Characterization of the 12q15 MDM2 and 12q13-14 CDK4 amplicons and clinical correlations in osteosarcoma.

The chromosomal region 12q13-15 is recurrently amplified in osteosarcoma (OS), but its importance in bone tumor development remains unknown. Although there are two major candidate genes (MDM2, a TP53 downregulator, and CDK4, involved in cell cycle progression) considered to be the driving genes in this region, the size of the amplicon and number of genes involved have not been determined. In this study, we used 130 classical OS and 15 parosteal OS to determine MDM2 and CDK4 amplification frequency in OS.

Oxytocin pretreatment decreases oxytocin-induced myometrial contractions in pregnant rats in a concentration-dependent but not time-dependent manner.

Recent biomolecular studies have shown that continuous exposure of human myometrial cells to oxytocin results in a significant loss of responsiveness to subsequent oxytocin stimulation, perhaps because of desensitization of the oxytocin receptors. However, it is unclear whether this phenomenon results in a reduction of the contractile activity of the uterine muscle in humans or animals. The objective of our study was to investigate the in vitro response of the uterine muscle of pregnant rats to oxytocin, following preexposure to varying concentrations of oxytocin, for varying durations.

Incidence and risk factors for cardiovascular events and death in pediatric renal transplant patients: a single center long-term outcome study.

There are considerable mortality data associated with renal transplantation in children; however, morbidity data, especially related to CV disease, are scarce. The objectives of this study were to determine incidence of non-fatal and fatal CV events and all-cause mortality in PRTx and evaluate risk factors for these conditions. Using a population-based retrospective cohort design, 274 PRTx with or without a functioning graft was followed until death or date of last contact (median follow-up 11.

COPS3 amplification and clinical outcome in osteosarcoma.

Background: Amplification of several genes that map to a region of chromosome 17p11.2, including COPS3, was observed in high-grade osteosarcoma. These genes were also shown to be overexpressed and may be involved in osteosarcoma tumorigenesis.

Invasive lobular carcinoma: to grade or not to grade.

Grading of invasive ductal carcinoma of no special type using the Nottingham combined histologic grading system provides independent prognostic information. The prognostic utility of grading invasive lobular carcinomas, however, has not been fully elucidated. In addition, the relationship between grade in invasive lobular carcinomas and expression of predictive biomarkers is less certain.

A clinicobiological model predicting survival in medulloblastoma.

Purpose: The purpose of this study was to determine the relative contributions of biological and clinical predictors of survival in patients with medulloblastoma (MB).

Experimental Design: Clinical presentation and survival information were obtained for 119 patients who had undergone surgery for MB at the Hospital for Sick Children (Toronto, Ontario, Canada) between 1985 and 2001. A tissue microarray was constructed from the tumor samples.

Amplification of the TOP2A gene does not predict high levels of topoisomerase II alpha protein in human breast tumor samples.

Recent clinical trials have suggested that patients whose breast tumors overexpress HER2 may derive particular benefit from anthracycline-containing chemotherapy compared to that without anthracycline. It has been proposed that the HER2 gene amplification reported in these tumors might mask an underlying TOP2A gene amplification that occurs frequently and concurrently with HER2 amplification. Topoisomerase II alpha, encoded by TOP2A, is a direct molecular target of anthracycline drug action and is potentially useful as a predictive marker of response to anthracycline therapy for breast cancer.

Angiotensinogen M235T genotype predicts progression in chronic renal allograft dysfunction.

Background: Genotypes of the renin-angiotensin system have been implicated in essential hypertension and in progression of native kidney diseases, but gene effects on progression in chronic renal allograft dysfunction are unclear.

Methods: To examine gene effects on long-term renal allograft function, we conducted a prospective cohort study of 210 nondiabetic renal allograft recipients younger than 36 years of age who underwent transplantation between 1980 and 1993 and were followed up through 1999. All grafts survived more than 1 year and all subjects received cyclosporine-based immunosuppression.

HER-2/neu status and tumor morphology of invasive breast carcinomas in Ashkenazi women with known BRCA1 mutation status in the Ontario Familial Breast Cancer Registry.

Background: The prevalence of BRCA1 germline mutations is greater in the Ashkenazi Jewish population than in the general North American population. The Ontario Familial Breast Cancer Registry collects clinical and family history data in familial breast carcinoma cases, and unselected Ashkenazi breast carcinomas, and acts as a tumor tissue repository.

Methods: Using this resource, we examined the tumor morphology, hormone receptor status, and HER-2/neu protein overexpression in Canadian Ashkenazi breast carcinoma patients whose germline BRCA1 mutation status is known.