The cause of acute lethality of mice exposed to a laser-induced shock wave to the brainstem.

Air embolism is generally considered the most common cause of death within 1 h of a blast injury. Shock lung, respiratory arrest, and circulatory failure caused by vagal reflexes contribute to fatal injuries that lead to immediate death; however, informative mechanistic data are insufficient. Here we used a laser-induced shock wave (LISW) to determine the mechanism of acute fatalities associated with blast injuries. We applied the LISW to the forehead, upper neck, and thoracic dorsum of mice and examined their vital signs. Moreover, the LISW method is well suited for creating site-specific damage. Here we show that only mice with upper neck exposure, without damage elsewhere, died more frequently compared with the other injured groups. The peripheral oxygen saturation (SpO2) of the former mice significantly decreased for < 1 min [p < 0.05] but improved within 3 min. The LISW exposure to the upper neck region was the most lethal factor, affecting the respiratory function. Protecting the upper neck region may reduce fatalities that are related to blast injuries.

Identification of Tumor-Suppressive miR-30e-3p Targets: Involvement of SERPINE1 in the Molecular Pathogenesis of Head and Neck Squamous Cell Carcinoma.

Recently, our studies revealed that some passenger strands of microRNAs (miRNAs) were closely involved in cancer pathogenesis. Analysis of miRNA expression signatures showed that the expression of miR-30e-3p (the passenger strand of pre-miR-30e) was significantly downregulated in cancer tissues. In this study, we focused on miR-30e-3p (the passenger strand of pre-miR-30e). We addressed target genes controlled by miR-30e-3p that were closely associated with the molecular pathogenesis of head and neck squamous cell carcinoma (HNSCC). Ectopic expression assays demonstrated that the expression of miR-30e-3p attenuated cancer cell malignant phenotypes (e.g., cell proliferation, migration, and invasive abilities). Our analysis of miR-30e-3p targets revealed that 11 genes (ADA, CPNE8, C14orf126, ERGIC2, HMGA2, PLS3, PSMD10, RALB, SERPINE1, SFXN1, and TMEM87B) were expressed at high levels in HNSCC patients. Moreover, they significantly predicted the short survival of HNSCC patients based on 5-year overall survival rates (p < 0.05) in The Cancer Genome Atlas (TCGA). Among these targets, SERPINE1 was found to be an independent prognostic factor for patient survival (multivariate Cox regression; hazard ratio = 1.6078, p < 0.05). Aberrant expression of SERPINE1 was observed in HNSCC clinical samples by immunohistochemical analysis. Functional assays by targeting SERPINE1 expression revealed that the malignant phenotypes (e.g., proliferation, migration, and invasion abilities) of HNSCC cells were suppressed by the silencing of SERPINE1 expression. Our miRNA-based approach will accelerate our understanding of the molecular pathogenesis of HNSCC.

Efficacy of Bioshell Calcium Oxide Water as Disinfectants to Enable Face Mask Reuse.

Bioshell calcium oxide (BiSCaO) is derived from scallop shells and after heat treatment exhibits broad microbicidal activity. BiSCaO Water is a disinfectant prepared by collecting the aqueous layer after adding BiSCaO powder to water, is colorless and transparent, and has a pH of 12.8. We compared the utility of commercially available BiSCaO Water, ethanol, sodium hypochlorite, hypochlorous acid and hydrogen peroxide solutions as sterilization agents to enable the reuse of surgical and N95 face masks. The microbicidal efficacy of each disinfectant was evaluated using pieces of surgical and N95 face masks contaminated with normal bacterial flora. The results suggest that BiSCaO Water has excellent disinfection activity toward contaminated polypropylene masks and has minimal adverse effect on the structure of non-woven masks.

Safety of Concentrated Bioshell Calcium Oxide Water Application for Surface and Skin Disinfections against Pathogenic Microbes.

Immediately post-production, commercially available bioshell calcium oxide (BiSCaO) water is colorless, transparent, and strongly alkaline (pH 12.8), and is known to possess deodorizing properties and broad microbicidal activity. However, BiSCaO Water may represent a serious safety risk to the living body, given the strong alkalinity. This study aimed to investigate the safety of BiSCaO Water for use as an antiseptic/disinfectant despite concerns regarding its high alkalinity. The change over time in pH of BiSCaO Water was measured during air contact (stirring BiSCaO Water in ambient air). When sprayed on metal, plastic, wood piece, paper, and skin surfaces, the pH of BiSCaO Water decreased rapidly, providing a white powder coating upon drying. Scanning electron microscopy images, energy dispersive X-ray elemental mapping, and X-ray diffractograms showed that the dried powder residues of BiSCaO Water were composed primarily of calcium carbonate. These results suggested that BiSCaO Water is a potent reagent that may overcome the obstacles of being strongly alkaline, making this material appropriate for use in disinfection against pathogenic microbes.

