Inhibition of misfolded N-CoR induced survival pathway in APL by Artemisinin

Master'sMASTER OF SCIENC

Prechemotherapy Levels of Plasma Dehydroepiandrosterone and Its Sulfated Form as Predictors of Cancer-Related Cognitive Impairment in Patients with Breast Cancer Receiving Chemotherapy.

Study objectiveDehydroepiandrosterone (DHEA) and its sulfated form (DHEAS)-jointly referred to as DHEA(S)-are neurosteroids known to regulate brain development and function that have been found to be positively correlated with cognitive function. It is unknown whether prechemotherapy plasma DHEA(S) levels are associated with the onset of cancer-related cognitive impairment (CRCI). The objective of this study was to evaluate whether an association exists between prechemotherapy plasma DHEA(S) levels and onset of CRCI in patients with breast cancer receiving chemotherapy.DesignMulticenter, prospective cohort study.SettingTwo specialized cancer centers in Singapore.PatientsEighty-one patients with early-stage breast cancer (stages I-III) who had no prior exposure to chemotherapy and/or radiotherapy and were scheduled to receive anthracycline-based or taxane-based chemotherapy treatment with curative intent.Measurements and main resultsPatients completed assessments for self-perceived and objective cognitive function at three time points: prechemotherapy (T1), during chemotherapy (T2), and after chemotherapy (T3). Plasma samples were collected prior to chemotherapy, and DHEA(S) levels were quantified by using ultra-high-performance liquid chromatography-tandem mass spectrometry. Multivariable logistic regression was used to adjust for clinically important factors and to evaluate the association between prechemotherapy plasma DHEA(S) levels and CRCI. Mean ± SD age was 48.9 ± 9.3 years, with 27.8% of patients experiencing clinically significant cognitive impairment based on global Functional Assessment of Cancer Therapy-Cognitive Function scores. The mean ± SD prechemotherapy plasma DHEAS and DHEA levels were 1.61 ± 0.91 μmol/L and 19.21 ± 13.13 nmol/L, respectively. Prechemotherapy DHEAS levels were found to be associated with impairment in the self-perceived cognitive domains of verbal fluency (adjusted odds ratio [OR] 0.27, 95% confidence interval [CI] 0.08-0.96) and mental acuity (adjusted OR 0.25, 95% CI 0.08-0.74). Conversely, DHEA levels were not associated with impairment in any cognitive subdomains.ConclusionOur findings suggest that patients with higher prechemotherapy DHEAS levels had lower odds of developing self-perceived cognitive impairment. Future studies are required to further investigate the effect of DHEA(S) on specific cognitive domains and to validate our findings in independent cohorts

Replication and Meta-analysis of the Association between BDNF Val66Met Polymorphism and Cognitive Impairment in Patients Receiving Chemotherapy.

Cancer-related cognitive impairment (CRCI) adversely affects cancer patients. We had previously demonstrated that the BDNF Val66Met genetic polymorphism is associated with lower odds of subjective CRCI in the multitasking and verbal ability domains among breast cancer patients receiving chemotherapy. To further assess our previous findings, we evaluated the association of BDNF Val66Met polymorphism with subjective and objective CRCI in a temporally separate cohort of patients and pooled findings from both the original (n = 145) and current (n = 193) cohorts in a meta-analysis. Subjective CRCI was assessed using FACT-Cog. Objective CRCI was evaluated using computerized neuropsychological tests. Genotyping was carried out using Sanger sequencing. The association of BDNF Val66Met genotypes and CRCI was examined with logistic regression. A fixed-effect meta-analysis was conducted using the inverse variance method. In the meta-analysis (n = 338), significantly lower odds of CRCI were associated with Met allele carriers based on the global FACT-Cog score (OR = 0.52, 95% CI 0.29-0.94). Furthermore, Met allele carriers were at lower odds of developing impairment in the domains of memory (OR = 0.34, 95% CI: 0.17-0.70), multitasking (OR = 0.33, 95% CI: 0.18-0.59), and verbal ability (OR = 0.46, 95% CI: 0.24-0.88). Consistent with the previous study, lower odds of subjective CRCI among patients with the BDNF Met allele was observed after adjusting for potential confounders in the multitasking (OR = 0.30, 95% CI: 0.14-0.67) domain. In conclusion, carriers of the BDNF Met allele were protected against global subjective CRCI, particularly in the domains of memory, multitasking, and verbal ability. Our findings further contribute to the understanding of CRCI pathophysiology

Adherence to Cancer Survivorship Care Guidelines and Health Care Utilization Patterns Among Nonmetastatic Breast Cancer Survivors in Singapore.

