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Immune Checkpoint Inhibitor with or without Radiotherapy in Melanoma Patients with Brain Metastases: A Systematic Review and Meta-Analysis

  • Pyeong Hwa Kim;Chong Hyun Suh;Ho Sung Kim;Kyung Won Kim;Dong Yeong Kim;Eudocia Q. Lee;Ayal A. Aizer;Jeffrey P. Guenette;Raymond Y. Huang
    • Korean Journal of Radiology
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    • v.22 no.4
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    • pp.584-595
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    • 2021
  • Objective: Immune checkpoint inhibitor (ICI) therapy has shown activity against melanoma brain metastases. Recently, promising results have also been reported for ICI combination therapy and ICI combined with radiotherapy. We aimed to evaluate radiologic response and adverse event rates of these therapeutic options by a systematic review and meta-analysis. Materials and Methods: A systematic literature search of Ovid-MEDLINE and EMBASE was performed up to October 12, 2019 and included studies evaluating the intracranial objective response rates (ORRs) and/or disease control rates (DCRs) of ICI with or without radiotherapy for treating melanoma brain metastases. We also evaluated safety-associated outcomes. Results: Eleven studies with 14 cohorts (3 with ICI combination therapy; 5 with ICI combined with radiotherapy; 6 with ICI monotherapy) were included. ICI combination therapy {pooled ORR, 53% (95% confidence interval [CI], 44-61%); DCR, 57% (95% CI, 49-66%)} and ICI combined with radiotherapy (pooled ORR, 42% [95% CI, 31-54%]; DCR, 85% [95% CI, 63-95%]) showed higher local efficacy compared to ICI monotherapy (pooled ORR, 15% [95% CI, 11-20%]; DCR, 26% [95% CI, 21-32%]). The grade 3 or 4 adverse event rate was significantly higher with ICI combination therapy (60%; 95% CI, 52-67%) compared to ICI monotherapy (11%; 95% CI, 8-17%) and ICI combined with radiotherapy (4%; 95% CI, 1-19%). Grade 3 or 4 central nervous system (CNS)-related adverse event rates were not different (9% in ICI combination therapy; 8% in ICI combined with radiotherapy; 5% in ICI monotherapy). Conclusion: ICI combination therapy or ICI combined with radiotherapy showed better local efficacy than ICI monotherapy for treating melanoma brain metastasis. The grade 3 or 4 adverse event rate was highest with ICI combination therapy, and the CNS-related grade 3 or 4 event rate was similar. Prospective trials will be necessary to compare the efficacy of ICI combination therapy and ICI combined with radiotherapy.

Clinical Study of Anaphylaxis on Bee-Venom Acupuncture (봉독약침 후 발생한 Anaphylaxis 에 관한 임상적 연구)

  • Hwang, Yoo-Jin;Lee, Byung-Chul
    • Journal of Acupuncture Research
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    • v.17 no.4
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    • pp.149-159
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    • 2000
  • Bee-venom Acupucture has good effect on pain control but We may be anxious about the problem of side-effect. Bee-venom components are composed of phospholipase $A_2$, hyaluronidase, melitin, apamin, MCD peptide, citrate and so on. Especially Apamin, MCD peptide and histamine cause severe reacting that is named Anaphylaxis. Anaphylaxis is a clinical syndrome characterized by the acute system reaction of multiple organ systems to an IgE-mediated immunologic mediator release in previously sensitized individuals. Respiratory and dermatologic manifestations are the most commonly expressed clinical features of anaphylaxis, and a majority of anaphylactic reactions initially appear to be localized to these two systems. Anaphylatic reaction of bee-venom are expressed clinically ulticaria, itching sensation, erythema, dizziness, nausea, hypotension and so on. Especially ulticaria and erythema are end points of increased vascular permeability and vasodilatation at the other extreme of the clinical spectrum, Gastrointestinal mucosal edema and smooth muscle contraction can result in cramping abdominal pain, nausea, and vomiting. Therefore, we have observed anaphylatic reaction of bee-venom in 11 patients, who visited WonKwang University Kunpo Oriental Medical Center, treated bee venom. The results were summarized as follows : 1. The patient distribution ratio, in regard to sex, was shown to be 1 : 2.67 for male to females. In regard to age, it was shown that people in their 30's was the most predominant case, followed by people in their 20's, 30's, 50's and 60's, respectively. 2. When Anaphylaxis was occured, it was observed to abnormality of CBC, LFT, IgE, IgG. 3. In regard to patient condition, it was observed that fatigue was most frequent. 4. In regard to the number of times and quantity of bee venom inj., it was observed that anaphylaxis is most frequent at 7-10 times(1.6-2.0cc) 5. In regard to duration of reaction, it was observed that people in their l0min' was most frequent. In disappearing duration of anaphylaxic reaction, The results showed under 60min lcases(9%), 60-120min 7cases(64%) and 180-240min 3cases(27%). 6. In symptoms of anaphylaxis, The results showed hypotension 8cases(19%), itching sensation 7cases(16%), nausea 4cases(9%), erythema 4cases(9%) and dizziness 4cases(9%). In mentality, The results showed drowsy 8case(73%) and alert 3cases(27%). 7. Generally, patients were treated with Avil, Dexa IM and PDS, peniramine, cimetidine, Q-zyme per os after H/S, N/S inj. $O_2$ was supplied according to patient's symptom. In 1 severe case, Dopamine was iv injected.

