Immune checkpoint inhibition has been established as a new treatment option for various types of carcinoma, and many clinical trials are being actively conducted as a treatment for advanced or metastatic gastric cancer, either as a monotherapy with an immune checkpoint inhibitor or as a combination therapy with standard chemotherapy. In the CheckMate-649 clinical trial to confirm the efficacy of the combination of nivolumab and chemotherapy (FP) in advanced gastric cancer and gastroesophageal junction cancer, nivolumab group showed improvement in overall survival in programmed death ligand 1-positive cancer patients compared with placebo group. Also, the combination therapy of pembrolizumab, trastuzumab and chemotherapy (FP) in first-line treatment was tested through the KEYNOTE-811 trial. The pembrolizumab group showed 22.7% of improvement in objective response rate compared with placebo group. Accordingly, the combination of nivolumab/pembrolizumab with standard chemotherapy was approved for the first-line treatment. In KEYNOTE-059 trials for patients with progressive disease after at least two lines of chemotherapy, pembrolizumab monotherapy showed improvement in objective response rate and overall survival, and the use of pembrolizumab was approved for the third-line or more treatment. In this article, we review the result of clinical trials related to immune checkpoint inhibitors that have been recently introduced in the treatment of gastric cancer.
Panda, A.K.;Raju, M.V.L.N.;Rao, S.V. Rama;Lavanya, G.;Reddy, E. Pradeep Kumar;Sunder, G. Shyam
Asian-Australasian Journal of Animal Sciences
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제23권12호
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pp.1626-1631
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2010
An experiment was conducted to evaluate the effect of dietary replacement of normal maize (NM) with quality protein maize (QPM) on performance, immune response and carcass characteristics of broiler (Krishibro) chickens. Six experimental diets were prepared separately for starter and finisher phases. Diet 1 was a control diet formulated with NM and soybean meal. In diets 2-5, the NM was replaced with QPM at 25, 50, 75 and 100%, respectively. Diet 6 was the same as the control diet, but supplemented with synthetic lysine similar to the industry standard. Each test diet was fed to 8 replicates, each of 5 chicks, reared in stainless steel battery brooders. The AME content of QPM (3382 kcal/kg) was similar to that of NM (3,352 kcal/kg), but protein (9.91 vs. 8.94%), lysine (0.40 vs. 0.26%) and tryptophan (0.09 vs. 0.07%) contents of QPM were higher than NM. Dietary replacement of NM with 50% QPM significantly (p<0.05) improved body weight gain, feed conversion ratio, humoral immune response, relative bursa weight, and breast muscle yield and lowered abdominal fat content. No further improvement in these parameters was recorded by increasing the level of replacement of NM with QPM to either 75% or 100%. Further, the improvement noticed in the 50% QPM group was similar to the group fed the NM diet with lysine supplementation, and thus dietary replacement of NM with QPM at 50% did not need extra synthetic lysine supplementation. It is concluded that dietary replacement of NM with QPM at the 50% level resulted in optimum performance, higher breast muscle yield and higher immune response in broiler chickens.
Objectives : This study was performed to investigate the effects of anti-cancer and changes In immune response of Lonicerge Flos Herbal-acupuncture. Methods Experimental studies were evaluated through the anti-cancer and immune response activities such as, cell viability, BNA fragmentation, Apoptosis, survival time, pulmonary colonization, and productivity of interleukins & $interferon-{\gamma}$. In order to study the effects of anti-cancer and changes in immune response of Lonicerae Flos Herbal-acupuncture, the groups were divided into five groups ; Normal group(non treated group), Control A group(0.2ml Normal saline for oral administration), Control B group(administration of intramuscular injection with 0.2ml Lonicerae Flos Herbal-acupuncture solution), Acupuncture group(AT, administration of acupuncture at Chungbu(L1)), and Herbal-Acupuncture group(HAT, administration of Lonicerae Flos Herbal-acupuncture at Chungbu(L1)). Results : 1. Lonicerae Flos Herbal-acupuncture(>300mg/ml) could lead cancer cell to cell death. 2. Lonicerae Flos Herbal - acupuncture (40mg/ml) caused DNA cleavage. 3. Lonicerae Flos Herbal-acupuncture(400mg/ml) caused apoptosis in the cancer cell line. 4. In mouse survival time, all of experimental groups didn't show any significant compared to the control group. 5. In pulmonary colonization assay, Lonicerae Flos Herbal-acupuncture group was less than Control A group at 7 days after induction of cancer. 6. In comparison Control A group, there was significant decrease of Interleukin-2 level in Lonicerae Flos Herbal-acupuncture group. 7. In comparison Control group, there was decrease of Interleukin-4 level in the Acupuncture group. 8. In comparison Control group, there was decrease of Interleukin-10 level in the Acupuncture group. 9. In comparison Control group, there was significant increase of Interleukin-12 level in Acupuncture group and Lonicerae Flos Herbal-acupuncture group. 10. In comparison Control group, there was significant increase of $Interferon-{\gamma}$ level in Acupuncture group. Conclusion : According to above mentioned results, Lonicerae Flos Herbal- acupuncture is expected to be effective for anticancer and improvement in immune response.
