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1.
Sci Rep ; 10(1): 9497, 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32528160

RESUMO

Zr-based metallic glasses are prepared by quenching supercooled liquid under pressure. These glasses are stable in ambient conditions after decompression. The High Pressure Quenched glasses have a distinct structure and properties. The pair distribution function shows redistribution of the Zr-Zr interatomic distances and their shift towards smaller values. These glasses exhibit higher density, hardness, elastic modulus, and yield stress. Upon heating at ambient pressure, they show volume expansion and distinct relaxation behavior, reaching an equilibrated state above the glass transition. These experimental results are consistent with an idea of pressure-induced low to high density liquid transition in the supercooled melt.

2.
J Dent Res ; 94(2): 320-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25425581

RESUMO

Mortality and morbidity associated with oral squamous cell carcinoma (OSCC) remain unacceptably high with disfiguring treatment options and a death rate of 1 per hour in the United States. The approval of cituximab for advanced OSCC has been the only new treatment for these patients since the 1970s, although it has not significantly increased overall survival. To address the paucity of effective new therapies, we undertook a high-throughput screen to discover small molecules and natural products that could induce endoplasmic reticulum (ER) stress and enforce a terminal unfolded protein response (UPR) in OSCC. The terpenoid cantharidin (CNT), previously used to treat various malignancies in culture-specific medical practices for over 2,000 y, emerged as a hit. CNT and its analog, cantharidic acid, potently induced protein and gene expression profiles consistent with the activation of ER stress, the UPR, and apoptosis in OSCC cells. Murine embryonic fibroblasts null for the UPR-associated transcription factors Atf4 or Chop were significantly protected from CNT, implicating a key role for the UPR in the death response. These data validate that our high-throughput screen can identify novel modulators of UPR signaling and that such compounds might provide a new therapeutic approach to treating patients with OSCC.


Assuntos
Antineoplásicos/farmacologia , Cantaridina/farmacologia , Carcinoma de Células Escamosas/patologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Neoplasias Bucais/patologia , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Fator 4 Ativador da Transcrição/genética , Animais , Apoptose/efeitos dos fármacos , Arilamina N-Acetiltransferase/antagonistas & inibidores , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Células CHO , Morte Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cricetinae , Cricetulus , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Ensaios de Triagem em Larga Escala , Humanos , Zíper de Leucina/genética , Camundongos , RNA Interferente Pequeno/genética , Fator de Transcrição CHOP/genética
3.
Laryngoscope ; 111(8): 1434-9, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11568581

RESUMO

OBJECTIVE: To identify features of major salivary gland cancers that are prognostic for disease-free survival. STUDY DESIGN: A retrospective study of 78 patients with major salivary gland cancer (64 parotid and 14 submandibular gland) who underwent surgery for definitive treatment from 1976 to 1996. A select group of patients also received adjuvant radiation (56%) and/or chemotherapy (13%). METHOD: Clinical and pathological risk factors were obtained from patients' charts and pathology reports. Age, gender, tumor site, T-stage, facial paralysis, histologic neck involvement, perineural invasion, and cancer grade were analyzed with respect to disease-free survival. The role of adjuvant treatment in terms of clinical outcome was also investigated. RESULTS: In our series, the 5-year disease-free survival was 65%. Examining clinical and histologic features one at a time, we found poorer prognosis was associated with submandibular tumors compared with parotid (P =.02), higher T-stage (P =.001), positive cervical nodes (P <.001), perineural invasion (P =.002), and high-grade or adenoid cystic tumors (P =.002). A multivariable analysis indicated that positive lymph nodes (P =.07) and perineural invasion (P =.03) were important histologic predictors of shorter disease-free survival. Receipt of both adjuvant radiation and cisplatin-based chemotherapy (P =.05) was an independent predictor of longer disease-free survival. CONCLUSION: Our study indicated that the presence of positive lymph nodes and perineural invasion is important independent predictors of disease-free survival. Our limited data also suggest that adjuvant chemotherapy and radiation therapy may improve disease-free survival.


