SEC22B inhibition attenuates colorectal cancer aggressiveness and autophagic flux under unfavorable environment.

Autophagy has bidirectional functions in cancer by facilitating cell survival and death in a context-dependent manner. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are a large family of proteins essential for numerous biological processes, including autophagy; nevertheless, their potential function in cancer malignancy remains unclear. Here, we explored the gene expression patterns of SNAREs in tissues of patients with colorectal cancer (CRC) and discovered that SEC22B expression, a vesicle SNARE, was higher in tumor tissues than in normal tissues, with a more significant increase in metastatic tissues. Interestingly, SEC22B knockdown dramatically decreased CRC cell survival and growth, especially under stressful conditions, such as hypoxia and serum starvation, and decreased the number of stress-induced autophagic vacuoles. Moreover, SEC22B knockdown successfully attenuated liver metastasis in a CRC cell xenograft mouse model, with histological signs of decreased autophagic flux and proliferation within cancer cells. Together, this study posits that SEC22B plays a crucial role in enhancing the aggressiveness of CRC cells, suggesting that SEC22B might be an attractive therapeutic target for CRC.

The Small-Molecule Wnt Inhibitor ICG-001 Efficiently Inhibits Colorectal Cancer Stemness and Metastasis by Suppressing MEIS1 Expression.

Recurrence and metastasis remain major obstacles in colorectal cancer (CRC) treatment. Recent studies suggest that a small subpopulation of cells with a self-renewal ability, called cancer stem-like cells (CSCs), promotes recurrence and metastasis in CRC. Unfortunately, no CSC inhibitor has been demonstrated to be more effective than existing chemotherapeutic drugs, resulting in a significant unmet need for effective CRC therapies. In this study, transcriptomic profiling of metastatic tumors from CRC patients revealed significant upregulation in the Wnt pathway and stemness genes. Thus, we examined the therapeutic effect of the small-molecule Wnt inhibitor ICG-001 on cancer stemness and metastasis. The ICG-001 treatment efficiently attenuated self-renewal activity and metastatic potential. Mechanistically, myeloid ecotropic viral insertion site 1 (MEIS1) was identified as a target gene of ICG-001 that is transcriptionally regulated by Wnt signaling. A series of functional analyses revealed that MEIS1 enhanced the CSC behavior and metastatic potential of the CRC cells. Collectively, our findings suggest that ICG-001 efficiently inhibits CRC stemness and metastasis by suppressing MEIS1 expression. These results provide a basis for the further clinical investigation of ICG-001 as a targeted therapy for CSCs, opening a new avenue for the development of novel Wnt inhibitors for the treatment of CRC metastasis.

Anti-allergic effect of luteolin in mice with allergic asthma and rhinitis.

AIM OF THE STUDY: We aimed to evaluate the anti-allergic effect of luteolin treatment in mice with allergic asthma and rhinitis. MATERIAL AND METHODS: Thirty-two BALB/c mice (n = 8 for each group) were used. Mice in group A (nonallergic group) were exposed to saline, while those in Group B (allergic group) were exposed to ovalbumin (OVA) intraperitoneal (i.p.) injection and intranasal (i.n.) challenge. Null treatment group (Group C) received sterile saline (150 µl) i.p. injection, 30 minutes before each i.n. challenge. Finally, the treatment group (Group D) received luteolin (0.1 mg/kg) by i.p. injection, 30 minutes before each i.n. challenge. We evaluated the number of inflammatory cells including eosinophils, neutrophils and lymphocytes in bronchoalveolar lavage (BAL) fluid, the titers of IL-4, IL-5 and IL-13 in lung homogenate, and we also evaluated histopathologic findings, including infiltration of inflammatory cells into the pulmonary parenchyma and nasal mucosa. RESULTS: After the OVA challenge, the number of eosinophils, neutrophils and lymphocytes in BAL fluid was significantly increased in group B, compared to group A (p < 0.001). Mice in group C had no significant difference (p > 0.05). On the other hand, group D showed a significant decrease in all inflammatory cells compared to group B (p < 0.05). Also, group D showed a significant decrease in IL-4, IL-5 and IL-13 in their lung homogenate compared to groups B and C (p < 0.05). Group D also showed a significant decrease in inflammatory cell infiltration after luteolin treatment (p < 0.05). CONCLUSION: Luteolin had an anti-allergic effect in a murine model of allergic asthma and rhinitis.

