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1.
Braz. j. otorhinolaryngol. (Impr.) ; 88(1): 9-14, Jan.-Feb. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1364580

ABSTRACT

Abstract Introduction Traumatic large tympanic membrane perforations usually fail to heal and require longer healing times. Few studies have compared the healing and hearing outcomes between gelatin sponge patching and ofloxacin otic solution. Objectives To compare the healing outcomes of large traumatic tympanic membrane perforations treated with gelatin sponge, ofloxacin otic solution, and spontaneous healing. Methods Traumatic tympanic membrane perforations >50% of the entire eardrum were randomly divided into three groups: ofloxacin otic solution, gelatin sponge patch and spontaneous healing groups. The healing outcome and hearing gain were compared between the three groups at 6 months. Results A total of 136 patients with large traumatic tympanic membrane perforations were included in analyses. The closure rates were 97.6% (40/41), 87.2% (41/47), and 79.2% (38/48) in the ofloxacin otic solution, gelatin sponge patch, and spontaneous healing groups, respectively (p = 0.041). The mean times to closure were 13.12 ± 4.61, 16.47 ± 6.24, and 49.51 ± 18.22 days in these groups, respectively (p < 0.001). Conclusions Gelatin sponge patch and ofloxacin otic solution may serve as effective and inexpensive treatment strategies for traumatic large tympanic membrane perforations. However, ofloxacin otic solution must be self-applied daily to keep the perforation edge moist, while gelatin sponge patching requires periodic removal and re-patching.


Resumo Introdução As grandes perfurações traumáticas da membrana timpânica geralmente apresentam falha de cicatrização e requerem tempos de cicatrização mais longos; poucos estudos compararam os resultados de cicatrização e a audição dessas perfurações obtidos com curativo de Gelfoam® e solução otológica de ofloxacina. Objetivo Comparar os resultados de cicatrização de grandes perfurações traumáticas da membrana timpânica tratadas com Gelfoam®, solução otológica de ofloxacina e cicatrização espontânea. Método Perfurações traumáticas de > 50% de todo o tímpano foram divididas aleatoriamente em três grupos: tratamento com solução otológica de ofloxacina, com curativo de Gelfoam® e grupo de cicatrização espontânea. O resultado da cicatrização e o ganho auditivo foram comparados entre os três grupos após 6 meses. Resultados Foram incluídos nas análises 136 pacientes com grandes perfurações traumáticas de membrana timpânica. As taxas de cicatrização foram de 97,6% (40/41), 87,2% (41/47) e 79,2% (38/48) com a solução otológica de ofloxacina, curativo de Gelfoam® e grupos de cicatrização espontânea, respectivamente (p = 0,041). O tempo médio de cicatrização foi de 13,12 ± 4,61, 16,47 ± 6,24 e 49,51 ± 18,22 dias nesses grupos, respectivamente (p < 0,001). Conclusões O curativo de Gelfoam® e a solução otológica de ofloxacina podem servir como estratégias de tratamento eficazes e de baixo custo para grandes perfurações traumáticas de membrana timpânica. Entretanto, a solução otológica de ofloxacina deve ser autoaplicada diariamente para manter a borda da perfuração úmida, enquanto o curativo de Gelfoam® requer sua remoção e reaplicação periódicas.

2.
Braz J Otorhinolaryngol ; 88(1): 9-14, 2022.
Article in English | MEDLINE | ID: mdl-32456874

ABSTRACT

INTRODUCTION: Traumatic large tympanic membrane perforations usually fail to heal and require longer healing times. Few studies have compared the healing and hearing outcomes between gelatin sponge patching and ofloxacin otic solution. OBJECTIVES: To compare the healing outcomes of large traumatic tympanic membrane perforations treated with gelatin sponge, ofloxacin otic solution, and spontaneous healing. METHODS: Traumatic tympanic membrane perforations >50% of the entire eardrum were randomly divided into three groups: ofloxacin otic solution, gelatin sponge patch and spontaneous healing groups. The healing outcome and hearing gain were compared between the three groups at 6 months. RESULTS: A total of 136 patients with large traumatic tympanic membrane perforations were included in analyses. The closure rates were 97.6% (40/41), 87.2% (41/47), and 79.2% (38/48) in the ofloxacin otic solution, gelatin sponge patch, and spontaneous healing groups, respectively (p=0.041). The mean times to closure were 13.12±4.61, 16.47±6.24, and 49.51±18.22 days in these groups, respectively (p<0.001). CONCLUSIONS: Gelatin sponge patch and ofloxacin otic solution may serve as effective and inexpensive treatment strategies for traumatic large tympanic membrane perforations. However, ofloxacin otic solution must be self-applied daily to keep the perforation edge moist, while gelatin sponge patching requires periodic removal and re-patching.