Assuntos
Neoplasias Parotídeas/mortalidade , Neoplasias da Glândula Submandibular/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Criança , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Parotídeas/patologia , Prognóstico , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias da Glândula Submandibular/patologia
4.
Otolaryngol Head Neck Surg ; 125(3): 245-52, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11555761

RESUMO

OBJECTIVE: We review our experience and present our approach to treating craniocervical necrotizing fasciitis (CCNF). STUDY DESIGN: All cases of CCNF treated at Wayne State University/Detroit Receiving Hospital from January 1989 to April 2000 were reviewed. Patients were analyzed for source and extent of infection, microbiology, co-morbidities, antimicrobial therapy, hospital days, surgical interventions, complications, and outcomes. RESULTS: A review of 250 charts identified 10 cases that met the study criteria. Five cases (50%) had spread of infection into the thorax, with only 1 (10%) fatality. An average of 24 hospital days (7 to 45), 14 ICU days (6 to 21), and 3 surgical procedures (1 to 6) per patient was required. CONCLUSION: Aggressive wound care, broad-spectrum antibiotics, and multiple surgical interventions resulted in a 90% (9/10) overall survival and 80% (4/5) survival for those with thoracic extension. SIGNIFICANCE: This is the largest single institution report of CCNF with thoracic extension identified to date.


Assuntos
Fasciite Necrosante , Adulto , Desbridamento , Fasciite Necrosante/diagnóstico por imagem , Fasciite Necrosante/cirurgia , Fasciite Necrosante/terapia , Feminino , Cabeça , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pescoço , Cuidados Pós-Operatórios , Radiografia , Estudos Retrospectivos , Doenças Dentárias/microbiologia , Cicatrização
5.
Arch Otolaryngol Head Neck Surg ; 127(6): 665-9, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11405865

RESUMO

BACKGROUND: Severely comminuted frontal sinus fractures are difficult to contour and immobilize. Frequently, plates or wires are inadequate in fixating all fragments together, resulting in less than optimal outcomes. Advancements in the development of biomaterials have now made titanium mesh a new option for the repair of severely comminuted fractures. METHODS: Fourteen patients with severely comminuted frontal sinus fractures were treated with titanium mesh from 1994 to 1999. The fractures were reduced and immobilized using a simple algorithm: (1) Isolated anterior table fractures were repaired with reduced bony fragments attached to titanium mesh. (2) Anterior table fractures with nasofrontal duct involvement were repaired by sinus obliteration and anterior wall reconstruction with reduced bony fragments attached to titanium mesh. (3) Anterior and posterior table fractures with cerebrospinal fluid leak or displacement were treated with the cranialization of the sinus and anterior wall reconstruction with reduced bony fragments attached to titanium mesh. RESULTS: Of the 14 patients treated, 12 were available for postoperative evaluation. Parameters such as nasal function, cranial nerve V and VII function, cosmesis, and complications (hardware extrusions, sinusitis, meningitis, osteomyelitis, mucopyocele, brain abscess, pneumocephalus, and cerebrospinal fluid leak) were evaluated. All patients had good function of the superior division of cranial nerves V and VII. Two patients (16%) had minor wound infections, which resolved under treatment with antibiotics. All had excellent cosmetic results as measured by postreduction radiographs and personal and family perceptions of forehead contour. CONCLUSION: Titanium mesh reconstruction of severely comminuted frontal sinus fractures has few complications while providing excellent forehead contour and cosmesis.


Assuntos
Fraturas Cominutivas/cirurgia , Seio Frontal/lesões , Fraturas Cranianas/cirurgia , Telas Cirúrgicas , Adulto , Algoritmos , Fixação Interna de Fraturas , Humanos , Pessoa de Meia-Idade , Titânio/uso terapêutico
6.
Clin Cancer Res ; 7(5): 1237-45, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11350889

RESUMO

PURPOSE: We conducted a Phase 1 study to determine the maximal tolerated dose and maximum biologically active dose of the E1A gene delivered by intratumoral injection as a lipid complex with 3 beta[N-(n',n'-dimethylaminoethane)-carbamoyl] cholesterol/dioleoylphosphatidyl-ethanolamine (tgDCC-E1A). The E1A adenovirus gene functions as a tumor inhibitor gene by repressing oncogene transcription; modulating gene expression, resulting in cellular differentiation; and inducing apoptosis of cancer cells. E1A also sensitizes cancer cells to chemotherapeutic drugs such as etoposide, cisplatin, and taxol. EXPERIMENTAL DESIGN: Nine patients with recurrent and unresectable breast cancer and nine patients with head and neck cancer were enrolled. One tumor nodule in each patient was injected with tgDCC-E1A. Safety, tumor response, E1A gene transfer, and down-regulation of HER-2/neu were evaluated. RESULTS: No dose-limiting toxicity was observed in the four dose groups (15, 30, 60, and 120 microg DNA/cm of tumor). All patients tolerated the injections, although several experienced pain and bleeding at the injection site. A maximally tolerated dose was not reached in this study. E1A gene transfer was demonstrated in 14 of 15 tumor samples tested, and down-regulation of HER-2/neu was demonstrated in two of the five patients who overexpressed HER-2/neu at baseline. HER-2/neu could not be assessed in other posttreatment tumor samples because of extensive necrosis. In one breast cancer patient, no pathological evidence of tumor was found on biopsy of the treated tumor site at week 12. In 16 patients evaluable for tumor response, 2 had minor responses, 8 had stable disease, and 6 had progressive disease. CONCLUSIONS: Gene therapy with an E1A gene:lipid complex appears to be safe and warrants further testing.


