Thu, Vu Thi;Kim, Hyoung Kyu;Long, Le Thanh;Thuy, To Thanh;Huy, Nguyen Quang;Kim, Soon Ha;Kim, Nari;Ko, Kyung Soo;Rhee, Byoung Doo;Han, Jin
The Korean Journal of Physiology and Pharmacology
/
v.20
no.3
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pp.305-314
/
2016
Inflammatory and fibrotic responses are accelerated during the reperfusion period, and excessive fibrosis and inflammation contribute to cardiac malfunction. NecroX compounds have been shown to protect the liver and heart from ischemia-reperfusion injury. The aim of this study was to further define the role and mechanism of action of NecroX-5 in regulating inflammation and fibrosis responses in a model of hypoxia/reoxygenation (HR). We utilized HR-treated rat hearts and lipopolysaccharide (LPS)-treated H9C2 culture cells in the presence or absence of NecroX-5 ($10{\mu}mol/L$) treatment as experimental models. Addition of NecroX-5 significantly increased decorin (Dcn) expression levels in HR-treated hearts. In contrast, expression of transforming growth factor beta 1 ($TGF{\beta}1$) and Smad2 phosphorylation (pSmad2) was strongly attenuated in NecroX-5-treated hearts. In addition, significantly increased production of tumor necrosis factor alpha ($TNF{\alpha}$), $TGF{\beta}1$, and pSmad2, and markedly decreased Dcn expression levels, were observed in LPS-stimulated H9C2 cells. Interestingly, NecroX-5 supplementation effectively attenuated the increased expression levels of $TNF{\alpha}$, $TGF{\beta}1$, and pSmad2, as well as the decreased expression of Dcn. Thus, our data demonstrate potential antiinflammatory and anti-fibrotic effects of NecroX-5 against cardiac HR injuries via modulation of the $TNF{\alpha}/Dcn/TGF{\beta}1/Smad2$ pathway.
TIAF1 is a TGF-${\beta}$1-induced anti-apoptotic factor that plays a critical role in blocking TNF (tumor necrosis factor) cytotoxicity in mouse fibroblasts and participates in TGF-${\beta}$-mediated growth regulation. In this study, we obtained the full-length cDNA sequence of the porcine TIAF1 gene. Real-time PCR further revealed that the TIAF1 gene was expressed at the highest level in liver and kidney with prominent expressions detected in uterus, and lower levels detected in heart, spleen, lung, stomach, small intestine, skeletal muscle and fat of Large White pigs. Sequence analysis indicated that a 6 base-pair deletion mutation existed in the exon of the TIAF1 gene between Meishan and Large White pigs. This mutation induced deletion of Gln and Val amino acids. PCR-RFLP was used to detect the polymorphism in 394 pigs of a "Large White${\times}$Meishan" $F_{2}$ resource population and four purebred pig populations. The frequencies of the A allele (with a 6 bp deletion) were dominant in Chinese Meishan and Bamei pigs, and the frequencies of the B allele (no 6 bp deletion) were dominant in Large White and Landrace pigs. Association analyses revealed that the deletion mutation had highly significant associations (p<0.01) with meat marbling score of the thorax-waist longissimus dorsi (LD) muscle (MM1) and intramuscular fat percentage (IMF), and significant associations (p<0.05) with carcass length (CL). The results presented here supply evidence that the 6 bp deletion mutation in the TIAF1 gene affects porcine meat quality and provides useful information for further porcine breeding.
