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Background@#and PurposeThe correlation between dopamine transporter (DAT) imaging and neuromelanin-sensitive magnetic resonance imaging (NM-MRI) in early-stage Parkinson’s disease (PD) has not yet been established. This study aimed to determine the correlation between NM-MRI and DAT positron-emission tomography (PET) in patients with early-stage PD. @*Methods@#Fifty drug-naïve patients with early-stage PD who underwent both 0.8-mm isovoxel NM-MRI and DAT PET were enrolled retrospectively. Using four regions of interest (nigrosome 1 and nigrosome 2 [N1 and N2] regions) from a previous study, the contrast ratios (CRs) of 12 regions were measured: N1, N2, flipped N1, flipped N2, combined N1 and N2, and whole substantia nigra pars compacta [SNpc] (all on both sides). The clinically more affected side was separately assessed. The standardized uptake value ratios (SUVRs) were measured in the striatum using DAT PET. A partial correlation analysis was performed between the SUVR and CR measurements. @*Results@#CR of the flipped left N1 region was significantly correlated with SUVR of the right posterior putamen (p=0.047), and CR values of the left N1 region, left N2 region, flipped right N1 region, and combined left N1 and N2 regions were significantly correlated with SUVR of the left posterior putamen (p=0.011, 0.038, 0.020, and 0.010, respectively). SUVR of the left anterior putamen was significantly correlated with CR of the left N2 region (p=0.027). On the clinically more affected side, the CR values of the N1 region, combined N1 and N2 regions, and the whole SNpc were significantly correlated with SUVR of the posterior putamen (p=0.001, 0.024, and 0.021, respectively). There were significant correlations between the SUVR of the anterior putamen and the CR values of the N1 region, combined N1 and N2 regions, and whole SNpc (p=0.027, 0.001, and 0.036, respectively). @*Conclusions@#This study found that there were significant correlations between CR values in the SNpc on NM-MRI and striatal SUVR values on DAT PET on both sides in early-stage PD.
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Background@#Numerous studies have shown the effect of particulate matter exposure on brain imaging markers. However, little evidence exists about whether the effect differs by the level of low-grade chronic systemic inflammation. We investigated whether the level of c-reactive protein (CRP, a marker of systemic inflammation) modifies the associations of particulate matter exposures with brain cortical gray matter thickness and white matter hyperintensities (WMH). @*Methods@#We conducted a cross-sectional study of baseline data from a prospective cohort study including adults with no dementia or stroke. Long-term concentrations of particulate matter ≤ 10 µm in diameter (PM10) and ≤ 2.5 µm (PM2.5) at each participant’s home address were estimated. Global cortical thickness (n = 874) and WMH volumes (n = 397) were estimated from brain magnetic resonance images. We built linear and logistic regression models for cortical thickness and WMH volumes (higher versus lower than median), respectively. Significance of difference in the association between the CRP group (higher versus lower than median) was expressed as P for interaction. @*Results@#Particulate matter exposures were significantly associated with a reduced global cortical thickness only in the higher CRP group among men (P for interaction = 0.015 for PM10 and 0.006 for PM2.5). A 10 μg/m3 increase in PM10 was associated with the higher volumes of total WMH (odds ratio, 1.78; 95% confidence interval, 1.07–2.97) and periventricular WMH (2.00; 1.20–3.33). A 1 μg/m3 increase in PM2.5 was associated with the higher volume of periventricular WMH (odds ratio, 1.66; 95% confidence interval, 1.08–2.56). These associations did not significantly differ by the level of high sensitivity CRP. @*Conclusion@#Particulate matter exposures were associated with a reduced global cortical thickness in men with a high level of chronic inflammation. Men with a high level of chronic inflammation may be susceptible to cortical atrophy attributable to particulate matter exposures.
