Schisandrol A and gomisin N from Schisandra chinensis extract improve hypogonadism via anti-oxidative stress in TM3 Leydig cells

BACKGROUND/OBJECTIVES@#Male hypogonadism is a condition where the body does not produce enough testosterone and significantly impacts health. Age, obesity, genetics, and oxidative stress are some physiological factors that may contribute to testosterone deficiency.Previous studies have shown many pharmacological benefits of Schisandra chinensis (S. chinensis) Baillon as an anti-inflammatory and antioxidant. However, the molecular mechanism of attenuating hypogonadism is yet to be well established. This research was undertaken to study the effects of S. chinensis extract (SCE) on testosterone deficiency.MATERIALS/METHODS: S. chinensis fruit was pulverized and extracted using 60% aqueous ethanol. HPLC analysis was performed to analyze and quantify the lignans of the SCE. @*RESULTS@#The 2,2-diphenyl-2-picrylhydrazyl and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) scavenging assays confirmed that the SCE and its major lignans (schisandrol A and gomisin N) inhibit oxidative stress. Effects of SCE analysis on the testosterone level under oxidative stress conditions revealed that both schisandrol A and gomisin N were able to recover the lowered testosterone levels. Through mRNA expression of TM3 Leydig cell, we observed that the SCE lignans were able to induce the enzymes involved in testosterone biosynthesis-related genes such as 3β-HSD4 (P < 0.01 for SCE, and P < 0.001 for schisandrol A and gomisin N), 17β-HSD3 (P < 0.001 for SCE, schisandrol A and gomisin N), and 17, 20-desmolase (P < 0.01 for schisandrol A, and P < 0.001 for SCE and gomisin N). @*CONCLUSIONS@#These results support that SCE and its active components could be potential therapeutic agents for regulating and increasing testosterone production.

Therapeutic Potentiality of Celtis choseniana Nakai on Androgenic Alopecia through Repression of Androgen Action and Modulation of Wnt/β-catenin Signaling

In this study, we investigated the efficacy of Celtis choseniana Nakai (C. choseniana) as complementary herbal medicine to ameliorate androgenic alopecia (AGA). The effects of C. choseniana on AGA were evaluated using testosterone propionate-induced AGA mouse model and dihydrotestosterone-treated human hair follicle dermal papilla cells. In vivo, C. choseniana treatment deactivated androgen signaling by reducing the concentration of serum dihydrotestosterone level and expressions of 5α-reductase 2 and androgen receptor. Next, C. choseniana treatment increased the hair regrowth rate. Histological studies demonstrated that C. choseniana induced the anagen phase in testosterone propionate-induced AGA mouse model. Cellular proliferation was promoted by C. choseniana treatment via increasing the expression of proliferation factors, such as proliferating cell nuclear antigen and cyclin D1. Furthermore, C. choseniana treatment increased the expression of proteins related to the Wnt/β-catenin signaling pathway. In addition, dickkopf-1, a Wnt inhibitor, was downregulated with C. choseniana treatment. Likewise, C. choseniana treatment promoted cellular proliferation in vitro. This study demonstrated the inhibitory effect of C. choseniana on androgen-induced AGA. Moreover, C. choseniana induced activation of Wnt/β-catenin signaling, resulting in prolonged anagen and cellular proliferation. Therefore, we suggest that C. choseniana can be used as a therapeutic agent to alleviate AGA.

Efficacy of preoperative chemoradiotherapy in patients with cT2N0 distal rectal cancer