Kim, Haeyoung;Choi, Doo Ho;Park, Won;Huh, Seung Jae;Nam, Seok Jin;Lee, Jeong Eon;Ahn, Jin Seok;Im, Young-Hyuck
Radiation Oncology Journal
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v.31
no.4
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pp.222-227
/
2013
Purpose: This study was performed to evaluate prognostic factors for survival from first relapse (SFFR) in stage I-III breast cancer patients. Materials and Methods: From June 1994 to June 2008, 3,835 patients were treated with surgery plus postoperative radiotherapy and adjuvant chemotherapy for stage I-III breast cancer at Samsung Medical Center. Among them, a total of 224 patients died by June 2009, and 175 deaths were of breast cancer. Retrospective review was performed on medical records of 165 patients who met the inclusion criteria of this study. Univariate and multivariate analysis were done on survivals according to variables, such as age, stage, hormone status of tumor, disease-free interval (DFI), sites of first failure, number of organs involved by recurrent disease (NOR), application of salvage treatments, and existence of brain or liver metastasis (visceral metastasis). Results: Patients' median overall survival time was 38 months (range, 8 to 123 months). Median SFFR was 17 months (range, 5 to 87 months). Ninety percent of deaths occurred within 40 months after first recurrence. The patients with SFFR ${\leq}1$ year had tendency of triple-negativity, shorter DFI (${\leq}2$ years), larger NOR (>3), visceral metastasis for first relapse than the patients with SFFR >1 year. In multivariate analysis, longer DFI (>2 vs. ${\leq}2$ years), absence of visceral metastasis, and application of salvage treatments were statistically significant prognosticators for longer SFFR. Conclusion: The DFI, application of salvage treatments, and visceral metastasis were significant prognostic factors for SFFR in breast cancer patients.
Jeong, Hyung Joo;Ahn, Yo Han;Park, Eujin;Choi, Youngrok;Yi, Nam-Joon;Ko, Jae Sung;Min, Sang Il;Ha, Jong Won;Ha, Il-Soo;Cheong, Hae Il;Kang, Hee Gyung
Clinical and Experimental Pediatrics
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v.60
no.3
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pp.86-93
/
2017
Purpose: To evaluate the clinical spectrum of posttransplantation lymphoproliferative disorder (PTLD) after solid organ transplantation (SOT) in children. Methods: We retrospectively reviewed the medical records of 18 patients with PTLD who underwent liver (LT) or kidney transplantation (KT) between January 1995 and December 2014 in Seoul National University Children's Hospital. Results: Eighteen patients (3.9% of pediatric SOTs; LT:KT, 11:7; male to female, 9:9) were diagnosed as having PTLD over the last 2 decades (4.8% for LT and 2.9% for KT). PTLD usually presented with fever or gastrointestinal symptoms in a median period of 7 months after SOT. Eight cases had malignant lesions, and all the patients except one had evidence of Epstein-Barr virus (EBV) involvement, assessed by using in situ hybridization of tumor tissue or EBV viral load quantitation of blood. Remission was achieved in all patients with reduction of immunosuppression and/or rituximab therapy or chemotherapy, although 1 patient had allograft kidney loss and another died from complications of chemotherapy. The first case of PTLD was encountered after the introduction of tacrolimus for pediatric SOT in 2003. The recent increase in PTLD incidence in KT coincided with modification of clinical practice since 2012 to increase the tacrolimus trough level. Conclusion: While the outcome was favorable in that all patients achieved complete remission, some patients still had allograft loss or mortality. To prevent PTLD and improve its outcome, monitoring for EBV infection is essential, which would lead to appropriate modification of immunosuppression and enhanced surveillance for PTLD.