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Purpose@#The role of medical staff gained immense significance in the context of the prolonged coronavirus disease (COVID-19) pandemic.However, few studies had explored the impact of simulation-based education on the ability of nursing students to care for the patients of COVID-19. This study provided nursing students with simulation-based education in caring for the patients of COVID-19 and confirmed its effectiveness. @*Methods@#This study used a non-equivalent control group pretest-posttest design. The participants were recruited from the nursing departments of two universities in Korea through convenience sampling. A total of 79 participants were included: 37 in the intervention group and 42 in the control group. The intervention group received four sessions of simulation training based on the National League for Nursing Jeffries simulation theory. @*Results@#The intervention group showed an improvement compared to the control group in terms of knowledge related to coronavirus, confidence in performing infection control skills, and perception of preparedness for caring for the patients of COVID-19, with a high-level of satisfaction and self-confidence in learning. There was no significant difference between the two groups in terms of anxiety. @*Conclusion@#This simulation is expected to be a significant strategy for alleviating the global burden in terms of staff safety and patient outcomes by improving the competencies of prospective medical staff in responding to pandemics.
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Background@#To deliver therapeutics into the brain, it is imperative to overcome the issue of the blood-brain-barrier (BBB). One of the ways to circumvent the BBB is to administer therapeutics directly into the brain parenchyma. To enhance the treatment efficacy for chronic neurodegenerative disorders, repeated administration to the target location is required. However, this increases the number of operations that must be performed. In this study, we developed the IntraBrain Injector (IBI), a new implantable device to repeatedly deliver therapeutics into the brain parenchyma. @*Methods@#We designed and fabricated IBI with medical grade materials, and evaluated the efficacy and safety of IBI in 9 beagles. The trajectory of IBI to the hippocampus was simulated prior to surgery and the device was implanted using 3D-printed adaptor and surgical guides. Ferumoxytol-labeled mesenchymal stem cells (MSCs) were injected into the hippocampus via IBI, and magnetic resonance images were taken before and after the administration to analyze the accuracy of repeated injection. @*Results@#We compared the planned vs. insertion trajectory of IBI to the hippocampus.With a similarity of 0.990 ± 0.001 (mean ± standard deviation), precise targeting of IBI was confirmed by comparing planned vs. insertion trajectories of IBI. Multiple administrations of ferumoxytol-labeled MSCs into the hippocampus using IBI were both feasible and successful (success rate of 76.7%). Safety of initial IBI implantation, repeated administration of therapeutics, and long-term implantation have all been evaluated in this study. @*Conclusion@#Precise and repeated delivery of therapeutics into the brain parenchyma can be done without performing additional surgeries via IBI implantation.
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Background@#and Purpose Alzheimer’s disease (AD) does not always mean amyloid positivity. [ 18 F]THK-5351 has been shown to be able to detect reactive astrogliosis as well as tau accompanied by neurodegenerative changes. We evaluated the [ 18 F]THK-5351 retention patterns in positron-emission tomography (PET) and the clinical characteristics of patients clinically diagnosed with AD dementia who had negative amyloid PET findings. @*Methods@#We performed 3.0-T magnetic resonance imaging, [ 18 F]THK-5351 PET, and amyloid PET in 164 patients with AD dementia. Amyloid PET was visually scored as positive or negative. [ 18 F]THK-5351 PET were visually classified as having an intratemporal or extratemporal spread pattern. @*Results@#The 164 patients included 23 (14.0%) who were amyloid-negative (age 74.9±8.3 years, mean±standard deviation; 9 males, 14 females). Amyloid-negative patients were older, had a higher prevalence of diabetes mellitus, and had better visuospatial and memory functions. The frequency of the apolipoprotein E ε4 allele was higher and the hippocampal volume was smaller in amyloid-positive patients. [ 18 F]THK-5351 uptake patterns of the amyloid-negative patients were classified into intratemporal spread (n=10) and extratemporal spread (n=13).Neuropsychological test results did not differ significantly between these two groups. The standardized uptake value ratio of [ 18 F]THK-5351 was higher in the extratemporal spread group (2.01±0.26 vs. 1.61±0.15, p=0.001). After 1 year, Mini Mental State Examination (MMSE) scores decreased significantly in the extratemporal spread group (-3.5±3.2, p=0.006) but not in the intratemporal spread group (-0.5±2.8, p=0.916). The diagnosis remained as AD (n=5, 50%) or changed to other diagnoses (n=5, 50%) in the intratemporal group, whereas it remained as AD (n=8, 61.5%) or changed to frontotemporal dementia (n=4, 30.8%) and other diagnoses (n=1, 7.7%) in the extratemporal spread group. @*Conclusions@#Approximately 70% of the patients with amyloid-negative AD showed abnormal [ 18 F]THK-5351 retention. MMSE scores deteriorated rapidly in the patients with an extratemporal spread pattern.
