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1.
Iran J Otorhinolaryngol ; 36(4): 551-558, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39015689

RESUMO

Introduction: To develop and validate a click-based mobile "Audiclick" app employing click noises for hearing assessments. Materials and Methods: This prospective comparative study compares the "AudiClick" app as a hearing screening tool to pure tone audiometry. Participants listened to sounds through wired earbud headphones that were connected to an Android or iOS device. Results: The study involved 110 participants aged between 18 to 80 years old. All degrees of hearing loss severity corresponds to pure tone average (p < 0.01) results. The app was also found to be effective at identifying hearing loss (80-99% sensitivity, specificity, positive predictive value, and accuracy). Test-retest reliability had also shown excellent ICC scores of 0.93. Conclusions: This study demonstrates that a mobile app using click sounds can be as efficient as pure tone audiometry for field screenings, while being more cost-effective and easier to develop.

2.
Cureus ; 16(2): e53681, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38455780

RESUMO

The removal of an ectopic molar tooth at the pterygomaxillary junction may be challenging. This paper presents the use of three-dimensional (3D) printing of the paranasal sinus for careful planning in a way that reduces the risk and makes surgical procedures more effective. A 26-year-old gentleman presented to the ENT department with a left antrochoanal polyp and an incidental ectopic tooth at the pterygomaxillary junction. Pre-operative 3D reconstruction of the maxillary cavity and subsequent 3D printing were used to guide the surgery and counsel the patient on potential outcomes. Left anterior functional endoscopic sinus surgery was subsequently done, and the antrochoanal polyp was completely removed. The preoperative computed tomography scan allowed for the production of the printed model to the exact size and dimensions of the ectopic molar tooth to facilitate the planning of the surgery and to aid in consenting the patient for the treatment.

4.
Indian J Otolaryngol Head Neck Surg ; 75(2): 1259-1262, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37275017

RESUMO

Background: Endoscopic nasal surgery is often a tedious process due to repeated removal of the Hopkins rod telescope from the nasal cavity for manual defogging of the tip due to the presence of blood, smoke, and secretions. Objective: To design and print a 3-dimensional (3D) low-cost telescopic sleeve to allow the defogging solution to clean the rigid telescope tip without removing it from the nasal cavity. In addition, the sleeve must also act as a conduit for suction and irrigation to provide a clear surgical field view intraoperatively. Results and conclusion: A 3D printed low-cost telescopic sleeve, when used in conjunction with other add-ons, can be a helpful and cost-effective adjunct during endoscopic nasal surgery. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03281-0.

5.
Indian J Otolaryngol Head Neck Surg ; 74(Suppl 3): 5033-5036, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36742682

RESUMO

To describe the technique and outcome of a novel dual staged supraglottoplasty for the treatment of neurological induced adult onset laryngomalacia. A 55 year old male had a diagnosed neurodegenerative disorder with suspected Pompe's disease associated with Trap door epiglottis and proximal myopathy.This was complicated with emergency airway distress and subsequent tracheostomy.Trap-door epiglottis (also known as adult-onset laryngomalacia) associated with neurodegenerative disorders constitute a surgical challenge as it is often coupled with failure of tracheostomy decannulation when present. The patient underwent a novel dual staged endoscopic supraglottoplasty whereby an initial stage of epiglottopexy and submucosal diathermy was made at the vallecula.This was then followed by an interval of 6 weeks whereby a partial epiglottotectomy was made at the upper 3rd of the epiglottis and reduction of lingual tonsils was done using radiofrequency ablation.Trachesotomy was decannulated 1 month after the second stage procedure and his airway remains asymptomatic after 1 year of surgical treatment. This case report describes the success of tracheostomy decannulation after a novel dual staged supraglottoplasty for adult onset laryngomalcia (also known as trap-door epiglottis) .

