• Title/Summary/Keyword: Treat-to-target

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Immune checkpoint inhibitors: recent progress and potential biomarkers

  • Darvin, Pramod;Toor, Salman M.;Nair, Varun Sasidharan;Elkord, Eyad
    • Experimental and Molecular Medicine
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    • v.50 no.12
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    • pp.10.1-10.11
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    • 2018
  • Cancer growth and progression are associated with immune suppression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. Monoclonal antibodies that target immune checkpoints provided an immense breakthrough in cancer therapeutics. Among the immune checkpoint inhibitors, PD-1/PD-L1 and CTLA-4 inhibitors showed promising therapeutic outcomes, and some have been approved for certain cancer treatments, while others are under clinical trials. Recent reports have shown that patients with various malignancies benefit from immune checkpoint inhibitor treatment. However, mainstream initiation of immune checkpoint therapy to treat cancers is obstructed by the low response rate and immune-related adverse events in some cancer patients. This has given rise to the need for developing sets of biomarkers that predict the response to immune checkpoint blockade and immune-related adverse events. In this review, we discuss different predictive biomarkers for anti-PD-1/PD-L1 and anti-CTLA-4 inhibitors, including immune cells, PD-L1 overexpression, neoantigens, and genetic and epigenetic signatures. Potential approaches for further developing highly reliable predictive biomarkers should facilitate patient selection for and decision-making related to immune checkpoint inhibitor-based therapies.

In silico investigation of Panax ginseng lead compounds against COVID-19 associated platelet activation and thromboembolism

  • Yixian Quah;Yuan Yee Lee;Seung-Jin Lee;Sung Dae Kim;Man Hee Rhee;Seung-Chun Park
    • Journal of Ginseng Research
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    • v.47 no.2
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    • pp.283-290
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    • 2023
  • Hypercoagulability is frequently observed in patients with severe coronavirus disease-2019 (COVID-19). Platelets are a favorable target for effectively treating hypercoagulability in COVID-19 patients as platelet hyperactivity has also been observed. It is difficult to develop a treatment for COVID-19 that will be effective against all variants and the use of antivirals may not be fully effective against COVID-19 as activated platelets have been detected in patients with COVID-19. Therefore, patients with less severe side effects often turn toward natural remedies. Numerous phytochemicals are being investigated for their potential to treat a variety of illnesses, including cancer and bacterial and viral infections. Natural products have been used to alleviate COVID-19 symptoms. Panax ginseng has potential for managing cardiovascular diseases and could be a treatment for COVID-19 by targeting the coagulation cascade and platelet activation. Using molecular docking, we analyzed the interactions of bioactive chemicals in P. ginseng with important proteins and receptors involved in platelet activation. Furthermore, the SwissADME online tool was used to calculate the pharmacokinetics and drug-likeness properties of the lead compounds of P. ginseng. Dianthramine, deoxyharrtingtonine, and suchilactone were determined to have favorable pharmacokinetic profiles.

Molecular Docking Study of Naturally-derived Neuraminidase Inhibitors Isolated from Phellinus Baumii

  • Babu, Sathya
    • Journal of Integrative Natural Science
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    • v.8 no.3
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    • pp.209-213
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    • 2015
  • Influenza A virus (H1N1) causes and spreads infectious diseases and becomes a major health threat in humans. Among the subtypes of influenza virus, neuraminidase (NA) plays an important role in viral life cycle and becomes an attractive therapeutic target. Currently two NA inhibitors namely Zanamivir and Oseltamivir are available for treating infectious diseases. Recently five naturally derived polyphenols extracted from Phellinus baumii was reported as inhibitors against NA. Molecular docking is powerful tool in computer aided drug designing which aids in exploring and elucidating the properties of the molecules from their 3D structure. Hence, in the present study, molecular docking was carried out on reported polyphenols isolated from ethanolic extract of fruiting bodies of Phellinus baumii. The objective of this work was to study the interaction and to propose the binding mode of these compounds within the binding site of H1N1 neuraminidase. The results showed these compounds had better binding energy and H-bond interactions with the important active site residues of the receptor which authenticate these compounds contributes to inhibitory activity of neuraminidase to treat influenza infection.