Development of prediction models for the sensitivity of oral squamous cell carcinomas to preoperative S-1 administration.

S-1 is an anticancer agent that is comprised of tegafur, gimeracil, and oteracil potassium, and is widely used in various carcinomas including oral squamous cell carcinoma (OSCC). Although an established prediction tool is not available, we aimed to develop prediction models for the sensitivity of primary OSCC cases to the preoperative administration of S-1. We performed DNA microarray analysis of 95 cases with OSCC. Using global gene expression data and the clinical data, we developed two different prediction models, namely, model 1 that comprised the complete response (CR) + the partial response (PR) versus stable disease (SD) + progressive disease (PD), and model 2 that comprised responders versus non-responders. Twelve and 18 genes were designated as feature genes (FGs) in models 1 and 2, respectively, and, of these, six genes were common to both models. The sensitivity was 96.3%, the specificity was 91.2%, and the accuracy was 92.6% for model 1, and the sensitivity was 95.6%, the specificity was 85.2%, and the accuracy was 92.6% for model 2. These models were validated using receiver operating characteristic analysis, and the areas under the curves were 0.967 and 0.949 in models 1 and 2, respectively. The data led to the development of models that can reliably predict the sensitivity of patients with OSCC to the preoperative administration of S-1. The mechanism that regulates S-1 sensitivity remains unclear; however, the prediction models developed provide hope that further functional investigations into the FGs will lead to a greater understanding of drug resistance.

Bioshell Calcium Oxide-Containing Liquids as a Sanitizer for the Reduction of Histamine Production in Raw Japanese Pilchard, Japanese Horse Mackerel, and Chub Mackerel.

Recently, there has been an increase in the number of food poisoning cases associated with histamine in food, mainly in relation to histamine in fish. Here, we investigated methods to decrease histamine levels in Japanese pilchard, Japanese horse mackerel, and chub Mackerel, stored at 10 °C using various concentrations of heated scallop bioshell calcium oxide (BiSCaO) suspension, dispersion (BiSCaO + Na2HPO4), colloidal dispersion (BiSCaO + NapolyPO4), scallop shell powder (SSP) Ca(OH)2 in pure water (PW) or saline, and BiSCaO water. BiSCaO in a high alkaline pH solution chemically decomposes histamine poorly, but the partial flocculation/precipitation of histamine was observed with 1 and 0.2 wt.% BiSCaO dispersion and BiSCaO colloidal dispersion, respectively. Cleaning fish samples with BiSCaO suspension, dispersion, colloidal dispersion, or BiSCaO water remarkably reduced histamine levels and normal bacterial flora (coliform bacteria (CF) and total viable bacterial cells (TC)) after storage for four days at 10 °C, while much higher histamine levels were observed after cleaning with saline. These results suggest that cleaning fish with BiSCaO dispersion, colloidal dispersion, or BiSCaO water can significantly reduce histamine levels through their bactericidal activity against histamine-producing bacteria.

Concentrated Bioshell Calcium Oxide (BiSCaO) Water Kills Pathogenic Microbes: Characterization and Activity.

Bioshell calcium oxide (BiSCaO) exhibits deodorizing properties and broad microbicidal activity. In this study, we examined possible utility of BiSCaO Water for that purpose. BiSCaO Water was prepared by adding 10 wt% BiSCaO to clean water and gently collecting the supernatant in a bottle. The same volume of clean water was gently poured onto the BiSCaO precipitate and the supernatant was gently collected in a bottle; this process was repeated fifty times. The produced BiSCaO Water contained nanoparticles (about 400-800 nm) composed of smaller nanoparticles (100-200 nm), and was colorless and transparent, with a pH > 12.7. In vitro assays demonstrated that BiSCaO Water eliminated more than 99.9% of influenza A (H1N1) and Feline calicivirus, Escherichia coli such as NBRC 3972 and O-157:H7, Pseudomonas aeruginosa, Salmonella, and Staphylococcus aureus within 15 min. We compared BiSCaO Water with the other microbicidal reagents such as ethanol, BiSCaO, BiSCa(OH)2 suspensions, povidone iodine, NaClO, BiSCaO dispersion and colloidal dispersion with respect to deodorization activity and microbicidal efficacy. The results showed that BiSCaO Water was a potent reagent with excellent deodorization and disinfection activities against pathogenic bacteria and viruses (including both enveloped and nonenveloped viruses).

