• antitumor immunity
• bile acid
• colorectal cancer
• immune evasion
• pre‑metastatic niche

• Humans
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/metabolism
• Bile Acids and Salts/metabolism
• Liver Neoplasms/secondary
• Liver Neoplasms/metabolism
• Liver Neoplasms/immunology
• Tumor Microenvironment/immunology
• Gastrointestinal Microbiome
• Signal Transduction
• Animals
• Dysbiosis
• Biomarkers, Tumor/metabolism
• Clinical Relevance

• medical research
• oncology

• Humans
• Eicosapentaenoic Acid
• Arachidonic Acid
• Pilot Projects
• Lung Neoplasms/drug therapy
• Carcinoma, Non-Small-Cell Lung/drug therapy
• Antibodies, Monoclonal, Humanized

• JP21H03369 Japan Society for the Promotion of Science

• DHA
• EPA
• LC n-3 PUFA
• colorectal cancer
• molecular mechanisms

• Humans
• Colorectal Neoplasms/drug therapy
• Fatty Acids, Omega-3/pharmacology
• Fatty Acids, Omega-3/administration & dosage
• Animals
• Apoptosis/drug effects
• Eicosapentaenoic Acid/pharmacology
• Eicosapentaenoic Acid/administration & dosage
• Signal Transduction/drug effects
• Docosahexaenoic Acids/pharmacology
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use

• Arginine metabolism
• Colorectal cancer
• Invasion
• LC-MS/MS
• Metabolomics
• Migration
• Proliferation
• Quinazoline
• Redox hemostasis

• 5-fluorouracil
• Chemotherapy
• Combination therapy
• Melatonin

• Hematoma, Subdural, Chronic/metabolism
• Hematoma, Subdural, Chronic/physiopathology
• Hematoma, Subdural, Chronic/therapy
• Humans
• Patient Care Management/methods
• Patient Care Management/trends

• R01 HL163019 NHLBI NIH HHS

• Cancer-Associated Fibroblasts
• Colorectal Cancer
• Cyclooxygenase-2
• Esophageal Cancer
• Gastric Cancer
• Prostaglandin E2
• Tumor Immune Evasion
• Tumor-Associated Angiogenesis

• COX-2
• chemoradiotherapy
• cyclooxygenase-2
• radiotherapy
• rectal adenocarcinoma
• rectal cancer

• AMP kinase
• breast carcinoma
• cyclooxygenase-2
• mTOR
• metformin

• Chinese medicine
• T lymphocytes
• colorectal cancer
• emodin
• inflammation
• tumor microenvironment

Background and objectives: The effectiveness of neoadjuvant therapy, which is commonly used for stage II-III rectal cancer (RC) treatment, is limited. Genes associated with the pathogenesis of RC could determine response to this treatment. Therefore, the aim of this study was to investigate the potential predictive value of VEGFA, COX2, HUR and CUGBP2 genes and the associations between post-treatment changes in gene expression and the efficacy of neoadjuvant therapy. Materials and Methods: Biopsies from RC and healthy rectal tissue of 28 RC patients were collected before neoadjuvant therapy and 6-8 weeks after neoadjuvant therapy. The expression levels of VEGFA, COX2, HUR, CUGBP2 genes were evaluated using a quantitative real-time polymerase chain reaction. Results: The results reveal a significantly higher expression of VEGFA, COX2 and HUR mRNA in RC tissue compared to healthy rectal tissue (p < 0.05), and elevated VEGFA gene expression in pre-treatment tissues was associated with a better response to neoadjuvant therapy based on T-stage downstaging (p < 0.05). The expression of VEGFA, HUR and CUGBP2 genes significantly decreased after neoadjuvant therapy (p < 0.05). Responders to treatment demonstrated a significantly stronger decrease of VEGFA and COX2 expression after neoadjuvant therapy than non-responders (p < 0.05). Conclusions: The findings of this study suggest that the pre-treatment VEGFA gene expression might have predictive value for the response to neoadjuvant therapy, while the post-treatment decrease in VEGFA and COX2 gene expression could indicate the effectiveness of neoadjuvant therapy in RC patients.

