Search

Background: Previous findings regarding declines in cognitive functioning among patients with breast cancer (BC) before and after chemotherapy have been inconsistent. The present study explored the effect of BC and cancer-related chemotherapies on cognitive functioning., Methods: A cross-sectional design was adopted to compare BC patients before their chemotherapy treatment, BC patients 3 ~ 9 months after the completion of chemotherapy, and noncancer controls. Evaluations of cognitive functioning included subjective and objective dimensions, with focus on memory, executive functioning, attention, and language. ANCOVA and Pearson's correlation analysis were used to examine the relationship among cancer, chemotherapy, cognitive performance, and psychological distress., Results: After adjustment for intelligence quotient, anxiety, and depression, we found significant differences in the Semantic Association of Verbal Fluency between post-chemotherapy (C/T) patients and noncancer controls. Specifically, post-C/T patients scored lower than controls (p = 0.03, η 2  = 0.07). No significant differences were found in other objective cognitive measures. However, both subjective and objective cognitive scores were significantly associated with depression, anxiety, and fatigue. In BC patients, levels of anxiety were positively correlated with measures of executive function. Among pre-C/T patients, self-perceived interference by fatigue was positively associated with better performances in some of the objective cognitive measures., Conclusion: Our findings suggest cognitive impairments in the domain of executive functioning among patients with BC who received chemotherapy. Providing relevant suggestions or strategies of managements for these negative consequences may help increase the long-term quality of life of patients with BC.

The control strategies preventing subclinical transmission differed among countries. A stochastic transmission model was used to assess the potential effectiveness of control strategies at controlling the COVID-19 outbreak. Three strategies included lack of prevention of subclinical transmission (Strategy A), partial prevention using testing with different accuracy (Strategy B) and complete prevention by isolating all at-risk people (Strategy C, Taiwan policy). The high probability of containing COVID-19 in Strategy C is observed in different scenario, had varied in the number of initial cases (5, 20, and 40), the reproduction number (1.5, 2, 2.5, and 3.5), the proportion of at-risk people being investigated (40%, 60%, 80%, to 90%), the delay from symptom onset to isolation (long and short), and the proportion of transmission that occurred before symptom onset (<1%, 15%, and 30%). Strategy C achieved probability of 80% under advantageous scenario, such as low number of initial cases and high coverage of epidemiological investigation but Strategy B and C rarely achieved that of 60%. Considering the unsatisfactory accuracy of current testing and insufficient resources, isolation of all at-risk people, as adopted in Taiwan, could be an effective alternative., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In this study, we examined the differential associations of various proinflammatory and anti-inflammatory cytokines with depression severity from the development of breast cancer to subsequent chemotherapy treatment., Methods: A cross-sectional study was conducted on a sample of 116 women: 29 controls without cancer, 55 patients with breast cancer who were not receiving chemotherapy, and 32 patients with breast cancer who were receiving chemotherapy. Blood samples were assayed to evaluate serum levels of the following cytokines: interferon-γ, interleukin (IL)-12 (p70), IL-1β, IL-2, tumor necrosis factor (TNF)-α, IL-4, IL-5, IL-10, IL-13, IL-6, and IL-17A. Depression severity was assessed using the Patient Health Questionnaire., Results: After adjustment for sociodemographics, consistent patterns of the association between cytokine and depression were noted in the different groups. No significant associations were observed in the controls. Inverse associations were observed between cytokines levels and depression severity in patients with breast cancer who were not receiving chemotherapy, whereas positive associations were noted in patients with breast cancer who were receiving chemotherapy. Specific differential relationships between IL-5 levels and depression severity were found between patients with breast cancer who were receiving and not receiving chemotherapy., Conclusions: Our study revealed differential relationships between cytokine levels and depression severity with the development of cancer. Immunostimulation and immunosuppression in breast cancer and cancer treatment may account for the differential responses with the development of breast cancer.

