1.Primary Tumor Suppression and Systemic Immune Activation of Macrophages through the Sting Pathway in Metastatic Skin Tumor
Chun-Bong SYNN ; Dong Kwon KIM ; Jae Hwan KIM ; Youngseon BYEON ; Young Seob KIM ; Mi Ran YUN ; Ji Min LEE ; Wongeun LEE ; Eun Ji LEE ; Seul LEE ; You-Won LEE ; Doo Jae LEE ; Hyun-Woo KIM ; Chang Gon KIM ; Min Hee HONG ; June Dong PARK ; Sun Min LIM ; Kyoung-Ho PYO
Yonsei Medical Journal 2022;63(1):42-55
Purpose:
Agonists of the stimulator of interferon genes (STING) play a key role in activating the STING pathway by promoting the production of cytokines. In this study, we investigated the antitumor effects and activation of the systemic immune response of treatment with DMXAA (5,6-dimethylxanthenone-4-acetic acid), a STING agonist, in EML4-ALK lung cancer and CT26 colon cancer.
Materials and Methods:
The abscopal effects of DMXAA in the treatment of metastatic skin nodules were assessed. EML4-ALK lung cancer and CT26 colon cancer models were used to evaluate these effects after DMXAA treatment. To evaluate the expression of macrophages and T cells, we sacrificed the tumor-bearing mice after DMXAA treatment and obtained the formalin-fixed paraffin-embedded (FFPE) tissue and tumor cells. Immunohistochemistry and flow cytometry were performed to analyze the expression of each FFPE and tumor cell.
Results:
We observed that highly infiltrating immune cells downstream of the STING pathway had increased levels of chemokines after DMXAA treatment. In addition, the levels of CD80 and CD86 in antigen-presenting cells were significantly increased after STING activation. Furthermore, innate immune activation altered the systemic T cell-mediated immune responses, induced proliferation of macrophages, inhibited tumor growth, and increased numbers of cytotoxic memory T cells. Tumor-specific lymphocytes also increased in number after treatment with DMXAA.
Conclusion
The abscopal effect of DMXAA treatment on the skin strongly reduced the spread of EML4-ALK lung cancer and CT26 colon cancer through the STING pathway and induced the presentation of antigens.
2.SYNCRIP controls miR-137 and striatal learning in animal models of methamphetamine abstinence.
Baeksun KIM ; Sung Hyun TAG ; Eunjoo NAM ; Suji HAM ; Sujin AHN ; Juhwan KIM ; Doo-Wan CHO ; Sangjoon LEE ; Young-Su YANG ; Seung Eun LEE ; Yong Sik KIM ; Il-Joo CHO ; Kwang Pyo KIM ; Su-Cheol HAN ; Heh-In IM
Acta Pharmaceutica Sinica B 2022;12(8):3281-3297
Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome. Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA-target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine (MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR, LC-MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.
3.Clinical and radiological outcomes of ultrasound-guided barbotage using a spinal needle and subacromial steroid injection for calcific tendinitis of the shoulder
Jun Pyo LEE ; Doo Sup KIM ; Jin Young HAN ; Seung Hoon BAIK ; Ji Woong KWAK ; Sung Hwa KIM
Clinics in Shoulder and Elbow 2022;25(2):140-144
Methods:
Thirty-six patients with calcific tendinitis of the shoulder treated by US-guided barbotage with a spinal needle and subacromial steroid injection were included in the study. We evaluated clinical outcomes based on American Shoulder and Elbow Surgeons (ASES) score, Constant score, and visual analog scale (VAS) for pain score. Radiological outcomes were assessed by X-ray imaging at each visit.
Results:
Our results showed that US-guided barbotage and subacromial steroid injection produced good clinical and radiological outcomes in patients with calcific tendinitis of the shoulder. Of the 36 patients, only one required surgical treatment, while the others showed improvement without any complications. Compared to values before the procedure, calcific deposit size and VAS, ASES, and Constant scores showed significant improvement 6 weeks after the procedure. No significant correlation was found between the initial calcific deposit size and clinical outcomes at each time point.
Conclusions
In patients with calcific tendinitis of the shoulder, US-guided barbotage using a spinal needle and subacromial steroid injection can yield satisfactory clinical and radiological results.
