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Toll like receptors and colon cancer

Daoyan Wu, Mei Cao, Jingshan Peng, Ningzhe Li, Sijun Yi, Liju Song, Xuege Wang, Mao Zhang, Jian Zhao
Colonization of Helicobacter pylori (H. pylori) induces immune and inflammatory response in gastric mucosa. Trimethylamine N-oxide (TMAO), from diet and metabolite through the action of gut microbiota, has been linked to inflammatory diseases. To investigate the effects of TMAO and H. pylori infection on gene expression in gastric epithelial cells, Human gene chip Affymetrix HTA 2.0 was used in this study. 1312 genes were identified as differentially expressed genes in GES-1 cells with H. pylori and TMAO co-treatment compared to the control...
February 2017: International Immunopharmacology
Rekha Loganathan, Mehnaz Nazeer, Vaishnavi Goda, Panneer Devaraju, Mohammed Ali, Premkumar Karunakaran, Megala Jayaraman
Toll like receptors (TLRs) are a class of molecular pattern recognition receptors, elicits a strong inflammatory immune response against pathogens. Helicobacter pylori (H. pylori), a gram negative flagellate colonizes the human stomach, is responsible for the development of chronic gastritis and gastric carcinoma. The higher incidence of H. pylori infection and gastric cancer in South Indian Tamils demands a genetic study to unravel the influence of TLR4 and TLR9 polymorphisms associated with chronic H. pylori infection...
December 16, 2016: Human Immunology
Hung-Sheng Shang, Jia-You Liu, Hsu-Feng Lu, Han-Sun Chiang, Chia-Hain Lin, Ann Chen, Yuh-Feng Lin, Jing-Gung Chung
Casticin, a polymethoxyflavone, derived from natural plant Fructus Viticis exhibits biological activities including anti-cancer characteristics. The anti-cancer and alter gene expression of casticin on human colon cancer cells and the underlying mechanisms were investigated. Flow cytometric assay was used to measure viable cell, cell cycle and sub-G1 phase, reactive oxygen species (ROS) and Ca(2+) productions, level of mitochondria membrane potential (ΔΨm ) and caspase activity. Western blotting assay was used to detect expression of protein level associated with cell death...
November 14, 2016: Environmental Toxicology
Ga Bin Park, Daejin Kim
Toll-like receptor 4 (TLR4) activation is a key contributor to the carcinogenesis of colon cancer. Overexpression of galectin-1 (Gal-1) also correlates with increased invasive activity of colorectal cancer. Lactate production is a critical predictive factor of risk of metastasis, but the functional relationship between intracellular lactate and Gal-1 expression in TLR4-activated colon cancer remains unknown. In this study, we investigated the underlying mechanism and role of Gal-1 in metastasis and invasion of colorectal cancer (CRC) cells after TLR4 stimulation...
November 12, 2016: Molecular and Cellular Biochemistry
Darlene A Monlish, Sima T Bhatt, Laura G Schuettpelz
Toll-like receptors (TLRs) are a family of pattern recognition receptors that shape the innate immune system by identifying pathogen-associated molecular patterns and host-derived damage-associated molecular patterns. TLRs are widely expressed on both immune cells and non-immune cells, including hematopoietic stem and progenitor cells, effector immune cell populations, and endothelial cells. In addition to their well-known role in the innate immune response to acute infection or injury, accumulating evidence supports a role for TLRs in the development of hematopoietic and other malignancies...
2016: Frontiers in Immunology
Yoon Hee Chung, Daejin Kim
BACKGROUND: Phosphorylation of glycogen synthase kinase 3β (GSK3β) by phosphatidyl-inositide 3-kinase (PI3K)/protein kinase B (AKT) or inhibition of GSK3β with small-molecule inhibitor attenuates cell survival and proliferation and increases apoptosis in most cancer cell lines. In this study, we investigated the role of phosphorylated GSK3β activated by enhanced toll-like receptor 4 (TLR4) expression in drug-treated colon cancer cells as a model of post-chemotherapy cancer cells. MATERIALS AND METHODS: The effect of TLR4 stimulation on metastasis and apoptosis in drug-exposed colon cancer cells was determined by real-time polymerase chain reaction (PCR) and immunoblotting...
July 2016: Anticancer Research
Wei-Ting Kuo, Tsung-Chun Lee, Linda Chia-Hui Yu
Colorectal carcinogenesis is affected by overexpression of the lipopolysaccharide (LPS) receptors CD14 and TLR4, which antagonize each other by affecting epithelial cell proliferation and apoptosis. Eritoran is an investigational drug for sepsis treatment that resembles the lipid A moiety of LPS and therefore acts as a TLR4 inhibitor. In the present study, we explored the potential therapeutic uses and mechanisms of action of eritoran in reducing colon cancer progression. Eritoran administration via intracolonic, intragastric, or intravenous routes significantly reduced tumor burden in a chemically induced mouse model of colorectal carcinoma...
