• CD147
• EP1
• EP2
• EP3
• EP4
• HIF1α
• PGE2
• PTGES1
• PTGES2
• PTGES3
• RT-qPCR
• VEGFA
• angiogenesis
• feline oral squamous cell carcinoma
• inflammation

• Animals
• Hypoxia-Inducible Factor 1, alpha Subunit/genetics
• Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
• Vascular Endothelial Growth Factor A/genetics
• Vascular Endothelial Growth Factor A/metabolism
• Cell Line, Tumor
• Cats
• Mouth Neoplasms/veterinary
• Mouth Neoplasms/metabolism
• Mouth Neoplasms/genetics
• Carcinoma, Squamous Cell/veterinary
• Carcinoma, Squamous Cell/metabolism
• Carcinoma, Squamous Cell/genetics
• Gene Expression Regulation, Neoplastic
• Cat Diseases/metabolism
• Cat Diseases/genetics
• Prostaglandin-E Synthases/genetics
• Prostaglandin-E Synthases/metabolism
• Receptors, Prostaglandin E/genetics
• Receptors, Prostaglandin E/metabolism
• Dinoprostone/metabolism

• Zoetis
• Natural Sciences and Engineering Research Council of Canada
• Mitacs

• autophagy
• ferroptosis
• ferroptosis inducers
• oral squamous cell carcinoma
• prognosis
• signature

• drugs
• head and neck cancer
• miRNAs
• network biology
• pathways

• RS-2023-00235511 Korea Research Foundation Grant

• PTGS2
• VEGF
• Oral cancer
• angiogenesis
• gene expression
• metastasis

• Humans
• Squamous Cell Carcinoma of Head and Neck/genetics
• Carcinoma, Squamous Cell/pathology
• Mouth Neoplasms/pathology
• Cyclooxygenase 2/genetics
• Vascular Endothelial Growth Factor A/genetics
• DNA, Complementary
• Head and Neck Neoplasms

• 00000676 Manipal Academy of Higher Education
• Manipal Academy of Higher Education

• COX-2
• drug design
• dual-target inhibitor
• structure–activity relationship

• Humans
• Antineoplastic Agents/adverse effects
• Antineoplastic Agents/chemistry
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Cyclooxygenase 2/chemistry
• Cyclooxygenase 2/metabolism
• Cyclooxygenase 2 Inhibitors/adverse effects
• Cyclooxygenase 2 Inhibitors/chemistry
• Cyclooxygenase 2 Inhibitors/pharmacology
• Cyclooxygenase 2 Inhibitors/therapeutic use
• Models, Molecular
• Protein Structure, Tertiary
• Structure-Activity Relationship
• Neoplasms/drug therapy

• 2022KF-01 and 2022KF-02 Precision Medicine Key Laboratory of Sichuan Province
• 2022NSFSC1365, 2023NSFSC0041 and 2022NSFSC0785 Natural Science Foundation of Sichuan Province
• 92159302 and 32170592 National Natural Science Foundation of China

• biomarkers
• cyclooxygenase-2
• heat shock proteins
• heme oxygenase
• laryngeal cancer
• larynx
• metallothioneins
• micro ribonucleic acid
• nuclear factor erythroid 2-related factor 2

• COX-2
• Colorectal cancer
• Metastasis
• Prognosis

Novel compounds significantly interfering with the mitochondrial energy production may have therapeutic value in triple-negative breast cancer (TNBC). This criterion is clearly fulfilled by desethylamiodarone (DEA), which is a major metabolite of amiodarone, a widely used antiarrhythmic drug, since the DEA previously demonstrated anti-neoplastic, anti-metastasizing, and direct mitochondrial effects in B16F10 melanoma cells. Additionally, the more than fifty years of clinical experience with amiodarone should answer most of the safety concerns about DEA. Accordingly, in the present study, we investigated DEA’s potential in TNBC by using a TN and a hormone receptor positive (HR+) BC cell line. DEA reduced the viability, colony formation, and invasive growth of the 4T1 cell line and led to a higher extent of the MCF-7 cell line. It lowered mitochondrial transmembrane potential and induced mitochondrial fragmentation. On the other hand, DEA failed to significantly affect various parameters of the cellular energy metabolism as determined by a Seahorse live cell respirometer. Cyclooxygenase 2 (COX-2), which was upregulated by DEA in the TNBC cell line only, accounted for most of 4T1’s DEA resistance, which was counteracted by the selective COX-2 inhibitor celecoxib. All these data indicate that DEA may have potentiality in the therapy of TNBC.

