Prognostic impact of MGMT promoter methylation and MGMT and CD133 expression in colorectal adenocarcinoma

Background: New biomarkers are needed for the prognosis of advanced colorectal cancer, which remains incurable by conventional treatments. O6-methylguanine DNA methyltransferase (MGMT) methylation and protein expression have been related to colorectal cancer treatment failure and tumor progression. Moreover, the presence in these tumors of cancer stem cells, which are characterized by CD133 expression, has been associated with chemoresistance, radioresistance, metastasis, and local recurrence. The objective of this study was to determine the prognostic value of CD133 and MGMT and their possible interaction in colorectal cancer patients. Methods: MGMT and CD133 expression was analyzed by immunohistochemistry in 123 paraffin-embedded colorectal adenocarcinoma samples, obtaining the percentage staining and intensity. MGMT promoter methylation status was obtained by using bisulfite modification and methylation-specific PCR (MSP). These values were correlated with clinical data, including overall survival (OS), disease-free survival (DFS), tumor stage, and differentiation grade. Results: Low MGMT expression intensity was significantly correlated with shorter OS and was a prognostic factor independently of treatment and histopathological variables. High percentage of CD133 expression was significantly correlated with shorter DFS but was not an independent factor. Patients with low-intensity MGMT expression and ≥50% CD133 expression had the poorest DFS and OS outcomes. Conclusions: Our results support the hypothesis that MGMT expression may be an OS biomarker as useful as tumor stage or differentiation grade and that CD133 expression may be a predictive biomarker of DFS. Thus, MGMT and CD133 may both be useful for determining the prognosis of colorectal cancer patients and to identify those requiring more aggressive adjuvant therapies. Future studies will be necessary to determine its clinical utility.This study was supported by FEDER, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III (FIS) through Project no. PI11/01862 and by the Consejería de Salud de la Junta de Andalucía through Project no. PI-0338. The authors are grateful to the Biobank of the Andalusian Public Healthcare System (Granada, Spain) for invaluable assistance

The Use of Data from the Parkinson's KinetiGraph to Identify Potential Candidates for Device Assisted Therapies

Device-assisted therapies (DAT) benefit people with Parkinsons Disease (PwP) but many referrals for DAT are unsuitable or too late, and a screening tool to aid in identifying candidates would be helpful. This study aimed to produce such a screening tool by building a classifier that models specialist identification of suitable DAT candidates. To our knowledge, this is the first objective decision tool for managing DAT referral. Subjects were randomly assigned to either a construction set (n = 112, to train, develop, cross validate, and then evaluate the classifier's performance) or to a test set (n = 60 to test the fully specified classifier), resulting in a sensitivity and specificity of 89% and 86.6%, respectively. The classifier's performance was then assessed in PwP who underwent deep brain stimulation (n = 31), were managed in a non-specialist clinic (n = 81) or in PwP in the first five years from diagnosis (n = 22). The classifier identified 87%, 92%, and 100% of the candidates referred for DAT in each of the above clinical settings, respectively. Furthermore, the classifier score changed appropriately when therapeutic intervention resolved troublesome fluctuations or dyskinesia that would otherwise have required DAT. This study suggests that information from objective measurement could improve timely referral for DAT

Measurement of Axial Rigidity and Postural Instability Using Wearable Sensors

Axial Bradykinesia is an important feature of advanced Parkinson's disease (PD). The purpose of this study is to quantify axial bradykinesia using wearable sensors with the long-term aim of quantifying these movements, while the subject performs routine domestic activities. We measured back movements during common daily activities such as pouring, pointing, walking straight and walking around a chair with a test system engaging a minimal number of Inertial Measurement (IM) based wearable sensors. Participants included controls and PD patients whose rotation and flexion of the back was captured by the time delay between motion signals from sensors attached to the upper and lower back. PD subjects could be distinguished from controls using only two sensors. These findings suggest that a small number of sensors and similar analyses could distinguish between variations in bradykinesia in subjects with measurements performed outside of the laboratory. The subjects could engage in routine activities leading to progressive assessments of therapeutic outcomes

Objective measurement in routine care of people with Parkinson's disease improves outcomes