6.
Indian J Otolaryngol Head Neck Surg ; 74(Suppl 3): 6032-6038, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36742789

RESUMO

Preoperative radiological assessment of parotid tumours represents a crucial step in the planning of a parotidectomy in order to avoid post-operative facial nerve paralysis. The purpose of this study is to determine the reliability of the novel 'M-line' in predicting the facial nerve position and compare it to various radiological methods in the same context. 66 patients whom had underwent parotidectomy for parotid tumours from January 2012 to February 2021 were analyzed. Parotid tumour location were identified using the retromandibular vein, facial nerve line, Conn's arc, Utrecht line and the 'M'-line were compared to the intraoperative location of parotid tumours.The 'M'-line is a novel hypothetical line (drawn between the lateral surface of the mandible to the lateral border of the mastoid process) used to identify the location of the facial nerve radiologically. The 'M-Line' and other methods of radiological assessments were associated with statistical significance in predicting if the parotid tumours were superficial or deep to the facial nerve (p-value < 0.05).The 'M-line' had demonstrated a sensitivity of 73.6% and 92.3% specificity.It had also yielded the highest accuracy (77.3%) in the prediction of the parotid tumour location in relation to the facial nerve. While the radiological lines represented by the Retromandibular vein,facial nerve line,Utrecht line and Conn's arc were statistically significant in predicting the location of the parotid tumour in relation to the facial nerve, the M-line was the most accurate and sensitive predictor in our study.The M-Line is a potentially useful tool to predict the location of the facial nerve in relation to a parotid tumour.

7.
Medeni Med J ; 36(3): 281-286, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34915688

RESUMO

IgG4-related disease (IgG4-RD) is a fibro-inflammatory condition associated with tumefactive lesions at multiple sites. IgG4-RD was initially recognized in 2001 in a case of autoimmune pancreatitis. However, the disease was not limited to the pancreas but involved other organs such as the bile ducts, lacrimal glands, lymph nodes and salivary glands. IgG4-RD is rarely seen with an estimated incidence of 0.2 to 1/100.000 as reported in Japan, but with minimal to no incidence data have been published in Western countries. We hereby report a case of an IgG4-related mass arising from the nasolacrimal duct, masquerading as a sinonasal mass.

9.
Iran J Otorhinolaryngol ; 31(107): 383-386, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31857983

RESUMO

INTRODUCTION: Branchial arch anomalies represent defects in embryological developments whereby parts of the branchial arch persist in the head and neck regions as sinuses, fistulas, or cysts. These anomalies usually present as a unilateral lesion in the head and neck of young adults and children, which are excised upon the emergence of complications. CASE REPORT: Herein, we presented a rare case of a 4-year-old child, who had been diagnosed with a complete bilateral second arch branchial fistula. The excision was made using the bilateral stepladder approach and tonsillectomy. CONCLUSION: The bilateral stepladder approach was a feasible method in excising a complete bilateral branchial fistula. However, larger-scale studies should be conducted on the surgical techniques of bilateral branchial fistulae excision in order to optimize the cosmetic outcome of the surgery.

10.
Otolaryngol Head Neck Surg ; 159(4): 783-788, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30126325

RESUMO

Objective To objectively compare the nasal decongestion potency of lidocaine/phenylephrine when delivered with a nasal nebulizer and a nasal spray before a rigid nasoendoscopic examination. Study Design Open-label randomized controlled trial. Setting Multicenter study. Methods This prospective clinical trial involved 106 participants with untreated chronic rhinitis. Fifty-three participants had 400 µL of lidocaine/phenylephrine administered into the right nostril with a nasal nebulizer, while the remaining 53 participants had 400 µL administered with a nasal spray. The control was the left nostril. Nasal resistance at 150-Pa fixed pressure was evaluated with an active anterior rhinomanometry at 5, 10, 15, and 30 minutes postintervention. Pain score was assessed subjectively by applying pressure to the inferior turbinate 30 minutes after intervention. Results There was an overall reduction in nasal resistance of the right nostril when lidocaine/phenylephrine was administered with the nasal nebulizer in comparison with the nasal spray. However, a statistically significant difference in nasal resistance was seen only at 5 minutes ( P = .047), 15 minutes ( P = .016), and 30 minutes ( P = .036). The examining endoscopist further supported the degree of nasal decongestion via subjective assessment of the nasal cavity ( P = .001). Pain scores obtained after the intervention showed a significant decrease in pain threshold when the nasal nebulizer was used instead of the nasal spray ( P = .040). Conclusions This study suggests that the delivery of lidocaine/phenylephrine to the nasal cavity by the nasal nebulizer provides better decongestive and analgesic potency as compared with the delivery by nasal sprays.