August 15, 2016: Cancer Research
Wei-Ting Kuo, Tsung-Chun Lee, Linda Chia-Hui Yu
Gut microbiota and lipopolysaccharide (LPS) signaling have been associated with colon cancer development. Our recent findings demonstrated that LPS receptor subunits expressed on colonocytes have antagonistic roles in cell death and tumorigenesis: epithelial toll-like receptor 4 (TLR4) confers resistance to the apoptosis induced by its co-receptor CD14 and contributes to epithelial transition to cancer.
January 2016: Molecular & Cellular Oncology
Mingyang Han, Yucheng Song, Xuedong Zhang
OBJECTIVE: The migration and invasion features, which were associated with inflammatory response, acted as vital roles in the development of colon cancer. Quercetin, a bioflavonoid compound, was widely spread in vegetables and fruits. Although quercetin exerts antioxidant and anticancer activities, the molecular signaling pathways in human colon cancer cells remain unclear. Hence, the present study was conducted to investigate the suppression of quercetin on migratory and invasive activity of colon cancer and the underlying mechanism...
May 2016: Pharmacognosy Magazine
M G Varga, C L Shaffer, J C Sierra, G Suarez, M B Piazuelo, M E Whitaker, J Romero-Gallo, U S Krishna, A Delgado, M A Gomez, J A D Good, F Almqvist, E P Skaar, P Correa, K T Wilson, M Hadjifrangiskou, R M Peek
Helicobacter pylori (H. pylori) is the strongest identified risk factor for gastric cancer, the third most common cause of cancer-related death worldwide. An H. pylori constituent that augments cancer risk is the strain-specific cag pathogenicity island, which encodes a type IV secretion system (T4SS) that translocates a pro-inflammatory and oncogenic protein, CagA, into epithelial cells. However, the majority of persons colonized with CagA(+) H. pylori strains do not develop cancer, suggesting that other microbial effectors also have a role in carcinogenesis...
December 1, 2016: Oncogene
Ephraim A Ansa-Addo, Jessica Thaxton, Feng Hong, Bill X Wu, Yongliang Zhang, Caroline W Fugle, Alessandra Metelli, Brian Riesenberg, Katelyn Williams, Daniel T Gewirth, Gabriela Chiosis, Bei Liu, Zihai Li
As an endoplasmic reticulum heat shock protein (HSP) 90 paralogue, glycoprotein (gp) 96 possesses immunological properties by chaperoning antigenic peptides for activation of T cells. Genetic studies in the last decade have unveiled that gp96 is also an essential master chaperone for multiple receptors and secreting proteins including Toll-like receptors (TLRs), integrins, the Wnt coreceptor, Low Density Lipoprotein Receptor-Related Protein 6 (LRP6), the latent TGFβ docking receptor, Glycoprotein A Repetitions Predominant (GARP), Glycoprotein (GP) Ib and insulin-like growth factors (IGF)...
2016: Current Topics in Medicinal Chemistry
Bill X Wu, Feng Hong, Yongliang Zhang, Ephraim Ansa-Addo, Zihai Li
As an endoplasmic reticulum heat-shock protein 90 (HSP90) paralog, GRP94 (glucose-regulated protein 94)/gp96 (hereafter referred to as GRP94) has been shown to be an essential master chaperone for multiple receptors including Toll-like receptors, Wnt coreceptors, and integrins. Clinically, expression of GRP94 correlates with advanced stage and poor survival in a variety of cancers. Recent preclinical studies have also revealed that GRP94 expression is closely linked to cancer growth and metastasis in melanoma, ovarian cancer, multiple myeloma, lung cancer, and inflammation-associated colon cancer...
2016: Advances in Cancer Research
Craig M Brackett, Bojidar Kojouharov, Jean Veith, Kellee F Greene, Lyudmila G Burdelya, Sandra O Gollnick, Scott I Abrams, Andrei V Gudkov
Activation of an anticancer innate immune response is highly desirable because of its inherent ability to generate an adaptive antitumor T-cell response. However, insufficient safety of innate immune modulators limits clinical use to topical applications. Toll-like receptor 5 (TLR5) agonists are favorably positioned as potential systemic immunotherapeutic agents because of unusual tissue specificity of expression, uniquely safe profile of induced cytokines, and antitumor efficacy demonstrated in a number of animal models...
February 16, 2016: Proceedings of the National Academy of Sciences of the United States of America
Feng Wen, Yongmei Liu, Wei Wang, Meng Li, Fuchun Guo, Yaxiong Sang, Qing Qin, Yongsheng Wang, Qiu Li
Toll-like receptors (TLRs)/NF-κB activation stimulated by lipopolysaccharide (LPS) was associated with diverse biological response in colon cancer, but the underlying mechanism was largely unknown. In the current study, we reported cell proliferation was elevated in adenomatous polyposis coli (APC) mutated- and APC knockdown cell lines, while the proliferation was inhibited in APC wild-type cell lines. Besides, in vivo experiments showed that LPS promoted APC knockdown tumor growth while inhibited proliferation of APC wild type...