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Background@#and Purpose: The expression of the 18-kDA mitochondrial translocator protein (TSPO) in the brain is an attractive target to study neuroinflammation. However, the binding properties of TSPO ligands are reportedly dependent on genetic polymorphism of the TSPO gene (rs6971). The objective of this study is to investigate the rs6971 gene polymorphism in the Korean population. @*Methods@#We performed genetic testing on 109 subjects including patients with mild cognitive impairment, Alzheimer’s disease (AD) dementia, non-AD dementia, and cognitively unimpaired participants. Magnetic resonance imaging scans and detailed neuropsychological tests were also performed, and 29 participants underwent 18 F-DPA714 PET scans. Exon 4 of the TSPO gene containing the polymorphism rs6971 (Ala or Thr at position 147) was polymerase chain reaction amplified and sequenced using the Sanger method. The identified rs6971 genotype codes (C/C, C/T, or T/T) of the TSPO protein generated high-, mixed-, or lowaffinity binding phenotypes (HABs, MABs, and LABs), respectively. @*Results@#We found that 96.3% of the study subjects were HAB (105 out of 109 subjects), and 3.7% of the subjects were MAB (4 out of 109 subjects). 18 F-DPA-714 PET scans showed nonspecific binding to the thalamus and brainstem, and increased tracer uptake throughout the cortex in cognitively impaired patients. The participant with the MAB polymorphism had a higher DPA714 signal throughout the cortex. @*Conclusions@#The majority of Koreans are HAB (approx. 96%). Therefore, the polymorphism of the rs6971 gene would have a smaller impact on the availability of second-generation TSPO PET tracers.
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Purpose@#This study investigated the association of insulin, metformin, and statin use with survival and whether the association was modified by the hormone receptor status of the tumor in patients with breast cancer. @*Materials and Methods@#We studied 7,452 patients who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded prescription of each drug within 12 months before the diagnosis of breast cancer. @*Results@#Patients with prior insulin or statin use were more likely to be older than 50 years at diagnosis and had a higher comorbidity index than those without it (p < 0.01 for both). The hazard ratio (HR) for death with insulin use was 5.7 (p < 0.01), and the effect was attenuated with both insulin and metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)–negative breast cancer. Statin use was associated with increased overall mortality only in patients with ER-positive breast cancer with HR for death of 1.5 (p=0.05). @*Conclusion@#Insulin or statin use before the diagnosis of breast cancer was associated with an increase in all-cause mortality. Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.
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Dietary management is an important factor in glycemic control among patients with diabetes mellitus. However, the range of food choices in diabetic diets is limited, increasing the amount of effort and time required to prepare meals. Home meal replacement and delivery meal services are a convenient and easy way to obtain meals prepared outside the home. The market is growing rapidly due to the increase in single-person households and the lifestyle change that prioritizes convenience. Therefore, in this paper, we review the recent revised notices from the Ministry of Food and Drug Safety related to home meal replacement and delivery meal services, and consider how home meal replacement and delivery meal services will affect blood sugar management in patients with diabetes mellitus.