Assuntos
Proteínas E1A de Adenovirus/uso terapêutico , Neoplasias da Mama/terapia , Terapia Genética , Neoplasias de Cabeça e Pescoço/terapia , Proteínas E1A de Adenovirus/efeitos adversos , Proteínas E1A de Adenovirus/genética , Idoso , Neoplasias da Mama/genética , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Feminino , Técnicas de Transferência de Genes , Neoplasias de Cabeça e Pescoço/genética , Humanos , Lipossomos , Masculino , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Recidiva , Transfecção , Resultado do Tratamento
7.
Arch Otolaryngol Head Neck Surg ; 126(11): 1313-8, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11074827

RESUMO

OBJECTIVE: To identify alterations in angiogenesis and cell cycle regulation as preneoplastic cells progress to cancer in an in vitro model of head and neck tumor progression. METHODS: Immortal human gingival keratinocyte (IHGK) cells (preneoplastic) were derived from normal oral keratinocytes and were immortalized with human papillomavirus 16. Transformation of IHGK cells with a carcinogen (NNK, 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone) gave rise to IHGKN cells. We determined the growth rates, cell cycle phase, expression of cell cycle regulators, and expression of vascular endothelial growth factor along with the organotypic features of these cells and compared them with characteristics of head and neck cancer cells. RESULTS: IHGK and IHGKN cells grown in raft culture were morphologically similar to severe dysplasia and carcinoma, respectively. The proportion of cells in G(0)/G(1) was similar between IHGK and IHGKN. However, the proportion of IHGK cells was 35% greater in S phase as compared with the IHGKN cells, while a greater percentage (40%) of IHGKN cells were in G(2)/M. The expression of the other cell cycle regulators tested was unchanged. IHGK cells secreted less vascular endothelial growth factor on day 1 when compared with IHGKN (50.6 vs 245.6 pg/mL), along with a lower overall production rate (79% vs 133%). CONCLUSIONS: Transformation of IHGK cells resulted in the activation of vascular endothelial growth factor associated with angiogenesis. Inactivation of the G(1) cell cycle regulation occurred during immortalization and before transformation, and was sustained after carcinogen exposure. These alterations correspond to changes observed in patients with head and neck squamous cell carcinoma. This model can be useful in testing novel therapeutic and preventive strategies.


Assuntos
Carcinoma de Células Escamosas/patologia , Transformação Celular Neoplásica , Neoplasias de Cabeça e Pescoço/patologia , Queratinócitos/patologia , Western Blotting , Proteínas de Ciclo Celular/análise , Transformação Celular Neoplásica/metabolismo , Fatores de Crescimento Endotelial/metabolismo , Gengiva/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Linfocinas/metabolismo , Neovascularização Patológica , Isoformas de Proteínas/metabolismo , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
8.
Clin Cancer Res ; 6(10): 4142-7, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11051268

RESUMO

Recent advances in combined modality treatment of locally advanced head and neck cancer have improved local and regional disease control and survival with better functional outcome. However, the local and regional failure rate after radiation therapy is still high for tumors that respond poorly to cisplatin-based neoadjuvant chemotherapy. This clinical observation suggests a common biological mechanism for resistance to cisplatin and photon irradiation. In this report, we investigated the molecular basis underlying cisplatin resistance in head and neck squamous carcinoma (HNSCC) cells and asked if fast neutron radiation enhances cisplatin cytotoxicity in cisplatin-resistant cells. We found that cisplatin sensitivity correlates with caspase induction, a cysteine proteinase family known to initiate the apoptotic cell death pathway, suggesting that apoptosis may be a critical determinant for cisplatin cytotoxicity. Neutron radiation effectively enhanced cisplatin cytotoxicity in HNSCCs including cisplatin-resistant cells, whereas photon radiation had little effect on cisplatin cytotoxicity. Interestingly, neutron-enhanced cisplatin cytotoxicity was associated neither with apoptosis nor with cell cycle regulation, as determined by caspase activity assay, annexin V staining, and flow cytometric analysis. Taken together, the present study provides a molecular insight into cisplatin resistance and may also provide a basis for more effective multimodality protocols involving neutron radiation for patients with locally advanced head and neck cancer.