Advanced Imaging Applications for Locally Advanced Cervical Cancer

  • Petsuksiri, Janjira;Jaishuen, Atthapon;Pattaranutaporn, Pittayapoom;Chansilpa, Yaowalak
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.1713-1718
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    • 2012
  • Advanced imaging approaches (computed tomography, CT; magnetic resonance imaging, MRI; $^{18}F$-fluorodeoxyglucose positron emission tomography, FDG PET) have increased roles in cervical cancer staging and management. The recent FIGO (International Federation of Gynecology and Obstetrics) recommendations encouraged applications to assess the clinical extension of tumors rather than relying on clinical examinations and traditional non-cross sectional investigations. MRI appears to be better than CT for primary tumors and adjacent soft tissue involvement in the pelvis. FDG-PET/CT has increased in usage with a particular benefit for whole body evaluation of tumor metabolic activity. The potential benefits of advanced imaging are assisting selection of treatment based upon actual disease extent, to adequately treat a tumor with minimal normal tissue complications, and to predict the treatment outcomes. Furthermore, sophisticated external radiation treatment and brachytherapy absolutely require advanced imaging for target localization and radiation dose calculation.

Dose Characteristics of Stereotatic Radiosurgery CONE used for ML-6M Linear Accelerator (ML-6M LINAC에 장착한 Radiosurgery Cone의 Beam 특성에 대한 고찰)

  • Moon, Un-Chull;Kim, Hyun-Jin;Kim, Young-Suk
    • The Journal of Korean Society for Radiation Therapy
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    • v.7 no.1
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    • pp.15-31
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    • 1995
  • The radiosurgery treatment is one time, non surgical approach to the treatment of patients with intracranial disorders whose conditions would be difficult or dangerous to treat with conventional sugical procedures. The LINAC based radiosurgery is based on the combination of multiple isocentric arc irradiation with small fields centered in the stereotactic target. The absorption of the beam in a tissue equivalent medium, such as water, as well as the uniformity, or profile, of the beam must be precisely documented. The beam characteristics and dosimetric measurememts of the 6MV X-ray beam from a ML-6M linear accelerator are examined. The percent depth dose (PDD) and beam profile (including flatness, symmetry and penumbra) is calibrated with the radiosurgery cone in water phantom. The cone is made of lead which size is from $10{\times}10mm{\phi}$ to $30{\times}30mm{\phi}$ All of these dosimetric measurements sufficiently characterized the beam to permit safe clinical use.

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Mechanism of TCE Removal with Foundry Sands and Design of Permeable ]Reactive Barriers (주물사의 TCE 제거 메커니즘과 반응벽체에의 적용가능성)

  • ;Benson, Craig H
    • Journal of the Korean Geotechnical Society
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    • v.18 no.5
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    • pp.143-157
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    • 2002
  • Batch and column tests were conducted with common groundwater contaminants (i.e., trichloroethylene) to determine transport parameters and reactivity of the foundry sands. The reactivities of foundry sands for common groundwater contaminants are comparable to or slightly higher than those for Peerless iron a common medium used in permeable reactive barriers. In addition, the TOC and clay in foundry sands can significantly retard the movement of target contaminants, which may result in lower effluent concentrations of contaminants due to biodegradation. In general, permeable reactive barriers with the thickness of 1m can be constructed with many foundry sands to treat typical groundwater comtaminants provided the zero-valent iron content in the foundry sand is higher than 1%.

Panorama Image Processing for Condition Monitoring with Thermography in Power Plant (공업플랜트의 상태감시를 위한 열화상 파노라마 이미지 처리기법 연구)

  • Jeon, Byoung-Joon;Kim, Tae-Hwan;Kim, Soon-Geol;Mo, Yoon-Syub;Kim, Won-Tae
    • Journal of the Korean Society for Nondestructive Testing
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    • v.30 no.2
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    • pp.98-103
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    • 2010
  • In this paper, imaging processing study obtained from CCD image and thermography image was performed in order to treat easily thermographic data without any risks of personnels who conduct the condition monitoring for the abnormal or failure status occurrable in industrial power plants. This imaging processing is also applicable to the predictive maintenance. For confirming the broad monitoring, a methodology producting single image from the panorama technique was developed no matter how many cameras are employed, including fusion method for discrete configuration for the target. As results, image fusion from quick realtime processing was obtained and it was possible to save time to track the location monitoring in matching the images between CCTV and thermography.

