Gene expression profiling reveals novel biomarkers in nonsmall cell lung cancer.

The development of reliable gene expression profiling technology is having an increasing impact on our understanding of lung cancer biology. Our study aimed to determine any correlation between the phenotypic heterogeneity and genetic diversity of lung cancer. Microarray analysis was performed on a set of 46 tumor samples and 45 paired nontumor samples of nonsmall cell lung cancer (NSCLC) samples to establish gene signatures in primary adenocarcinomas and squamous-cell carcinomas, determine differentially expressed gene sequences at different stages of the disease and identify sequences with biological significance for tumor progression.

[Comparison of the severity index in Cushing's syndrome between patients with endogenous and iatrogenic disease].

Unlabelled: Cushing's syndrome (CS) is a rare condition that is most often secondary to glucocorticoid (GC) intake. Definitive data on the distinction between endogenous CS (ECS) and yatrogenic (YCS) have not been published.

Objective: To compare the severity index in Cushing's syndrome (SICS) score in the two etiologies, endogenous and yatrogenic, and identify which clinical parameters of the SICS are the most frequent and representative of CS.

P450C17 (CYP17) deficiency in native Mexican patient with a novel CYP17A1 mutation.

Objective: To report a case of congenital adrenal hyperplasia due to CYP17 deficiency caused by a novel CYP17A1 mutation.

Methods: We describe the clinical, biochemical, genetic, and radiologic findings of a sporadic case of congenital adrenal hyperplasia due to CYP17 deficiency in a young patient.

Results: An 18-year-old woman presented with hypogonadism and progressive muscle weakness and had not yet undergone thelarche, adrenarche, and menarche.

Gene expression signatures in breast cancer distinguish phenotype characteristics, histologic subtypes, and tumor invasiveness.

Background: The development of reliable gene expression profiling technology is having an increasing impact on the understanding of breast cancer biology.

Methods: In this study, microarray analysis was performed to establish gene signatures for different breast cancer phenotypes, to determine differentially expressed gene sequences at different stages of the disease, and to identify sequences with biologic significance for tumor progression. Samples were taken from patients before their treatment.

Analysis of population characteristics related to the total effective xenoestrogen burden: a biomarker of xenoestrogen exposure in breast cancer.

To analyse the link between breast cancer and the combined effect of environmental xenoestrogens, we developed, standardised and applied a biomarker of exposure to assess the total effective xenoestrogen burden (TEXB) in human adipose tissue in a case-control study. Environmental oestrogens (TEXB-alpha) are separated from endogenous oestrogens (TEXB-beta), and the combined oestrogenic effect is determined from its proliferative effect (E-Screen assay). The aim of the study was to identify potential confounders, effect modifiers or other covariates associated with higher TEXB levels.

Biomonitoring of environmental estrogens in human tissues.

Two examples are presented for the application of the total effective xenoestrogen burden as biomarker of chemical exposure measured in tissue samples from patients recruited for two case-control studies. The first study focused on environmental chemicals with hormone mimicking activity, the so-called environmental estrogens, and their participation in the etiology of breast cancer. The second study investigated mother-child exposure to persistent organochlorine chemicals and assessed their combined effect on the risk of male urogenital malformations in the newborn.

Environmental and lifestyle factors for organochlorine exposure among women living in Southern Spain.

Southern Spain has the largest area of intensive greenhouse agriculture in Europe, and may constitute a special case of occupational and female exposure, because this type of farming requires considerable pesticide use and employs many women. We measured adipose tissue levels of 14 organochlorine pesticides in 458 women living in this area and analyzed the relationship between pesticide level/presence and sociodemographic characteristics, reproductive history or life-style factors that may influence this exposure. Pesticide presence was determined by gas chromatography with electron-capture detector.

Effect on tumour control of time interval between surgery and postoperative radiotherapy: an empirical approach using Monte Carlo simulation.

In this work, a procedure, based on Monte Carlo techniques, to analyse the effect on the tumour control probability of the time interval between surgery and postoperative radiotherapy is presented. The approach includes the tumour growth as well as the survival of tumour cells undergoing fractionated radiotherapy. Both processes are described in terms of the binomial distribution.

Breast cancer risk and the combined effect of environmental estrogens.

