Telomere Length Shows No Association with BRCA1 and BRCA2 Mutation Status

This study aimed to determine whether telomere length (TL) is a marker of cancer risk or genetic status amongst two cohorts of BRCA1 and BRCA2 mutation carriers and controls. The first group was a prospective set of 665 male BRCA1/2 mutation carriers and controls (mean age 53 years), all healthy at time of enrolment and blood donation, 21 of whom have developed prostate cancer whilst on study. The second group consisted of 283 female BRCA1/2 mutation carriers and controls (mean age 48 years), half of whom had been diagnosed with breast cancer prior to enrolment. TL was quantified by qPCR from DNA extracted from peripheral blood lymphocytes. Weighted and unweighted Cox regressions and linear regression analyses were used to assess whether TL was associated with BRCA1/2 mutation status or cancer risk. We found no evidence for association between developing cancer or being a BRCA1 or BRCA2 mutation carrier and telomere length. It is the first study investigating TL in a cohort of genetically predisposed males and although TL and BRCA status was previously studied in females our results don't support the previous finding of association between hereditary breast cancer and shorter TL

Adjuvant or radical fractionated stereotactic radiotherapy for patients with pituitary functional and nonfunctional macroadenoma

Purpose: To evaluate the efficacy and toxicity of stereotactic fractionated radiotherapy (SFRT) for patients with pituitary macroadenoma (PMA).Methods and Materials: Between March 2000 and March 2009, 27 patients (male to female ratio, 1.25) with PMA underwent SFRT (median dose, 50.4 Gy). Mean age of the patients was 56.5 years (range, 20.3 - 77.4). In all but one patient, SFRT was administered for salvage treatment after surgical resection (transphenoidal resection in 23, transphenoidal resection followed by craniotomy in 2 and multiple transphenoidal resections in another patient). In 10 (37%) patients, the PMAs were functional (3 ACTH-secreting, 3 prolactinomas, 2 growth hormone-secreting and 2 multiple hormone-secretion). Three (11.1%) and 9 (33.3%) patients had PMA abutting and compressing the optic chiasm, respectively. Mean tumor volume was 2.9 +/- 4.6 cm(3). Eighteen (66.7%) patients had hypopituitarism prior to SFRT. The mean follow-up period after SFRT was 72.4 +/- 37.2 months.Results: Tumor size decreased for 6 (22.2%) patients and remained unchanged for 19 (70.4%) other patients. Two (7.4%) patients had tumor growth inside the prescribed treatment volume. The estimated 5-year tumor growth control was 95.5% after SFRT. Biochemical remission occurred in 3 (30%) patients with functional PMA. Two patients with normal anterior pituitary function before SFRT developed new deficits 25 and 65 months after treatment. The 5-year survival without new anterior pituitary deficit was thus 95.8%. Five patients with visual field defect had improved visual function and 1 patient with no visual defect prior to SFRT, but an optic chiasm abutting tumor, had a decline in visual function. The estimated 5-year vision and pituitary function preservation rates were 93.2% and 95.8%, respectively.Conclusions: SFRT is a safe and effective treatment for patients with PMA, although longer follow-up is needed to evaluate long-term outcomes. In this study, approximately 1 patient with visual field defect out of two had an improved visual

Effects of supervised exercise on cancer-related fatigue in breast cancer survivors: a systematic review and meta-analysis

