• Title/Summary/Keyword: site-response effects

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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.

Pushover Analysis of a 5-Story RC OMRF Considering Inelastic Shear Behavior of Beam-Column Joint (보-기둥 접합부 비탄성 전단거동을 고려한 5층 철근콘크리트 보통모멘트골조의 푸쉬오버해석)

  • Kang, Suk-Bong;Kim, Tae-Yong
    • Journal of the Korea Concrete Institute
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    • v.24 no.5
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    • pp.517-524
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    • 2012
  • In this study, the effects of the inelastic shear behavior of beam-column joint and the vertical distribution of lateral load are evaluated considering higher modes on the response of RC OMRF using the pushover analysis. A structure used for the analysis was a 5-story structure located at site class SB and seismic design category C, which was designed in accordance with KBC2009. Bending moment-curvature relationship for beam and column was identified using fiber model. Also, bending moment-rotation relationship for beam-column joint was calculated using simple and unified joint shear behavior model and moment equilibrium relationship for the joint. The results of pushover analysis showed that, although the rigid beam-column joint overestimated the stiffness and strength of the structure, the inelastic shear behavior of beam-column joint could be neglected in the process of structural design since the average response modification factor satisfied the criteria of KBC2009 for RC OMRF independent to inelastic behavior of joint.

Amino Acids and Protein Digestibility and Metabolizable Energy Availability of Barley Ration in Response to Grind® Enzyme in Broiler Chickens

  • Saki, Ali Asghar;Mirzayi, S.;Ghazi, Sh.;Moini, M.M.;Naseri Harsini, R.
    • Asian-Australasian Journal of Animal Sciences
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    • v.23 no.5
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    • pp.614-621
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    • 2010
  • Increasing accuracy of broiler diet formulation based on amino acid digestibility in comparison to application of total amino acids could lead to more feed efficiency and productivity. This experiment was conducted for determination of sampling site (excreta and ileum) and recognition of the effects of a commercial enzyme ($Grind^{(R)}$ Danisco, Finland) on metabolizable energy, protein and amino acid digestibility of barley. This study was modulated by a marker in 21-day old Arbor Acres chickens. Corn-soybean meal was used as a control diet and, in the other two treatments, barley (at a level of 40%) with and without enzyme as the test ingredient were supplemented to the basal diet. Chromic oxide was included in all diets (0.5%) as an indigestible marker. Apparent metabolizable energy (AME), corrected by nitrogen (AMEn) and apparent digestibility of aspartic acid, glutamic acid, serine, glycine, alanine, tyrosine, valine and methionine were significantly (p<0.05) higher in feces than ileum. Protein digestibility of diet and barley was significantly (p<0.05) higher in the ileum than in feces. Apparent digestibility of tryptophan, proline, methionine, phenylalanine and lysine was increased significantly (p<0.05) by enzyme supplementation. In contrast, no response was observed in AME, AMEn, and protein digestibility of the diet and barley by enzyme supplementation. The results of this study have shown that AME and amino acid digestibility were increased in feces, in contrast an adverse effect was observed for protein digestibility of the diet and barley.

Bispecific Antibody-Bound T Cells as a Novel Anticancer Immunotherapy

  • Cho, Jaewon;Tae, Nara;Ahn, Jae-Hee;Chang, Sun-Young;Ko, Hyun-Jeong;Kim, Dae Hee
    • Biomolecules & Therapeutics
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    • v.30 no.5
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    • pp.418-426
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    • 2022
  • Chimeric antigen receptor T (CAR-T) cell therapy is one of the promising anticancer treatments. It shows a high overall response rate with complete response to blood cancer. However, there is a limitation to solid tumor treatment. Additionally, this currently approved therapy exhibits side effects such as cytokine release syndrome and neurotoxicity. Alternatively, bispecific antibody is an innovative therapeutic tool that simultaneously engages specific immune cells to disease-related target cells. Since programmed death ligand 1 (PD-L1) is an immune checkpoint molecule highly expressed in some cancer cells, in the current study, we generated αCD3xαPD-L1 bispecific antibody (BiTE) which can engage T cells to PD-L1+ cancer cells. We observed that the BiTE-bound OT-1 T cells effectively killed cancer cells in vitro and in vivo. They substantially increased the recruitment of effector memory CD8+ T cells having CD8+CD44+CD62Llow phenotype in tumor. Interestingly, we also observed that BiTE-bound polyclonal T cells showed highly efficacious tumor killing activity in vivo in comparison with the direct intravenous treatment of bispecific antibody, suggesting that PD-L1-directed migration and engagement of activated T cells might increase cancer cell killing. Additionally, BiTE-bound CAR-T cells which targets human Her-2/neu exhibited enhanced killing effect on Her-2-expressing cancer cells in vivo, suggesting that this could be a novel therapeutic regimen. Collectively, our results suggested that engaging activated T cells with cancer cells using αCD3xαPD-L1 BiTE could be an innovative next generation anticancer therapy which exerts simultaneous inhibitory functions on PD-L1 as well as increasing the infiltration of activated T cells having effector memory phenotype in tumor site.