• COX2
• CUGBP2
• HUR
• VEGFA
• neoadjuvant therapy
• rectal cancer

Reduced expression of cluster of differentiation (CD) 133 and cyclo‐oxygenase (COX) 2, and increased density of CD8+ tumour‐infiltrating lymphocytes, are associated with a favourable tumour response to preoperative chemoradiotherapy (CRT). This study aimed to evaluate these markers in relation to tumour response after preoperative CRT in two rectal cancer cohorts.

Patients with low rectal cancer who underwent radical resection and preoperative short‐term CRT in 2001–2007 (retrospective cohort) and long‐term CRT in 2011–2017 (prospective cohort) were analysed. Pretreatment biopsies were stained immunohistochemically using antibodies to determine CD133 and COX‐2 expression, and increased CD8+ density. Outcome measures were tumour regression grade (TRG), tumour downstaging and survival.

For 95 patients in the retrospective cohort, the incidence of TRG 3–4 was 67 per cent when two or three immunohistochemistry (IHC) features were present, but only 20 per cent when there were fewer features (P < 0·001). The incidence of tumour downstaging was higher in patients with at least two IHC features (43 versus 22 per cent with fewer features; P = 0·029). The 49 patients in the prospective cohort had similar rates to those in the retrospective cohort (TRG 3–4: 76 per cent for two or more IHC features versus 25 per cent with fewer features, P < 0·001; tumour downstaging: 57 versus 25 per cent respectively, P = 0·022). Local recurrence‐free survival rates in patients with more or fewer IHC features were similar in the retrospective and prospective cohort (P = 0·058 and P = 0·387 respectively).

Assessment of CD133, COX‐2 and CD8 could be useful in predicting a good response to preoperative CRT in patients with lower rectal cancer undergoing neoadjuvant therapy. Further studies are needed to validate the results in larger cohorts and investigate a survival benefit.

• Aceclofenac (CID: 71771)
• Aspirin (CID: 2244)
• Celecoxib (CID: 2662)
• Cyclooxygenase 2 inhibitors
• Cyclooxygenase inhibitors
• Dexibuprofen (CID: 39912)
• Diclofenac (CID: 3033)
• Etodolac (CID: 3308)
• Etoricoxib (CID: 123619)
• Fenbufen (CID: 3335)
• Fenoprofen (CID: 3342)
• Flurbiprofen (CID: 3394)
• Ibuprofen (CID:3672)
• Indomethacin (CID: 3715)
• Ketoprofen (CID: 3825)
• Ketorolac (CID: 3826)
• Lornoxicam (CID: 54690031)
• Lumiracoxib (CID: 151166)
• Meloxicam (CID: 54677470)
• Meta-analysis
• Nabumetone (CID: 4409)
• Naproxen (CID: 156391)
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Phenylbutazone (CID: 4781)
• Piroxicam (CID: 54676228)
• Rofecoxib (CID: 5090)
• Salsalate (CID: 5161)
• Skin cancer (SC)
• Sub-diseases
• Sulindac (CID: 1548887)
• Tenoxicam (CID: 54677971)
• Tiaprofenic acid (CID: 5468)
• Tolfenamic acid (CID: 610479)
• Tolmetin (CID: 5509)
• Valdecoxib (CID: 119607)

Cancer represents one of the leading causes of death worldwide. Progresses in treatment of cancer have continued at a rapid pace. However, undesirable side effects and drug resistance remain major challenges for therapeutic success. Natural products represent a valuable starting point to develop new anticancer strategies. Polyphenols, well-known as antioxidant, exert anticancer effects through the modulation of multiple pathways and mechanisms. Oat (Avena sativa L., Poaceae) is a unique source of avenanthramides (AVAs), a group of polyphenolic alkaloids, considered as its signature compounds. The present review aims to offer a comprehensive and critical perspective on the chemopreventive and chemotherapeutic potential of AVAs. AVAs prevent cancer mainly by blocking reactive species. Moreover, they exhibit potential therapeutic activity through the modulation of different pathways including the activation of apoptosis and senescence, the block of cell proliferation, and the inhibition of epithelial mesenchymal transition and metastatization. AVAs are promising chemopreventive and anticancer phytochemicals, which need further clinical trials and toxicological studies to define their efficacy in preventing and reducing the burden of cancer diseases.

