• Title/Summary/Keyword: ALK-5

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A Case Report of Advanced Non-Small Cell Lung Cancer Patient Treated with Samchilchoongcho-Jung in Conjunction with Alectinib (알렉티닙과 삼칠충초정을 병용하여 호전된 진행성 비소세포성 폐암환자 1례)

  • Ko, Myung-hyun;Myong, Ji-soo;Park, So-jung;Jeon, Hyung-joon;Lee, Yeon-weol;Cho, Chong-kwan;Yoo, Hwa-seung
    • Journal of Korean Traditional Oncology
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    • v.24 no.1
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    • pp.1-9
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    • 2019
  • Objective: The purpose of this study is to report the clinical effectiveness of advanced non-small cell lung cancer (NSCLC) with Samchilchoongcho-Jung (HAD-B1) in conjunction with Alectinib. Methods: The patient was diagnosed with Anaplastic lymphoma kinase (ALK) mutated (2+) non-small cell lung cancer adenocarcinoma stage IV, suffering from edema of lower extremities, dyspnea, pleural effusion, general weakness, insomnia. The patient being treated with Alectinib was treated with Samchilchoongcho-Jung (HAD-B1) for disease control and symptom management. The clinical outcomes were measured by National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), Numeral rating scale (NRS) and Eastern Cooperative Oncology Group (ECOG). Results: After treatment, dyspnea and edema of lower extremities was relieved from NRS 7 to 5, and 6 to 1 respectively. And ECOG score of the patient was improved from grade 3 to 2. During and after treatment, we didn't find any severe toxicities on laboratory findings. Conclusion: This case study suggests that Samchilchoongcho-Jung (HAD-B1) may improve symptom relief and life quality of NSCLC patient in conjunction with Alectinib.

Design and Synthesis of an Anticancer Diarylurea Derivative with Multiple-Kinase Inhibitory Effect

  • El-Gamal, Mohammed I.;Oh, Chang-Hyun
    • Bulletin of the Korean Chemical Society
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    • v.33 no.5
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    • pp.1571-1576
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    • 2012
  • A diarylurea compound 1 possessing pyrrolo[3,2-$c$]pyridine nucleus was designed and synthesized with structure similarity to Sorafenib. Compound 1 was tested over 60-cancer cell line panel at a single dose concentration of 10 ${\mu}M$ and showed high activity. It was further tested in a five-dose mode to determine its $IC_{50}$, TGI, and $LC_{50}$ values over the 60 cell lines. Compound 1 showed high potency and good efficacy, and was accordingly tested at a single dose concentration of 10 ${\mu}M$ over a panel of 40 kinases. At this concentration, it completely inhibited the enzymatic activities of a number of oncogenic kinases, including ABL, ALK, c-RAF, FLT3, KDR, and TrkB. The target compound was subsequently tested over these 6 kinases in 10-dose testing mode in order to determine its $IC_{50}$ values.

Epidemiology of Lung Cancer in Korea: Recent Trends

  • Park, Ji Young;Jang, Seung Hun
    • Tuberculosis and Respiratory Diseases
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    • v.79 no.2
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    • pp.58-69
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    • 2016
  • Lung cancer causes the most cancer deaths in Korea. Although the smoking rate has begun to decrease, the prevalence of lung cancer is still increasing. We reviewed the national lung cancer registry data and the data published about lung cancer in Korea. In 2012, the crude incidence rate of lung cancer was 43.9 per 100,000. The age-standardized mortality rate of lung cancer was 19.8 per 100,000. The 5-year relative survival rate for lung cancer was 11.3% from 1993 to 1995 and increased to 21.9% in the period from 2008 to 2012. Lung cancer occurring in never-smokers was estimated to increase in Korea. Adenocarcinoma is steadily increasing in both women and men and has replaced squamous cell carcinoma as the most common type of lung cancer in Korea. In patients with adenocarcinoma, the frequency of EGFR mutations was 43% (range, 20%-56%), while that of the EMK4-ALK gene was less than 5%.