Feeding by heterotrophic dinoflagellates and ciliates on the free-living dinoflagellate Symbiodinium sp. (Clade E).

To investigate heterotrophic protists grazing on Symbiodinium sp., we tested whether the common heterotrophic dinoflagellates Gyrodinium dominans, Gyrodinium moestrupii, Gyrodinium spirale, Oblea rotundata, Oxyrrhis marina, and Polykrikos kofoidii and the ciliates Balanion sp. and Parastrombidinopsis sp. preyed on the free-living dinoflagellate Symbiodinium sp. (clade E). We measured the growth and ingestion rates of O. marina and G. dominans on Symbiodinium sp. as a function of prey concentration. Furthermore, we compared the results to those obtained for other algal prey species. In addition, we measured the growth and ingestion rates of other predators at single prey concentrations at which these rates of O. marina and G. dominans were saturated. All predators tested in the present study, except Balanion sp., preyed on Symbiodinium sp. The specific growth rates of O. marina and G. dominans on Symbiodinium sp. increased rapidly with increasing mean prey concentration < ca. 740-815 ng C/ml (7,400-8,150 cells/ml), but became saturated at higher concentrations. The maximum growth rates of O. marina and G. dominans on Symbiodinium sp. (0.87 and 0.61/d) were much higher than those of G. moestrupii and P. kofoidii (0.11 and 0.04/d). Symbiodinium sp. did not support positive growth of G. spirale, O. rotundata, and Parastrombidinopsis sp. However, the maximum ingestion rates of P. kofoidii and Parastrombidinopsis sp. (6.7-10.0 ng C/predator/d) were much higher than those of O. marina and G. dominans on Symbiodinium sp. (1.9-2.1 ng C/predator/d). The results of the present study suggest that Symbiodinium sp. may increase or maintain the populations of some predators.

Gymnodinium smaydae n. sp., a new planktonic phototrophic dinoflagellate from the coastal waters of Western Korea: morphology and molecular characterization.

The marine phototrophic dinoflagellate Gymnodinium smaydae n. sp. is described from cells prepared for light, scanning, and transmission electron microscopy. Also, sequences of the small (SSU) and large subunits (LSU) and the internal transcribed spacer region (ITS1-5.8S-ITS2) of ribosomal DNA were analyzed. This newly isolated dinoflagellate possessed nuclear chambers, nuclear fibrous connective, an apical groove running in a counterclockwise direction around the apex, and a major accessory pigment peridinin, which are four key features for the genus Gymnodinium. The epicone was conical with a round apex, while the hypocone was ellipsoid. Cells growing photosynthetically were 6.3-10.9 µm long and 5.1-10.0 µm wide, and therefore smaller than any other Gymnodinium species so far reported except Gymnodinium nanum. Cells were covered with polygonal amphiesmal vesicles arranged in 11 horizontal rows, and the vesicles were smaller than those of the other Gymnodinium species. This dinoflagellate had a sharp and elongated ventral ridge reaching half way down the hypocone, unlike other Gymnodinium species. Moreover, displacement of the cingulum was 0.4-0.6 × cell length while in other known Gymnodinium species it is less than 0.3 × cell length. In addition, the new species possessed a peduncle, permanent chloroplasts, pyrenoids, trichocysts, pusule systems, and small knobs along the apical furrow, but it lacked an eyespot, nematocysts, and body scales. The sequence of the SSU, ITS1-5.8S-ITS2, and LSU rDNA region differed by 1.5-3.8%, 6.0-17.4%, and 9.1-17.5%, respectively, from those of the most closely related species. The phylogenetic trees demonstrated that the new species belonged to the Gymnodinium clade at the base of a clade consisting of Gymnodinium acidotum, Gymnodinium dorsalisulcum, Gymnodinium eucyaneum, etc. Based on morphological and molecular data, we suggest that the taxon represents a new species, Gymnodinium smaydae n. sp.

