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Challenges to addressing the unmet medical needs for immunotherapy targeting cold colorectal cancer

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World Journal of Gastrointestinal Oncology 2023年第2期15卷 215-224页

作者： keun-yeong jeong Research and Development Center PearlsinMiresSeoul 03690South Korea

With the establishment of the immune surveillance mechanism since the 1950s,attempts have been made to activate the immune system for cancer treatment through the discovery of various cytokines or the development of antibodies up to *** fruits of these efforts have contributed to the recognition of the 3rd generation of anticancer immunotherapy as the mainstream of cancer ***,the limitations of cancer immunotherapy are also being recognized through the conceptual establishment of cold tumors recently,and colorectal cancer(CRC)has become a major issue from this therapeutic point of ***,it is emphasized that non-clinical strategies to overcome the immunosuppressive environment and clinical trials based on these basic investigations are being made on the journey to achieve better treatment outcomes for the treatment of cold CRC.

关键词： Colorectal cancer Immunotherapy Cell therapy Checkpoint inhibitor Cancer vaccine Cytokine therapy

Poly adenosine diphosphate-ribosylation, a promising target for colorectal cancer treatment

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World Journal of Gastrointestinal Oncology 2021年第6期13卷 574-588页

作者： keun-yeong jeong Minhee Park Research and Development Metimedi PharmaceuticalsIncheon 22006South Korea

The development of colorectal cancer(CRC)can result from changes in a variety of cellular systems within the tumor ***,it is primarily associated with genomic instability that is the gradual accumulation of genetic and epigenetic changes consisting of a characteristic set of mutations crucial for pathways in CRC *** on this background,the potential to focus on poly[adenosine diphosphate(ADP)-ribose]polymerase(PARP)-1 and poly-ADP ribosylation(PARylation)as the main causes of malignant formation of CRC may be *** of the important functions of PARP-1 and PARylation is its deoxyribonucleic acid(DNA)repair function,which plays a pivotal role in the DNA damage response and prevention of DNA damage maintaining the redox homeostasis involved in the regulation of oxidation and ***-1 and PARylation can also alter epigenetic markers and chromatin structure involved in transcriptional regulation for the oncogenes or tumor suppressor genes by remodeling histone and chromatin *** the high importance of these processes in CRC,it can be considered that PARP-1 and PARylation are at the forefront of the pathological changes required for CRC ***,this review addresses the current molecular biological features for understanding the multifactorial function of PARP-1 and PARylation in CRC related to the aforementioned roles;furthermore,it presents a summary of recent approaches with PARP-1 inhibition in non-clinical and clinical studies targeting *** understanding could help embrace the importance of targeting PARP-1 and PARylation in the treatment of CRC,which may present the potential to identify various research topics that can be challenged both nonclinically and clinically.

关键词： Colorectal cancer Poly adenosine diphosphate-ribose polymerase-1 Poly adenosine diphosphate-ribose Poly-adenosine diphosphate ribosylation

Inhibition of poly(ADP-Ribose)polymerase:A promising strategy targeting pancreatic cancer with BRCAness phenotype

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World Journal of Gastrointestinal Oncology 2021年第11期13卷 1544-1550页

作者： keun-yeong jeong Haejun Lee R&D Center Metimedi PharmaceuticalsIncheon 22006South Korea Department of Nuclear Medicine Gil Medical CenterIncheon 21565South Korea

The use of chemotherapeutic regimens for the treatment of pancreatic cancer is still limited because pancreatic cancer is usually diagnosed at an advanced stage as a refractory disease in which symptoms are difficult to recognize in the early ***,at advanced stages,there are important challenges to achieve clinical benefit and symptom resolution,even with the use of an expanded spectrum of anticancer ***,a point of reduced susceptibility to conventional chemotherapies by breast cancer susceptibility gene(BRCA)mutations led to a new perspective for overcoming the resistance of pancreatic cancer within the framework of increased genome ***(ADP-Ribose)polymerase(PARP)-1 is an enzyme that can regulate intrinsic functions,such as response to DNA ***,in an environment where germline mutations in BRCAs(BRCAness)inhibit homologous recombination in DNA damage,resulting in a lack of DNA damage response,a key role of PARP-1 for the adaptation of the genome instability could be further ***,we summarized the key functional role of PARP-1 in genomic instability of pancreatic cancer with the BRCAness phenotype and listed clinical applications and outcomes of PARP-1 inhibitors to highlight the importance of targeting PARP-1 activity.