Bioshell Calcium Oxide (BiSCaO) Ointment for the Disinfection and Healing of Pseudomonas aeruginosa-Infected Wounds in Hairless Rats.

Bioshell calcium oxide (BiSCaO) possesses deodorizing properties and broad microbicidal activity. This study aimed to investigate the application of BiSCaO ointment for the prevention and treatment of infection in chronic wounds in healing-impaired patients, without delaying wound healing. The bactericidal activities of 0.04, 0.2, 1, and 5 wt% BiSCaO ointment, 3 wt% povidone iodine ointment, and control (ointment only) were compared to evaluate the in vivo disinfection and healing of Pseudomonas aeruginosa-infected wounds in hairless rats. Treatment of the infected wounds with 0.2 wt% BiSCaO ointment daily for 3 days significantly enhanced wound healing and reduced the in vivo bacterial counts compared with povidone iodine ointment and control (no wound cleaning). Although 5 wt% BiSCaO ointment provided the lowest bacterial counts during 3 days' treatment, it delayed wound healing. Histological examinations showed significantly advanced granulation tissue and capillary formation in wounds treated with 0.2 wt% BiSCaO ointment for 3 days compared to wounds treated with the other ointments. This study suggested that using 0.2 wt% BiSCaO ointment as a disinfectant for infected wounds and limiting disinfection to 3 days may be sufficient to avoid the negative effects of BiSCaO on wound repair.

Bioshell calcium oxide (BiSCaO) for cleansing and healing Pseudomonas aeruginosa-infected wounds in hairless rats.

BACKGROUND: Scallop shell powder is called bioshell calcium oxide (BiSCaO), which is known to possess deodorizing properties and broad antimicrobial activity against various pathogenic microbes, including viruses, bacteria, spores, and fungi. OBJECTIVE: This study aims to investigate the applications of BiSCaO suspension cleansing in clinical situations, for instance for the prevention and treatment of infections in chronic wounds in healing-impaired patients, without delaying wound healing. METHODS: The bactericidal activities of 1000 ppm BiSCaO suspension; 500 ppm hypochlorous acid; 1000 ppm povidone iodine; and saline were compared to evaluate in vivo disinfection and healing of Pseudomonas aeruginosa-infected wounds in hairless rats. RESULTS: Cleansing of the infected wounds with BiSCaO suspension daily for 3 days significantly enhanced wound healing and reduced the in vivo bacterial counts, in comparison to hypochlorous acid, povidone iodine, and saline. Furthermore, histological examinations showed significantly advanced granulation tissue and capillary formation in the wounds cleansed with BiSCaO suspension than in those cleansed with the other solutions. CONCLUSIONS: This study suggested that the possibility of using BiSCaO suspension as a disinfectant for infected wounds and limiting disinfection to 3 days may be sufficient to avoid the negative effects on wound repair.

Skin Cleansing Technique with Disinfectant using Improved High-Velocity Steam-Air Micromist Jet Spray.

Application of a high-velocity steam-air micromist jet spray (HVS-AMJS) with disinfectants for cleansing the skin is proposed. Low-pressure steam is mixed with compressed air in a nozzle and then sprayed onto a surface of skin or material located approximately 22 cm from the nozzle. The temperature on the sprayed surface was controlled between 40ºC and 45 ºC. The improved HVS-AMJS installed scattering prevention cover with tap water effectively removed normal bacterial flora (total viable count and coliform bacteria) from contaminated skin pieces and pig skin wounds. Furthermore, the cleansing efficacy increased by advanced-treating with bio-shell calcium oxide (BiSCaO), hypochlorous acid (HClO), sodium hypochlorite (NaClO), povidone iodine, or chlorhexidine gluconate. Especially, the improved HVS-AMJS combined with BiSCaO had higher bactericidal activity than when combined with other disinfectants. This study suggests that application of the HVS-AMJS with disinfectants, especially BiSCaO, may be useful for skin cleansing to prevent infection.

