Adaptive changes in physiological and perceptual responses during 10-day heat acclimation training using a water-perfused suit

Abstract Background While active heat acclimation strategies have been robustly explored, not many studies highlighted passive heat acclimation strategies. Particularly, little evidence demonstrated advantages of utilizing a water-perfused suit as a passive heating strategy. This study aimed to explore heat adaptive changes in physiological and perceptual responses during 10-day heat acclimation training using a water-perfused suit. Methods Nineteen young males were divided into three experimental groups: exercise condition (N = 6, HAEXE, 1-h exercise at 6 km h−1 followed by 1-h rest in a sitting position), exercise and passive heating condition (N = 6, HAEXE+SUIT, 1-h exercise at 6 km h−1 followed 1-h passive heating in a sitting position), and passive heating condition (N = 7, HASUIT, 2-h passive heating in a sitting position). All heating programs were conducted for 10 consecutive days in a climatic chamber maintained at 33 °C with 60% relative humidity. The passive heating was conducted using a newly developed water-perfused suit with 44 °C water. Results Greater whole-body sweat rate and alleviated perceptual strain were found in HASUIT and HAEXE+SUIT after 5 and/or 10 days (P < 0.05) but not in the exercise-only condition (HAEXE). Lower rectal temperature and heart rate were found in all conditions after the training (P < 0.05). Heat adaptive changes appeared earlier in HASUIT except for sweat responses. Conclusions For heat acclimation in hot humid environments, passive and post-exercise heat acclimation training using the suit (water inflow temperature 44 °C) were more effective than the mild exercise (1-h walking at 6 km h−1). This form of passive heating (HASUIT) may be an especially effective strategy for the elderly and the disabled who are not able to exercise in hot environments

Chfr is linked to tumour metastasis through the downregulation of HDAC1

Chfr is a ubiquitin ligase that functions in the mitotic checkpoint by delaying entry into metaphase in response to mitotic stress. It has been suggested that Chfr is a tumour suppressor as Chfr is frequently silenced in human cancers. To better understand how Chfr activity relates to cell-cycle progression and tumorigenesis, we sought to identify Chfr-interacting proteins using affinity purification combined with mass spectrometry. Histone deacetylase 1 (HDAC1), which represses transcription by deacetylating histones, was newly isolated as a Chfr-interacting protein. Chfr binds and downregulates HDAC1 by inducing its polyubiquitylation, both in vitro and in vivo. Ectopic expression of Chfr in cancer cells that normally do not express it results in downregulation of HDAC1, leading to upregulation of the Cdk inhibitor p21^(CIP1/WAF1) and the metastasis suppressors KAI1 and E-cadherin. Coincident with these changes, cells arrest in the G1 phase of the cell cycle and become less invasive. Collectively, our data suggest that Chfr functions as a tumour suppressor by regulating HDAC1

Genomic alterations of primary tumor and blood in invasive ductal carcinoma of breast

<p>Abstract</p> <p>Background</p> <p>Genomic alterations are important events in the origin and progression of various cancers, with DNA copy number changes associated with progression and treatment response in cancer. Array CGH is potentially useful in the identification of genomic alterations from primary tumor and blood in breast cancer patients. The aim of our study was to compare differences of DNA copy number changes in blood and tumor tissue in breast cancer.</p> <p>Methods</p> <p>DNA copy number changes in blood were compared to those in tumor tissue using array-comparative genomic hybridization in samples obtained from 30 breast cancer patients. The relative degree of chromosomal changes was analyzed using log2 ratios and data was validated by real-time polymerase chain reaction.</p> <p>Results</p> <p>Forty-six regions of gains present in more than 30% of the tissues and 70 regions of gains present in more than 30% of blood were identified. The most frequently gained region was chromosome 8q24. In total, agreement of DNA copy numbers between primary tumor and blood was minimal (Kappa = 0.138, p < 0.001).</p> <p>Conclusion</p> <p>Although there was only a slight agreement of DNA copy number alterations between the primary tumor and the blood samples, the blood cell copy number variation may have some clinical significance as compared to the primary tumor in IDC breast cancer patients.</p

Patient-Specific Orthotopic Glioblastoma Xenograft Models Recapitulate the Histopathology and Biology of Human Glioblastomas In Situ

SummaryFrequent discrepancies between preclinical and clinical results of anticancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable “patient tumor’s phenocopy” that represents molecular and functional heterogeneity of GBMs