Assuntos
Lidocaína/administração & dosagem , Mucosa Nasal/efeitos dos fármacos , Obstrução Nasal/tratamento farmacológico , Sprays Nasais , Nebulizadores e Vaporizadores , Fenilefrina/administração & dosagem , Rinite/complicações , Administração Intranasal , Combinação de Medicamentos , Endoscopia/métodos , Feminino , Seguimentos , Humanos , Malásia , Masculino , Descongestionantes Nasais/administração & dosagem , Obstrução Nasal/etiologia , Estudos Prospectivos , Rinite/diagnóstico , Resultado do Tratamento
11.
Iran J Otorhinolaryngol ; 30(99): 225-229, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30083529

RESUMO

INTRODUCTION: This study aims to report a rare case of a respiratory epithelial adenomatoid hamartoma (REAH) of the lateral nasal wall that had initially presented as a fungating mass, similar to that of a sinonasal malignancy, and its complete removal from the lateral nasal wall. CASE REPORT: We report the case of a 58-year-old woman who presented to us with a chief complaint of recurrent right-sided epistaxis and nasal blockage for the past 4 months, which was progressively worsening. Histopathological examination confirmed the presence of a REAH instead of a sinonasal malignancy. The tumor was surgically excised from the lateral nasal wall using electrocautery under endoscopic guidance. The patient was then carefully followed-up after surgery, and the wound was successfully healed 3 months after the initial surgery. There was no evidence of recurrence 6 months after the initial surgery. CONCLUSION: This case demonstrates the rare presentation of a REAH, which had arisen from the lateral nasal wall. Clinically, it is difficult to distinguish a REAH from a more notorious mass such as a sinonasal malignancy. Therefore, biopsy is mandatory in all cases of lateral nasal mass in order to rule out malignancy before confirming nasal REAH. Fortunately, as seen in this case, a lateral nasal REAH, once diagnosed, can be safely and easily removed from the lateral nasal wall using electrocautery with good surgical outcomes and a low rate of recurrence.

12.
Int J Pediatr Otorhinolaryngol ; 109: 50-53, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29728184

RESUMO

OBJECTIVE: To study the audiological outcome and early screening of pre-school going children with craniosynostosis under follow-up at the University of Malaya Medical Center(UMMC), Kuala Lumpur, Malaysia over a 10 year period. METHODS: A retrospective descriptive cohort study on the audiological findings detected during the first hearing assessment done on a child with craniosynostosis using otoacoustic emissions, pure tone audiometry or auditory brainstem response examination. The main aim of this study was to evaluate the type and severity of hearing loss when compared between syndromic and non-sydromic craniosynostosis, and other associated contributory factors. RESULTS: A total of 31 patients with 62 ears consisting of 14 male patients and 17 female patients were evaluated. Twenty two patients (71%) were syndromic and 9 (29%) were non-syndromic craniosynostosis. Amongst the syndromic craniosynostosis, 9 (41%) had Apert syndrome, 7 (32%) had Crouzon syndrome, 5 (23%) had Pfieffer syndrome and 1 (4%) had Shaethre Chotzen syndrome. Patients with syndromic craniosynostosis were more likely to present with all types and severity of hearing loss, including severe to profound sensorineural hearing loss while children with non-syndromic craniosynostosis were likely to present with normal hearing (p < 0.05). In addition, when the first hearing test was done at a later age, a hearing loss including sensorineural hearing loss is more likely to be present in a child with syndromic craniosynostosis (p < 0.05). CONCLUSION: Our study suggested that children who are born with syndromic craniosynostosis were more likely to suffer from a hearing loss, including that of a severe to profound degree compared to children with non-syndromic craniosynostosis. In addition to that, hearing loss is more likely to be detected when the first hearing test is done at a later age, and this can be an irreversible sensorineural hearing loss. We would like to advocate the need for early audiological screening and follow up in children with syndromic craniosynostosis.


Assuntos
Disostose Craniofacial/complicações , Craniossinostoses/complicações , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva/etiologia , Acrocefalossindactilia/complicações , Audiometria de Tons Puros , Pré-Escolar , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Perda Auditiva/diagnóstico , Perda Auditiva/fisiopatologia , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/fisiopatologia , Humanos , Lactente , Masculino , Emissões Otoacústicas Espontâneas , Estudos Retrospectivos
13.
Oman Med J ; 33(2): 167-170, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29657688

RESUMO

Langerhans cell histiocytosis (LCH) is a rare proliferative disorder, which commonly arises in the bone and may involve other systems. To date, the diagnosis of temporal bone LCH remains a challenge as it may masquerade as a common ear infection. We report a case of a child who presented to us with persistent bilateral ear discharge for four months and was not responding to treatment. Her condition subsequently worsened, with clinical features and radiological findings suggestive of mastoid cellulitis. Nevertheless, further histopathology study revealed LCH.