Heparinoid Complex-Based Heparin-Binding Cytokines and Cell Delivery Carriers.

Heparinoid is the generic term that is used for heparin, heparan sulfate (HS), and heparin-like molecules of animal or plant origin and synthetic derivatives of sulfated polysaccharides. Various biological activities of heparin/HS are attributed to their specific interaction and regulation with various heparin-binding cytokines, antithrombin (AT), and extracellular matrix (ECM) biomolecules. Specific domains with distinct saccharide sequences in heparin/HS mediate these interactions are mediated and require different highly sulfated saccharide sequences with different combinations of sulfated groups. Multivalent and cluster effects of the specific sulfated sequences in heparinoids are also important factors that control their interactions and biological activities. This review provides an overview of heparinoid-based biomaterials that offer novel means of engineering of various heparin-binding cytokine-delivery systems for biomedical applications and it focuses on our original studies on non-anticoagulant heparin-carrying polystyrene (NAC-HCPS) and polyelectrolyte complex-nano/microparticles (N/MPs), in addition to heparin-coating devices.

Application of Colloidal Dispersions of Bioshell Calcium Oxide (BiSCaO) for Disinfection.

Bioshell calcium oxide (BiSCaO) is a scallop-shell powder heated at a high temperature. BiSCaO is composed mainly of calcium oxide and exhibits broad microbicidal properties. The aim of this study is to evaluate the disinfection and decontamination abilities of BiSCaO colloidal dispersions with that of commercially available bioshell calcium hydroxide (BiSCa(OH)2) following the formation of flocculants/precipitates under strongly alkaline conditions (pH 11.5-12.2). Various concentrations of BiSCaO and BiSCa(OH)2 colloidal dispersions were prepared by mixing with Na-polyPO4 (PP) and Na-triPO4 (TP) as flocculating agents. The microbicidal activities, and the degree of flocculation/precipitation of trypan blue, albumin, chondroitin sulfate, heparin, non-anticoagulant heparin carrying polystyrene (NAC-HCPS), and low-molecular-weight heparin/protamine nanoparticles (LMWH/P NPs) were dependent on the pH, the average particle diameter, and the concentration of BiSCaO or BiSCa(OH)2 and of the phosphate compound. BiSCaO (average particle diameter: 6 µm) colloidal dispersions (0.2 wt.%) containing 0.15 wt.% PP or TP exhibited substantially stronger microbicidal activity and flocculation/precipitation under strongly alkaline conditions. These results suggest that BiSCaO colloidal dispersions together with phosphate compounds have practical applicability for disinfection.

Preparation and Application of Bioshell Calcium Oxide (BiSCaO) Nanoparticle-Dispersions with Bactericidal Activity.

Scallop-shell powder (SSP) heated at high temperature exhibits high pH and broad antimicrobial activity. Bioshell calcium oxide (BiSCaO) is an SSP composed mainly of calcium oxide. It is poorly water-soluble under alkaline conditions and the generated precipitate can plug spray nozzles. The aim of this study was to establish that BiSCaO dispersion caused no significant CaO loss and plugging of spray nozzles, and to evaluate its deodorization and microbicidal abilities and its ability to reduce the concentrations of NO2- and NO3-. BiSCaO dispersions were prepared by mixing various concentrations of BiSCaO suspension, while phosphate compounds such as Na3PO4, Na2HPO4 or NaH2PO4 and the pH, average diameter, zeta potential, and form of the compounds with cryo-SEM were evaluated. We evaluated deodorization using tainted pork meat and microbicidal efficacy using contaminated suspension with normal bacterial flora. The concentration of NO2- and NO3- after mixing BiSCaO dispersion and pure water containing a high proportion of NO2- and NO3- were measured. BiSCaO dispersion formed with Na2HPO4, whose ratio to BiSCaO was 60%, showed a high pH (>12), a small particle diameter (>181 nm) and was stable for seven days. The BiSCaO dispersion showed higher deodorization and microbicidal activities than SSP-Ca(OH)2, which was mainly composed of Ca(OH)2. BiSCaO, but not SSP-Ca(OH)2, could reduce the concentration of NO2- and NO3- by more than 90% within 15 min. We developed a stable BiSCaO dispersion, and it had high deodorization and microbicidal efficacy. These activities of BiSCaO might result from the high pH caused by CaO hydration and a reduction activity causing active radical species.

