• Title/Summary/Keyword: ALK

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Development of an RNA sequencing panel to detect gene fusions in thyroid cancer

  • Kim, Dongmoung;Jung, Seung-Hyun;Chung, Yeun-Jun
    • Genomics & Informatics
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    • v.19 no.4
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    • pp.41.1-41.10
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    • 2021
  • In addition to mutations and copy number alterations, gene fusions are commonly identified in cancers. In thyroid cancer, fusions of important cancer-related genes have been commonly reported; however, extant panels do not cover all clinically important gene fusions. In this study, we aimed to develop a custom RNA-based sequencing panel to identify the key fusions in thyroid cancer. Our ThyChase panel was designed to detect 87 types of gene fusion. As quality control of RNA sequencing, five housekeeping genes were included in this panel. When we applied this panel for the analysis of fusions containing reference RNA (HD796), three expected fusions (EML4-ALK, CCDC6-RET, and TPM3-NTRK1) were successfully identified. We confirmed the fusion breakpoint sequences of the three fusions from HD796 by Sanger sequencing. Regarding the limit of detection, this panel could detect the target fusions from a tumor sample containing a 1% fusion-positive tumor cellular fraction. Taken together, our ThyChase panel would be useful to identify gene fusions in the clinical field.

Caspase Cleavage of Receptor Tyrosine Kinases in the Dependence Receptor Family

  • Gyu Hwan Park;Yoo Kyung Kang;Seung-Mann Paek;Chan Young Shin;Sun-Young Han
    • Biomolecules & Therapeutics
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    • v.31 no.4
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    • pp.359-369
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    • 2023
  • Dependence receptors are a group of receptor proteins with shared characteristics of transducing two different signals within cells. They can transduce a positive signal of survival and differentiation in the presence of ligands. On the other hand, dependence receptors can transduce an apoptosis signal in the absence of ligands. The function of these receptors depends on the availability of their ligands. Several receptor tyrosine kinases (RTKs) have been reported as dependence receptors. When cells undergo apoptosis by dependence receptors, the intracellular domain of some RTKs is cleaved by the caspases. Among the RTKs that belong to dependence receptors, we focused on eight RTKs (RET, HER2, MET, ALK, TrkC, EphA4, EphB3, and c-KIT) that are cleaved by caspases. In this review, we describe the features of the receptors, their cleavage sites, and the fate of the cleaved products, as well as recent implications on them being used as potential therapeutics for cancer treatment.

A Study on the Changes of Blood Mineral and Enzyme Activity During Growth Period of Velvet Antler in Korean Spotted Deer(Cervus Nippon) (꽃사슴의 녹용 성장기간 중 혈액 내 미네랄 및 효소활성 변화에 관한 연구)

  • Kim, M.H.;Moon, S.H.;Lee, C.H.;Jeon, B.T.
    • Journal of Animal Science and Technology
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    • v.45 no.6
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    • pp.1031-1038
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    • 2003
  • This study was aimed at investigating the change of blood mineral and enzyme activity during growth period of velvet antler in Korean spotted deer. Samples of blood, obtained from the jugular vein of twenty-five deer(4 to 6 year-old males), were taken in 10 days interval from just after casting to 50 days. Deer were randomly selected from the farm, and samples were analyzed for blood parameters like mineral concentration and enzyme activities. No significant differences found in calcium and phosphorus concentration in blood whereas sodium, potassium and chloride concentration were significantly changed with antler growth. There were no significant differences in alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, $\gamma$-glutamyl transferase and lactate dehydrogenase during growth of antler, but alkaline phosphatase concentration was increased with growth of antler, and the highest concentration was obtained on the 50 days after casting. Creatine kinase and lactate dehydrogenase activities for the deer tested in this experiment were higher than those of other animals.