关键词： Pancreatic cancer BRCAness Poly(ADP-Ribose)polymerase-1 PARylation Poly(ADP-Ribose)polymerase-1 inhibitor

Cancer-specific metabolism:Promising approaches for colorectal cancer treatment

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World Journal of Gastrointestinal Oncology 2019年第10期11卷 768-772页

作者： keun-yeong jeong The Research Center Metimedi Pharmaceuticals

Investigation of cancer-specific metabolism has made it possible to establish the principle that atypically reconstituted metabolism is considered a hallmark of cancer due to changes in physiological ***,a variety of targets depending on the prompted aerobic glycolysis process,starting from the abnormal uptake of glucose,and cancer-specific metabolism due to impaired mitochondrial function and abnormal expression of drug-metabolizing enzymes have been investigated and *** that most solid cancers rely on cancer-specific metabolism to support their growth,it is necessary to examine closely the specific processes of cancer metabolism and have a detailed understanding of how cellular metabolism is altered in colorectal cancer(CRC)related to CRC survival and *** development of key methods to regulate efficiently cancer-specific metabolism in CRC is still in the initial ***,targeting cancer-specific metabolism will yield treatable methods that are critical as a new area of development strategies for CRC treatment.

关键词： Colorectal cancer Cancer metabolism Warburg effect Aerobic glycolysis Mitochondria metabolism

Inhibiting focal adhesion kinase:A potential target for enhancing therapeutic efficacy in colorectal cancer therapy

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World Journal of Gastrointestinal Oncology 2018年第10期10卷 290-292页

作者： keun--yeong jeong Division of Research and Development Metimedi Pharmaceuticals

Focal adhesion kinase(FAK) is a major integrin- dep-endent tyrosine phosphorylated protein, recently, FAK association with colorectal cancer(CRC) has gained at-tention. The various cancer-promoting mechanisms that associated with FAK can be implicated in the progression of CRC. The interactions between structural features of FAK and various kinases could be closely related to growth, survival, and metastasis in CRC cells. These interactions include human epithelial growth factor re-ceptor, c-Met, platelet-derived growth factor receptor, vascular endothelial growth factor receptor, and Src. Such interactions can trigger the survival signaling of CRC cells and are also involved signaling downstream of phosphatidylinositol 3-kinase, AKT, and the extracellular regulated kinase. Based on this scientific background, many pharmaceutical companies are taking efforts to develop FAK inhibitors to treat solid cancer including CRC. Although the anti-cancer efficacies have been noted in many studies, the commercial drugs have not been deve-loped yet. Therefore, the FAK research on CRC is expec-ted to gain momentum and be highly appreciated as a potential field for developing the new drugs. Therefore, the studies on FAK that effect on the progression of human CRC s would be possible to suggest various app-roaches to CRC treatment, and FAK could be a potential target as an anticancer candidate for CRC therapies.

关键词： Colorectal cancer Focal adhesion kinase Focal adhesion kinase inhibitor Anticancer effect

Accumulation of poly(adenosine diphosphate-ribose)by sustained supply of calcium inducing mitochondrial stress in pancreatic cancer cells

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World Journal of Gastroenterology 2022年第27期28卷 3422-3434页

作者： keun-yeong jeong Jae Jun Sim Minhee Park Hwan Mook Kim Research and Development Metimedi PharmaceuticalsIncheon 22006South Korea

BACKGROUND The biochemical phenomenon defined as poly adenosine diphosphate(ADP)-ribosylation(PARylation)is essential for the progression of pancreatic ***,the excessive accumulation of poly ADP-ribose(PAR)induces apoptosis-inducing factor(AIF)release from mitochondria and energy deprivation resulting in the caspase-independent death of cancer *** To investigate whether sustained calcium supply could induce an anticancer effect on pancreatic cancer by PAR *** Two pancreatic cancer cell lines,AsPC-1 and CFPAC-1 were used for the *** influx and mitochondrial reactive oxygen species(ROS)were observed by fluorescence *** in enzyme levels,as well as PAR accumulation and energy metabolism,were measured using assay ***-dependent cell death was investigated followed by confirming in vivo anticancer effects by sustained calcium *** Mitochondrial ROS levels were elevated with increasing calcium influx into pancreatic cancer ***,excess PAR accumulation,decreased PAR glycohydrolase and ADP-ribosyl hydrolase 3 levels,and energy deprivation were *** vitro and in vivo antitumor effects were confirmed to accompany elevated AIF *** This study visualized the potential anticancer effects of excessive PAR accumulation by sustained calcium supply on pancreatic cancer,however elucidating a clear mode of action remains a challenge,and it should be accompanied by further studies to assess its potential for clinical application.

