• Title/Summary/Keyword: Targeted cancer therapy

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The Clinical, Molecular, and Mechanistic Basis of RUNX1 Mutations Identified in Hematological Malignancies

  • Yokota, Asumi;Huo, Li;Lan, Fengli;Wu, Jianqiang;Huang, Gang
    • Molecules and Cells
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    • v.43 no.2
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    • pp.145-152
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    • 2020
  • RUNX1 plays an important role in the regulation of normal hematopoiesis. RUNX1 mutations are frequently found and have been intensively studied in hematological malignancies. Germline mutations in RUNX1 cause familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML). Somatic mutations of RUNX1 are observed in various types of hematological malignancies, such as AML, acute lymphoblastic leukemia (ALL), myelodysplastic syndromes (MDS), myeloproliferative neoplasm (MPN), chronic myelomonocytic leukemia (CMML), and congenital bone marrow failure (CBMF). Here, we systematically review the clinical and molecular characteristics of RUNX1 mutations, the mechanisms of pathogenesis caused by RUNX1 mutations, and potential therapeutic strategies to target RUNX1-mutated cases of hematological malignancies.

Performance of DNA Methylation on the Molecular Pathogenesis of Helicobacter pylori in Gastric Cancer; targeted therapy approach

  • Vahidi, Sogand;Mirzajani, Ebrahim;Norollahi, Seyedeh Elham;Aziminezhad, Mohsen;Samadani, Ali Akbar
    • Journal of Pharmacopuncture
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    • v.25 no.2
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    • pp.88-100
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    • 2022
  • Gastric cancer (GC) is a significant cause of cancer mortality which has led to focused exploration of the pathology of GC. The advent of genome-wide analysis methods has made it possible to uncover genetic and epigenetic fluctuation such as abnormal DNA methylation in gene promoter regions that is expected to play a key role in GC. The study of gastric malignancies requires an etiological perspective, and Helicobacter pylori (H. pylori) was identified to play a role in GC. H. pylori infection causes chronic inflammation of the gastric epithelium causing abnormal polyclonal methylation, which might raise the risk of GC. In the last two decades, various pathogenic factors by which H. pylori infection causes GC have been discovered. Abnormal DNA methylation is triggered in several genes, rendering them inactive. In GC, methylation patterns are linked to certain subtypes including microsatellite instability. Multiple cancer-related processes are more usually changed by abnormal DNA methylation than through mutations, according to current general and combined investigations. Furthermore, the amount of acquired abnormal DNA methylation is heavily linked to the chances of developing GC. Therefore, we investigated abnormal DNA methylation in GC and the link between methylation and H. pylori infection.

Artificial Intelligence in the Pathology of Gastric Cancer

  • Sangjoon Choi;Seokhwi Kim
    • Journal of Gastric Cancer
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    • v.23 no.3
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    • pp.410-427
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    • 2023
  • Recent advances in artificial intelligence (AI) have provided novel tools for rapid and precise pathologic diagnosis. The introduction of digital pathology has enabled the acquisition of scanned slide images that are essential for the application of AI. The application of AI for improved pathologic diagnosis includes the error-free detection of potentially negligible lesions, such as a minute focus of metastatic tumor cells in lymph nodes, the accurate diagnosis of potentially controversial histologic findings, such as very well-differentiated carcinomas mimicking normal epithelial tissues, and the pathological subtyping of the cancers. Additionally, the utilization of AI algorithms enables the precise decision of the score of immunohistochemical markers for targeted therapies, such as human epidermal growth factor receptor 2 and programmed death-ligand 1. Studies have revealed that AI assistance can reduce the discordance of interpretation between pathologists and more accurately predict clinical outcomes. Several approaches have been employed to develop novel biomarkers from histologic images using AI. Moreover, AI-assisted analysis of the cancer microenvironment showed that the distribution of tumor-infiltrating lymphocytes was related to the response to the immune checkpoint inhibitor therapy, emphasizing its value as a biomarker. As numerous studies have demonstrated the significance of AI-assisted interpretation and biomarker development, the AI-based approach will advance diagnostic pathology.

