• Title/Summary/Keyword: TME

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Vemurafenib Enhances NK cell Expansion and Tumor-killing Activity for Cancer Immunotherapy

  • Min Hwa Shin
    • Biomedical Science Letters
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    • v.29 no.4
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    • pp.371-375
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    • 2023
  • Natural killer (NK) cells are innate immune cells and play important roles as the first immune cells to recognize and kill cancer. In patients with advanced and terminal cancer, NK cells are often inactivated, suggesting that NK cells may play important roles in cancer treatment. In particular, the proportion of NK cells among immune cells infiltrating tumor tissues is often low, which suggests that NK cells do not survive in tumor microenvironment (TME). In order to overcome these hurdles of NK cells in cancer treatment, it is critical to develop strategies that enhance the proliferation and cytolytic activity of NK cells. We applied Vemurafenib to NK cells and measured the degree of NK cell proliferation and functional activation. We obtained unexpected results of increased NK cell numbers and anti-tumor activity after Vemurafenib treatment. Although further investigation is required to uncover the detailed mechanisms, our results suggest that Vemurafenib is a promising candidate to increase the efficacy of cancer immunotherapy using NK cells.

Current Development Status of Cytokines for Cancer Immunotherapy

  • Kyoung Song
    • Biomolecules & Therapeutics
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    • v.32 no.1
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    • pp.13-24
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    • 2024
  • Cytokines influence the overall cancer immune cycle by triggering tumor antigen expression, antigen presenting, immune cell priming and activation, effector immune cell recruitment and infiltration to cancer, and cancer killing in the tumor microenvironment (TME). Therefore, cytokines have been considered potential anti-cancer immunotherapy, and cytokine-based anti-cancer therapies continue to be an active area of research and development in the field of cancer immunotherapy, with ongoing clinical trials exploring new strategies to improve efficacy and safety. In this review, we examine past and present clinical developments for major anticancer cytokines, including interleukins (IL-2, IL-15, IL-12, IL-21), interferons, TGF-beta, and GM-CSF. We identify the current status and changes in the technology platform being applied to cytokine-based immune anti-cancer therapeutics. Through this, we discuss the opportunities and challenges of cytokine-based immune anti-cancer treatments in the current immunotherapy market and suggest development directions to enhance the clinical use of cytokines as immuno-anticancer drugs in the future.

Effects of Alpha-galactosidase Supplementation to Corn-soybean Meal Diets on Nutrient Utilization, Performance, Serum Indices and Organ Weight in Broilers

  • Wang, C.L.;Lu, W.Q.;Li, Defa;Xing, J.J.
    • Asian-Australasian Journal of Animal Sciences
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    • v.18 no.12
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    • pp.1761-1768
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    • 2005
  • Effects of alpha-galactosidase (GAL) on broiler corn-soybean meal diet was investigated. In experiment 1, sixty cockerels were allocated to five groups, including three enzyme treatments (GAL added at 0, 500, and 1,000 mg/kg diet), a nitrogen-free diet group and a fast group. The true nitrogen-corrected ME (TME$_n$) and true amino acid availability were determined. In experiment 2, 324 day-old chicks were used in a 2${\times}$3 factorial design consisting of two energy contents (high and low) and three GAL levels (0, 250, and 500 mg/kg). Three feeding phases, comprising 0-21 d, 22-35 d and 36-48 d, were involved. GAL addition improved TME$_n$ and the availability of methionine and cystine (p<0.05). The apparent ME (AME) or nitrogen-corrected AME (AME$_n$) and digestibility of dry matter, organic matter, calcium, and phosphorus were improved significantly on d 21, so was crude protein and an interaction of energy and GAL on AME$_n$ (p<0.05) was found on d 35. However, daily intake and daily gain were significantly improved with GAL addition (p<0.05) during 21 d. The small intestine relative weight decreased at 250 mg/kg GAL (p<0.05) on d 35, whereas presented an interaction between GAL and energy on d 21 (p<0.05). Likewise, this treatment increased breast muscle ratio (p<0.05). On d 21, triglycerides level of broilers showed interaction between energy and enzyme levels (p<0.05). Uric acid level in 500 mg/kg GAL declined linearly (p<0.05). On d 35, quadratic effects (p<0.05) were observed in total protein, albumin, globulin and cholesterol content for enzyme supplementation. And the interactive effects of energy and GAL on serum values showed more obviously. The study implies that GAL improved energy and nutrient availability of corn-soybean meal diet in broiler. The GAL supplementation to corn-soybean meal based diet can improve performance of broilers in early stages of growth.

