Breast cancer detection among young survivors of pediatric Hodgkin lymphoma with screening magnetic resonance imaging

BACKGROUND Female survivors of pediatric Hodgkin lymphoma (HL) who have received chest radiotherapy are at increased risk of breast cancer. Guidelines for early breast cancer screening among these survivors are based on little data regarding clinical outcomes. This study reports outcomes of breast cancer screening with MRI and mammography (MMG) after childhood HL. METHODS We evaluated the results of breast MRI and MMG screening among 96 female survivors of childhood HL treated with chest radiotherapy. Outcomes measured included imaging sensitivity and specificity, breast cancer characteristics, and incidence of additional imaging and breast biopsy. RESULTS Median age at first screening was 30 years, and the median number of MRI screening rounds was 3. Ten breast cancers were detected in 9 women at a median age of 39 years (range, 24-43 years). Half were invasive and half were preinvasive. The median size of invasive tumors was 8 mm (range, 3-15 mm), and none had lymph node involvement. Sensitivity and specificity of the screening modalities were as follows: for MRI alone, 80% and 93.5%, respectively; MMG alone, 70% and 95%, respectively; both modalities combined, 100% and 88.6%, respectively. All invasive tumors were detected by MRI. Additional investigations were required in 52 patients, (54%), and 26 patients (27%) required breast biopsy, with 10 patients requiring more than 1 biopsy. CONCLUSIONS Screening including breast MRI with MMG has high sensitivity and specificity in pediatric HL survivors, with breast cancers detected at an early stage, although it is associated with a substantial rate of additional investigations. Cancer 2014;120:2507–2513. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. Screening female survivors of pediatric Hodgkin Lymphoma for breast cancer with MRI and mammography detected tumors at an earlier stage than prior studies of mammography alone, although a substantial proportion of women required additional tests for benign imaging findings. The 5-year cumulative incidence of invasive or preinvasive tumors after initiating screening was 10.8%

Tetraspanin (TSP-17) Protects Dopaminergic Neurons against 6-OHDA-Induced Neurodegeneration in <i>C. elegans</i>

Parkinson's disease (PD), the second most prevalent neurodegenerative disease after Alzheimer's disease, is linked to the gradual loss of dopaminergic neurons in the substantia nigra. Disease loci causing hereditary forms of PD are known, but most cases are attributable to a combination of genetic and environmental risk factors. Increased incidence of PD is associated with rural living and pesticide exposure, and dopaminergic neurodegeneration can be triggered by neurotoxins such as 6-hydroxydopamine (6-OHDA). In C. elegans, this drug is taken up by the presynaptic dopamine reuptake transporter (DAT-1) and causes selective death of the eight dopaminergic neurons of the adult hermaphrodite. Using a forward genetic approach to find genes that protect against 6-OHDA-mediated neurodegeneration, we identified tsp-17, which encodes a member of the tetraspanin family of membrane proteins. We show that TSP-17 is expressed in dopaminergic neurons and provide genetic, pharmacological and biochemical evidence that it inhibits DAT-1, thus leading to increased 6-OHDA uptake in tsp-17 loss-of-function mutants. TSP-17 also protects against toxicity conferred by excessive intracellular dopamine. We provide genetic and biochemical evidence that TSP-17 acts partly via the DOP-2 dopamine receptor to negatively regulate DAT-1. tsp-17 mutants also have subtle behavioral phenotypes, some of which are conferred by aberrant dopamine signaling. Incubating mutant worms in liquid medium leads to swimming-induced paralysis. In the L1 larval stage, this phenotype is linked to lethality and cannot be rescued by a dop-3 null mutant. In contrast, mild paralysis occurring in the L4 larval stage is suppressed by dop-3, suggesting defects in dopaminergic signaling. In summary, we show that TSP-17 protects against neurodegeneration and has a role in modulating behaviors linked to dopamine signaling

Stem Cell Niche Dynamics: From Homeostasis to Carcinogenesis

The stem cell microenvironment is involved in regulating the fate of the stem cell with respect to self-renewal, quiescence, and differentiation. Mathematical models are helpful in understanding how key pathways regulate the dynamics of stem cell maintenance and homeostasis. This tight regulation and maintenance of stem cell number is thought to break down during carcinogenesis. As a result, the stem cell niche has become a novel target of cancer therapeutics. Developing a quantitative understanding of the regulatory pathways that guide stem cell behavior will be vital to understanding how these systems change under conditions of stress, inflammation, and cancer initiation. Predictions from mathematical modeling can be used as a clinical tool to guide therapy design. We present a survey of mathematical models used to study stem cell population dynamics and stem cell niche regulation, both in the hematopoietic system and other tissues. Highlighting the quantitative aspects of stem cell biology, we describe compelling questions that can be addressed with modeling. Finally, we discuss experimental systems, most notably Drosophila, that can best be used to validate mathematical predictions

Friction and anti-wear property of aqueous tri-block copolymer solutions in metal forming

Friction and anti-wear property of aqueous symmetrical tri-block normal PEOm-PPOn-PEOm and reverse PPOn-PEOm-PPOn copolymer solutions have been studied. The study focuses on the effect of the solution bulk temperatures and the copolymer block structures. It was found that the concentration and the length of the copolymer blocks affect the solution cloud points, friction and anti-wear property. When solution was supplied at bulk temperature above their cloud point, aqueous copolymer solutions were not able to develop effective adsorbed film resulting in high friction and severe wear. When the bulk temperatures were below the cloud point, the anti-wear property improved significantly and the dynamic friction is lower than that when the temperatures were above the cloud point. This demonstrates the importance of the supply temperature of this type of lubricant in metal forming. However by adding ethyl phosphate ester to the copolymer solutions further improved friction reducing property of the solutions was observed and the friction and anti-wear property of the lubricant become insensitive to bulk temperature. In the effort to understand the lubrication mechanism of the aqueous solutions, wear tracks were studied using scanning electron microscope (SEM) and atomic force microscope (AFM), and the surface wetting ability via contact angle measurements