• 제목/요약/키워드: Molecular diagnostics

검색결과 172건 처리시간 0.029초

Characterization of CEBPA Mutations and Polymorphisms and their Prognostic Relevance in De Novo Acute Myeloid Leukemia Patients

  • Sarojam, Santhi;Raveendran, Sureshkumar;Vijay, Sangeetha;Sreedharan, Jayadevan;Narayanan, Geetha;Sreedharan, Hariharan
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권9호
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    • pp.3785-3792
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    • 2015
  • The CCAAT/enhancer-binding protein-alpha (CEBPA) is a transcriptional factor that plays a crucial role in the control of proliferation and differentiation of myeloid precursors. This gene was recognized as the target of genetic alterations and were associated with clinical complexity among AML. We here analyze the frequency and types of CEBPA mutations and polymorphisms in a de novo AML patients from South India and tried to find out associations of these variations with different clinical parameters and the prognostic significance in AML. Study was carried out in 248 de novo AML patients, cytogenetic analysis was performed from the bone marrow samples and was karyotyped. PCR-SSCP analysis and sequencing was performed for the detection of CEBPA gene variations. All the statistical analysis was performed using SPSS 17 (statistical package for social sciences) software. Pearson Chi-square test, Mann-Whitney U test, Kaplan-Meier survival analysis and log rank tests were performed. CEBPA mutations were detected in 18% and CEBPA polymorphisms were detected in 18.9% of AML cases studied. Most of the mutations occured at the C terminal region. Polymorphisms were detected in both N and C terminal region. with most common being, c.584_589dup ACCCGC and c.690G>T. A significant association was not observed for the mutation and polymorphism with respect to clinical and laboratory parameters. Survival advantage was observed for the mutated cases compared to non mutated cases, especially for the normal karyotype groups. Polymorphisms has no effect on the survival pattern of AML patients. CEBPA mutation and polymorphisms were observed with similar frequency and was identified in all the FAB subtypes as well as in cytogenetic risk groups in our study population, but CEBPA mutations alone confer a prognostic value for NK AML patients.

Proof-of-concept study of the caninized anti-canine programmed death 1 antibody in dogs with advanced non-oral malignant melanoma solid tumors

  • Masaya Igase;Sakuya Inanaga;Shoma Nishibori;Kazuhito Itamoto;Hiroshi Sunahara;Yuki Nemoto;Kenji Tani;Hiro Horikirizono;Munekazu Nakaichi;Kenji Baba;Satoshi Kambayashi;Masaru Okuda;Yusuke Sakai;Masashi Sakurai;Masahiro Kato;Toshihiro Tsukui;Takuya Mizuno
    • Journal of Veterinary Science
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    • 제25권1호
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    • pp.15.1-15.15
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    • 2024
  • Background: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. Objective: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM. Methods: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%). Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively. Conclusions: The present study demonstrated that ca-4F12-E6 was well-tolerated in non-OMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs.

Recent Advancement of the Molecular Diagnosis in Pediatric Brain Tumor

  • Bae, Jeong-Mo;Won, Jae-Kyung;Park, Sung-Hye
    • Journal of Korean Neurosurgical Society
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    • 제61권3호
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    • pp.376-385
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    • 2018
  • Recent discoveries of brain tumor-related genes and fast advances in genomic testing technologies have led to the era of molecular diagnosis of brain tumor. Molecular profiling of brain tumor became the significant step in the diagnosis, the prediction of prognosis and the treatment of brain tumor. Because traditional molecular testing methods have limitations in time and cost for multiple gene tests, next-generation sequencing technologies are rapidly introduced into clinical practice. Targeted sequencing panels using these technologies have been developed for brain tumors. In this article, focused on pediatric brain tumor, key discoveries of brain tumor-related genes are reviewed and cancer panels used in the molecular profiling of brain tumor are discussed.