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Purpose@#The purpose of this study was to explore nurses’ experience with caring for COVID-19 patients in a negative pressure room amid the spread of the pandemic. @*Methods@#This study was a qualitative research, and focus group interviews were used to collect data. Three focus groups comprising 19 nurses were interviewed from February 17 to 25, 2021. All interviews were recorded and transcribed verbatim with the consent of the participants. The verbatim transcripts were scrutinized using thematic analysis. @*Results@#Two main themes emerged from the analysis: ‘Struggling in an isolated space’ and ’Limitations of nursing infrastructure and system’. The nurses caring for COVID-19 patients experienced anxiety and fear about the infection, physical exhaustion, emotional burnout, and a sense of duty as a nurse. They also acknowledged the lack of guidelines, increased task and burden, limitations of nursing care, and the demand for improving the limitations of the nursing system. @*Conclusion@#The results of this study demonstrate that nurses caring for COVID-19 patients encounter physical and emotional problems within the limited healthcare system. The study suggests that comprehensive interventions are needed for nurses. Furthermore, detailed guidelines, strengthening of nursing personnel, and improvements to the nursing system are vital to effectively cope with the pandemic. The government and medical institutions should be aware of the needs of nurses and what they are going through, and make efforts to improve the quality of life of healthcare workers and create a safe healthcare environment.
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Purpose@#Following the outbreak and global spread of the coronavirus disease 2019 (COVID-19), an increasing number of people have turned to cycling. This study aims to investigate the epidemiology of bicycle-related injuries before and after the emergence of the COVID-19. @*Methods@#In this retrospective study, we collected medical records of those patients who visited the emergency room for orthopedic injuries related to bicycle accidents. The “COVID-19 period” consisted of the patients identified from April 1 to November 31 in the year 2020, while the “pre-COVID-19 period” consisted of those identified during the same months of the year 2019. @*Results@#A total of 519 patients were identified. The bicycle-related injuries increased by 5.1% during the COVID-19, in comparison to the pre-COVID-19 period. Among these, 76.3% were men. The highest incidence of the injuries was seen for 10– 19 years of age during the pre-COVID-19, and for 50– 59 years of age during the COVID-19 period. Overall, upper limb injuries were the commonest, consisting of 32.2% of all injuries. The shoulder injuries were the commonest in the pre-COVID-19, while the knee injuries were the commonest in the COVID-19 period. Assessing the severity of the injuries, contusion (81.8%) was the commonest. Of the injuries requiring hospital admissions, hip injuries had the highest incidence at 76.5%. @*Conclusion@#During the COVID-19, the total number of bicycle-related injuries did not increase significantly. In the bicycle-related injuries, the middle-age group had the highest proportion during the COVID-19 period. More efficient prevention strategies for middle-aged riders are necessary.
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Purpose@#Sentinel lymph node biopsy (SLNB) has become a standard axillary staging surgery for early breast cancer, and the proportion of patients requiring axillary lymph node dissection (ALND) is decreasing. We aimed to evaluate the association between the number of sentinel lymph nodes (SLNs) retrieved and the risk of lymphedema of the ipsilateral arm. @*Methods@#Prospectively collected medical records of 910 patients were reviewed.Lymphedema was defined as a difference in circumference > 2 cm compared to the contralateral arm and/or having clinical records of lymphedema treatment in the rehabilitation clinic. @*Results@#Together with an objective and subjective assessment of lymphedema, 36 patients (6.1%) had lymphedema in the SLNB group and 85 patients (27.0%) had lymphedema in the ALND group (p < 0.001). In a multivariate analysis of the whole cohort, risk factors significantly associated risk with the development of lymphedema were body mass index, mastectomy (vs.breast-conserving surgery), ALND, and radiation therapy. In logistic regression models in the SLNB group only, there was no correlation between the number of retrieved SLNs and the incidence of lymphedema. In addition, in the Pearson correlation analysis, no correlation was observed between the number of retrieved SLNs and the difference in circumference between the ipsilateral and contralateral upper extremities (correlation coefficients = 0.067, p = 0.111). @*Conclusion@#The risk of lymphedema in breast cancer surgery and adjuvant treatments is multifactorial. The number of retrieved lymph nodes during sentinel biopsy was not associated with the incidence of lymphedema.