Additive anti-allergic effects of anti-interleukin-33 and anti-Siglec-F treatments in a murine model of allergic asthma.

BACKGROUND: Anti-interleukin-33 (anti-IL-33) and anti-Siglec-F antibodies have potent anti-allergic effects on murine allergic asthma and rhinitis and induce eosinophil apoptosis. OBJECTIVE: We aimed to determine whether post-sensitization with anti-IL-33/anti-Siglec-F treatments exhibited more potent effects compared to individual treatments in a murine allergic asthma model. MATERIAL AND METHODS: Twenty-five BALB/c mice were separated into five groups (n = 5): Group A (control), Group B (ovalbumin [OVA] challenge), Group C (OVA + anti-IL-33), Group D (OVA + anti-Siglec-F), and Group E (OVA + anti-IL-33 + anti-Siglec-F). Serum total/ OVA-specific IgE, bronchoalveolar lavage (BAL) inflammatory cells and cytokines (IL-4 and IL-5), histopathological lung properties, and airway hyperreactivity were compared. RESULTS: Ovalbumin challenge induced strong immune and inflammatory responses with > 6-fold IgE level increases; 10- to 25-fold BAL eosinophil, neutrophil, and lymphocyte count increases; and > 1.5-fold IL-4 and IL-5 level increases (p < 0.05). Whereas anti-IL-33 reduced neutrophil counts, anti-Siglec-F and anti-IL-33/anti-Siglec-F reduced both eosinophil and neutrophil counts (p < 0.05). Individual treatments reduced OVA-mediated bronchiolar infiltration by 50% (p <0.05). Ovalbumin challenge increased airway hyperreactivity by 4-fold (Group B; 2000.0 ±671.8% increase in Penh) compared to controls (Group A; 445.7 ±33.5% increase in Penh) (p = 0.016). The anti-IL-33 (Group C: 1579.4 ±973.6% increase in Penh) and anti-Siglec-F (Group D: 930.4 ±236.5%) groups demonstrated significantly reduced hyperreactivity (p = 0.029). Anti-IL-33/anti-Siglec-F therapy showed synergism towards neutrophil counts, IL-5 concentrations, bronchial infiltration, and hyperreactivity (p < 0.05). CONCLUSIONS: Combination treatment with anti-IL-33/anti-Siglec-F had more potent anti-allergic effects, reducing eosinophilic infiltration through their additive effects in a murine allergic asthma model.

Exposure to hypergravity increases serum interleukin-5 and pulmonary infiltration in mice with allergic asthma.

OBJECTIVE: We evaluated the effect of acute hypergravity (HG) on the immune response in a murine model of allergic asthma. MATERIAL AND METHODS: Twenty-eight BALB/c mice were used. Group A (control group, n = 7) mice were sensitized and challenged with normal saline. Group B (control HG exposure group, n = 7) mice were sensitized, challenged with saline, and exposed to acute HG (+10 Gz) for 4 hours. Group C (asthma group, n = 7) mice were challenged with intraperitoneal and intranasal ovalbumin (OVA) to induce asthma. Group D (asthma HG exposure group, n = 7) mice were exposed to HG for 4 hours after the induction of asthma. We estimated the total and OVA-specific serum IgE, serum titers of various cytokines, and the number of eosinophils, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL) fluid. Histopathology of the lung was also evaluated. RESULTS: The serum level of interleukin (IL)-5 was significantly higher in Group D (12.9 ±4.9 pg/ml) compared to that in Group C (4.7 ±6.5 pg/ml, p = 0.017). In BAL fluid, the number of neutrophils was significantly increased in Group D compared to Group C (p = 0.014). Group D demonstrated a higher infiltration of inflammatory cells (9973.8 ±1642.7 cells/mm(2)) compared to Group C (7666.3 ±586.5 cells/mm(2), p = 0.017). This tendency of increase in infiltration was not significant in non-asthmatic animals (Group A: 4488.8 ±176.1 cells/mm(2) vs. Group B: 4946.3 ±513.7 cells/mm(2), p > 0.05). CONCLUSIONS: Acute HG exacerbated the allergic response by increasing serum IL-5 levels and promoting pulmonary infiltration of inflammatory cells.