Subject(s)
Gelatin , Tympanic Membrane Perforation , Humans , Ofloxacin , Tympanic Membrane , Tympanic Membrane Perforation/drug therapy , Wound Healing
3.
Ann Clin Lab Sci ; 51(3): 302-309, 2021 May.
Article in English | MEDLINE | ID: mdl-34162559

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the effects and mechanism of thalidomide on pancreatic stellate cell (PSC) activation in mice and to find the optimal timing of thalidomide administration. METHODS: PSCs, isolated from mouse pancreas tissue, were divided into five groups with specific treatments: (A) control PSCs (PSC), (B) PSCs induced by TGF-ß1 (PSC+TGF-ß1), (C) PSCs induced by TGF-ß1 followed by thalidomide (PSC+TGF-ß1+Thalidomide), (D) PSCs receiving TGF-ß1 and thalidomide simultaneously (PSC+(TGF-ß1+Thalidomide)), and (E) PSCs treated with thalidomide only (PSC+Thalidomide). We measured the effects of thalidomide on PSC activation by detecting the expression of α-SMA, collagen type I, and the TGF-ß/Smad pathway through quantitative real-time PCR and Western blot analysis. RESULTS: Compared with TGF-ß1 alone, thalidomide significantly inhibited PSC activation by reducing α-SMA expression (P<0.05) and decreasing collagen type I deposition (P<0.05). PSCs treated with thalidomide alone showed lower expression of α-SMA and collagen type I than those treated with thalidomide and TGF-ß1 at random order (P<0.01). Thalidomide downregulated TGF-ß1 and Smad3 and upregulated Smad7 (P<0.05). CONCLUSION: Thalidomide could repress PSC activation and alleviate fibrosis by regulating the TGF-ß/Smad pathway. Preventive use of thalidomide had maximum effect, and there was no evidence for the reversal of the activation of quiescent PSCs.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Pancreatic Stellate Cells/drug effects , Smad3 Protein/metabolism , Smad7 Protein/metabolism , Thalidomide/pharmacology , Transforming Growth Factor beta/metabolism , Actins/genetics , Actins/metabolism , Animals , Collagen Type I/genetics , Collagen Type I/metabolism , Male , Mice , Mice, Inbred C57BL , Pancreatic Stellate Cells/metabolism , Signal Transduction , Smad3 Protein/genetics , Smad7 Protein/genetics , Transforming Growth Factor beta/genetics
4.
Ear Nose Throat J ; 100(5_suppl): 549S-553S, 2021 Sep.
Article in English | MEDLINE | ID: mdl-31779475

ABSTRACT

OBJECTIVE: The objective is to reduce the rates of misdiagnosis and inappropriate treatment of laryngeal tuberculosis (LTB). STUDY DESIGN: Retrospective case series. MATERIALS AND METHODS: Medical records of 3 histopathology-confirmed cases at a tertiary medical center from 2000 to 2018. RESULTS: Seventeen patients with LTB included in this study. Of the 17 patients, 16 patients were male and 1 was female; 11 patients had a history of smoking. Odynophagia was the chief complaint in 6 cases, and 11 patients complained of hoarseness. The appearance of the affected larynx was ranged from diffuse swelling (n = 7, 41.2%), mucosa white lesion (n = 5,29.4%), and granulomatous tumors (n = 2, 11.76%), and these features presented together (n = 2, 11.76%). Seventeen patients with LTB were misdiagnosed as acute epiglottitis in 4 (23.5%) patients, acute laryngitis in 1 (5.9%) patient, leukoplakia in 5 (29.4%) patients, laryngopharyngeal reflux (LPR) in 6 (35.3%) patients, and laryngocarcinoma in 1 (5.9%) patient. Chest computed tomography reported old pulmonary tuberculosis in 2 (11.7%) patients, active pulmonary tuberculosis in 7 (41.2%) patients, and normal lung status in 8 (47.1%) patients. Histopathological examination reported Mycobacterium tuberculosis infection by revealing epithelioid cell granulomas with Langhans-type giant cells in 14 (82.4%) patients and epithelioid cell granulomas with caseous necrosis and Langhans-type giant cells in 3 (17.6%) patients. CONCLUSIONS: Laryngeal tuberculosis was easily misdiagnosed as acute epiglottitis or leukoplakia because of diffuse swelling of the epiglottis or white lesions over the true vocal cord, especially patients with increasing LTB were misdiagnosed as LPR with the enhancement of LPR awareness among otolaryngologist. Clinicians should be aware of the possibility of LTB for chronic intractable laryngitis with failure treatment of proton pump inhibitor and recurrent acute epiglottitis with foreign body injury.