February 16, 2016: Oncotarget
Tiangeng Dong, Tuo Yi, Mengxuan Yang, Shengli Lin, Wenxiang Li, Xingyuan Xu, Jianwei Hu, Lijun Jia, Xinqiang Hong, Weixin Niu
Dendritic cells (DCs) and invariant natural killer T (iNKT) cells play important roles in linking innate immunity and adaptive immunity. Mature DCs activated by Toll-like receptor (TLR) agonists directly activate iNKT cells and the iNKT ligand α-galactosylceramide (α-Galcer) can induce DC maturation, resulting in enhanced protective immune responses. In the present study, we aimed to boost anti-tumour immunity in a murine colon cancer model by synergizing DCs and iNKT cells using α-Galcer-loaded tumour cells (tumour-Gal) and the TLR9 agonist cytosine-phosphorothioate-guanine (CpG1826)...
January 1, 2016: Biochemical Journal
Manh-Cuong Vo, Hyun-Ju Lee, Jong-Seok Kim, My-Dung Hoang, Nu-Ri Choi, Joon Haeng Rhee, Vinoth-Kumar Lakshmanan, Sung-Jae Shin, Je-Jung Lee
Dendritic cell (DC)-based vaccines are considered useful in cancer immunotherapy, and the interaction of DC and adjuvants is important in the design of the next generation vaccines. In this study, whether DC combined with Rv2299c derived from mycobacteria could improve anti-tumor immune responses in a colon cancer mouse model was evaluated. MC38 cell lines were injected subcutaneously to establish colon-cancer-bearing mice and the following four groups were evaluated: PBS control, tumor antigen (TA) loaded-DC, Rv2299c, and a combination of TA-loaded-DC and Rv2299c...
October 20, 2015: Oncotarget
Junjie Zhao, Katarzyna Bulek, Muhammet F Gulen, Jarod A Zepp, Georgio Karagkounis, Bradley N Martin, Hao Zhou, Minjia Yu, Xiuli Liu, Emina Huang, Paul L Fox, Matthew F Kalady, Sanford D Markowitz, Xiaoxia Li
BACKGROUND & AIMS: Single immunoglobulin and toll-interleukin 1 receptor (SIGIRR), a negative regulator of the Toll-like and interleukin-1 receptor (IL-1R) signaling pathways, controls intestinal inflammation and suppresses colon tumorigenesis in mice. However, the importance of SIGIRR in human colorectal cancer development has not been determined. We investigated the role of SIGIRR in development of human colorectal cancer. METHODS: We performed RNA sequence analyses of pairs of colon tumor and nontumor tissues, each collected from 68 patients...
December 2015: Gastroenterology
Sukhontip Klahan, Chi-Cheng Huang, Shu-Chen Chien, Mei-Shin Wu, Henry Sung-Ching Wong, Chien-Yu Huang, Wei-Chiao Chang, Po-Li Wei
Colorectal cancer is one of the most common cancers worldwide. Surgery is usually the primary treatment for colon cancers that have not spread to distant sites. However, chemotherapy may be considered after surgery to eliminate remaining cancer cells or in case the cancer has a high risk of recurrence. Oxaliplatin is often used in combination regimens such as FOLFOX, CapeOX, and FOLFOXIRI because of the cost-effectiveness of adjuvant treatment for patients and also the good tolerability profile. However, some patients show resistance to oxaliplatin which causes poor treatment outcomes...
January 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Teruko Honda, Hiroyuki Inagawa
BACKGROUND/AIM: The increased mRNA expression of chemotaxis- and angiogenesis-related factors in human monocytes following interaction with colon cancer cells has been shown to be suppressed by pre-treatment with low-dose lipopolysaccharide (LPS) (100 pg/ml). It has been demonstrated that low-dose LPS reduced the expression of RelB, a member of the nuclear factor (NF)-κB transcription factor family, in mouse macrophages and the NF-κB signaling pathway was important for tumor initiation and growth in tumor-associated macrophages...
August 2015: Anticancer Research
Svasti Haricharan, Powel Brown
Breast cancer is a leading cause of cancer-related death, and it is important to understand pathways that drive the disease to devise effective therapeutic strategies. Our results show that Toll-like receptor 4 (TLR4) drives breast cancer cell growth differentially based on the presence of TP53, a tumor suppressor. TP53 is mutationally inactivated in most types of cancer and is mutated in 30-50% of diagnosed breast tumors. We demonstrate that TLR4 activation inhibits growth of TP53 wild-type cells, but promotes growth of TP53 mutant breast cancer cells by regulating proliferation...
June 23, 2015: Proceedings of the National Academy of Sciences of the United States of America
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