Assuntos
Apoptose , Carcinoma/tratamento farmacológico , Cisplatino/uso terapêutico , Nêutrons Rápidos/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Anexina A5/metabolismo , Caspases/metabolismo , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Terapia Combinada , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Resistencia a Medicamentos Antineoplásicos , Citometria de Fluxo , Humanos , Fótons/uso terapêutico , Fatores de Tempo , Células Tumorais Cultivadas
10.
Arch Otolaryngol Head Neck Surg ; 126(4): 473-9, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10772300

RESUMO

OBJECTIVES: To test whether T-cell CD3 responses are altered in patients with advanced-stage head and neck squamous cell carcinoma (HNSCC) and whether anti-CD3/anti-CD28 (alphaCD3/alphaCD28) bead stimulation could reverse CD3 unresponsiveness. DESIGN: Anti-CD3 (alphaCD3) monoclonal antibody immobilized on tissue culture plastic was used to stimulate lymph node mononuclear cells (LNMCs) and peripheral blood mononuclear cells (PBMCs) from patients with advanced-stage HNSCC. Proliferation, T-cell phenotype, and cytokines were measured during 8-day in vitro stimulation. Immune-enhancing properties of alphaCD3/ alphaCD28 beads were also tested on LNMCs and PBMCs. Cytotoxicity of bead-activated T cells (ATCs) was measured against autologous and allogeneic HNSCC. RESULTS: Six patients were nonresponders to alphaCD3 stimulation defined by tritium (3H) incorporation of less than 3500 cpm, whereas 11 patients were responders with 3H incorporation of 3500 cpm or more. Responders produced higher levels of interleukin (IL)-12 and interferon gamma (IFN-gamma) after alphaCD3 stimulation than nonresponders. No phenotypic or clinical differences were identified between groups. Stimulation with alphaCD3/alphaCD28 beads enhanced IFN-gamma and IL-2 produced by both groups. Bead ATCs were generated from PBMCs of patient 11 in the responder group and lysed (+/- SD) 100% +/-1% of autologous tumor and 49% +/-1% of allogeneic tumor. Bead ATCs from LNMCs of this patient lysed 58%+/-1% of autologous tumor and 63%+/-1% of allogeneic tumor. CONCLUSIONS: A subpopulation of patients with HNSCC who are nonresponders to alphaCD3 stimulation has been identified, showing reduced proliferation and IL-12 and IFN-gamma secretion. Nonresponders stimulated with alphaCD3/alphaCD28 beads reversed immune unresponsiveness and induced a type 1 cytokine response. Bead-generated ATCs from patient 11 in the responder group lysed autologous and allogeneic HNSCC in vitro, suggesting a possible effective immunotherapeutic modality in the treatment of HNSCC.


Assuntos
Antígenos CD28/imunologia , Complexo CD3/imunologia , Carcinoma de Células Escamosas/imunologia , Neoplasias de Cabeça e Pescoço/imunologia , Linfócitos T/imunologia , Anticorpos Monoclonais , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Tolerância Imunológica/imunologia , Imunoterapia , Técnicas In Vitro , Interferon gama/imunologia , Interleucina-12/imunologia , Ativação Linfocitária/imunologia , Pessoa de Meia-Idade
11.
Cancer Res ; 60(4): 892-5, 2000 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-10706101

