Modulations of glycerophosphorylcholine and phosphorylcholine in Friend erythroleukemia cells upon in vitro-induced erythroid differentiation: a 31P NMR study

AbstractA 31P NMR study has been carried out on Friend erythroleukemia cells (FLC) induced to undergo erythroid differentiation in vitro. Significant levels of glycerophosphorylcholine (GroPCho) and phosphorylcholine (P-Cho) were identified both in the untreated cells and in their PCA extracts. In FLC treated 4 days in vitro with either dimethylsulfoxide (DMSO) or hexamethylenebisacetamide (HMBA), the intracellular concentration of P-Cho was markedly increased, whereas that of GroPCho appeared to be significantly reduced. HMBA was more effective than DMSO in producing this effect. The concomitant modulations of GroPCho and P-Cho in differentiated FLC suggest the hypothesis that erythroid differentiation involves modifications of the regulatory mechanisms controlling biosynthesis and catabolism of phospholipids

Multicenter comparative multimodality surveillance of women at genetic-familial risk for breast cancer (HIBCRIT study): interim results.

PURPOSE: To prospectively compare clinical breast examination (CBE), mammography, ultrasonography (US), and contrast material-enhanced magnetic resonance (MR) imaging for screening women at genetic-familial high risk for breast cancer and report interim results, with pathologic findings as standard. MATERIALS AND METHODS: Institutional review board of each center approved the research; informed written consent was obtained. CBE, mammography, US, and MR imaging were performed for yearly screening of BRCA1 or BRCA2 mutation carriers, first-degree relatives of BRCA1 or BRCA2 mutation carriers, or women enrolled because of a strong family history of breast or ovarian cancer (three or more events in first- or second-degree relatives in either maternal or paternal line; these included breast cancer in women younger than 60 years, ovarian cancer at any age, and male breast cancer at any age). RESULTS: Two hundred seventy-eight women (mean age, 46 years +/- 12 [standard deviation]) were enrolled. Breast cancer was found in 11 of 278 women at first round and seven of 99 at second round (14 invasive, four intraductal; eight were <or=10 mm in diameter). Detection rate per year was 4.8% (18 of 377) overall; 4.3% (11 of 258) in BRCA1 or BRCA2 mutation carriers and first-degree relatives of BRCA1 or BRCA2 mutation carriers versus 5.9% (seven of 119) in women enrolled because of strong family history; and 5.3% (nine of 169) in women with previous personal breast and/or ovarian cancer versus 4.3% (nine of 208) in those without. In six (33%) of 18 patients, cancer was detected only with MR imaging. Sensitivity was as follows: CBE, 50% (95% confidence interval [CI]: 29%, 71%); mammography, 59% (95% CI: 36%, 78%); US, 65% (95% CI: 41%, 83%); and MR imaging, 94% (95% CI: 82%, 99%). Positive predictive value was as follows: CBE, 82% (95% CI: 52%, 95%); mammography, 77% (95% CI: 50%, 92%); US, 65% (95% CI: 41%, 83%); and MR imaging, 63% (95% CI: 43%, 79%). CONCLUSION: Addition of MR imaging to the screening regimen for high-risk women may enable detection of otherwise unsuspected breast cancers. (c) RSNA, 2007

Breast cancer in kurdish women of northern Iraq: incidence, clinical stage, and case control analysis of parity and family risk

<p>Abstract</p> <p>Background</p> <p>Breast cancer in the Middle-East occurs in relatively young women and frequently presents as advanced disease. A protective effect of multiparity is not apparent, and high familial risk is reported in some countries. This study investigates breast cancer rates and clinical stage related to age in the Kurdish region of Iraq and evaluates risk associated with parity and family history. Findings are compared with nearby countries and the West.</p> <p>Methods</p> <p>Sulaimaniyah Directorate of Health records identified 539 women diagnosed with breast cancer during 2006-2008. Clinical survey forms were completed on 296 patients and on 254 age-matched controls. Age specific incidence rates were calculated from Directorate of Health population estimates.</p> <p>Results</p> <p>Average patient age was 47.4 ± 11 years and 59.5% were pre-menopausal. Diagnosis was at clinical stage 1 for 4.1%, stage 2 for 43.5%, stage 3 for 26.0%, and stage 4 for 8.1% of patients. For 18.2%, stage was unknown. Annual breast cancer incidence rates per 100,000 women peaked at 168.9 at age 55 to 59 and declined to 57.3 at 60 and above. Patients had an average of 5.0 ± 3.3 children compared to 5.4 ± 3.5 for controls, <it>P </it>= 0.16. A first degree family member had breast cancer among 11.1% of patients and 2.1% of controls (<it>P </it>< 0.001) with > 50% of these patients and controls being ≥50 years old. No statistically significant relationship was found between tumor stage and age, <it>P </it>= 0.59.</p> <p>Conclusions</p> <p>In Kurdish Iraq, breast cancer is predominantly a disease of pre-menopausal women having multiple pregnancies. For younger patients, breast cancer incidence was similar to the West and possibly higher than many Middle-Eastern countries, but unlike the West, the estimated rates declined markedly in the elderly. The familial breast cancer risk for both older and younger women was within the general population risk of Western countries. Clinical stages were advanced and indicated delays in diagnosis that were unrelated to patient age.</p

