• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7069-7074
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• 2013

Programmed cell death is a basic cellular process that is critical to maintaining tissue homeostasis. In contrast to apoptosis, necrosis was previously regarded as an unregulated and uncontrollable process. However, as research has progressed, necrosis, also known as necroptosis or programmed necrosis, is drawing increasing attention, not least becasu of its possible impications for cancer research. Necroptosis exhibits a unique signaling pathway that requires the involvement of receptor interaction protein kinases 1 and 3 (RIP1 and RIP3), mixed lineage kinase domain-like (MLKL), and phosphoglycerate mutase 5 (PGAM5) and can be specifically inhibited by necrostatins. Not only does necroptosis serve as a backup cell death program when apoptosis is inhibited, but it is now recognized to play a pivotal role in regulating various physiological processes and the pathogenesis of a variety of human diseases such as ischemic brain injury, immune system disorders and cancer. The control of necroptosis by various defined trigger factors and signaling pathways now offers the opportunity to target this cellular process for therapeutic purposes. The purpose of this paper is to review current findings concerning the connections between various trigger factors and the RIP1/RIP3 signaling pathway as it relates to necroptosis.

• Journal of Veterinary Clinics
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• v.29 no.1
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• pp.98-102
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• 2012

A 1.5-year-old male Golden Retriever was presented with worsening lameness of two month duration. Abnomral findings of blood works and serum chemistry included anemia, thrombocytopenia, hypercalcemia and hyperglobulinemia. Radiography revealed osteolysis of polyostotic regions including right femur and tibia, bilateral ilium, and spinous processes from the 13th thoracic vertebra to 5th lumbar vertebra. Enlarged multiple lymph nodes and mixed echo pattern of muscular region ventral to vertebra were observed with ultrasonography. Because concentrations of both parathyroid hormone and parathyroid hormone related peptide were all within reference ranges, humoral hypercalcemia by tumor was ruled out and extensive osteolysis was considered as the cause of hypercalcemia. Based on radiographic and ultrasonographic study, lymphoma, multiple myeloma and osteomyelitis were included in differential diagnosis. Fungal serologic test was negative. Monoclonal gammopathy was not found on serum protein electrophoresis. Cytological and histopathological examinations of the lytic lesions revealed neoplastic lymphoid proliferation, and B cell type clonal expansion was detected by polymerase chain reaction for the antigen receptor gene rearrangement. The case was diagnosed as B cell lymphoma involving polyostotic regions.

• YAKHAK HOEJI
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• v.52 no.6
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• pp.488-493
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• 2008

2-Aminothiazole ring as a bioisoster of catechol in dopamine has provided with good oral availability and lipophilic property. 2-Aminoindan, is a rigid form of dopamine, was evaluated as a dopamine D3 agonist with low neurotoxicity. Dopamine D3 agonist was evaluated as selective for the treatment of Parkinson's disease. In order to develop a novel dopamine D3 agonist, we tried to synthesize the aminothiazoloindenoxazine derivative that is a hybrid structure of aminoindenoxazine and thiazole ring. cis-2-Amino-1-indanol (2) was synthesized from 1,2-indandione-2-oxime by catalytic hydrogenation and it was treated with chloroacetyl chloride and NaH in benzene solution to give (${\pm}$)-cis-4,4a,5,9b-tetrahydroindeno[1,2-b][1,4]oxazin-3(2H)-one (6). Nitration of 6 by the mixed acid gave 8-nitro compound (7) and the carbonyl group of 7 was reduced with $LiAlH_4$ to afford compound (8). 8 was reduced to form (${\pm}$)-cis-8-amino-2,3,4,4a,5,9b-hexahydroindeno[1,2-b][1,4]oxazine (9) and finally it was cyclized with KSCN in glacial acetic acid to yield (${\pm}$)-cis-8-amino-2,3,4,4a,5,10b-hexahydrothiazolo[4,5-f]indeno[1,2-b][1,4]oxazine (10).

• Korean Journal of Fisheries and Aquatic Sciences
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• v.55 no.1
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• pp.17-22
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• 2022

Successful reproduction in vertebrates necessitates complex interactions along the brain-pituitary-gonad axis, it is determined by gonadotropin releasing hormone produced in the hypothalamus of the brain, gonadotropin synthesized in the pituitary gland, and sex hormone secreted by the gonads. The goal of this study was to secure and test technology for controlling (inhibiting) sexual maturation hormones such as maturation hormones through hormone regulation. We studied the effect on sexual maturation of zebrafish Danio rerio by tamoxifen, anastrozole, exemestane and dopamine 4 kinds of sexual maturation inhibitors to feed and after administration. As a result, 4 kinds of sexual maturation inducing substances were mixed with zebrafish feed, it could be concluded that all of them were effective in inhibiting sexual maturation by reducing mRNA levels of genetic materials related to sexual maturation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.1
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• pp.64-70
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• 2010