Identification of Alternative Splicing and Fusion Transcripts in Non-Small Cell Lung Cancer by RNA Sequencing

  • Hong, Yoonki;Kim, Woo Jin;Bang, Chi Young;Lee, Jae Cheol;Oh, Yeon-Mok
    • Tuberculosis and Respiratory Diseases
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    • v.79 no.2
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    • pp.85-90
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    • 2016
  • Background: Lung cancer is the most common cause of cancer related death. Alterations in gene sequence, structure, and expression have an important role in the pathogenesis of lung cancer. Fusion genes and alternative splicing of cancer-related genes have the potential to be oncogenic. In the current study, we performed RNA-sequencing (RNA-seq) to investigate potential fusion genes and alternative splicing in non-small cell lung cancer. Methods: RNA was isolated from lung tissues obtained from 86 subjects with lung cancer. The RNA samples from lung cancer and normal tissues were processed with RNA-seq using the HiSeq 2000 system. Fusion genes were evaluated using Defuse and ChimeraScan. Candidate fusion transcripts were validated by Sanger sequencing. Alternative splicing was analyzed using multivariate analysis of transcript sequencing and validated using quantitative real time polymerase chain reaction. Results: RNA-seq data identified oncogenic fusion genes EML4-ALK and SLC34A2-ROS1 in three of 86 normal-cancer paired samples. Nine distinct fusion transcripts were selected using DeFuse and ChimeraScan; of which, four fusion transcripts were validated by Sanger sequencing. In 33 squamous cell carcinoma, 29 tumor specific skipped exon events and six mutually exclusive exon events were identified. ITGB4 and PYCR1 were top genes that showed significant tumor specific splice variants. Conclusion: In conclusion, RNA-seq data identified novel potential fusion transcripts and splice variants. Further evaluation of their functional significance in the pathogenesis of lung cancer is required.

Evaluation of the Frequency of the IL-28 Polymorphism (rs8099917) in Patients with Chronic Hepatitis C Using Zip Nucleic Acid Probes, Kerman, Southeast of Iran

  • Iranmanesh, Zahra;Mollaie, Hamid Reza;Arabzadeh, Seyed Alimohammad;Zahedi, Mohammad Javad;Fazlalipour, Mehdi;Ebrahimi, Saeede
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1919-1924
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    • 2015
  • Polymorphisms in the region of the interleukin IL-28 gene on chromosome 19 have been related with clearance of hepatitis C virus (HCV), a major human pathogen responsible for chronic hepatitis, cirrhosis and hepatocellular carcinoma. About 3% of the world's population is infected with HCV. The long-term response to therapy is influenced by many host and viral factors, and recent evidence has indicated that some host genetic polymorphisms related to IL-28 are the most powerful predictors of virological response in patients with HCV. This study assessed frequency of the IL-28 polymorphism (rs8099917) in 50 patients (39 men and 11 women) with chronic hepatitis C using ZNA probe real time PCR new method. All patients were tested for genotype of HCV and the HCV viral load. In parallel, the levels of SGOT, SGPT and ALK enzymes were assessed. Treatment using Peg-interferon alpha with ribavirin was conducted for patients and subsequently samples were collected to detect any change in viral load or liver enzyme rates. The overall frequency of the TT allele is 74%, TG allele 20% and GG allele 6% and the percent of patients who had T allele was 84%. Clear reduction in viral load and liver enzymes was reported in patients with the T allele. Especially for genotype 1 which is relatively resistant to treatment, these alleles may have a role in this decline. In conclusion, we showed that IL-28 polymorphism rs8099917 strongly predicts virological response in HCV infection and that real-time PCR with Zip nucleic acid probes is a sensitive, specific and rapid detection method for detection of SNPs which will be essential for monitoring patients undergoing antiviral therapy.

An Analytical Study on Health Characteristics of Obesity of Adulthood (성인 비만의 건강특성에 관한 분석적 연구)