Comparison of Various Disinfectants on Bactericidal Activity Under Organic Matter Contaminated Environments.

The bactericidal activity of heated bio-shell calcium oxide (BiSCaO) powder suspension (pH 12.4) , hypochlorous acid (HClO; pH 6), sodium hypochlorite (NaClO; pH 8) , povidone-iodine (Isodine solution®) , and chlorhexidine gluconate (Hibiscrub®) under organic matter contaminated environments were compared for tests conducted on wood scraps and pig skin pieces that were incubated with normal bacterial flora (total viable counts and coliform bacteria) . The test results showed that BiSCaO suspension had higher bactericidal activity than HClO and NaClO. Furthermore, more than 10-fold higher concentrations of antiseptics such as povidone-iodine and chlorhexidine gluconate were required to achieve bactericidal activity comparable to that of BiSCaO suspension. Our results demonstrate the possibility of using BiSCaO suspension under organic matter contaminated environments as a disinfectant for environmental and food hygiene applications.

Behavior of Nitrate-Nitrogen and Nitrite-Nitrogen in Drinking Water.

Nitrate-nitrogen (NO3-N) and nitrite-nitrogen (NO2-N) are constituents of the nitrogen cycle. NO3-N is toxic to humans, primarily due to its reduction to NO2-N. In Japan, NO3-N and NO2-N levels in tap water must not exceed 10 mg/L and only NO2-N alone not 0.04 mg/L, respectively. In this study, we verified the effect of microorganisms and ultraviolet (UV) to increase of NO2-N in water. First, all tested drinking-waters including tap water and commercial mineral water in PET bottles had < 2 mg/L NO3-N and undetectable levels (< 0.01 mg/L) of NO2-N. However, we found that NO2-N was generated in tap water left to stand at room temperature for several days, leading to increases in CF and TC counts and reduction of NO3-N. We also demonstrated that direct UV and sunlight irradiation of NO3-N-containing drinking water generated NO2-N in 1-2 h, with NO2-N reaching > 0.04 mg/mL by 4-6 h. On the other hand, NO3-N and NO2-N were undetectable in commercially purified water.

Reflex arc of the teeth clenching-induced pressor response in rats.

Although "teeth clenching" induces pressor response, the reflex tracts of the response are unknown. In this study, dantrolene administration inhibited teeth clenching generated by electrical stimulation of the masseter muscles and completely abolished the pressor response. In addition, trigeminal ganglion block or hexamethonium administration completely abolished the pressor response. Local anesthesia of molar regions significantly reduced the pressor response to 27 ± 10%. Gadolinium (mechanoreceptor blocker of group III muscle afferents) entrapment in masticatory muscles also significantly reduced the pressor response to 62 ± 7%. Although atropine methyl nitrate administration did not change the pressor response, a significant dose-dependent augmentation of heart rate was observed. These results indicate that both periodontal membrane and mechanoreceptors in masticatory muscles are the receptors for the pressor response, and that the afferent and efferent pathways of the pressor response pass through the trigeminal afferent nerves and sympathetic nerves, respectively.

Protective effect of FGF-2 and low-molecular-weight heparin/protamine nanoparticles on radiation-induced healing-impaired wound repair in rats.

We examined the effectiveness of localized administration of fibroblast growth factor-2 containing low-molecular-weight heparin/protamine nanoparticles (FGF-2&LMWH/P NPs) on apoptosis in vivo and on healing of radiation-induced skin injury in a rat model. FGF-2 binds onto LMWH/P NPs, which can significantly enhance and stabilize FGF-2 as a local carrier. X-irradiation at a dose of 25 Gy was administered to the lower part of the back (using a lead sheet with two holes) 1 h before the administration of FGF-2&LMWH/P NPs. Cutaneous full-thickness defect wounds were then formed in X-irradiated areas to examine the time-course of wound healing, and the wound tissues were microscopically and histologically compared and examined. Wound healing was significantly delayed by X-irradiation, but FGF-2&LMWH/P NPs administration prior to irradiation led to a significantly shorter delay compared with FGF-2 alone, LMWH/P NPs alone, and controls. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining showed that the proportions of apoptotic dermal fibroblasts in X-irradiated skin were significantly lower in rats administered FGF-2&LMWH/P NPs than in controls. However, 8-hydroxy-2'-deoxyguanosine (8-OHdG) staining showed no differences. Thus, localized administration of FGF-2&LMWH/P NPs prior to irradiation may alleviate X-irradiation-induced healing-impaired wound repair in normal tissue.