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Microwave Dielectric Properties of La2O3-B2O3-TiO2 Glass-Ceramic and BaNd2Ti5O14Ceramic System for LTCC Application (저온동시소성(LTCC)을 위한 결정화 유리(La2O3-B2O3-TiO2계)와 BaNd2Ti5O14 세라믹을 이용한 마이크로파 유전체 특성)

  • 황성진;김유진;김형순
    • Journal of the Korean Ceramic Society
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    • v.41 no.8
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    • pp.599-604
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    • 2004
  • The LTCCs (Low-Temperature Co-fired Ceramics) are very important for electronic industry to build smaller RF modules and to fulfill the necessity for miniaturization of devices in wireless communication industry. The dielectric materials with sintering temperature $T_{sint}$<90$0^{\circ}C$ are required. In this study, BaO-N $d_2$ $O_3$-Ti $O_2$ (BNT : 20∼40 wt%) for ceramic materials and L $a_2$ $O_3$- $B_2$ $O_3$-Ti $O_2$ (LBT : 80∼60 wt%) for crystallizable glasses were used. The glass/ceramic composites were investigated for sintering behavior, phase evaluation, densities, interface reaction and microwave dielectric properties. It was found that the addition LBT glass frist significantly lowered the sintering temperature to below 90$0^{\circ}C$ and the densification with increasing addition LBT glass frist developed rapidly which was meant to be namely 90% of relative density. The sintered bodies ekhibited applicable dielectric properties, namely 15 for $\varepsilon$$_{r}$,, 10000 GHz for Q* $f_{0}$. The results suggest that the composites have good potential as a new candidate for LTCC materials.

The Effect of TuRo (Qi dance therapy) on the psychological health in adolescent female students (투로(套路)(기무요법(氣舞療法) : TuRo)가 여중생들의 정신건강에 미치는 효과)

  • Lee, Hwa-Jin;Chae, Youn-Byoung;An, Kyung-Eh;Hahm, Dae-Hyun;Park, Hi-Joon;Lee, Hye-Jung
    • Korean Journal of Acupuncture
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    • v.23 no.2
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    • pp.69-78
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    • 2006
  • Objectives: TuRo, defined as a dance therapy applying the meridian Qi system into the dancing movements, may have effects on ameliorating the psychological symptoms that often appear in adolescent students in a stressful situation. The Objective of the present study was to examine whether TuRo training relieves the psychological symptoms in adolescent female students. Methods: Symptom Check List-90-Revision (SCL-90-R), a 5 point Likert scale, consisted of 90 items that represent psychological symptoms, were used to measure the psychological health status in healthy adolescent female. Twenty two adolescent female students were trained TuRo dancing for two months while 29 in control group were trained mimicked movements without the concept of Qi for the same period. Changes in Somatization, Obsessive-Compulsive behaviors, Interpersonal Sensitivity, Depression, Anxiety, Hostility, Phobic Anxiety, Parinoid Ideation and Psychotic symptoms by the two months of training were compared between TuRo and control groups using SCL-9Q-R. Results: Among the nine-categorized psychological symptoms, the somatization and hostility were significantly reduced in TuRo group (p

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Anti-atopic dermatitis effects of Parasenecio auriculatus via simultaneous inhibition of multiple inflammatory pathways

