• Title/Summary/Keyword: Disease Progression

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A1E Induces Apoptosis via Targeting HPV E6/E7 Oncogenes and Intrinsic Pathways in Cervical Cancer Cells

  • Ham, Sun Young;Bak, Ye Sol;Kwon, Tae Ho;Kang, Jeong Woo;Choi, Kang Duk;Han, Tae Young;Han, Il Young;Yang, Young;Jung, Seung Hyun;Yoon, Do Young
    • Journal of Applied Biological Chemistry
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    • v.57 no.2
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    • pp.103-111
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    • 2014
  • A1E is an extract from traditional Asian medicinal plants that has therapeutic activities against cancers, metabolic disease, and other intractable conditions. However, its mechanism of action on cervical cancer has not been studied. In order to ascertain if A1E would have pronounced anti-cervical cancer effect, cervical cancer cells were incubated with A1E and apoptosis was detected by nuclear morphological changes, annexin V-FITC/PI staining, cell cycle analysis, western blotting, Reverse-transcription polymerase chain reaction, and measurement of mitochondrial membrane potential. Expression of human papiloma virus E6 and E7 oncogenes was down-regulated in A1E-treated cervical cancer cells, while p53 and retinoblastoma protein levels were enhanced. A1E also perturbed cell cycle progression at sub-G1 and altered cell cycle regulatory factors in SiHa cervical cancer cells. A1E activated apoptotic intrinsic pathway markers such as caspase-9, caspase-3 and poly ADP-ribose polymerase, and down-regulated expression of Bcl-2 and Bcl-xl. A1E induced mitochondrial membrane potential collapse and cytochrome c release, and inhibited phosphatidylinositol 3-kinase (PI3K)/Akt, key factors involved in cell survival signaling. Taken all these results, A1E induced apoptosis via activation of the intrinsic pathway and inhibition of the PI3K/Akt survival-signaling pathway in SiHa cervical cancer cells. In conclusion, A1E exerts anti-proliferative action growth inhibition on cervical cancer cells through apoptosis which demonstrates its anti-cervical cancer properties.

The Study of Radiation Exposure Reduction by Developing Corpus Striatum Phantom (두개골-선조체 팬텀을 이용한 선량 저감화 방안 연구)

  • Kim, Jung-Soo;Park, Chan-Rok
    • Journal of radiological science and technology
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    • v.40 no.4
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    • pp.595-603
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    • 2017
  • The study is to produced a brain phantom simulating corpus striatum, which can evaluate the progression of parkinson's disease, to investigate possibility of reducing the brain exposure dose to CT while maintaining optimal image quality during PET-CT examinations. CT scans were performed by varying tube voltage (100, 120 kVp) and tube current (80, 140, 200 mAs) with $^{18}F$ FP-CIT injected into the phantom's hot sphere and background (radioactivity ratio 3:1)(reference condition; 120 kVp, 140 mAs). Estimated effective dose was calculated by using conversion factor according to each condition, and image quality was evaluated by setting SNR and CRChot image evaluation factors. Experimental results showed that the predicted effective dose below the CT imaging reference condition was reduced by at least 10% and by up to 60%, and the predicted effective dose beyond the reference condition was increased by 40%. In addition, there was no significant difference between SNR and CRChot of PET images, and it was confirmed that brain dose decreased with decrease of tube voltage and tube current. At the same time, there was no significant change in the quality of the image in terms of SNR and CRChot despite the change in scan conditions. This fact suggests that the quality of the images acquired under the existing dose conditions can be obtained even at low dose conditions and it is expected that it will be possible to use the brain PET-CT scan as a basic data for the research on reduction of dose and improvement of image quality.

