1.The relationship between low survival and acute increase of tumor necrosis factor α expression in the lung in a rat model of asphyxial cardiac arrest.
Yoonsoo PARK ; Hyun Jin TAE ; Jeong Hwi CHO ; In Shik KIM ; Taek Geun OHK ; Chan Woo PARK ; Joong Bum MOON ; Myoung Cheol SHIN ; Tae Kyeong LEE ; Jae Chul LEE ; Joon Ha PARK ; Ji Hyeon AHN ; Seok Hoon KANG ; Moo Ho WON ; Jun Hwi CHO
Anatomy & Cell Biology 2018;51(2):128-135
Cardiac arrest (CA) is sudden loss of heart function and abrupt stop in effective blood flow to the body. The patients who initially achieve return of spontaneous circulation (RoSC) after CA have low survival rate. It has been known that multiorgan dysfunctions after RoSC are associated with high morbidity and mortality. Most previous studies have focused on the heart and brain in RoSC after CA. Therefore, the aim of this research was to perform serological, physiological, and histopathology study in the lung and to determine whether or how pulmonary dysfunction is associated with low survival rate after CA. Experimental animals were divided into sham-operated group (n=14 at each point in time), which was not subjected to CA operation, and CA-operated group (n=14 at each point in time), which was subjected to CA. The rats in each group were sacrificed at 6 hours, 12 hours, 24 hours, and 2 days, respectively, after RoSC. Then, pathological changes of the lungs were analyzed by hematoxylin and eosin staining, Western blot and immunohistochemistry for tumor necrosis factor α (TNF-α). The survival rate after CA was decreased with time past. We found that histopathological score and TNF-α immunoreactivity were significantly increased in the lung after CA. These results indicate that inflammation triggered by ischemia-reperfusion damage after CA leads to pulmonary injury/dysfunctions and contributes to low survival rate. In addition, the finding of increase in TNF-α via inflammation in the lung after CA would be able to utilize therapeutic or diagnostic measures in the future.
Animals
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Blotting, Western
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Brain
;
Eosine Yellowish-(YS)
;
Heart
;
Heart Arrest*
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Hematoxylin
;
Humans
;
Immunohistochemistry
;
Inflammation
;
Lung*
;
Models, Animal*
;
Mortality
;
Rats*
;
Survival Rate
;
Tumor Necrosis Factor-alpha*
2.High prevalence of TP53 mutations is associated with poor survival and an EMT signature in gliosarcoma patients.
Sung Yup CHO ; Changho PARK ; Deukchae NA ; Jee Yun HAN ; Jieun LEE ; Ok Kyoung PARK ; Chengsheng ZHANG ; Chang Ohk SUNG ; Hyo Eun MOON ; Yona KIM ; Jeong Hoon KIM ; Jong Jae KIM ; Shin Kwang KHANG ; Do Hyun NAM ; Jung Won CHOI ; Yeon Lim SUH ; Dong Gyu KIM ; Sung Hye PARK ; Hyewon YOUN ; Kyuson YUN ; Jong Il KIM ; Charles LEE ; Sun Ha PAEK ; Hansoo PARK
Experimental & Molecular Medicine 2017;49(4):e317-
Gliosarcoma (GS) is a rare variant (2%) of glioblastoma (GBM) that poses clinical genomic challenges because of its poor prognosis and limited genomic information. To gain a comprehensive view of the genomic alterations in GS and to understand the molecular etiology of GS, we applied whole-exome sequencing analyses for 28 GS cases (6 blood-matched fresh-frozen tissues for the discovery set, 22 formalin-fixed paraffin-embedded tissues for the validation set) and copy-number variation microarrays for 5 blood-matched fresh-frozen tissues. TP53 mutations were more prevalent in the GS cases (20/28, 70%) compared to the GBM cases (29/90, 32%), and the GS patients with TP53 mutations showed a significantly shorter survival (multivariate Cox analysis, hazard ratio=23.9, 95% confidence interval, 2.87–199.63, P=0.003). A pathway analysis showed recurrent alterations in MAPK signaling (EGFR, RASGRF2 and TP53), phosphatidylinositol/calcium signaling (CACNA1s, PLCs and ITPRs) and focal adhesion/tight junction (PTEN and PAK3) pathways. Genomic profiling of the matched recurrent GS cases detected the occurrence of TP53 mutations in two recurrent GS cases, which suggests that TP53 mutations play a role in treatment resistance. Functionally, we found that TP53 mutations are associated with the epithelial–mesenchymal transition (EMT) process of sarcomatous components of GS. We provide the first comprehensive genome-wide genetic alternation profiling of GS, which suggests novel prognostic subgroups in GS patients based on their TP53 mutation status and provides new insight in the pathogenesis and targeted treatment of GS.
