• Title/Summary/Keyword: Translational research

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Recent Advances of MALDI-Mass Spectrometry Imaging in Cancer Research

  • Jung, Joohee
    • Mass Spectrometry Letters
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    • v.10 no.3
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    • pp.71-78
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    • 2019
  • For several decades, cancer has been the primary cause of mortality worldwide. New diagnosis and regimens have been developed to improve the chemotherapeutic efficacy and the quality of life of the patients. However, cancer tissues are complex and difficult to assess. Understanding the various properties of the tumor and its environment is crucial for cancer and pharmaceutical research. Several analytical techniques have been providing new insights into cancer research. Recently, matrix-assisted laser desorption ionization (MALDI)-mass spectrometry imaging (MSI), an advanced analytical technique, has been applied to translational research. Proteomic and lipidomic profiling obtained by MALDI-MSI has been critical for biomarker discovery and for monitoring heterogenous tumor tissues. In this review, we discuss technical approaches, benefits and recent applications of MALDI-MSI as a valuable tool in cancer research, namely for diagnosis, therapy, prognosis.

Enhanced delivery of protein fused to cell penetrating peptides to mammalian cells

  • Moon, Jung-Il;Han, Min-Joon;Yu, Shin-Hye;Lee, Eun-Hye;Kim, Sang-Mi;Han, Kyuboem;Park, Chang-Hwan;Kim, Chun-Hyung
    • BMB Reports
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    • v.52 no.5
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    • pp.324-329
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    • 2019
  • Recent progress in cellular reprogramming technology and lineage-specific cell differentiation has provided great opportunities for translational research. Because virus-based gene delivery is not a practical reprogramming protocol, protein-based reprogramming has been receiving attention as a safe way to generate reprogrammed cells. However, the poor efficiency of the cellular uptake of reprogramming proteins is still a major obstacle. Here, we reported key factors which improve the cellular uptake of these proteins. Purified red fluorescent proteins fused with 9xLysine (dsRED-9K) as a cell penetrating peptide were efficiently delivered into the diverse primary cells. Protein delivery was improved by the addition of amodiaquine. Furthermore, purified dsRED-9K was able to penetrate all cell lineages derived from mouse embryonic stem cells efficiently. Our data may provide important insights into the design of protein-based reprogramming or differentiation protocols.

Extracellular Vesicles in Psychiatry Research in the Context of RDoC Criteria

  • Ilgin, Can;Topuzoglu, Ahmet
    • Psychiatry investigation
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    • v.15 no.11
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    • pp.1011-1018
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    • 2018
  • The analysis of extracellular vesicles has been accelerated because of the technological advancements in omics methods in recent decades. Extracellular vesicles provide multifaceted information regarding the functional status of the cells. This information would be critical in case of central nervous system cells, which are confined in a relatively sealed biological compartment. This obstacle is more dramatic in psychiatric disorders since their diagnosis primarily depend on the symptoms and signs of the patients. In this paper, we reviewed this rapidly advancing field by discussing definition of extracellular vesicles, their biogenesis and potential use as clinical biomarkers. Then we focused on their potential use in psychiatric disorders in the context of diagnosis and treatment of these disorders. Finally, we tried to combine the RDoC (Research Domain Criteria) with the use of extracellular vesicles in psychiatry research and practice. This review may offer new insights in both basic and translational research focusing on psychiatric disorders.

The Role of Nuclear Receptor Subfamily 1 Group H Member 4 (NR1H4) in Colon Cancer Cell Survival through the Regulation of c-Myc Stability