Background: Cancer-related fatigue (CRF) is the most common and distressing symptom in breast cancer survivors. Approximately 40% to 80% of cancer patients undergoing active treatment suffer from CRF. Exercise improves overall quality of life and CRF; however, the specific effects of the training modalities are not well understood.Methods: This study aimed to determine the pooled effects of supervised exercise interventions on CRF in breast cancer survivors. We searched PubMed/MEDLINE, EMBASE, Scopus, CENTRAL and CINAHL databases between December 2013 and January 2014 without language restrictions. Risk of bias and methodological quality were evaluated using the PEDro score. Pooled effects were calculated with a random-effects model according to the DerSimonian and Laird method. Heterogeneity was evaluated with the I2 test.Results: Nine high-quality studies (n = 1156) were finally included. Supervised aerobic exercise was statistically more effective than conventional care in improving CRF among breast cancer survivors (SMD = −0.51, 95%CI −0.81 to −0.21), with high statistical heterogeneity (P = 0.001; I2 = 75%). Similar effects were found for resistance training on CRF (SMD = −0.41, 95%CI −0.76 to −0.05; P = 0.02; I2 = 64%). Meta-regression analysis revealed that exercise volume parameters are closely related with the effect estimates on CRF. Egger’s test suggested moderate evidence of publication bias (P = 0.04).Conclusions: Supervised exercise reduces CRF and must be implemented in breast cancer rehabilitation settings. High-volume exercises are safe and effective in improving CRF and overall quality of life in women with breast cancer. Further research is encouraged.The authors would like to acknowledge Universidad Santo Tomás, Bogotá for the financial support to the GICAEDS Group (Project: Práctica del autoexamen de seno y los conocimientos, factores de riesgo y estilos de vida relacionados al cáncer de mama en mujeres jóvenes de la USTA – Number: 4110060001-008)

Differential expression of CTLA-4 among T cell subsets

CTLA-4 (CD152), the CD28 homologue, is a costimulatory molecule with negative effects on T cell activation. In addition to its role in the termination of activation, CTLA-4 has been implicated in anergy induction and the function of regulatory cells. As an intracellular molecule, it must first relocate to the cell surface and be ligated, in order to inhibit activation. Although some studies have investigated CTLA-4 expression on CD4(+) T cells, evidence is lacking regarding the kinetics of expression, and expression on T cell subpopulations. We have investigated CTLA-4 kinetics on human purified peripheral CD4(+), naïve, memory, CD4(+)CD25(–), CD4(+)CD25(+) regulatory T cells, and T cell clones. Intracellular stores of CTLA-4 were shown to be very low in naïve T cells, whilst significant amounts were present in memory T cells and T cell clones. Cell surface CTLA-4 expression was then investigated on CD4(+)CD45RA(+) (naïve), CD4(+)CD45RO(+) (memory), CD4(+)CD25(–), and CD4(+)CD25(+) T cells. CD25 and CD45RO are both expressed by regulatory T cells. On naïve and CD4(+)CD25(–) T cells, CTLA-4 expression declined after four hours. In contrast, on memory and CD4(+)CD25(+) T cells, high levels of expression were maintained until at least 48 hours. In addition, significant CTLA-4 expression was observed on T cell clones following anergy induction, indicating the potential involvement of CTLA-4 also in this form of tolerance

Cochlear delay and medial olivocochlear functioning in children with suspected auditory processing disorder

Behavioral manifestations of processing deficits associated with auditory processing disorder (APD) have been well documented. However, little is known about their anatomical underpinnings, especially cochlear processing. Cochlear delays, a proxy for cochlear tuning, measured using stimulus frequency otoacoustic emission (SFOAE) group delay, and the influence of the medial olivocochlear (MOC) system activation at the auditory periphery was studied in 23 children suspected with APD (sAPD) and 22 typically developing (TD) children. Results suggest that children suspected with APD have longer SFOAE group delays (possibly due to sharper cochlear tuning) and reduced MOC function compared to TD children. Other differences between the groups include correlation between MOC function and SFOAE delay in quiet in the TD group, and lack thereof in the sAPD group. MOCmediated changes in SFOAE delay were in opposite directions between groups: increase in delay in TD vs. reduction in delay in the sAPD group. Longer SFOAE group delays in the sAPD group may lead to longer cochlear filter ringing, and potential increase in forward masking. These results indicate differences in cochlear and MOC function between sAPD and TD groups. Further studies are warranted to explore the possibility of cochlea as a potential site for processing deficits in APD