• Akt pathway
• Seahorse
• amiodarone
• apoptosis
• colony formation
• invasive growth
• mitochondrial fragmentation
• therapy resistance
• ΔΨm

• Amiodarone/analogs & derivatives
• Amiodarone/pharmacology
• Animals
• Antineoplastic Agents/pharmacology
• Celecoxib/pharmacology
• Cell Line, Tumor
• Cell Movement/drug effects
• Cell Survival/drug effects
• Cyclooxygenase 2/metabolism
• Drug Resistance, Neoplasm/drug effects
• Drug Synergism
• Energy Metabolism/drug effects
• Enzyme Activation/drug effects
• Gene Expression Regulation, Enzymologic/drug effects
• Gene Expression Regulation, Neoplastic/drug effects
• Humans
• MCF-7 Cells
• Membrane Potential, Mitochondrial/drug effects
• Mice
• Mitochondria/drug effects
• Mitochondria/metabolism
• Triple Negative Breast Neoplasms/drug therapy
• Triple Negative Breast Neoplasms/metabolism
• Up-Regulation/drug effects

Laboratory rodents are the most common animal models used in preclinical cancer research. Companion animals with naturally occurring cancers are an under-utilized natural model for the development of new anti-cancer drugs. Dogs and cats develop several types of cancers that resemble those arising in humans with similar clinical and histopathological features and often with similar molecular and genetic backgrounds. Exposure to environmental carcinogens, including air, food and water are also common between people and their pets. Dogs and cats are a unique model that could be integrated between the preclinical laboratory animal model and human clinical trials.

Companion animals with naturally occurring cancers can provide an advantageous model for cancer research and in particular anticancer drug development. Compared to commonly utilized mouse models, companion animals, specifically dogs and cats, share a closer phylogenetical distance, body size, and genome organization. Most importantly, pets develop spontaneous, rather than artificially induced, cancers. The incidence of cancer in people and companion animals is quite similar and cancer is the leading cause of death in dogs over 10 years of age. Many cancer types in dogs and cats have similar pathological, molecular, and clinical features to their human counterparts. Drug toxicity and response to anti-cancer treatment in dogs and cats are also similar to those in people. Companion animals share their lives with their owners, including the environmental and socioeconomic cancer-risk factors. In contrast to humans, pets have a shorter life span and cancer progression is often more rapid. Clinical trials in companion animals are cheaper and less time consuming compared to human trials. Dogs and cats with naturally occurring cancers are an ideal and unique model for human cancer research. Model selection for the specific type of cancer is of pivotal importance. Although companion animal models for translational research have been reviewed previously, this review will try to summarize the most important advantages and disadvantages of this model. Feline oral squamous cell carcinoma as a model for head and neck squamous cell carcinoma and canine oral melanoma as a model for mucosal melanoma and immunotherapy in people will be discussed as examples.

• companion animal model
• feline oral squamous cell carcinoma
• head and neck carcinoma
• immunotherapy
• mucosal oral melanoma

• Oct4
• inflammation
• invasion
• migration
• oral squamous cell carcinoma (OSCC)

• Breast cancer
• NSAIDs
• celecoxib
• combination therapy
• metabolomics
• raloxifene

• cancer stemness
• chemoresistance
• cyclooxygenase-2
• head and neck cancer
• hypopharyngeal carcinoma
• prostaglandin E receptor 2

• Adult
• Aged
• Aged, 80 and over
• Animals
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/metabolism
• Carcinoma, Squamous Cell/pathology
• Cell Cycle Proteins/genetics
• Cell Cycle Proteins/metabolism
• Cell Line, Tumor
• Female
• Forkhead Transcription Factors/genetics
• Forkhead Transcription Factors/metabolism
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Head and Neck Neoplasms/genetics
• Head and Neck Neoplasms/metabolism
• Head and Neck Neoplasms/pathology
• Humans
• Kaplan-Meier Estimate
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• Middle Aged
• Peroxiredoxins/genetics
• Peroxiredoxins/metabolism
• Young Adult
• Mice

Schneiderian papillomas (SP) are aggressive sinonasal tumors that occasionally extend into areas that are surgically unresectable.

evaluate the signifcance of cyclo-oxygenase-2 (COX-2) expression in SP.