Purpose@#This study was designed to determine the feasibility of preoperative chemoradiotherapy (PCRT) in patients with clinical T2N0 distal rectal cancer. @*Methods@#Patients who underwent surgery for clinical T2N0 distal rectal cancer between January 2008 and December 2016 were included. Patients were divided into PCRT and non-PCRT groups. Non-PCRT patients underwent radical resection or local excision (LE) according to the surgeon’s decision, and PCRT patients underwent surgery according to the response to PCRT. Patients received 50.0 to 50.4 gray of preoperative radiotherapy with concurrent chemotherapy. @*Results@#Of 127 patients enrolled, 46 underwent PCRT and 81 did not. The mean distance of lesions from the anal verge was lower in the PCRT group (P=0.004). The most frequent operation was transanal excision and ultralow anterior resection in the PCRT and non-PCRT groups, respectively. Of the 46 patients who underwent PCRT, 21 (45.7%) achieved pathologic complete response, including 15 of the 24 (62.5%) who underwent LE. Rectal sparing rate was significantly higher in the PCRT group (11.1% vs. 52.2%, P<0.001). There were no significant differences in 3- and 5-year overall survival and recurrence-free survival regardless of PCRT or surgical procedures. @*Conclusion@#PCRT in clinical T2N0 distal rectal cancer patients increased the rectal sparing rate via LE and showed acceptable oncologic outcomes. PCRT may be a feasible therapeutic option to avoid abdominoperineal resection in clinical T2N0 distal rectal cancer.

Molecular characterization of dysplasia-initiated colorectal cancer with assessing matched tumor and dysplasia samples

Purpose@#Ulcerative colitis (UC) is known to have an association with the increased risk of colorectal cancer (CRC), and UC-associated CRC does not follow the typical progress pattern of adenoma-carcinoma. The aim of this study is to investigate molecular characteristics of UC-associated CRC and further our understanding of the association between UC and CRC. @*Methods@#From 5 patients with UC-associated CRC, matched normal, dysplasia, and tumor specimens were obtained from formalin-fixed paraffin-embedded (FFPE) samples for analysis. Genomic DNA was extracted and whole exome sequencing was conducted to identify somatic variations in dysplasia and tumor samples. Statistical analysis was performed to identify somatic variations with significantly higher frequencies in dysplasia-initiated tumors, and their relevant functions were investigated. @*Results@#Total of 104 tumor mutation genes were identified with higher mutation frequencies in dysplasia-initiated tumors. Four of the 5 dysplasia-initiated tumors (80.0%) have TP53 mutations with frequent stop-gain mutations that were originated from matched dysplasia. APC and KRAS are known to be frequently mutated in general CRC, while none of the 5 patients have APC or KRAS mutation in their dysplasia and tumor samples. Glycoproteins including mucins were also frequently mutated in dysplasia-initiated tumors. @*Conclusion@#UC-associated CRC tumors have distinct mutational characteristics compared to typical adenoma-carcinoma tumors and may have different cancer-driving molecular mechanisms that are initiated from earlier dysplasia status.

Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group / Journal of the Korean Cancer Association, 대한암학회지

Next-generation sequencing (NGS) is becoming essential in the fields of precision oncology. With implementation of NGS in daily clinic, the needs for continued education, facilitated interpretation of NGS results and optimal treatment delivery based on NGS results have been addressed. Molecular tumor board (MTB) is multidisciplinary approach to keep pace with the growing knowledge of complex molecular alterations in patients with advanced solid cancer. Although guidelines for NGS use and MTB have been developed in western countries, there is limitation for reflection of Korea’s public health environment and daily clinical practice. These recommendations provide a critical guidance from NGS panel testing to final treatment decision based on MTB discussion.

Suicide Risk in Patients With Diabetes Varies by the Duration of Diabetes: The Korea National Health and Nutrition Examination Survey (2019)

Objective@#The objectives of this study were to investigate the suicide risk in diabetes patients and evaluate the variations in suicide risk by the duration of diabetes using a large population sample in South Korea. @*Methods@#Data from 6,296 adults in the 2019 Korea National Health and Nutrition Examination Survey were included. The suicidal ideation, suicide plans, and suicidal behavior of diabetes patients were compared to the general population. After classifying the patients into ≤1 year, 2 to 9 years, and ≥10 years of diabetes duration, we evaluated the relationship between the duration of diabetes and the suicide risk. @*Results@#Diabetes patients had higher prevalences of suicidal ideation (9.1%, p<0.001) and suicide plans (3.6%, p<0.001) than the general population. After adjusting for potential confounding factors, suicide plans (adjusted odds ratio [aOR]=2.926, 95% confidence interval [CI]=1.325–6.463) were significantly associated with diabetes. In the 2 to 9 years group of diabetes patients, we found an increase in the risk of suicidal ideation (aOR=2.035, 95% CI=1.129–3.670), suicide plans (aOR=3.507, 95% CI=1.538–7.996), and suicidal behavior (aOR=7.130, 95% CI=2.035–24.978) after adjusting for the covariates. However, no increases in suicide risk were observed ≤1 year and ≥10 years after diabetes diagnosis. @*Conclusion@#In adults, diabetes is associated with an increase in suicide risk. Suicide risk in diabetes patients showed an inverted U-shaped depending upon the duration of diabetes.