RESUMO

Promoter hypermethylation is an important pathway for repression of gene transcription in cancer cells. We analyzed aberrant DNA methylation at four genes in primary tumors from 95 head and neck cancer patients and then used the presence of this methylation as a marker for cancer cell detection in serum DNA. These four genes were tested by methylation-specific PCR and included: p16 (CDKN2A), O6-methylguanine-DNA-methyltransferase, glutathione S-transferase P1, and death-associated protein kinase (DAP-kinase). Fifty-five % (52 of 95) of the primary tumors displayed promoter hypermethylation in at least one of the genes studied: 27% (26/95) at p16, 33% (31 of 95) at O6-methylguanine-DNA-methyltransferase; and 18% (17 of 92) at DAP-kinase. No promoter hypermethylation was observed at the glutathione S-transferase P1 gene promoter. We detected a statistically significant correlation between the presence of DAP-kinase gene promoter hypermethylation and lymph node involvement (P = 0.014) and advanced disease stage (P = 0.016). In 50 patients with paired serum available for epigenetic analysis, the same methylation pattern was detected in the corresponding serum DNA of 21 (42%) cases. Among the patients with methylated serum DNA, 5 developed distant metastasis compared with the occurrence of metastasis in only 1 patient negative for serum promoter hypermethylation (P = 0.056). Promoter hypermethylation of key genes in critical pathways is common in head and neck cancer and represents a promising serum marker for monitoring affected patients.


Assuntos
Metilação de DNA , Neoplasias de Cabeça e Pescoço/genética , Regiões Promotoras Genéticas , Proteínas Reguladoras de Apoptose , Proteínas Quinases Dependentes de Cálcio-Calmodulina/genética , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/genética , Proteínas Quinases Associadas com Morte Celular , Genes p16 , Neoplasias de Cabeça e Pescoço/sangue , Humanos , O(6)-Metilguanina-DNA Metiltransferase/genética
12.
Laryngoscope ; 110(3 Pt 1): 386-90, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10718424

RESUMO

PURPOSE: Define radiological and histological features in which patients with head and neck cancer would benefit from a carotid artery resection. Resection of the carotid artery has been advocated for local control of advanced squamous cell carcinoma of the head and neck. To provide appropriate preoperative counseling and optimize the utilization of resources, the criteria for patient selection has to be defined. METHODS: Thirty-four patients underwent carotid artery resection based on the clinical impression of tumor fixation. Eighteen and 28 patients were evaluated using computed tomography (CT) and histological analysis, respectively. The distance between the tumor cells and external elastic lamina was measured. CT scans were examined to determine the circumference of tumor attachment around the carotid artery. RESULTS: Clinical assessment predicted tumor within 1.8 mm of the carotid artery in 68% of cases. The overall survival for patients with tumor greater than 1.8 mm (N = 9) was better than that of patients with less (N = 19) than 1.8 mm (33.3% vs. 5.3%; median 24 versus 9 mo, P = .0899). Three of six patients (50%) with less than 180 degrees circumference tumor attachment had tumor within 1.8 mm from the external elastic lamina. Eight of twelve patients (67%) with tumors encompassing more than 180 degrees of the artery wall had tumor within 1.8 mm from the external elastic lamina. The overall survival rates for patients with tumor attachment greater and less than 180 degrees were 8.3% and 33%, respectively. DISCUSSION: Tumor invasion into the carotid artery was the strongest predictor of outcome. Clinical assessment was as predictive as CT for tumor invasion. If tumor involvement of the carotid artery is less than 180 degrees, peeling the tumor is an alternative to carotid artery resection.


Assuntos
Carcinoma de Células Escamosas/patologia , Artérias Carótidas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Planejamento de Assistência ao Paciente , Neoplasias Vasculares/patologia , Análise Atuarial , Biópsia , Carcinoma de Células Escamosas/secundário , Artérias Carótidas/cirurgia , Meios de Contraste , Aconselhamento , Tecido Elástico/patologia , Feminino , Seguimentos , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Seleção de Pacientes , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Neoplasias Vasculares/cirurgia
13.
Skull Base Surg ; 10(3): 109-17, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-17171134

RESUMO

The retromaxillary-infratemporal fossa (RM-ITF) dissection, using a preauricular incision, was initially popularized for the treatment of temporomandibular joint disorders, facial fractures, and orbital tumors. This approach has been expanded for the treatment of advanced head and neck and skull base tumors extending into the infratemporal fossa. We studied prospectively eight consecutive patients requiring a RM-ITF dissection. Pre- and postoperative functional outcomes measured were mastication, speech, swallowing, cranial nerve function, pain, and cosmesis. A significant reduction in pain was noted postoperatively in all patients studied. Limited changes were identified in mastication, speech, swallowing, vision, hearing, or cosmesis postoperatively. The RM-ITF dissection should be considered when resecting advanced head and neck/skull base lesions that extend into this region. We have found minimal morbidity associated with this dissection. This procedure may have a useful place in palliation of patients with incurable pain caused by tumor invasion into the infratemporal fossa.