Clinical outcome of proton therapy for patients with chordomas

  • Youn, Sang Hee;Cho, Kwan Ho;Kim, Joo-Young;Ha, Boram;Lim, Young Kyung;Jeong, Jong Hwi;Lee, Sang Hyun;Yoo, Heon;Gwak, Ho-Shin;Shin, Sang Hoon;Hong, Eun Kyung;Kim, Han Kyu;Hong, Je Beom
    • Radiation Oncology Journal
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    • v.36 no.3
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    • pp.182-191
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    • 2018
  • Purpose: To investigate the clinical outcome of proton therapy (PT) in patients with chordoma. Materials and Methods: Fifty-eight patients with chordoma treated with PT between June 2007 and December 2015 at the National Cancer Center, Korea, were retrospectively analyzed. The median total dose was 69.6 cobalt gray equivalent (CGE; range, 64.8 to 79.2 CGE). Local progression-free survival (LPFS), distant metastasis-free survival (DMFS), overall survival (OS), and disease-specific survival (DSS) rates were calculated by the Kaplan-Meier method. Results: With the median follow-up of 42.8 months (range, 4 to 174 months), the 5-year LPFS, DMFS, OS, and DSS rates were 87.9%, 86.7%, 88.3%, and 92.9%, respectively. The tumor location was associated with the patterns of failure: the LPFS rates were lower for cervical tumors (57.1%) than for non-cervical tumors (93.1%) (p = 0.02), and the DMFS rates were lower for sacral tumors (53.5%) than for non-sacral tumors (100%) (p = 0.001). The total dose was associated with both the LPFS rate and DMFS rate. The initial tumor size was associated with the DMFS rate, but was not associated with the LPFS rate. Three patients had grade 3 late toxicity with none ≥grade 4. Conclusion: PT is an effective and safe treatment in patients with chordomas. The tumor location was associated with the patterns of failure: local failure was common in cervical tumors, and distant failure was common in sacral tumors. Further refinement of PT, such as the utilization of intensity modulated PT for cervical tumors, is warranted to improve the outcome.

Repurposing Auranofin, an Anti-Rheumatic Gold Compound, to Treat Acne Vulgaris by Targeting the NLRP3 Inflammasome

  • Yang, Gabsik;Lee, Seon Joo;Kang, Han Chang;Cho, Yong-Yeon;Lee, Hye Suk;Zouboulis, Christos C.;Han, Sin-Hee;Ma, Kyung-Ho;Jang, Jae-Ki;Lee, Joo Young
    • Biomolecules & Therapeutics
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    • v.28 no.5
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    • pp.437-442
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    • 2020
  • Activation of the NLRP3 inflammasome is critical for host defense as well as the progression of inflammatory diseases through the production of the proinflammatory cytokine IL-1β, which is cleaved by active caspase-1. It has been reported that overactivation of the NLRP3 inflammasome contributes to the development and pathology of acne vulgaris. Therefore, inhibiting activation of the NLRP3 inflammasome may provide a new therapeutic strategy for acne vulgaris. In this study, we investigated whether auranofin, an anti-rheumatoid arthritis agent, inhibited NLRP3 inflammasome activation, thereby effectively treating acne vulgaris. Auranofin suppressed NLRP3 inflammasome activation induced by Propionibacterium acnes, reducing the production of IL-1β in primary mouse macrophages and human sebocytes. In a P. acnes-induced acne mouse model, injection of P. acnes into the ears of mice induced acne symptoms such as redness, swelling, and neutrophil infiltration. Topical application of auranofin (0.5 or 1%) to mouse ears significantly reduced the inflammatory symptoms of acne vulgaris induced by P. acnes injection. Topical application of auranofin led to the downregulation of the NLRP3 inflammasome activated by P. acnes in mouse ear skin. These results show that auranofin inhibits the NLRP3 inflammasome, the activation of which is associated with acne symptoms. The results further suggest that topical application of auranofin could be a new therapeutic strategy for treating acne vulgaris by targeting the NLRP3 inflammasome.

