• Title/Summary/Keyword: relapse tendency

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Application of Molecular Diagnostics Technology in the Development of a Companion Diagnostics for Malignant Solid Tumors (악성 고형암의 항암제 동반진단 기술에서 분자진단기술의 적용)

  • Kim, Jin-Hee
    • The Journal of the Korea Contents Association
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    • v.19 no.3
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    • pp.365-374
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    • 2019
  • Unlike benign tumors, malignant tumors are capable of metastasis, easy to relapse, poor survival, and low quality of life. In Korea, here is a tendency to treat the tumors collectively according to the General Principles of Cancer Chemotherapy(GPCC) of the Health Insurance Review & Assessment Service (HIRA). But recently, companion diagnostics(CDx) is recommended rather than unilateral medication because biomarker-based molecular diagnostics is possible to predict the drug response of patients before drug treatment. Not only domestic but also overseas Food and Drug Administratio (FDA) recommends the development of the CDx system at the stage of drug development to ensure the responsiveness and safety of medicines. In this study, I focused on the necessity of CDx development direction as well as CDx development status through literature review. Furthermore I also discussed CDx types according to the molecular diagnostic technology such as immunohistochemistry (IHC), polymerase chain reaction (PCR), in situ hybridization (ISH), and next-generation sequencing (NGS) not only in the approved CDx but also in the developing one by US FDA. And I suggested the technology issue of CDx development process such as a selection of molecular diagnostics at the time of release, a clear understanding of the CDx mechanism, and a convergence of drug with CDx development. The necessity of social insurance system also was proposed for CDx development.

MRI study of temporomandibular joint disorder in orthodontic patients (교정환자에서 MRI를 이용한 측두하악관절 장애의 연구)

  • Kim, Tae-Woo;Byun, Eun-Sun;Baek, Seung-Hak;Chang, Young-Il;Nahm, Dong-Seok;Yang, Won-Sik
    • The korean journal of orthodontics
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    • v.30 no.2 s.79
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    • pp.235-243
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    • 2000
  • Magnetic resonance imaging(MRI) of the temporomandibular joint(TMJ) is very useful method to diagnose internal derangement of the TMJ because of its high specificity foy identification of condyle-disc relationships. The purpose of this study was to evaluate the existence, incidence and severity o』 internal derangement o』 the TMJ by the MRI of Patients who are suspected to have TMJ disorder. MRI sample was composed of 50 subjects(10 males, 40 females) and the mean age was 22.9 years. 43 subjects of the sample were found to have positive findings. $56\%$ of the subjects with positive findings had ADD(anterior disc displacement) without reduction, and $65\%$ had internal derangement of bilateral joints. Distributions in the types of malocclusion in patients with positive findings, the Angle's classification had shown : the largest $41.9\%$ for Cl II ($39.6\%$ for Cl II div 1 and $2.3\%$ for Cl II div 2), $37.2\%$ for Cl I, $18.6\%$ for Cl III, and $2.3\%$ for the unidentified. $8.6\%$ of the subjects with positive findings had facial asymmetry and $55.8\%$ had openbite. We can conclude that the percentage of Cl II is the highest in patients with internal derangement of the TMJ. Openbite or facial asymmetry is considered to be uncompensated or compensated deformity which results from facial skeleton remodeling in the process of degenerative joint disease(DJD) due to TMJ degeneration. Therefore it is recommended to screen the patients with facial asymmetry or openbite by MRI before the beginning of orthodontic treatment. Differential diagnosis is essential because the tendency of relapse is high after the orthodontic treatment and continuous observation of TMJ is needed in patients with TMJ disorder.

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Correlation of p53 Protein Overexpression, Gene Mutation with Prognosis in Resected Non-Small Cell Lung Cancer(NSCLC) Patients (비소세포폐암에서 p53유전자의 구조적 이상 및 단백질 발현이 예후에 미치는 영향)

  • Lee, Y.H.;Shin, D.H.;Kim, J.H.;Lim, H.Y.;Chung, K.Y.;Yang, W.I.;Kim, S.K.;Chang, J.;Roh, J.K.;Kim, S.K.;Lee, W.Y.;Kim, B.S.;Kim, B.S.
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.4
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    • pp.339-353
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    • 1994
  • Background : The p53 gene codes for a DNA-binding nuclear phosphoprotein that appears to inhibit the progression of cells from the G1 to the S phase of the cell cycle. Mutations of the p53 gene are common in a wide variety of human cancers, including lung cancer. In lung cancers, point mutations of the p53 gene have been found in all histological types including approximately 45% of resected NSCLC and even more frequently in SCLC specimens. Mutant forms of the p53 protein have transforming activity and interfere with the cell-cycle regulatory function of the wild-type protein. The majority of p53 gene mutations produce proteins with altered conformation and prolonged half life; these mutant proteins accumulate in the cell nucleus and can be detected by immunohistochemical staining. But protein overexpression has been reported in the absence of mutation. p53 protein overexpression or gene mutation is reported poor prognostic factor in breast cancer, but in lung cancer, its prognostic significance is controversial. Method : We investigated the p53 abnormalities by nucleotide sequencing, polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP), and immunohistochemical staining. We correlated these results with each other and survival in 75 patients with NSCLC resected with curative intent. Overexpression of the p53 protein was studied immunohistochemically in archival paraffin- embedded tumor samples using the D07(Novocastra, U.K.) antibody. Overexpression of p53 protein was defined by the nuclear staining of greater than 25% immunopositive cells in tumors. Detection of p53 gene mutation was done by PCR-SSCP and nucleotide sequencing from the exon 5-9 of p53 gene. Result: 1) Of the 75 patients, 36%(27/75) showed p53 overexpression by immunohistochemical stain. There was no survival difference between positive and negative p53 immunostaining(overall median survival of 26 months, disease free median survival of 13 months in both groups). 2) By PCR-SSCP, 27.6%(16/58) of the patients showed mobility shift. There was no significant difference in survival according to mobility shift(overall median survival of 27 in patients without mobility shift vs 20 months in patients with mobility shift, disease free median survival of 8 months vs 10 months respectively). 3) Nucleotide sequence was analysed from 29 patients, and 34.5%(10/29) had mutant p53 sequence. Patients with the presence of gene mutations showed tendency to shortened survival compared with the patients with no mutation(overall median survival of 22 vs 27 months, disease free median survival of 10 vs 20 months), but there was no statistical significance. 4) The sensitivity and specificity of immunostain based on PCR-SSCP was 67.0%, 74.0%, and that of the PCR-SSCP based on the nucleotide sequencing was 91.8%, 96.2% respectively. The concordance rate between the immunostain and PCR-SSCP was 62.5%, and the rate between the PCR-SSCP and nucleotide sequencing was 95.3%. Conclusion : In terms of detection of p53 gene mutation, PCR-SSCP was superior to immunostaining. p53 gene abnormalities either overexpression or mutation were not a significant prognostic factor in NSCLC patients resected with curative intent. However, patients with the mutated p53 gene showed the trends of early relapse.

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