  • Kwon, Yujin;Cho, Su-Yeon;Kwon, Jaeyoung;Hwang, Min;Hwang, Hoseong;Kang, Yoon Jin;Lee, Hyeon-Seong;Kim, Jiyoon;Kim, Won Kyu
    • BMB Reports
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    • v.55 no.6
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    • pp.275-280
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    • 2022
  • The treatment of atopic dermatitis (AD) is challenging due to its complex etiology. From epidermal disruption to chronic inflammation, various cells and inflammatory pathways contribute to the progression of AD. As with immunosuppressants, general inhibition of inflammatory pathways can be effective, but this approach is not suitable for long-term treatment due to its side effects. This study aimed to identify a plant extract (PE) with anti-inflammatory effects on multiple cell types involved in AD development and provide relevant mechanistic evidence. Degranulation was measured in RBL-2H3 cells to screen 30 PEs native to South Korea. To investigate the anti-inflammatory effects of Parasenecio auriculatus var. matsumurana Nakai extract (PAE) in AD, production of cytokines and nitric oxide, activation status of FcεRI and TLR4 signaling, cell-cell junction, and cell viability were evaluated using qRT-PCR, western blotting, confocal microscopy, Griess system, and an MTT assay in RBL-2H3, HEK293, RAW264.7, and HaCaT cells. For in vivo experiments, a DNCBinduced AD mouse model was constructed, and hematoxylin and eosin, periodic acid-Schiff, toluidine blue, and F4/80-staining were performed. The chemical constituents of PAE were analyzed by HPLC-MS. By measuring the anti-degranulation effects of 30 PEs in RBL-2H3 cells, we found that Paeonia lactiflora Pall., PA, and Rehmannia glutinosa (Gaertn.) Libosch. ex Steud. show an inhibitory activity of more than 50%. Of these, PAE most dramatically and consistently suppressed cytokine expression, including IL-4, IL-9, IL-13, and TNF-α. PAE potently inhibited FcεRI signaling, which mechanistically supports its basophil-stabilizing effects, and PAE downregulated cytokines and NO production in macrophages via perturbation of toll-like receptor signaling. Moreover, PAE suppressed cytokine production in keratinocytes and upregulated the expression of tight junction molecules ZO-1 and occludin. In a DNCB-induced AD mouse model, the topical application of PAE significantly improved atopic index scores, immune cell infiltration, cytokine expression, abnormal activation of signaling molecules in FcεRI and TLR signaling, and damaged skin structure compared with dexamethasone. The anti-inflammatory effect of PAE was mainly due to integerrimine. Our findings suggest that PAE could potently inhibit multi-inflammatory cells involved in AD development, synergistically block the propagation of inflammatory responses, and thus alleviate AD symptoms.

Green perilla leaf extract ameliorates long-term oxidative stress induced by a high-fat diet in aging mice

  • Edward, Olivet Chiamaka;Thomas, Shalom Sara;Cha, Kyung-Ok;Jung, Hyun-Ah;Han, Anna;Cha, Youn-Soo
    • Nutrition Research and Practice
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    • v.16 no.5
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    • pp.549-564
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    • 2022
  • BACKGROUND/OBJECTIVES: Oxidative stress is caused by an imbalance between harmful free radicals and antioxidants. Long-term oxidative stress can lead to an "exhausted" status of antioxidant defense system triggering development of metabolic syndrome and chronic inflammation. Green perilla (Perilla frutescens) is commonly used in Asian cuisines and traditional medicine in southeast Asia. Green perilla possesses numerous beneficial effects including anti-inflammatory and antioxidant functions. To investigate the potentials of green perilla leaf extract (PE) on oxidative stress, we induced oxidative stress by high-fat diet (HFD) in aging mice. MATERIALS/METHODS: C57BL/6J male mice were fed HFD continuously for 53 weeks. Then, mice were divided into three groups for 12 weeks: a normal diet fed reference group (NDcon), high-fat diet fed group (HDcon), and high-fat diet PE treated group (HDPE, 400 mg/kg of body weight). Biochemical analyses of serum and liver tissues were performed to assess metabolic and inflammatory damage and oxidative status. Hepatic gene expression of oxidative stress and inflammation related enzymes were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: PE improved hepatopathology. PE also improved the lipid profiles and antioxidant enzymes, including hepatic glutathione peroxidase (GPx) and superoxide dismutase (SOD) and catalase (CAT) in serum and liver. Hepatic gene expressions of antioxidant and anti-inflammatory related enzymes, such as SOD-1, CAT, interleukin 4 (IL-4) and nuclear factor erythroid 2-related factor (Nrf2) were significantly enhanced by PE. PE also reduced the levels of hydrogen peroxide (H2O2) and malondialdehyde (MDA) in the serum and liver; moreover, PE suppressed hepatic gene expression involved in pro-inflammatory response; Cyclooxygenase-2 (COX-2), nitric oxide synthase (NOS), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). CONCLUSIONS: This research opens opportunities for further investigations of PE as a functional food and possible anti-aging agent due to its attenuative effects against oxidative stress, resulting from HFD and aging in the future.