Alteration in Response to Chemicals Induced by Physical Exercise (육체운동에 의해 유발되는 화학물질에 대한 반응성의 변화)

  • 김영철
    • Toxicological Research
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    • v.18 no.3
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    • pp.215-226
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    • 2002
  • Acute or repeated physical exercise affects a large number of physiological parameters including hemodynamics, respiration, pH, temperature, gastrointestinal function and biotransformation, which determine the pharmacokinetics of drugs and chemicals. The rate and the amount of a chemical reaching the active site are altered by physical exercise, which results in significant changes in pharmacolosical/toxicological activity of the chemical. This aspect of physical exercise has vast implication in therapeutics and in safety evaluation, particularly for chemicals that have a low margin of safety. However there appears to be a wide inter- and intraindividual variation in the effects of physical exercise depend-ing on the duration, intensity and type of exercise, and also on the properties of each chemical. It is suggested that more studies need to be done to determine which factor(s) plays a major role in the disposition of chemicals in human/animals performing physical exercise. Certain chemicals induce severe toxicity due to metabolic conversion to reactive intermediate metabolites. it is suggested that repeated exercise may enhance the free radical scavenging system by increasing the activity of antioxidant enzymes. This area of research remain to be explored to elucidate the interaction of exercise and chemical on the antioxidant system.

Structural performance assessment of fixed offshore platform based on in-place analysis

  • Raheem, Shehata E. Abdel;Aal, Elsayed M. Abdel;AbdelShafy, Aly G.A.;Mansour, Mahmoud H.;Omar, Mohamed
    • Coupled systems mechanics
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    • v.9 no.5
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    • pp.433-454
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    • 2020
  • In-place analysis for offshore platforms is essentially required to make proper design for new structures and true assessment for existing structures. The structural integrity of platform components under the maximum and minimum operating loads of environmental conditions is required for risk assessment and inspection plan development. In-place analyses have been executed to check that the structural member with all appurtenances robustness and capability to support the applied loads in either storm condition or operating condition. A nonlinear finite element analysis is adopted for the platform structure above the seabed and the pile-soil interaction to estimate the in-place behavior of a typical fixed offshore platform. The analysis includes interpretation of dynamic design parameters based on the available site-specific data, together with foundation design recommendations for in-place loading conditions. The SACS software is utilized to calculate the natural frequencies of the model and to obtain the response of platform joints according to in-place analysis then the stresses at selected members, as well as their nodal displacements. The directions of environmental loads and water depth variations have important effects on the results of the in-place analysis behavior. The result shows that the in-place analysis is quite crucial for safe design and operation of offshore platform and assessment for existing offshore structures.

Risk Factors for Oral Cancer in Northeast Thailand

  • Loyha, Kulchaya;Vatanasapt, Patravoot;Promthet, Supannee;Parkin, Donald Maxwell
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.5087-5090
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    • 2012
  • Oral cancer is a common site of head and neck cancer, and is relatively frequent in Northeast Thailand. The objective of this hospital-based, case-control study was to determine associations with risk factors. A total of 104 oral cancer cases diagnosed between July 2010 and April 2011 in 3 hospitals were matched with control subjects by age, sex and hospital. Data were collected by personal interview. There were significant associations between oral cancer and tobacco smoking (OR=4.47; 95%CI=2.00 to 9.99), alcohol use among women (OR=4.16; 95%CI=1.70 to 10.69), and betel chewing (OR=9.01; 95%CI=3.83 to 21.22), and all three showed dose-response effects. Smoking is rare among Thai women (none of the control women were smokers), but betel chewing, especially among older women, is relatively common. We did not find any association between practicing oral sex and oral cancer.

