Ganoderma lucidum derived ganoderenic acid B reverses ABCB1-mediated multidrug resistance in HepG2/ADM cells. PUMID/DOI：DOI: 10.3892/ijo.2015.2925 Int J Oncol. 2015 May;46(5):2029-38. Chemotherapy is one of the most common therapeutic option for metastatic tumors and hematological malignancies. ABCB1-mediated multidrug resistance is the major obstacle for chemotherapy. Natural products with diversified structures are ideal source of ABCB1 modulators. Ganoderenic acid B, a lanostane-type triterpene isolated from Ganoderma lucidum, exhibited potent reversal effect on ABCB1-mediated multidrug resistance of HepG2/ADM cells to doxorubicin, vincristine and paclitaxel. Similarly, ganoderenic acid B could also significantly reverse the resistance of ABCB1-overexpressing MCF-7/ADR cells to doxorubicin. Furthermore, ganoderenic acid B notably enhanced intracellular accumulation of rhodamine-123 in HepG2/ADM cells through inhibition of its efflux. ABCB1 siRNA interference assay indicated that the reversal activity of ganoderenic acid B was dependent on ABCB1. Further mechanistic investigations found that ganoderenic acid B did not alter the expression level of ABCB1 and the activity of ABCB1 ATPase. Molecular docking model displayed that the positions of ganoderenic acid B binding to ABCB1 were different from the region of verapamil interacted with ABCB1. Collectively, ganoderenic acid B can enhance the cytotoxicity of chemotherapeutics towards ABCB1-mediated MDR cancer cells via inhibition of the transport function of ABCB1. These findings provide evidence that ganoderenic acid B has the potential to be developed into an ABCB1-mediated multidrug resistance reversal agent.
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Detecting errors and adjusting behaviour appropriately are fundamental cognitive abilities that are known to improve through adolescence. The cognitive and neural processes underlying this development, however, are still poorly understood. To address this knowledge gap, we performed a thorough investigation of error processing in a Flanker task in a cross-sectional sample of participants 8 to 19 years of age (n = 98). We examined age-related differences in event-related potentials known to be associated with error processing, namely the error-related negativity (ERN) and the error positivity (Pe), as well as their relationships with task performance, post-error adjustments and regional cingulate cortex thickness and surface area. We found that ERN amplitude increased with age, while Pe amplitude remained constant. A more negative ERN was associated with higher task accuracy and faster reaction times, while a more positive Pe was associated with higher accuracy, independently of age. When estimating post-error adjustments from trials following both incongruent and congruent trials, post-error slowing and post-error improvement in accuracy both increased with age, but this was only found for post-error slowing when analysing trials following incongruent trials. There were no age-independent associations between either ERN or Pe amplitude and cingulate cortex thickness or area measures.
Adolescence, Cognitive development, Error positivity, Error related negativity, MRI, Post-error adjustments
Error processing in the adolescent brain: Age-related differences in electrophysiology, behavioral adaptation, and brain morphology
Knut Overbye,a,⁎ Kristine B. Walhovd,a,b Tomaš Paus,c,d Anders M. Fjell,a,b Rene J. Huster,e and Christian K. Tamnesf,g,h
Although it is widely accepted that hormone receptor (HR) status is associated with later post-diagnostic periods, a debate exists as to whether the association is independent of age. The aim of our study was to confirm the impact of HR status on later period breast cancer-specific death (LP-BCSD) and later period non-breast cancer-specific death (LP-non-BCSD) in different age subgroups.
Surveillance, Epidemiology, and End Results databases were utilized to identify 181,108 breast cancer patients with > 5 years survival. The cumulative incidence of LP-BCSD and LP-non-BCSD was calculated using the Gray method. The subdistribution hazard ratio (SHR) of variables was estimated via the Fine and Gray proportional hazard regression model. Subgroup analyses for LP-BCSD and LP-non-BCSD were performed according to the HR status.
The risk of LP-BCSD was exceeded by that of LP-non-BCSD at > 5 years since the diagnosis, particularly in old women. The competing risk regression model indicated that hormone receptor-positive (HR+) was an independent factor for more LP-BCSD (hazard ratio, 1.54; 95% confidence interval, 1.44-1.54; p < 0.001). However, stratified analysis indicated that HR+ was only associated with more LP-BCSD in the young women subgroup. Although HR+ was associated with more LP-non-BCSD, the predictive value of HR+ for LP-non-BCSD was eliminated after adjusting for age. Conclusions HR+ was related to LP-BCSD in the premenopausal population. LP-BCSD should be an optimal endpoint in future trials designed to evaluate the role of extended adjuvant endocrine therapy.