The Influence of Biomarker Mutations and Systemic Treatment on Cerebral Metastases from NSCLC Treated with Radiosurgery

  • Lee, Min Ho;Kong, Doo-Sik;Seol, Ho Jun;Nam, Do-Hyun;Lee, Jung-Il
    • Journal of Korean Neurosurgical Society
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    • v.60 no.1
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    • pp.21-29
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    • 2017
  • Objective : The purpose of this study was to analyze outcomes and identify prognostic factors in patients with cerebral metastases from non-small cell lung cancer (NSCLC) treated with gamma knife radiosurgery (GKS) particularly, focusing on associations of biomarkers and systemic treatments. Methods : We retrospectively reviewed the medical records of 134 patients who underwent GKS for brain metastases due to NSCLC between January 2002 and December 2012. Representative biomarkers including epidermal growth factor receptor (EGFR) mutation, K-ras mutation, and anaplastic lymphoma kinase (ALK) mutation status were investigated. Results : The median overall survival after GKS was 22.0 months (95% confidence interval [CI], 8.8-35.1 months). During follow-up, 63 patients underwent salvage treatment after GKS. The median salvage treatment-free survival was 7.9 months (95% CI, 5.2-10.6 months). Multivariate analysis revealed that lower recursive partition analysis (RPA) class, small number of brain lesions, EGFR mutation (+), and ALK mutation (+) were independent positive prognostic factors associated with longer overall survival. Patients who received target agents 30 days after GKS experienced significant improvements in overall survival and salvage treatment-free survival than patients who never received target agents and patients who received target agents before GKS or within 30 days (median overall survival: 5.0 months vs. 18.2 months, and 48.0 months with p-value=0.026; median salvage treatment-free survival: 4.3 months vs. 6.1 months and 16.6 months with p-value=0.006, respectively). To assess the influence of target agents on the pattern of progression, cases that showed local recurrence and new lesion formation were analyzed according to target agents, but no significant effects were identified. Conclusion : The prognosis of patients with brain metastases of NSCLC after GKS significantly differed according to specific biomarkers (EGFR and ALK mutations). Our results show that target agents combined with GKS was related to significantly longer overall survival, and salvage treatment-free survival. However, target agents were not specifically associated with improved local control of the lesion treated by GKS either development of new lesions. Therefore, it seems that currently popular target agents do not affect brain lesions themselves, and can prolong survival by controlling systemic disease status.

A Case of Multiple System Atrophy-Parkinsonism Type (MSA-P) with Gait Disturbance and Posture Instability Treated with Korean Medicine (보행 장애와 자세 이상 등을 호소하는 다계통 위축증(MSA-P) 한의 치험 1례)

  • Lee, Sang-hwa;Shin, Hee-yeon;Jeong, Hye-seon;Kim, Seo-young;Yang, Seung-bo;Cho, Seung-yeon;Park, Jung-mi;Ko, Chang-nam;Park, Seong-uk
    • The Journal of Internal Korean Medicine
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    • v.40 no.5
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    • pp.743-751
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    • 2019
  • This case report suggests the potential effects of Korean medicine for the gait disturbance and posture instability of Multiple System Atrophy-Parkinsonism (MSA-P). A patient with MSA-P who had gait disturbance and posture instability was given a series of Korean medicine, including acupuncture, pharmacopuncture, electro-acupuncture, moxibustion, and herbal medicine, for 15 days of hospitalization. During the hospitalization period, the severity and progression of the disease was measured with the Unified Multiple System Atrophy Rating Scale (UMSARS) and a video recording of a 20-meter round timed walking test. The UMSARS Part I and II scores decreased from 14 to 5 and 9 to 5, respectively. An improvement was also noted in standing and walking posture, and the walking time was shortened from 30 to 25 seconds in the 20-meter round-trip walking test. Dysarthria, dysphagia, and non-motoring symptoms like sleep behavioral disorders and constipation were also improved. The findings of this case study suggest that this series of Korean medicine has potential therapeutic effects for patients with MSA-P with motor and non-motor symptoms.