Clinical Efficacy and Possible Applications of Genomics in Lung Cancer

  • Alharbi, Khalid Khalaf
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1693-1698
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    • 2015
  • The heterogeneous nature of lung cancer has become increasingly apparent since introduction of molecular classification. In general, advanced lung cancer is an aggressive malignancy with a poor prognosis. Activating alterations in several potential driver oncogenic genes have been identified, including EGFR, ROS1 and ALK and understanding of their molecular mechanisms underlying development, progression, and survival of lung cancer has led to the design of personalized treatments that have produced superior clinical outcomes in tumours harbouring these mutations. In light of the tsunami of new biomarkers and targeted agents, next generation sequencing testing strategies will be more appropriate in identifying the patients for each therapy and enabling personalized patients care. The challenge now is how best to interpret the results of these genomic tests, in the context of other clinical data, to optimize treatment choices. In genomic era of cancer treatment, the traditional one-size-fits-all paradigm is being replaced with more effective, personalized oncologic care. This review provides an overview of lung cancer genomics and personalized treatment.

Targeting the Transforming Growth Factor-β Signaling in Cancer Therapy

  • Sheen, Yhun Yhong;Kim, Min-Jin;Park, Sang-A;Park, So-Yeon;Nam, Jeong-Seok
    • Biomolecules & Therapeutics
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    • v.21 no.5
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    • pp.323-331
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    • 2013
  • TGF-${\beta}$ pathway is being extensively evaluated as a potential therapeutic target. The transforming growth factor-${\beta}$ (TGF-${\beta}$) signaling pathway has the dual role in both tumor suppression and tumor promotion. To design cancer therapeutics successfully, it is important to understand TGF-${\beta}$ related functional contexts. This review discusses the molecular mechanism of the TGF-${\beta}$ pathway and describes the different ways of tumor suppression and promotion by TGF-${\beta}$. In the last part of the review, the data on targeting TGF-${\beta}$ pathway for cancer treatment is assessed. The TGF-${\beta}$ inhibitors in pre-clinical studies, and Phase I and II clinical trials are updated.

Biopsy and Mutation Detection Strategies in Non-Small Cell Lung Cancer

  • Jung, Chi Young
    • Tuberculosis and Respiratory Diseases
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    • v.75 no.5
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    • pp.181-187
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    • 2013
  • The emergence of new therapeutic agents for non-small cell lung cancer (NSCLC) implies that histologic subtyping and molecular predictive testing are now essential for therapeutic decisions. Histologic subtype predicts the efficacy and toxicity of some treatment agents, as do genetic alterations, which can be important predictive factors in treatment selection. Molecular markers, such as epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement, are the best predictors of response to specific tyrosine kinase inhibitor treatment agents. As the majority of patients with NSCLC present with unresectable disease, it is therefore crucial to optimize the use of tissue samples for diagnostic and predictive examinations, particularly for small biopsy and cytology specimens. Therefore, each institution needs to develop a diagnostic approach requiring close communication between the pulmonologist, radiologist, pathologist, and oncologist in order to preserve sufficient biopsy materials for molecular analysis as well as to ensure rapid diagnosis. Currently, personalized medicine in NSCLC is based on the histologic subtype and molecular status. This review summarizes strategies for tissue acquisition, histologic subtyping and molecular analysis for predictive testing in NSCLC.

Free Radical-mediated Ring Expansion Reactions:Endocyclic Cleavage of Cyclopropylcarbinyl Radicals

  • Lee, Pil Ho;Lee, Byeong Cheol;Lee, Gu Yeon;Lee, Chang Hui;Jang, Suk Bok
    • Bulletin of the Korean Chemical Society
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    • v.21 no.6
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    • pp.595-603
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    • 2000
  • Ring expansion reactions via endocyclic cleavage of cyclopropylcarbinyl radicals derived from the reaction of [1-benzyloxycarbonylbicyclo[n. 1.O]alk-(n+l)-yl] -1-imidazolethiocarboxylates with tributyltin hydride/AIBN proceeded to produce 3-cycloalkenecarboxylates in good yields. Benzyl (5'-phenoxypentyl) -3-cyclohepten-1 -carboxylate was obtained in 33% yield from the reaction of benzyl 5-methylenebicyclo [4. 1.0]- 1-carboxylates with 4-phenoxybutyl iodide under radical conditions. Selective cleavage of endocyclic bond in cyclopropane to the cyclohexane, results from stabilization of the resultant radical by the carbonyl groups, such as the benzyloxycarbonyl group, which lower the transition state energy for the final cyclopropane cleavage in the ring expansion.