The microsurgical reconstruction is necessary for elderly patients to treat severe trauma and head and neck tumor. The aim of this study is to analyze the risks of microvascular surgery and whether or not happening of more complication in elderly patients who are older than 60 years old and to suggest the solution of the complication. The retrospective study included 41 elderly patients who underwent treatment of 44 microsurgical reconstructions among total 271 cases of microsurgical reconstruction from July, 1988 to December, 1998. Their ages ranged from 61 years to 79 years. There were 26 males and 15 females. The involved sites were 23 head and necks, 13 upper gastrointestinal tracts, 3 lower extremities, 1 chest and 1 sacral region. The causes of microsurgical reconstruction were 36 head and neck tumors, 2 radionecrosis, 2 traumas and 1 melanoma in lower limb. The used flaps were 14 radial forearm flaps, 13 jejunal flaps, 10 latissimus dorsi muscle flaps, 3 rectus abdominis muscle flaps, 2 lateral arm flaps, 1 scapular flap, and 1 iliac osteocutaneous flap. They had medical problems which were 29 tobacco abuse, 14 hypertensions, 13 alcohol abuse, 10 chronic obstructive pulmonary diseases, 7 diabetes mellituses, 3 ischemic heart diseases. All patients have had successful results without specific complications except 3 cases of free flap failure and 3 perioperative death. The causes of 3 flap failures were 2 flap necrosis due to arterial insufficiency and 1 flap loss due to secondary infection. All of these cases were treated with secondary free flap surgery. However 3 patients died perioperatively due to 2 respiratory arrests and 1 sepsis. It was not related to operate microsurgical reconstruction itself, but was correlated with the complication of postoperative care after head and neck surgery. We conclude that plastic surgeons consider the importance of prevention of expected complication as thorough analysis of operative risk factor and appropriate treatment. We had to select the donor and recipient vessel appropriately to perform successful microsurgery in elderly patients and consider vein graft and end-to-side anastomosis to reduce complication if necessary. In addition, we emphasize the importance of pre, peri and postoperative care in head and neck cancer patients to reduce postoperative complication and morbidity.
IMRT optimization method on multiple slice has been developed by using gradient based algorithm. On about 10-30 CT slices including treatment region of a patient, dose optimization has been performed slice by slice to meet the condition that each organ should be exposed below maximum tolerable doses and that the tumor dose within the range of 100$\pm$5 %. Field size was limited to 8$\times$8 cm$^2$ and in this condition, beam divergence was not taken into account to calculate dose distribution. Total dose distribution was calculated by superposing each beamlet whose dose distribution had been precalculated. In order to investigate beam number dependency, dose optimization was performed for one, three, five, seven, and nine coplanar beams and then each optimization index was evaluated. It is found that optimization time was proportional to number of slices to be optimized, and the most efficient plan was obtained from the case of three-to-seven incident beams with respect to calculation time and optimization index. In conclusion, dose optimization of multiple slice was able to be obtained by repeating dose optimization of single slice under condition that the beam size is not too large to ignore beam divergence. And it turns out that result of dose optimization was so sensitive to the position of isocenter that some method to optimize isocenter position is needed to improve it.
Background: Radiotherapy is an important treatment of choice for breast cancer patients after breast-conserving surgery, and we compare the feasibility of using dual arc volumetric modulated arc therapy (VMAT2), single arc volumetric modulated arc therapy (VMAT1) and Multi-beam Intensity Modulated Radiotherapy (M-IMRT) on patients after breast-conserving surgery. Materials and Methods: Thirty patients with breast cancer (half right-sided and half left-sided) treated by conservative lumpectomy and requiring whole breast radiotherapy with tumor bed boost were planned with three different radiotherapy techniques: 1) VMAT1; 2) VMAT2; 3) M-IMRT. The distributions for the planning target volume (PTV) and organs at risk (OARs) were compared. Dosimetries for all the techniques were compared. Results: All three techniques satisfied the dose constraint well. VMAT2 showed no obvious difference in the homogeneity index (HI) and conformity index (CI) of the PTV with respect to M-IMRT and VMAT1. VMAT2 clearly improved the treatment efficiency and can also decrease the mean dose and V5Gy of the contralateral lung. The mean dose and maximum dose of the spinal cord and contralateral breast were lower for VMAT2 than the other two techniques. The very low dose distribution (V1Gy) of the contralateral breast also showed great reduction in VMAT2 compared with the other two techniques. For the ipsilateral lung of right-sided breast cancer, the mean dose was decreased significantly in VMAT2 compared with VMAT1 and M-IMRT. The V20Gy and V30Gy of the ipsilateral lung of the left-sided breast cancer for VMAT2 showed obvious reduction compared with the other two techniques. The heart statistics of VMAT2 also decreased considerably compared to VMAT1 and M-IMRT. Conclusions: Compared to the other two techniques, the dual arc volumetric modulated arc therapy technique reduced radiation dose exposure to the organs at risk and maintained a reasonable target dose distribution.
