• Title/Summary/Keyword: BRAF

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Use and advantage of Red algae fiber as reinforcement of Biocomposite (홍조류 섬유를 보강재로 사용한 바이오복합재료의 특성)

  • Lee, Min-Woo;Seo, Yung-Bum;Han, Seong-Ok
    • Proceedings of the Korea Technical Association of the Pulp and Paper Industry Conference
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    • 2007.11a
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    • pp.93-102
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    • 2007
  • Biocomposite was organized with biodegradable polymer and natural fiber that has potential to be used as replacement for glass fiber reinforced polymer composite with the benefits of low cost, low density, acceptable specific strength, biodegradability, etc. Until now, non-wood fibers have been used as reinforcements of biocomposite which are all plant-based fibers. The present study focused on investigating the fabrication and characterization of biocomposite reinforced with red algae fiber. The bleached red algae fiber(BRAF) showed very similar crystallinity to the cellulose. It has high stability against thermal degradation (maximum thermal decomposition temperature of 359.3$^{\circ}C$) and thermal expansion. Biocomposites reinforced with BRAF have been fabricated by a compression molding method and their mechanical and thermal properties have been studied. The storage modulus and the thermomechanical stability of PBS matrix are markedly improved with reinforcing the BRAF. These results support that the red algae fiber can be used as an excellent reinforcement of biocomposites as "green-composite" or "eco-composite".

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Use of Red Algae Fiber as Reinforcement of Biocomposite (홍조류 섬유를 보강재로 사용한 바이오복합재료의 특성)

  • Lee, Min-Woo;Seo, Yung-Bum;Han, Seong-Ok
    • Journal of Korea Technical Association of The Pulp and Paper Industry
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    • v.40 no.1
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    • pp.62-67
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    • 2008
  • Biocomposite was fabricated with biodegradable polymer and natural fiber that has potential to be used as replacement for glass fiber reinforced polymer composite with the benefits of low cost, low density, acceptable specific strength, biodegradability, etc. Until now, mostly natural cellulosic fibers on land have been used as reinforcement for biocomposite. The present study focused on investigating the fabrication and the characterization of biocomposite reinforced with red algae fibers from the sea. The bleached red algae fiber (BRAF) showed very similar crystallinity to the wood cellulose. It has high stability against thermal degradation (maximum thermal decomposition temperature of 359.3$^{\circ}C$) and thermal expansion. Biocomposites reinforced with BRAF have been fabricated by a compression molding method and their mechanical and thermal properties have been studied. The storage modulus and the thermomechanical stability of PBS (polybuthylenesuccinate) matrix are markedly improved by reinforcing with the BRAF. These results indicate that red algae fiber can be used as an excellent reinforcement of biocomposites, which are sometimes called as "green-composites" or "eco-composites".

Sensitive High-Resolution Melting Analysis for Screening of KRAS and BRAF Mutations in Iranian Human Metastatic Colorectal Cancers

  • Niya, Mohammad Hadi Karbalaie;Basi, Ali;Koochak, Aghigh;Tameshkel, Fahimeh Safarnezhad;Rakhshani, Nasser;Zamani, Farhad;Imanzade, Farid;Rezvani, Hamid;Adib sereshki, Mohammad Mahdi;Sohrabi, Masoud Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.12
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    • pp.5147-5152
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    • 2016
  • Background: Investigations of methods for detection of mutations have uncovered major weaknesses of direct sequencing and pyrosequencing, with their high costs and low sensitivity in screening for both known and unknown mutations. High resolution melting (HRM) analysis is an alternative tool for the rapid detection of mutations. Here we describe the accuracy of HRM in screening for KRAS and BRAF mutations in metastatic colorectal cancer (mCRCs) samples. Materials and Methods: A total of 1000 mCRC patients in Mehr Hospital, Tehran, Iran, from Feb 2008 to May 2012 were examined for KRAS mutations and 242 of them were selected for further assessment of BRAF mutations by HRM analysis. In order to calculate the sensitivity and specificity, HRM results were checked by pyrosequencing as the golden standard and Dxs Therascreen as a further method. Results: In the total of 1,000 participants, there were 664 (66.4%) with wild type and 336 (33.6%) with mutant codons 12 and/or 13 of the KRAS gene. Among 242 samples randomly checked for the BRAF gene, all were wild type by HRM. Pyrosequencing and Dxs Therascreen results were in line with those of the HRM. In this regard, the sensitivity and specificity of HRM were evaluated as 100%. Conclusion: The findings suggest that the HRM, in comparison with DNA sequencing, is a more appropriate method for precise scanning of KRAS and BRAF mutations. It is also possible to state that HRM may be an attractive technique for the detection of known or unknown somatic mutations in other genes.