Subject(s)
Diagnostic Errors , Laryngopharyngeal Reflux/diagnosis , Leukoplakia/diagnosis , Mycobacterium tuberculosis , Tuberculosis, Laryngeal/diagnosis , Adult , Aged , Diagnosis, Differential , Epiglottis/pathology , Epiglottitis/diagnosis , Female , Humans , Larynx/diagnostic imaging , Larynx/microbiology , Lung/diagnostic imaging , Lung/microbiology , Male , Middle Aged , Retrospective Studies , Tuberculosis, Laryngeal/microbiology , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/diagnostic imaging , Vocal Cords/pathology
5.
J BUON ; 25(3): 1579-1586, 2020.
Article in English | MEDLINE | ID: mdl-32862607

ABSTRACT

PURPOSE: MicroRNA-215 (miR-215) has been reported to show different effects in human cancers. However, the function of miR-215 remains unclear in nasopharyngeal carcinoma (NPC). Hence, this research was designed to investigate the effect of miR-215 on the development of NPC. METHODS: The expression levels of miR-215 and RB1 were examined in NPC via the qRT-PCR assay. The protein expression was observed through immunocytochemical assay and western blot. MTT (methyl thiazolyl tetrazolium) and Transwell assays were employed to explore the effect of miR-215. The relationship between miR-215 and retinoblastoma (RB)1 was assessed by dual luciferase assay. RESULTS: Upregulation of miR-215 was identified in NPC tissues and predicted worse prognosis of NPC. Cell proliferation, migration and invasion were promoted by overexpression of miR-215 in NPC. Furthermore, miR-215 directly targeted RB1 which was downregulated in NPC. MiR-215 promoted the progression of NPC through targeting RB1. In particular, miR-215 promoted EMT (epithelial-mesenchymal transition) and activated Wnt/ß-catenin pathway in NPC. CONCLUSION: MiR-215 promoted the development of NPC through suppressing RB1 and activating Wnt/ß-catenin pathway.


Subject(s)
MicroRNAs/genetics , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Neoplasms/genetics , Retinoblastoma Binding Proteins/genetics , Ubiquitin-Protein Ligases/genetics , Wnt Signaling Pathway/genetics , beta Catenin/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Disease Progression , Down-Regulation/genetics , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic/genetics , Humans , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/pathology , Up-Regulation/genetics
7.
Biomed Res Int ; 2019: 7267816, 2019.
Article in English | MEDLINE | ID: mdl-31309113

ABSTRACT

BACKGROUND: Vestibular schwannoma (VS) is benign, slow-growing brain tumor that negatively impacts patient quality of life, which may cause even death. This study aimed to explore key genes and microRNAs (miRNAs) associated with VS. METHODS: The mRNA and miRNA expression profiles of VS downloaded from Gene Expression Omnibus (GEO) database were included in this study to perform an integrated analysis. The differentially expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs) were identified. Then, functional annotation and protein-protein interaction networks (PPI) of DEmRNAs were constructed. DEmiRNA-target DEmRNAs analysis and functional annotation of DEmiRNA-target DEmRNAs were performed. RESULTS: A total of 2627 DEmRNAs (1194 upregulated and 1433 downregulated DEmRNAs) and 21 DEmiRNAs (12 upregulated and 9 downregulated DEmiRNAs) were identified. ISG15, TLE1, and XPC were three hub proteins of VS-specific PPI network. A total of 2970 DEmiRNAs-DEmRNAs pairs were obtained. Among which, hsa-miR-181a-5p, hsa-miR-106-5p, and hsa-miR-34a-5p were the top three DEmiRNAs that covered most DEmRNAs. The functional annotation of DEmiRNA-target DEmRNAs revealed that the DEmiRNA-target DEmRNAs were significantly enriched in cGMP-PKG signaling pathway, adrenergic signaling in cardiomyocytes, and pathways in cancer. CONCLUSION: The results of this present study may provide a comprehensive understanding for the roles of DEmRNAs and DEmiRNAs in the pathogenesis of VS and developing potential biomarkers of VS.