Response Properties of Acupuncture Stimulation by Meridian Electrical Potential Measurement (침구경략전위 측정에 의한 침 자극 반응 특성)

  • Ryu, Yeon-Hang;Jung, Byung-Jo;Lee, Yong-Heum
    • Journal of Biomedical Engineering Research
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    • v.29 no.5
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    • pp.408-413
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    • 2008
  • Human body has a complete left and right symmetry structure, and the left and right balance by Yin and Yang. When the balance is broken, the left and right Meridian becomes abnormal condition. Acupuncture is a kind of therapy to recover from energy unbalance of the left and right Meridian to a new balance condition. In the study, we observed the electric potential along the stomach meridian (ST) in order to verify the energy consensus phenomenon by transportation of bio-energy between operator and subject during acupuncture. The acupuncture effects on opposite meridian site were investigated by comparing the electric potentials between the right and left ST sites. Meridian electrical potentials (MEPs) between operator and subject were simultaneously generated during the acupuncture and the polarity of MEPs was opposite. The results might imply the bio-energy transportation between operator and subject. In addition, we observed three different patterns of MEPs on both ST sites which might represent the condition of the related meridians because meridians in the body are organically interconnected.

The Phosphorylation Status of Merlin Is Important for Regulating the Ras-ERK Pathway

  • Jung, Ju Ri;Kim, Hongtae;Jeun, Sin-Soo;Lee, Joo Yong;Koh, Eun-Jeoung;Ji, Cheol
    • Molecules and Cells
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    • v.20 no.2
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    • pp.196-200
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    • 2005
  • The neurofibromatosis type2 (NF2) tumor suppressor gene product, merlin, is structurally related to the ezrin-radixin-moesin (ERM) family of proteins that anchor the actin cytoskeleton to specific membrane proteins and participate in cell signaling. However, the basis of the tumor suppressing activity of merlin is not well understood. Previously, we identified a role of merlin as an inhibitor of the Ras-ERK signaling pathway. Recent studies have suggested that phosphorylation of merlin, as of other ERM proteins, may regulate its function. To determine whether phosphorylation of merlin affects its suppression of Ras-ERK signaling, we generated plasmids expressing full-length merlin with substitutions of serine 518, a potential phosphorylation site. A substitution that mimics constitutive phosphorylation (S518D) abrogated the ability of merlin to suppress effects of the Ras-ERK signaling pathway such as Ras-induced SRE transactivation, Elk-mediated SRE transactivation, Ras-induced ERK phosphorylation and Ras-induced focus formation. On the other hand, an S518A mutant, which mimics nonphosphorylated merlin, acted like wild type merlin. These observations show that mimicking merlin phosphorylation impairs not only growth suppression by merlin but also its inhibitory action on the Ras-ERK signaling pathway.

Characteristics of shear strength of coarse-grained materials using large triaxial test equipment (대형삼축시험 장비를 이용한 조립재료의 전단강도 특성)

  • Jin, Guang-Ri;Snin, Dong-Hoon;Im, Eun-Sang;Kim, Ki-Young
    • Proceedings of the Korean Geotechical Society Conference
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    • 2009.09a
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    • pp.1017-1024
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    • 2009
  • In the past few decades, the rockfill embankment dam, which has superior workability and economy, has become a major trend. In Korea, most of the embankment dams are rockfill dams, but recently, in response to the demand for sustainable development and environmentally-friendly water resource development, the sand and gravel in streams has become a major construction material for dams, rather than the non-economic rockfill, and its application examples have also increased. In this study, a large triaxial test was performed, with construction samples of different maximum sizes, in parallel with the grading method at the 'B Dam' construction site in Korea, and the effects of the different maximum sizes on the strain of the dam construction material and on the shear strength characteristics were analyzed to provide the basic data for determining the strength characteristics of the coarse-grained materials by the maximum size.

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