scholarly journals CCL2 and IL18 expressions may associate with the anti-proliferative effect of noncontact electro capacitive cancer therapy in vivo

F1000Research ◽  
2020 ◽  
Vol 8 ◽  
pp. 1770
Author(s):  
Rarastoeti Pratiwi ◽  
Nyoman Yudi Antara ◽  
Lalu Gunawan Fadliansyah ◽  
Syamsul Arif Ardiansyah ◽  
Luthfi Nurhidayat ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Breast Tumor ◽  
Metastatic Breast ◽  
Intermediate Frequency ◽  
Necrosis Factor Alpha ◽  
Breast Tumor Tissue ◽  
Proliferative Effect ◽  
Tumor Tissues ◽  
Tnf Α

Background: Noncontact Electro Capacitive Cancer Therapy (ECCT) is a novel treatment modality in cancer. Chemokine (C-C motif) ligand 2 (CCL2) has a major role in the outgrowth of metastatic breast cancer. Interleukin 18 (IL18) plays a role in macrophage alteration, which leads to excessive angiogenesis. This study aims to elaborate on the association of CCL2, IL18, IL23α, and TNF-α (tumor necrosis factor-alpha) expression with the anti-proliferative effect of ECCT in rat breast tumor tissue.   Methods: Low intensity (18 Vpp) and intermediate frequency (150 kHz) alternating current-electric field (AC-EF) between two capacitive electrodes were exposed as external EF to a rat cage. Twenty-four rats were divided into four groups of six replicates. Breast tumor tissues were collected from 7, 12-dimethylbenz[a]anthracene (DMBA)-induced rats. Two groups were non DMBA-induced rats without ECCT exposure (NINT) and with (NIT). The other two groups were DMBA-induced rats without ECCT exposure (INT) and with (IT). Mammary glands and breast tumor tissues were collected from each group and preserved. Hematoxylin-eosin and immunohistochemistry staining were performed on paraffin sections of tissues using anti-PCNA, anti-ErbB2, anti-Caspase3, and anti-CD68. CCL2, IL18, IL23α, and TNF-α mRNA relative expressions were analyzed using qRT-PCR. Results: ECCT exposure may cause the reduction of PCNA protein expression as well as ErbB2 on breast tumor tissues, but it causes the increase of Caspase3 and macrophage CD68 protein. In rat breast tumor tissues of IT groups, the mRNA expression of CCL2 and IL18 are significantly down-regulated, in contrast with the up-regulated expression of these cytokines in tumor tissues of the INT group. IL23α and TNF- α expression remained similar in both groups. Conclusion: CCL2 and IL18 expressions have an association with the inhibition of breast tumor cell proliferation affected by ECCT exposure

scholarly journals CCL2 and IL18 expressions may associate with the anti-proliferative effect of noncontact electro capacitive cancer therapy in vivo

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1770 ◽  
Author(s):  
Rarastoeti Pratiwi ◽  
Nyoman Yudi Antara ◽  
Lalu Gunawan Fadliansyah ◽  
Syamsul Arif Ardiansyah ◽  
Luthfi Nurhidayat ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Breast Tumor ◽  
Metastatic Breast ◽  
Intermediate Frequency ◽  
Necrosis Factor Alpha ◽  
Breast Tumor Tissue ◽  
Proliferative Effect ◽  
Tumor Tissues ◽  
Tnf Α