The extract of Celtis choseniana Nakai alleviates testosterone-induced benign prostatic hyperplasia through inhibiting 5α reductase type 2 and the Akt/NF-κB/AR pathway / 中国天然药物

Benign prostatic hyperplasia (BPH) is a chronic male disease characterized by the enlarged prostate. Celtis chosenianaNakai (C. choseniana) is medicinally used to alleviate pain, gastric disease, and lung abscess. In this study, the effect of C. choseniana extract on BPH was investigated using testosterone-induced rats. Sprague Dawley rats were divided into five groups: control, BPH (testosterone 5 mg·kg-1), Fina (finasteride 2 mg·kg-1), and C. choseniana (50 and 100 mg·kg-1). After four weeks of TP treatment with finasteride or C. choseniana, prostate weights and DHT levels were measured. In addition, the prostates were histopathologically examined and measured for protein kinase B (Akt)/nuclear factor-κB (NF-κB)/AR signaling, proliferation, apoptosis, and autophagy. Prostate weight and epithelial thickness were reduced in the C. choseniana groups compared with that in the BPH group. The extract of C. choseniana acted as a 5α reductase inhibitor, reducing DHT levels in the prostate. Furthermore, the extract of C. choseniana blocked the activation of p-Akt, nuclear NF-κB activation and reduced the expression of AR and PSA compared with BPH. Moreover, the expression of Bax, PARP-1, and p53 increased, while the expression of bcl-2 decreased. The present study demonstrated that C. choseniana extract alleviated testosterone-induced BPH by suppressing 5α reductase and Akt/NF-κB activation, reducing AR signaling and inducing apoptosis and autophagy in the prostate. These results suggested that C. choseniana probably contain potential herbal agents to alleviate BPH.

Mediation Effect of the Coping Strategies on the Relation Between Stress and Sleep Quality

Objective@#Recently data has been accumulated regarding the role of coping strategies in the relationship between stress and sleep quality. Therefore, we set out to identify the mediating effects of coping strategies between stress and sleep quality. @*Methods@#A online-based cross-sectional study was performed using the Perceived Stress Scale-10, the Pittsburgh Sleep Quality Index, and a simplification of the 60-item Coping Orientation to Problems Experienced (Brief COPE) inventory in the nonclinical adult sample. The 24 items of Brief COPE were categorized into four factors (social support, problem solving, avoidance, positive thinking). Then, we used the PROCESS macro to conduct the multiple mediation analysis for the four coping styles as potential mediators in the relationship between stress and sleep quality, and an additional subgroup analysis was examined to identify a gender difference for the mediation effect. @*Results@#As a group, four coping styles mediated significantly the association between perceived stress and poor sleep quality. And avoidance has maintained its significance thought all regression analyses. Finally, this results remained as same in the females. @*Conclusion@#The effect of perceived stress on poor sleep quality was mediated by coping strategies, especially by avoidance. Thus, further research should consider the coping styles of individuals to reduce the influence of stress on sleep quality.