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Purpose@#Following the outbreak and global spread of the coronavirus disease 2019 (COVID-19), an increasing number of people have turned to cycling. This study aims to investigate the epidemiology of bicycle-related injuries before and after the emergence of the COVID-19. @*Methods@#In this retrospective study, we collected medical records of those patients who visited the emergency room for orthopedic injuries related to bicycle accidents. The “COVID-19 period” consisted of the patients identified from April 1 to November 31 in the year 2020, while the “pre-COVID-19 period” consisted of those identified during the same months of the year 2019. @*Results@#A total of 519 patients were identified. The bicycle-related injuries increased by 5.1% during the COVID-19, in comparison to the pre-COVID-19 period. Among these, 76.3% were men. The highest incidence of the injuries was seen for 10– 19 years of age during the pre-COVID-19, and for 50– 59 years of age during the COVID-19 period. Overall, upper limb injuries were the commonest, consisting of 32.2% of all injuries. The shoulder injuries were the commonest in the pre-COVID-19, while the knee injuries were the commonest in the COVID-19 period. Assessing the severity of the injuries, contusion (81.8%) was the commonest. Of the injuries requiring hospital admissions, hip injuries had the highest incidence at 76.5%. @*Conclusion@#During the COVID-19, the total number of bicycle-related injuries did not increase significantly. In the bicycle-related injuries, the middle-age group had the highest proportion during the COVID-19 period. More efficient prevention strategies for middle-aged riders are necessary.
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Purpose@#Sentinel lymph node biopsy (SLNB) has become a standard axillary staging surgery for early breast cancer, and the proportion of patients requiring axillary lymph node dissection (ALND) is decreasing. We aimed to evaluate the association between the number of sentinel lymph nodes (SLNs) retrieved and the risk of lymphedema of the ipsilateral arm. @*Methods@#Prospectively collected medical records of 910 patients were reviewed.Lymphedema was defined as a difference in circumference > 2 cm compared to the contralateral arm and/or having clinical records of lymphedema treatment in the rehabilitation clinic. @*Results@#Together with an objective and subjective assessment of lymphedema, 36 patients (6.1%) had lymphedema in the SLNB group and 85 patients (27.0%) had lymphedema in the ALND group (p < 0.001). In a multivariate analysis of the whole cohort, risk factors significantly associated risk with the development of lymphedema were body mass index, mastectomy (vs.breast-conserving surgery), ALND, and radiation therapy. In logistic regression models in the SLNB group only, there was no correlation between the number of retrieved SLNs and the incidence of lymphedema. In addition, in the Pearson correlation analysis, no correlation was observed between the number of retrieved SLNs and the difference in circumference between the ipsilateral and contralateral upper extremities (correlation coefficients = 0.067, p = 0.111). @*Conclusion@#The risk of lymphedema in breast cancer surgery and adjuvant treatments is multifactorial. The number of retrieved lymph nodes during sentinel biopsy was not associated with the incidence of lymphedema.
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Background@#and PurposeMild cognitive impairment (MCI) is a condition with diverse clinical outcomes and subgroups. Here we investigated the topographic distribution of tau in vivo using the positron emission tomography (PET) tracer [18F]THK5351 in MCI subgroups. @*Methods@#This study included 96 participants comprising 38 with amnestic MCI (aMCI), 21 with nonamnestic MCI (naMCI), and 37 with normal cognition (NC) who underwent 3.0-T MRI, [18F]THK5351 PET, and detailed neuropsychological tests. [18F]flutemetamol PET was also performed in 62 participants. The aMCI patients were further divided into three groups: 1) verbal-aMCI, only verbal memory impairment; 2) visual-aMCI, only visual memory impairment; and 3) both-aMCI, both visual and verbal memory impairment. Voxel-wise statistical analysis and region-of-interest -based analyses were performed to evaluate the retention of [18F]THK5351 in the MCI subgroups. Subgroup analysis of amyloid-positive and -negative MCI patients was also performed. Correlations between [18F]THK5351 retention and different neuropsychological tests were evaluated using statistical parametric mapping analyses. @*Results@#[18F]THK5351 retention in the lateral temporal, mesial temporal, parietal, frontal, posterior cingulate cortices and precuneus was significantly greater in aMCI patients than in NC subjects, whereas it did not differ significantly between naMCI and NC participants. [18F] THK5351 retention was greater in the both-aMCI group than in the verbal-aMCI and visualaMCI groups, and greater in amyloid-positive than amyloid-negative MCI patients. The cognitive function scores were significantly correlated with cortical [18F]THK5351 retention. @*Conclusions@#[18F]THK5351 PET might be useful for identifying distinct topographic patterns of [18F]THK5351 retention in subgroups of MCI patients who are at greater risk of the progression to Alzheimer's dementia.