The dysadherin/FAK axis promotes individual cell migration in colon cancer.

Dysregulation of cancer cell motility is a key driver of invasion and metastasis. High dysadherin expression in cancer cells is correlated with invasion and metastasis. Here, we found the molecular mechanism by which dysadherin regulates the migration and invasion of colon cancer (CC). Comprehensive analysis using single-cell RNA sequencing data from CC patients revealed that high dysadherin expression in cells is linked to cell migration-related gene signatures. We confirmed that the deletion of dysadherin in tumor cells hindered local invasion and distant migration using in vivo tumor models. In this context, by performing cell morphological analysis, we found that aberrant cell migration resulted from impaired actin dynamics, focal adhesion turnover and protrusive structure formation upon dysadherin expression. Mechanistically, the activation of focal adhesion kinase (FAK) was observed in dysadherin-enriched cells. The dysadherin/FAK axis enhanced cell migration and invasion by activating the FAK downstream cascade, which includes the Rho family of small GTPases. Overall, this study illuminates the role of dysadherin in modulating cancer cell migration by forcing actin dynamics and protrusive structure formation via FAK signaling, indicating that targeting dysadherin may be a potential therapeutic strategy for CC patients.

Machine learning with in silico analysis markedly improves survival prediction modeling in colon cancer patients.

BACKGROUND: Predicting the survival of cancer patients provides prognostic information and therapeutic guidance. However, improved prediction models are needed for use in diagnosis and treatment. OBJECTIVE: This study aimed to identify genomic prognostic biomarkers related to colon cancer (CC) based on computational data and to develop survival prediction models. METHODS: We performed machine-learning (ML) analysis to screen pathogenic survival-related driver genes related to patient prognosis by integrating copy number variation and gene expression data. Moreover, in silico system analysis was performed to clinically assess data from ML analysis, and we identified RABGAP1L, MYH9, and DRD4 as candidate genes. These three genes and tumor stages were used to generate survival prediction models. Moreover, the genes were validated by experimental and clinical analyses, and the theranostic application of the survival prediction models was assessed. RESULTS: RABGAP1L, MYH9, and DRD4 were identified as survival-related candidate genes by ML and in silico system analysis. The survival prediction model using the expression of the three genes showed higher predictive performance when applied to predict the prognosis of CC patients. A series of functional analyses revealed that each knockdown of three genes reduced the protumor activity of CC cells. In particular, validation with an independent cohort of CC patients confirmed that the coexpression of MYH9 and DRD4 gene expression reflected poorer clinical outcomes in terms of overall survival and disease-free survival. CONCLUSIONS: Our survival prediction approach will contribute to providing information on patients and developing a therapeutic strategy for CC patients.

Oncologic outcome after preoperative chemoradiotherapy in patients with pathologic T0 (ypT0) rectal cancer.