Background: Noncontact Electro Capacitive Cancer Therapy (ECCT) is a novel treatment modality in cancer. Chemokine (C-C motif) ligand 2 (CCL2) has a major role in the outgrowth of metastatic breast cancer. Interleukin 18 (IL18) plays a role in macrophage alteration, which leads to excessive angiogenesis. This study aims to elaborate on the association of CCL2, IL18, IL23α, and TNF-α (tumor necrosis factor-alpha) expression with the anti-proliferative effect of ECCT in rat breast tumor tissue.   Methods: Low intensity (18 Vpp) and intermediate frequency (150 kHz) alternating current-electric field (AC-EF) between two capacitive electrodes were exposed as external EF to a rat cage. Twenty-four rats were divided into four groups of six replicates. Breast tumor tissues were collected from 7, 12-dimethylbenz[a]anthracene (DMBA)-induced rats. Two groups were none DMBA-induced rats without ECCT exposure (NINT) and with (NIT). The other two groups were DMBA-induced rats without ECCT exposure (INT) and with (IT). Mammary glands and breast tumor tissues were collected from each group and preserved. Hematoxylin-eosin and immunohistochemistry staining were performed on paraffin sections of tissues using anti-PCNA, anti-ErbB2, anti-Caspase3, and anti-CD68. CCL2, IL18, IL23α, and TNF-α mRNA relative expressions were analyzed using qRT-PCR. Results: ECCT exposure may cause the reduction of PCNA protein expression as well as ErbB2 on breast tumor tissues, but it causes the increase of Caspase3 and macrophage CD68 protein. In rat breast tumor tissues of IT groups, the mRNA expression of CCL2 and IL18 are significantly down-regulated, in contrast with the up-regulated expression of these cytokines in tumor tissues of the INT group. IL23α and TNF- α expression remained similar in both groups. Conclusion: CCL2 and IL18 expressions have an association with the inhibition of breast tumor cell proliferation affected by ECCT exposure

scholarly journals Analysis of the Heterogeneity of CD4+CD25+ T Cell TCR β CDR3 Repertoires in Breast Tumor Tissues, Lung Metastatic Tissues, and Spleens from 4T1 Tumor-Bearing BALB/c Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-21
Author(s):  
Teng Zhang ◽  
Fangfang Duan ◽  
Danhua Su ◽  
Long Ma ◽  
Jiezuan Yang ◽  
...  
Keyword(s):  
T Cells ◽  
Breast Tumor ◽  
High Throughput Sequencing ◽  
Intermediate Frequency ◽  
Breast Tumor Tissue ◽  
Tumor Bearing ◽  
Tumor Tissues ◽  
Great Heterogeneity ◽  
Breast Tissues ◽  
Complementarity Determining Region

To study the homogeneity and heterogeneity of CD4+CD25+ T cells receptor β-chain complementarity determining region 3 (TCR β CDR3) repertoires in breast tumor tissues, lung metastatic tissues, and spleens from 4T1 tumor-bearing BALB/c mice. We used high-throughput sequencing to analyze the characteristics and changes of CD4+CD25+ TCR β CDR3 repertoires among tumor tissues, lung metastatic tissues, and spleens. The diversity of the CD4+CD25+ TCR β CDR3 repertoires in breast tumor tissue was similar to that of lung metastatic tissues and less pronounced than that of spleen tissues. Breast tumor tissues and lung metastatic tissues had a greater number of high-frequency CDR3 sequences and intermediate-frequency CDR3 sequences than those of spleens. The proportion of unique productive CDR3 sequences in breast tumor tissues and lung metastatic tissues was significantly greater than that in the spleens. The diversity and frequency of the CDR3 repertoires remained homogeneous in breast tumors and lung metastatic tissues and showed great heterogeneity in the spleens, which suggested that the breast tissues and lung metastatic tissues have characteristics of CD4+CD25+ T cells that relate to the tumor microenvironment. However, the number and characteristics of overlapping CDR3 sequences suggested that there were some different CD4+CD25+ T cells in tumors and in the circulatory immune system. The study may be used to further explore the characteristics of the CDR3 repertoires and determine the source of the CD4+CD25+ T cells in the breast cancer microenvironment.

scholarly journals Transcription Factor AP-2α Is Preferentially Cleaved by Caspase 6 and Degraded by Proteasome during Tumor Necrosis Factor Alpha-Induced Apoptosis in Breast Cancer Cells

2001 ◽  
Vol 21 (15) ◽  
pp. 4856-4867 ◽  
Author(s):  
Okot Nyormoi ◽  
Zhi Wang ◽  
Dao Doan ◽  
Maribelis Ruiz ◽  
David McConkey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Cells ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Caspase 6 ◽  
Induced Apoptosis ◽  
Necrosis Factor