• anticancer mechanisms
• avenanthramides
• cancer chemoprevention
• cancer therapy
• oat
• pharmacokinetics
• toxicological profile

Colorectal carcinoma (CRC) is the most common neoplasm of the gastrointestinal tract. COX-2 plays an important role in CRC development and is a key target for the regression of colorectal tumorigenesis by non-steroidal anti-inflammatory drugs. The present study was conducted to examine the relationship of the levels of COX-2 in CRC patients with the clinico-pathological parameters and also to assess its usefulness as a potential biomarker for diagnosis of CRC.

Prior to surgery, 30 CRC patients were enrolled and the samples from colon tumors and surrounding tissues were taken after they underwent surgical intervention at PGIMER, Chandigarh. mRNA expression levels of COX-2 were examined in 30 CRC and adjacent normal colonic mucosa by quantitative polymerase chain reaction (qPCR). The expression of COX-2 was assessed by immunohistochemical method using rabbit polyclonal antibodies against human COX-2 protein.

The quantitative relative expression of COX-2 mRNA was observed to be significantly higher (p<0.05) in colorectal cancer tissues as compared to adjacent normal colon tissues. Also, female CRC patients showed significantly higher (p<0.009) expression of COX-2 mRNA vis-a-vis male colorectal cancer patients. This is the first study which has reported a direct relationship between COX-2 mRNA expressions in male colorectal cancer patients versus females. Further, immunohistochemistry of COX-2 confirmed the quantitative real time-PCR findings.

Our study shows that COX-2 over expression in colorectal carcinoma patients is closely associated with clinico-pathological parameters and is more pronounced in males versus females. Further, COX-2 mRNA expression can serve as a potential biomarker for the diagnosis of CRC.

• Cyclooxygenase-2
• Gene expression
• Real-Time Polymerase Chain Reaction
• colorectal cancer

• COX-2
• Hippo pathway
• NF-κB
• TAZ
• TEADs
• Yes-associated protein (YAP)
• cell signaling
• cytokine
• histone deacetylase (HDAC)
• inflammation

• Azoxymethane
• Chronic inflammation
• Colitis-associated colorectal cancer
• MyD88
• Myeloid cells

Breast cancer is one of the most prevalent cancers in women, and nearly half of breast cancer patients develop distant metastatic disease after therapy. Despite the significant advances that have been achieved in understanding breast cancer metastasis in the past decades, metastatic cancer is still hard to cure. Here, we demonstrated an anti-cancer mechanism of docosahexaenoic acid (DHA) that suppressed lung metastasis in breast cancer. DHA could inhibit proliferation and invasion of breast cancer cells in vitro, and this was mainly through blocking Cox-2-PGE₂-NF-κB-MMPs cascades. DHA treatment significantly decreased Cox-2 and NF-κB expression as well as nuclear translocation of NF-κB in MDA-MB-231 cells. In addition, DHA also reduced NF-κB binding to DNA which may lead to inactivation of MMPs. Moreover, in vivo studies using Fat-1 transgenic mice showed remarkable decrease of tumor growth and metastasis to EO771 cells to lung in DHA-rich environment. In conclusion, DHA attenuated breast cancer progression and lung metastasis in part through suppressing MMPs, and these findings suggest chemoprevention and potential therapeutic strategy to overcome malignant breast cancer.