关键词： Pancreatic cancer Calcium Reactive oxygen species Poly adenosine diphosphate-ribose Poly adenosine diphosphate-ribosylation Poly adenosine diphosphate-ribose polymerase Apoptosis-inducing factor Nicotinamide adenine dinucleotide Anticancer effect

Multifunctional MXene/Carbon Nanotube Janus Film for Electromagnetic Shielding and Infrared Shielding/Detection in Harsh Environments

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Nano-Micro Letters 2024年第10期16卷 543-560页

作者： Tufail Hassan Aamir Iqbal Byungkwon Yoo Jun Young Jo Nilufer Cakmakci Shabbir Madad Naqvi Hyerim Kim Sungmin Jung Noushad Hussain Ujala Zafar Soo yeong Cho Seunghwan jeong Jaewoo Kim Jung Min Oh Sangwoon Park Youngjin jeong Chong Min Koo School of Advanced Materials Science and Engineering Sungkyunkwan UniversitySeobu-ro 2066Jangan-guSuwon-siGyeonggi-do 16419Republic of Korea Department of Materials Science and Engineering Soongsil UniversitySeoul 06978Republic of Korea Institute of Advanced Composite Materials Korea Institute of Science and Technology92 Chudong-roBongdong-eupWanju-gunJeollabuk-do 55324Republic of Korea R&D Center INNOMXENE Co. Ltd.Daejeon 34365Republic of Korea School of Chemical Engineering Sungkyunkwan UniversitySeobu-ro 2066Jangan-guSuwon-siGyeonggi-do 16419Republic of Korea

Multifunctional,flexible,and robust thin films capable of operating in demanding harsh temperature environments are crucial for various cutting-edge *** study presents a multifunctional Janus film integrating highly-crystalline Ti_(3)C_(2)T_(x) MXene and mechanically-robust carbon nanotube(CNT)film through strong hydrogen *** hybrid film not only exhibits high electrical conductivity(4250 S cm^(-1)),but also demonstrates robust mechanical strength and durability in both extremely low and high temperature environments,showing exceptional resistance to thermal *** hybrid Janus film of 15μm thickness reveals remarkable multifunctionality,including efficient electromagnetic shielding effectiveness of 72 dB in X band frequency range,excellent infrared(IR)shielding capability with an average emissivity of 0.09(a minimal value of 0.02),superior thermal camouflage performance over a wide temperature range(−1 to 300℃)achieving a notable reduction in the radiated temperature by 243℃ against a background temperature of 300℃,and outstanding IR detection capability characterized by a 44%increase in resistance when exposed to 250 W IR *** multifunctional MXene/CNT Janus film offers a feasible solution for electromagnetic shielding and IR shielding/detection under challenging conditions.

关键词： MXene/carbon nanotube Janus film Electromagnetic interference shielding Infrared shielding Thermal camouflage Infrared detection

Enhancement of porcine in vitro embryonic development through luteolin‑mediated activation of the Nrf2/Keap1 signaling pathway

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Journal of Animal Science and Biotechnology 2024年第2期15卷 600-613页

作者： Se-Been Jeon Pil-Soo jeong Min Ju Kim Hyo-Gu Kang Bong-Seok Song Sun-Uk Kim Seong-keun Cho Bo-Woong Sim Futuristic Animal Resource&Research Center(FARRC) Korea Research Institute of Bioscience and Biotechnology(KRIBB)Cheongju 28116Republic of Korea Department of Animal Science College of Natural Resources&Life SciencePusan National UniversityMiryang 50463Republic of Korea Department of Animal Science and Biotechnology College of Agriculture and Life ScienceChungnam National UniversityDaejeon 34134Republic of Korea Department of Functional Genomics University of Science and TechnologyDaejeon 34113Republic of Korea Department of Animal Science Life and Industry Convergence Research Institute(RICRI)College of Natural Resources&Life SciencePusan National UniversityMiryang 50463Republic of Korea