ABSTRACT Several reports have linked activating protein 2α (AP-2α) to apoptosis, leading us to hypothesize that AP-2α is a substrate for caspases. We tested this hypothesis by examining the effects of tumor necrosis factor alpha (TNF-α) on the expression of AP-2 in breast cancer cells. Here, we provide evidence that TNF-α downregulates AP-2α and AP-2γ expression posttranscriptionally during TNF-α-induced apoptosis. Both a general caspase antagonist (zVADfmk) and a caspase 6-preferred antagonist (zVEIDfmk) inhibited TNF-α-induced apoptosis and AP-2α downregulation. In vivo tests showed that AP-2α was cleaved by caspases ahead of the DNA fragmentation phase of apoptosis. Recombinant caspase 6 cleaved AP-2α preferentially, although caspases 1 and 3 also cleaved it, albeit at 50-fold or higher concentrations. Activated caspase 6 was detected in TNF-α-treated cells, thus confirming its involvement in AP-2α cleavage. All three caspases cleaved AP-2α at asp19 of the sequence asp-arg-his-asp (DRHD19). Mutating D19 to A19abrogated AP-2α cleavage by all three caspases. TNF-α-induced cleavage of AP-2α in vivo led to AP-2α degradation and loss of DNA-binding activity, both of which were prevented by pretreatment with zVEIDfmk. AP-2α degradation but not cleavage was inhibited in vivo by PS-431 (a proteasome antagonist), suggesting that AP-2α is degraded subsequent to cleavage by caspase 6 or caspase 6-like enzymes. Cells transfected with green fluorescent protein-tagged mutant AP-2α are resistant to TNF-α-induced apoptosis, further demonstrating the link between caspase-mediated cleavage of AP-2α and apoptosis. This is the first report to demonstrate that degradation of AP-2α is a critical event in TNF-α-induced apoptosis. Since the DRHD sequence in vertebrate AP-2 is widely conserved, its cleavage by caspases may represent an important mechanism for regulating cell survival, proliferation, differentiation, and apoptosis.

Morin Promotes the Production of Th2 Cytokine by Modulating Bone Marrow-Derived Dendritic Cells

2006 ◽  
Vol 34 (04) ◽  
pp. 667-684 ◽  
Author(s):  
Chia-Yang Li ◽  
Jau-Ling Suen ◽  
Bor-Luen Chiang ◽  
Pei-Dawn Lee Chao ◽  
Shih-Hua Fang
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Dendritic Cells ◽  
Interleukin 12 ◽  
Th2 Response ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Th Differentiation ◽  
Th1 And Th2 Responses

Our previous studies had reported that morin decreased the interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-α) production in lipopolysaccharide (LPS)-activated macrophages, suggesting that morin may promote helper T type 2 (Th2) response in vivo. Dendritic cells (DCs) are the most potent antigen presenting cells and known to play a major role in the differentiation of helper T type 1 (Th1) and Th2 responses. This study aimed to reveal whether morin is able to control the Th differentiation through modulating the maturation and functions of DCs. Bone marrow-derived dendritic cells (BM-DCs) were incubated with various concentrations of morin and their characteristics were studied. The results indicated that morin significantly affects the phenotype and cytokine expression of BM-DCs. Morin reduced the production of IL-12 and TNF-α in BM-DCs, in response to LPS stimulation. In addition, the proliferative response of stimulated alloreactive T cells was significantly decreased by morin in BM-DCs. Furthermore, allogeneic T cells secreted higher IL-4 and lower IFN-γ in response to morin in BM-DCs. In conclusion, these results suggested that morin favors Th2 cell differentiation through modulating the maturation and function of BM-DCs.

scholarly journals Role of Activated Protein C in Helicobacter pylori-Associated Gastritis