PurposeCurrently, limited information is available on care provided to breast cancer survivors in Singapore. This study aims to assess the quality of post-treatment cancer survivorship care among breast cancer survivors on the basis of compliance with international guidelines up to 5 years post-primary treatment.MethodsThis study analyzed a cohort of 189 nonmetastatic breast cancer survivors recruited from the National Cancer Centre Singapore, Changi General Hospital, and KK Women's and Children's Hospital between November 2011 and September 2015. Data were retrieved from electronic medical records in 6-month intervals. Adherence to guidelines was assessed in four areas: (1) recurrent cancer surveillance, (2) monitoring and detecting late effects, (3) health care resource utilization, and (4) preventive care. Descriptive statistics, Kaplan-Meier, and regression analyses were conducted.ResultsAnnual surveillance mammogram adherence rates were ≥ 83% consistently. The most common new diagnosis was osteoporosis at an incidence rate of 102 (95% CI, 77.6 to 135) cases per 1,000 person-years. Overall, ≤ 10.1% of survivors had an emergency department or hospitalization visit. Oncologist services were overutilized, with a median of 6 (interquartile range: 4-10) visits in the first 6 months before reducing to a median of 2 (interquartile range: 1-3) visits biannually 3 years post-treatment. Bone mineral density test utilization rate adhered to guidelines for 92.2% of aromatase inhibitor recipients but only for 36.4% of premenopausal tamoxifen recipients.ConclusionOverall, adherence rates to surveillance and osteoporosis preventive care were high. Extensive utilization of oncologist services up to 5 years post-primary treatment could be reversed with strategies to engage and coordinate survivorship care with primary care providers, leveraging their strengths to improve adherence to health promotion and chronic disease management

Evaluation of plasma brain-derived neurotrophic factor levels and self-perceived cognitive impairment post-chemotherapy: a longitudinal study

Abstract Background Preliminary evidence suggests that changes in plasma brain-derived neurotrophic factor (BDNF) levels may contribute to the occurrence of chemotherapy-associated cognitive impairment (CACI), and a previous study suggested that carriers of the BDNF Met homozygous genotype are protected from CACI. Methods This multicenter, prospective cohort study involved chemotherapy-receiving early-stage breast cancer (ESBC) patients. Self-perceived cognitive function was longitudinally assessed using the validated FACT-Cog (ver. 3) across three time points: Prior to chemotherapy (T1), during chemotherapy (T2), and at the end of chemotherapy (T3). Plasma BDNF levels were quantified using enzyme-linked immunosorbent assay. Genotyping was performed using Sanger Sequencing. Results A total of 51 chemotherapy-receiving ESBC patients (mean age: 52.6 ± 9.5 years) were recruited, and 11 patients (21.6%) reported subjective cognitive impairment post-chemotherapy. Overall, there was a reduction in median plasma BDNF levels over time (T1: 5423.0 pg/ml; T2: 5313.6 pg/ml; T3: 4050.3 pg/ml; p < 0.01). After adjusting for confounding factors, longitudinal analysis revealed that BDNF levels were associated with self-reported concentration deficit (p = 0.032). Carriers of Val/Val (p = 0.011) and Val/Met (p = 0.003) BDNF genotypes demonstrated a significant reduction in plasma BDNF levels over time; however, plasma BDNF levels were similar across all time points among Met homozygous carriers (p = 0.107). Conclusion There was a statistically significant change in BDNF levels post-chemotherapy in ESBC patients, and plasma BDNF levels were associated with self-perceived concentration deficit in patients receiving chemotherapy

Controversies and progress on standardization of large-scale brain network nomenclature

Progress in scientific disciplines is accompanied by standardization of terminology. Network neuroscience, at the level of macro-scale organization of the brain, is beginning to confront the challenges associated with developing a taxonomy of its fundamental explanatory constructs. The Workgroup for HArmonized Taxonomy of NETworks (WHATNET) was formed in 2020 as an Organization for Human Brain Mapping (OHBM)-endorsed best practices committee to provide recommendations on points of consensus, identify open questions, and highlight areas of ongoing debate in the service of moving the field towards standardized reporting of network neuroscience results. The committee conducted a survey to catalog current practices in large-scale brain network nomenclature. A few well-known network names (e.g., default mode network) dominated responses to the survey, and a number of illuminating points of disagreement emerged. We summarize survey results and provide initial considerations and recommendations from the workgroup. This perspective piece includes a selective review of challenges to this enterprise, including 1) network scale, resolution, and hierarchies; 2) inter-individual variability of networks; 3) dynamics and non-stationarity of networks; 4) consideration of network affiliations of subcortical structures; and 5) consideration of multi-modal information. We close with minimal reporting guidelines for the cognitive and network neuroscience communities to adopt