Biomarker-directed Targeted Therapy in Colorectal Cancer

  • John M. Carethers
    • Journal of Digestive Cancer Research
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    • v.3 no.1
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    • pp.5-10
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    • 2015
  • With advances in the understanding of the biology and genetics of colorectal cancer (CRC), diagnostic biomarkers that may predict the existence or future presence of cancer or a hereditary condition, and prognostic and treatment biomarkers that may direct the approach to therapy have been developed. Biomarkers can be ascertained and assayed from any tissue that may demonstrate the diagnostic or prognostic value, including from blood cells, epithelial cells via buccal swab, fresh or archival cancer tissue, as well as from cells shed into fecal material. For CRC, current examples of biomarkers for screening and surveillance include germline testing for suspected hereditary CRC syndromes, and stool DNA tests for screening average at-risk patients. Molecular biomarkers for CRC that may alter patient care and treatment include the presence or absence of microsatellite instability, the presence or absence of mutant KRAS, BRAF or PIK3CA, and the level of expression of 15-PGDH in the colorectal mucosa. Molecularly targeted therapies and some general therapeutic approaches rely on biomarker information. Additional novel biomarkers are on the horizon that will undoubtedly further the approach to precision or individualized medicine.

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Extracranial systemic antitumor response through the abscopal effect induced by brain radiation in a patient with metastatic melanoma

  • D'Andrea, Mark A.;Reddy, G.K.
    • Radiation Oncology Journal
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    • v.37 no.4
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    • pp.302-308
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    • 2019
  • The abscopal effect is a term that has been used to describe the phenomenon in which localized radiation therapy treatment of a tumor lesion triggers a spontaneous regression of metastatic lesion(s) at a non-irradiated distant site(s). Radiation therapy induced abscopal effects are believed to be mediated by activation and stimulation of the immune system. However, due to the brain's distinctive immune microenvironment, extracranial abscopal responses following cranial radiation therapy have rarely been reported. In this report, we describe the case of 42-year-old female patient with metastatic melanoma who experienced an abscopal response following her cranial radiation therapy for her brain metastasis. The patient initially presented with a stage III melanoma of the right upper skin of her back. Approximately 5 years after her diagnosis, the patient developed a large metastatic lesion in her upper right pectoral region of her chest wall and axilla. Since the patient's tumor was positive for BRAF and MEK, targeted therapy with dabrafenib and trametinib was initiated. However, the patient experienced central nervous system (CNS) symptoms of headache and disequilibrium and developed brain metastases prior to the start of targeted therapy. The patient received radiation therapy to a dose of 30 Gy delivered in 15 fractions to her brain lesions while the patient was on dabrafenib and trametinib therapy. The patient's CNS metastases improved significantly within weeks of her therapy. The patient's non-irradiated large extracranial chest mass and axilla mass also shrank substantially demonstrating the abscopal effect during her CNS radiation therapy. Following radiation therapy of her residual chest lesions, the patient was disease free clinically and her CNS lesions had regressed. However, when the radiation therapy ended and the patient continued her targeted therapy alone, recurrence outside of her previously treated fields was noted. The disease recurrence could be due to the possibility of developing BRAF resistance clones to the BRAF targeted therapy. The patient died eventually due to wide spread systemic disease recurrence despite targeted therapy.