Subject(s)
Gene Expression Regulation, Neoplastic/genetics , MicroRNAs/genetics , Neuroma, Acoustic/genetics , RNA, Messenger/genetics , Down-Regulation/genetics , Gene Expression Profiling/methods , Humans , Myocytes, Cardiac/physiology , Protein Interaction Maps/genetics , Signal Transduction/genetics , Up-Regulation/genetics
8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 47(5): 714-717, 2016 Sep.
Article in Chinese | MEDLINE | ID: mdl-28598085

ABSTRACT

OBJECTIVES: To determine the effect of sphingosine-1-phosphate receptor 2 (S1PR2) on vascular permeability in mice. METHODS: Acute lung injury models of mice were constructed with intra-tracheal administration of lipopolysaccharide (LPS) and compared with the controls with intra-tracheal administration of saline. The effect of S1PR2 on vascular permeability was observed by detecting leakage of Evans blue into lung tissues, pulmonary vascular leakage of fluorescein isothiocyanate (FITC)-dextran, and the wet/dry mass ratio of lungs. The effect of vascular endothelial growth factor (VEGF) on vascular endothelial permeability was detected by Miles analysis. RESULTS: LPS injections induced significant Evans blue leakage, FITC-dextran pulmonary vascular leakage and pulmonary edema, which appeared to be more serious in S1PR2-deleted mice compared with those in wild-type mice. LPS enhanced Evans blue leakage associated with VEGF in a dose-dependent way in both S1PR2-deleted mice and wild type mice. But the vascular permeability response in subcutaneous tissues induced by VEGF was higher in S1PR2-deleted mice than that in wild-type mice. CONCLUSIONS: S1PR2 is involved in endothelial cell barrier protections, which inhibits vascular permeability.


Subject(s)
Acute Lung Injury/metabolism , Capillary Permeability , Endothelial Cells/cytology , Receptors, Lysosphingolipid/metabolism , Animals , Mice , Sphingosine-1-Phosphate Receptors , Vascular Endothelial Growth Factor A/metabolism
9.
Eur Arch Otorhinolaryngol ; 271(6): 1653-9, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24477342

ABSTRACT

Luteolin, a naturally occurring flavonoid, possesses anti-cancer activities against several human cancers, but the exact molecular and biochemical mechanisms of above findings are not very clear, and its activity against head and neck squamous cell carcinoma (HNSCC) is seldom mentioned. In this study, we investigated luteolin against human laryngeal squamous cell line Hep-2 cells, using MTT assay, flow cytometry, Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Luteolin inhibited Hep-2 cells proliferation at the inhibitive concentrations of 50% (IC50) near to 50 µM and induced the apoptosis in Hep-2 cells through caspase-3 and caspase-8 activation. Up-regulation of Fas and down-regulation of long form cellular FLICE-like inhibitory protein (c-FLIPL) protein were also involved after luteolin treatment at both protein and mRNA levels. Luteolin could not only inhibit cell proliferation but also induce apoptosis by activating the Fas signaling pathway at the receptor level in laryngeal squamous cell line Hep-2 cells.


Subject(s)
Apoptosis/drug effects , CASP8 and FADD-Like Apoptosis Regulating Protein/drug effects , Carcinoma, Squamous Cell , Caspase 3/drug effects , Caspase 8/drug effects , Head and Neck Neoplasms , Laryngeal Neoplasms , Luteolin/pharmacology , Signal Transduction/drug effects , fas Receptor/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Humans , Squamous Cell Carcinoma of Head and Neck , Up-Regulation
10.
Anticancer Res ; 29(4): 1411-5, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19414395

ABSTRACT

Etoposide [4'-demethylepipodophyllotoxin-9-(4,6-O-ethylidene)-beta-D-glucopyranoside] is a substrate for P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A. This study was designed to investigate the effects of quercetin (3,5,7,3',4'-pentahydroxyflavanone), a P-gp and CYP3A inhibitor, on the pharmacokinetics of etoposide in rats. Etoposide was administered to rats orally (9 mg/kg) or i.v. (3 mg/kg) without or with quercetin (1, 5 or 15 mg/kg). The plasma concentration of etoposide was determined by high performance liquid chromatography (HPLC) equipped with a fluorescence detector. In the presence of quercetin, the pharmacokinetic parameters of etoposide were significantly altered in the oral group, but not in the i.v. group. The presence of quercetin significantly (5 mg/kg, p<0.05; 15 mg/kg, p<0.01) increased the area under the plasma concentration-time curve (AUC) of orally administered etoposide from 43.0 or 53.2% . The presence of 5 or 15 mg/kg of quercetin significantly (p<0.05) decreased the total body clearance (CL/F) of oral etoposide. Consequently, compared to the control group (8.87%), the presence of quercetin significantly (5 mg/kg, p<0.05; 15 mg/kg, p<0.01) increased the absolute bioavailability (AB) of etoposide to 12.7 or 13.6% . The enhanced oral bioavailability of etoposide by quercetin could mainly be due to inhibition of P-gp-mediated efflux and CYP3A-catalyzed metabolism in the intestine by quercetin. The dosage regimen of etoposide in cancer therapy should take drug interaction into consideration when etoposide is administered with quercetin or dietary supplements containing quercetin.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/pharmacokinetics , Antioxidants/pharmacology , Etoposide/administration & dosage , Etoposide/pharmacokinetics , Quercetin/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , ATP Binding Cassette Transporter, Subfamily B, Member 1/pharmacokinetics , ATP Binding Cassette Transporter, Subfamily B, Member 1/pharmacology , Administration, Oral , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Biological Availability , Chromatography, High Pressure Liquid , Drug Combinations , Drug Interactions , Etoposide/pharmacology , Infusions, Intravenous , Male , Metabolic Clearance Rate/drug effects , Rats , Rats, Sprague-Dawley
11.
Arch Pharm Res ; 32(1): 133-8, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19183886