Breast neoplasms, Drug therapy, Estrogen receptors, Prognosis
Young Patients with Hormone Receptor-Positive Breast Cancer Have a Higher Long-Term Risk of Breast Cancer Specific Death
Jianfei Fu,1,* Chenhan Zhong,2,3,* Lunpo Wu,4,5 Dan Li,2,3 Tiantian Xu,6 Ting Jiang,7 Jiao Yang,8 and Jinlin Ducorresponding author9
Governments and health systems are increasingly using mobile devices to communicate with patients and the public. Targeted digital client communication is when the health system transmits information to particular individuals or groups of people, based on their health or demographic status. Common types of targeted client communication are text messages that remind people to go to appointments or take their medicines. Other types include phone calls, interactive voice response, or multimedia messages that offer healthcare information, advice, monitoring, and support.
To explore clients’ perceptions and experiences of targeted digital communication via mobile devices on topics related to reproductive, maternal, newborn, child, or adolescent health (RMNCAH).
We searched MEDLINE (OvidSP), MEDLINE In‐Process & Other Non‐Indexed Citations (OvidSP), Embase (Ovid), World Health Organization Global Health Library, and POPLINE databases for eligible studies from inception to 3‐6 July 2017 dependant on the database (See appendix 2).
We included studies that used qualitative methods for data collection and analysis; that explored clients’ perceptions and experiences of targeted digital communication via mobile device in the areas of RMNCAH; and were from any setting globally.
Data collection and analysis
We used maximum variation purposive sampling for data synthesis, employing a three‐step sampling frame. We conducted a framework thematic analysis using the Supporting the Use of Research Evidence (SURE) framework as our starting point. We assessed our confidence in the findings using the GRADE‐CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach. We used a matrix approach to explore whether potential implementation barriers identified in our synthesis had been addressed in the trials included in the related Cochrane Reviews of effectiveness.
We included 35 studies, from a wide range of countries on six continents. Nineteen studies were conducted in low‐ and middle‐income settings and sixteen in high‐income settings. Some of the studies explored the views of people who had experienced the interventions, whereas others were hypothetical in nature, asking what people felt they would like from a digital health intervention. The studies covered a range of digital targeted client communication, for example medication or appointment reminders, prenatal health information, support for smoking cessation while pregnant, or general sexual health information.
Our synthesis showed that clients’ experiences of these types of programmes were mixed. Some felt that these programmes provided them with feelings of support and connectedness, as they felt that someone was taking the time to send them messages (moderate confidence in the evidence). They also described sharing the messages with their friends and family (moderate confidence).
However, clients also pointed to problems when using these programmes. Some clients had poor access to cell networks and to the internet (high confidence). Others had no phone, had lost or broken their phone, could not afford airtime, or had changed their phone number (moderate confidence). Some clients, particularly women and teenagers, had their access to phones controlled by others (moderate confidence). The cost of messages could also be a problem, and many thought that messages should be free of charge (high confidence). Language issues as well as skills in reading, writing, and using mobile phones could also be a problem (moderate confidence).
Clients dealing with stigmatised or personal health conditions such as HIV, family planning, or abortion care were also concerned about privacy and confidentiality (high confidence). Some clients suggested strategies to deal with these issues, such as using neutral language and tailoring the content, timing, and frequency of messages (high confidence).
Clients wanted messages at a time and frequency that was convenient for them (moderate confidence). They had preferences for different delivery channels (e.g. short message service (SMS) or interactive voice response) (moderate confidence). They also had preferences about message content, including new knowledge, reminders, solutions, and suggestions about health issues (moderate confidence). Clients’ views about who sent the digital health communication could influence their views of the programme (moderate confidence).
For an overview of the findings and our confidence in the evidence, please see the ‘Summary of qualitative findings’ tables.
Our matrix shows that many of the trials assessing these types of programmes did not try to address the problems we identified, although this may have been a reporting issue.
Our synthesis identified several factors that can influence the successful implementation of targeted client communication programmes using mobile devices. These include barriers to use that have equity implications. Programme planners should take these factors into account when designing and implementing programmes. Future trial authors also need to actively address these factors and to report their efforts in their trial publications.
Clients’ perceptions and experiences of targeted digital communication accessible via mobile devices for reproductive, maternal, newborn, child, and adolescent health: a qualitative evidence synthesis
Monitoring Editor: Heather MR Ames,corresponding author Claire Glenton, Simon Lewin, Tigest Tamrat, Eliud Akama, Natalie Leon, and Cochrane Consumers and Communication Group