Immunohistochemistry for COX-2 was performed on SP samples and middle turbinates from chronic rhinosinusitis without nasal polyps controls obtained during surgical resection between 2009–2017. A positive stain was defined as having 10% or more cells exhibiting diffuse immunoreactivity. Comparisons were performed using Fisher Exact tests, t-tests, and ANOVA.

The study included 67 tumor samples and 9 controls from two academic institutions. The mean age of the SP group was 55.4 years and 53.2 years in the control group (p = 0.71). Thirty-nine (58.2%) SP patients had previous surgery compared to 1 (11.1%) in the control group (p = 0.01). The most common tumor attachment sites were the maxillary (47.8%) and ethmoid (25.4%) sinuses. Fifteen (22.4%) SP samples stained strongly positive for COX-2 and 24 (35.8%) stained weakly positive compared to no positive stains in the control group (p < 0.01). When stratified by COX-2 intensity, there were no statistically significant differences in gender, smoking history, history of previous sinus surgery, site of attachment, papilloma subtype, or future recurrence between SP samples.

COX-2 was overexpressed in 58.2% of SP cases, and strongly positive in 22.4% of cases, compared to no positive staining among controls. No significant differences in COX-2 expression were observed between SP subtypes or recurrent tumors. Further studies are warranted to evaluate COX-2 as a possible therapeutic target in tumors that overexpress the enzyme.

• COX-2
• Schneiderian papilloma
• cyclo-oxygenase
• inverted papilloma
• oncocytic papilloma
• sinonasal tumor

The cyclooxygenase-2 (COX-2) is a potent enzyme that converts arachidonic acid to prostaglandins (PG), including PGE2, a key mediator of inflammation and angiogenesis. Importantly, COX-2 is activated in response to inflammatory stimuli, where it is also believed to promote the development and progression of head and neck cancers (HNC). COX-2 can mediate its protumorigenic effect through various mechanisms, such as inducing cell proliferation, inhibition of apoptosis, and suppressing the host’s immune response. Furthermore, COX-2 can induce the production of vascular endothelial growth factors, hence, promoting angiogenesis. Indeed, the ability of COX-2 inhibitors to selectively restrict the proliferation of tumor cells and mediating apoptosis provides promising therapeutic targets for cancer patients. Thus, in this comprehensive review, we summarized the reported differential expression patterns of COX-2 in different stages of head and neck carcinogenesis—from potentially premalignant lesions to invasive carcinomas. Furthermore, we examined the available meta-analysis evidence for COX-2 role in the carcinogenesis of HNC. Finally, further understanding of the biological processes of COX-2 and its role in orchestrating cell proliferation, apoptosis, and angiogenesis may give therapeutically beneficial insight to develop the management plan of HNC patients and improve their clinical outcomes.

• carcinogenesis
• cyclooxygenase-2
• head and neck cancers
• head and neck squamous cell carcinoma
• inflammation
• potentially premalignant lesions
• prostaglandins

While prostaglandins (PGs), short-range lipid signals, regulate single cell migration, their roles in collective migration remain unclear. To address this, we use Drosophila border cell migration, an invasive, collective migration that occurs during Stage 9 of oogenesis. Pxt is the Drosophila cyclooxygenase-like enzyme responsible for PG synthesis. Loss of Pxt results in both delayed border cell migration and elongated clusters, whereas somatic Pxt knockdown causes delayed migration and compacted clusters. These findings suggest PGs act in both the border cells and nurse cells, the substrate on which the border cells migrate. As PGs regulate the actin bundler Fascin, and Fascin is required for on-time migration, we assessed whether PGs regulate Fascin to promote border cell migration. Coreduction of Pxt and Fascin results in delayed migration and elongated clusters. The latter may be due to altered cell adhesion, as loss of Pxt or Fascin, or coreduction of both, decreases integrin levels on the border cell membranes. Conversely, integrin localization is unaffected by somatic knockdown of Pxt. Together these data lead to the model that PG signaling controls Fascin in the border cells to promote migration and in the nurse cells to maintain cluster cohesion.

