• Title/Summary/Keyword: 분자 진단

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Expression and Clinical Significance of the N-myc Downstream Regulated Gene-1 in Hypopharyngeal Cancer (하인두암에서의 N-myc Downstream Regulated Gene-1 발현의 임상적 의의)

  • Sohn, In-Kyung;Han, Nam-Soo;Shin, Yoo-Seob;Kim, Jang-Hee;Kim, Chul-Ho
    • Korean Journal of Head & Neck Oncology
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    • v.27 no.1
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    • pp.22-26
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    • 2011
  • 목 적 : 두경부 암은 발생 순위에서 전체 6위에 해당하는 다빈도 암이나 최근 20여년 동안의 노력에도 불구하고 두경부 암의 독톡한 특성상 생존률에서 뚜렷한 향상을 보이지 못하고 있다. 특히, 하인두 암은 원발 부위의 점막하 침윤이 흔하며, 주변 림프절 전이와 원격 전이가 흔하고, 2차 원발 암종 발생이 흔하여 두경부 암 중에서도 가장 불량한 예후를 보이고 있는 악성 종양이다. 최근에 이러한 암을 치료하고 진단하기 위한 방법으로 분자생물학적 접근법들이 많이 시도 되고 있으며, 그 중 하나로 N-myc downstream regulated gene-1(Ndrg-1)이라는 유전자가 유방, 전립선, 방광 암 등의 타 악성 종양에서 종양의 전이 및 진행 양상과 관련되어 있다는 보고가 있었다. 이에 본 연구는 하인두 암에서의 Ndrg-1의 발현 양상을 살펴보고 이와 임상 양상과의 연관관계를 살펴보고자 하였다. 방 법 : 1996년부터 2003년까지 수술 받은 하인두 암 환자 56명을 대상으로 면역조직화학검사를 시행하여 Ndrg-1 발현을 확인하였고, 3명의 신선 조직을 대상으로 RT-PCR, Western blot을 시행하였다. 결 과 : Ndrg-1은 RT-PCR에서 정상 조직과 악성종양 조직 모두에서 비슷한 수준으로 발현되었다. 그러나 Western blot에서는 정상 조직에서 뚜렷한 증가 양상을 보여 타 연구와 동일한 결과를 보였고, 이는 불필요하며 비효율적인 mRNA수준에서의 발현이 있지만 최종적인 단백 산물 발현에서는 암종의 진행과 연계되어 악성 종양 진행군에서 발현이 억제되는 결과로 해석된다. 면역조직화학검사에서는 정상 상피조직에서 Ndrg-1 발현이 확인되었으며, 통계적으로 유의하지는 않으나 불량한 예후를 가진 그룹에서 대체로 발현이 억제되는 악성 종양과의 역 연관 관계를 확인할 수 있었고, 특히 림프절 전이를 보인 그룹과 그렇지 않은 그룹 사이에서는 통계적으로 유의미한 결과가 확인되었다. 결 론 : 즉, 림프절 전이가 없는 그룹에서 Ndrg-1이 종양의 전이에 관여할 것이라는 타 연구와 일관된 결과로 하인두 암에서도 그 역할이 있음을 나타내는 결과라 할 수 있다.