4.Comparison of Anterior Translation among Three Sternoclavicular Reconstruction Methods in Cadaver Study.
Doo Sup KIM ; Hoe Jeong CHUNG ; Il Hwan PARK ; Ji Su SHIN ; Jun Pyo LEE ; Young Hwan JANG
The Journal of the Korean Orthopaedic Association 2017;52(2):178-184
PURPOSE: Currently, biomechanics and function comparison of the reconstruction of structures play important roles in the sternoclavicular joint stability is not much. In order to confirm the improvement in the functional aspects of the sternoclavicular joint after the three most widely used reconstruction methods, we measured the degree of anterior translation of the sternoclavicular joint after the operation using cadavers. MATERIALS AND METHODS: We studied 24 sternoclavicular joints in the cadavers. First, we measured the anterior translation of the clavicle, which was compared with the sternum in 24 normal sternoclavicular joints. We divided the cadaver into three groups and performed each of the three current operations: figure of eight hamastring tendon reconstruction operation (Group 1), subclavius tendon reconstruction operation (Group 2), and hamstring tendon reconstruction operation (Group 3); then we compared the degree of anterior translation in each group. We did the measurement by adding 10 degrees to the glenohumeral joint each time from 0 degrees to 90 degrees. RESULTS: In the normal joint, the clavicle was significantly ascended compared with the sternum. The Group 1 had a 1.68±0.25 mm anterior translation while the Group 2 had 1.81±0.23 mm and Group 3 had 2.8±0.58 mm (Group 1: p=0.004, Group 2: p=0.001, Group 3: p=0.002). The Group 1 showed a low ascending rate of up to 60 degrees, which showed no significant difference with that of the normal joint. However, after 60 degrees, the ascending rate showed a significant increase. In the case of Group 2, there was no significant difference with normal joint of up to 50 degrees. Group 3 showed significant anterior ascending from 20 degree. CONCLUSION: Through measuring the anterior translation of subjects that underwent three representative sternoclavicular joint reconstructions, we found that the result from the Group 1 was most comparable normal translation of the sternoclavicular joint.
Biomechanical Phenomena
;
Cadaver*
;
Clavicle
;
Dislocations
;
Joints
;
Methods*
;
Shoulder Joint
;
Sternoclavicular Joint
;
Sternum
;
Tendons
5.Multiple Rice Body Formation in Subacromial and Subdeltoid Bursal Spaces.
John Junghun SHIN ; Jun Pyo LEE ; Doo Sup KIM
Clinics in Shoulder and Elbow 2016;19(2):96-100
We encountered a rare condition of rice body in subacromial and subdeltoid spaces in a patient with unremarkable medical history. Although it is uncommon, there have been continued reports on its formation in certain type of infective and inflammatory arthritis. However, except for a traumatic event, evaluation yielded no known and conceivable cause for his chronic inflammatory bursitis. Relatively typical findings for rice body on magnetic resonance imaging have been described, and in our case the imaging prompted us to schedule early removal, which is generally accepted as the management of choice to prevent further progression of symptoms. The symptoms of the shoulder showed significant improvement, and a close follow-up schedule has been recommended for observation of recurrence and development of any foreseeable underlying cause.
Appointments and Schedules
;
Arthritis
;
Bursitis
;
Follow-Up Studies
;
Humans
;
Magnetic Resonance Imaging
;
Recurrence
;
Shoulder
;
Shoulder Joint
6.Gender Differences in Somatic Symptoms and Current Suicidal Risk in Outpatients with Major Depressive Disorder.
Hong Jin JEON ; Jong Min WOO ; Hyo Jin KIM ; Maurizio FAVA ; David MISCHOULON ; Seong Jin CHO ; Sung Man CHANG ; Doo Heum PARK ; Jong Woo KIM ; Ikki YOO ; Jung Yoon HEO ; Jin Pyo HONG
Psychiatry Investigation 2016;13(6):609-615
OBJECTIVE: Although somatic symptoms are common complaints of patients with major depressive disorder (MDD), their associations with suicide are still unclear. METHODS: A total of 811 MDD outpatients of aged between 18 to 64 years were enrolled nationwide in Korea with the suicidality module of the Mini-International Neuropsychiatric Interview (MINI) and the Depression and Somatic Symptom Scale (DSSS). RESULTS: On stepwise regression analysis, current suicidality scores were most strongly associated with chest pain in men, and neck or shoulder pain in women. Severe chest pain was associated with higher current suicidality scores in men than in women, whereas severe neck or shoulder pain showed no significant differences between the genders. In conclusion, MDD patients of both sexes with suicidal ideation showed significantly more frequent and severe somatic symptoms than those without. Current suicidal risk was associated with chest pain in men, and neck or shoulder pain in women. CONCLUSION: We suggest that clinicians pay attention to patients' somatic symptoms in real world practice.
