• Tuberculosis and Respiratory Diseases
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• v.80 no.2
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• pp.187-193
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• 2017

Background: Third-generation tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKIs) have proved efficacious in treating non-small cell lung cancer (NSCLC) patients with acquired resistance resulting from the T790M mutation. However, since almost 50% patients with the acquired resistance do not harbor the T790M mutation, retreatment with first- or second-generation EGFR-TKIs may be a more viable therapeutic option. Here, we identified positive response predictors to retreatment, in patients who switched to a different EGFR-TKI, following initial treatment failure. Methods: This study retrospectively reviewed the medical records of 42 NSCLC patients with EGFR mutations, whose cancers had progressed following initial treatment with gefitinib or erlotinib, and who had switched to a different first-generation EGFR-TKI during subsequent retreatment. To identify high response rate predictors in the changed EGFR-TKI retreatment, we analyzed the relationship between clinical and demographic parameters, and positive clinical outcomes, following retreatment with EGFR-TKI. Results: Overall, 30 (71.4%) patients received gefitinib and 12 (28.6%) patients received erlotinib as their first EGFR-TKI treatment. Following retreatment with a different EGFR-TKI, the overall response and disease control rates were 21.4% and 64.3%, respectively. There was no significant association between their overall responses. The median progression-free survival (PFS) after retreatment was 2.0 months. However, PFS was significantly longer in patients whose time to progression was ${\geq}10months$ following initial EGFR-TKI treatment, who had a mutation of exon 19, or whose treatment interval was <90 days. Conclusion: In patients with acquired resistance to initial EGFR-TKI therapy, switched EGFR-TKI retreatment may be a salvage therapy for individuals possessing positive retreatment response predictors.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.4 no.1
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• pp.211-232
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• 1998

Because there were lots of side effects and tolerances to the existing anticancer therapeutics, the experiment extracting the anticancer effect from medicinal herbs is in progress liviely. Therefore the purpose of this study were to research the tendency and the course of anticancer studies. To research the tendency of anticancer studies, medicinal herbs of fifty three experimental papers were analyzed and to examine the course of studies, anticancer papers in the medical world were used. The obtained results were as follows: Methods of herbal medicinal treatments were elimination the pathogenic factor(祛邪) and supporting healthy energy(扶正) method used. In this study, immediately tumor bearing and immune response were the most important point. The subject of immediately tumor bearing was not in the specific cancer but in the influence on the life span of general cencerous cells. In the experimental study of immune response, the effect on NK cell activity of medicinal herbs most studied. The combined usage of medicinal herbs and anticancer agent mostly intended to know whether it inhibits the tumor cell growth. The serum test and blood cell number test show if medicinal herbs inhibit side effect of anticancer agent. More than 80 percents of used medicinal herbs, there were anticancer activities. However anticancer experimental studies using medicinal herbs two weak points. The one, it was difficult to choose a prescription according to differentiation of symptoms and signs(辨證論) of the Oriental Medicine, because we put to the test not a man but a mouse. The other, as we observed the indirect effect of the whole physiological regulation caused by synergic effects of the complex prescription, we don't understand the detailed mechanism of the herb. Therefore, if the anticancer effect of the herb is proved the experiment, we should research the concrete medical action of medicinal herbs and immunological analysis of herbal medicines to the body.

• Proceedings of the Korea Society of Poultry Science Conference
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• 2000.11a
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• pp.81-84
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• 2000