A Case of Cardiofaciocutaneous Syndrome caused by BRAF gene mutation (BRAF 유전자의 돌연변이로 진단된 Cardiofaciocutaneous 증후군 1례)

  • Lee, Beom-Hee;Kim, Jae-Min;Lee, Jin-Joo;Kim, Gu-Hwan;Yoo, Han-Wook
    • Journal of Genetic Medicine
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    • v.6 no.1
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    • pp.87-90
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    • 2009
  • Cardiofaciocutaneous (CFC) syndrome is characterized by dysmorphic features, cardiac anomalies, and cutaneous abnormalities. CFC syndrome belongs to the class of Noonan-related diseases. CFC syndrome can be clinically differentiated from other Noonan-related diseases by the distinct craniofacial features of sparse hair, a hypoplastic supraorbital ridge, exophthalmos and nystagmus, and skin manifestations such as ichthyosis and hyperkeratosis. However, phenotypes can overlap among Noonan-related syndromes, including CFC syndrome. Recently, several genes in the RAS-MAPK pathway have been identified as disease-causing genes for Noonan-related diseases. Here, we report on a Korean girl diagnosed with CFC syndrome caused by a V-raf murine sarcoma viral oncogene homolog B1 (BRAF) gene mutation, and we discuss the phenotype-genotype heterogeneities in Noonan syndrome and Noonan-related diseases.

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Pathological Factors Affecting DNA Quality in BRAF, EGFR, and KRAS Gene Molecular Tests (BRAF, EGFR, KRAS 유전자 분자병리검사에서 DNA 품질에 영향을 미치는 병리학적인 인자에 관한 연구)

  • Yun, Hyon-Goo;Kim, Bo-Ra;Lee, Joo-Mi;Song, Eun-Ha;Kim, Dong-Hoon
    • Korean Journal of Clinical Laboratory Science
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    • v.52 no.4
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    • pp.381-388
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    • 2020
  • The quality control of pathological specimens is important for accurate molecular pathology testing. This study evaluated that specimen factors affecting the DNA quality during tissue processing and sample types for BRAF, EGFR, and KRAS mutations tests. One thousand seven hundred and seventy-two molecular pathology tests were investigated for the factors influencing the DNA quality, such as sample type, formalin fixation time, and reexamination status. Cytology samples stored in a saline solution had better DNA quality than commercial cytology preservation. Tissue samples fixed in formalin within 24 hours had better DNA quality than the samples fixed over 24 hours. Between the types of samples, fresh tissue samples and tissue samples with a high tumor cell density had relatively better DNA quality than the formalin-fixed paraffin-embedded (FFPE) tissues and cytology specimens. Of real-time PCR, the non-PNA Ct value increased proportionally with samples held for longer than 24 hours in formalin, and that the formalin-fixed time affects the sample DNA quality. In conclusion, the appropriate tumor cellularity and 10% neutral formalin fixation time are the most important factors for maintaining the DNA quality. These factors should be managed properly for an accurate pathological molecular test to ensure optimal DNA quality.

What's New in Molecular Targeted Therapies for Thyroid Cancer? (갑상선암 표적치료의 최신지견)

  • Min, Seonyoung;Kang, Hyunseok
    • Korean Journal of Head & Neck Oncology
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    • v.37 no.2
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    • pp.1-9
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    • 2021
  • Thyroid cancer refers to various cancers arising from thyroid gland. Differentiated thyroid cancers (DTCs) include papillary, follicular, and Hurthle cell carcinomas and represent cancers retain normal thyroid functions such as iodine uptake. Radioactive iodine (RAI) is generally used for upfront treatment of metastatic DTCs, but RAI refractory DTCs remain to be clinical challenges. Sorafenib and lenvatinib were approved for the treatment of RAI refractory DTCs and more recently, genomics-based targeted therapies have been developed for NTRK and RET gene fusion-positive DTCs. Poorly differentiated and anaplastic thyroid cancers (ATCs) are extremely challenging diseases with aggressive courses. BRAF/MEK inhibition has been proven to be highly effective in BRAF V600E mutation-positive ATCs and immune checkpoint inhibitors have shown promising activities. Medullary thyroid cancers, which arise from parafollicular cells of thyroid, represent a unique subset of thyroid cancer and mainly driven by RET mutation. In addition to vandetanib and cabozantinib, highly specific RET inhibitors such as selpercatinib and pralsetinib have demonstrated impressive activity and are in clinical use.

