Browsing by Author "Lin, Chen-Si"

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A potential role for Helicobacter pylori heat shock protein 60 in gastric tumorigenesis
(2010-02-05)
Lin, Chen-Si
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He, Pei-Juin
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Tsai, Nu-Man
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Li, Chi-Han
;
Yang, Shang-Chih
Helicobacter pylon has been found to promote the malignant process leading to gastric cancer. Heat shock protein 60 of H. pylori (HpHSP60) was previously been identified as a potent immunogene. This Study investigates the role of HpHSP60 in gastric cancer carcinogenesis. The effect of HpHSP60 on cell proliferation, anti-death activity, angiogenesis and cell migration were explored. The results showed that HpHSP60 enhanced migration by gastric cancer cells and promoted tube formation by umbilical vein endothelial cells (HUVECs); however, HpHSP60 did not increase cell Proliferation nor was this protein able to rescue gastric cancer cells from death. Moreover, the results also indicated HpHSP60 had different effects on AGS gastric cancer cells or THP-1 monocytic cells in terms of their expression of pro-inflammatory cytokines, which are known to be important to cancer development. We propose that HpHSP60 may trigger the initiation of carcinogenesis by inducing pro-inflammatory cytokine release and by promoting angiogenesis and metastasis. Thus, this extracellular pathogen-derived HSP60 is potentially a vigorous virulence factor that can act as a carcinogen during gastric tumorigenesis. (C) 2010 Elsevier Inc. All rights reserved.
Antibodies against Helicobacter pylori heat shock protein 60 aggravate HSP60-mediated proinflammatory responses
(2011-08-01)
Liao, Kuang-Wen
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Lin, Chen-Si
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Chen, Wen-Liang
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Yang, Chu-Ting
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Lin, Ching-Min
Anti-Helicobacter pylori heat shock protein 60 (HpHSP60) antibodies are Usually found in H. pylori-infected patients and are known to be associated with the progression of gastric diseases. However, the effects of these antibodies on the functions of HpHSP60 have not been identified. This study aims to investigate the effects of the interaction between anti-HSP60 antibodies and HpHSP60 on inflammatory responses. Anti-HpHSP60 polyclonal sera and monoclonal antibodies (mAbs) were produced to evaluate their effects on HpHSP60-induced IL-8 and TNF-alpha activity. The results indicated that anti-HpHSP60 polyclonal sera collected from patients infected with H. pylori or from rabbit and mice immunized with HpHSP60 could significantly enhance HpHSP60-mediated IL-8 and TNF-alpha secretion from monocytic THP-1 cells. Similar effects were also found with anti-HpHSP60 mAbs. Further analysis revealed that this phenomenon was only carried out by anti-HpHSP60 antibody but not by other non-specific mAbs. Moreover, the non-specific mAbs decreased the synergism of HpHSP60 and anti-HpHSP60 mAbs in proinflammatory cytokine induction. Herein, we have examined the role of anti-HpHSP60 antibody in host immune responses for the first time. This study demonstrated that H. pylori HSP60/mAbs could modulate helico-bacterial pathogenesis by increasing IL-8 and TNF-alpha production. The pathogen-specific antibodies may execute potential immune functions rather than recognize or neutralize microbes. (C) 2011 Elsevier Ltd. All rights reserved.
Enhancement of anti-murine colon cancer immunity by fusion of a SARS fragment to a low-immunogenic carcinoembryonic antigen
(1970-01-01)
Lin, Chen-Si
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Kao, Shih-Han
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Chen, Yu-Cheng
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Li, Chi-Han
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Hsieh, Yuan-Ting
"Background: It is widely understood that tumor cells express tumor-associated antigens (TAAs), of which many are usually in low immunogenicity; for example, carcinoembryonic antigen (CEA) is specifically expressed on human colon cancer cells and is viewed as a low-immunogenic TAA. How to activate host immunity against specific TAAs and to suppress tumor growth therefore becomes important in cancer therapy development. Results: To enhance the immune efficiency of CEA in mice that received, we fused a partial CEA gene with exogenous SARS-CoV fragments. Oral vaccination of an attenuated Salmonella typhimurium strain transformed with plasmids encoding CEA-SARS-CoV fusion gene into BALB/c mice elicited significant increases in TNF-alpha and IL-10 in the serum. In addition, a smaller tumor volume was observed in CT26/CEA-bearing mice who received CEA-SARS-CoV gene therapy in comparison with those administered CEA alone. Conclusion: The administration of fusing CEA-SARS-CoV fragments may provide a promising strategy for strengthening the anti-tumor efficacy against low-immunogenic endogenous tumor antigens."