Failure patterns and survival outcomes in triple negative breast cancer (TNBC): a 15 year comparison of 448 non-Hispanic black and white women

Purpose: Triple negative breast cancer (TNBC) is a distinct subtype of breast cancer with unique pathologic, molecular and clinical behavior. It occurs more frequently in young blacks and has been reported to have a shorter disease-free interval. We undertook this study to analyze the demographic characteristics, failure patterns, and survival outcomes in this disease. Methods: A total of 448 non-Hispanic black and white women were identified over a 15 year period from 1996 to 2011. Demographic and clinical information including age, race, menopausal status, stage, tumor characteristics, and treatments were collected. Fisher’s exact test and multivariable Cox regression were used to compare failure patterns and survival outcomes between races. Results: 49 % (n = 223) were black. 59 % patients were between 41 and 60 years, with 18 % ≤40 years. 57 % were premenopausal and 89 % had grade 3 tumors. Stage II (47 %) was most frequent stage at diagnosis followed by stage III (28 %). 32 % had lymphovascular invasion. Adjusting for age, stage, and grade, there was no difference in survival outcomes (OS, DFS, LFFS, and DFFS) between the two races. 62 (14 %) patients failed locally either in ipsilateral breast or chest wall, and 19 (4 %) failed in the regional lymphatics. Lung (18 %) was the most frequent distant failure site with <12 % each failing in brain, liver and bones. Conclusion: Failure patterns and survival outcomes did not differ by race in this large collection of TNBC cases. Lung was the predominate site of distant failure followed by brain, bone, and liver. Few patients failed in the regional lymphatics

1H nuclear magnetic resonance spectroscopy characterisation of metabolic phenotypes in the medulloblastoma of the SMO transgenic mice

BACKGROUND: Human medulloblastomas exhibit diverse molecular pathology. Aberrant hedgehog signalling is found in 20-30% of human medulloblastomas with largely unknown metabolic consequences. METHODS: Transgenic mice over-expressing smoothened (SMO) receptor in granule cell precursors with high incidence of exophytic medulloblastomas were sequentially followed up by magnetic resonance imaging (MRI) and characterised for metabolite phenotypes by ¹H MR spectroscopy (MRS) in vivo and ex vivo using high-resolution magic angle spinning (HR-MAS) ¹H MRS. RESULTS: Medulloblastomas in the SMO mice presented as T₂ hyperintense tumours in MRI. These tumours showed low concentrations of N-acetyl aspartate and high concentrations of choline-containing metabolites (CCMs), glycine, and taurine relative to the cerebellar parenchyma in the wild-type (WT) C57BL/6 mice. In contrast, ¹H MRS metabolite concentrations in normal appearing cerebellum of the SMO mice were not different from those in the WT mice. Macromolecule and lipid ¹H MRS signals in SMO medulloblastomas were not different from those detected in the cerebellum of WT mice. The HR-MAS analysis of SMO medulloblastomas confirmed the in vivo ¹H MRS metabolite profiles, and additionally revealed that phosphocholine was strongly elevated in medulloblastomas accounting for the high in vivo CCM. CONCLUSIONS: These metabolite profiles closely mirror those reported from human medulloblastomas confirming that SMO mice provide a realistic model for investigating metabolic aspects of this disease. Taurine, glycine, and CCM are potential metabolite biomarkers for the SMO medulloblastomas. The MRS data from the medulloblastomas with defined molecular pathology is discussed in the light of metabolite profiles reported from human tumours

Imaging with non-FDG PET tracers: outlook for current clinical applications

Apart from the historical and clinical relevance of positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG), various other new tracers are gaining a remarkable place in functional imaging. Their contribution to clinical decision-making is irreplaceable in several disciplines. In this brief review we aimed to describe the main non-FDG PET tracers based on their clinical relevance and application for patient care

Metabolomics: A Novel Approach to Early and Noninvasive Prostate Cancer Detection

Prostate cancer (PCa) is the most commonly diagnosed visceral cancer in men and is responsible for the second highest cancer-related male mortality rate in Western countries, with increasing rates being reported in Korea, Japan, and China. Considering the low sensitivity of prostate-specific antigen (PSA) testing, it is widely agreed that reliable, age-independent markers of the presence, nature, and progression of PCa are required to facilitate diagnosis and timely treatment. Metabolomics or metabonomics has recently emerged as a novel method of PCa detection owing to its ability to monitor changes in the metabolic signature, within biofluids or tissue, that reflect changes in phenotype and function. This review outlines the physiology of prostate tissue and prostatic fluid in health and in malignancy in relation to metabolomics as well as the principles underlying the methods of metabolomic quantification. Promising metabolites, metabolic profiles, and their correlation with the presence and stage of PCa are summarized. Application of metabolomics to biofluids and in vivo quantification as well as the direction of current research in supplementing and improving current methods of detection are discussed. The current debate in the urology literature on sarcosine as a potential biomarker for PCa is reviewed and discussed. Metabolomics promises to be a valuable tool in the early detection of PCa that may enable earlier treatment and improved clinical outcomes