The Effect of the Unsaturated Oil on the Normal Liver and Lipid Metabolism of Rats Fed Several Plant Oils (불포화도가 다른 식물성 유지를 섭취시킨 흰쥐에서 정상적 간 및 지질대사변화의 고찰)

  • 서화중;김선희;정두례
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.20 no.5
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    • pp.426-432
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    • 1991
  • To investigate the effect of the unsaturated plant oil on the normal liver and lipid metabalism rats were fed the daily dose of 1.57ml/kg body weight of perilla oil (Iodine value 190~207), corn oil (Iodine value 115~130) and olive oil (Iodine value 80~85) respectively for 28 days. The results were as follows. For the 14 days the test groups showed normal weight gain with 7.86~20.89% increase rate. In the period of the 3rd and the 4th week the increase rate of the perilla oil group was decreased significantly under 17.53~13.8% of control level, but the remainders(corn oil, olive oil) keep normal. The feeding of corn and olive oil for 28 days did show any harmful effect on normal GOT, GPT activity, ALK-P, serum cholesterol and serum triglyceride value of rat. The perilla oil feeding for 21~28 days slightly increased the GOT, GPT activity as 174.87, 93.46u but decreased the cholesterol and triglycerids value as 54.6~0.36mg/dl compared to control. In the pathological finding of test group liver some rats in 28 days feeding group showed reactive vesicula nuclei in corn oil group and mild fatty metamorphosis in olive oil group. But most subjects did not show any characterized sign of acute or subacute liver damage.

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Lung Adenocarcinoma Gene Mutation in Koreans: Detection Using Next Generation Sequence Analysis Technique and Analysis of Concordance with Existing Genetic Test Methods (한국인의 폐선암 유전자 돌연변이: 차세대 염기서열 분석법을 이용한 검출 및 기존 유전자 검사법과의 일치도 분석)

  • Jae Ha BAEK;Kyu Bong CHO
    • Korean Journal of Clinical Laboratory Science
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    • v.55 no.1
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    • pp.16-28
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    • 2023
  • Lung adenocarcinoma accounts for about 40% of all lung cancers. With the recent development of gene profiling technology, studies on mutations in oncogenes and tumor suppressor genes, which are important for the development and growth of tumors, have been actively conducted. Companion diagnosis using next-generation sequencing helps improve survival with targeted therapy. In this study, formalin-fixed paraffin-embedded tissues of non-small cell lung cancer patients were subjected to hematoxylin and eosin staining for detecting genetic mutations that induce lung adenocarcinoma in Koreans. Immunohistochemical staining was also performed to accurately classify lung adenocarcinoma tissues. Based on the results, next-generation sequencing was applied to analyze the types and patterns of genetic mutations, and the association with smoking was established as the most representative cause of lung cancer. Results of next-generation sequencing analysis confirmed the single nucleotide variations, copy number variations, and gene rearrangements. In order to validate the reliability of next-generation sequencing, we additionally performed the existing genetic testing methods (polymerase chain reaction-epidermal growth factor receptor, immunohistochemistry-anaplastic lymphoma kinase (D5F3), and fluorescence in situ hybridiation-receptor tyrosine kinase 1 tests) to confirm the concordance rates with the next-generation sequencing test results. This study demonstrates that next-generation sequencing of lung adenocarcinoma patients simultaneously identifies mutation.

Effects of Daidzein on mRNA Expression of Bone Morphogenetic Protein Receptor Type I and II Genes in the Ovine Granulosa Cells

  • Chen, A Qin;Xu, Zi Rong;Yu, Song Dong;Yang, Zhi Gang
    • Asian-Australasian Journal of Animal Sciences
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    • v.23 no.3
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    • pp.326-332
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    • 2010
  • Daidzein, a natural isoflavonoid phytoestrogen, structurally resembles estradiol (E2) and possesses estrogenic activity. This study was designed to test the hypothesis that daidzein may mimic the effects of E2 on ovine follicle development by regulation of the mRNA expression of bone morphogenetic protein receptor genes and thereby influence the reproductive system. Granulosa cells were cultured in serum-free McCoy's 5A medium with and without supplementation of daidzein. Results showed that daidzein (10-100 ng/ml) significantly increased the proliferation of ovine granulosa cells (p<0.05), but inhibited the growth of granulosa cells at a dose of 1,000 ng/ml (p<0.01). Daidzein inhibited progesterone production in a dose dependent manner; however, it did not affect estradiol production by granulosa cells. We also investigated the effects of daidzein on BMPRII, BMPRIB and ALK-5 mRNA expression in ovine granulosa cells by quantitative real-time PCR. Treatment of granulosa cells with daidzein increased significantly expression of these genes at 10-100 ng/ml. Thus, these data suggested that a low concentration of daidzein (10-100 ng/ml) had a direct stimulatory effect on ovine granulosa cells while a high concentration was toxic.