  • 탁기천;류규수
    • Korean Journal of Health Education and Promotion
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    • v.18 no.2
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    • pp.115-128
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    • 2001
  • This study was carried out to offer the basic data for more qualitative lives of the adulthood with obesity through their health maintenance and control. So, the researcher reviewed and analyzed the health problems of the subjects according to sex, age, and positive rate on the screening tests. The subjects were 91 obese persons in K university hospital in Seoul from December 1, 2000 to January 31, 2001. A Questionnaire developed by researcher to obtain subject's general characteristics, main symptoms, medical examination, diagnosed disease was used as the tool for the study. The results of this study are as follows: 1. For the distribution of diagnosis in subjects, liver disease was most frequent and hypertension was second. 2 The most common complaints were indigestion in the digestive system, throat pain in the respiratory system, dyspnea in cardiovascular system, thirsty in endocrine system, frequent urine in the urinary system, vertigo in the hematologic system. 3. The main symptoms according to sex were for females, a statistically significant higher rate of complaints in the digestive system, musculoskeletal system as compared to males. 4. The main symptoms according to age were that in the fourth decade there were higher rate of complaints in the musculoskeletal system. 5. In screening tests according to sex, males showed a higher positive rate for Alk-Phosphatase and females, in FBS, urine-micro, VDRL. 6. In screening tests according to age, higher positive rates of BP, Chest X-ray, mammography, ESR, CRP were seen in the fourth decades. 7. Obesity was positively related to cardiovascular system, endocrine system, urinary system, musculoskeletal system, mental and nervous system in main symptoms. 8. Obesity was positively related to BP, Sonography, FBS, SGOT, SGPT in screening tests.

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Calcifying Fibrous Tumor Mimicking a Foreign Body of the Stomach: A Case Report (위 내 이물로 오인한 석회화 섬유 종양 1예)

  • Jeong, Ji-Eun;Lee, Kyung-Hun;Sung, Hyun-Jung;Cho, Chang-Ho
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.12 no.1
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    • pp.57-63
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    • 2009
  • Calcifying fibrous tumors (CFTs) are unusual benign tumors of childhood, located primarily in soft tissues, pleura, and peritoneum. The cause and pathogenesis are unclear. We report a rare case of a CFT in a 2-year-old boy who presented with vomiting and abdominal distension. An abdominal X-ray showed an elliptical, calcific shadow in the LUQ area mimicking a foreign body. An internally protruding mass along the lesser curvature of the gastric body was an incidental finding during upper endoscopy, biopsies of which were negative. Abdominal CT showed a 4.5${\times}$3.2 cm soft tissue mass of the gastric wall with calcifications. A diagnosis of gastric submucosal mass was suspected and a wedge resection of the stomach was performed. On microscopic examination, the tumor was composed of whorls of dense hyalinized collagen bundles with a few fibroblasts. There were also amorphous dystrophic calcifications and nodular aggregates of mononuclear inflammatory cells. Immunohistochemically, spindle cells did not stain for anaplastic lymphoma kinase-1 (ALK-1), CK, smooth muscle actin (SMA), or desmin. Taken together, the mass was compatible with a CFT of the gastric wall. This is the first reported case of CFT in a Korean child.

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Affection of Blood Calcium, Ino-Phosphorus and Alkaline Phosphatase Activity Inject with Paraquat on Rats

  • Lee, Wha-Jae
    • Biomedical Science Letters
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    • v.8 no.2
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    • pp.71-75
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    • 2002
  • Paraquat (N,N'-dimethyl-4,4'-bipyrrimidinium-dichlorides (PQ): MW 186.6) has been used to killing verierty of hubside plants. For this study were use Sprague-dawely rats (190$\pm$10 gm) and injection 40 mg/kg BW of paraquat (LD$_{50}$) to 24 hrs PQ and 4 days PQ group excepte normal control. For the measurement of blood calcium Ino-phosphorus and activity of alkaline phosphatase (ALP) by HITTACH 746. In serum phosphoruse of normal control were 8.0$\pm$1.2 mg/dl and 24 hrs PQ group were 8.9$\pm$1.0 mg/dl (P<0.05) and 4 days PQ group were 8.8$\pm$0.42 gmm/dl (P<0.05). In serum phosphorus were very sensitive uptaked to 10% within only 24 hours, but 4 days of PQ were similar uptake level than 24 hrs PQ. So this 8.9 mg/dl of sem phosphorus may be thought threshold level becouse does not more encrease. In blood calcium normal of rats were measured 9.51$\pm$0.3 mg/dl and 24 hrs of PQ group were 9.9$\pm$0.51 mg/dl (uptaked 4.5%, p>0.05). This uptake cannot fined meaning mathmatic statistics but 4 days PQ groups of calcium were 10.43$\pm$0.37 gm/dl (uptaked 10%, p<0.05). That 24 hrs PQ groups of caclium dose not reacted sensitive to irritated by PQ. So, when use oxidants of PQ, the blood calcium and Ino-phosphorus were linear correlated uptake that reasone thought may be move out form hardness bone tissue to in blood it does not take feeding to hunger for 4 days. In ALP normal of rats were measured 991$\pm$106 unit/L. In 24 hrs irritated PQ rats were fall down by 629$\pm$91 unit/L (P<0.001) but in 4 days of PQ rats were 792$\pm$85 unit/L (P<0.0011) that the activity of level were mild recovered activity from 629 unit (63%) to 792 unit (80%). So, that the reasone of ALP were very sensitive activity and reverse correlated to blood calcium or phosphorus irritated by PQ.