DNA의 구조적, 기능적 특성과 이의 환경, 의료 분야에의 응용

  • Lee, Jeong-Heon;Odom, Teri;Lu, Yi
    • Proceedings of the Materials Research Society of Korea Conference
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    • 2012.05a
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    • pp.55.1-55.1
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    • 2012
  • In the first part of this talk, I will introduce an effort to use gold nanoparticles and UO22+ (uranyl) specific DNAzyme for development of highly sensitive and selective colorimetric uranyl sensors. In addition, I will discuss how DNA aptamers can be delivered by nanoparticles to cancer cell nucleus and released by ultrafast femtosecond pulsed laser for targeted cancer therapy. Finally, I will show how proteins such as streptavidin and myoglobin, or nanoparticles can be precisely aligned on DNA with nanometer resolution via backbone-modified phosphorothioate DNA and bifunctional linkers. These interesting functional and structural properties of DNA can provide new opportunities to develop dynamic DNA structures for potential use as intracellular sensors and drug delivery agents.

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Cellular senescence in cancer

  • Kim, Young Hwa;Park, Tae Jun
    • BMB Reports
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    • v.52 no.1
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    • pp.42-46
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    • 2019
  • Cellular senescence, a process of cell proliferation arrest in response to various stressors, has been considered to be important factor in age-related disease. Identification of senescent cells in tissues is limited and the role of senescent cells is poorly understood. Recently however, several studies showed the characterization of senescent cells in various pathologic conditions and the role of senescent cells in disease progression is becoming important. Senescent cells are growth-arrested cells, however, the senescence associated secretory phenotype (SASP) of senescent cells could modify the tissues' microenvironment. Here, we discuss the progress and understanding of the role of senescent cells in tissues of pathologic conditions and discuss the development of new therapeutic paradigms, such as senescent cells-targeted therapy.

In vivo Trafficking of Liposomes Containing Boron Compounds for Boron Neutron Capture Therapy (BNCT)

  • Huu Bao Nguyen;Jeongsoo Yoo
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.9 no.1
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    • pp.43-48
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    • 2023
  • For over 50 years, boron neutron capture therapy (BNCT) has been steadily developed for treating various cancers. This is a non-invasive, selective, and targeted radiotherapy wherein boron-rich molecules accumulate at the tumor site. Liposomal vesicles have become a popular and effective drug delivery system for BNCT, with strategies including surface decoration, bilayer integration, and hydrophilic core encapsulation. This review highlights the state-of-the-art uses of liposomes in BNCT and elucidates a new perspective where BNCT can be used with radiotracer guidance in all-in-one delivery systems.

Screening of Photosensitizer for Photodynamic Therapy (광역동 항암치료를 위한 광과민제 스크리닝 연구)

  • Kim, So-Young;Yoo, Gui-Jae;Park, Keun-Hyoung;Lim, Byung-Lak;Kim, Shi-Surk;Yom, Heng-Cherl;Chae, Hee-Jeong
    • KSBB Journal
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    • v.22 no.5
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    • pp.318-321
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    • 2007
  • Photodynamic therapy (PDT) is a targeted-tumor treatment system using a photosensitizer, light and oxygen to treat malignant tumor. We have investigated the cytotoxicity of 4 types of phthalocyanine derivative (silver phthalocyanine, iron (III) phthalocyanine, copper (II) phthalocyanine, nickel (II) phthalocyanine) against lung and breast cancers based on photodynamic therapy. As a result, phthalocyanine derivatives indicated a higher anticancer activity on a breast cancer cell line. Among the tested phthalocyanines, silver phthalocyanine (AgPc) showed a lower cytotoxicity against a normal cell line. In addition AgPc gave a good color characteristic when it is solubilized in water. Finally AgPc was selected as a potential antitumor agent for breast cancer.

