Impact of mitomycin C on the mRNA expression signatures of immunological biomarkers in eosinophilic nasal polyposis.

BACKGROUND: The topical application of mitomycin C has been evaluated as a complementary therapy for eosinophilic nasal polyposis (ENP). However, the mechanism underlying the additional benefits of mitomycin C for the control of eosinophilic inflammation and prevention of posttherapeutic relapse remains to be elucidated. In this work, the aim was to characterize the gene expression profile by quantitative real-time polymerase chain reaction (qPCR) of proinflammatory and regulatory biomarkers that are typically associated with ENP and to assess the impact of the topical application of mitomycin C on the nasal mucosal tissue immunologic milieu after ENP surgery. METHODS: We have selected 20 patients with ENP that were recommended to undergo surgical intervention. Normal mucosal tissue was obtained from healthy nasal mucosa from six patients with absence of eosinophilic infiltration. To test the effect of mitomycin C, one side of the maxillary sinus mucosa was selected for topical application of this drug and the other received no further treatment and acted as the control. The genes interleukin-4 (IL-4), IL-5, IL-10, IL-13, chemokine (C-C motif) ligand 5 (CCL5), CCL24, colony-stimulating factor 2 (CSF2), transforming growth factor beta 1 (TGFB1), tumor necrosis factor alpha (TNF-alpha), and beta actin (ACTB) were selected for gene expression analysis by qPCR. RESULTS: The data showed higher expression of proinflammatory biomarkers and lower levels of regulatory TGFB1 transcripts in ENP mucosal tissue. Surgery with topical application of mitomycin C induced a prominent transcriptional down-regulation of the immunologic biomarkers, CCL24, TNF-alpha, CSF2, and IL-5, in ENP mucosal tissue. Additionally, this treatment restored the levels of chemokines and cytokines to those observed in the nasal mucosal tissue of control subjects, except for TGFB1, which remained below the reference pattern. Moreover, CSF2 was identified as a putative biomarker with significant predictive value for complementary prophylactic purposes after surgery in ENP patients. CONCLUSION: After the characterization of the expression signatures of immunologic biomarkers in ENP, we observed that the topical use of mitomycin C is important for the reestablishment of the immunologic microenvironment of a normal expression profile of biomarkers involved in ENP mucosal tissue.

Impact of mitomycin C on the mRNA expression signatures of immunological biomarkers in eosinophilic nasal polyposis.

BACKGROUND: The topical application of mitomycin C has been evaluated as a complementary therapy for eosinophilic nasal polyposis (ENP). However, the mechanism underlying the additional benefits of mitomycin C for the control of eosinophilic inflammation and prevention of posttherapeutic relapse remains to be elucidated. In this work, the aim was to characterize the gene expression profile by quantitative real-time polymerase chain reaction (qPCR) of proinflammatory and regulatory biomarkers that are typically associated with ENP and to assess the impact of the topical application of mitomycin C on the nasal mucosal tissue immunologic milieu after ENP surgery. METHODS: We have selected 20 patients with ENP that were recommended to undergo surgical intervention. Normal mucosal tissue was obtained from healthy nasal mucosa from six patients with absence of eosinophilic infiltration. To test the effect of mitomycin C, one side of the maxillary sinus mucosa was selected for topical application of this drug and the other received no further treatment and acted as the control. The genes interleukin-4 (IL-4), IL-5, IL-10, IL-13, chemokine (C-C motif) ligand 5 (CCL5), CCL24, colony-stimulating factor 2 (CSF2), transforming growth factor beta 1 (TGFB1), tumor necrosis factor alpha (TNF-alpha), and beta actin (ACTB) were selected for gene expression analysis by qPCR. RESULTS: The data showed higher expression of proinflammatory biomarkers and lower levels of regulatory TGFB1 transcripts in ENP mucosal tissue. Surgery with topical application of mitomycin C induced a prominent transcriptional down-regulation of the immunologic biomarkers, CCL24, TNF-alpha, CSF2, and IL-5, in ENP mucosal tissue. Additionally, this treatment restored the levels of chemokines and cytokines to those observed in the nasal mucosal tissue of control subjects, except for TGFB1, which remained below the reference pattern. Moreover, CSF2 was identified as a putative biomarker with significant predictive value for complementary prophylactic purposes after surgery in ENP patients. CONCLUSION: After the characterization of the expression signatures of immunologic biomarkers in ENP, we observed that the topical use of mitomycin C is important for the reestablishment of the immunologic microenvironment of a normal expression profile of biomarkers involved in ENP mucosal tissue.