BACKGROUND: Little is known about the oncologic outcomes of patients with ypT0 rectal cancer after preoperative chemoradiotherapy. OBJECTIVE: To evaluate the clinicopathologic characteristics and oncologic outcomes of patients with ypT0 rectal cancer after preoperative chemoradiotherapy and curative radical surgery. DESIGN AND SETTINGS: This was a retrospective review of factors influencing outcome of patients treated with preoperative chemoradiotherapy for rectal cancer at a tertiary care university medical center in Seoul, Korea between 2000 and 2008. PATIENTS: A total of 830 rectal cancer patients underwent surgery after preoperative chemoradiotherapy. Patients were included in the study if they had a pretreatment clinical classification of T3-4 or N+ (or T2N0 and preoperative chemoradiotherapy for sphincter preservation) and if they were classified on pathologic examination as ypT0 after preoperative CRT and curative radical surgery. Patients were classified as. MAIN OUTCOME MEASURES: Overall survival and disease-free survival were evaluated in relation to ypT0N0 or ypT0N1-2 status and other factors that might influence outcome. RESULTS: Of 91 patients included in the study, 54 (59.3%) were men; the mean patient age was 55 (SD, 11) years, and mean follow-up duration was 44 (SD, 23) months. Surgical procedures included low anterior resection in 68 patients, abdominoperineal resection in 21, and intersphincteric resection in 2. Mean tumor distance from the anal verge was 4.7 (SD, 1.8) cm. Of the 91 patients, 85 were classified as ypT0N0 and 6 as ypT0N1-2. No patient experienced local recurrence. A total of 11 patients (12.1%) had distant metastases, after a mean 11.1 months, including 7 (8.2%) with ypT0N0 and 4 (66.7%) with ypT0N1-2 tumors. One patient with ypT0N0 and 2 patients with ypT0N1-2 tumors died of metastasis. In patients classified as ypT0N0, the 5-year disease free survival and overall survival rates were 82.3% and 89.2%, respectively. Multivariate analysis showed that ypN1-2 status (p = 0.001) was a significant independent risk factor for recurrence (decreased 5-year disease-free survival), but no factor was associated with 5-year overall survival. LIMITATIONS: The study is limited by its retrospective nature. CONCLUSION: Oncologic outcomes in patients with ypT0N0 rectal cancer were excellent. The presence of residual cancer cells in mesorectal lymph nodes represents a risk factor for distant metastasis.

Beneficial effect of anti-interleukin-33 on the murine model of allergic inflammation of the lower airway.

OBJECTIVE: Interleukin (IL)-33, which mediates the T(h)2 allergic pathway, may play a key role in allergic airway inflammation. This study was conducted to evaluate the therapeutic potential of anti-IL-33 antibody for treatment of allergic inflammation of the lower airway in a murine model. METHODS: Twenty-four BALB/c mice were used in this study. Saline was used for sensitization and challenge of mice in Group A (control group, n = 6). Mice in Group B (ovalbumin (OVA) group, n = 6) received intraperitoneal (ip) and intranasal OVA challenge. In Group C (control IgG group, n = 6), mice received ip injection with control IgG prior to OVA challenge. Mice in Group D (anti-IL-33 group, n = 6) received an ip injection of anti-IL-33 prior to challenge. Measurements of serum total and OVA-specific IgE and the number of eosinophils, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL) fluid were performed. We performed histopathologic examination to evaluate the degree of eosinophilic infiltration in lung tissue. Airway hyperreactivity was measured according to change of enhanced pause (Penh). RESULTS: A significant decrease in serum total and OVA-specific IgE and the number of eosinophils and neutrophils in BAL fluid was observed in Group D, compared with Group B or Group C (p < .05). In Group D, treatment with anti-IL-33 resulted in a significant decrease in eosinophilic infiltration in lung tissue, compared with Group B and Group C (p < .05). Degree of airway hyperreactivity, measured by Penh, showed a significant decrease in the anti-IL-33 treatment group, compared with the OVA group or the control IgG treatment group (p < .01, at 50 mg/mL of methacholine). CONCLUSIONS: Anti-IL-33 has therapeutic potential for treatment of allergic inflammation of the lower airway.

Feasibility of transanal minimally invasive surgery for mid-rectal lesions.