Stability of Weakly Acidic Hypochlorous Acid Solution with Microbicidal Activity.

　Hypochlorous acid (HOCl) solution (200 ppm, pH 6) was prepared and evaluated for their stabilities and microbicidal activities. We demonstrated that HOCl is unstable against ultraviolet (UV) light, sunshine, contact with air, and elevated temperature (≧25℃). Furthermore, in the HOCl solution, the presence of excess NH2- or CHO-containing organic compounds such as proteins and carbohydrates, or of inorganic ions such as NO2-, SO3-, PO3-, Fe2+, Cu2+, and CuS, resulted in the rapid consumption of HOCl by oxidation reactions, and significantly decreased the microbicidal activity of the HOCl solution against coliform bacteria and total viable cell count. Thus, production of stable HOCl solution requires formulation in pure water harboring concentrations as low as possible of various compounds and ions, as well as storage in dark and cool conditions (<10℃) to maintain the concentration of HOCl molecules and microbicidal activity.

Cleansing technique using high-velocity steam-air micromist jet spray.

Application of a high-velocity steam-air micromist jet spray (HVS-AMJS; micromist average diameter: 2.4 µm) for cleansing the skin is proposed. Low-pressure steam is mixed with compressed air (pH 6.5) in a nozzle, and then sprayed at a pressure of ≦0.25 MPa and a velocity of ≧0.34 m/s on the skin or surface of material located approximately 5-10 cm from the nozzle. The temperature on the sprayed surface and water flow rate could be controlled between 42 °C and 46 °C and at approximately 50 mL/min, respectively. Compared with ultrasonic cleansing with tap water and rubbing with only tap water, the HVS-AMJS successfully removed fluorescent lotion covering pieces of wood and significantly reduced both the number of coliforms and the total viable counts on pieces of wood and gauze. Furthermore, the HVS-AMJS effectively removed oily ink from the skin of hairless rats, and temporarily elevated the skin temperature and blood flow, indicating massage effects. The striking characteristics of this cleansing technique using HVS-AMJS are not only its ability to remove microbes and residue without using any chemicals or detergents but also its massage effects.

Cavin-2 in oral cancer: A potential predictor for tumor progression.

Cavin-2 (CVN2) affects formation of large caveolae, which are membrane-rich cholesterol domains associated with several functions in signal transduction. Accumulating evidence suggests that CVN2 is present in many cellular types; however, the molecular mechanisms of CVN2 in cancers and its clinical relevance are unknown. We proposed a mechanism by which CVN2 regulates caveolin-1 expression leading to slow cellular proliferation by inactivation of the extracellular regulated kinase (ERK) pathway. Quantitative reverse transcriptase-polymerase chain reaction and immunoblot analyses were used to assess the CVN2 regulation mechanism in oral squamous cell carcinoma (OSCC). Immunohistochemistry (IHC) was performed to analyze the correlation between CVN2 expression and clinical behavior in 115 patients with OSCC. A CVN2 overexpressed model of OSCC cells (oeCVN2 cells) was used for functional experiments. CVN2 expression was down-regulated significantly (P < 0.05) in OSCCs compared with normal counterparts in vitro and in vivo. In addition to the findings that a serum deprivation culture induced up-regulation of CVN2 and slowed cellular proliferation, oeCVN2 cell growth decreased because of cell-cycle arrest at the G1 phase resulting from up-regulated cyclin-dependent kinase inhibitors (p21(Cip1) and p27(Kip1) ) and down-regulated cyclins (cyclin D1, cyclin E) and cyclin-dependent kinases (CDK2, CDK4, and CDK6). Interestingly, CVN2 overexpression facilitated caveolin-1 recruitment and colocalization with each other. We also found decreased ERK phosphorylation levels, an upstream event in cell-cycle arrest. Clinically, IHC data from primary OSCCs showed high tumoral progression in CVN2-negative patients with OSCC. CVN2 may be a possible key regulator of OSCC progression via the CVN2/caveolin-1/ERK pathway and a potential therapeutic target for developing new treatments for OSCCs. © 2015 Wiley Periodicals, Inc.