Glioblastoma
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Gliosarcoma*
;
Humans
;
Prevalence*
;
Prognosis
3.Childhood Acute Immune Thrombocytopenic Purpura in Korea: Multicenter Study of Korean Society of Pediatric Hematology/Oncology.
Eun Jin CHOI ; Sun Min LEE ; Kun Soo LEE ; Dae Chul JEONG ; Hack Ki KIM ; Heung Sik KIM ; Soon Kyum KIM ; Gwang Chul LEE ; Don Hee AHN ; Im Joo KANG ; Young Ho LEE ; Hee Young SHIN ; Hyo Seop AHN ; Hae Lim JEONG ; Hong Hoe KOO ; Moon Kyu KIM ; Hwang Min KIM ; Chuhl Joo LYU ; Chang Hyun YANG ; Jeong Ohk HA ; Jong Jin SEO ; Thad T GHIM ; Chee Gwan KIM ; Chul Joo JEONG ; Kyu Chu CHOI ; Kyung Ha YOO ; Eun Seon YOO ; Soon Yong LEE ; Sang Woo KIM ; Soon Ki KIM ; Hoon KOOK ; Tai Ju HWANG ; Pyung Han HWANG ; Kyung Duck PARK ; Hyun Jin PARK ; Kwang Nam KIM ; Ki Joong KIM
Korean Journal of Pediatric Hematology-Oncology 2003;10(1):14-21
PURPOSE: Childhood acute immune thrombocytopenic purpura (ITP) is a benign hematologic disease. Therapy does not affect the natural history of the illness. We evaluated the clinical and laboratory findings, treatment and prognosis of childhood acute ITP in Korea through a retrospective multicenter study. METHODS: We analyzed retrospectively the data of 1, 829 children with acute ITP through survey of 33 hospitals among 43 hospitals in Korea from Sep. 1992 to Aug. 2001. RESULTS: Male to female ratio was 1.3: 1 and the median age at the diagnosis of ITP was 2.9 (0.1 17) years. Median duration of follow up was 6 months. One hundred and forty nine cases of the total 1, 829 patients (8.1%) received no treatment. The initial median platelet count of the non-treated group was 42, 500/mm3. Among the 861 cases who were followed up over 6 months, 315 cases (36.6%) progressed into chronic ITP. Associated with this high rate of chronicity of childhood acute ITP patients in Korea, we must consider the fact that acute ITP patients with fast improvement in the first episode tend not to follow up. Considering that fact, the rate of chronicity becomes 17.2% of the 1, 829 acute ITP patients. The treated group used many kinds of treatment methods. Intravenous immunoglobulins (IVIG) with or without prednisolone (PD) (67.5%) were the most commonly used regimens. In the group treated with IVIG alone, the platelet count began to rise above 50, 000/mm3 at 2.6 days, 100, 000/mm3 at 3.7 days and 150, 000/mm3 at 4.9 days. Four hundred and twenty two cases of the 1, 686 (25.0%) cases followed up after first episode of ITP relapsed. The relapse rate was significantly higher in older patients and in girls than in younger patients and in boys (P< 0.05). The chronicity of ITP statistically increased with age (P< 0.05) and that was the only valuable factor. CONCLUSION: Despite the fact that childhood acute ITP is a pretty common disaese, there is no agreement on the best treatment method for this disease. The establishment of Korean treatment guideline of childhood acute ITP, based on an analysis of multicenters, seems to be needed.
Child
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Diagnosis
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Female
;
Follow-Up Studies
;
Hematologic Diseases
;
Humans
;
Immunoglobulins, Intravenous
;
Korea*
;
Male
;
Natural History
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Platelet Count
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Prednisolone
;
Prognosis
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Purpura, Thrombocytopenic, Idiopathic*
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Recurrence
;
Retrospective Studies