BACKGROUND: Transanal minimally invasive surgery (TAMIS) has emerged as an alternative to transanal endoscopic microsurgery. We assessed the feasibility of TAMIS for lesions located in the mid rectum. METHODS: From July 2010 to October 2011, 16 consecutive patients with rectal pathology underwent TAMIS. After a single-incision laparoscopic surgery port was introduced into the anal canal, pneumorectum was established with a laparoscopic device, followed by transanal excision with conventional laparoscopic instruments, including graspers, monopolar electrocautery, and needle drivers. Clinicopathological findings, surgical procedure results, and perioperative outcomes were determined prospectively. RESULTS: Of the 16 patients, 11 had rectal cancers (3 T1 lesions and 8 after preoperative chemoradiotherapy), 4 had neuroendocrine tumors, and 1 had a mucocele. The median length of the lesions from anal verge was 7.5 cm (range 4-10 cm). All procedures were completed laparoscopically without conversion to conventional transanal approach. The median operating time was 86 min (range 33-160 min), and the median estimated blood loss was 15 ml (range 0-150 ml) with no patient requiring intraoperative transfusions. There was no surgical morbidity or mortality, but one patient died during follow-up due to synchronous advanced gastric cancer. The median postoperative hospital stay was 3 days (range 2-6 days). CONCLUSIONS: TAMIS seems to be a feasible and safe treatment option for lesions located in the mid rectum.

Dysadherin awakens mechanical forces and promotes colorectal cancer progression.

Rationale: Dysadherin is a tumor-associated, membrane-embedded antigen found in multiple types of cancer cells, and associated with malignant behavior of cancer cells; however, the fundamental molecular mechanism by which dysadherin drives aggressive phenotypes of cancer is not yet fully determined. Methods: To get a mechanistic insight, we explored the physiological relevance of dysadherin on intestinal tumorigenesis using dysadherin knockout mice and investigated its impact on clinicopathological features in patients with advanced colorectal cancer (CRC). Next, to discover the downstream signaling pathways of dysadherin, we applied bioinformatic analysis using gene expression data of CRC patient tumors and dysadherin knockout cancer cells. Additionally, comprehensive proteomic and molecular analyses were performed to identify dysadherin-interacting proteins and their functions. Results: Dysadherin deficiency suppressed intestinal tumorigenesis in both genetic and chemical mouse models. Moreover, increased dysadherin expression in cancer cells accounted for shorter survival in CRC patients. Comprehensive bioinformatics analyses suggested that the effect of dysadherin deletion is linked to a reduction in the extracellular matrix receptor signaling pathway. Mechanistically, the extracellular domain of dysadherin bound fibronectin and enhanced cancer cell adhesion to fibronectin, facilitating the activation of integrin-mediated mechanotransduction and leading to yes-associated protein 1 activation. Dysadherin-fibronectin interaction promoted cancer cell growth, survival, migration, and invasion, effects collectively mediated the protumor activity of dysadherin. Conclusion: Our results highlight a novel function of dysadherin as a driver of mechanotransduction that stimulates CRC progression, providing a potential therapy strategy for CRC.

DCLK1 promotes colorectal cancer stemness and aggressiveness via the XRCC5/COX2 axis.

Rationale: Doublecortin-like kinase 1 (DCLK1) is a serine/threonine kinase that selectively marks cancer stem-like cells (CSCs) and promotes malignant progression in colorectal cancer (CRC). However, the exact molecular mechanism by which DCLK1 drives the aggressive phenotype of cancer cells is incompletely determined. Methods: Here, we performed comprehensive genomics and proteomics analyses to identify binding proteins of DCLK1 and discovered X-ray repair cross-complementing 5 (XRCC5). Thus, we explored the biological role and downstream events of the DCLK1/XRCC5 axis in human CRC cells and CRC mouse models. Results: The results of comprehensive bioinformatics analyses suggested that DCLK1-driven CRC aggressiveness is linked to inflammation. Mechanistically, DCLK1 bound and phosphorylated XRCC5, which in turn transcriptionally activated cyclooxygenase-2 expression and enhanced prostaglandin E2 production; these events collectively generated the inflammatory tumor microenvironment and enhanced the aggressive behavior of CRC cells. Consistent with the discovered mechanism, inhibition of DCLK1 kinase activity strongly impaired the tumor seeding and growth capabilities in CRC mouse models. Conclusion: Our study illuminates a novel mechanism that mediates the pro-inflammatory function of CSCs in driving the aggressive phenotype of CRC, broadening the biological function of DCLK1 in CRC.