Background: Chromothripsis is an event of genomic instability leading to complex chromosomal alterations in cancer. Frequent long-range chromatin interactions between transcription factors (TFs) and targets may promote extensive translocations and copy-number alterations in proximal contact regions through inappropriate DNA stitching. Although studies have proposed models to explain the initiation of chromothripsis, few discussed how TFs influence this process for tumor progression., Methods: This study focused on genomic alterations in amplification associated regions within chromosome 17. Inter-/intra-chromosomal rearrangements were analyzed using whole genome sequencing data of breast tumors in the Cancer Genome Atlas (TCGA) cohort. Common ERα binding sites were defined based on MCF-7, T47D, and MDA-MB-134 breast cancer cell lines using univariate K-means clustering methods. Nanopore sequencing technology was applied to validate frequent rearrangements detected between ATC loci on 17q23 and an ERα hub on 20q13. The efficacy of pharmacological inhibition of a potentially druggable target gene on 17q23 was evaluated using breast cancer cell lines and patient-derived circulating breast tumor cells., Results: There are five adjoining regions from 17q11.1 to 17q24.1 being hotspots of chromothripsis. Inter-/intra-chromosomal rearrangements of these regions occurred more frequently in ERα-positive tumors than in ERα-negative tumors. In addition, the locations of the rearrangements were often mapped within or close to dense ERα binding sites localized on these five 17q regions or other chromosomes. This chromothriptic event was linked to concordant upregulation of 96 loci that predominantly regulate cell-cycle machineries in advanced luminal tumors. Genome-editing analysis confirmed that an ERα hub localized on 20q13 coordinately regulates a subset of these loci localized on 17q23 through long-range chromosome interactions. One of these loci, Tousled Like Kinase 2 (TLK2) known to participate in DNA damage checkpoint control, is an actionable target using phenothiazine antipsychotics (PTZs). The antiproliferative effect of PTZs was prominent in high TLK2-expressing cells, compared to low expressing cells., Conclusion: This study demonstrates a new approach for identifying tumorigenic drivers from genomic regions highly susceptible to ERα-related chromothripsis. We found a group of luminal breast tumors displaying 17q-related chromothripsis for which antipsychotics can be repurposed as treatment adjuncts.

Delta opioid receptor (DOR) is well known to be involved in heroin dependence. This study tested the hypothesis that single nucleotide polymorphisms (SNPs) in the opioid receptor delta 1 (OPRD1) gene coding region are associated with treatment responses in a methadone maintenance therapy (MMT) cohort in Taiwan. Three hundred forty-four MMT patients were recruited. Diastolic/systolic blood pressure, heart rate, methadone dosage, and plasma concentrations of methadone were recorded. Twenty-five SNPs located within the OPRD1 genetic region were selected and genotyped from the genomic DNA of all 344 participants. After pairwise tagger analyses, tagger SNP rs204047 showed a significant association with methadone dosage (P = 0.0019), and tagger SNPs rs204047 and rs797397 were significantly associated with plasma R, S-methadone concentrations (P < 0.0006) in patients tested negative in the urine morphine test, which indicated patients with a better response to MMT. The major genotype carriers showed a higher methadone dosage and higher plasma concentrations of R, S-methadone than the minor genotype carriers. The results indicated that OPRD1 genetic variants were associated with methadone dosage and methadone plasma concentration in MMT patients with a negative morphine test result.

Background/purpose: Hepatitis B virus (HBV) reactivation may occur in >10% of patients with lymphoma and resolved HBV infection who undergo rituximab-containing chemotherapy. Preventive strategies may have marked impact on resource allocation in HBV endemic areas. This study aims to compare the cost-effectiveness between prophylactic antiviral therapy and HBV DNA monitoring for the prevention of HBV-related complications., Methods: Data sources are studies of HBV-related events and survival for patients with lymphoma and resolved HBV infection published since 2006. Decision tree analysis was used to compare the incremental cost-effectiveness ratio (ICER) of preventing HBV-related death or liver decompensation for patients who undergo first-line rituximab-containing chemotherapy. Sensitivity analysis was performed to examine the impact of the preventive efficacy, the duration of prophylactic antiviral therapy, and the cost of different interventions. The direct medical cost was derived from the database of the NHI Administration, Taiwan. The time frame of our analysis was set to 3 years after the completion of chemotherapy., Results: The median ICER of prophylactic antiviral therapy, according to current practice guidelines, ranged between USD 150,000 and 250,000 if we apply the guidelines generally. When a long-course (12 months after completion of chemotherapy according to clinical guidelines) prophylactic therapy was assumed, Option A was cheaper and more effective only in the anti-HBs-negative subgroup (median ICER US$149,932 vs. US$161,526, p = 0.013)., Conclusion: Identification of anti-HBs-negative subgroups is critical to improve the cost-effectiveness of prophylactic antiviral therapy in lymphoma patients with resolved HBV infection., (Copyright © 2019 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Aplastic anemia (AA) is a rare disease characterized by pancytopenia and bone marrow failure. The incidence of AA tends to be higher in Asia than in the West, but real-world data about AA in Asia remain limited. We aimed to describe the basic data, treatment, and outcome of AA patients from our institute and evaluate the incidence of AA in Taiwan with a nationwide population-based cohort from National Health Insurance Research Database (NHIRD). We identified patients older than 2 years with AA in the Registry of Catastrophic Illness of NHIRD between 2001 and 2010 and excluded patients with any diagnosis suggestive of congenital or secondary bone marrow failure. With a total of 1270 patients, the overall incidence was 5.67 per million people per year, and there was a biphasic age distribution of incidence rate, highest in ≥ 70 years (19.83 per million people per year) and another peak at age 2-9 years (5.26 per million people per year). Overall, the 5-year survival was 60.0%. Hematopoietic stem cell transplantation (HSCT) and anti-thymocyte globulin-based immunosuppressive therapy (IST) were the major first-line treatments in patients younger than 40 years and were linked with good survival. In contrast, the majority of patients older than 60 years were treated with androgen, and the survival was poor. In multivariate analysis, "severe AA," "very severe AA," and "treatment other than HSCT, IST, or androgen" were independent risk factors for inferior survival. In conclusion, the incidence of AA in Taiwan is consistent with nearby Asian countries and is higher than in the West. Advanced age is associated with higher incidence and poorer outcome.