The herb of Allium victorialis var. platyphyllum (Liliaceae) has been used as an edible wild herb and to treat heart failure and gastritis. We have already reported antihyperlipidemic anti-tumor effects of this plant. To enlarge the commercial availability of this food, it was investigated whether the extracts of A. victorialis var. platyphyllum reduce hyperlipidemia and obesity or not. The plants tested in this experiment were collected from two eco-types of Is. Ullung and Mt. Odae cultivated at Pyongchang. Extracts were prepared by extracting the fresh leaves and those dried at $36^{\circ}C$ and $90^{\circ}C$, respectively. Pretreatment with the ethanolic extracts for two weeks(p.o.) reduced serum triglyceride-, total cholesterol- and LDL-cholesterol contents in rats induced by Triton WR-1339, respectively. Furthermore, oral administration of the extracts also inhibited the hyperlipidemia induced with oral diet of 30% corn oil. In the other attempt to find to alleviate the obesity, the model rats with obesity were induced by the high fat-diet for six weeks. Post-treatment with the extracts for two weeks significantly reduced the hyperlipidemia. Retroperitoneal-, epidymal- and total abdominal fat pad weights were considerably reduced at 100 mg/kg oral administration of the extracts. Increased feces lipid contents were also found in the rat treated with the extracts. The extract may lead to the higher activity in treatment of hyperlipidemia and obesity than of the dried one.
Primary malignant neoplasm of the pericardium is very rare, Neoplastic involvement of the pericardium may result in rapidly developing hemorrhagic effusion. A 30-year-old male who occasionally suffered from chest tightness was referred to our hospital under the diagnosis of unstable angina. He presented with acute chest pain and severe dyspnea that had developed one day previously. The diagnostic investigations such as echocardiography, chest CT and magnetic resonance image suggested cardiac tamponade that was caused by rupture of the pericardial teratoma. An operation to remove the tumor and effusion was performed. The pericardial mass was completely excised, and the result of the frozen biopsy favored malignancy. The final pathologic report was malignant fibrosarcoma of the pericardium and no malignant cells were found on the cytology of the pericardial effusion. The patient had a smooth postoperative course and was referred to another hospital for additional radiation therapy. We report here on this case of cardiac tamponade that was caused by primary pericardial fibrosarcoma, and this required urgent diagnosis and surgical management.
Background: Acyl protein thioesterase-1 (APT1) is a cytosolic protein that may function in the depalmitoylation of numerous proteins, including the Ras family. However, the clinical role of depalmitoyl thioesterase in human cancer is not known. We evaluated the APT1 expression in lung cancer tissue and its clinicopathological findings according APT1 expression pattern. Methods: APT1 expression was examined by immunohistochemistry in the tumor tissue from 79 patients, who had undergone curative surgical removal of the primary lesion; all patients had been diagnosed with stage I non-small cell lung cancer between 1993 and 2004, at Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. Results: The APT1 expression was seen in 50 out of 79 (63.3%) cases. The positive APT1 expression was significantly related with histologic subtype and T stage, but was not influenced by differentiation. The positive APT1 expression was not significantly related to patient age, gender, or smoking history. The median follow-up duration was 10.0 years; the 5-year survival rate was 71.0%. The positive APT1 expression group showed significantly worse overall survival and worse disease-free survival without statistical significance. Conclusion: We conclude that positive APT1 expression in stage I lung cancer after surgery is closely associated with overall survival. To evaluate APT1 as a prognostic marker in lung cancer, comprehensive studies on advanced stage cases are needed.
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