Clinical characteristics and survival of colorectal cancer patients in Korea stratified by age

Background/Aims@#This nationwide study was undertaken to determine differences in clinicopathologic characteristics and survival of patients with colorectal cancer (CRC) according to age using big data from the Korean National Health Insurance Service (NHIS). @*Methods@#The NHIS data including quality assessment of CRC by the Health Insurance Review & Assessment Service in Korea between 2011 and 2014 were analyzed. Based on age, patients were divided into three groups: not-old patients (< 65), young-old patients (65 to 74 years old) and old-old patients (≥ 75 years old). @*Results@#We included 71,513 CRC patients. The median follow-up duration was 3.2 years (range, 0.003 to 5.5). Male patients constituted 60%. The median age of patients was 65 years (range, 18 to 102). Colon was the cancer site in 59.8% of not-old patients, 62.9% of young-old patients, and 66.1% of old-old patients. Compared to not-old patients, young-old and old-old patients were more likely to be diagnosed with colon adenocarcinoma and well/moderate differentiation or adequate differentiation (all p < 0.001). Old patients underwent more emergency operation (p < 0.001) and received less adjuvant therapy in stage I–III (p < 0.001). The probability of 3-year survival of young-old or old-old patients was worse than that for not-old patients (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.46 to 1.64) (HR, 3.19; 95% CI, 3.03 to 3.37). @*Conclusions@#Old patients with CRC show different histology from younger patients. They are more frequently to have colon as primary lesion. They undergo less adjuvant therapy. Further studies and evidence-based guidelines for older patients with CRC are warranted to improve their outcome.

Predictors of 1-Year Rehospitalization for Patients with Major Depressive Disorder: A Retrospective Study in a University Hospital / 우울ㆍ조울병

Background@#This study aimed to assess the clinical characteristics of patients with major depressive disorder who were rehospitalized within 1 year and to determine whether the 1-year rehospitalization rate varied depending on the type of medication and treatment method. @*Methods@#Clinical characteristics of 531 patients hospitalized for major depressive disorder were assessed. The use and type of antidepressants, antipsychotics, mood stabilizers, and hypnotics were also evaluated. @*Results@#Of the 531 subjects, 68 (12.8%) were rehospitalized within a year. The number of past depressive episodes (1.56±2.67 vs. 0.90±1.18) (p=0.048) and the number of previous psychiatric hospitalizations (0.82±1.93 vs. 0.29±0.83 times) (p=0.029) were high in the 1-year rehospitalization group. The rate of family history of mood disorder (25.0% vs. 13.6%) (p=0.014) and the rate of comorbid personality disorder (16.2% vs. 8.6%) (p=0.049) were also high in the 1-year rehospitalization group. Multiple logistic regression analysis showed that the number of previous psychiatric hospitalizations affected the rate of 1-year rehospitalization (p=0.003). @*Conclusion@#The number of previous psychiatric hospitalizations could be used to predict rehospitalizations of patients with major depressive disorder within 1 year. In addition, family history of mood disorders and comorbidity of personality disorders may affect rehospitalization of such patients.

Clinical characteristics and survival of colorectal cancer patients in Korea stratified by age

Background/Aims@#This nationwide study was undertaken to determine differences in clinicopathologic characteristics and survival of patients with colorectal cancer (CRC) according to age using big data from the Korean National Health Insurance Service (NHIS). @*Methods@#The NHIS data including quality assessment of CRC by the Health Insurance Review & Assessment Service in Korea between 2011 and 2014 were analyzed. Based on age, patients were divided into three groups: not-old patients (< 65), young-old patients (65 to 74 years old) and old-old patients (≥ 75 years old). @*Results@#We included 71,513 CRC patients. The median follow-up duration was 3.2 years (range, 0.003 to 5.5). Male patients constituted 60%. The median age of patients was 65 years (range, 18 to 102). Colon was the cancer site in 59.8% of not-old patients, 62.9% of young-old patients, and 66.1% of old-old patients. Compared to not-old patients, young-old and old-old patients were more likely to be diagnosed with colon adenocarcinoma and well/moderate differentiation or adequate differentiation (all p < 0.001). Old patients underwent more emergency operation (p < 0.001) and received less adjuvant therapy in stage I–III (p < 0.001). The probability of 3-year survival of young-old or old-old patients was worse than that for not-old patients (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.46 to 1.64) (HR, 3.19; 95% CI, 3.03 to 3.37). @*Conclusions@#Old patients with CRC show different histology from younger patients. They are more frequently to have colon as primary lesion. They undergo less adjuvant therapy. Further studies and evidence-based guidelines for older patients with CRC are warranted to improve their outcome.