It is common in medicine to titrate therapy according to target ranges of objectively measured parameters. Objective measurement of motor function is available for Parkinson's Disease (PD), making it possible to optimise therapy and clinical outcomes. In this study, an accelerometry based measurement and predefined target ranges were used to assess motor function in a Northern Tasmania PD cohort managed by a Movement Disorder clinic. Approximately 40% (n = 103) of the total PD population participated in this study and motor scores were within target in 22%. In the 78% above target, changes in oral therapy were recommended in 74%, Advanced Therapy in 12% and treatment was contraindicated in 9%. Following changes in oral therapy, there was a further objective measurement and clinical consultation to establish whether scores had reached target range: if so subjects left the study, otherwise further changes of therapy were recommended (unless contraindications were present). Seventy-seven cases completed the study, with 48% achieving target (including 22% at outset), Advanced Therapy recommended in 19% and contraindications preventing any change in therapy in 17%. In the 43% of cases in whom oral therapy was changed, total UPDRS improved significantly (effect size = 8) as did the PDQ39 in cases reaching target. NMS Quest and MOCA scores also improved significantly. This study shows that many people in a representative cohort of PD would benefit from objective assessment and treatment of their PD features against a target

The use of accelerometry as a tool to measure disturbed nocturnal sleep in Parkinson's disease

Sleep disturbances are common in Parkinson's disease (PD). We used the Parkinson's KinetiGraph (PKG), an objective movement recording system for PD to assess night time sleep in 155 people aged over 60 and without PD (controls), 72 people with PD (PwP) and 46 subjects undergoing a Polysomnogram (PSG: 36 with sleep disorder and 10 with normal sleep). The PKG system uses a wrist worn logger to capture acceleration and derive a bradykinesia score (BKS) every 2 min over 6 days. The BKS ranges from 0-160 with higher scores associated with lesser mobility. Previously we showed that BKS > 80 were associated with day time sleep and used this to produce scores for night time sleep: Efficiency (Percent time with BKS > 80), Fragmentation (Average duration of runs of BKS > 80) and Sleep Quality (BKS > 111 as a representation of atonia). There was a fair association with BKS score and sleep level as judged by PSG. Using these PKG scores, it was possible to distinguish between normal and abnormal PSG studies with good Selectivity (86%) and Sensitivity (80%). The PKG's sleep scores were significantly different in PD and Controls and correlated with a subject's self-assessment (PDSS 2) of the quality, wakefulness and restlessness. Using both the PDSS 2 and the PKG, it was apparent that sleep disturbances were apparent early in disease in many PD subjects and that subjects with poor night time sleep were more likely to have day time sleepiness. This system shows promise as a quantitative score for assessing sleep in Parkinson's disease

The Iranian Society of Nuclear Medicine practical guideline on radioligand therapy in metastatic castration-resistant prostate cancer using 177Lu-PSMA

Prostate-specific membrane antigen (PSMA) is a type II transmembrane protein, which is anchored in the cell membrane of prostate epithelial cells. It is highly expressed on prostate epithelial cells and strongly up-regulated in prostate cancer. Although, 177Lu-PSMA has been recently introduced for radionuclide therapy of metastatic castration-resistant prostate cancer (mCRPC) with continuously increasing interest and use worldwide. This guideline is intended to assist nuclear medicine physicians in evaluating and managing patients with mRCPC for whom radioligand therapy (RLT) using 177Lu-PSMA is a promising treatment option. In addition, more information could be provided by subsequent investigative studies in the field of RLT. © 2018 Tehran University of Medical Sciences. All rights reserved

The Iranian Society of Nuclear Medicine practical guideline on radioligand therapy in metastatic castration-resistant prostate cancer using 177Lu-PSMA

Prostate-specific membrane antigen (PSMA) is a type II transmembrane protein, which is anchored in the cell membrane of prostate epithelial cells. It is highly expressed on prostate epithelial cells and strongly up-regulated in prostate cancer. Although, 177Lu-PSMA has been recently introduced for radionuclide therapy of metastatic castration-resistant prostate cancer (mCRPC) with continuously increasing interest and use worldwide. This guideline is intended to assist nuclear medicine physicians in evaluating and managing patients with mRCPC for whom radioligand therapy (RLT) using 177Lu-PSMA is a promising treatment option. In addition, more information could be provided by subsequent investigative studies in the field of RLT. © 2018 Tehran University of Medical Sciences. All rights reserved