Psychosomatic Integrative Care for Psychosocial Distress of Patients With Breast Cancer (유방암 환자의 정신사회적 디스트레스에 대한 정신신체의학적 통합치료)

  • Yang, Chan-Mo;Jang, Seung-Ho;Lee, Hye-Jin;Lee, Sang-Yeol
    • Korean Journal of Psychosomatic Medicine
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    • v.29 no.2
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    • pp.77-85
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    • 2021
  • Breast cancer is the most prevalent oncological disease among women. Various psychosocial distress is common at the diagnosis, treatment, and posttreatment phase of breast cancer. For the treatment of breast cancer, not only medical treatment but also psychosomatic integrative care will be needed. Patients with breast cancer may lead to increased vulnerability to stress, adjustment disorder, anxiety disorder, and depressive disorder, and these psychiatric diseases and conditions are associated with recurrence or exacerbation of breast cancer. Psychosocial treatment of anxiety and depression could increase the quality of life of patients and decrease the recurrence and progression of breast cancer. In this article, we reviewed 5 clinical breast cancer survivorship guidelines focused on psychosomatic integrative care including psychosocial treatment and alternative treatment for psychosocial distress. Because 5 treatment guidelines were using various definitions of evidence, we confirmed evidence of various psychosocial treatments for patients with breast cancer based on the definition of evidence by the US Preventive Service Task Force (USPSTF) guideline. We also reviewed the effect size of psychosocial treatment for anxiety, depression, mood, and quality of life in patients with breast cancer. This article discusses the barrier to the delivery of psychosomatic integrative care and suggests integrative care planning for breast cancer. Multi-disciplinary teams, patient's needs assessment, information technology support, patient and caregiver engagement, planned periodic monitoring of psychosocial distress by a psychosomatic specialist or consultation-liaison psychiatrist are recommended as key features of a psychosomatic integrated care plan.

A Measurement Method for Cervical Neural Foraminal Stenosis Ratio using 3-dimensional CT (3차원 컴퓨터단층촬영상을 이용한 신경공 협착률 측정방법)

  • Kim, Yon-Min
    • Journal of the Korean Society of Radiology
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    • v.14 no.7
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    • pp.975-980
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    • 2020
  • Cervical neural foraminal stenosis is a very common spinal disease that affects a relatively large number of people of all ages. However, since imaging methods that quantitatively provide neural foraminal stenosis are lacking, this study attempts to present quantitative measurement results by reconstructing 3D computed tomography images. Using a 3D reconstruction software, the surrounding bones were removed, including the spinous process, transverse process, and lamina of the cervical spine so that the neural foramen were well observed. Using Image J, a region of interest including the neural foramen area of the 3D image was set, and the number of pixels of the neural foramen area was measured. The neural foramen area was calculated by multiplying the number of measured pixels by the pixel size. In order to measure the widest area of the neural foramen, it was measured between 40-50 degrees in the opposite direction and 15-20 degrees toward the head. The measured cervical neural foramen area showed consistent measurement values. The largest measured area of the right neural foramen C5-6 was 12.21 ㎟, and after 2 years, the area was measured to be 9.95 ㎟, indicating that 18% stenosis had progressed. Since 3D reconstruction using axial CT scan images, no additional radiation exposure is required, and the area of stenosis can be objectively presented. In addition, it is good to explain to patients with neural stenosis while viewing 3D images, and it is considered a good method to be used in the evaluation of the progression of stenosis and post-operative evaluation.

The Association between Mortality and the Oxygen Saturation and Fraction of Inhaled Oxygen in Patients Requiring Oxygen Therapy due to COVID-19-Associated Pneumonia