Helicobacter pylori-derived Heat shock protein 60 enhances angiogenesis via a CXCR2-mediated signaling pathway
(2010-06-25)
Lin, Chen-Si
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He, Pei-Juin
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Hsu, Wei-Tung
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Wu, Ming-Shiang
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Wu, Chang-Jer
Helicobacter pylori is a potent carcinogen associated with gastric cancer malignancy. Recently. H. pylori Heat shock protein 60 (HpHSP60) has been reported to promote cancer development by inducing chronic inflammation and promoting tumor cell migration. This study demonstrates a role for HpHSP60 in angiogenesis, a necessary precursor to tumor growth. We showed that HpHSP60 enhanced cell migration and tube formation, but not cell proliferation, in human umbilical vein endothelial cells (HUVECs). HpHSP60 also indirectly promoted HUVEC proliferation when HUVECs were co-cultured with supernatants collected from HpHSP60-treated AGS or THP-1 cells. The angiogenic array showed that HpHSP60 dramatically induced THP-1 cells and HUVECs to produce the chemotactic factors IL-8 and GRO. Inhibition of CXCR2, the receptor for IL-8 and GRO, or downstream PLC beta 2/Ca2+-mediated signaling, significantly abolished HpHSP60-induced tube formation. In contrast, suppression of MAP K or PI3 K signaling did not affect HpHSP60-mediated tubulogenesis. These data suggest that HpHSP60 enhances angiogenesis via CXCR2/PLC beta 2/Ca2+ signal transduction in endothelial cells. (C) 2010 Elsevier Inc. All rights reserved.
Immunopathogenic behaviors of canine transmissible venereal tumor in dogs following an immunotherapy using dendritic/tumor cell hybrid
(2011-02-15)
Pai, Chien-Chun
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Kuo, Tzong-Fu
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Mao, Simon J. T.
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Chuang, Tien-Fu
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Lin, Chen-Si
Canine transmissible venereal tumor (CTVT) is a naturally occurring tumor that can be transmitted between dogs via live tumor cell inoculation. It is also a spontaneous self-regression tumor and its behavior is closely related to host immune responses. Since CTVT had been widely used for tumor models in canine cancers, whether this self-regression may overtake the immunity elicited from an exogenous tumor vaccine remains unclear and certainly worthwhile to be investigated. In this study, we used DCs/tumor hybrids as a tumor vaccine to evaluate the CTVT model. We prepared mature allogeneic dendritic cells from bone marrow and then assessed their phenotype (CD80, CD83, CD86, CD1a, CD11c, CD40 and MHC II), antigen uptake and presenting abilities. Fused dendritic cell/CTVT hybrids were then used as a vaccine, administered three times at two-week intervals via subcutaneous injection near the bilateral auxiliary and inguinal lymph nodes. In comparison with unvaccinated dogs (spontaneous regressed group), within a period of 2.5 months, the vaccinations substantially inhibited tumor progression (p<0.05) and accelerated the rate of regression by a mechanism involving amplification of the host tumor-specific adaptive immune responses and NK cytotoxicity (p<0.001). Pathologic examination revealed early massive lymphocyte infiltration resulting in final tumor necrosis. In addition, there are not any detectable effects on routine physical, body temperature or blood chemistry examinations. In conclusion, our data furnishes a reference value showing that CTVT is a model of potential use for the study of immunity elicited by vaccines against tumors, and also enable early-phase evaluation of the dendritic cell/tumor vaccine in terms of raising host immunity. (C) 2010 Elsevier B.V. All rights reserved.
Inhibiting autophagy potentiates the antitumor efficacy ofEuphorbia royleanafor canine mammary gland tumors
(2020-06-12)
Huang, Yu-Ya
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Chen, Chia-Hung
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Hsu, Chia-Hui
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Kuo, Tsun-Yung
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Liu, Cheng-Chi
Background Canine mammary gland tumors (cMGTs) are the most common neoplasms in intact female canines and viewed as a suitable model for studying human breast cancers.Euphorbia royleanahas been reported to have a variety of antitumor efficacies. We have prepared the crude extracts ofE. royleanain ethanol and hexane solvents to evaluate the anti-tumor effects for cMGT in vitro and in vivo. Results The results showed thatE. royleanacould inhibit cell proliferation and colony formation in cMGT cells. The suppression of tumor cell growth resulted from necrosis and cell cycle arrest. Moreover, autophagy appears to play a critical role inE. royleana-mediated cell death by triggering cell apoptosis. The in vivo results also revealed thatE. royleanatreatment could reduce the size of solid tumors while exhibiting low toxicity in cMGT-bearing nude mice. Conclusions The anti-tumor mechanisms ofE. royleanawere firstly verified to show it would cause autophagic cell death, apoptosis, and cell cycle arrest in canine mammary tumor cells. The in vitro and in vivo findings in the present study revealedE. royleanahas potential anticancer effects for the treatment of canine mammary gland tumors.