14.
Int J Gynecol Cancer ; 28(3): 428-436, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29465505

RESUMO

BACKGROUND: Mucinous epithelial ovarian cancers (mEOCs) respond poorly to conventional chemotherapy and have a poor prognosis in advanced stages. The genomic landscape for mEOC in the Asian settings is ill defined. We seek to identify various mutational aberrations present in mEOC and correlate them with clinical outcomes. METHODS: A total of 199 cases of mEOC were identified from a prospectively maintained gynecologic oncology tumor database. DNA was extracted and analyzed for KRAS mutations by using Sanger sequencing. Further MassArray sequencing was performed on 45 samples. Clinicopathologic correlation was performed with the results obtained. FINDINGS: KRAS mutation status was evaluable in 124 cases. Fifty-five percent (68/124) were KRAS negative, whereas 45% (56/124) harbored a KRAS mutation, lower than that in Western populations. Successful ascertainment of both KRAS and HER2 statuses by Sanger sequencing occurred for 105 cases. The proportion of the double-positive subtype (HER2+ and KRAS positive) was 8% (8/105); double-negative subtype (HER2- and KRAS negative), 34% (36/105); and cases with mutation in either KRAS or HER2, 58% (61/105). The KRAS mutation rate was 44%, 50%, and 29% among Chinese, Indians, and Malays, respectively. There was no significant difference in overall survival (P = 0.952) or progression-free survival (P = 0.635) between KRAS-positive and KRAS-negative patients. Similar results were observed for progression-free survival (P = 0.206) and overall survival (P = 0.440) when outcomes were examined between the 4 groups based on KRAS and HER2 mutation. Patients in the double-negative mutation subgroup had higher risk for death/progression compared with patients in the other 3 mutation subgroups. Further MassARRAY multiplexed profiling was performed in patients with sufficient DNA material (n = 45) and yielded KRAS mutations (n = 16), PDGFRA mutations (n = 3), PIK3CA (n = 1) and KIT (n = 1), and HRAS, FGFR, MET, and NRAS (n = 1 each). CONCLUSIONS: Our study provides further knowledge about the mutational aberrations in mEOC in Asian populations. Neither the presence of KRAS mutation nor their correlation with HER2 mutations influenced outcomes.


Assuntos
Adenocarcinoma Mucinoso/genética , Povo Asiático/genética , Mutação , Neoplasias Ovarianas/genética , Adenocarcinoma Mucinoso/patologia , Adulto , Análise Mutacional de DNA , DNA de Neoplasias/genética , DNA de Neoplasias/isolamento & purificação , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Hibridização In Situ , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Receptor ErbB-2/genética
15.
BMJ Case Rep ; 20162016 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-27793872

RESUMO

Sialolithiasis is among the most common disease affecting the major salivary glands whereby the submandibular gland or its duct is affected in the majority of cases. We report a case of the surgical removal of a giant sialolith along with the submandibular gland using the transcervical approach and its clinical outcome.


Assuntos
Cálculos das Glândulas Salivares/cirurgia , Doenças da Glândula Submandibular/cirurgia , Adulto , Humanos , Masculino , Radiografia Panorâmica , Cálculos das Glândulas Salivares/diagnóstico por imagem , Doenças da Glândula Submandibular/diagnóstico por imagem
16.
BMJ Case Rep ; 20162016 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-27566213

RESUMO

An acquired persistent tracheopharyngeal fistula secondary to an infected tracheopharyngeal voice prosthesis is a common cause of recurrent aspiration pneumonia in a postlaryngectomy patient. We report a case of a successfully treated tracheopharyngeal fistula whereby both the sternocleidomastoid muscles were used as muscular flaps to close the defect and its outcome.