Synthesis of dimeric fluorescent TSPO ligand for detection of glioma

  • Tien Tan Bui;Hee-Kwon Kim
    • 대한방사성의약품학회지
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    • 제7권1호
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    • pp.56-65
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    • 2021
  • TSPO, an 18-kDa translocator protein, is a peripheral-type benzodiazepine receptor that has been associated to a variety of biological activities such as apoptosis, steroidogenesis, and cell proliferation. Because TSPO overexpression has been found in various forms of cancer, it has recently become one of the most appealing biological targets for cancer therapies and detection. In order to create new optical imaging agents for improved diagnostics, we synthesized a novel dimeric fluorescent TSPO ligand based on PRB28 structure and SCy5.5. Following the preparation of the novel TSPO ligand, in vivo and ex vivo imaging tests were performed to examine the tumor uptake characteristics of the fluorescent TSPO ligand in a glioma animal model, and it was found that novel TSPO ligand was accumulated in glioma. These results suggested that novel dimeric fluorescent TSPO ligand will be applied to detect glioma.

뎅기 바이러스 검출기술 관련 특허동향 분석 (Analysis of Patent Trend on Dengue Virus Detection Technology)

  • 최재원;조병관;김학용
    • 한국콘텐츠학회논문지
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    • 제19권2호
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    • pp.259-268
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    • 2019
  • 뎅기 바이러스는 대표적인 모기-매개 바이러스로, 전 세계 인구의 약 절반에 가까운 인구가 감염 위험에 노출되어 있다. 뎅기 바이러스는 뎅기열과 같은 비교적 경미한 증상을 나타내지만, 적절한 치료를 받지 않을 경우 치사율이 20%가 넘는 뎅기 출혈열 및 뎅기 쇼크 증후군과 같은 심각한 증상을 유발하기도 한다. 뎅기 바이러스 검출을 통해 감염 여부를 조기에 진단한다면 치사율을 1% 미만으로 낮출 수 있는 것으로 보고되고 있기 때문에, 뎅기 바이러스 검출기술의 개발이 매우 중요한 상황이다. 본 연구에서는 특허 5대 강대국인 한국 미국 유럽 일본 중국을 대상으로 뎅기 바이러스 검출기술 및 뎅기열 진단기술과 관련된 특허문헌 검색을 수행하였다. 검색된 특허문헌으로부터 관련도가 높은 유효 특허문헌 69건을 대상으로 국가별 연도별 특허권자별 정량분석을 수행하였으며, 모든 특허문헌을 검토하여 유전자 검출 기반의 분자진단, 단백질 검출 기반의 면역진단, 세포배양법을 통한 진단 등의 3가지 분류로 나누어 정성분석을 수행하였다. 이를 종합하여 뎅기 바이러스 검출기술 및 뎅기열 진단기술 관련 특허동향을 파악하였으며, 현재 수준에서의 분자진단과 면역진단의 특징 및 한계점을 분석하였다. 더 나아가 한계점을 극복하기 위한 기술개발 방향과 앞으로의 전망에 대해 논의하였다.

열역학법을 이용한 DNA hybridization 특성 검출 및 해석 (Detection and Analysis of DNA Hybridization Characteristics by using Thermodynamic Method)

  • 김도균;권영수
    • 대한전기학회논문지:전기물성ㆍ응용부문C
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    • 제51권6호
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    • pp.265-270
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    • 2002
  • The determination of DNA hybridization reaction can apply the molecular biology research, clinic diagnostics, bioengineering, environment monitoring, food science and application area. So, the improvement of DNA hybridization detection method is very important for the determination of this hybridization reaction. Several molecular biological techniques require accurate predictions of matched versus mismatched hybridization thermodynamics, such as PCR, sequencing by hybridization, gene diagnostics and antisense oligonucleotide probes. In addition, recent developments of oligonucleotide chip arrays as means for biochemical assays and DNA sequencing requires accurate knowledge of hybridization thermodynamics and population ratios at matched and mismatched target sites. In this study, we report the characteristics of the probe and matched, mismatched target oligonucleotide hybridization reaction using thermodynamic method. Thermodynamic of 5 oligonucleotides with central and terminal mismatch sequences were obtained by measured UV-absorbance as a function of temperature. The data show that the nearest-neighbor base-pair model is adequate for predicting thermodynamics of oligonucleotides with average deviations for $\Delta$H$^{0}$ , $\Delta$S$^{0}$ , $\Delta$G$_{37}$ $^{0}$ and T$_{m}$, respectively.>$^{0}$ and T$_{m}$, respectively.