14.
Laryngoscope ; 109(3): 376-82, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10089961

RESUMO

OBJECTIVES: To qualitatively and quantitatively describe aesthetic and functional outcomes following Mohs ablative surgery involving the alar subunit, using a paramedian or subcutaneous melolabial island flap. STUDY DESIGN: Retrospective review. METHODS: A single surgeon's results in 38 consecutive patients were analyzed. Objective measures (alar rim thickness, donor scar width and length), subjective assessment (seven aesthetic parameters) by three academic otolaryngologists, and patient satisfaction questionnaires were evaluated. Student t test was used to ascertain statistically significant differences between reconstructive groups. RESULTS: Questionnaire results demonstrate a significant (P = .026) difference in donor site rating favoring melolabial group responses. Objective scar measurements and subjective ratings of textural quality and alar notching also favored melolabial reconstructions. CONCLUSIONS: More favorable aesthetic and functional outcomes are seen with single subunit cutaneous alar defects reconstructed with the melolabial island flap than with deep composite or extensive unilateral nasal defects reconstructed with the paramedian forehead flap.


Assuntos
Carcinoma Basocelular/cirurgia , Carcinoma de Células Escamosas/cirurgia , Cirurgia de Mohs , Neoplasias Nasais/cirurgia , Rinoplastia , Neoplasias Cutâneas/cirurgia , Retalhos Cirúrgicos , Idoso , Idoso de 80 Anos ou mais , Cicatriz/etiologia , Estética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento
15.
Laryngoscope ; 109(3): 455-9, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10089975

RESUMO

OBJECTIVE/HYPOTHESIS: We examined whether p53 gene mutations were predictive of clinical behavior in laryngeal cancer. STUDY DESIGN: Retrospective study of 45 patients with laryngeal cancer from 1985 to 1997. METHODS: DNA was extracted from tumor tissue and subject to polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP) as well as DNA sequencing. The clinical outcome was correlated to the presence or absence of a p53 mutation. RESULTS: The p53 gene was analyzed by direct DNA sequencing and was found to be mutated in 33% (15/45) of patients. The presence of a p53 mutation was associated with a significant improvement in overall survival (80% vs. 43%, P < .03) and a trend toward improved disease-free survival (87% vs. 60%, P = .08). When other prognostic factors were adjusted, multivariate analysis revealed a trend toward improvement in overall survival as well as disease-free survival. CONCLUSION: Depending on the location of a p53 mutation, the suppressive functions or clinical outcome may or may not be affected. Fifty-three percent of mutations were detected in nonconserved regions as opposed to 17% as reported in colon cancer. In colon cancer, mutations in conserved regions of the p53 gene predicted a poorer survival, whereas nonconserved gene mutations were not predictive. In our group of patients. p53 mutations predicted a better prognosis, which may be due to a large proportion of mutations that lie within nonconserved areas. The predictive power of p53 gene mutations may depend on functional loss and inactivation of highly conserved areas and must be tested in a prospective trial.


Assuntos
Análise Mutacional de DNA , Neoplasias Laríngeas/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Sequência de Aminoácidos/genética , Sequência Conservada/genética , Feminino , Humanos , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Laringectomia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Repetições de Trinucleotídeos/genética
16.
J Natl Cancer Inst ; 88(21): 1580-6, 1996 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-8901856