Chest Pain
;
Depression
;
Depressive Disorder, Major*
;
Female
;
Humans
;
Korea
;
Male
;
Neck
;
Outpatients*
;
Shoulder Pain
;
Suicidal Ideation
;
Suicide
7.Multiple Rice Body Formation in Subacromial and Subdeltoid Bursal Spaces
John Junghun SHIN ; Jun Pyo LEE ; Doo Sup KIM
Journal of the Korean Shoulder and Elbow Society 2016;19(2):96-100
We encountered a rare condition of rice body in subacromial and subdeltoid spaces in a patient with unremarkable medical history. Although it is uncommon, there have been continued reports on its formation in certain type of infective and inflammatory arthritis. However, except for a traumatic event, evaluation yielded no known and conceivable cause for his chronic inflammatory bursitis. Relatively typical findings for rice body on magnetic resonance imaging have been described, and in our case the imaging prompted us to schedule early removal, which is generally accepted as the management of choice to prevent further progression of symptoms. The symptoms of the shoulder showed significant improvement, and a close follow-up schedule has been recommended for observation of recurrence and development of any foreseeable underlying cause.
Appointments and Schedules
;
Arthritis
;
Bursitis
;
Follow-Up Studies
;
Humans
;
Magnetic Resonance Imaging
;
Recurrence
;
Shoulder
;
Shoulder Joint
8.The first private-hospital based proton therapy center in Korea; status of the Proton Therapy Center at Samsung Medical Center.
Kwangzoo CHUNG ; Youngyih HAN ; Jinsung KIM ; Sung Hwan AHN ; Sang Gyu JU ; Sang Hoon JUNG ; Yoonsun CHUNG ; Sungkoo CHO ; Kwanghyun JO ; Eun Hyuk SHIN ; Chae Seon HONG ; Jung Suk SHIN ; Seyjoon PARK ; Dae Hyun KIM ; Hye Young KIM ; Boram LEE ; Gantaro SHIBAGAKI ; Hideki NONAKA ; Kenzo SASAI ; Yukio KOYABU ; Changhoon CHOI ; Seung Jae HUH ; Yong Chan AHN ; Hong Ryull PYO ; Do Hoon LIM ; Hee Chul PARK ; Won PARK ; Dong Ryul OH ; Jae Myung NOH ; Jeong Il YU ; Sanghyuk SONG ; Ji Eun LEE ; Bomi LEE ; Doo Ho CHOI
Radiation Oncology Journal 2015;33(4):337-343
PURPOSE: The purpose of this report is to describe the proton therapy system at Samsung Medical Center (SMC-PTS) including the proton beam generator, irradiation system, patient positioning system, patient position verification system, respiratory gating system, and operating and safety control system, and review the current status of the SMC-PTS. MATERIALS AND METHODS: The SMC-PTS has a cyclotron (230 MeV) and two treatment rooms: one treatment room is equipped with a multi-purpose nozzle and the other treatment room is equipped with a dedicated pencil beam scanning nozzle. The proton beam generator including the cyclotron and the energy selection system can lower the energy of protons down to 70 MeV from the maximum 230 MeV. RESULTS: The multi-purpose nozzle can deliver both wobbling proton beam and active scanning proton beam, and a multi-leaf collimator has been installed in the downstream of the nozzle. The dedicated scanning nozzle can deliver active scanning proton beam with a helium gas filled pipe minimizing unnecessary interactions with the air in the beam path. The equipment was provided by Sumitomo Heavy Industries Ltd., RayStation from RaySearch Laboratories AB is the selected treatment planning system, and data management will be handled by the MOSAIQ system from Elekta AB. CONCLUSION: The SMC-PTS located in Seoul, Korea, is scheduled to begin treating cancer patients in 2015.