Effects of Enzyme Treated Palm Kernel Expeller on Metabolizable Energy, Growth Performance, Villus Height and Digesta Viscosity in Broiler Chickens

  • Saenphoom, P.;Liang, J.B.;Ho, Y.W.;Loh, T.C.;Rosfarizan, M.
    • Asian-Australasian Journal of Animal Sciences
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    • v.26 no.4
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    • pp.537-544
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    • 2013
  • This study examined whether pre-treating palm kernel expeller (PKE) with exogenous enzyme would degrade its fiber content; thus improving its metabolizable energy (ME), growth performance, villus height and digesta viscosity in broiler chickens fed diets containing PKE. Our results showed that enzyme treatment decreased (p<0.05) hemicellulose and cellulose contents of PKE by 26.26 and 32.62%, respectively; and improved true ME (TME) and its nitrogen corrected value ($TME_n$) by 38% and 33%, respectively, compared to the raw sample. Average daily gain (ADG), feed intake and feed conversion ratio (FCR) of chickens fed on different dietary treatments in the grower period were not significantly different. Although there was no difference in feed intake (p>0.05) among treatment groups in the finisher period, ADG of chickens in the control (PKE-free diet) was higher (p<0.05) than in all treatment groups fed either 20 or 30% PKE, irrespective of with or without enzyme treatment. However, ADG of birds fed with 20% PKE was higher than those fed with 30% PKE. The FCR of chickens in the control was the lowest (2.20) but not significantly different from those fed 20% PKE diets while birds in the 30% PKE diets recorded higher (p>0.05) FCR. The intestinal villus height and crypt depth (duodenum, jejunum and ileum) were not different (p>0.05) among treatments except for duodenal crypt depth. The villus height and crypt depth of birds in enzyme treated PKE diets were higher (p<0.05) than those in the raw PKE groups. Viscosity of the intestinal digesta was not different (p>0.05) among treatments. Results of this study suggest that exogenous enzyme is effective in hydrolyzing the fiber (hemicellulose and cellulose) component and improved the ME values of PKE, however, the above positive effects were not reflected in the growth performance in broiler chickens fed the enzyme treated PKE compared to those received raw PKE. The results suggest that PKE can be included up to 5% in the grower diet and 20% in the finisher diet without any significant negative effect on FCR in broiler chickens.

Adrenergic receptor β2 activation by stress promotes breast cancer progression through macrophages M2 polarization in tumor microenvironment

  • Qin, Jun-fang;Jin, Feng-jiao;Li, Ning;Guan, Hai-tao;Lan, Lan;Ni, Hong;Wang, Yue
    • BMB Reports
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    • v.48 no.5
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    • pp.295-300
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    • 2015
  • Stress and its related hormones epinephrine (E) and norepinephrine (NE) play a crucial role in tumor progression. Macrophages in the tumor microenvironment (TME) polarized to M2 is also a vital pathway for tumor deterioration. Here, we explore the underlying role of macrophages in the effect of stress and E promoting breast cancer growth. It was found that the weight and volume of tumor in tumor bearing mice were increased, and dramatically accompanied with the rising E level after chronic stress using social isolation. What is most noteworthy, the number of M2 macrophages inside tumor was up-regulated with it. The effects of E treatment appear to be directly related to the change of M2 phenotype is reproduced in vitro. Moreover, E receptor $ADR{\beta}2$ involved in E promoting M2 polarization was comprehended simultaneously. Our results imply psychological stress is influential on specific immune system, more essential for the comprehensive treatment against tumors. [BMB Reports 2015; 48(5): 295-300]

Transport Characteristics and Screening of Penetration Enhancer through Buccal Mucosa of Butorphanol Tartrate from [P(AA-co-PEGMM)] Copolymer Films ([P(AA-co-PEGMM)] 공중합체 필름으로부터 Butorphanol Tartrate의 구강점막 투과 특성 및 투과촉진제의 검색)

  • Kim, Joun-Sik;Park, Jeong-Sook;Jeong, Yeon-Bok;Han, Kun
    • Journal of Pharmaceutical Investigation
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    • v.33 no.3
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    • pp.157-162
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    • 2003
  • The feasibility of [P(AA-co-PEGMM)] film as a buccal mucoadhesive patch was previously reported by estimating mucoadhesiveness and release characteristics. To find a rational penetration enhancer of [P(AA-co-PEGMM)] film containing butorphanol tartrate (Bt), penetration of Bt from [P(AA-co-PEGMM)] film which contained various additives was estimated by measuring its flux, Papp and lag tme in in vitro buccal membrane of porcine. EDTA showed almost no increase of Bt permeability, wherease SGC, STDHF and SLS increased the permeability of Bt with the order of SGC > STDHF > SLS. The rational additive concentration of SGC was 4% and its Papp and lag time were $1.93{\times}10^{-4}{\pm}4.21{\times}10^{-6},\;126.60{\pm}21.88min\;(control\;:\;Papp\;0.45{\times}10^{-4};\;lag\;time\;211.01{\pm}16.77\;min)$, respectively.

A Bayesian Approach for the Analysis of Times to Multiple Events : An Application on Healthcare Data (다사건 시계열 자료 분석을 위한 베이지안 기반의 통계적 접근의 응용)

  • Seok, Junhee;Kang, Yeong Seon
    • Journal of the Korean Operations Research and Management Science Society
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    • v.39 no.4
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    • pp.51-69
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    • 2014
  • Times to multiple events (TMEs) are a major data type in large-scale business and medical data. Despite its importance, the analysis of TME data has not been well studied because of the analysis difficulty from censoring of observation. To address this difficulty, we have developed a Bayesian-based multivariate survival analysis method, which can successfully estimate the joint probability density of survival times. In this work, we extended this method for the analysis of precedence, dependency and causality among multiple events. We applied this method to the electronic health records of 2,111 patients in a children's hospital in the US and the proposed analysis successfully shows the relation between times to two types of hospital visits for different medical issues. The overall result implies the usefulness of the multivariate survival analysis method in large-scale big data in a variety of areas including marketing, human resources, and e-commerce. Lastly, we suggest our future research directions based multivariate survival analysis method.