Mutational Analysis of Key EGFR Pathway Genes in Chinese Breast Cancer Patients

  • Tong, Lin;Yang, Xue-Xi;Liu, Min-Feng;Yao, Guang-Yu;Dong, Jian-Yu;Ye, Chang-Sheng;Li, Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5599-5603
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    • 2012
  • Background: The epidermal growth factor receptor (EGFR) is a potential therapeutic target for breast cancer treatment; however, its use does not lead to a marked clinical response. Studies of non-small cell lung cancer and colorectal cancer showed that mutations of genes in the PIK3CA/AKT and RAS/RAF/MEK pathways, two major signalling cascades downstream of EGFR, might predict resistance to EGFR-targeted agents. Therefore, we examined the frequencies of mutations in these key EGFR pathway genes in Chinese breast cancer patients. Methods: We used a high-throughput mass-spectrometric based cancer gene mutation profiling platform to detect 22 mutations of the PIK3CA, AKT1, BRAF, EGFR, HRAS, and KRAS genes in 120 Chinese women with breast cancer. Results: Thirteen mutations were detected in 12 (10%) of the samples, all of which were invasive ductal carcinomas (two stage I, six stage II, three stage III, and one stage IV). These included one mutation (0.83%) in the EGFR gene (rs121913445-rs121913432), three (2.50%) in the KRAS gene (rs121913530, rs112445441), and nine (7.50%) in the PIK3CA gene (rs121913273, rs104886003, and rs121913279). No mutations were found in the AKT1, BRAF, and HRAS genes. Six (27.27%) of the 22 genotyping assays called mutations in at least one sample and three (50%) of the six assays queried were found to be mutated more than once. Conclusions: Mutations in the EGFR pathway occurred in a small fraction of Chinese breast cancers. However, therapeutics targeting these potential predictive markers should be investigated in depth, especially in Oriental populations.

OTUB1 knockdown promotes apoptosis in melanoma cells by upregulating TRAIL expression

  • Lee, Bok-Soon;Kang, Sung Un;Huang, Mei;Kim, Yeon Soo;Lee, Young-Sun;Park, Jae-Yong;Kim, Chul-Ho
    • BMB Reports
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    • v.54 no.12
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    • pp.608-613
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    • 2021
  • Melanoma, the most serious type of skin cancer, exhibits a high risk of metastasis. Although chemotherapeutic treatment for metastatic melanoma improves disease outcome and patient survival, some patients exhibit resistance or toxicity to the drug treatment regime. OTUB1 is a deubiquitinating enzyme overexpressed in several cancers. In this study, we investigated the effects of inhibiting OTUB1 expression on melanoma-cell proliferation and viability and identified the underlying molecular mechanism of action of OTUB1. We did endogenous OTUB1 knockdown in melanoma cells using short interfering RNA, and assessed the resulting phenotypes via MTT assays, Western blotting, and cell-cycle analysis. We identified differentially expressed genes between OTUB1-knockdown cells and control cells using RNA sequencing and confirmed them via Western blotting and reverse transcription polymerase chain reaction. Furthermore, we investigated the involvement of apoptotic and cell survival signaling pathways upon OTUB1 depletion. OTUB1 depletion in melanoma cells decreased cell viability and caused simultaneous accumulation of cells in the sub-G1 phase, indicating an increase in the apoptotic-cell population. RNA sequencing of OTUB1-knockdown cells revealed an increase in the levels of the apoptosis-inducing protein TRAIL. Additionally, OTUB1-knockdown cells exhibited increased sensitivity to PLX4032, a BRAF inhibitor, implying that OTUB1 and BRAF act collectively in regulating apoptosis. Taken together, our findings show that OTUB1 induces apoptosis of melanoma cells in vitro, likely by upregulating TRAIL, and suggest that approaches targeting OTUB1 can be developed to provide novel therapeutic strategies for treating melanoma.