Use of porous high-density polyethylene (Medpor) for spreader or extended septal graft in rhinoplasty: aesthetics, functional outcomes, and long-term complications.

In this study, 29 patients with porous high-density polyethylene (group A) and 29 patients with septal cartilage (group B) were enrolled for either spreader or extended septal graft. By questionnaire or telephone survey, the authors evaluated patients' cosmetic satisfaction and complications. The authors also used postoperative photographs to evaluate cosmetic results. For the functional analysis, the change of visual analog scale of nasal obstruction and change of minimal cross-sectional area using acoustic rhinometry were compared. Of 29 patients in group A, 27 were totally satisfied with the results. There was no complication except for 2 cases of extrusion during 5.3 ± 1.8 years. The patients in group A showed more decrease of nasal obstruction by visual analog scale and more improvement of minimal cross-sectional area as compared with those in group B. Therefore, porous high-density polyethylene is an ideal alloplastic material for spreader or extended septal graft in rhinoplasty in both cosmetic and functional aspects. And it is also safe and stable over a long-term period.

The value of local botulinum toxin A injection in the treatment of the pain of aphthous ulcer.

To determine the effectiveness of botulinum toxin type A to reduce pain of recurrent aphthous ulcer, a single blinded placebo controlled trial of botulinum toxin A injection was performed. A total of 70 patients were enrolled and randomly received a botulinum toxin type A 1 unit or placebo. The patients were asked to note the level of pain on the visual analogue scale for 6 days. They also had to record any eventual side effects or recurrence for 6 months. More patients quickly recovered following Botulinum toxin type A injection than placebo; they would feel almost no pain after about 3 days. Botulinum toxin type A exhibits quick pain treatment effect following injection on aphthous ulcer. The author also believes that it can prevent recurrence for at least 6 months after injection.

A comparison of the effects of botulinum toxin A and steroid injection on nasal allergy.

OBJECTIVES: To compare the effects of botulinum toxin A (BTX-A) with intranasal steroid injections on nasal symptoms in patients with allergic rhinitis (AR). STUDY DESIGN: A randomized, placebo-controlled, single-blinded clinical trial (patients were blinded). MATERIAL AND METHODS: Thirty-nine patients were included in the study. AR was diagnosed by means of history, clinical examination, and skin prick test. Patients were randomly divided into three subgroups as follows: in group A, 25 units of BTX-A were injected into each inferior turbinate (total 50 units); in group B, 1 cc (20 mg/mL) of triamcinolone was injected into each inferior turbinate; and in group C, 1 cc of isotonic saline was injected as placebo. The symptoms of AR were scored by the patient on a six-point scale. RESULTS: At all time points, group A was significantly better than group C. In the nasal obstruction and rhinorrhea scores, group A was significantly better than group B after 8 weeks. CONCLUSION: BTX-A may provide better AR symptom relief in terms of duration and degree than a steroid injection.

Evaluation of acoustic rhinometry in a nasal provocation test with allergic rhinitis.

OBJECTIVE: The nasal provocation test is not widely available due to lack of standardized methods and related research. We evaluated the clinical utility of the nasal provocation test using acoustic rhinometry. STUDY DESIGN: All patients underwent skin tests and were graded according to severity of reaction. METHODS: We performed nasal provocation tests using acoustic rhinometry in patients with allergic rhinitis from January 2003 to December 2006. A total of 836 patients participated in our study. The mean age was 36 years and the male:female ratio was 5:4. RESULTS: The mean nasal volume was 10.86 cm(3) and the mean minimal cross-sectional area (MCA) was 0.66 cm(3) before the study. Relationship between the severity of the reaction and change in mean nasal volume and MCA was statistically significant. The relationship between the severity of the reaction against the antigen and the severity of clinical symptoms was also statistically significant. CONCLUSION: The nasal provocation test can be helpful in evaluating the severity of allergic rhinitis. However, we must be careful in interpreting the results alone.