• DHA
• MMP
• breast cancer
• omega-3 PUFA

Combinatorial therapies that target multiple signaling pathways may provide improved therapeutic responses over monotherapies. Celecoxib and curcumol are two highly hydrophobic drugs which show bioavailability problems due to their poor aqueous solubility. In the present study, we evaluated the effects of celecoxib and curcumol alone and in combination on cell proliferation, invasion, migration, cell cycle and apoptosis induction in non-small cell lung cancer (NSCLC) cells using in vitro and in vivo experiments. Our data showed that the sensitivity of a combined therapy using low concentration of celecoxib and curcumol was higher than that of celecoxib or curcumol alone. Suppression of NF-κB transcriptional activity, activation of caspase-9/caspase-3, cell cycle G1 arrest, and inhibition of survival MAPK and PI3K/AKT signaling pathway contributed to the synergistic effects of this combination therapy for induction of apoptosis. Additionally, either celecoxib alone or in combination with curcumol inhibited NSCLC cell migration and invasion by suppressing FAK and matrix metalloproteinase-9 activities. Furthermore, the combined treatment reduced tumor volume and weight in xenograft mouse model, and significantly decreased tumor metastasis nodules in lung tissues by tail vein injection. Our results confirm and provide mechanistic insights into the prominent anti-proliferative activities of celecoxib and/or curcumol on NSCLC cells, which provide a rationale for further detailed preclinical and potentially clinical studies of this combination for the therapy of lung cancer.

• apoptosis
• celecoxib
• curcumol
• synergism
• tumor metastasis

• Anti-cancer
• bioavailability
• clinical pharmacokinetics
• curcumin
• interaction
• metabolism
• pharmacodynamics

Whether the intake of eicosapentaenoic acid (EPA) or arachidonic acid (AA) affects the risk of cancer remains unclear, and the association between the serum EPA:AA ratio and cancer risk has not been fully evaluated in general populations.

A total of 3098 community-dwelling subjects aged ≥40 years were followed up for 9.6 years (2002–2012). The levels of the serum EPA:AA ratio were categorized into quartiles (<0.29, 0.29–0.41, 0.42–0.60, and >0.60). The risk estimates were computed using a Cox proportional hazards model. The same analyses were conducted for the serum docosahexaenoic acid to arachidonic acid (DHA:AA) ratio and individual fatty acid concentrations.

During the follow-up period, 121 subjects died of cancer. Age- and sex-adjusted cancer mortality increased with lower serum EPA:AA ratio levels (P trend<0.05). In the multivariable-adjusted analysis, the subjects in the first quartile of the serum EPA:AA ratio had a 1.93-fold (95% confidence interval, 1.15–3.22) greater risk of cancer death than those in the fourth quartile. Lower serum EPA concentrations were marginally associated with higher cancer mortality (P trend<0.11), but the serum DHA or AA concentrations and the serum DHA:AA ratio were not (all P trend>0.37). With regard to site-specific cancers, lower serum EPA:AA ratio was associated with a higher risk of death from liver cancer. However, no such associations were detected for deaths from other cancers.

These findings suggest that decreased level of the serum EPA:AA ratio is a significant risk factor for cancer death in the general Japanese population.

•

Lower serum EPA:AA ratio was significantly associated with higher cancer mortality.

• Arachidonic acid
• Cohort studies
• Eicosapentaenoic acid
• Mortality
• Neoplasms

Chronic inflammation is recognized as a threat factor for cancer progression. Release of inflammatory molecules generates microenvironment which is highly favorable for development of tumor, cancer progression and metastasis. In cases of latent viral infections, generation of such a microenvironment is one of the major predisposing factors related to virus mediated tumorigenesis. Among various inflammatory mediators implicated in pathological process associated with cancer, the cyclooxygenase (COX) and its downstream effector molecules are of greater significance. Though the role of infectious agents in causing inflammation leading to transformation of cells has been more or less well established, however, the mechanism by which inflammation in itself modulates the events in life cycle of infectious agent is not very much clear. This is specifically important for gammaherpesviruses infections where viral life cycle is characterized by prolonged periods of latency when the virus remains hidden, immunologically undetectable and expresses only a very limited set of genes. Therefore, it is important to understand the mechanisms for role of inflammation in virus life cycle and tumorigenesis. This review is an attempt to summarize the latest findings highlighting the significance of COX-2 and its downstream signaling effectors role in life cycle events of gammaherpesviruses leading to progression of cancer.