ABSTRACT

This study was to investigate the effect of kaempferol on the pharmacokinetics of etoposide after oral or intravenous administration of etoposide in rats. The oral (6 mg/kg) or intravenous (2 mg/kg) etoposide was administered to rats alone or 30 min after the oral kaempferol (1, 4, or 12 mg/kg) administration. Compared to the oral control group, the presence of kaempferol significantly (4 mg/kg, P < 0.05; 12 mg/kg, P < 0.01) increased the area under the plasma concentrationtime curve (AUC) and the peak concentration (C(max)) of the oral etoposide. Kaempferol decreased significantly (4 or 12 mg/kg, P < 0.05) the total body clearance (CL/F) of oral etoposide, while there was no significant change in the terminal halflife (t(1/2)), the elimination rate constant (K(el)) and the time to reach the peak concentration (T(max)) of etoposide in the presense of kaempferol. Consequently, the absolute bioavailability (AB%) of oral etoposide with kaempferol was significantly higher (4 mg/kg, P < 0.05; 12 mg/kg, P < 0.01) than those from the control group. Compared to the intravenous control group, the presence of kaempferol enhanced the AUC of intravenously administered etoposide, however, only presence of 12 mg/kg of kaempferol significant (P < 0.05) increased AUC of etoposide. The enhanced bioavailability of oral etoposide by kaempferol could have been due to an inhibition of cytochrom P450 (CYP) 3A and P-glycoprotein (P-gp) in the intestinal or decreased total body clearance in the liver by kaempferol. The dosage regimen of etoposide should be taken into consideration for potential drug interaction when combined with kaempferol or dietary supplements containing kaempferol in patients.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/pharmacokinetics , Dietary Supplements , Etoposide/administration & dosage , Etoposide/pharmacokinetics , Kaempferols/administration & dosage , ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Administration, Oral , Animals , Biological Availability , Cytochrome P-450 CYP3A/metabolism , Cytochrome P-450 CYP3A Inhibitors , Drug Interactions , Injections, Intravenous , Intestines/drug effects , Intestines/enzymology , Liver/drug effects , Liver/enzymology , Male , Rats , Rats, Sprague-Dawley
12.
Eur J Drug Metab Pharmacokinet ; 33(3): 159-64, 2008.
Article in English | MEDLINE | ID: mdl-19007041

ABSTRACT

Etoposide is mainly metabolized by cytochrome P450 (CYP) 3A and is a substrate for P-glycoprotein (P-gp). This study examined the effects of verapamil, a CYP3A and P-gp inhibitor, on the pharmacokinetics of etoposide in rats. A single dose of etoposide was administered via oral (p.o.; 10 mg/kg) or intravenous (i.v.; 3.3 mg/kg) routes to rats alone (control animals) or together in combination with verapamil (2 or 6 mg/kg; experimental animals). The presence of verapamil significantly increased the area under the plasma concentration-time curve (AUC); (P < 0.05; 39.2-47.6%) and significantly reduced (P < 0.01; 27.8-31.2%) the total body clearance (CLt) of p.o. administered etoposide. The absolute bioavailability (F) of etoposide increased by 1.38- to 1.47-fold. The presence of verapamil significantly increased (P < 0.01; 38.3-38.9%) the AUC and significantly reduced (P < 0.01; approximately 27%) the total body clearance (CLt) of i.v. administered etoposide. This increased bioavailability suggests that verapamil inhibits metabolic activity and elimination etoposide. The increased bioavailability of etoposide in the presence of verapamil should be taken into consideration for dosage regimens due to a potential drug interaction (DI).