Neuroprotective Effect of Wild Radish Extract on Scopolamine Induced Memory Impairment (갯무 추출물의 스코폴라민 유도 기억력 저하 모델에서의 뇌신경 보호 효과)

  • Hur, Jinyoung;Choi, Sang Yoon;Yeom, Mijung
    • Journal of the Korean Society of Food Culture
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    • v.36 no.6
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    • pp.633-639
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    • 2021
  • Raphanus sativus var. hortensis f. raphanistroides Makino (Korean wild radish [WR]) are root vegetables belonging to the Brassicaceae family. These radish species mostly grow in sea areas in Asia, where they have been traditionally used as a medicinal food to treat various diseases. To investigate the effect of WR on neuronal cell death in SH-SY5Y cells, beta-amyloid was used to develop the cell death model. WR attenuated neuronal cell death in SH-SY5Y and regulated the mitogen-activated protein kinase (MAPK) signaling. WR extract also inhibited acetylcholinesterase inhibitor activity. Additionally, the WR treatment group ameliorated the behavior of the memory-impaired mice in a scopolamine-induced mouse model. In the behavior test, WR treated mice showed shorter escape latency and swimming distance and improved the platform-crossing number and the swimming time within the target quadrant. Furthermore, WR prevented histological loss of neurons in hippocampal CA1 regions induced by scopolamine. This study shows that WR can prevent memory impairment which may be a crucial way for the prevention and treatment of memory dysfunction and neuronal cell death.

MicroRNA-296-5p Promotes Invasiveness through Downregulation of Nerve Growth Factor Receptor and Caspase-8

  • Lee, Hong;Shin, Chang Hoon;Kim, Hye Ree;Choi, Kyung Hee;Kim, Hyeon Ho
    • Molecules and Cells
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    • v.40 no.4
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    • pp.254-261
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    • 2017
  • Glioblastomas (GBM) are very difficult to treat and their aggressiveness is one of the main reasons for this as well as for the frequent recurrences. MicroRNAs post-transcriptionally regulate their target genes through interaction between their seed sequence and 3'UTR of the target mRNAs. We previously reported that miR-296-3p is regulated by neurofibromatosis 2 (NF2) and enhances the invasiveness of GBM cells via SOCS2/STAT3. In this study, we investigated whether miR-296-5p, which originates from the same precursor miRNA as miR-296-3p, can increase the invasiveness of GBM cells. It was observed that miR-296-5p potentiated the invasion of various GBM cells including LN229, T98G, and U87MG. Through bioinformatics approaches, two genes were identified as miR-296-5p targets: caspase-8 (CASP8) and nerve growth factor receptor (NGFR). From results obtained from Ago2 immunoprecipitation and luciferase assays, we found that miR-296-5p downregulates CASP8 and NGFR through direct interaction between seed sequence of the miRNA and 3'UTR of the target mRNA. Knockdown of CASP8 or NGFR also increased the invasive ability of GBM cells, indicating that CASP8 and NGFR are involved in potentiation of invasiveness by miR-296-5p. Consistent with our findings, CASP8 was downregulated in brain metastatic lung cancer cells, which have a high level of miR-296-5p, compared to parental cells, suggesting that miR-296-5p may be generally associated with the acquisition of invasiveness. Collectively, our results implicate miR-296-5p as a potential cause of invasiveness in cancer and suggest it as a promising therapeutic target for GBM.

Erratum to: Upstream signalling of mTORC1 and its hyperactivation in type 2 diabetes (T2D)

  • Ali, Muhammad;Bukhari, Shazia Anwer;Ali, Muhammad;Lee, Han-Woong
    • BMB Reports
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    • v.51 no.1
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    • pp.45-53
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    • 2018
  • Mammalian target of rapamycin complex 1 (mTORC1) plays a major role in cell growth, proliferation, polarity, differentiation, development, and controls transitioning between anabolic and catabolic states of the cell. It collects almost all extracellular and intracellular signals from growth factors, nutrients, and maintains cellular homeostasis, and is involved in several pathological conditions including, neurodegeneration, Type 2 diabetes (T2D), obesity, and cancer. In this review, we summarize current knowledge of upstream signaling of mTORC1 to explain etiology of T2D and hypertriglyceridemia, in which state, the role of telomere attrition is explained. We discuss if chronic inhibition of mTORC1 can reverse adverse effects resulting from hyperactivation. In conclusion, we suggest the regulatory roles of telomerase (TERT) and hexokinase II (HKII) on mTORC1 as possible remedies to treat hyperactivation. The former inhibits mTORC1 under nutrient-rich while the latter under starved condition. We provide an idea of TOS (TOR signaling) motifs that can be used for regulation of mTORC1.