Effects of different photoperiod regimens on the cellular and humoral immunity in broiler chickens were studied(Exp 1). Total one hundred ninety two one-day-old commercial broiler chicks(Cobb$\times$Cobb) were raised between constant lighting(CL) and intermittent lighting (1h light: 3h darkness(IL; 1l; 3D) Body weight, feed intake and feed conversion were measured for seven week. Peripheral blood and splenic lymphocyte activities were tested at 3 and 5 wk of age by performing a mitogen cellproliferation assay with a polyclonal T-cell mitogen, concanavalin A (Con A), and B-cell mitogen, lipopolysaccharide (LPS). To investigate the effect of photoperiod on the humoral immunity, chicks were immunized with sheep red blood cell(SRBC) and iinactivated Newcastle disease virus(NDV) vaccine. Total immunoglobulin G(IgG) concentration was also determined. Diurnal change of melatonin was tested in sera. In experiment 2, 0.1ml melatonin were subcutaneously injected from three to five weeks old if immunomodulation effect of lighting regimen was due to the melatonin or not. Injections of melatonin were made at 0700h and the dosage was 10ng (M2), 100ng(M3), 1$\mu\textrm{g}$(M4) per bird daily, respectively. control were quivalent injections of vehicle(M1). Lymphocyte activities were tested and humoral immunities were examined at 5 weeks of age. Blood melatonin concentration was determined at 0h, 1, h, 2h, and 3h posterior to injection at five weeks old. It was higher in CL chicks than IL chickens during the subsequent period of 3 to 5 wk of age. However, weight gain of chicks raised IL were significantly higher at 6 wk of age than CL(P<0.05). Antibody response to NDV was not affected by both photoperiod regimens and melatonin injection, whereas anti-SRMB titer and IgG concentration were enhanced. Lymphocyte activity of chickens raised under IL was sighificantly higher than those of chickens raised under CL. Melatonin injection also increased lymphocyte activity. When peripheral blood lymphocytes were used, proliferation response to LPS and Con A were significantly increased in M2 and respectively. The results of this experiments suggest that IL improved host immune response and melatonin have immunomodulatory roles.

• The Korea Journal of Herbology
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• v.32 no.5
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• pp.27-38
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• 2017

Objective : In the present study, we examined whether Canavalia gladiata D.C. (CG) and Arctium lappa L., Redix (AL) mixture (CGAL), their components, lupeol and chicoric acid, regulate immune system and suppress the tumor in vitro and in vivo. Methods : LPS-induced reactive oxygen species (ROS) and nitric oxide (NO) were measured after treatment with CG extract (CGE), CGAL, lupeol, chicoric acid and lupeol and chicoric acid mixture (lupeol+CA) in Raw264.7 cell. To determine the effect of CGE on immune responses, immune cell population and IgG production were assessed in mice. To investigate the effect of CGAL and their component on anti-tumor activity, tumor volume and weight were measured, cell cycles and immune cell population were analyzed in MC38 injected tumor bearing mice. Also, NK cell activity was determined in splenocyte isolated from tumor bearing mice. Results : CGE, CGAL, lupeol, chicoric acid and lupeol+CA decreased the LPS-induced ROS and NO production without cell toxicity in RAW264.7 cells. CGE increased the immune cell populations of $CD4^+T$, $CD8^+T$ and macrophages in various immune organ of mice. In tumor bearing mice, CGAL, lupeol, chicoric acid and lupeol+CA suppressed tumor volume and weight. In cell cycle analysis, they decreased the percentages of S phase. In addition, CGAL, lupeol, chicoric acid and lupeol+CA immune cell populations of $CD4^+T$, $CD8^+Tcell$, NK cell and macrophage in tumor as well as NK cell activity. Conclusion : CGAL and its compounds may enhance immune responses and suppress tumor growth, and may be capable of developing health functional foods.

• BMB Reports
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• v.49 no.10
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• pp.554-559
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• 2016

Mycobacterium abscessus, a member of the group of non-tuberculous mycobacteria, has been identified as an emerging pulmonary pathogen in humans. However, little is known about the protective immune response of antigen-presenting cells, such as dendritic cells (DCs), which guard against M. abscessus infection. The M. abscessus gene MAB1843 encodes ᴅ-alanyl-ᴅ-alanine dipeptidase, which catalyzes the hydrolysis of ᴅ-alanyl-ᴅ-alanine dipeptide. We investigated whether MAB1843 is able to interact with DCs to enhance the effectiveness of the host's immune response. MAB1843 was found to induce DC maturation via toll-like receptor 4 and its downstream signaling pathways, such as the mitogen-activated protein kinase and nuclear factor kappa B pathways. In addition, MAB1843-treated DCs stimulated the proliferation of T cells and promoted Th1 polarization. Our results indicate that MAB1843 could potentially regulate the immune response to M. abscessus, making it important in the development of an effective vaccine against this mycobacterium.