Hypergravity enhances the therapeutic effect of dexamethasone in allergic asthma and rhinitis animal model.

We investigated whether the therapeutic effects of dexamethasone for allergic asthma and rhinitis were enhanced in mice when exposed to hypergravity. Forty mice were divided into 5 groups (n = 8/group): Control group received saline intraperitoneally (i.p.) and intranasally (i.n.); Asthma group received i.p./i.n. ovalbumin (OVA) for inducing allergic asthma/rhinitis; Dexa group received i.n. dexamethasone (0.75 mg/kg) 30 minutes before each OVA challenge; Hypergravity group was subjected to allergic asthma/rhinitis as well as exposed to 5 G hypergravity for 30 days; Finally in Dexa/Hypergravity group, hypergravity and dexamethasone were used simultaneously during induction of allergic asthma/rhinitis. Dexa group and Hypergravity group showed a significant decrease in serum total IgE levels compared to the Asthma group (p<0.05). Dexa/Hypergravity group showed greater IgE decrease compared with Dexa group (p = 0.040). Compared with the monotherapy groups, Dexa/Hypergravity group showed significantly fewer eosinophils in BAL fluid (p<0.05). Dexa/Hypergravity group showed significantly decreased eosinophilic infiltration into the lungs and nasal cavity (p<0.05). EC-SOD (extracellular superoxide dismutase) expression was significantly upregulated in the Hypergravity group and Dexa/Hypergravity group, compared with the Dexa group (p<0.05). In conclusion, hypergravity enhanced the therapeutic effect of dexamethasone in a murine model of allergic asthma and rhinitis. Therefore, combination could be a promising strategy, and one of its mechanisms could be up-regulation of EC-SOD expression.

Correlation of Nasal Eosinophilia and Response after Nasal Provocation Test in Patients with Nonallergic Rhinitis.

Objectives We aimed to evaluate the relationship between nasal eosinophilia and nasal hyperresponsiveness to allergen extract. Study Design Retrospective chart review. Setting Academic tertiary rhinologic practice. Subjects and Methods We performed allergy tests (skin prick test and multiple allergosorbent test) and nasal cytology for 194 patients with rhinitis symptoms (76 males and 118 females; age, 11-69 years). According to the results, they were classified into 4 groups: group A (allergic rhinitis with eosinophilia, n = 26), group B (allergic rhinitis without eosinophilia, n = 77), group C (nonallergic rhinitis with eosinophilia syndrome, n = 20), and group D (nonallergic rhinitis without eosinophilia, n = 71). We performed a nasal provocation test (NPT) using house dust mite extract and assessed the changes in symptoms and the decrease in acoustic parameters (total nasal volume and minimal cross-sectional area [MCA]). Results Patients in group C were more likely to have severe rhinorrhea and sneezing than those in group D ( P < .001). After NPT, group C had greater aggravation of nasal obstruction than group D ( P < .001). Group C also showed markedly greater MCA changes as compared with group D 15 minutes after the antigen challenge ( P = .002). There was significant correlation between the number of eosinophils and an increase in nasal obstruction ( r = 0.319, P = .0009), rhinorrhea ( r = 0.302, P = .0017), sneezing ( r = 0.219, P = .0241), change in the total nasal volume 15 minutes after NPT ( r = 0.287, P = .0028), and change in the MCA 15 minutes ( r = 0.322, P = .0008) and 30 minutes ( r = 0.250, P = .0098) after NPT. Conclusion In patients with NAR, nasal eosinophilia is associated with provocative response after NPT. Further research should be performed to elucidate the mechanisms that underlie this phenomenon.