Cyclotrons
;
Helium
;
Humans
;
Korea*
;
Metallurgy
;
Particle Accelerators
;
Patient Positioning
;
Proton Therapy*
;
Protons*
;
Radiation Oncology
;
Respiratory System
;
Seoul
9.The Relationship between Type D Personality and Suicidality in Low-Income, Middle-Aged Adults.
Dae Hyun YOON ; Seog Ju KIM ; Jong Ha LEE ; Pyo Min KIM ; Doo Heum PARK ; Seung Ho RYU ; Jaehak YU ; Jee Hyun HA
Psychiatry Investigation 2015;12(1):16-22
OBJECTIVE: Low-income adults are considered to be a group at high risk for suicide. We sought to examine the effect of type D personality and other socio-demographic factors on suicidality in low-income, middle-aged Koreans. METHODS: In total, 306 low-income, middle-aged Koreans [age: 49.16+/-5.24 (40-59) years, 156 males, 150 females] were enrolled from the Korean National Basic Livelihood Security System. Socio-demographic data, including employment status, income, health, marital status, and educational attainment, were gathered. Beck's 19-item Scale for Suicidal Ideation (SSI) was applied to evaluate suicidality, and the DS14 was used to assess type D personality. RESULTS: Unemployment (p<0.01) and absence of spouse (p=0.03) predicted higher SSI scores independent of other socioeconomic factors. All type D personality scores [i.e., negative affectivity (NA), social inhibition (SI), and total score] predicted higher SSI scores independent of all socioeconomic factors (all, p<0.001). Subjects with type D personality had higher SSI scores (p<0.001), and the association between suicidality and socio-demographic factors (employment or physical health) could be found only in subjects without type D personality. CONCLUSION: Type D personality was a risk factor for suicide in low-income Koreans, independently from socio-economic factors. In addition, the socio-demographic factors were less prominently associated with suicidality in those with type D personality.
Adult*
;
Employment
;
Humans
;
Male
;
Marital Status
;
Risk Factors
;
Socioeconomic Factors
;
Spouses
;
Suicidal Ideation
;
Suicide
;
Type D Personality*
;
Unemployment
10.Native Valve Infective Endocarditis due to Staphylococcus lugdunensis Confirmed by 16S Ribosomal RNA Sequencing.
Young Eun HA ; Seong Yeol RYU ; Kwan Soo KO ; Eun Jeong JOO ; So Yeon PARK ; Hyun Ah KIM ; Min Hee LIM ; Cheol In KANG ; Doo Ryeon CHUNG ; Jae Hoon SONG ; Pyo Won PARK ; Kyong Ran PECK
Infection and Chemotherapy 2011;43(4):372-376
Staphylococcus lugdunensis is a Gram-positive, coagulase-negative Staphylococcus (CNS) species that is found as a skin commensal and has been implicated in fulminant invasive diseases such as infective endocarditis. S. lugudunensis infections resemble Staphylococcus aureus infections in terms of virulence, tissue destruction and clinical course. Although correct identification and determination of the susceptibility profile are important, some commercial systems may misidentify S. lugdunensis. We report a case of native valve infective endocarditis caused by S. lugdunensis, which was misidentified by the Vitek 2 system but identified correctly by 16S ribosomal RNA (rRNA) gene sequencing in a 72-year-old male patient. The patient had multiple vegetations on his mitral valve, and the largest one was found on the posterior mitral valve leaflet. It was 2.5 cm in size and hypermobile. Diffuse valvular abscess was also observed. He had persistent bacteremia for appoximately 8 days, which was resolved after immediate surgery and antibiotic therapy. When a patient with severe sepsis syndrome grows S. aureus or CNS other than S. lugdunensis on a commercial automatic culture system, the possibility of S. lugdunensis should be considered and further confirmatory testing such as 16S rRNA sequencing may be very useful.
Abscess
;
Aged
;
Bacteremia
;
Endocarditis
;
Humans
;
Male
;
Mitral Valve
;
RNA, Ribosomal, 16S
;
Sepsis
;
Skin
;
Staphylococcus
;
Staphylococcus aureus
;
Staphylococcus lugdunensis

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