Background Oxidative stress,caused by an imbalance in the production and elimination of intracellular reactive oxygen species(ROS),has been recognized for its detrimental effects on mammalian embryonic ***(Lut)has been documented for its protective effects against oxidative stress in various ***,its specific role in embryonic development remains *** study aims to investigate the influence of Lut on porcine embryonic development and to elucidate the underlying *** After undergoing parthenogenetic activation(PA)or in vitro fertilization,embryos supplemented with 0.5μmol/L Lut displayed a significant enhancement in cleavage and blastocyst formation rates,with an increase in total cell numbers and a decrease in the apoptosis rate compared to the *** on D2 and D6 revealed that embryos with Lut supplementation had lower ROS levels and higher glutathione levels compared to the ***,Lut supplementation significantly augmented mitochondrial content and membrane ***,activation of the Nrf2/Keap1 signaling pathway was observed in embryos supplemented with Lut,leading to the upregulation of antioxidant-related gene transcription *** further validate the relationship between the Nrf2/Keap1 signaling pathway and effects of Lut in porcine embryonic development,we cultured PA embryos in a medium supplemented with brusatol,with or without the inclusion of *** positive effects of Lut on developmental competence were negated by brusatol *** Our findings indicate that Lut-mediated activation of the Nrf2/Keap1 signaling pathway contributes to the enhanced production of porcine embryos with high developmental competence,and offers insight into the mechanisms regulating early embryonic development.

关键词： Luteolin Mitochondrial function Nrf2/Keap1 signaling pathway Oxidative stress Porcine embryo development

A pilot clinical study to evaluate feasibility of using single patient classifier as a prognostic test in stage Ⅱ-Ⅲ gastric cancer patients

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Chinese Journal of Cancer Research 2024年第4期36卷 368-377页

作者： Ji yeong An Sung Eun Oh Soomin Ahn Hyoung-II Kim Yoo Min Kim Minah Cho keun Won Ryu Hong Man Yoon Young Kyu Park In Gyu Kwon Sung Hoon Noh Kyung Hee Lee In Cho Myoung Won Son Jong Won Kim Young-Woo Kim Department of Surgery Samsung Medical CenterSungkyunkwan University School of MedicineSeoul 06351Republic of Korea Department of Pathology and Translational Genomics Samsung Medical CenterSungkyunkwan University School of MedicineSeoul 06351Republic of Korea Department of Surgery Yonsei University College of MedicineSeoul 03722Republic of Korea Gastric Cancer Center Yonsei Cancer CenterYonsei University Health SystemSeoul 03722Republic of Korea Center for Gastric Cancer National Cancer CenterGoyang 10408Republic of Korea Department of Surgery Chonnam National University Hwasun HospitalChonnam National University College of MedicineGwangju 58128Republic of Korea Department of Surgery Gangnam Severance HospitalYonsei University College of MedicineSeoul 06273Republic of Korea Department of Hematology-Oncology Yeungnam University Medical CenterDaegu 42415Republic of Korea Department of Surgery Soonchunhyang University College of MedicineBucheon 14584Republic of Korea Department of Surgery Soonchunhyang University Cheonan HospitalSoonchunhyang University College of MedicineCheonan 31151Republic of Korea Department of Surgery Chung-Ang University HospitalChung-Ang University College of MedicineSeoul 06973Republic of Korea

Objective:Precision medicine approaches emphasize the importance of reliable prognostic tools for guiding individualized therapy *** this study,we evaluated the clinical feasibility of the single patient classifier(SPC)test,a new clinical-grade prognostic assay,in stageⅡ-Ⅲgastric cancer ***:A prospective multicenter study was conducted,involving 237 patients who underwent gastrectomy between September 2019 and August 2020 across nine *** SPC test was employed to stratify patients into risk groups,and its feasibility and performance were *** primary endpoint was the proportion of the cases in which the test results were timely delivered before selecting postoperative ***,3-year disease-free survivals of risk groups were ***:The SPC test met the primary endpoint *** 99.5%of SPC tests were timely delivered to hospitals before the postoperative treatment *** a clinical setting,the median time from the specimen transfer to laboratory to the result delivery to hospital was 4 ***,3-year disease-free survivals were significantly different between risk groups classified with SPC ***:This study highlights the SPC test's feasibility in offering crucial information timely delivered for making informed decisions regarding postoperative treatment *** also provides evidence to support the implementation of a future prospective clinical trial aimed at evaluating the clinical utility of the SPC test in guiding personalized treatment decisions for gastric cancer patients.

关键词： Prognostic test advanced gastric cancer adjuvant chemotherapy feasibility gastrectomy