Exosomes derived from microRNA-584 transfected mesenchymal stem cells: novel alternative therapeutic vehicles for cancer therapy

  • Kim, Ran;Lee, Seokyeon;Lee, Jihyun;Kim, Minji;Kim, Won Jung;Lee, Hee Won;Lee, Min Young;Kim, Jongmin;Chang, Woochul
    • BMB Reports
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    • v.51 no.8
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    • pp.406-411
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    • 2018
  • Exosomes are small membranous vesicles which contain abundant RNA molecules, and are transferred from releasing cells to uptaking cells. MicroRNA (miRNA) is one of the transferred molecules affecting the adopted cells, including glioma cells. We hypothesized that mesenchymal stem cells (MSCs) can secrete exosomes loading miRNA and have important effects on the progress of gliomas. To determine these effects by treating exosomal miRNA in culture media of miRNA mimic transfected MSCs, we assessed the in vitro cell proliferation and invasion capabilities, and the expression level of relative proteins associated with cell apoptosis, growth and migration. For animal studies, the mice injected with U87 cells were exposed to exosomes derived from miRNA-584-5p transfected MSCs, to confirm the influence of exosomal miRNA on the progress of glioma. Based on our results, we propose a new targeted cancer therapy wherein exosomes derived from miRNA transfected MSCs could be used to modulate tumor progress as the anticancer vehicles.

Clinical Implementation of Precision Medicine in Gastric Cancer

  • Jeon, Jaewook;Cheong, Jae-Ho
    • Journal of Gastric Cancer
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    • v.19 no.3
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    • pp.235-253
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    • 2019
  • Gastric cancer (GC) is one of the deadliest malignancies in the world. Currently, clinical treatment decisions are mostly made based on the extent of the tumor and its anatomy, such as tumor-node-metastasis staging. Recent advances in genome-wide molecular technology have enabled delineation of the molecular characteristics of GC. Based on this, efforts have been made to classify GC into molecular subtypes with distinct prognosis and therapeutic response. Simplified algorithms based on protein and RNA expressions have been proposed to reproduce the GC classification in the clinical field. Furthermore, a recent study established a single patient classifier (SPC) predicting the prognosis and chemotherapy response of resectable GC patients based on a 4-gene real-time polymerase chain reaction assay. GC patient stratification according to SPC will enable personalized therapeutic strategies in adjuvant settings. At the same time, patient-derived xenografts and patient-derived organoids are now emerging as novel preclinical models for the treatment of GC. These models recapitulate the complex features of the primary tumor, which is expected to facilitate both drug development and clinical therapeutic decision making. An integrated approach applying molecular patient stratification and patient-derived models in the clinical realm is considered a turning point in precision medicine in GC.

Epigenetic Silencing of CHOP Expression by the Histone Methyltransferase EHMT1 Regulates Apoptosis in Colorectal Cancer Cells

  • Kim, Kwangho;Ryu, Tae Young;Lee, Jinkwon;Son, Mi-Young;Kim, Dae-Soo;Kim, Sang Kyum;Cho, Hyun-Soo
    • Molecules and Cells
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    • v.45 no.9
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    • pp.622-630
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    • 2022
  • Colorectal cancer (CRC) has a high mortality rate among cancers worldwide. To reduce this mortality rate, chemotherapy (5-fluorouracil, oxaliplatin, and irinotecan) or targeted therapy (bevacizumab, cetuximab, and panitumumab) has been used to treat CRC. However, due to various side effects and poor responses to CRC treatment, novel therapeutic targets for drug development are needed. In this study, we identified the overexpression of EHMT1 in CRC using RNA sequencing (RNA-seq) data derived from TCGA, and we observed that knocking down EHMT1 expression suppressed cell growth by inducing cell apoptosis in CRC cell lines. In Gene Ontology (GO) term analysis using RNA-seq data, apoptosis-related terms were enriched after EHMT1 knockdown. Moreover, we identified the CHOP gene as a direct target of EHMT1 using a ChIP (chromatin immunoprecipitation) assay with an anti-histone 3 lysine 9 dimethylation (H3K9me2) antibody. Finally, after cotransfection with siEHMT1 and siCHOP, we again confirmed that CHOP-mediated cell apoptosis was induced by EHMT1 knockdown. Our findings reveal that EHMT1 plays a key role in regulating CRC cell apoptosis, suggesting that EHMT1 may be a therapeutic target for the development of cancer inhibitors.