Assuntos
Fístula/cirurgia , Laringe Artificial/efeitos adversos , Doenças Faríngeas/cirurgia , Retalhos Cirúrgicos , Doenças da Traqueia/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Faríngeas/etiologia , Doenças da Traqueia/etiologia
17.
Cell Oncol (Dordr) ; 39(2): 175-86, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26868260

RESUMO

BACKGROUND: Melanoma-associated antigen (MAGE)-A3 is a member of the family of cancer-testis antigens and has been found to be epigenetically regulated and aberrantly expressed in various cancer types. It has also been found that MAGE-A3 expression may correlate with an aggressive clinical course and with chemo-resistance. The objectives of this study were to assess the relationship between MAGE-A3 promoter methylation and expression and (1) gastric cancer patient survival and (2) its functional consequences in gastric cancer-derived cells. METHODS: Samples from two independent gastric cancer cohorts (including matched non-malignant gastric samples) were included in this study. MAGE-A3 methylation and mRNA expression levels were determined by methylation-specific PCR (MSP) and quantitative real-time PCR (qPCR), respectively. MAGE-A3 expression was knocked down in MKN1 gastric cancer-derived cells using miRNAs. In addition, in vitro cell proliferation, colony formation, apoptosis, cell cycle, drug treatment, immunohistochemistry and Western blot assays were performed. RESULTS: Clinical analysis of 223 primary patient-derived samples (ntumor = 161, nnormal = 62) showed a significant inverse correlation between MAGE-A3 promoter methylation and expression in the cancer samples (R = -0.63, p = 5.99e-19). A lower MAGE-A3 methylation level was found to be associated with a worse patient survival (HR: 1.5, 95 % CI: 1.02-2.37, p = 0.04). In addition, we found that miRNA-mediated knockdown of MAGE-A3 expression in MKN1 cells caused a reduction in its proliferation and colony forming capacities, respectively. Under stress conditions MAGE-A3 was found to regulate the expression of Bax and p21. MAGE-A3 knock down also led to an increase in Puma and Noxa expression, thus contributing to an enhanced docetaxel sensitivity in the gastric cancer-derived cells. CONCLUSIONS: From our results we conclude that MAGE-A3 expression is regulated epigenetically by promoter methylation, and that its expression contributes to gastric cell proliferation and drug sensitivity. This study underscores the potential implications of MAGE-A3 as a therapeutic target and prognostic marker in gastric cancer patients.


Assuntos
Antígenos de Neoplasias/metabolismo , Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas de Neoplasias/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Antígenos de Neoplasias/genética , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Metilação de DNA/genética , Docetaxel , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Humanos , Proteínas de Neoplasias/genética , Regiões Promotoras Genéticas , Estresse Fisiológico/efeitos dos fármacos , Análise de Sobrevida , Taxoides/farmacologia , Ensaio Tumoral de Célula-Tronco
18.
Dis Model Mech ; 8(7): 743-53, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-26035378

RESUMO

Hepatocellular carcinoma (HCC) is a deadly disease, often unnoticed until the late stages, when treatment options become limited. Thus, there is a crucial need to identify biomarkers for early detection of developing HCC, as well as molecular pathways that would be amenable to therapeutic intervention. Although analysis of human HCC tissues and serum components may serve these purposes, inability of early detection also precludes possibilities of identification of biomarkers or pathways that are sequentially perturbed at earlier phases of disease progression. We have therefore explored the option of utilizing mouse models to understand in a systematic and longitudinal manner the molecular pathways that are progressively deregulated by various etiological factors in contributing to HCC formation, and we report the initial findings in characterizing their validity. Hepatitis B surface antigen transgenic mice, which had been exposed to aflatoxin B1 at various stages in life, were used as a hepatitis model. Our findings confirm a synergistic effect of both these etiological factors, with a gender bias towards males for HCC predisposition. Time-based aflatoxin B1 treatment also demonstrated the requirement of non-quiescent liver for effective transformation. Tumors from these models with various etiologies resemble human HCCs histologically and at the molecular level. Extensive molecular characterization revealed the presence of an 11-gene HCC-expression signature that was able to discern transformed human hepatocytes from primary cells, regardless of etiology, and from other cancer types. Moreover, distinct molecular pathways appear to be deregulated by various etiological agents en route to formation of HCCs, in which common pathways converge, highlighting the existence of etiology-specific as well as common HCC-specific molecular perturbations. This study therefore highlights the utility of these mouse models, which provide a rich resource for the longitudinal analysis of molecular changes and biomarkers associated with HCC that could be exploited further for therapeutic targeting.