  • Lee, Yun Jeong;Lee, Eun-Young;Choi, Bo Hee;Jang, Hyonchol;Myung, Jae-Kyung;You, Hye Jin
    • Molecules and Cells
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    • v.43 no.5
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    • pp.459-468
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    • 2020
  • Nuclear receptor subfamily group H member 4 (NR1H4), also known as farnesoid X receptor, has been implicated in several cellular processes in the liver and intestine. Preclinical and clinical studies have suggested a role of NR1H4 in colon cancer development; however, how NR1H4 regulates colon cancer cell growth and survival remains unclear. We generated NR1H4 knockout (KO) colon cancer cells using clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 nuclease (CAS9) technology and explored the effects of NR1H4 KO in colon cancer cell proliferation, survival, and apoptosis. Interestingly, NR1H4 KO cells showed impaired cell proliferation, reduced colony formation, and increased apoptotic cell death compared to control colon cancer cells. We identified MYC as an important mediator of the signaling pathway alterations induced by NR1H4 KO. NR1H4 silencing in colon cancer cells resulted in reduced MYC protein levels, while NR1H4 activation using an NR1H4 ligand, chenodeoxycholic acid, resulted in time- and dose-dependent MYC induction. Moreover, NR1H4 KO enhanced the anti-cancer effects of doxorubicin and cisplatin, supporting the role of MYC in the enhanced apoptosis observed in NR1H4 KO cells. Taken together, our findings suggest that modulating NR1H4 activity in colon cancer cells might be a promising alternative approach to treat cancer using MYC-targeting agents.

Protection and Dissection of Recurrent Laryngeal Nerve in Salvage Thyroid Cancer Surgery to Patients with Insufficient Primary Operation Extent and Suspicious Residual Tumor

  • Yu, Wen-Bin;Zhang, Nai-Song
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7457-7461
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    • 2015
  • Some thyroid cancer patients undergone insufficient tumor removal in the primary surgery in China. our aim is to evaluate the impact of dissection of the recurrent laryngeal nerve during a salvage thyroid cancer operation in these patients to prevent nerve injury. Clinical data of 49 enrolled patients who received a salvage thyroid operation were retrospectively reviewed. Primary pathology was thyroid papillary cancer. The initial procedure performed included nodulectomy (20 patients), partial thyroidectomy (19 patients) and subtotal thyroidectomy (10 patients). The effect of dissection and protection of the recurrent laryngeal nerve and the mechanism of nerve injury were studied. The cervical courses of the recurrent laryngeal nerves were successfully dissected in all cases. Nerves were adherent to or involved by scars in 22 cases. Three were ligated near the place where the nerve entered the larynx, while another three were cut near the intersection of inferior thyroid artery with the recurrent laryngeal nerve. Light hoarseness occurred to four patients without a preoperative voice change. In conclusion, accurate primary diagnosis allows for a sufficient primary operation to be performed, avoiding insufficient tumor removal that requires a secondary surgery. The most important cause of nerve damage resulted from not identifying the recurrent laryngeal nerve during first surgery, and meticulous dissection during salvage surgery was the most efficient method to avoid nerve damage.

TRAIL Mediated Signaling in Pancreatic Cancer

  • Nogueira, Daniele Rubert;Yaylim, Ilhan;Aamir, Qurratulain;Kahraman, OzlemTimirci;Fayyaz, Sundas;Naqvi, Syed Kamran-Ul-Hassan;Farooqi, Ammad Ahmad
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.5977-5982
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    • 2014
  • Research over the years has progressively shown substantial broadening of the tumor necrosis factor alpha-related apoptosis-inducing ligand (TRAIL)-mediated signaling landscape. Increasingly it is being realized that pancreatic cancer is a multifaceted and genomically complex disease. Suppression of tumor suppressors, overexpression of oncogenes, epigenetic silencing, and loss of apoptosis are some of the extensively studied underlying mechanisms. Rapidly accumulating in vitro and in vivo evidence has started to shed light on the resistance mechanisms in pancreatic cancer cells. More interestingly a recent research has opened new horizons of miRNA regulation by DR5 in pancreatic cancer cells. It has been shown that DR5 interacts with the core microprocessor components Drosha and DGCR8, thus impairing processing of primary let-7. Xenografting DR5 silenced pancreatic cancer cells in SCID-mice indicated that there was notable suppression of tumor growth. There is a paradigm shift in our current understanding of TRAIL mediated signaling in pancreatic cancer cells that is now adding new layers of concepts into the existing scientific evidence. In this review we have attempted to provide an overview of recent advances in TRAIL mediated signaling in pancreatic cancer as evidenced by findings of in vitro and in vivo analyses. Furthermore, we discuss nanotechnological advances with emphasis on PEG-TRAIL and four-arm PEG cross-linked hyaluronic acid (HA) hydrogels to improve availability of TRAIL at target sites.