Esculetin이 PI3K/MAPK 경로 하향 조절을 통해 collagen 유도의 혈소판 응집 억제에 미치는 효과 (Inhibitory Effects of Esculetin Through the Down-Regulation of PI3K/MAPK Pathway on Collagen-Induced Platelets Aggregation)

  • 박창은;이동하
    • 생약학회지
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    • 제52권3호
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    • pp.127-133
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    • 2021
  • Platelet activation plays a major role in cardiovascular disorders (CVDs). Thus, disrupting platelet activation represents an attractive therapeutic target on CVDs. Esculetin, a bioactive 6,7-dihydroxy derivative of coumarin, possesses pharmacological activities against obesity, diabetes, renal failure, and CVDs. In other report, the effect of esculetin has been examined in human platelet activation and experimental mouse models, and esculetin inhibited collagen- and arachidonic acid-induced platelet aggregation in washed human platelets. However, it had no effects on other agonists such as thrombin and U46619, and its mechanism is not also clearly known. This study investigated the effect of esculetin on collagen-induced human platelet aggregation, and we clarified the mechanism. Esuletin has effects on the down regulation of PI3K/Akt and MAPK, phosphoproteins that act in the signaling process in platelet aggregation. The effects of esculetin reduced of TXA2 production and phospholipase A2 activation, and intracellular granule secretion including ATP and serotonin, leading to inhibit platelet aggregation. These results clearly clarified the effect of esculetin in inhibiting platelet activity and thrombus formation in humans.

U46619-유도의 혈소판에서 PI3K/Akt 및 MAPK 조절을 통한 Artemether의 응집억제효과 (Anti-aggregation Effect of Artemether Through Regulation of PI3K/Akt and MAPK in U46619-induced Platelets)

  • 박창은;이동하
    • 생약학회지
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    • 제53권2호
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    • pp.64-69
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    • 2022
  • When blood vessels are damaged, a rapid hemostatic response should occur in order to lower blood loss and keep normal circulation, and platelet activation and aggregation are essential. Nevertheless, abnormal or excessive platelet aggregation can be a reason of cardiovascular diseases including thrombosis, atherosclerosis, and stroke. Therefore, the screening for a substance which can regulate platelet activation and suppress aggregation reaction is very important for treatment and prevention of cardiovascular diseases. Artemether is a methyl ether derivative of artemisinin, which is isolated from the antimalarial plant Artemisia annua, but research on platelet aggregation or its mechanisms is still insufficient. This study identified the effects of artemether on U46619-induced human platelet aggregation and their granule secretion (ATP and serotonin release). In addition, the effects of artemether on the phosphorylation of PI3K/Akt or MAPK, which are related to signal transduction in platelet aggregation, were studied. As the results, artemether significantly lowered PI3K/Akt and MAPK phosphorylation, which inhibited platelet aggregation through granule secretion (ATP and serotonin release) dose-dependently. Therefore, we suggest that artemether is an antiplatelet substance that regulates PI3K/Akt and MAPK pathway and is of value as a therapeutic and preventive agent for platelet-derived cardiovascular diseases.

호흡기 감염병 진단 기술 동향 (Trends in Diagnostic Technology for Respiratory Infectious Disease)

  • 박정원;서홍석;허철;박수준
    • 전자통신동향분석
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    • 제39권4호
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    • pp.54-62
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    • 2024
  • The emergence and resurgence of novel respiratory infectious diseases since the turn of the millennium, including SARS, H1N1 flu, MERS, and COVID-19, have posed a significant global health threat. Efforts to combat these threats have involved various approaches, however, continued research and development are crucial to prepare for the possibility of emerging viruses and viral variants. Direct detection methods for viral pathogens include molecular diagnostic techniques and immunodiagnostic methods, while indirect diagnostic methods involve detecting changes in the condition of infected patients through imaging diagnostics, gas analysis, and biosignal measurement. Molecular diagnostic techniques, utilizing advanced technologies such as gene editing, are being developed to enable faster detection than traditional PCR methods, and research is underway to improve the efficiency of diagnostic devices. Diagnostic technologies for infectious diseases continue to evolve, and several key trends are expected to emerge in the future. Automation will facilitate widespread adoption of rapid and accurate diagnostics, portable diagnostic devices will enable immediate on-site diagnosis by healthcare professionals, and advancements in AI-based deep learning diagnostic models will enhance diagnostic accuracy.