Effect of glucose level on chemical hypoxia- and hydrogen peroxide-induced chemokine expression in human glioblastoma cell lines

  • Jung, Yieun;Ahn, So-Hee;Park, Sang Hui;Choi, Youn-Hee
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.5
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    • pp.509-518
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    • 2017
  • Glioblastoma multiforme (GBM) is the most common primary intracranial tumor in adults and has poor prognosis. The GBM-specific tumor microenvironment (TME) plays a crucial role in tumor progression, immune escape, local invasion, and metastasis of GBM. Here, we demonstrate that hypoxia, reactive oxygen species (ROS), and differential concentration of glucose influence the expression of cytokines and chemokines, such as IL-6, IL-8, and IP-10, in human glial cell lines. Treatment with cobalt chloride ($CoCl_2$) and hydrogen peroxide ($H_2O_2$) significantly increased the expression levels of IL-6, IL-8, and IP-10 in a dose-dependent manner in CRT-MG and U251-MG astroglioma cells, but not in microglia cells. However, we found strikingly different patterns of expression of cytokines and chemokines between $H_2O_2$-treated CRT-MG cells cultured in low- and high-glucose medium. These results suggest that astroglioma and microglia cells exhibit distinct patterns of cytokine and chemokine expression in response to $CoCl_2$ and $H_2O_2$ treatment, and different concentrations of glucose influence this expression under either hypoxic or oxidant-enriched conditions.

Resistance of Varieties Bred by Crossing with Asominori to Bacterial Leaf Blight (벼 아소미노리 교배조합 품종의 벼흰잎마름병 저항성)

  • 심재성
    • Korean Journal of Plant Resources
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    • v.10 no.2
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    • pp.128-134
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    • 1997
  • This study was conducted to test on the resistance of varieties bred by crossing with Asominori to bacterial leaf blight. Nakdongbyeo and Dongjinbyeo which were susceptible to HB 9011, 8 resistant varieties including Ilmibyeo derived from Asominori and Asominori, Hwangok, 13 varieties including Chukoku 45 which were resistance to HB 9011, HB 9022 and HB 9033 were used to screen their res ponce depending on the various screening methods such as the true resistance, the secondary infection resistance and the disease common field test methods, and the results are as follows: Among 13 varieties tested, 11 varieties including llmibyeo showed tme resistance to HB 9011. Less than 1.0cm of disease lesion were developed on these varieties. Disease lesion was not developed on most of the Asominori lines including Daechongbyeo against IIB9011 and 1lmibyeo was also resistance to HB 9011, on this variety disease lesion area rate was 1.2%, and 7 varieties including Hwajinbyeo showed field resistance to HB 9022. Disease lesion area rate were 19.6% on Nakdongbyeo. 15.6% on Dongjinbyeo, from 3.0% to 2.4% on Asominori lines, and 0.5% on the Asominori when screened at disease common area. Disease was not developed on Keumnambyeo. Significant correlation coefficiences were found between the results from the test methods of the true resistance, the field resistance ancl the field resistance at disease common field tests on Asominori lines, but in some cases, even the varieties on which disease lesions developed, showed field resistance to HB 9022 and HB 9033.

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Nutrient Digestibility of Palm Kernel Cake for Muscovy Ducks

  • Mustafa, M.F.;Alimon, A.R.;Zahari, M.W.;Idris, I.;Bejo, M. Hair
    • Asian-Australasian Journal of Animal Sciences
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    • v.17 no.4
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    • pp.514-517
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    • 2004
  • Expeller pressed and solvent extracted palm kernel cake (PKC) were force-fed to male and female Muscovy ducks at 7 weeks of age. The nutrient digestibility, apparent metabolizable energy (AME), true metabolizable energy (TME) and true available amino acid (TAAA) digestibilities were determined. There was no significant (p>0.05) effect of the type of PKC used on crude protein (CP), ether extract (EE), metabolizable energy (ME) and amino acid (AA) digestibilities. However, digestibilities of dry matter (DM) and neutral detergent fibre (NDF) was found to be higher in solvent extracted compared to expeller pressed PKC. The average digestibility of DM, CP, NDF and EE were 43, 58, 39 and 89%, espectively. It was found that the ducks utilized about 47% of the gross energy of PKC. The respective average AMEn and TMEn values of PKC for Muscovy ducks was 1,743 and 1,874 kcal/kg. The overall TAAA of PKC for Muscovy ducks was 65%. The data on the TMEn and digestible AA for PKC obtained from this study provide new information with regard to diet formulation for Muscovy ducks.