Soybean is of particular interest as a food supplement of isoflavones for inhibiting bone resorption in postmenopausal woman. These beneficial effects of isoflavones are caused by functioning as partial agonists or antagonists of estrogen, of which anti-resorptive effect is mediated indirectly through paracrine factors produced by osteoblasts that act on osteoclasts. In this study, the indirect effect of soybean on osteoclastic differentiation of RAW264.7 cells were investigated. The conditioned medium was collected from MC3T3-E1 osbeoblasts treated with 0.001 mg/mL~0.1 mg/mL soybean extracts for 6 days, mixed in 1:1 ratio with osteoclast medium, and then added into RAW264.7 cells with receptor activator of nuclear factor kappa B ligand (RANKL), a differentiation inducer for 3 days. Of paracrine factors in the conditioned medium, the protein expression of osteoprotegerin (OPG) with soybean extract was specifically higher in a dose dependent manner than with $10^{-9}$ M~$10^{-6}$ M of estrogen, genistein or daidzein standards. In RAW264.7 cells, the conditioned medium with soybean inhibited RANKL induced osteoclastic differentiation as total number of multinucleated tartrateresistant alkaline phosphatase (TRAP)-positive osteoclasts and protein expression of MMP-9 were significantly decreased. Coupled with the low expression of estrogen receptor $\alpha$ and $\beta$ proteins in RANKL treated RAW264.7 cells, we demonstrate that the conditioned medium of soybean treated osteoblasts inhibits RANKL induced differentiation of osteoclasts with the selective expression of OPG in osteoblasts.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.689-692
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• 2015

Background: Incorporation of molecular analysis of the epidermal growth factor receptor (EGFR) gene into routine clinical practice has shown great promise to provide personalized therapy of the non-small cell lung cancer (NSCLC) in the developed world. However, the genetic testing of EGFR mutations has not yet become routine clinical practice in territories remote from the central regions of Russia. Therefore, we aimed to study the frequency of major types of activating mutations of the EGFR gene in NSCLC patients residing in West Siberia. Materials and Methods: We examined EGFR mutations in exons 19 and 21 in 147 NSCLC patients (excluding squamous cell lung carcinomas) by real time polymerase chain reaction. Results: EGFR mutations were detected in 28 of the 147 (19%) patients. There were 19 (13%) cases with mutations in exon 19 and 9 cases (6%) in exon 21. Mutations were more frequently observed in women (42%, p=0.000) than in men (1%). A significantly higher incidence of EGFR mutations was observed in bronchioloalveolar carcinomas (28%, p=0.019) and in adenocarcinomas (21%, p=0.024) than in large cell carcinomas, mixed adenocarcinomas, and NOS (4%). The EGFR mutation rate was much higher in never-smokers than in smokers: 38% vs. 3% (p=0.000). The frequency of EGFR mutations in the Kemerovo and Tomsk regions was 19%. Conclusions: The incorporation of molecular analysis of the EGFR gene into routine clinical practice will allow clinicians to provide personalised therapy, resulting in a significant increase in survival rates and improvement in life quality of advanced NSCLC patients.

• Korean Journal of Poultry Science
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• v.49 no.2
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• pp.99-108
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• 2022

Avian leukosis virus (ALV) is a highly contagious retrovirus that causes tumors and has resulted in great economic loss worldwide owing to its high transmission rate. Various ALV viral subgroups exist, with infections occurring via specific host receptors. The susceptibility or resistance of avian species to the ALV-A and K subgroups is determined by the host receptor, the tumor virus locus A (tva) gene, while that to ALV-B depends on another host receptor, the tumor virus locus B (tvb) gene. The resistance alleles of tva and tvb have primarily been identified in China, but none have beendetected in Korea. We analyzed the frequencies of tva and tvb genotypes in White Leghorn (WL), Korean Ogye (KO), and Korean native chicken (KNC) breeds, and assessed the resistance to ALV subgroups. In WL, both tva and tvb had various genotypes, including susceptibility and resistance alleles, whereas in KO, tva and tvb resistance alleles were dominant. In KNC, tva susceptibility and resistance alleles were mixed, whereas tvb resistance alleles were dominant. In addition, we showed that there were differences in the splicing pattern of tva transcripts and the expression level of tvb transcripts within breeds. Finally, we confirmed that ALV resistance depended on KO and KNC genotypes by in vitro infection of chicken embryonic fibroblasts with ALV. These results highlight that some KO and KNC individuals are naturally resistant to ALV subgroups A, B, and K, and will facilitate the preservation of economically superior traits through selective breeding.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.657-662
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• 2014