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacokinetics , Calcium Channel Blockers/pharmacology , Etoposide/pharmacokinetics , Verapamil/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , Administration, Oral , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/blood , Chromatography, High Pressure Liquid , Cytochrome P-450 CYP3A , Cytochrome P-450 Enzyme Inhibitors , Dose-Response Relationship, Drug , Drug Interactions , Etoposide/administration & dosage , Etoposide/blood , Injections, Intravenous , Male , Rats , Rats, Sprague-Dawley , Time Factors
13.
J Cancer Res Clin Oncol ; 134(5): 609-15, 2008 May.
Article in English | MEDLINE | ID: mdl-17922291

ABSTRACT

PURPOSE: The aim of this study was to determine the expression of cellular FLICE-like inhibitory protein (cFLIP) in head and neck squamous cell carcinoma (HNSCC) and revealed its possible correlation to Fas protein and tumour clinical parameters. METHODS: The expression of cFLIP was analysed in 58 HNSCC samples and 30 morphologically normal tissues adjacent to the carcinomas using immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. Furthermore, its possible correlation to the expression of Fas protein and tumour clinicopathologic parameters were discussed. RESULTS: Cellular FLICE-like inhibitory protein was demonstrated to be up regulated in most HNSCC than in normal tissues by immunohistochemistry (p<0.01). Although the mRNA levels of both isoforms of cFLIP, long form (cFLIP(L)) and short form (cFLIP(S)), in HNSCC were higher than those in normal tissues (p<0.01), only cFLIP(L) protein could be detected by western blot. Furthermore, the expression of cFLIP(L) protein was significantly associated with tumour clinical stage (p<0.01) and lymph node metastasis (p=0.01). Since all of the tumours with Fas immunostaining also express cFLIP protein, there was no significant correlation between them (p>0.05). CONCLUSIONS: Overexpression of cFLIP(L) is a frequent event in HNSCC and HNSCC cells in vivo may need it to evade apoptosis mediated by Fas or other receptors, which might contribute to tumour development and progression.


Subject(s)
Biomarkers, Tumor/analysis , CASP8 and FADD-Like Apoptosis Regulating Protein/biosynthesis , Carcinoma, Squamous Cell/metabolism , Head and Neck Neoplasms/metabolism , Adult , Aged , Blotting, Western , Carcinoma, Squamous Cell/pathology , Electrophoresis, Polyacrylamide Gel , Female , Gene Expression , Head and Neck Neoplasms/pathology , Humans , Immunohistochemistry , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , fas Receptor/biosynthesis
14.
Article in Chinese | MEDLINE | ID: mdl-17432351

ABSTRACT

OBJECTIVE: To investigate the classification, incidence and influential factors of severe complications occurred in endoscopic sinus surgery (ESS) and how to deal with them. METHODS: One thousand and one hundred two patients with chronic sinusitis and nasal polyps treated by ESS were analyzed. RESULTS: Twenty-one patients had severe complications. The types of complication included intraorbital hematoma (n=3), medial rectus injury (n=2), blindness (n=1), intracranial, hematoma (n=1), cerebrospinal rhinorrhea (n=3), nasolacrimal duct injury (n=3), nasal septum perforation (n=2), hemorrhage (n=2), thrombosis in legs (n=2) and asthma (n=2). The total incidence of severe complications was 1.91% (21/1102), most of which were complications in orbit (0.54%) and cranium (0.36%). The extent of the lesion, the surgical history of the patients, the technique and experience of the surgeons were the most important influential factors to severe complications. CONCLUSIONS: Although there are many influential factors to severe complications in ESS, subjective factors are the more important, especial, the technique and the experience of the surgeon.


Subject(s)
Endoscopy/adverse effects , Otorhinolaryngologic Surgical Procedures/adverse effects , Postoperative Complications , Adult , Chronic Disease , Female , Humans , Male , Middle Aged , Nasal Polyps/surgery , Rhinitis/surgery , Sinusitis/surgery
15.
Biopharm Drug Dispos ; 28(3): 151-6, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17315145