RESUMO

BACKGROUND: The p53 gene (also known as TP53) may be the most common genetic target involved in the malignant transformation of human cells. Direct sequence analysis has demonstrated that alteration of this gene occurs in approximately 45% of head and neck squamous cell carcinomas. The consequences of p53 mutations in these cancers with respect to tumor behavior and patient survival have not been rigorously determined. PURPOSE: We evaluated the implications of p53 mutations in relation to the control of locoregional disease and overall survival following radiation therapy. METHODS: Data from 110 consecutive patients with invasive disease who were treated with primary radiation therapy (given with curative intent) or with adjuvant radiation therapy (following complete surgical extirpation of gross disease) were included in the analysis. A 1.8-kilobase fragment of the p53 gene encompassing exons 5-9 was amplified from the DNA of stored (frozen) tumor specimens; the amplified DNA was cloned and sequenced by use of standard techniques. Overall survival and locoregional disease-free survival after the completion of radiation therapy were estimated by the Kaplan-Meier method; survival comparisons were made by use of the logrank test or proportional hazards regression models. Reported P values are two-sided. RESULTS: Fortyeight (44%) of the 110 tumors had cells bearing p53 mutations. The risk of locoregional recurrence following either primary or adjuvant radiation therapy was significantly greater (i.e., the time to recurrence was shorter) for patients whose tumors contained mutant p53 genes (univariate model hazard ratio [HR] for p53 mutation versus wild-type = 2.2; 95% confidence interval [CI] = 1.2-4.1; P = .02). The presence of regional lymph node metastases (presence versus absence, HR = 2.0; 95% CI = 1.0-4.2; P = .05) and treatment type (primary radiation therapy versus surgery plus adjuvant radiation therapy, HR = 2.3; 95% CI = 1.2-4.3; P = .01) were also associated with greater risks of locoregional failure. The presence of p53 mutations and lymph node metastases and treatment with primary, as opposed to adjuvant, radiation therapy remained significant risk factors in multivariate regression analysis. No relationship was demonstrated between p53 status and overall survival (mutant versus wild-type, HR = 1.1; 95% CI = 0.6-2.1; P = .66); however, a relationship was shown for tumor stage and overall survival (stages III and IV [more advanced] versus stages I and II [less advanced], HR = 3.3; 95% CI = 1.0-10.8; P = .05). Mutation of the p53 gene was not associated with patient age, sex, tumor stage, primary tumor site, regional lymph node status, degree of tumor cell differentiation, or treatment method. CONCLUSIONS: Mutation of the p53 gene is associated with an increased risk of locoregional failure in patients with invasive head and neck squamous cell carcinoma who are treated with radiation therapy.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Genes p53/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia , Mutação , DNA de Neoplasias/genética , Intervalo Livre de Doença , Humanos , Reação em Cadeia da Polimerase , Análise de Sobrevida , Falha de Tratamento
17.
Yonsei Med J ; 37(1): 72-80, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8967113

RESUMO

The ryanodine receptor/channel (RyR) mediates the release of calcium from the sarcoplasmic reticulum (SR) in both skeletal and cardiac muscle cells. There are three isoforms of the RyR: RyR1, RyR2, and RyR3. RyR1 is specifically expressed in skeletal muscles and RyR2 in cardiac muscles. RyR3 is yet another isoform found in non-muscle cells such as neuronal cells. Single channel recordings of RyR1 and RyR2 reconstituted in artificial lipid bilayer show that the characteristics of two isoforms are very distinct. RyR1 has a shorter mean open time and is activated at a higher concentration of Ca2+ than RyR2. In this study, we isolated the heavy SR membranes from canine latissimus dorsi muscles and investigated the single channel activities from the heavy SR membrane fraction using Cs+ as a charge carrier. Two different types of activities were observed. The fast-gating type (FG) with the mean open time of 0.9 ms was more frequently recorded (n = 12) than the slow-gating type (SG) with the mean open time of 269.2 ms. From the I-V relation, the slope conductance of the FG was calculated to be 514.7 pS and the SG, to 625.6 pS. The activity of the fast gating type increased by raising the concentration of Ca2+ in the cis-solution up to 100 microM. The appearance of the SG in the canine heavy SR membrane fraction suggests a possibility that two types of RyR isoform are co-expressed in mammalian skeletal muscle as well as in avian, amphibian and piscine fast twitch muscles.


Assuntos
Canais de Cálcio/metabolismo , Ativação do Canal Iônico , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Retículo Sarcoplasmático/metabolismo , Animais , Cães , Bicamadas Lipídicas , Microssomos/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina , Tórax , Fatores de Tempo
18.
Cancer Res ; 54(17): 4603-6, 1994 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-8062250

RESUMO

Our recent allelic analysis of head and neck squamous cell carcinomas identified a high incidence of chromosomal loss on 13q. To further define an area of minimal loss, we tested 60 primary head and neck squamous cell carcinomas in 59 patients for loss of heterozygosity (LOH) by using 10 polymorphic microsatellite markers spanning the long arm of chromosome 13. We examined the same primary tumors for inactivation of the retinoblastoma (Rb) gene by immunohistochemical analysis of paraffin-embedded specimens. Thirty-one of 60 (52%) tumors demonstrated LOH in at least one 13q marker. Twenty-nine of 31 (94%) lost a portion of 13q that included D13s133, which lies just telomeric to the Rb gene at 13q14.3. However, immunohistochemical staining revealed absence of Rb protein in only 6 of these 31 tumors (19.4%) with LOH. All but one tumor without LOH on 13q displayed normal Rb protein staining. Although Rb may be inactivated by an unusual mechanism in some head and neck squamous cell carcinomas, our data suggest that another tumor suppressor gene locus at 13q14 is likely to be involved in head and neck tumor progression.