Epithelial-Mesenchymal Transition (EMT) and angiogenesis are crucial events for development of aggressive and often fatal Oral Squamous Cell Carcinomas (OSCCs). Both promote cancer progression and metastasis development, but while the former induces the loss of E-cadherin expression and, hence cadherin switching; the latter produces hematic blood vessel neo-formation and contribute to OSCC cell growth, tumor mass development, and dissemination. Cyclooxygenase-2 (COX-2) has an important role, not only in angiogenic mechanisms, but also in favoring cancer invasion. Indeed it decreases the expression of E-cadherin and leads to phenotypic changes in epithelial cells (EMT) enhancing their carcinogenic potential. Our aim is to evaluate the interplay between E-cadherin cytoplasmic delocalization, COX-2 up-regulation and COX-2 induced neo-angiogenesis in 120 cases of OSCC. We have analyzed the distribution and the number of neo-formed endothelial buds surrounding infiltrating cells that express COX-2, as well as the neo-formed vessels in chronic inflammatory infiltrate, which surround the tumor. A double immunostaining method was employed in order to verify co-localization of endothelial cell marker (CD34) and COX-2. IHC has also been used to assess E-cadherin expression. Our data demonstrate that the OSCC cells, which lose membranous E-cadherin staining, acquiring a cytoplasmic delocalization, overexpress COX-2. Moreover, we find a new CD34+ vessel formation (sprouting angiogenesis). Only basaloid type of OSCC showes low level of COX-2 expression together with very low level of neo-angiogenesis and consequent tumor necrosis. The well-known anti-metastatic effect of certain COX-2 inhibitors suggests that these molecules might have clinical utility in the management of advanced cancers.

• Prostaglandins
• CD-34
• Cox-2
• E-cadherin
• OSCC
• TMA
• neo-angiogenesis
• tumor microenvironment

• cancer
• colon
• cyclooxygenase-2
• invasion
• prostaglandin

• Angiogenesis
• Apoptosis
• Arachidonic acid
• Cell growth
• Cyclooxygenase-2
• Immunity
• Invasion
• Metastasis
• Microenvironment
• NSAID
• Prostaglandin
• Regulation
• Structure
• Tumor
• Tumorigenesis

Periodontitis is one of the most common chronic oral inflammatory conditions worldwide and is associated with a risk of developing oral squamous cell carcinoma (OSCC). Porphyromonas gingivalis is a major pathogen in periodontitis, and its lipopolysaccharide (LPS) promotes the expression of cyclooxygenase-2 (COX-2) in OSCC both in vivo and in vitro. Celecoxib is a selective COX-2 inhibitor; however, its antitumor effects on P. gingivalis LPS-stimulated OSCC and the underlying molecular mechanism remain unclear. To elucidate the association between periodontitis and OSCC, the effect of P. gingivalis-derived LPS on OSCC cell proliferation was examined both in vitro and in vivo in the present study. The expression levels of COX-2 and p53 in OSCC cells with/without celecoxib treatment were determined via western blotting. The therapeutic potential of celecoxib in LPS-stimulated OSCC was evaluated by staining for Ki-67 and p21, as well as with terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling staining. LPS treatment significantly increased OSCC cell proliferation in vitro, and celecoxib significantly inhibited cell proliferation with/without LPS treatment. Celecoxib treatment of OSCC cells downregulated the protein expression levels of COX-2 compared with untreated cells, but there was little change in p53 expression. In the mouse xenograft model, oral administration of celecoxib significantly suppressed tumor growth, reduced the expression of Ki-67, increased the apoptosis index and induced p21 expression with/without LPS treatment. The results from the present study demonstrate that P. gingivalis' LPS can stimulate tumor growth by interacting with OSCC cells. In conclusion, these results suggest that celecoxib could be used for the effective prevention and treatment of LPS-stimulated OSCC.