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Because of repeated failures of clinical trials, the concept of Alzheimer's disease (AD) has been changing rapidly in recent years. As suggested by the National Institute on Aging and the Alzheimer's Association Research Framework, the diagnosis and classification of AD is now based on biomarkers rather than on symptoms, allowing more accurate identification of proper candidates for clinical trials by pathogenesis and disease stage. Recent development in neuroimaging has provided a way to reveal the complex dynamics of amyloid and tau in the brain in vivo, and studies of blood biomarkers are taking another leap forward in diagnosis and treatment of AD. In the field of basic and translational research, the development of animal models and a deeper understanding of the role of neuroinflammation are taking a step closer to clarifying the pathogenesis of AD. Development of big data and the Internet of Things is also incorporating dementia care and research into other aspects. Largescale genetic research has identified genetic abnormalities that can provide a foundation for precision medicine along with the aforementioned digital technologies. Through the first international conference of the Korean Dementia Association, experts from all over the world gathered to exchange opinions with association members on these topics. The Academic Committee of the Korean Dementia Association briefly summarizes the contents of the lectures to convey the depth of the conference and discussions. This will be an important milestone in understanding the latest trends in AD's pathogenesis, diagnostic and therapeutic research and in establishing a future direction.
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Purpose@#Hereditary cancer syndrome means that inherited genetic mutations can increase a person's risk of developing cancer. We assessed the frequency of germline mutations using an nextgeneration sequencing (NGS)–based multiple-gene panel containing 64 cancer-predisposing genes in Korean breast cancer patients with clinical features of hereditary breast and ovarian cancer syndrome (HBOC). @*Materials and Methods@#A total of 64 genes associated with hereditary cancer syndrome were selected for development of an NGS-based multi-gene panel. Targeted sequencing using the multi-gene panel was performed to identify germline mutations in 496 breast cancer patients with clinical features of HBOC who underwent breast cancer surgery between January 2002 and December 2017. @*Results@#Of 496 patients, 95 patients (19.2%) were found to have 48 deleterious germline mutations in 16 cancer susceptibility genes. The deleterious mutations were found in 39 of 250 patients (15.6%) who had breast cancer and another primary cancer, 38 of 169 patients (22.5%) who had a family history of breast cancer (≥ 2 relatives), 16 of 57 patients (28.1%) who had bilateral breast cancer, and 29 of 84 patients (34.5%) who were diagnosed with breast cancer at younger than 40 years of age. Of the 95 patients with deleterious mutations, 60 patients (63.2%) had BRCA1/2 mutations and 38 patients (40.0%) had non-BRCA1/2 mutations. We detected two novel deleterious mutations in BRCA2 and MLH1. @*Conclusion@#NGS-based multiple-gene panel testing improved the detection rates of deleterious mutations and provided a cost-effective cancer risk assessment.
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Purpose@#Diabetes Mellitus (DM) is a leading cause of death with a prevalence rate of 12.4% in South Korea. Self-management is crucial for patients with DM, because many studies have reported that self-management intervention based on the Health Belief Model (HBM) is effective. The purpose of this study was to investigate the current state of HBM based intervention studies and the components and effects of the theories used in the study for diabetes patients. @*Methods@#A systematic review was conducted using the Pubmed, Cochrane Library and Embase databases from January 2009 to May 2019. We reviewed characteristics of intervention based on the HBM in randomized controlled clinical trials (RCTs), quasi-experimental study intervention. @*Results@#Eight studies published in English between 2009 and 2019 were included in this review. The key components of the health behavior promotion program applied to the DM patients were perceived susceptibility, perceived severity, perceived benefits, perceived barriers and self-efficacy. The intervention based on these components has reported to significantly increase the health behavior change, likelihood of taking health action and improve physiological indicators (HbA1c, and fasting blood sugar etc.). @*Conclusion@#This study highlighted the importance of intervention programs based on the HBM for DM patients.