Allogeneic clonal mesenchymal stem cell therapy for refractory graft-versus-host disease to standard treatment: a phase I study

  • Yi, Hyeon Gyu;Yahng, Seung-Ah;Kim, Inho;Lee, Je-Hwan;Min, Chang-Ki;Kim, Jun Hyung;Kim, Chul Soo;Song, Sun U.
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.1
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    • pp.63-67
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    • 2016
  • Severe graft-versus-host disease (GVHD) is an often lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). The safety of clinical-grade mesenchymal stem cells (MSCs) has been validated, but mixed results have been obtained due to heterogeneity of the MSCs. In this phase I study, the safety of bone marrow-derived homogeneous clonal MSCs (cMSCs) isolated by a new subfractionation culturing method was evaluated. cMSCs were produced in a GMP facility and intravenously administered to patients who had refractory GVHD to standard treatment resulting after allogeneic HSCT for hematologic malignancies. After administration of a single dose ($1{\times}10^6cells/kg$), 11 patients were evaluated for cMSC treatment safety and efficacy. During the trial, nine patients had 85 total adverse events and the rate of serious adverse events was 27.3% (3/11 patients). The only one adverse drug reaction related to cMSC administration was grade 2 myalgia in one patient. Treatment response was observed in four patients: one with acute GVHD (partial response) and three with chronic GVHD. The other chronic patients maintained stable disease during the observation period. This study demonstrates single cMSC infusion to have an acceptable safety profile and promising efficacy, suggesting that we can proceed with the next stage of the clinical trial.

The Current Status of BCG Vaccination in Young Children in South Korea

  • Lee, Hye-Jon;Dockrell, Hazel M.;Kim, Deok-Ryun;Floyd, Sian;Oh, Sue-Yeon;Lee, Jin-Bum;Kim, Hee-Jin
    • Tuberculosis and Respiratory Diseases
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    • v.72 no.4
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    • pp.374-380
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    • 2012
  • Background: Delivery of Bacille Calmette-Gur$\acute{e}$in (BCG) Tokyo vaccine, with the multipuncture device, has been much preferred over BCG Pasteur, with the intradermal method, possibly due to the easier manner of administration, a desire to avoid any trouble with scars, as well as side effects and higher profits to providers in South Korea. Methods: To determine BCG scar status in 0~6 year old children vaccinated with two BCG vaccines (Pasteur BCG vaccine with intradermal method and BCG Tokyo vaccine with percutaneous method), the data from the national BCG scar survey in 2006 was analyzed. Results: Based on the national survey, the high proportion that were vaccinated with BCG Tokyo vaccines with the multipuncture method (64.5%) was noted in 0~6 year old Korean children. From inspection of scar formation, as an indicator of vaccination, the median number of the visible pin scars from the percutaneous method was 16 (interquartile range, 12~18) in the Korean children, and pin scars decreased as the age of the children increased (p<0.001). Conclusion: The findings in this survey clearly showed a growing preference of parents for the BCG Tokyo vaccines by the multipuncture method in South Korea.

FK506 immunosuppression for submandibular salivary gland allotransplantation in rabbit

  • Almansoori, Akram Abdo;Khentii, Namuun;Ju, Kyung Won;Kim, Bongju;Kim, Soung Min;Lee, Jong-Ho
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.46 no.3
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    • pp.197-203
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    • 2020
  • Objectives: We compared the outcomes of two different doses of FK506 (tacrolimus) for immunosuppression in submandibular salivary gland (SMG) allotransplantation. Materials and Methods: Three SMG allotransplantation groups were established (n=6 per group) as follows: allograft rejection control (Allo-Ctrl), low dose (0.08 mg/kg) of FK506 (FK506-L), and high dose (0.16 mg/kg) of FK506 (FK506-H). Allograft survival and rejection were assessed by clinical observation, interleukin-2 levels as determined by enzyme-linked immunosorbent assay, blood sampling for complete blood count (CBC), and histological evaluation. Results: Body weight and anorexia were higher in the FK506-H group but without a significant difference compared with the FK506-L population. CBC revealed a non-significantly reduced number of changes in the FK506-L group. Four glands in the FK506-H group and two glands in the FK506- L group were viable and functioning post-transplantation. Conclusion: The survival rate of allotransplanted glands was higher in conjunction with the high dose of 0.16 mg/kg of FK506, with no major difference in the side-effect profile when compared with the low dose of 0.08 mg/kg short-term outcomes.