• Porphyromonas gingivalis
• celecoxib
• lipopolysaccharide
• oral squamous cell carcinoma
• periodontal disease

Prostaglandins (PGs) are lipid signaling molecules with numerous physiologic functions, including pain/inflammation, fertility, and cancer. PGs are produced downstream of cyclooxygenase (COX) enzymes, the targets of non-steroidal anti-inflammatory drugs (NSAIDs). In numerous systems, PGs regulate actin cytoskeletal remodeling, however, their mechanisms of action remain largely unknown. To address this deficiency, we undertook a pharmaco-genetic interaction screen during late-stage Drosophila oogenesis. Drosophila oogenesis is as an established model for studying both actin dynamics and PGs. Indeed, during Stage 10B, cage-like arrays of actin bundles surround each nurse cell nucleus, and during Stage 11, the cortical actin contracts, squeezing the cytoplasmic contents into the oocyte. Both of these cytoskeletal properties are required for follicle development and fertility, and are regulated by PGs. Here we describe a pharmaco-genetic interaction screen that takes advantage of the fact that Stage 10B follicles will mature in culture and COX inhibitors, such as aspirin, block this in vitro follicle maturation. In the screen, aspirin was used at a concentration that blocks 50% of the wild-type follicles from maturing in culture. By combining this aspirin treatment with heterozygosity for mutations in actin regulators, we quantitatively identified enhancers and suppressors of COX inhibition. Here we present the screen results and initial follow-up studies on three strong enhancers – Enabled, Capping protein, and non-muscle Myosin II Regulatory Light Chain. Overall, these studies provide new insight into how PGs regulate both actin bundle formation and cellular contraction, properties that are not only essential for development, but are misregulated in disease.

• Capping protein
• Drosophila melanogaster
• Enabled
• non-muscle myosin II regulatory light chain
• prostaglandins

• Cyclooxygenase-2
• immunohistochemistry
• oral submucous fibrosis
• salivary expression

• cancer
• colon cancer
• nerve blocks
• regional anesthesia

This study aimed to observe the cyclooxygenase-2 expression and its correlation with tumour size and lymph node involvement in nasopharyngeal carcinoma.

This study was cross-sectional, that enrolled 126 samples diagnosed with nasopharyngeal carcinoma in Haji Adam Malik General Hospital, Medan, Indonesia which fulfilled the inclusion criteria.

Based on this study, we found that the age peak incidence of nasopharyngeal carcinoma patients about a 41-60-year-old group (57.1%), dominated by men (71.4%). Through histopathological examination, non-keratinizing squamous cell carcinoma is the most predominant type (79.4%). We also found T3 is the most prevalent primary tumour size (32.5%) with prominent lymph node involvement N3 (45.2%), and stage IV (54.8%). Cyclooxygenase-2 overexpression is prevalent among nonkeratinizing squamous cell carcinoma (81.1%), T3 primary tumour size (41.1%), N3 node involvement (60.0%), and IV clinical stage (71.6%). In addition, we found a significant relationship between cyclooxygenase-2 expressions towards tumor size (p < 0.001) and lymph node involvement (p < 0.001) in nasopharyngeal carcinoma.

It is proved that the overexpression of cyclooxygenase-2 will increase the susceptibility of nasopharyngeal carcinoma patients having advanced primary tumour size and lymph node involvement.

• Cyclooxygenase (COX)-2
• Lymph node involvement
• Nasopharyngeal carcinoma
• Overexpression
• Tumor Size

• WNT signalling
• haematopoietic stem cell transplantation
• mesenchymal stromal cells
• nuclear hormone transcription factors
• prostaglandins

• Animals
• Cyclooxygenase 2/immunology
• Female
• Hematopoietic Stem Cells/immunology
• Hematopoietic Stem Cells/pathology
• Humans
• Leukemia, Myeloid, Acute/immunology
• Leukemia, Myeloid, Acute/pathology
• Male
• Mesenchymal Stem Cells/immunology
• Mesenchymal Stem Cells/pathology
• Mice
• Mice, Inbred NOD
• Mice, Knockout
• Mice, SCID
• Neoplasm Proteins/immunology
• Nuclear Receptor Subfamily 4, Group A, Member 1/immunology
• Nuclear Receptor Subfamily 4, Group A, Member 2/immunology
• Wnt Signaling Pathway/immunology