• Journal of Life Science
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• v.34 no.5
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• pp.356-364
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• 2024

Lymph nodes (LNs) are crucial sites where immune responses are initiated to combat invading pathogens in the body. LNs are organized into distinctive compartments by stromal cells. Stromal cell subsets constitute special niches supporting the trafficking, activation, differentiation, and crosstalk of immune cells in LNs. Fibroblastic reticular cells (FRC) are a type of stromal cell that form the three-dimensional structure networks of the T cell-rich zones in LNs, providing guidance paths for immigrating T lymphocytes. FRCs imprint immune responses by supporting LN architecture, recruiting immune cells, coordinating immune cell crosstalk, and presenting antigens. During inflammation, FRCs exert both spatial and molecular regulation on immune cells through their topological and secretory responses, thereby steering immune responses. Here, we propose a model in which FRCs regulate immune responses through a three-part scheme: setting up, supporting, or suppressing immune responses. FRCs engage in bidirectional interactions that enhance T cell biological efficiency. In addition, FRCs have profound effects on the innate immune response through phagocytosis. Thus, FRCs in LNs act as gatekeepers of immune responses. Overall, this study aims to highlight the emerging roles of FRCs in controlling both innate and adaptive immunity. This collaborative feedback loop mediated by FRCs may help maintain tissue function during inflammatory responses.

• Parasites, Hosts and Diseases
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• v.50 no.1
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• pp.29-35
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• 2012

The aim of the study is to characterize the phenotypes of $CD4^+$ $CD25^+$ T regulatory cells within the liver granulomas and association with both Foxp-3 gene expression and splenic cytokines. Naive C57BL/6 mice were intravenously injected with multiple doses of the soluble egg antigen (SEA) 7 days before cercarial infection. The immunized and infected control groups were sacrificed 8 and 16 weeks post-infection (PI). Histopathology, parasitological parameters, splenic phenotypes for T regulatory cells, the FOXP-3 expression in hepatic granuloma using real-time PCR, and the associated splenic cytokines were studied. Histopathological examination of the liver revealed remarkable increase in degenerated ova within hepatic granuloma which decreased in diameter at weeks 8 and 16 PI ($P$<0.01). The percentage of T regulatory cells ($CD4^+$ $CD25^+$) increased significantly ($P$<0.01) in the immunized group compared to the infected control at weeks 8 and 16 PI. The FOXP-3 expression in hepatic granulomas increased from 10 at week 8 to 30 fold at week 16 PI in the infected control group. However, its expression in the immunized group showed an increase from 30 at week 8 to 70 fold at week 16 PI. The splenic cytokine levels of pro-inflammatory cytokines, IFN-${\gamma}$, IL-4, and TNF-${\alpha}$, showed significant decreases ($P$<0.05) compared to the infected control group. In conclusion, the magnitude and phenotype of the egg-induced effects on T helper responses were found to be controlled by a parallel response within the T regulatory population which provides protection in worm parasite-induced immunopathology.