ABSTRACT

This study investigated the effects of orally administered morin, an inhibitor of CYP isozyme and P-glycoprotein (P-gp), on the pharmacokinetics of intravenous and orally administered etoposide in rats. It was reported that etoposide is a substrate for P-gp and metabolized mainly via CYP3A4 and to a lesser degree via CYP1A2 and 2E1. Etoposide was administered through intravenous (2 mg/kg) or oral (6 mg/kg) routes to rats with or without orally administered morin (5 or 15 mg/kg), which was administered 30 min before etoposide. The pharmacokinetic parameters of etoposide intravenously administered were not significantly different from other groups, suggesting that CYP 3A-mediated metabolism and the P-gp mediated efflux of etoposide in the liver and kidney seemed not to be markedly inhibited by orally administered morin. However, orally administered morin (15 mg/kg) significantly increased the AUC (45.8%), C(max) (32.0%) and the absolute bioavailability (35.9%) of orally administered etoposide compared with the control, which could be mainly due to inhibition of CYP isoenzyme and P-gp in the intestine by morin. The dosage regimen of etoposide should be taken into consideration for toxic reactions when combined with morin or dietary supplements containing morin in patients.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacokinetics , Antioxidants/pharmacology , Etoposide/pharmacokinetics , Flavonoids/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , Administration, Oral , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Antioxidants/administration & dosage , Area Under Curve , Biological Availability , Cytochrome P-450 Enzyme System/drug effects , Drug Interactions , Etoposide/administration & dosage , Flavonoids/administration & dosage , Humans , Injections, Intravenous , Kidney/drug effects , Kidney/metabolism , Liver/drug effects , Liver/metabolism , Male , Random Allocation , Rats , Rats, Sprague-Dawley
16.
Int J Pharm ; 337(1-2): 188-93, 2007 Jun 07.
Article in English | MEDLINE | ID: mdl-17267149

ABSTRACT

As many anticancer agents paclitaxel is a substrate for ATP-binding cassette (ABC) transporters such as P-glycoprotein-mediated efflux, and its metabolism in humans mainly catalyzed by CYP 3A4 and 2C8. Genistein, an isoflavonoid, is supposed to be an inhibitor of some ABC transporters, and its oxidative metobolism catalyzed by CYP 3A4 and 2C8. The purpose of this study was to investigate the effect of orally administered genistein on the pharmacokinetics of paclitaxel administered through oral and intravenous (i.v.) route in rats. A single dose of paclitaxel administered orally (30 mg/kg) or i.v. (3mg/kg) alone or 30 min after oral administration of genistein (3.3mg/kg or 10mg/kg). The presence of 10mg/kg genistein significantly (p<0.05) increased the area under the plasma concentration-time curve (AUC, 54.7% greater) of orally administered paclitaxel, which was due to the significantly (p<0.05) decreased total plasma clearance (CL/F) of paclitaxel (35.2% lower). Genistein also increased the peak concentration (C(max)) of paclitaxel significantly (p<0.05 by 3.3mg/kg, 66.8% higher; p<0.01 by 10mg/kg, 91.8% higher). Consequently, the absolute bioavailability (F) of paclitaxel in the presence of genistein was 0.020-0.025, which was elevated more than the control group (0.016); and the relative bioavailability (Fr) of orally administered paclitaxel was increased from 1.26- to 1.55-fold. Ten milligrams per kilogram genistein also significantly (p<0.05) increased the AUC (40.5% greater) and reduced the total clearance (CLt, 30% lower) of i.v. administered paclitaxel. The presence of genistein improved the systemic exposure of paclitaxel in this study. The pharmacokinetic interaction between them should be taken into consideration when paclitaxel is used with genistein or the dietary supplements full of genistein.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/pharmacokinetics , Genistein/pharmacology , Herb-Drug Interactions , Nonprescription Drugs , Paclitaxel/administration & dosage , Paclitaxel/pharmacokinetics , Phytoestrogens/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Administration, Oral , Animals , Antineoplastic Agents, Phytogenic/blood , Area Under Curve , Aryl Hydrocarbon Hydroxylases/metabolism , Biological Availability , Cytochrome P-450 CYP3A , Cytochrome P-450 Enzyme System/metabolism , Genistein/administration & dosage , Genistein/metabolism , Injections, Intravenous , Male , Metabolic Clearance Rate/drug effects , Paclitaxel/blood , Phytoestrogens/administration & dosage , Phytoestrogens/metabolism , Rats , Rats, Sprague-Dawley
17.
Lin Chuang Er Bi Yan Hou Ke Za Zhi ; 20(17): 777-9, 783, 2006 Sep.
Article in Chinese | MEDLINE | ID: mdl-17087112

ABSTRACT

OBJECTIVE: To explore the possible roles of three neuropeptides in the pathogenesis of vasomotor rhinitis by studying the expression and distribution of neuropeptides in the mucosa of vasomotor rhinitis, such as Substance P(SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide(VIP). METHOD: The mucosa specimens of thirty vasomotor rhinitis patients who had typical symptoms and signs were selected randomly as the experiment group and were divided into two subgroups depending on if received treatment or not. While the normal middle turbinate mucosa specimens of nine cases were selected as the control group. The expression and distribution of neuropeptides were examined by immunohistochemical SP method and computer image disposing and analyzing system. RESULT: The terminals of SP, CGRP and VIP in the treated experiment group wer and untreated experiment group were markedly increased in density of immunostaining compared to the control group,and the difference is significant (P < 0.01). CONCLUSION: Neuropeptides, such as SP, CGRP and VIP, may play important roles in the pathophysiological mechanism of vasomotor rhinitis.