Study on the Feasibility of Space Weapon Development Utilizing Active Debris Removal Techniques and Understanding of Space Maneuver Warfare (우주 쓰레기 제거기술을 활용한 우주무기 개발 개연성 고찰 및 우주기동전(Space Maneuver Warfare)의 이해)

  • Seonghwan Choi
    • Journal of Space Technology and Applications
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    • v.3 no.2
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    • pp.165-198
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    • 2023
  • According to the studies recently published through advanced maui optical and space surveillance technologies (AMOS) Conference 2021, LEO conjunction assessment revolves around not on operating satellites but space debris such as rocket bodies and non-operational satellites, hence suggesting a solution through space traffic management. Against this backdrop, the issue of active debris removal (ADR) has emerged to the surface as an international challenge throughout the globe. In step with this, the United Nations General Assembly approved a resolution calling on nations to halt tests of direct-ascent anti-satellites, to which U.S. and twelve other nations included Republic of Korea were original signatories. ADR techniques are also actively being researched in the civil sector, and these commercial services, if successfully developed, could possibly be utilized for military use as well. As such, this paper will help readers' understanding for the current status of ADR techniques, space threat assessments, on-orbit rendezvous and proximity operations by looking at previous cases, reflecting on space-faring nations' ADR techniques and its development probability in relation to space weapons. As a conclusion, this study will propose the needs of developing space propulsion system by understanding Space Maneuver Warfare in preparation for the future space battlefield.

A Systematic Classification of Korean Fagaceae by the Pollen (화분(花粉)에 의한 한국산(韓國產) 참나무과(科) 계통분류(系統分類))

  • Park, Seung Young
    • Journal of Korean Society of Forest Science
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    • v.80 no.2
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    • pp.151-161
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    • 1991
  • I tried to specify the taxa of Fagaceae in Korea by the character of their pollen grains. The light microscope(LM) and the Scanning electron microscope(SEM) were used to examine the pollen grains of 19 taxa, 5 genera. The result are as follows. 1. The pollen of Fagaceae in Korea could be grouped into four types and 4 subtypes. 1) Fagus type 2) Castanea type 3) Lithocarpus, Castanopsis type 4) Quercus type (1) Cyclobalanopsis subtype (2) Prinus subtype (3) Dentatae subtype (4) Cerris subtype. 2. The morphology of the granula on the pollen of Quercus was closely related to the differantiation of the shape of the cup scales. 1) The uniformity of branching granula on the pollen grain surface corresponds to the morphological features of the concentric arrangement of cup scales. 2) The morphological features of the pollen grain surface intermingled with large or small granula, simple-granula and tuber granula which have small points of circular prominence, corresponded to those of short cup scales. 3) The morphological features of the polllen grain surface intermingled with large or small granula, simple-granula and tuber granula with an apex of amoeba type corresponded to those of Q. dentata Thunb, with thin, fine and long cup scales. 4) The morphological features of the pollen grain surface intermingled with large of small granula of with only simple-granula, corresponded to those of Q. acutissima carr. with thick, fine and long cup scales. 3. The result of cluster analysis by coding the sculpture pattern of the pollen grain surface, the existence and nonexistence of surface perforate, the grain size and granula type were coincident with the system of classification of plants and showed an intimated relationship even under th level of species.