Lipoplex-based targeted gene therapy for the suppression of tumours with VEGFR expression by producing anti-angiogenic molecules
(2020-04-09)
Ho, Shu-Yi
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Chen, Pin-Rong
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Chen, Chia-Hung
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Tsai, Nu-Man
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Lin, Yu-Hsin
Background The anti-angiogenic fusion protein RBDV-IgG1 Fc (RBDV), which comprises the receptor-binding domain of vascular endothelial growth factor-A (VEGF-A), has shown antitumour effects by reducing angiogenesis in vivo. This study used the cationic lipoplex lipo-PEG-PEI-complex (LPPC) to simultaneously encapsulate both the RBDV targeting protein and the RBDV plasmid (pRBDV) without covalent bonds to assess VEGFR targeting gene therapy in mice with melanoma in vivo. Results LPPC protected the therapeutic transgene from degradation by DNase, and the LPPC/RBDV complexes could specifically target VEGFR-positive B16-F10 cells both in vitro and in vivo. With or without RBDV protein-targeting direction, the pRBDV-expressing RBDV proteins were expressed and reached a maximal concentration on the 7th day in the sera after transfection in vivo and significantly elicited growth suppression against B16-F10 melanoma but not IgG1 control proteins. In particular, LPPC/pRBDV/RBDV treatment with the targeting molecules dramatically inhibited B16-F10 tumour growth in vivo to provide better therapeutic efficacy than the treatments with gene therapy with IgG1 protein targeting or administration of a protein drug with RBDV. Conclusions The simultaneous combination of the LPPC complex with pRBDV gene therapy and RBDV protein targeting might be a potential tool to conveniently administer targeted gene therapy for cancer therapy.
Potential enhancement of host immunity and anti-tumor efficacy of nanoscale curcumin and resveratrol in colorectal cancers by modulated electro- hyperthermia
(2020-06-29)
Kuo, I-Ming
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Lee, Jih-Jong
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Wang, Yu-Shan
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Chiang, Hsin-Chien
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Huang, Cheng-Chung
BackgroundModulated electro-hyperthermia (mEHT) is a form of hyperthermia used in cancer treatment. mEHT has demonstrated the ability to activate host immunity by inducing the release of heat shock proteins, triggering apoptosis, and destroying the integrity of cell membranes to enhance cellular uptake of chemo-drugs in tumor cells. Both curcumin and resveratrol are phytochemicals that function as effective antioxidants, immune activators, and potential inhibitors of tumor development. However, poor bioavailability is a major obstacle for use in clinical cancer treatment.MethodsThis purpose of this study was to investigate whether mEHT can increase anti-cancer efficacy of nanosized curcumin and resveratrol in in vitro and in vivo models. The in vitro study included cell proliferation assay, cell cycle, and apoptosis analysis. Serum concentration was analyzed for the absorption of curcumin and resveratrol in SD rat model. The in vivo CT26/BALB/c animal tumor model was used for validating the safety, tumor growth curve, and immune cell infiltration within tumor tissues after combined mEHT/curcumin/resveratrol treatment.ResultsThe results indicate co-treatment of mEHT with nano-curcumin and resveratrol significantly induced cell cycle arrest and apoptosis of CT26 cells. The serum concentrations of curcumin and resveratrol were significantly elevated when mEHT was applied. The combination also inhibited the growth of CT26 colon cancer by inducing apoptosis and HSP70 expression of tumor cells while recruiting CD3+ T-cells and F4/80+ macrophages.ConclusionsThe results of this study have suggested that this natural, non-toxic compound can be an effective anti-tumor strategy for clinical cancer therapy. mEHT can enable cellular uptake of potential anti-tumor materials and create a favorable tumor microenvironment for an immunological chain reaction that improves the success of combined treatments of curcumin and resveratrol.