• Animal cells and systems
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• v.13 no.4
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• pp.429-437
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• 2009

The control mechanism of gonadotropin-releasing hormone (GnRH) on gonadotropin (GTH) release was studied using cultured pituitary cell or cultured whole pituitary obtained from Testosterone (T) treated and control immature rainbow trout. The release of FSH was not changed by salmon type GnRH (sGnRH), chiken-II type (cGnRH-II), GnRH analogue ([des-$Gly^{10}D-Ala^6$] GnRH ethylamide) and GnRH antagonist ([Ac-3, 4-dehydro-$Pro^1$, D-p-F-$Phe^2$, D-$Trp^{3,6}$] GnRH) in cultured pituitary cells of T-treated and control fish. Indeed, FSH release was not also altered by sGnRH in cultured whole pituitary. All tested drugs had no effect on the release of LH in both culture systems of control fish. The levels of LH, in contrast, such as the pituitary content, basal release and responsiveness to GnRH were increased by T administration in both culture systems. In addition, the release of LH in response to sGnRH or cGnRH-II induced in a dose-dependent manner from cultured pituitary cells of T-treated fish, but which is not significantly different between in both GnRH at the concentration examined. Indeed, LH release was also increased by sGnRH in cultured whole pituitary of T-treated fish. GnRH antagonist suppressed the release of LH by sGnRH ($10^{-8}\;M$) and GnRH analogue ($10^{-8}\;M$) stimulation in a dose-dependent manner from cultured pituitary cells of T-treated fish, and which were totally inhibited by $10^{-7}\;M$ GnRH antagonist. These results indicate that the sensitivity of pituitary cells to GnRH is elevated probably through the T treatment, and that GnRH is involved in the regulation of LH release. GnRH-stimulated LH release is inhibited by GnRH antagonist in a dose-dependent manner. The effects of gonadal steroids on FSH levels are less clear.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.2
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• pp.278-286
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• 2004

The objective of the current study was to determine the effects of arabinoxylane and PSP on mouse splenocytes, T cells, B cells and macrophages in vitro. Arabinoxylane and PSP directly induced the proliferation of spleen cells in a dose-dependent manner and increased IFN-${\gamma}$ synthesis. Especially, PSP induced IL-2, IL-4 and IL-10 production, Both arabinoxylane and PSP increased PFC (plaque forming cell) and RFC (rosette forming cell) formation. Arabinoxylane was not induced the proliferation of T cells, but PSP directly induced the proliferation of T cells in a high dose. Arabinoxylane and PSP increased the proliferation of B cells and the phagocytic effects of macrophage. When arabinoxylane and PSP were used in macrophage cell line stimulation, there was a marked induction of NO synthesis in a dose-dependent and an increased TNF-$\alpha$ and IL-6 synthesis. Especially, PSP also induced IL-1$\beta$ production. When arabinoxylane and PSP treated in macrophage cell line, there was induction of MHC class II expression. These results suggest that the capacity of arabinoxylane andPSP seem to act as a potent immunomodulator causing augmentation of immune cell activity, and with the absence of notable side-effects, arabinoxylane and PSP could be used as a biological response modifier having possible therapeutic effects against immunological disorders.

• Toxicological Research
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• v.21 no.4
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• pp.333-338
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• 2005

Many of thyroid hormones disrupting chemicals induce effects via interaction with thyroid hormone and retinoic acid receptors and responsive elements intrinsic in target cells. We studied thyroid hormones disrupting effects of food additives and contaminants including BHA, BHT, ethoxyquin, propionic acid, sorbic acid, benzoic acid, CPM, aflatoxin B1, cadmium chloride, genistein, TCDD, PCBs and TDBE in recombinant HeLa cells containing plasmid construct for thyroxin responsive elements. The limit of response of the recombinant cells to T3 and T4 was $1\times10^{-12}\;M$. BHA. genistein, cadmium and TBDE were interacted with thyroid receptors with dose-responsive pattern. In addition, BHA, BHT, ethoxyquin, propionic acid, benzoic acid, sorbic acid, and TBDE showed synergism while cadmium chloride antagonism for T3-induced activity. This study elucidates that recombinant HeLa cell is sensitive and high-throughput system for the detection of chemicals that induce thyroid hormonal disruption via thyroid hormone receptors and responsive elements. Also this study raised suspect of BHA. BHT, ethoxyquin, propionic acid, benzoic acid, sorbic acid, TBDE, genisteine and cadmium chloride as thyroid hormonal system disruptors.