2000 ◽  
Vol 68 (5) ◽  
pp. 2863-2869 ◽  
Author(s):  
Satoko Oka ◽  
Esteban Cesar Gabazza ◽  
Yukiko Taguchi ◽  
Michihiko Yamaguchi ◽  
Shigehito Nakashima ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Protein C ◽  
Activated Protein C ◽  
Mucosal Damage ◽  
Gastric Mucosal Damage ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Gastric Corpus ◽  
H Pylori

ABSTRACT The protein C (PC) pathway has recently been suggested to play a role in the regulation of the inflammatory response. To further extend the anti-inflammatory effect of activated PC (APC) in vivo, particularly its biological relevance to human disease, the activity of APC in the mucosa of patients with Helicobacter pylori-associated gastritis and the effect of vacuolating cytotoxin (VacA), cytotoxin-associated antigen (CagA), andH. pylori lipopolysaccharide (LPS) on PC activation were evaluated. This study comprised 35 patients with chronic gastritis. There were 20 patients with and 15 without H. pylori infection. The levels of PC and APC-PC inhibitor (PCI) complex were measured by immunoassays. The level of PC was significantly decreased and the level of APC-PCI complex was significantly increased in biopsy specimens from gastric corpus and antrum in patients with H. pylori-associated gastritis as compared to H. pylori-negative subjects. The concentrations of VacA, CagA, and LPS were significantly correlated with those of the APC-PCI complex in biopsy mucosal specimens from the gastric corpus and antrum. H. pylori LPS, VacA, and CagA induced a dose-dependent activation of PC on the surface of monocytic cells. APC inhibited the secretion of tumor necrosis factor alpha (TNF-α) induced by H. pylori LPS. Overall, these results suggest that H. pylori infection is associated with increased APC generation in the gastric mucosa. The inhibitory activity of APC on TNF-α secretion may serve to protect H. pylori-induced gastric mucosal damage.

scholarly journals Micrococcus luteus Teichuronic Acids Activate Human and Murine Monocytic Cells in a CD14- and Toll-Like Receptor 4-Dependent Manner

2001 ◽  
Vol 69 (4) ◽  
pp. 2025-2030 ◽  
Author(s):  
Shuhua Yang ◽  
Shunji Sugawara ◽  
Toshihiko Monodane ◽  
Masahiro Nishijima ◽  
Yoshiyuki Adachi ◽  
...  
Keyword(s):  
Lipid A ◽  
Micrococcus Luteus ◽  
Dependent Manner ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Necrosis Factor Alpha ◽  
Monocytic Cells ◽  
Tnf Α

ABSTRACT Teichuronic acid (TUA), a component of the cell walls of the gram-positive organism Micrococcus luteus (formerlyMicrococcus lysodeikticus), induced inflammatory cytokines in C3H/HeN mice but not in lipopolysaccharide (LPS)-resistant C3H/HeJ mice that have a defect in the Toll-like receptor 4 (TLR4) gene, both in vivo and in vitro, similarly to LPS (T. Monodane, Y. Kawabata, S. Yang, S. Hase, and H. Takada, J. Med. Microbiol. 50:4–12, 2001). In this study, we found that purified TUA (p-TUA) induced tumor necrosis factor alpha (TNF-α) in murine monocytic J774.1 cells but not in mutant LR-9 cells expressing membrane CD14 at a lower level than the parent J774.1 cells. The TNF-α-inducing activity of p-TUA in J774.1 cells was completely inhibited by anti-mouse CD14 monoclonal antibody (MAb). p-TUA also induced interleukin-8 (IL-8) in human monocytic THP-1 cells differentiated to macrophage-like cells expressing CD14. Anti-human CD14 MAb, anti-human TLR4 MAb, and synthetic lipid A precursor IVA, an LPS antagonist, almost completely inhibited the IL-8-inducing ability of p-TUA, as well as LPS, in the differentiated THP-1 cells. Reduced p-TUA did not exhibit any activities in J774.1 or THP-1 cells. These findings strongly suggested that M. luteus TUA activates murine and human monocytic cells in a CD14- and TLR4-dependent manner, similar to LPS.