Relationship between Energy Dosage and Apoptotic Cell Death by Modulated Electro-Hyperthermia
(2020-06-02)
Kao, Patrick Hung-Ju
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Chen, Chia-Hung
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Tsang, Yuk-Wah
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Lin, Chen-Si
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Chiang, Hsin-Chien
Modulated electro-hyperthermia (mEHT) is a form of mild hyperthermia (HT) used for cancer treatment. The principle utility of HT is the ability not only to increase cell temperature, but also to increase blood flow and associated pO(2) to the microenvironment. While investigational evidence has shown the unique ability of mEHT to elicit apoptosis in cancer cells, in vivo and in vitro, the same trait has not been observed with conventional HT. There is dissension as to what allows mEHT to elicit apoptosis despite heating to only mild temperatures, with the predominant opinion in favor of increased temperature at a cellular level as the driving force. For this study, we hypothesized that in addition to temperature, the amount of electrical energy delivered is a major factor in induction of apoptosis by mEHT. To evaluate the impact of electrical energy on apoptosis, we divided generally practiced mEHT treatment into 3 phases: Phase I (treatment start to 10min. mark): escalation from 25 degrees C to 37 degrees C Phase II (10min. mark to 15min. mark): escalation from 37 degrees C to 42 degrees C Phase III (15min. mark to 45min. mark): maintenance at 42 degrees C Combinations of mEHT at 18W power, mEHT at 7.5W power, water bath, and incubator were applied to each of the three phases. Power output was recorded per second and calculated as average power per second. Total number of corresponding Joules emitted per each experiment was also recorded. The biological effect of apoptotic cell death was assayed by annexin-V assay. In group where mEHT was applied for all three phases, apoptosis rate was measured at 31.18 +/- 1.47%. In group where mEHT was only applied in Phases II and III, apoptosis rate dropped to 20.2 +/- 2.1%. Where mEHT was only applied in Phase III, apoptosis was 6.4 +/- 1.7%. Interestingly, when mEHT was applied in Phases I and II, whether Phase III was conducted in either water bath at 42 degrees C or incubator at 37 degrees C, resulted in nearly identical apoptosis rates, 26 +/- 4.4% and 25.9 +/- 3.1%, respectively. These results showed that accumulation of mEHT at high-powered setting (18W/sec) during temperature escalation (Phase I and Phase II), significantly increased apoptosis of tested cancer cells. The data also showed that whereas apoptosis rate was significantly increased during temperature escalation by higher power (18W/sec), apoptosis was limited during temperature maintenance with lower power (7.5W/sec). This presents that neither maintenance of 42 degrees C nor accumulation of Joules by mEHT has immediate correlating effect on apoptosis rate. These findings may offer a basis for direction of clinical application of mEHT treatment.
The treatment of propofol induced the TGF-beta 1 expression in human endothelial cells to suppress endocytosis activities of monocytes
(2010-12-01)
Li, Chi-Han
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Lee, Ru-Ping
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Lin, Yu-Ling
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Lin, Chen-Si
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Hsu, Bang-Gee
Propofol anesthesia and sedation are known to downregulate the functions of many hematopoietic cells, such as macrophages and neutrophils, in vivo. However, the effects of propofol on secretion of the regulatory cytokine transforming growth factor beta 1 (TGF-beta 1) in vivo are unknown. In this study, the effects of propofol on TGF-beta 1 expression in human peripheral blood mononuclear cells, umbilical vein endothelial cells (HUVECs), lymphocytes (Jurkat) and monocytes (THP-1) were tested. Moreover, these sera were also tested for regulatory activity on monocyte endocytosis with or without treatment with the TGF-beta 1 pathway inhibitor SB431542. Propofol raised levels of both total and activated TGF-beta 1 in propofol-treated patient sera after surgical operations. Furthermore, propofol induced secretion of latent TGF-beta 1 in HUVEC cells and enhanced TGF-beta 1 activation in THP-1 and Jurkat cells in vitro. Additionally, sera from propofol-treated patients suppressed monocyte endocytosis ex vivo, an effect that was abrogated by the TGF-beta 1 pathway inhibitor SB431542. (C) 2010 Elsevier Ltd. All rights reserved.
Utilization of I kappa B-EGFP Chimeric Gene as an Indicator to Identify Microbial Metabolites with NF-kappa B Inhibitor Activity
(2010-12-01)
Lin, Yu-Ling
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Chen, Yen-Shun
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Hsieh, Jui-Hung
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Lin, Ching-Min
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Wu, Hsin-Yi
NF-kappa B regulates several important expressions, such as cytokine release, anti-apoptosis, adhesion molecule expression, and cell cycle processing. Several NF-kappa B inhibitors have been discovered as an anti-tumor or anti-inflammatory drug. The activity of NF-kappa B transcription factor is negatively regulated by I kappa B binding. In this study, I kappa B assay system was established and I kappa B-EGFP fusion protein was used as an indicator to monitor the effects of substances on the I kappa B degradation. The results indicated that the chosen hydroquinone could inhibit the I kappa B degradation and cause the cell de-attachment from the bottom of culture plate. In addition, this system could also monitor the I kappa B degradation of microbial metabolite of natural mixtures of propolis. Thus, the I kappa B assay system may be a good system for drug discovery related to microbial metabolite.