Pharmacogenomics in Cancer Research

  • Rha Sun-Young
    • Proceedings of the Korean Society for Bioinformatics Conference
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    • 2006.02a
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    • pp.91-96
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    • 2006
  • 현대의학의 발전으로 많은 질병들의 치료율이 개선되고 있으나, 암은 여전히 낮은 치료율과 약제 내성 및 부작용으로 많은 환자들이 의학적 고통 뿐 아니라 정신적, 경제적 문제점들을 호소하고있다. 이와같은 문제점은 동일한 병리학적 특성을 가지는 종양이라도 사람마다 그 생물학적 특성이 다르며, 동일한 환자안에서도 종양의 시기에 따라 다양한 특성의 세포들이 공존하며 다양한 문제를 발생하는 tumor heterogeneity에서 기인하게된다. 다행히 최근의 분자생물학의 발전과 인간유전체연구들의 활성화로 이와같은 다양한 암의 특성과 환자들의 특성을 이해하는 연구 방법들의 개발로 환자의 특성에 맞는 항암제를 효율적으로 투여하는 맞춤치료를 향한 노력을 지속하고 있다. 이와같은 맞춤치료의 일환으로 약제의 환자에서의 반응과 부작용을 예측하고자 최신의 high-throughput 기법을 도입한 것이 Pharmacogenomics이다. 즉, 지금까지의 항암치료는 암의 종류에 따라 임상연구 결과에 근거한 항암제를 선택하고 있다. 그러나 앞서 설명한 것처럼 암의 특성과 환자 반응의 다양화로 실제 항암효과는 기대에 미치지 못하여 많은 수의 환자들이 치료에 내성을 보일 뿐 아니라 치명적인 부작용으로 새로운 문제에 대면하게 되었다. 따라서 각 항암제011 최대의 효과를 보이며 최소의 부작용을 나타내는 최선의 치료책을 선정하는 것이 중요한 과제이다. 이를 위해서 암환자의 치료 단계에서 정확한 진단 및 병기 설정, 생물학적 특성 이해 뿐 아니라, 치료 반응을 예측할 수 있는 생물학적 표지자를 찾고자 하는 노력의 결과로 현재 임상에 사용되는 몇 가지 종양표지자를 포함하여 다양한 유전자 칩들이 연구단계에 있다. 특히 다양한 생물학적 현상이 많은 유전자들의 변화에 의한다는 근거하여 약제의 효과와 부작용을 예측할 수 있는 표지자 발굴도 DNA chip 등의 high-throughput technology를 사용하여 그 특이도와 민감도가 향상된 표지자 발굴이 시도되고 있다. 아직은 시작단계이고 많은 검증이 필요하나 여러 가지 가능성의 증거들로 멀지않은 시기에 맞춤치료가 가능하리라 기대하며, 암 연구에 있어서 pharmacogenomics의 현황을 소개하고자 한다.

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Productivity, Isolation and Purification of Egg Yolk Antibody(IgY) againt Food Poisoning Bacteria (Salmonella typhimurium) (식중독균 항원(Salmonella typhimurium)에 의한 계란항체(IgY) 생산성과 분리 정제)

  • 한준표;백반석;배만종
    • Journal of the East Asian Society of Dietary Life
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    • v.9 no.2
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    • pp.200-206
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    • 1999
  • This study was carried out to get a industrial information about a possibility of IgY antibody production, antimicrobial activity and Properties of IgY antibody in egg yolk. After the initial immunization the anti-Salmonella typhimurium IgY antibody level gradually were decreased from firth week to tenth week. On the other hand, the antibody level in the serum were increased from the first week, reaching its peak in the sixth week. Molecular weights of IgY were estimated approximately 72-75KD in a heavy chain and 30-40KD in a light chain by electrophoresis.

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Repetitive Pregnancy Loss in inv(22)(p13q12) Carrier

  • Kim, Do-Hoon;Ha, Jung-Sook;Rhee, Jeong-Ho
    • Journal of Genetic Medicine
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    • v.7 no.1
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    • pp.78-81
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    • 2010
  • Pericentric inversion is not rare in humans and is usually benign. However, pericentric inversion can lead to production of an unbalanced recombinant and might be a cause of repetitive pregnancy loss. Pericentric inversion of chromosome 22 is rare and only a few cases have been reported. We report a case of inv(22)(p13q12) carrier who had history of repetitive pregnancy loss including three spontaneous abortions and one fetal hydrops in which the chromosomal complement was rec(22)dup(22q) inv(22)(p13q12)mat. The maternal inv(22) and fetal rec(22) were confirmed by fluorescence in situ hybridization using region-specific probes (TUPLE1 on 22q11.2 and ARSA on 22q13). Because the identification of inv(22) or rec(22) in conventional karyotyping might be easily overlooked, great attention and additional molecular tests are required for accurate diagnosis of inv(22) and rec(22).

