Glioblastoma (GBM) is a highly malignant type of primary brain tumor with a high mortality rate. Although the current standard therapy consists of surgery followed by radiation and temozolomide (TMZ), chemotherapy can extend patient’s post-operative survival but most cases eventually demonstrate resistance to TMZ. O6-methylguanine-DNA methyltransferase (MGMT) repairs the main cytotoxic lesion, as O6-methylguanine, generated by TMZ, can be the main mechanism of the drug resistance. In addition, mismatch repair and BER also contribute to TMZ resistance. TMZ treatment can induce self-protective autophagy, a mechanism by which tumor cells resist TMZ treatment. Emerging evidence also demonstrated that a small population of cells expressing stem cell markers, also identified as GBM stem cells (GSCs), contributes to drug resistance and tumor recurrence owing to their ability for self-renewal and invasion into neighboring tissue. Some molecules maintain stem cell properties. Other molecules or signaling pathways regulate stemness and influence MGMT activity, making these GCSs attractive therapeutic targets. Treatments targeting these molecules and pathways result in suppression of GSCs stemness and, in highly resistant cases, a decrease in MGMT activity. Recently, some novel therapeutic strategies, targeted molecules, immunotherapies, and microRNAs have provided new potential treatments for highly resistant GBM cases. In this review, we summarize the current knowledge of different resistance mechanisms, novel strategies for enhancing the effect of TMZ, and emerging therapeutic approaches to eliminate GSCs, all with the aim to produce a successful GBM treatment and discuss future directions for basic and clinical research to achieve this end.
The present study aimed to compare the accuracy of estimating the percentage of total body fat (%TBF) among three bioelectrical impedance analysis (BIA) devices: a singlefrequency BIA with four tactile electrodes (SF-BIA4), a single-frequency BIA with eight tactile electrodes (SF-BIA8) and a multi-frequency BIA with eight tactile electrodes (MF-BIA8). Dual-energy x-ray absorptiometry (DXA) and hydrostatic weighing (HW) were used as references for the measured values. Forty-five healthy college student volunteers (21 males: 172.9Ϯ5.5 cm and 65.8Ϯ9.1 kg and 24 females: 160.7Ϯ6.6 cm, 52.6Ϯ6.2 kg) were the subjects. Correlation coefficients between the BIA measurements and the references were calculated. The standard error of estimation (SEE) was calculated by regression analysis when estimating the reference measures (DXA and HW) from the predictor (SF-BIA4, SF-BIA8 and MF-BIA8). The differences in %TBF between the reference and the predictor, calculated by the reference minus the predictor, were plotted against the %TBF measured by the references. The MF-BIA 8 here showed the highest correspondence to the reference and the least estimation error compared with the other BIA methods. It is considered that there is a limit to directly estimate FFM from a regression equation using impedance, weight, height and age as independent variables, and that %TBF can be more accurately estimated by measuring segmental impedances using eight electrodes and multi-frequency electric currents and then estimating total body water from these impedances.
This study aimed to determine the factor structure of the center of foot pressure (CFP) movement during static upright posture, and to objectively categorize and summarize parameters to evaluate CFP movement. The subjects were 220 healthy young males and females. The measurement of CFP was carried out 3 times with 1 min rest and the mean of trials 2 and 3 was used for the analysis. The measurement device was an Anima's stabilometer G5500. The data sampling frequency was 20 Hz. Thirty-four parameters with high reliability were selected from the following 6 domains except for the center position which is a fundamental attribute: distance, distribution of amplitude, area, velocity, power spectrum, and body sway vector. Factor analysis (principal factor method and promax rotation) was applied to a correlation matrix consisting of 32 parameters. Four factors abstracted were interpreted as follows; unit time sway, front and back sway, left and right sway and high frequency band of power spectrum. The reliability coefficient (ICCϭ0.89-0.95) and the congruence coefficient (fϭ0.80-0.97) between factors abstracted from the original and the cross-validity groups were very high. It was considered that the CFP movement consists of the above 4 factors that evaluate the amount of body sway and can be synthetically evaluated by them.
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