Kim, Ji Young;Choung, Sorim;Lee, Eun-Ju;Kim, Young Joo;Choi, Young-Chul
Molecules and Cells
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제24권2호
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pp.247-254
/
2007
Improvement in the pharmacokinetic properties of short interfering RNAs (siRNAs) is a prerequisite for the therapeutic application of RNA interference technology. When injected into mice as unmodified siRNAs complexed to DOTAP/Chol-based cationic liposomes, all 12 tested siRNA duplexes caused a strong induction of cytokines including interferon ${\alpha}$, indicating that the immune activation by siRNA duplexes is independent of sequence context. When modified by various combinations of 2'-OMe, 2'-F, and phosphorothioate substitutions, introduction of as little as three 2'-OMe substitutions into the sense strand was sufficient to suppress immune activation by siRNA duplexes, whereas the same modifications were much less efficient at inhibiting the immune response of single stranded siRNAs. It is unlikely that Toll-like receptor 3 (TLR3) signaling is involved in immune stimulation by siRNA/liposome complexes since potent immune activation by ds siRNAs was induced in TLR3 knockout mice. Together, our results indicate that chemical modification of siRNA provides an effective means to avoid unwanted immune activation by therapeutic siRNAs. This improvement in the in vivo properties of siRNAs should greatly facilitate successful development of siRNA therapeutics.
In this paper, cell-mediated immune algorithm(CMIA) controller was proposed and applied for the autonomous guided vehicle(AGV) driving. It was based on specific immune response of the biological immune system which is the cell-mediated immunity. To verify the performance of the designed CMIA controller, some experiments were performed for the control of steering and speed of AGV. And then the displacement and speed tracking error of the AGV was mainly investigated. As results, the capability of realization and reliableness were proved by comparing the response characteristics of the classical controller with the proposed CMIA controller.
Objective : This study was purposed to investigate the anti-cancer and anti-metastasis and immune response of Aqua-acupuncture with Amomum amarum Lourerio infusion solution. Methods : The Amomum amarum Lourerio infusion solution put into Chung-wan(CV12) of BALB/c or C57BL6 mice were rised to cancer by B15-F10 and HT1080, S-180 cancer cell line. Results : The following result have been obtained 1. The effect on expression of MMP-9 gene about the HT1080 cancer cell line was increased in 100, $50{\mu}g/m{\ell}$ diluent groups, compared with control group. 2. The effect on expression of MMP-9 gene about the B15-F10 cancer cell line was increased in all the sample groups, compared with control group. 3. S-180 cancer cell line transplants in BALB/c mice were inhibited significantly in weight inctease in all the sample groups, compared with control group. 4. The effect on spleen cell proliferation was decreased in all the sample groups, compared with control group. 5. The $IFN-{\gamma}$ in all the sample groups and the $TNF-{\alpha}$ in 25 and $12.5{\mu}g/m{\ell}$ diluent groups was increased. 6. In flow cytometry, the number of CD4+, CD19+ cell in all the sample group was increased and the number of CD8+ cell in $100{\mu}g/m{\ell}$ diluent group, compared with control group. Conclusion : According to the result, Aqua-acupuncture with Amomum amarum Lourerio infusion solution has significant anti-cancer, anti-metastasis and Immune response improvement.
Object : Currently, the alteration of cytokine system has been known to play an important role in regard to depressive symptom. We focused on the relationship between immunological parameters and clinical improvement in major depressive disorder. Method : Data were collected on 26 patients with major depressive disorder using a 8-week prospective follow-up design. After 8-week treatment period with fluoxetine, patients were classified into a response group and a non-response group according to their psychopathological outcome as evaluated by Hamilton Depression Rating Scale. The differences of the immunological parameters between pre-treatment phase and post-treatment phase were compared among patients. The difference of those was also compared within each phase among them. The relationship between socio-demographic variables, depression, cytokine, mononuclear cells was examined by correlation analysis. Multiple regression analyses were performed to explore the predictors of clinical improvement of major depressive disorder. Result : Pre-treatment levels of IL-$1{\beta}$ in the response group were significantly higher than those in the non-response group. Pre-treatment levels of IL-$1{\beta}$ of all patients and in the response group were positively correlated with pre-treatment monocyte counts. Patients with subsequent remission showed significantly lower IL-6 values at baseline than those with non-response. Post-treatment values of IL-6 did not differ significantly among the patients. The correlation test showed more frequent relations among cytokines and mononuclear cells in the response group than in the non-responder group. Especially, serum level of IL-6 in pre-treatment phase was only significantly correlated with HAMD score after 8-week treatement phase, while other cytokines and mononuclear cells were not. Pretreatment level of IL-6 was of paramount importance in predicting clinical improvement of depressive symptom. Conclusion : The immune system of major depressive disorder patients might dichotomize the patients into subsequent responders and non-responders. Immune system might be of great influence on the clinical improvement of major depressive disorder. The mode of interaction between depression and cellular immune function and the mediators responsible for the cytokine production need to be studied further.