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Partial Nitrification of Wastewater with Strong N for Anaerobic Nitrogen Removal (혐기성 질소제거를 위한 고농도 질소폐수의 부분질산화)

  • Hwang, In-Su;Min, Kyung-Sok
    • Journal of Korean Society of Environmental Engineers
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    • v.28 no.4
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    • pp.414-420
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    • 2006
  • Effluent from an anaerobic digestion system with an elutriated phased treatment(ADEPT, Anaeorbic Digestion Elutriated Phase Treatment) for piggery waste treatment using anaerobic ammonium oxidation(ANAMMOX) process was used as a substrate of partial nitrification reactor. In mesophilic condition($35^{\circ}C$), controlling parameters of nitrite accumulation were HRT, pH, free ammonia(FA) and hydroxylamine rather than dissolved oxygen. Bicarbonate alkalinity consumption ratio including bicarbonate stripping and buffering was 8.78 g $Alk._{comsumed}/g\;NH_4-N_{converted}$. In steady state for 1 day of HRT and $2.7{\sim}4.4mg/L$ of DO, $NO_2-N/NH_4-N$ ratio of partial nitrification effluent was about $1{\sim}3$, which was applicable to ANAMMOX reactor influent for the combined partial nitrification-ANAMMOX process.

Promoting Effects of Sanguinarine on Apoptotic Gene Expression in Human Neuroblastoma Cells

  • Cecen, Emre;Altun, Zekiye;Ercetin, Pinar;Aktas, Safiye;Olgun, Nur
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9445-9451
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    • 2014
  • Neuroblastoma is the most common extracranial solid tumor in children. Approximately half of the affected patients are diagnosed with high-risk poor prognosis disease, and novel therapies are needed. Sanguinarine is a benzophenanthridine alkaloid which has anti-microbial, anti-oxidant and anti-inflammatory properties. The aim of this study is whether sanguinarine has in vitro apoptotic effects and which apoptotic genes might be affected in the human neuroblastoma cell lines SH-SY5Y (N-myc negative), Kelly (N-myc positive, ALK positive), and SK-N-BE(2). Cell viability was analysed with WST-1 and apoptotic cell death rates were determined using TUNEL. After RNA isolation and cDNA conversion, expression of 84 custom array genes of apoptosis was determined. Sanguinarine caused cell death in a dose dependent manner in all neuroblastoma cell lines except SK-N-BE(2) with rates of 18% in SH-SY5Y and 21% in Kelly human neuroblastoma cells. Cisplatin caused similar apoptotic cell death rates of 16% in SH-SY5Y and 23% in Kelly cells and sanguinarine-cisplatin combinations caused the same rates (18% and 20%). Sanguinarine treatment did not affect apoptototic gene expression but decreased levels of anti-apoptotic genes NOL3 and BCL2L2 in SH-SY5Y cells. Caspase and TNF related gene expression was affected by the sanguinarine-cisplatin combination in SH-SY5Y cells. The expression of regulation of apoptotic genes were increased with sanguinarine treatment in Kelly cells. From these results, we conclude that sanguinarine is a candidate agent against neuroblastoma.