  • Choi, Keum-Ju;Hong, Hyo-Lim;Kim, Eun Jin
    • Tuberculosis and Respiratory Diseases
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    • v.84 no.2
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    • pp.125-133
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    • 2021
  • Background: The coronavirus disease (COVID-19) can manifest in a range of symptoms, including both asymptomatic systems which appear nearly non-existent to the patient, all the way to the development of acute respiratory distress syndrome (ARDS). Specifically, COVID-19-associated pneumonia develops into ARDS due to the rapid progression of hypoxia, and although arterial blood gas analysis can assist in halting this deterioration, the current environment provided by the COVID-19 pandemic, which has led to an overall lack of medical resources or equipment, has made it difficult to administer such tests in a widespread manner. As a result, this study was conducted in order to determine whether the levels of oxygen saturation (SpO2) and the fraction of inhaled oxygen (FiO2) (SF ratio) can also serve as predictors of ARDS and the patient's risk of mortality. Methods: This was a retrospective cohort study conducted from February 2020 to Mary 2020, with the study's subjects consisting of COVID-19 pneumonia patients who had reached a state of deterioration that required the use of oxygen therapy. Of the 100 COVID-19 pneumonia cases, we compared 59 pneumonia patients who required oxygen therapy, divided into ARDS and non-ARDS pneumonia patients who required oxygen, and then investigated the different factors which affected their mortality. Results: At the time of admission, the ratios of SpO2, FiO2, and SF for the ARDS group differed significantly from those of the non-ARDS pneumonia support group who required oxygen (p<0.001). With respect to the predicting of the occurrence of ARDS, the SF ratio on admission and the SF ratio at exacerbation had an area under the curve which measured to be around 85.7% and 88.8% (p<0.001). Multivariate Cox regression analysis identified that the SF ratio at exacerbation (hazard ratio [HR], 0.916; 95% confidence interval [CI], 0.846-0.991; p=0.029) and National Early Warning Score (NEWS) (HR, 1.277; 95% CI, 1.010-1.615; p=0.041) were significant predictors of mortality. Conclusion: The SF ratio on admission and the SF ratio at exacerbation were strong predictors of the occurrence of ARDS, and the SF ratio at exacerbation and NEWS held a significant effect on mortality.

An Analysis of the Prevalence and Pattern Identification of Korean Medicine for Acute Stress Disorder and Post Traumatic Stress Disorder in Patients with Traffic Injuries (교통사고 상해증후군 환자의 급성 스트레스 장애와 외상 후 스트레스 장애의 유병률과 한의변증유형 분석)

  • Lee, Yu Jin;Lee, Sung Joon;Cheong, Moon Joo;Lim, Jung Hwa;Jo, Hee Geun;Kim, Bo Min;Chung, Sun-Yong;Kwak, Hui-Yong;Park, Bo Ra;Park, Tae-Yong;Shin, Byung-Cheul;Kang, Hyung Won
    • Journal of Oriental Neuropsychiatry
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    • v.32 no.1
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    • pp.1-11
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    • 2021
  • Objectives: To investigate the prevalence of acute stress disorder (ASD) and post-traumatic stress disorder (PTSD) in patients with traffic injuries. In addition, PTSD patients was classified using 'pattern identification for jing ji and zheng chong'. Methods: Questionnaires such as the primary care PTSD screen for DSM-5(PC-PTSD-5), Korean version of PTSD checklist-5 (PCL-5-K), and the instrument of pattern identification for jing ji and zheng chong were conducted on 195 patients within 3 days to 1 year after traffic accidents. Patients were recruited from six medical institutions. Collected data were used to determine the prevalence of acute stress disorder and post-traumatic stress disorder. Results: On PC-PTSD-5, the prevalence was 39.1% for ASD and 50% for PTSD. On PCL-5-K, the prevalence was 20.4% for ASD and 29.3% for PTSD. Satisfying both PC-PTSD-5 and PCL-5-K, the prevalence was 18.2% for ASD and 25.8% for PTSD. As a result of pattern identification for jing ji and zheng chong, 'weakness of heart and gall bladder type' accounted for the highest proportions in both ASD and PTSD groups. Conclusions: In this study, the prevalence was 39.1% for ASD and 50% for PTSD by PC-PTSD-5. Satisfying both PC-PTSD-5 and PCL-5-K, the prevalence was 18.2% for ASD and 25.8% for PTSD. Further large-scale prospective studies are needed to analyze the prevalence of ASD and PTSD, the rate of progression from ASD to PTSD, and the type of pattern identification.