Association between Glycemic Control in Patients with Diabetes and Mental Health Variables Including Depression / 우울ㆍ조울병

Background@#The purpose of this study was to measure several mental health variables according to HbA1c level and examine their relationship among diabetic patients. @*Methods@#Total 89 outpatients who attended diabetes education program at St. Vincent’s Hospital, The Catholic University of Korea College of Medicine, were enrolled this study. The Beck Depression Inventory (BDI), State-Trait Anxiety Inventory, Stress Response Inventory (SRI), abbreviated version of World Health Organization Quality of Life assessment instrument (WHOQOL-BREF), Insomnia Severity Index, and Epworth Sleepiness Scale (ESS) were administered to all patients. Significant differences between groups were assessed by t-test and chi-squared test. Pearson correlation and multiple linear regression analyses were used to identify the variables that affect HbA1c levels. @*Results@#The well-controlled group had a significantly lower BDI score than the poorly controlled group. The wellcontrolled group also showed significantly lower SRI and ESS. HbA1c, BDI, SRI, and ESS were positively correlated. Duration and BDI were the only variables affecting HbA1c levels. @*Conclusion@#Emphasis should be given to the identification and management of mental health problems, including especially depressive symptoms in patients with diabetes.

Management of isolated para-aortic lymph node recurrence after surgery for colorectal cancer

PURPOSE: The rare incidence of isolated para-aortic lymph node (PALN) recurrence of colorectal cancer has precluded the formulation of treatment guidelines. This study evaluated and compared the effects of different treatment modalities on survival outcomes in patients with PALN recurrence.METHODS: Patients diagnosed with isolated PALN recurrence after curative resection for primary colorectal cancer from January 2004 to December 2014 were evaluated retrospectively. Patients with isolated recurrence were selected using imaging modalities. Overall survival (OS) and survival after recurrence (SAR) were analyzed and compared between different treatments using the Kaplan-Meier method.RESULTS: The median OS was 64 months with a median follow-up time of 50 months. Of the 46 patients with PALN recurrence, 35 (76.1%) had isolated recurrences. Of these 35 patients, 16 underwent PALN resection and 19 received chemotherapy. Median SAR was significantly longer in patients who did than did not undergo resection (71 months vs. 39 months, P = 0.017). Median OS tended to be longer in patients who did than did not undergo resection (77 months vs. 62 months, P = 0.055). SAR was similar in patients who received radiotherapy and those who underwent resection (34 months vs. 46 months, P = 0.146). Three of 16 patients (18.8%) who underwent resection were found to be recurrence-free.CONCLUSION: Surgical resection of isolated PALN recurrence may benefit patients, with favorable survival outcomes and by providing definitive diagnosis for proper treatment planning.

Correlation between Sleep and C-reactive Protein of Patients in Amnestic Mild Cognitive Impairment and Alzheimer’s Dementia

Objective@#Sleep affects systemic inflammation and amyloid deposition, and sleep disturbance is known to be a risk factor for cognitive decline. To date, literatures on the relationship between peripheral inflammatory markers and sleep in Alzheimer’s de-mentia and mild cognitive impairment patients have been scarce. The aim of this study was to determine the correlation between sleep and C-reactive protein (CRP) in Alzheimer’s dementia and amnestic mild cognitive impairment patients. @*Methods@#A total of 81 patients were divided in to four groups: amyloid negative healthy control, amyloid negative amnestic mild cognitive impairment, amyloid positive amnestic mild cognitive impairment, and amyloid positive Alzheimer’s dementia.Demographic data and cognitive measurement through the Consortium to Establish a Registry for Alzheimer’s Disease were conducted. Amyloid positivity status was attained through positron emission tomography scans using [18F]-flutemetamol. The quality of sleep was evaluated by the sleep item of Korean Neuropsychiatric Inventory (K-NPI-SLEEP), and peripheral blood tests were conducted to measure CRP. @*Results@#There was no statistically difference in CRP levels or K-NPI-SLEEP scores among four groups. Moreover, there was no association between K-NPI-SLEEP and CRP in four groups. @*Conclusion@#Since K-NPI-SLEEP score shows overall, subjective sleep problems, further follow-up studies in consideration for objective sleep studies to unravel the relationship of peripheral inflammatory markers and sleep in amnestic mild cognitive impairment and Alzheimer’s dementia patients.