• COX-2
• gammaherpesvirus
• inflammation

• Anticancer drug
• Carcinogenesis
• Chemoprevention
• Derivative
• Polyphenol

• Animals
• Choroid/drug effects
• Choroid/metabolism
• Choroid/pathology
• Choroidal Neovascularization/drug therapy
• Choroidal Neovascularization/pathology
• Cyclooxygenase Inhibitors/pharmacology
• Cyclooxygenase Inhibitors/therapeutic use
• Disease Models, Animal
• Fibrosis
• Macrophages/drug effects
• Macrophages/pathology
• Mice, Inbred C57BL
• Nitrobenzenes/pharmacology
• Nitrobenzenes/therapeutic use
• Retina/drug effects
• Retina/pathology
• Retinal Pigment Epithelium/drug effects
• Retinal Pigment Epithelium/metabolism
• Retinal Pigment Epithelium/pathology
• Sulfonamides/pharmacology
• Sulfonamides/therapeutic use
• Transforming Growth Factor beta2/metabolism
• Vascular Endothelial Growth Factor A/metabolism

Enzymatic metabolism of the 20C polyunsaturated fatty acid (PUFA) arachidonic acid (AA) occurs via the cyclooxygenase (COX) and lipoxygenase (LOX) pathways, and leads to the production of various bioactive lipids termed eicosanoids. These eicosanoids have a variety of functions, including stimulation of homeostatic responses in the cardiovascular system, induction and resolution of inflammation, and modulation of immune responses against diseases associated with chronic inflammation, such as cancer. Because chronic inflammation is essential for the development of colorectal cancer (CRC), it is not surprising that many eicosanoids are implicated in CRC. Oftentimes, these autacoids work in an antagonistic and highly temporal manner in inflammation; therefore, inhibition of the pro-inflammatory COX-2 or 5-LOX enzymes may subsequently inhibit the formation of their essential products, or shunt substrates from one pathway to another, leading to undesirable side-effects. A better understanding of these different enzymes and their products is essential not only for understanding the importance of eicosanoids, but also for designing more effective drugs that solely target the inflammatory molecules found in both chronic inflammation and cancer. In this review, we have evaluated the cancer promoting and anti-cancer roles of different eicosanoids in CRC, and highlighted the most recent literature which describes how those molecules affect not only tumor tissue, but also the tumor microenvironment. Additionally, we have attempted to delineate the roles that eicosanoids with opposing functions play in neoplastic transformation in CRC through their effects on proliferation, apoptosis, motility, metastasis, and angiogenesis.

• Eicosanoids
• Cyclooxygenase
• Lipoxygenase
• Inflammation
• Colorectal cancer

• Animals
• Anti-Inflammatory Agents/therapeutic use
• Antineoplastic Agents/therapeutic use
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/pathology
• Eicosanoids/metabolism
• Fatty Acids, Unsaturated/metabolism
• Humans
• Inflammation/drug therapy
• Inflammation/metabolism
• Inflammation/pathology
• Molecular Targeted Therapy
• Signal Transduction/drug effects
• Tumor Microenvironment

• COX-2
• KDM2A
• c-Fos
• histone methylation

• Blotting, Western
• Carcinogens/pharmacology
• Cell Line, Tumor
• Chromatin Immunoprecipitation
• Cyclooxygenase 2/biosynthesis
• Cyclooxygenase 2/genetics
• F-Box Proteins/genetics
• F-Box Proteins/metabolism
• Gene Expression Regulation, Neoplastic/drug effects
• Gene Expression Regulation, Neoplastic/genetics
• Gene Knockdown Techniques
• Humans
• Immunoprecipitation
• Jumonji Domain-Containing Histone Demethylases/genetics
• Jumonji Domain-Containing Histone Demethylases/metabolism
• Lung Neoplasms/genetics
• Lung Neoplasms/metabolism
• Proto-Oncogene Proteins c-fos/genetics
• Proto-Oncogene Proteins c-fos/metabolism
• Reverse Transcriptase Polymerase Chain Reaction
• Tetradecanoylphorbol Acetate/pharmacology

Micro ribonucleic acid (miR-101) can regulate the expression of cyclooxygenase-2 (COX-2) and participate in the pathogenesis of malignant tumors. This study investigates the effects of miRNA-101 and COX-2 in lung cancer and the impact of miR-101 on the proliferation and invasion of human lung cancer A549 cell line.