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Purpose@#Paclitaxel is a cytotoxic chemotherapy commonly used in patients with triple negative breast cancer (TNBC); however, the resistance to paclitaxel is a cause of poor response in the patients. The aim of this study was to examine the role of protein phosphatase 1H (PPM1H) in paclitaxel resistance in breast cancer patients. @*Methods@#To investigate the function of PPM1H in paclitaxel treatment, we conducted in vitro assays and molecular experiments using a stable cell line (MDA-MB-231) in which PPM1H is overexpressed. We also performed molecular analyses on patient tissue samples. Molecular expression related to PPM1H in breast cancer patients was analyzed using TCGA data. @*Results@#We investigated whether PPM1H was associated with paclitaxel resistance in breast cancer. PPM1H expression was upregulated in breast cancer cells treated with paclitaxel. We also observed that overexpression of PPM1H in breast cancer cells resulted in increased sensitivity to paclitaxel in vitro. Additionally, paclitaxel treatment induced dephosphorylation of cyclin-dependent kinase (CDK) inhibitor p27 (p27), which was more evident in PPM1H-overexpressing cells. To understand how upregulation of PPM1H increases paclitaxel sensitivity, we determined the levels of p27, phospho-p27, and CDK2, since CDK2 exerts antagonistic effects against PPM1H on p27 phosphorylation. The patient-derived xenograft (PDX) tumors that did not respond to paclitaxel showed increased levels of CDK2 and phospho-p27 and decreased levels of total p27 compared to the other breast tumor tissues. The use of dinaciclib, a selective CDK inhibitor, significantly inhibited tumor growth in the PDX model. @*Conclusion@#CDK2 kinase activity was significantly upregulated in basal breast cancer tumors and was negatively correlated with p27 protein levels in the TCGA breast cancer dataset, suggesting that targeting CDK2 may be an effective treatment strategy for TNBC patients.
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Purpose@#Endocrine therapy is a standard treatment for hormone receptor-positive breast cancer, which accounts for 60%–75% of all breast cancer. Hormone receptor positivity is a prognostic and predictive biomarker in breast cancer. Approximately 50%–80% of breast cancer is also positive for androgen receptor (AR), but the prognostic and predictive value of AR expression in breast cancer is controversial. Here, we investigated AR expression and its prognostic value in patients with surgically resected breast cancer in Korea. @*Methods@#We retrospectively reviewed the medical records of patients who had surgically resected breast cancer to collect AR expression data and other clinicopathological data. The optimal cut-off for AR positivity was determined using a receiver operating characteristic curve analysis. @*Results@#We reviewed 957 patients with surgically resected breast cancer from June 2012 to April 2013. The median follow-up was 62 months, and relapse events occurred in 101 (10.6%) patients. Unlike the cut-off value of 1% or 10% in previous reports, 35% was determined to be best for predicting relapse-free survival (RFS) in this study. At the cut-off value of 35%, 654 (68.4%) patients were AR-positive. AR expression was more prevalent in luminal A (87.6%) and luminal B (73.1%) types than in human epidermal growth factor receptor 2-positive (56.2%) or triple-negative (20.6%) types. AR expression of ≥ 35% was significantly related to longer RFS in a multivariate analysis (hazard ratio, 0.430; 95% confidence interval, 0.260–0.709; p = 0.001). @*Conclusion@#We propose a cut-off value of 35% to best predict RFS in patients with surgically resected breast cancer. AR expression was positive in 68.4% of patients, and AR positivity was found to be an independent prognostic factor for longer RFS.
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In the article, “A Validation Study of a Multiple Reaction Monitoring-Based Proteomic Assay to Diagnose Breast Cancer” in Volume 22(4), page 579-586 was error in the table. In Table 1, the value of pN0 was incorrectly listed as 29 (56.9) in ‘diagnosed as normal by biomarker’ and corrected to 39 (76.5). The authors apologize for any inconvenience that this may have caused.