Korean Clinical Practice Guideline for the Diagnosis and Treatment of Insomnia in Adults

Objective@#We aim to present a clinical guideline for the diagnosis and treatment of insomnia in adults by reviewing and integrating existing clinical guidelines. The purpose of this guideline is to assist clinicians who perform evidence-based insomnia treatment. @*Methods@#We selected literature that may be appropriate for use in guideline development from evidence-based practice guidelines that have been issued by an academic or governmental institution within the last five years. The core question of this guideline was made in sentence form including Patient/Problem, Intervention, Comparison, Outcome (PICO) elements. After searching PubMed, EMBASE, and medical guideline issuing agencies, three guidelines were judged to be the most appropriately reviewed, up-to-date, and from trusted sources. @*Results@#The Appraisal of Guidelines for Research and Evaluation (AGREE) II tool was used to evaluate the quality of the three clinical guidelines. The final outcome of the guideline development process is a total of 15 recommendations that report the strength of the recommendation, the quality of evidence, a summary of content, and considerations in applying the recommendation. @*Conclusion@#It is vital for clinical guidelines for insomnia to be developed and continually updated in order to provide more accurate evidence-based treatments to patients.

A Phase II Study of Avelumab Monotherapy in Patients with Mismatch Repair–Deficient/Microsatellite Instability–High or POLE-Mutated Metastatic or Unresectable Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We evaluated the efficacy and safety of avelumab, an anti-PD-L1 antibody, in patients with metastatic or unresectable colorectal cancer (mCRC) with mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) or POLE mutations. @*Materials and Methods@#In this prospective, open-label, multicenter phase II study, 33 patients with mCRC harboring dMMR/MSI-H or POLE mutations after failure of ≥1st-line chemotherapy received avelumab 10 mg/kg every 2 weeks. dMMR/MSI-H was confirmed with immunohistochemical staining (IHC) by loss of expression of MMR proteins or polymerase chain reaction (PCR) for microsatellite sequences. POLE mutation was confirmed by next-generation sequencing (NGS). The primary endpoint was the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors ver. 1.1. @*Results@#The median age was 60 years, and 78.8% were male. Thirty patients were dMMR/MSI-H and three had POLE mutations. The ORR was 24.2%, and all of the responders were dMMR/MSI-H. For 21 patients with MSI-H by PCR or NGS, the ORR was 28.6%. At a median follow-up duration of 16.3 months, median progression-free survival and overall survival were 3.9 and 13.2 months in all patients, and 8.1 months and not reached, respectively, in patients with MSI-H by PCR or NGS. Dose interruption and discontinuation due to treatment-related adverse events occurred in 4 and 2 patients, respectively, with no treatment-related deaths. @*Conclusion@#Avelumab displayed antitumor activity with manageable toxicity in patients with previously treated mCRC harboring dMMR/MSI-H. Diagnosis of dMMR/MSI-H with PCR or NGS could be complementary to IHC to select patients who would benefit from immunotherapy.

Landscape of Actionable Genetic Alterations Profiled from 1,071 Tumor Samples in Korean Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. MATERIALS AND METHODS: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. RESULTS: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. CONCLUSION: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.