scholarly journals Mycoplasma pneumoniae-Derived Lipopeptides Induce Acute Inflammatory Responses in the Lungs of Mice

2007 ◽  
Vol 76 (1) ◽  
pp. 270-277 ◽  
Author(s):  
Takashi Shimizu ◽  
Yutaka Kida ◽  
Koichi Kuwano
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Inflammatory Responses ◽  
Lavage Fluid ◽  
Peritoneal Macrophages ◽  
Necrosis Factor Alpha ◽  
Chemokine Production ◽  
Cytokines And Chemokines ◽  
Tnf Α ◽  
Mouse Peritoneal Macrophages

ABSTRACT The pathogenesis of Mycoplasma pneumoniae infection is considered to be in part attributable to excessive immune responses. In this study, we investigated whether synthetic lipopeptides of subunit b of F0F1-type ATPase (F0F1-ATPase), NF-κB-activating lipoprotein 1 (N-ALP1), and N-ALP2 (named FAM20, sN-ALP1, and sN-ALP2, respectively) derived from M. pneumoniae induce cytokine and chemokine production and leukocyte infiltration in vivo. Intranasal administration of FAM20 and sN-ALP2 induced infiltration of leukocyte cells and production of chemokines and cytokines in bronchoalveolar lavage fluid, but sN-ALP1 failed to do so. The activity of FAM20 was notably higher than that of sN-ALP2. FAM20 and sN-ALP2 induced tumor necrosis factor alpha (TNF-α) through Toll-like receptor 2 in mouse peritoneal macrophages. Moreover, in the range of low concentrations of lipopeptides, FAM20 showed relatively high activity of inducing TNF-α in mouse peritoneal macrophages compared to synthetic lipopeptides such as MALP-2 and FSL-1, derived from Mycoplasma fermentans and Mycoplasma salivarium, respectively. These findings indicate that the F0F1-ATPase might be a key molecule in inducing cytokines and chemokines contributing to inflammatory responses during M. pneumoniae infection in vivo.

scholarly journals Metabolic Profiling of Buddleia indica Leaves using LC/MS and Evidence of their Antioxidant and Hepatoprotective Activity Using Different In Vitro and In Vivo Experimental Models

Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 412
Author(s):  
Fadia S. Youssef ◽  
Mohamed L. Ashour ◽  
Hesham A. El-Beshbishy ◽  
Abdel Nasser B. Singab ◽  
Michael Wink
Keyword(s):  
Antioxidant Properties ◽  
Lipid Peroxide ◽  
Hepatoprotective Activity ◽  
Experimental Models ◽  
Ionization Mass ◽  
Necrosis Factor Alpha ◽  
Stress Markers ◽  
Tnf Α

LC-ESI-MS (Liquid Chromatography coupled with Electrospray Ionization Mass Spectrometry profiling of a methanol extract from Buddleia indica (BIM) leaves revealed 12 main peaks in which verbascoside and buddlenoid B represent the major compounds. The antioxidant and hepatoprotective activities of BIM were investigated using different in vitro and in vivo experimental models. BIM exhibited substantial in vitro antioxidant properties in DPPH· and HepG2 assays. Regarding CCl4 (carbon tetrachloride) induced hepatotoxicity in a rat model, oxidative stress markers became significantly ameliorated after oral administration of BIM. Lipid peroxide levels showed a 51.85% decline relative to CCl4-treated rats. Super oxide dismutase (SOD), total antioxidant status (TAS), and catalase (CAT) revealed a marked increase by 132.48%, 187.18%, and 114.94% relative to the CCl4 group. In a tamoxifen-induced hepatotoxicity model, BIM showed a considerable alleviation in liver stress markers manifested by a 46.06% and 40% decline in ALT (Alanine Transaminase) and AST (Aspartate Transaminase) respectively. Thiobarbituric acid reactive substances (TBARS) were reduced by 28.57% and the tumor necrosis factor alpha (TNF-α) level by 50%. A virtual screening of major secondary metabolites of BIM to TNF-alpha employing the C-docker protocol showed that gmelinoside H caused the most potent TNF- α inhibition as indicated from their high fitting scores. Thus, BIM exhibited a potent hepatoprotective activity owing to its richness in antioxidant metabolites.