Background: The epidermal growth factor receptor (EGFR) mutation status of lung cancer is important because it means that EGFR-tyrosine kinase inhibitor treatment is indicated. The purpose of this prospective study is to determine whether EGFR mutation status could be identified with reference to preoperative factors. Materials and Methods: One hundred-forty eight patients with lung cancer (111 adenocarcinomas, 25 squamous cell carcinomas and 12 other cell types) were enrolled in this study. The EGFR mutation status of each lung cancer was analyzed postoperatively. Results: There were 58 patients with mutant EGFR lung cancers (mutant LC) and 90 patients with wild-type EGFR lung cancers (wild-type LC). There were significant differences in gender, smoking status, maximum tumor diameter in chest CT, type of tumor shadow, clinical stage between mutant LC and wild-type LC. EGFR mutations were detected only in adenocarcinomas. Maximum standardized uptake value (SUVmax:$3.66{\pm}4.53$) in positron emission tomography-computed tomography of mutant LC was significantly lower than that ($8.26{\pm}6.11$) of wild-type LC (p<0.0001). Concerning type of tumor shadow, the percentage of mutant LC was 85.7% (6/7) in lung cancers with pure ground glass opacity (GGO), 65.3%(32/49) in lung cancers with mixed GGO and 21.7%(20/92) in lung cancers with solid shadow (p<0.0001). For the results of discriminant analysis, type of tumor shadow (p=0.00036) was most significantly associated with mutant EGFR. Tumor histology (p=0.0028), smoking status (p=0.0051) and maximum diameter of tumor shadow in chest CT (p=0.047) were also significantly associated with mutant EGFR. The accuracy for evaluating EGFR mutation status by discriminant analysis was 77.0% (114/148). Conclusions: Mutant EGFR is significantly associated with lung cancer with pure or mixed GGO, adenocarcinoma, never-smoker, smaller tumor diameter in chest CT. Preoperatively, EGFR mutation status can be identified correctly in about 77 % of lung cancers.

• Korean Journal of Head & Neck Oncology
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• v.19 no.2
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• pp.121-126
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• 2003

Objectives: The c-kit gene encodes a transmembrane receptor-type tyrosine kinase, which is known to have a significant role in the normal migration and development of germ cells and melanocytes. In the previous studies of c-kit gene, c-kit expressions showed only in adenoid cystic carcinomas, lymphoepithelioma-like carcinomas and myoepithelial carcinomas, but not in others and mutation was not found in any types of salivary carcinoma. We investigate the c-kit expression which may be useful to differentiating adenoid cystic carcinomas from others, and mutation of the gene which may not be exist nor the mechanism of c-kit activation in salivary carcinomas. Material and Methods: The archival tissue samples from 42 salivary carcinomas of major and minor salivary glands were studied for c-kit expression by immunohistochemistry and gene mutation by polymerase chain reaction amplification and single strand conformational polymorphism. Results: The c-kit expressions were noted in 22/24 adenoid cystic carcinomas, 7/9 mucoepidermoid carcinomas, 2/3 acinic cell carcinomas, 3/4 malignant mixed tumors, and one undifferentiated carcinoma. The mutation of c-kit gene was found in 3/24 adenoid cystic carcinomas, 3/8 mucoepidermoid carcinomas, one acinic cell carcinoma, and 2/4 malignant mixed tumors. Conclusion: c-kit protein overexpression is seen in a variety of salivary gland carcinomas, and the mutation of the gene may be the mechanism of c-kit activation in these neoplasms.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.6
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• pp.996-999
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• 2011

This experiment was performed to investigate whether the combined-preparation of crude drugs (The $Well^{TM}$ Preparation, TW), has hypnotic effects and/or enhances pentobarbital-induced sleep behaviors. TW was mixed with water extracts of Ginseng Radix red, Germinated brown rice, cultured mountain ginseng, and 50% ethanol extracts of Longanae Arillus, Nelumbinis Folium and Chrysanthemi Flos. TW (100 mg/kg, p.o.) reduced sleep onset and prolonged sleep time induced by pentobarbital similar to muscimol (0.2 ${\mu}M$), a $GABA_A$ receptor agonist. Also, TW (2 ${\mu}g$/ml) and pentobarbital (2.5 ${\mu}M$) did not affect the chloride influx in primary cultured cerebellar granule cells, respectively, but the combined-treatment of TW (2 ${\mu}g$/ml) and pentobarbital (2.5 ${\mu}M$) increased the chloride influx onto the cells. In conclusion, TW augments pentobarbital-induced sleep behaviors; these effects may result from chloride channel activation.