Long-term Surgical and Chemical Castration Deteriorates Memory Function Through Downregulation of PKA/CREB/BDNF and c-Raf/MEK/ERK Pathways in Hippocampus / 대한배뇨장애요실금학회지

PURPOSE: Goserelin is a drug used for chemical castration. In a rat model, we investigated whether surgical and chemical castration affected memory ability through the protein kinase A (PKA)/cyclic adenosine monophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) and c-Raf/mitogen-activated protein kinases-extracellular signal–regulated kinases (MEK)/extracellular signal–regulated kinases (ERK) pathways in the hippocampus. METHODS: Orchiectomy was performed for surgical castration and goserelin acetate was subcutaneously transplanted into the anterior abdominal wall for chemical castration. Immunohistochemistry was done to quantify neurogenesis. To assess the involvement of the PKA/CREB/BDNF and c-Raf/MEK/ERK pathways in the memory process, western blots were used. RESULTS: The orchiectomy group and the goserelin group showed less neurogenesis and impaired short-term and spatial memory. Phosphorylation of PKA/CREB/BDNF and phosphorylation of c-Raf/MEK/ERK decreased in the orchiectomy and goserelin groups. CONCLUSIONS: Short-term memory and spatial memory were affected by surgical and chemical castration via the PKA/CREB/BDNF and c-Raf/MEK/ERK signaling pathways.

Hepatic resection after neoadjuvant chemotherapy for patients with liver metastases from colorectal cancer: need for cautious planning

PURPOSE: Current neoadjuvant chemotherapy (NAC) may enable therapies such as surgical resection and local ablation of metastases in patients with colorectal liver metastasis (CLM). We evaluated outcomes in CLM patients who underwent resection and/or local treatment after NAC and identified prognostic factors for oncologic outcomes. METHODS: Patients who received NAC followed by resection and/or local treatment of hepatic metastasis from 2013 to 2015 were included. Treatment and tumor-related variables were tabulated. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Cox regression analysis was used to identify factors associated with RFS and OS. RESULTS: Sixty-eight patients received NAC followed by resection and/or local treatment of hepatic metastases. Targeted therapy was administered in 50% of the patients. RFS was 35.8% at 1 year and 19.4% at 2 years postoperatively. OS was 95.6% at 1 year and 88.2% at 2 years postoperatively. In the multivariable analysis, R1 resection margin (hazard ratio [HR], 3.95; P = 0.008) of the liver metastases and ypN1/ypN2 (HR, 2.356 and 1.983, respectively; P = 0.041) were associated with poor RFS. Both factors were also significantly related to OS. CONCLUSION: Resection margin of the metastatic tumor and ypN status are the only relevant factors for RFS and OS in CLM patients treated with NAC. Despite early and high rates of recurrence, CLM patients treated with NAC who undergo resection and/or local treatment have acceptable OS. Multidisciplinary review of candidates for surgery and cautious planning are crucial for achieving optimal outcomes.

Albizzia julibrissin Suppresses Testosterone-induced Benign Prostatic Hyperplasia by Regulating 5α-Reductase Type 2 – Androgen Receptor Pathway

Albizzia julibrissin (AJ) is an herbal medicine that shows low toxicity, promotes promoting blood circulation and mitigates the inflammation and has mild side effects. Benign prostate hyperplasia (BPH) is one of the most common diseases that occurs in older males and often results in lower urinary tract symptoms. This study was conducted to evaluate the protective effect of AJ against BPH using LNCaP cells and Sprague Dawley rats treated with testosterone. Treatment with AJ extract reduced the expression of androgen receptor (AR) and prostate-specific antigen (PSA) in vitro. In vivo, rats were divided into 6 groups: 1 (Normal Control); 2 (Testosterone propionate (TP) alone); 3 (TP + finasteride); 4 (TP + AJ 10 mg/kg); 5 (TP + AJ 50 mg/kg); 6 (TP + AJ 300 mg/kg). The groups treated with AJ showed reduced the relative prostate weights and BPH-related proteins were altered, with decreased AR, PSA and proliferating cell nuclear antigen (PCNA) observed by western blot. Histopathological analysis revealed the therapeutic effect of AJ, with a decreased thickness of epithelial cells and reduced level of PCNA and 5α-reductase type 2. These results suggest that AJ extract could ameliorate testosterone-induced benign prostatic hyperplasia.