scholarly journals Targeted Cancer Therapy with Tumor Necrosis Factor-Alpha

2008 ◽  
Vol 1 ◽  
pp. BCI.S901 ◽  
Author(s):  
Weibo Cai ◽  
Zachary J. Kerner ◽  
Hao Hong ◽  
Jiangtao Sun
Keyword(s):  
Tumor Necrosis Factor ◽  
Cancer Therapy ◽  
Tumor Necrosis Factor Alpha ◽  
Fusion Proteins ◽  
Tumor Necrosis ◽  
Targeted Cancer Therapy ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Tumor necrosis factor-alpha (TNF-α), a member of the TNF superfamily, was the first cytokine to be evaluated for cancer biotherapy. However, the clinical use of TNF-α is severely limited by its toxicity. Currently, TNF-α is administered only through locoregional drug delivery systems such as isolated limb perfusion and isolated hepatic perfusion. To reduce the systemic toxicity of TNF-α, various strategies have been explored over the last several decades. This review summarizes current state-of-the-art targeted cancer therapy using TNF-α. Passive targeting, cell-based therapy, gene therapy with inducible or tissue-specific promoters, targeted polymer-DNA complexes, tumor pre-targeting, antibody-TNF-α conjugate, scFv/TNF-α fusion proteins, and peptide/TNF-α fusion proteins have all been investigated to combat cancer. Many of these agents are already in advanced clinical trials. Molecular imaging, which can significantly speed up the drug development process, and nanomedicine, which can integrate both imaging and therapeutic components, has the potential to revolutionize future cancer patient management. Cooperative efforts from scientists within multiple disciplines, as well as close partnerships among many organizations/entities, are needed to quickly translate novel TNF-α-based therapeutics into clinical investigation.

scholarly journals Modulation of Endotoxin- and Enterotoxin-Induced Cytokine Release by In Vivo Treatment with β-(1,6)-Branched β-(1,3)-Glucan

1999 ◽  
Vol 67 (1) ◽  
pp. 244-252 ◽  
Author(s):  
Jindrich Soltys ◽  
Mark T. Quinn
Keyword(s):  
Proinflammatory Cytokines ◽  
Necrosis Factor Alpha ◽  
Enhanced Production ◽  
Tnf Α ◽  
Host Mortality ◽  
Toxic Shock Syndrome Toxin ◽  
Stimulation Of ◽  
In Cells

ABSTRACT Leukocytes activated by endotoxin or enterotoxins release proinflammatory cytokines, thereby contributing to the cascade of events leading to septic shock. In the present studies, we analyzed the effects of in vivo administration of a soluble immunomodulator, β-(1,6)-branched β-(1,3)-glucan (soluble β-glucan), on toxin-stimulated cytokine production in monocytes and lymphocytes isolated from treated mice. In vitro stimulation of lymphocytes isolated from soluble β-glucan-treated mice with lipopolysaccharide (LPS) resulted in enhanced production of interleukin-6 (IL-6) and suppressed production of tumor necrosis factor alpha (TNF-α), while stimulation of these cells with staphylococcal enterotoxin B (SEB) or toxic shock syndrome toxin 1 (TSST-1) resulted in enhanced production of gamma interferon (IFN-γ) and suppressed production of IL-2 and TNF-α compared to that in cells isolated from untreated mice. In vitro stimulation of monocytes isolated from soluble β-glucan-treated mice with LPS also resulted in suppressed TNF-α production, while stimulation of these cells with SEB or TSST-1 resulted in suppressed IL-6 and TNF-α production compared to that in cells isolated from untreated mice. Thus, the overall cytokine pattern of leukocytes from soluble β-glucan-treated mice reflects suppressed production of proinflammatory cytokines, especially TNF-α. Taken together, our results suggest that treatment with soluble β-glucan can modulate the induction cytokines during sepsis, resulting in an overall decrease in host mortality.

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