Subject(s)
Calcitonin Gene-Related Peptide/metabolism , Nasal Mucosa/metabolism , Rhinitis, Vasomotor/pathology , Substance P/metabolism , Vasoactive Intestinal Peptide/metabolism , Adolescent , Adult , Female , Humans , Male , Middle Aged , Nasal Mucosa/pathology , Rhinitis, Vasomotor/metabolism , Young Adult
19.
Int J Pharm ; 313(1-2): 144-9, 2006 Apr 26.
Article in English | MEDLINE | ID: mdl-16516418

ABSTRACT

Orally administered tamoxifen undergoes a first-pass metabolism and substrates for multidrug resistance (MDR) transporters efflux in the liver and intestines, which obstructs its systemic exposure. This study investigated the effect of quercetin, a dual inhibitor of CYP3A4 and P-gp, on the bioavailability and pharmacokinetics of tamoxifen and one of its metabolites, 4-hydroxytamoxifen, in rats. The pharmacokinetic parameters of tamoxifen and 4-hydroxytamoxifen in plasma were determined after orally administering tamoxifen (10 mg/kg) with or without quercetin (2.5, 7.5 and 15 mg/kg). The coadministration of quercetin (2.5 and 7.5 mg/kg) significantly (p < 0.05) increased the absorption rate constant (K(a)), peak concentration (C(max)) and the areas under the plasma concentration-time curve (AUC) of tamoxifen. The absolute bioavailability (AB%) of tamoxifen with 2.5 and 7.5 mg/kg quercetin ranged from 18.0% to 24.1%, which was significantly higher than the control group, 15.0% (p < 0.05). The relative bioavailability (RB%) of tamoxifen coadministered with quercetin was 1.20-1.61 times higher than the control group. The coadministration of quercetin caused no significant changes in the terminal half-life (t(1/2)) and the time to reach the peak concentration (T(max)) of tamoxifen. Compared with the control group, the coadministration of 7.5 mg/kg quercetin significantly (p < 0.05) increased the AUC of 4-hydroxytamoxifen. However, the metabolite ratios (MR; AUC of 4-hydroxytamoxifen to tamoxifen) were significantly lower (p < 0.05). This suggests that quercetin inhibits the both MDR transporters efflux and first-pass metabolism of tamoxifen. The enhanced bioavailability of tamoxifen as a result of its coadministration with quercetin might be due to the effect of quercetin promoting the intestinal absorption and reducing the first-pass metabolism of tamoxifen. If the results are further confirmed in the clinical trials, the tamoxifen dosage should be adjusted when tamoxifen is administered with quercetin or quercetin-containing dietary supplements in order to avoid potential drug interactions.


Subject(s)
Enzyme Inhibitors/pharmacology , Estrogen Antagonists/pharmacokinetics , Quercetin/pharmacology , Tamoxifen/analogs & derivatives , ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Administration, Oral , Animals , Biological Availability , Cytochrome P-450 CYP3A/metabolism , Cytochrome P-450 CYP3A Inhibitors , Drug Interactions , Estrogen Antagonists/administration & dosage , Female , Intestinal Absorption/drug effects , Isoenzymes/antagonists & inhibitors , Isoenzymes/metabolism , Liver/drug effects , Liver/enzymology , Rats , Rats, Sprague-Dawley , Tamoxifen/administration & dosage , Tamoxifen/pharmacokinetics
20.
Lin Chuang Er Bi Yan Hou Ke Za Zhi ; 19(17): 779-81, 2005 Sep.
Article in Chinese | MEDLINE | ID: mdl-16334251

ABSTRACT

OBJECTIVE: To discuss the method, effect and the influence factors of nasal endoscopic surgery for the treatment of nasal inverted papilloma. METHOD: Retrospective analysis the clinical data of the 23 cases who received nasal endoscopic surgery for the treatment of nasal inverted papilloma. RESULT: Only one case had recurrence after four months and was then cured by a combined treatment of external nasal approach and radiotherapy. The other 22 cases had no recurrence in the follow-up period. CONCLUSION: Endoscopic sinus surgery for the treatment of nasal inverted papilloma has satisfactory effect, so it can be regard as the first-selecting operation mode for the nasal inverted papilloma. However, it's essential to pay enough attention to such influence factors as choosing suitable case, particular preoperative examination and selecting suitable operation mode.


Subject(s)
Endoscopy , Nose Neoplasms/surgery , Papilloma, Inverted/surgery , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult
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