Objective: The present study aimed to determine whether the combined effects of environmental estrogens measured as the total effective xenoestrogen burden (TEXB-alpha) are a risk factor for breast cancer over and above the risk potentially linked to specific pesticides.

Methods: We measured the levels of 16 organochlorine pesticides as well as TEXB in adipose tissue of 198 women at the time of breast cancer diagnosis. These were compared with findings in 260 age and hospital matched control women without breast cancer.

Human exposure to endocrine disrupters: standardisation of a marker of estrogenic exposure in adipose tissue.

In many epidemiological studies based on the direct measurement of exposure to organochlorines, the chemicals of concern are determined directly from adipose tissue samples. Although the measurement of all possible organochlorines, their metabolites, isomers and congeners may be desirable, it is expensive and time-consuming and many chemicals with hormonal activity may not yet have been identified. Testing systems are therefore required to screen for estrogenicity and to identify appropriate biomarkers of human exposure.

Determination of bisphenol A and related aromatic compounds released from bis-GMA-based composites and sealants by high performance liquid chromatography.

Most of the composites and sealants used in dentistry are based on bisphenol A diglycidylether methacrylate (Bis-GMA). Reports revealed that in situ polymerization is not complete and that free monomers can be detected by different analytic methods. Concerns about the estrogenicity of bisphenol A (BPA) and other aromatic components leached from commercial products have been expressed.

[Critical vision in the treatment of invasive vesical cancer with ionizing radiation].

Objective: To review the treatment of invasive bladder cancer with ionizing radiation.

Methods: Patient selection criteria, prognostic factors, treatment of different tumor types with radiation using different strategies alone or in combination with chemotherapy are analyzed in the literature.

Results/conclusions: The role of radiotherapy in the treatment of invasive carcinoma of the bladder is crucial: 1) preoperative radiotherapy in combination with radical surgery achieves results comparable with those of cystectomy in terms of survival and a higher local control rate; 2) used in combination with cisplatin post-TUR, irradiation is highly effective for local control of the tumor and bladder preservation, with complete remission rates ranging from 60-70%, which are higher than those of radical cystectomy; 3) in this latter therapeutic modality the effect of radiotherapy is dose-related and is influenced by factors such as tumor size, presence or absence of urinary obstruction, presence of multiple lesions on the bladder wall and extravesical spread.

DNA damage and prediction of radiation response in lymphocytes and epidermal skin human cells.

The success of radiotherapy in eradicating tumours depends on the total radiation dose, but what limits this dose is the tolerance of the normal tissues within the treatment volume. Studies involving fibroblast survival have demonstrated the theoretical feasibility of a predictive assay of radiation sensitivity, but such an assay is still far from clinical application. Using pulsed-field gel electrophoresis (PFGE), we have quantified the initial "apparent" number of DNA double-strand breaks (dsb) induced by the radiation as an alternative measure of sensitivity in 2 different normal cell types from the same patients, epidermal skin cells and lymphocytes.

The estrogenicity of bisphenol A-related diphenylalkanes with various substituents at the central carbon and the hydroxy groups.

The chemical structure of hydroxylated diphenylalkanes or bisphenols consists of two phenolic rings joined together through a bridging carbon. This class of endocrine disruptors that mimic estrogens is widely used in industry, particularly in plastics. Bisphenol F, bisphenol A, fluorine-containing bisphenol A (bisphenol AF), and other diphenylalkanes were found to be estrogenic in a bioassay with MCF7 human breast cancer cells in culture (E-SCREEN assay).

Juvenile kyphosis: effects of different variables on conservative treatment outcome.

We reviewed the records of 212 patients with idiopathic or Scheuermann-type juvenile kyphosis (Scheuermann's disease). The 200 patients available for follow-up were divided into three groups depending on the degree of angular deformity, and the influence of different variables on treatment outcome in each group was investigated. A very influential positive variable was combined treatment with a body cast plus brace; exercise treatment also produced acceptable results.

A comparison of p53 and p16 expression in human tumor cells treated with hyperthermia or ionizing radiation.

