

The management of stage I-II supradiaphragmatic Hodgkin's disease with chemotherapy alone.

The treatment of choice for patients with early stage Hodgkin's disease (HD) has been extended field or subtotal nodal irradiation. Remission rates of over 95% have been obtained, however, about 5% of stage I and II patients will suffer from progressive disease while on therapy and an additional 15-20% will relapse. Chemotherapy (Ch) alone has not been adequately tested in early-stage HD.

The topoisomerase IIalpha expression correlates with survival in patients with advanced Hodgkin's lymphoma.

Purpose: Topoisomerase (Topo) II isoenzymes are the targets for drugs, such as epidophyllotoxins and doxorubicin. The aim of this study was to determine whether the expression of Topo IIalpha and Ki67 in advanced Hodgkin's disease (HD) played a role as a prognostic factor or predictor of response to treatment.

Experimental Design: Forty-two patients who were homogeneously treated and had a long-term follow-up were selected for the study.

Concomitant expression of p16INK4a and p14ARF in primary breast cancer and analysis of inactivation mechanisms.

The INK4a/ARF locus encodes two tumour suppressor proteins, p16INK4a and p14ARF, which act in the two main cell-cycle control pathways, p16-Rb and p14-p53 respectively. The present study examined the mRNA expression of these genes by reverse transcription-polymerase chain reaction (RT-PCR), and the inactivation mechanisms that alter these levels, in 100 primary breast carcinomas. Furthermore, the interdependence of these mechanisms was examined, since it has been reported that p14ARF is altered in most tumours in concordance with p16INK4a.

Tumor DNA in plasma at diagnosis of breast cancer patients is a valuable predictor of disease-free survival.

Purpose: We examine prospectively whether the presence of plasma DNA with tumor characteristics before mastectomy is a predictive factor related to recurrence and disease-free survival (DFS).

Experimental Design: A series of 147 patients with breast carcinomas, selected sequentially, was analyzed. The characterization of plasma DNA, based on similar alterations in tumor and plasma DNA, was achieved with six polymorphic markers (D17S855, D17S654, D16S421, TH(2), D10S197, and D9S161) and mutations in the TP53 gene.

p14ARF promoter hypermethylation in plasma DNA as an indicator of disease recurrence in bladder cancer patients.

Purpose: Several genes are reported to be implicated in bladder carcinogenesis, including p53, p16INK4a, pRb, erbB-2, Cyclin D1, H-ras, EGFR, and c-myc. Gene alterations in plasma DNA identical to those observed within the tumor have been detected in various types of neoplasia.

Experimental Design: We analyzed loss of heterozygosity in six microsatellite markers (D17S695, D17S654, D13S310, TH2, D9S747, and D9S161), p53 and K-ras mutations, and the promoter status of p14ARF and p16INK4a in the mononuclear normal blood cells, tumor, and plasma DNA of 27 bladder cancer patients.

Persistence of tumor DNA in plasma of breast cancer patients after mastectomy.

Background: We investigated tumor DNA changes before and after mastectomy in the plasma of breast cancer patients with no disseminated disease and eventually investigated these changes' relationship to specific pathological parameters of the tumors.

Methods: We studied 41 patients. DNA extracted from tumor and normal breast tissues, mononuclear blood cells, and plasma was used for molecular studies.