Assuntos
Neoplasias Hepáticas Experimentais/etiologia , Neoplasias Hepáticas Experimentais/genética , Aflatoxina B1/toxicidade , Animais , Carcinogênese/induzido quimicamente , Carcinogênese/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proliferação de Células , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Hepatite B/complicações , Hepatite B/patologia , Antígenos de Superfície da Hepatite B/genética , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas Experimentais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
19.
Carcinogenesis ; 36(4): 441-51, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25742747

RESUMO

Gastric cancer (GC) is the second leading cause of global cancer mortality worldwide. However, the molecular mechanism underlying its carcinogenesis and drug resistance is not well understood. To identify novel functionally important genes that were differentially expressed due to combinations of genetic and epigenetic changes, we analyzed datasets containing genome-wide mRNA expression, DNA copy number alterations and DNA methylation status from 154 primary GC samples and 47 matched non-neoplastic mucosa tissues from Asian patients. We used concepts of 'within' and 'between' statistical analysis to compare the difference between tumors and controls within each platform, and assessed the correlations between platforms. This 'multi-regulated gene (MRG)' analysis identified 126 differentially expressed genes that underwent a combination of copy number and DNA methylation changes. Most genes were located at genomic loci associated with GC. Statistical enrichment analysis showed that MRGs were enriched for cancer, GC and drug response. We analysed several MRGs that previously had not been associated with GC. Knockdown of DDX27, TH1L or IDH3G sensitized cells to epirubicin or cisplatin, and knockdown of RAI14 reduced cell proliferation. Further studies showed that overexpression of DDX27 reduced epirubicin-induced DNA damage and apoptosis. Levels of DDX27 mRNA and protein were increased in early-stage gastric tumors, and may be a potential diagnostic and prognostic marker for GC. In summary, we used an integrative bioinformatics strategy to identify novel genes that are altered in GC and regulate resistance of GC cells to drugs in vitro.


Assuntos
Antineoplásicos/farmacologia , RNA Helicases DEAD-box/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteínas de Ligação ao Cálcio , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Cisplatino/farmacologia , Proteínas do Citoesqueleto/genética , RNA Helicases DEAD-box/biossíntese , Variações do Número de Cópias de DNA/genética , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/genética , Metilação de DNA/genética , Bases de Dados de Ácidos Nucleicos , Epirubicina/farmacologia , Mucosa Gástrica/citologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Histonas/genética , Humanos , Proteínas do Tecido Nervoso/genética , Prognóstico , Interferência de RNA , RNA Interferente Pequeno , Estudos Retrospectivos , Fatores de Transcrição/genética
20.
Nat Cell Biol ; 17(4): 511-23, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25774835

RESUMO

The functional significance of the overexpression of unmutated TAp73, a homologue of the tumour suppressor p53, in multiple human cancers is unclear, but raises the possibility of unidentified roles in promoting tumorigenesis. We show here that TAp73 is stabilized by hypoxia, a condition highly prevalent in tumours, through HIF-1α-mediated repression of the ubiquitin ligase Siah1, which targets TAp73 for degradation. Consequently, TAp73-deficient tumours are less vascular and reduced in size, and conversely, TAp73 overexpression leads to increased vasculature. Moreover, we show that TAp73 is a critical regulator of the angiogenic transcriptome and is sufficient to directly activate the expression of several angiogenic genes.  Finally, expression of TAp73 positively correlates with these angiogenic genes in several human tumours, and the angiogenic gene signature is sufficient to segregate the TAp73(Hi)- from TAp73(Low)-expressing tumours. These data demonstrate a pro-angiogenic role for TAp73 in supporting tumorigenesis, providing a rationale for its overexpression in cancers.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias/irrigação sanguínea , Neovascularização Patológica/genética , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Animais , Hipóxia Celular , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos SCID , Proteínas Nucleares/biossíntese , Proteínas Nucleares/genética , Ligação Proteica , Proteína Tumoral p73 , Proteínas Supressoras de Tumor/biossíntese , Proteínas Supressoras de Tumor/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Fator A de Crescimento do Endotélio Vascular/biossíntese
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