Methylation Abnormality in Body Fluid Cytology: A Supplemental Molecular Marker for the Diagnosis of Malignant Mesothelioma (체액 세포 도말 검사에서 메틸화 이상이 악성 중피종 진단의 부가적인 분자 표지자로서의 기능)

  • Song, Joon-Seon;Jung, Jin-Kyung;Kang, Ji-Hye;Hwang, Il-Seon;Jang, Se-Jin
    • The Korean Journal of Cytopathology
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    • v.19 no.2
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    • pp.126-135
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    • 2008
  • Malignant mesothelioma (MM) is a highly lethal neoplasm arising in pleura and the peritoneum and a rapid and accurate diagnosis is crucial for treatment of the disease. However, the sensitivity of cytological analysis using pleural or ascitic fluid is relatively low, yielding an accurate diagnosis in only $32{\sim}79%$ of cases. We tested the diagnostic value of epigenetic alterations in body fluid cytology as a supplement to conventional methods. Paraffin-embedded tissue blocks from 21 MM patients and associated body fluid cytology slides considered no evidence of malignancy were used to test for epigenetic alteration. Using methylation-specific PCR, we detected methylation of RASSF1A and p16 in 47.6% (10/21) of both surgically resected tumor samples, respectively. Body fluid samples of MM also showed abnormal methylation of RASSF1A and p16INK4a genes in 38.1% (8/21) and 33.3% (7/21) of cases. The concordance in the rates of RASSF1A and p16INK4a gene-methylation abnormalities determined from cytology samples and tissue samples were 61.9% (13/21) and 66.7% (14/21), respectively. Combining both genes increases the sensitivity of the test to 57.1 % (12 of 21) of cases. Our results suggest that testing for methylation abnormalities in selected individual genes or gene combinations has diagnostic value as an alternative or adjunct method to conventional cytological diagnosis.

A Case of Apert Syndrome with a P253R Mutation on FGFR2 Exon VIII (FGFR2 유전자의 8번째 엑손부위의 P253R 돌연변이로 진단된 Apert 증후군 1례)

  • Lee, Young-Jin;Ko, Jung-Min;Park, Seong-Shik;Cheon, Chong-Kun
    • Journal of Genetic Medicine
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    • v.7 no.2
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    • pp.151-155
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    • 2010
  • Apert syndrome is a rare congenital anomaly characterized by craniofacial malformations and severe symmetrical syndactyly of fingers and toes. This syndrome is caused by a genetic mutation; the S253 mutation is common, though the P253R mutation is not as frequent. Common symptoms include skeletal malformations, poor joint mobility, eye and ear problems, cleft palate, and orthodontic and other dental problems. We report a case of an infant with the common morphological features of Apert syndrome. Interestingly, she was found to have the P253R mutation in FGFR2 exon VIII, which has been less commonly observed in Korea. A brief review of the literature is included.

Antimicrobial Effects of Essential Oils for Multidrug-Resistant Acinetobacter baumanii (다제내성 아시네토박터 바우마니의 에센셜 오일에 대한 항균효과)

  • Park, Chang-Eun;Kwon, Pil Seung
    • Korean Journal of Clinical Laboratory Science
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    • v.50 no.4
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    • pp.431-437
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    • 2018
  • Acinetobacter baumannii is categorized as a red alert pathogen that is increasingly associated with a high mortality rate in infected patients because of its resistance to extensive antibiotics. This study evaluated the antibacterial activities of some essential oils (tee tree, rosemary, and lavender oils) against 18 clinical isolates of multidrug-resistant A. baumannii (MRAB). The carbapenemase screening Hodge test showed that all 20 strains of A. baumannii were resistant to imipenem. The identification of multidrug-resistant microbes was carried out using the VITEK system. The antimicrobial activity of essential oils was tested by a disk diffusion method against MRAB. In the disk diffusion method, tea tree showed the largest increase in inhibition size compared to lavender oil, and rosemary had no antibacterial effect. These results proved the antimicrobial effect of multidrug resistance A. baumannii. Tee tree oil would be a useful alternative natural product for the treatment and prevention of most common human pathogens and MRAB infections. This is expected to be used as an antimicrobial agent, such as hand disinfectant using natural essential oil in the future.