• P20 GM121322 NIGMS NIH HHS
• U54 GM104942 NIGMS NIH HHS

Several studies have assessed the clinicopathological and prognostic value of cyclooxygenase-2 (COX-2) expression in patients with head and neck cancer (HNC), but their results remain controversial. To address this issue, a meta-analysis was carried out. A total of 29 studies involving 2430 patients were subjected to final analysis. Our results indicated that COX-2 expression was not statistically associated with advanced tumor stage (OR, 1.23; 95% CI, 0.98–1.55) but correlated with high risk of lymph node metastasis (OR, 1.28; 95% CI, 1.03–1.60) and advanced TNM stage (OR, 1.33; 95% CI, 1.06–1.66). Moreover, COX-2 expression had significant effect on poor OS (HR, 1.93; 95% CI, 1.29–2.90), RFS (HR, 2.02; 95% CI, 1.00–4.08) and DFS (HR, 5.14; 95% CI, 2.84–9.31). The results of subgroup analyses revealed that COX-2 expression was related with high possibility of lymph node metastasis in oral cancer (OR, 1.49; 95% CI, 1.01–2.20) and advanced TNM stage in oral cancer (OR, 1.58; 95% CI, 1.05–2.37) and no site-specific HNC (OR, 1.64; 95% CI, 1.02–2.62). However, subgroup analyses only showed a tendency without statistically significant association between COX-2 expression and survival. Significant heterogeneity was not found when analyzing clinicopathological data, but it appeared when considering survival data. No publication bias was detected in this study. This meta-analysis suggested that COX-2 expression could act as a prognostic factor for patients with HNC.

• biomarker
• cyclooxygenase-2
• head and neck cancer
• meta-analysis
• prognosis

• Cyclooxygenase-2
• thyroid cancer
• gene polymorphism

• Adult
• Case-Control Studies
• Cyclooxygenase 2/genetics
• Female
• Humans
• Male
• Middle Aged
• Polymorphism, Single Nucleotide/genetics
• Thyroid Neoplasms/enzymology
• Thyroid Neoplasms/epidemiology
• Thyroid Neoplasms/genetics
• Turkey/epidemiology

Staphylococcus aureus is a major pathogen of varieties of oral mucous infection. Prostaglandin E2 (PGE₂) is a pro-inflammatory factor and Cyclooxygenase 2 (COX-2) is a critical enzyme of PGE₂ biosynthesis. The purpose of this study is to investigate whether Staphylococcus aureus can increase PGE₂ production of oral epithelial cells and how PGE₂ functions in the growth and adherence of Staphylococcus aureus. mRNA levels of COX-2, fnbpA and fnbpB were estimated by quantitative PCR. PGE₂ production was measured by Enzyme Linked Immunosorbent Assay (ELISA). The binding biomass of Staphylococcus aureus to human fibronectin was investigated by crystal violet staining and confocal laser scanning microscopy and the adherent force was measured by atomic force microscope (AFM). The COX-2 mRNA level and PGE₂ production were increased by Staphylococcus aureus. PGE₂ promoted the growth and biofilm formation of Staphylococcus aureus, enhanced the attachment of Staphylococcus aureus to the human fibronectin as well as to the HOK cells. The transcription of fnbpB was up-regulated by PGE₂ in both early and middle exponential phase but not fnbpA. These results suggest that the activation of COX-2/PGE₂ pathway in oral epithelial cell by Staphylococcus aureus can in turn facilitate the growth and the ability to adhere of the pathogen. These findings uncover a new function of PGE₂ and may lead to the potential of COX-2/PGE₂ targeting in the therapy of inflammation and cancer in both which the COX-2/PGE₂ pathway were observed activated.