The expression of miR-101 in 20 separate lung cancer tissues was detected by real time polymerase chain reaction; COX-2 expression was also detected. A549 cells were transfected with miR-101 or negative control oligonucleotide duplex mimic (miR-NC). In vivo tumorigenesis abilities were detected in localized human lung cancer xeno-transplant models in BALB/c nude mice.

MiR-101 expression was significantly lower and the level of COX-2 significantly higher in lung cancer tissues than in adjacent parenchyma (2.918 ± 1.006 vs. 5.953 ± 1.976, P = 0.001; 0.887 ± 0.260 vs. 0.355 ± 0.156, P = 0.001, respectively). Correlation analysis revealed that miR-101 negatively correlated with COX-2 in lung cancer tissues (R = −0.596, P = 0.002). Compared with A549-miR-NC cells, the expression of COX-2 was significantly decreased in A549 cells transfected with miR-101 (P < 0.001). The proliferation of A549 cells was markedly inhibited after transfection of miR-101. The in vivo tumor growth of A549 cells transfected with miR-101 was significantly slower than wide type A549 cells.

MiR-101 expression is decreased in lung cancer, inducing an increase in COX-2 level. Enforced expression of miR-101 can remarkably reduce the cell proliferation and invasion ability of lung cancer cells.

• COX-2
• lung cancer
• miRNA-101

• 3D Histology
• 3D, three-dimensional
• 5-HT, serotonin
• ICC
• ICC, interstitial cells of Cajal
• ICC-CM, ICC in the circular muscle
• ICC-LM, ICC in the longitudinal muscle
• ICC-MY, ICC around the myenteric plexus
• ICC-SM, ICC at the submucosal border
• Mural Cells
• NA, numerical aperture
• PBS, phosphate-buffered saline
• SCF, stem cell factor
• c-kit

• Addition and subtraction theory
• Da chaihu decoction
• Systems pharmacology
• Traditional Chinese medicine
• Xiao chaihu decoction

• Allosteric binding
• Anacardic acid
• Cyclooxygenase-2
• Enzyme kinetics
• Human 5-lipoxygenase

• COX-2
• Gastrointestinal cancers
• NSAIDs

• Anal sac adenocarcinoma
• COX-2
• Canine
• Immunohistochemistry

Vascular endothelial growth factor (VEGF) plays a critical role in tumor progression, angiogenesis and metastasis. Cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)2, MMP9 and wild-type (WT) p53 has been found to regulate the production of VEGF. Whether VEGF regulates the production of COX-2, MMP2, MMP9 and WTp53, however, has yet to be determined. This study examined the influence of the overexpression or knockdown of VEGF on the protein levels of COX-2, MMP2, MMP9 and WTp53 as well as cell growth and cell cycle progression in Lewis lung carcinoma (LLC) cells. LLC cells were transfected with pIRES2-VEGF-GFP in the VEGF-overexpressing group (LLC-VEGF), pIRES2-GFP in the mock group (LLC-GFP) or pSUPER-VEGF-GFP in the VEGF knockdown group (LLC-RNAi). Protein levels were detected by western blot analysis. LLC cell growth exhibited no marked change in the LLC-VEGF group, but was significantly retarded in the LLC-RNAi group. Further examination revealed that more cells entered the S stage in the LLC-VEGF group than in the control (or mock) group (45.3 vs. 29.1%, P<0.05), and that cell growth was retarded in the LLC-RNAi group. Moreover, COX-2 and MMP2 and MMP9 proteins were significantly increased in the LLC-VEGF group (approximately 1.84-, 1.89- and 1.83-fold, respectively, vs. control, P<0.05), but significantly decreased in the LLC-RNAi group, whereas the expression of WTp53 exhibited the opposite pattern of change. VEGF expression was positively correlated with COX-2, MMP2 and MMP9 expression (r=0.984, r=0.978, r=0.969, respectively, P<0.01) and negatively correlated with WTp53 (r=−0.833, p<0.01). The activities of MMP2 and MMP9 were increased in the LLC-VEGF group. In conclusion, VEGF overexpression may promote the expression of COX-2 and MMPs, but inhibits WTp53 production in LLC cells; VEGF underexpression may have an inverse effect. These changes are closely correlated with the infiltration and metastasis of lung cancer.