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A Study on Marketing of Cultured Laver Products (양식해태의 유통에 관한 조사 연구)

  • 유충열
    • The Journal of Fisheries Business Administration
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    • v.4 no.1_2
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    • pp.19-57
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    • 1973
  • Laver io one of the most necessary and seasonal items in Korean food from oldtimes. Laver is lagely eaten in dried form, and its supply depends entirely upon culture weeds. The history of laver culture in Korea about sixty or seventy years is older than in Japan. Significance of laver culture is divided into two aspects, one is food supply in the nation, and the other is export to other countries. Houses engaged in laver culture are about foully thousands, and laver production in 1972 is estimated as 1, 3 bitten sheets. (1 sheet is a dried laver of 20 cm sq, in the shape of paper) Especcially meaning of layer production is the concentration of labour input, and systematic management of labour. From around 1920, the method of laver culture was introduced by Japanese Imperialism for mono culture in shallow seas, and mass products of laver is provided to Japan market, DOMESTIC MARKET Fundamental consume function calculates at below, $D_{(68_71)}$=16354 $Y^{0.471}$ $P^{-1.0662}$ where D is total layer demand, Y income variable, P price variable. It means income elasticity is 476. in the whole country, and price elasticity is 1, 07. But generally income elasticity is higher in urban area than in rural area, as shown at 1, 3 in Seoul city. Expence of laver in house expenditure is mutually correlated with another expence, See Table 12 about the relative function. See Table 14 and 16 about the relation between the gathering and the changes of price in auction, wholesale and retail price support system is for two effects, one of which is constraint of the upper price, the other is rise of the lower price. Before the system control, the equation in three year average calculated as below, $Y_{b}$ =18, 907.7455+15435.9364 t (r=0.89) where the origin t=0 is the November and the units are month. Post the system control, $Y_{p}$ =30, 047.9636+1, 631.1721t (r=0.97) therefore, this system has an effect only on the rise of lower price, Average annual margins of laver products at four market levels according to the consumer spent is below. EXPORTING MARKET Japanese demand function of laver products is, Log D=5, 289+1, 108 Log Y-1, 395 Log P (r=0.987) where D is Japanese laver demand, Y income variable, P price variable. according to which income elasticity is 1. 1 and price elasticity is 1.4. Laver production in 1970 tile highest record till then, is estimated as six billion sheets. But the recent improvement of laver culture techniques, the production of seeds and freezing storage of seeds has been stabilized. Futher new culture farms have been developed by means of break- water fences or by floating culture method. These improvements have been backed up with increased demand of laver products. Import quantity and price of Korean laver products are restrained by three organizations, that is producer, distributor and consumer. This relationship calculated by regression equation shows that import is influenced only producer organization, at the sacrifice of consumer profit. For increase to export of laver products, we urgently require to open foreign trade of laver products for Japanese consumer, .and Japan has political responsibility to solve Korean laver structure. But with long run timeseries, as regards Japanese production and import quantity, importing function shows increasing trend as below, 250 million sheets <3, 947.1674+0.005 $L_{g}$ >) 600 million sheets where $L_{q}$ is relative production quantity of laver in Japan. (unit; 100 thousand sheets) Our Export effort should be put on the highly processed products whithin the restraind quote.ote.

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A Study on the Correlation Between Electrical Resistivity and Rock Classification (전기비저항과 암반분류의 상관관계에 대한 고찰)

  • Kwon, Hyoung-Seok;Hwang, Se-Ho;Baek, Hwan-Jo;Kim, Ki-Seog
    • Geophysics and Geophysical Exploration
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    • v.11 no.4
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    • pp.350-360
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    • 2008
  • Electrical resistivity is one of physical property of the earth and measured by electrical resistivity survey, electrical resistivity logging and laboratory test. Recently, electrical resistivity is widely used in determination of rock quality in support pattern design of road and railway tunnel construction sites. To get more reliable rock quality data from electrical resistivity, it needs a lot of test and study on correlation of resistivity and rock quality. Firstly, we did rock property test in laboratory, such as P wave velocity, Young's modulus, uniaxial compressive strength (UCS) and electrical resistivity. We correlate each test results and we found out that electrical resistivity has highly related to P wave velocity, Young's modulus and UCS. Next, we accomplished electrical resistivity survey in field site and carried out electrical resistivity logging at in-situ area. We also performed rock classification, such as RQD, RMR and Q-system and we correlate electrical resistivity to RMR data. We found out that electrical resistivity logging data are highly correlate to RMR. Also we found out that electrical resistivity survey data are lower than electrical resistivity logging data when there are faults or fractures. And it cause electrical resistivity survey data to lowly correlate to RMR.