Assuntos
Carcinoma de Células Escamosas/genética , Deleção Cromossômica , Cromossomos Humanos Par 13 , Genes do Retinoblastoma/genética , Neoplasias de Cabeça e Pescoço/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/química , Mapeamento Cromossômico , DNA de Neoplasias/análise , DNA Satélite/análise , Feminino , Neoplasias de Cabeça e Pescoço/química , Humanos , Masculino , Pessoa de Meia-Idade , Proteína do Retinoblastoma/análise
19.
Laryngoscope ; 104(7): 799-803, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8022240

RESUMO

Warthin's tumor previously has been thought to occur much more commonly in men than in women and rarely in African Americans. One hundred thirty-two cases of Warthin's tumor treated at The Johns Hopkins Hospital from 1952 to 1992 were retrospectively reviewed. There were 90 (68%) men and 42 (32%) women, with an overall man-to-woman ratio of 2.2:1. The number and percentage of women with Warthin's tumor increased over each consecutive decade: 1952 to 1962, 5 (21%); 1963 to 1972, 6 (29%); 1973 to 1982, 11 (31%); and 1983 to 1992, 20 (39%). A positive smoking history was found in 88% of the men and in 89% of the women with a Warthin's tumor. Eleven (8%) African Americans and 1 (0.75%) Asian American were diagnosed to have a Warthin's tumor. Also, the incidence of African Americans with a Warthin's tumor increased over each decade: 0 (0%), 1 (4.8%), 2 (5.5%), and 8 (16%). This study's results indicate a progressive increase in the occurrence of this tumor in women and in African Americans and a higher overall incidence in African Americans than previously reported.


Assuntos
Adenolinfoma/epidemiologia , Linfonodos , Neoplasias Mandibulares/epidemiologia , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Parotídeas/epidemiologia , Adenolinfoma/etnologia , Adenolinfoma/etiologia , Adenolinfoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , População Negra , Feminino , Hospitais Urbanos , Humanos , Incidência , Masculino , Neoplasias Mandibulares/etnologia , Neoplasias Mandibulares/etiologia , Neoplasias Mandibulares/cirurgia , Maryland , Pessoa de Meia-Idade , Pescoço , Recidiva Local de Neoplasia/cirurgia , Neoplasias Parotídeas/etnologia , Neoplasias Parotídeas/etiologia , Neoplasias Parotídeas/cirurgia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fumar/efeitos adversos , Fatores de Tempo
20.
Laryngoscope ; 104(5 Pt 1): 545-52, 1994 May.
Artigo em Inglês | MEDLINE | ID: mdl-8189984

RESUMO

Alloplastic reconstruction following segmental mandibulectomy is a simple way to maintain mandibular segmental relationships, partially preserving form and function for many patients. This study is a retrospective review of 40 patients who had mandibular reconstruction with metal plates over a 6-year period (April 1986 through August 1992). The results of reconstruction with titanium hollow-screw osseointegrating reconstruction plates (THORP [n = 12]) and solid screw (SS) steel and titanium plates (n = 28) are compared. One THORP has been removed as compared to 14 SS plates. While the improved results with THORP may be attributable in part to its advanced design, the success of soft-tissue reconstruction and tumor extirpation are important factors in the early outcome seen in this series. Longer follow-up is needed to determine if THORP can serve as a permanent implant. THORP is the authors' method of choice for alloplastic mandibular reconstruction.


Assuntos
Placas Ósseas , Parafusos Ósseos , Mandíbula/cirurgia , Neoplasias Mandibulares/cirurgia , Neoplasias Bucais/cirurgia , Aço , Titânio , Adulto , Idoso , Idoso de 80 Anos ou mais , Desenho de Equipamento , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Osseointegração , Complicações Pós-Operatórias/epidemiologia , Reoperação , Estudos Retrospectivos , Fatores de Tempo
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