A study on the Aptamer Specific Detection on P. gingivalis (P. gingivalis에 특이적으로 작용하는 앱타머에 관한 연구)

  • Shin, Ae-Ri
    • The Journal of the Korea Contents Association
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    • v.21 no.4
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    • pp.825-832
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    • 2021
  • In this study, by selecting specific aptamers that selectively detection on P. gingivalis, the main cause of periodontal disease, and purifying and identifying protein molecules that bind to the selected aptamers, the mechanism of action of P. gingivalis was investigated. A DNA library having 39 random sequences was prepared, and aptamers with specificity for P. gingivalis were selected using the SELEX method, and the nucleotide sequence was analyzed by cloning using PCR2.1 cloning vector. 8 of aptamers with different nucleotide sequences were selected, and modified weston blot was performed using APG-3 among the selected aptamers to identify 11 proteins that act directly, and proteins were analyzed. As a result, a protein that selectively binds to P. gingivalis was isolated and identified. Therefore, aptamer selectively binds and attaches to proteins related to inhibition of sugar metabolism and cell activity of P. gingivalis, suggesting the possibility of a sensor for diagnosis of periodontal disease.

Molecular Diagnosis of Streptococcus pneumoniae in Middle Ear Fluids from Children with Otitis Media with Effusion (삼출성 중이염 소아의 중이액에서 폐구균의 분자적 진단)

  • Byun, Sung Wan;Kim, Han Wool;Yoon, Seo Hee;Park, In Ho;Kim, Kyung-Hyo
    • Pediatric Infection and Vaccine
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    • v.22 no.2
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    • pp.106-112
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    • 2015
  • Purpose: The long-term administration of antibiotics interferes with bacterial culture in the middle ear fluids (MEFs) of young children with otitis media with effusion (OME). The purpose of this study is to determine whether molecular diagnostics can be used for rapid and direct detection of the bacterial pathogen in culture-negative MEFs. Methods: The specificity and sensitivity of both polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) to the lytA gene of Streptococcus pneumoniae were comparatively tested and then applied for pneumococcal detection in the clinical MEFs. Results: The detection limit of the PCR assay was approximately $10^4$ colony forming units (CFU), whereas that of LAMP was less than 10 CFU for the detection of S. pneumoniae. Both PCR and LAMP did not amplify nucleic acid at over $10^6$ CFU of H. influenzae or M. catarrhalis, both of which were irrelevant bacterial species. Of 22 culture-negative MEFs from children with OME, LAMP positivity was found in twelve MEFs (54.5%, 12/22), only three of which were PCR-positive (25%, 3/12). Our results showed that the ability of LAMP to detect pneumococcal DNA is over four times higher than that of PCR (P<0.01). Conclusions: As a high-resolution tool able to detect nucleic acid levels equivalent to <10 CFU of S. pneumoniae in MEFs without any cross-reaction with other pathogens, lytA -specific LAMP may be applied for diagnosing pneumococcus infection in OME as well as evaluating the impact of a pneumococcal conjugate vaccine against OME.

Detection of Multidrug Resistance Using Molecular Nuclear Technique (분자핵의학 기법을 이용한 다약제내성 진단)

  • Lee, Jae-Tae;Ahn, Byeong-Cheol
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.2
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    • pp.180-189
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    • 2004
  • Although the outcome of cancer patients after cytotoxic chemotherapy is related diverse mechanisms, multidrug resistance (MDR) for chemotherapeutic drugs due to cellular P-glycoprotein (Pgp) or multidrug-resistance associated protein (MRP) is most important factor in the chemotherapy failure to cancer. A large number of pharmacologic compounds, including verapamil, quinidine, tamoxifen, cyclosporin A and quinolone derivatives have been reported to overcome MDR. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are available for the detection of Pgp and MRP-mediated transporter. $^{99m}Tc$-MIBI and other $^{99m}Tc$-radiopharmaceuticals are substrates for Pgp and MRP, and have been used in clinical studies for tumor imaging, and to visualize blockade of PgP-mediated transport after modulation of Pgp pump. Colchicine, verapamil and daunorubicin labeled with $^{11}C$ have been evaluated for the quantification of Pgp-mediated transport with PET in vivo and reported to be feasible substrates with which to image Pgp function in tumors. Leukotrienes are specific substrates for MRP and $N-[^{11}C]acetyl-leukotriene$ E4 provides an opportunity to study MRP function non-invasively in vivo. SPECT and PET pharmaceuticals have successfully used to evaluate pharmacologic effects of MDR modulators. Imaging of MDR and reversal of MDR with bioluminescence in a living animal is also evaluated for future clinical trial. We have described recent advances in molecular imaging of MDR and reviewed recent publications regarding feasibility of SPECT and PET imaging to study the functionality of MDR transporters in vivo.