To assess the potential relationship between p53 and p16 proteins in the cellular response to stress, we have examined the levels of these proteins in a series of human tumor cell lines after treatment with either ionizing radiation or hyperthermia. We found that cells with abnormal radiation-induced G1 arrest (non-functional p53) had significantly higher constitutive levels of p16 than cells showing a normal G1 arrest (functional p53). Time-course experiments were done to test the effect of gamma-irradiation on intracellular levels of p16.

Radiosensitivity of human breast cancer cell lines of different hormonal responsiveness. Modulatory effects of oestradiol.

Treatments which inhibit or retard progression of the cell through the cell cycle have been reported to reduce the effectiveness of ionizing radiation by increasing cellular radioresistance. We studied cellular radiosensitivity and radiation-induced DNA damage (double-strand break, dsb) in both hormone-sensitive and non-sensitive human breast cancer cell lines. After 72h of culture in an oestradiol-deprived medium, MCF-7 BUS and T47D B8 breast cancer cells showed a significant delay in growth, whereas no effect was seen in EVSA-T cell line.

Relationship between DNA damage, rejoining and cell killing by radiation in mammalian cells.

The prevailing hypothesis on the mechanism of radiation-induced cell killing identifies the genetic material deoxyribonucleic acid (DNA) as the most important subcellular target at biologically relevant doses. In this review we present new data and summarize the role of the DNA double-strand breaks (dsb) induced by ionizing radiation and DNA dsb rejoining as determinants of cellular radiosensitivity. When cells were irradiated at high dose-rate, two molecular end-points were identified which often correlated with radiosensitivity: (1) the apparent number of DNA dsb induced per Gy per DNA unit and (2) the half-time of the fast component of the DNA dsb rejoining kinetics.

Estrogenicity of resin-based composites and sealants used in dentistry.

We tested some resin-based composites used in dentistry for their estrogenic activity. A sealant based on bisphenol-A diglycidylether methacrylate (bis-GMA) increased cell yields, progesterone receptor expression, and pS2 secretion in human estrogen-target, serum-sensitive MCF7 breast cancer cells. Estrogenicity was due to bisphenol-A and bisphenol-A dimethacrylate, monomers found in the base paste of the dental sealant and identified by mass spectrometry.

Relationship between p53 status and radiosensitivity in human tumour cell lines.

We examined the relationship between p53 levels before and after irradiation, radiation-induced cell cycle delays, apoptotic cell death and radiosensitivity in a panel of eight human tumour cell lines. The cell lines differed widely in their clonogenic survival after radiation, (surviving fraction at 2 Gy: SF2=0.18-0.

Relationship between doxorubicin cell sensitivity, drug-induced DNA double-strand breaks, glutathione content and P-glycoprotein in mammalian tumor cells.

We have measured the cytotoxic effect of 1 h exposure to doxorubicin (DOX) on a panel of tumor cell lines. Cellular effects were measured by monolayer colony-forming assay and a colorimetric cytotoxicity assay. As parameters of chemosensitivity we used two different end-points: the dose of DOX that reduces to 50% the number of colonies (ID50) and the dose of DOX that reduces the final optical density to 50% of the control value (IC50).

The E-screen assay: a comparison of different MCF7 cell stocks.

MCF7 human breast cancer cells have been studied extensively as a model for hormonal effects on breast cancer cell growth and specific protein synthesis. Because the proliferative effect of natural estrogen is considered the hallmark of estrogen action, it was proposed that this property be used to determine whether a substance is an estrogen. The E-screen assay, developed for this purpose, is based on the ability of MCF7 cells to proliferate in the presence of estrogens.

Xenoestrogens released from lacquer coatings in food cans.

We present data showing that some foods preserved in lacquer-coated cans and the liquid in them may acquire estrogenic activity. Hormonal activity was measured using the E-screen bioassay. The biological activity of vegetables packed in cans was a result of plastic monomers used in manufacturing the containers.

Radiation-induced DNA double-strand break rejoining in human tumour cells.

Five established human breast cancer cell lines and one established human bladder cancer cell line of varying radiosensitivity have been used to determine whether the rejoining of DNA double-strand breaks (dsbs) shows a correlation with radiosensitivity. The kinetics of dsb rejoining was biphasic and both components proceeded exponentially with time. The half-time (t1/2) of rejoining ranged from 18.