Gastric emptying of solids and semi-solids in morbidly obese and non-obese subjects: an assessment using the 13C-octanoic acid and 13C-acetic acid breath tests.

BACKGROUND: It has been suggested that obesity is associated with an altered rate of gastric emptying. The objective of the present study was to determine whether the rates of solid and semi-solid gastric emptying differ between morbidly obese patients and lean subjects. METHODS: The Gastric-emptying time (GET) of solid and semi-solid meals were compared between lean healthy subjects and morbidly obese patients enrolled in two previously published studies. GET of solid and semi-solid meals was measured using the 13C-octanoic acid breath test and 13C-acetic acid breath test, respectively, in 24 lean and 14 morbidly obese individuals of both sexes. Student t-test was used to compare the mean data between the lean and morbidly obese groups. The influence of sex, gender, BMI and morbid obesity on the GET of solid meals was verified by linear regression analysis. RESULTS: Mean t(1/2) values of solid GET (+/- standard deviation) were 203.6 +/- 76.0 min and 143.5 +/- 19.1 min for lean and obese subjects, respectively (P = 0.0010). Mean t(lag) values of solid GET were 127.3 +/- 42.7 min and 98.4 +/- 13.0 min for lean and obese subjects, respectively (P = -0.0044). No significant difference in semi-solid GET was observed between the lean and morbidly obese groups. CONCLUSION: The present study demonstrated a significantly enhanced gastric emptying of the solid meal test in morbidly obese patients when compared to lean subjects. This finding is compatible with the hypothesis that rapid gastric emptying in morbidly obese subjects increases caloric intake due to a more rapid loss of satiety.

Cheilitis granulomatosa associated with Melkersson-Rosenthal syndrome.

Melkersson-Rosenthal syndrome (MRS) consists of persistent or recurrent orofacial edema, relapsing facial palsy and fissured tongue. The complete triad of symptoms is uncommon, varying from 8 to 25%. The presentation of only one symptom is more common. The most frequent complaint is facial edema and enlargement of the lips. We describe a case of a 17-year-old Brazilian girl with limited edema of the lower lip and fissured tongue due to MRS. Her complaints had started two years before. She referred previous clinical treatments without success. We proposed intralesional injection of triamcinolone at 20 mg every 15 days associated with oral clofazimine at 50 mg/day for three months. The lip became normal after four triamcinolone injections. Recent studies have considered MRS a granulomatous disease, and possibly the initial presentation of Crohn's disease in orofacial area of some patients. MRS patients, therefore, should be screened and monitored for gastrointestinal symptoms. Corticosteroid treatment seems to be effective in reducing lip enlargement. We discuss the clinical features of this disease, the treatment, and the importance of corticosteroid therapy in cases of MRS-related facial palsy.

Effect of mitomycin C in eosinophilic nasal polyposis, in vivo: concentration of IL5 and GM-CSF, RT-PCR.

UNLABELLED: Eosinophilic nasosinusal polyposis is a chronic inflammatory infection with elevated infiltration of eosinophils, which presents high rate of recurrence after surgical treatment. The continuous inflammatory process that leads to the formation of polyps requires constant clinical treatment. Contributing to the maintenance of eosinophilia are cytokines IL5 (interleukin-5) and GM-CSF (granulocyte macrophages colony-stimulating factor), which show up in elevated concentrations. These oligoproteins diminish the rate of apoptosis and prolong the survival of eosinophils. AIM: By diminishing these cytokines, the action of Mitomycin C (MMC), an antineoplastic drug which inhibits the synthesis of DNA, was studied. In a recent study the power of this drug to cause apoptosis in eosinophils, in vitro, of nasal polyps was verified. METHODOLOGY: A biopsy of the nasal polyps was undertaken in 15 patients carriers of eosinophilic nasosinusal polyposis 24 hours after applying 0.5 mg/ml of MMC during five minutes. RT-PCR (reverse transcription of polymerase chain reaction) for IL5 and GM-CSF was the method used to obtain the results. RESULTS: The comparison of the results of GM-CSF pre- and post-application of MMC, when the paired T-test was used, showed p=0.041 and for IL5 we found p<0.001. CONCLUSION: Topic use of MMC in patients with eosinophilic nasosinusal polyposis shows statistically significant reduction for GM-CSF and significant and important reduction for IL5.