To develop accurate prognostic models is one of the biggest challenges in "omics"-based cancer research. Here, we propose a novel computational method for identifying dysregulated gene subnetworks as biomarkers to predict cancer recurrence. Applying our method to the DNA methylome of endometrial cancer patients, we identified a subnetwork consisting of differentially methylated (DM) genes, and non-differentially methylated genes, termed Epigenetic Connectors (EC), that are topologically important for connecting the DM genes in a protein-protein interaction network. The ECs are statistically significantly enriched in well-known tumorgenesis and metastasis pathways, and include known epigenetic regulators. Importantly, combining the DMs and ECs as features using a novel random walk procedure, we constructed a support vector machine classifier that significantly improved the prediction accuracy of cancer recurrence and outperformed several alternative methods, demonstrating the effectiveness of our network-based approach., (Copyright © 2016 Elsevier Inc. All rights reserved.)

T-cell lymphomas are generally aggressive malignancies with poor prognosis. There are no standard treatment guidelines for T-cell lymphomas, and the timing of stem cell transplantation (SCT) is not well known. In this study, we investigated the outcomes of Taiwanese patients with T-cell lymphomas after SCT. We retrospectively analyzed 131 patients with T-cell lymphomas receiving SCT (autologous: 90, allogeneic: 41) from 2009 to 2014. More autologous SCT recipients were ALCL or in complete remission, and more allogeneic recipients had advanced disease. 56 patients who were sensitive to chemotherapy underwent SCT as upfront setting. The 2-year PFS and OS rates were 67.0 and 64.5%, respectively. Regarding disease status before transplantation, patients with CR1 had the best outcomes. Among different subtypes, patients with natural killer/T-cell lymphomas showed the worst outcomes, with 2-year OS rate of 23.5%. The OS rates for the other three major subtypes were as follows: 72.9% for ALCL; 75.0% for AITL; and 51.4% for PTCL-NOS. For more rare subtypes, such as ATLL and SPTCL, data from our study show that SCT can be beneficial. We concluded that upfront autologous SCT is feasible and effective for patients with low PIT, and disease status at transplant is the strong predictor of outcome.

Valproic acid (VPA)-exposed rat offspring have demonstrated autism spectrum disorder (ASD) phenotypes and impaired N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD) in the lateral nucleus of the amygdala. NMDAR partial agonist D -cycloserine (DCS) has been reported to act as a cognitive enhancer by increasing the NMDAR response to improve autistic-like phenotypes in animals. However, the mechanism of DCS in alleviating the ASD is still unknown. Using combined behavioral, electrophysiological, and molecular approaches, we found that DCS administration rescued social interaction deficits and anxiety/repetitive-like behaviors observed in VPA-exposed offspring. In the amygdala synapses, DCS treatment reversed the decreased paired pulse ratio (PPR) and the impaired NMDAR-dependent LTD, increased the frequency and amplitude of miniature excitatory post-synaptic currents (mEPSCs), and resulted in a higher dendritic spine density at the amygdala synapses in the VPA-exposed offspring. Moreover, we found that DCS facilitated the removal of GluA2-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (GluA2/AMPARs) by inducing NMDAR-dependent LTD in the VPA-exposed offspring. We further established that the effects of DCS treatment, including increased GluA2/AMPAR removal and rescues of impaired social behavior, were blocked by Tat-GluA2 3Y , a GluA2-derived peptide that disrupted regulation of AMPAR endocytosis. These results provided the first evidence that rescue of the ASD-like phenotype by DCS is mediated by the mechanism of GluA2/AMPAR removal in VPA-exposed rat offspring.