An experiment was conducted using 20 male buffalo calves to study the effect of vitamin E and selenium supplementation on their immune response and plasma ${\alpha}$-tocopherol and selenium status. These buffalo calves (10-12 months old, average body weight $75.30{\pm}2.20 $ kg) were randomly allotted to four treatments on the basis of their body weights and were fed on wheat straw and concentrate mixture to meet their nutrient requirements of 500 g/d body weight gain. The buffalo calves were fed either a control diet (neither supplemented with Se nor VE) or diets supplemented with Se at 0.3 ppm (+Se), DL-alpha tocopheryl acetate at 300 IU (+VE), and both DL-alpha tocopheryl acetate at 300 IU and Se at 0.3 ppm (+Se+VE). These experimental diets were fed for 180 days. Blood samples were collected at day 0 and subsequently at 45 day intervals up to 180 days of experimental feeding to monitor plasma ${\alpha}$-tocopherol and Se concentrations. To assess humoral immune response, all calves were sensitized with formalin inactivated Pasteurella multocida antigen at 135 days of experimental feeding and blood was collected on 0, 7, 14, 21 and 28 days post vaccination (DPV) to measure antibody production using indirect ELISA. Cell mediated immune response of calves was assessed after 180 days of experimental feeding by in vivo delayed type hypersensitivity (DTH) reaction using phytohaemaglutinin-P (PHA-P) as a mitogen. Results revealed that feeding of VE and Se improved the plasma levels of these nutrients. Plasma levels of Se were affected by supplementation of both VE (p<0.001) and Se (p<0.001); however, no interaction ($Se{\times}VE$) was observed. Supplementation of Se improved the humoral immune response (p<0.008), whereas, VE showed a tendency towards improvement in cell mediated immune response (p<0.064). It was concluded that vitamin E and Se supplementation improved the status of these micronutrients and humoral immune response in buffalo calves.
Objectives and methods : To study on the anti-cancer, anti-metastasis and immune response improvement effects of Herbal-acupuncture with Sinomenii acuti Lignum infusion solution(SAL-HAS), we injected Sinomenii acuti Lignum infusion solution into Joksamni$(ST_{36})$ of C57BL/6 mouse which is corresponding to human Joksamni(ST36). We observed its effect on the number of $CD25^+/CD4^+,\;CD8^+/CD3e^+,\;CD69^+/B220^+,\;NK1.1^+/CD3e^+$ cells in mouse PBMCs(peripheral blood mononuclear cells), the number of the pulmonary colony, and the effect on MST(mean survival time) and ILS(increase in MST over control) of C57BL/6 mice implanted intravenously with B16-F10 melanoma. Results and Conclusions : 1. The spleen cells proliferation of the sample groups treated with SAL-HAS extract has increased significantly compared with that of the control group. 2. The percentage of the $CD25^+/CD4^+,\;CD8^+/CD3e^+,\;CD69^+/B220^+,\;NK1.1^+/CD3e^+$ cells in C57BL/6 mouse PBMCs of the sample groups treated with SAL-HAS has increased compared with that of the control group. 3. The pulmonary colony number of the sample groups SAL-HAS has decreased significantly compared with that of the control group. 4. MST and ILS of the sample groups SAL-HAS have increased significantly compared with those of the control group.
Objectives and methods : Study the anti-cancer, anti-metastasis and immune response improvement effects of Herbal-acupuncture with Evodiae Fructus infusion solution, we injected Evodiae Fructus infusion solution into Zusanli(St36) of C57BL/6 mouse which is corresponding to human Zusanli(St36). We observed its effect on the number of $CD25^+/CD4^+,\;CD8^+/CD3e^+,\;CD69^+/B220^+,\;NK1.1^+/CD3e^+$ cells in mouse PBMCs, the number of the pulmonary colony , MST and ILS of C57BL/6 mice implanted intravenously with B16-F10 melanoma. Results and Conclusions : The spleen cells proliferation of the sample groups treated with EDR-HAS extract has increased significantly compared with that of the control group. The percentage of the $CD25^+/CD4^+,\;CD8^+/CD3e^+,\;CD69^+/B220^+,\;NK1.1^+/CD3e^+$ cells in C57BL/6 mouse PBMCs of the sample groups treated with EDR herbal-acupuncture has increased compared with that of the control group. The lung colony number of the sample groups treated with EDR herbal-acupuncture has decreased significantly compared with that of the control group. MST and ILS of the sample groups treated with EDR herbal-acupuncture have increased significantly compared with those of the control group.
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