• Bacterial Adhesion/physiology
• Biofilms
• Cells, Cultured
• Cyclooxygenase 2/genetics
• Cyclooxygenase 2/metabolism
• Dinoprostone/biosynthesis
• Dinoprostone/physiology
• Enzyme-Linked Immunosorbent Assay
• Fibronectins/metabolism
• Humans
• Microscopy, Atomic Force
• Mouth Mucosa/enzymology
• Mouth Mucosa/metabolism
• Mouth Mucosa/microbiology
• Real-Time Polymerase Chain Reaction
• Staphylococcus aureus/growth & development
• Staphylococcus aureus/physiology

• the National Key Research and Development Program of China
• National Natural Science Foundation of China grant
• Recruitment Program for Young Professionals
• the Youth Grant of the Science and Technology Department of Sichuan Province

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

Cyclooxygenase-2 (COX-2) is an inducible form of the enzyme that catalyses the synthesis of prostanoids, including prostaglandin E2 (PGE₂), a major mediator of inflammation and angiogenesis. COX-2 is overexpressed in cancer cells and is associated with progressive tumour growth, as well as resistance of cancer cells to conventional chemotherapy and radiotherapy. These therapies are often delivered in multiple doses, which are spaced out to allow the recovery of normal tissues between treatments. However, surviving cancer cells also proliferate during treatment intervals, leading to repopulation of the tumour and limiting the effectiveness of the treatment. Tumour cell repopulation is a major cause of treatment failure. The central dogma is that conventional chemotherapy and radiotherapy selects resistant cancer cells that are able to reinitiate tumour growth. However, there is compelling evidence of an active proliferative response, driven by increased COX-2 expression and downstream PGE₂ release, which contribute to the repopulation of tumours and poor patient outcome. In this review, we will examine the evidence for a role of COX-2 in cancer stem cell biology and as a mediator of tumour repopulation that can be molecularly targeted to overcome resistance to therapy.

• cyclooxygenase-2
• hepatocellular carcinoma
• meta-analysis
• prognosis
• survival

• 5-FU
• AKT pathway
• Celecoxib
• reactive oxygen species
• squamous cell carcinoma

• correlation analysis
• laryngeal squamous cell carcinoma
• non-coding RNA

• bioinformatics analysis
• differentially expressed genes
• head and neck squamous cell carcinoma
• molecular mechanism

Fascin, a conserved actin-bundling protein, is not only cytoplasmic but also localizes to the nucleus and nuclear periphery in both Drosophila and mammalian cell contexts. In Drosophila, prostaglandin signaling regulates this localization. In addition, Fascin plays a critical role in nucleolar architecture in both Drosophila and mammalian cells.

Fascin, a highly conserved actin-bundling protein, localizes and functions at new cellular sites in both Drosophila and multiple mammalian cell types. During Drosophila follicle development, in addition to being cytoplasmic, Fascin is in the nuclei of the germline-derived nurse cells during stages 10B–12 (S10B–12) and at the nuclear periphery during stage 13 (S13). This localization is specific to Fascin, as other actin-binding proteins, Villin and Profilin, do not exhibit the same subcellular distribution. In addition, localization of fascin1 to the nucleus and nuclear periphery is observed in multiple mammalian cell types. Thus the regulation and function of Fascin at these new cellular locations is likely to be highly conserved. In Drosophila, loss of prostaglandin signaling causes a global reduction in nuclear Fascin and a failure to relocalize to the nuclear periphery. Alterations in nuclear Fascin levels result in defects in nucleolar morphology in both Drosophila follicles and cultured mammalian cells, suggesting that nuclear Fascin plays an important role in nucleolar architecture. Given the numerous roles of Fascin in development and disease, including cancer, our novel finding that Fascin has functions within the nucleus sheds new light on the potential roles of Fascin in these contexts.

• Carcinoma epidermoide de laringe
• Cervical lymphatic metastases
• Immunohistochemistry
• Imunohistoquímica
• Metástase
• Squamous cell carcinoma of larynx
• VEGF

• cyclooxygenase-2 (COX-2)
• microsomal prostaglandin-E synthase-1 (mPGES-1)
• oral cavity
• recurrent squamous cell carcinoma (SCC)
• salvage surgery