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We experimentally demonstrate that ptychographic coherent diffractive imaging can be used to simultaneously characterize the amplitude and phase of bichromatic orbital angular momenta-shaped vortex beams, which consist of a fundamental field, together with its copropagating second-harmonic field. In contrast to most other orbital angular momentum characterization methods, this approach solves for the complex field of a hyperspectral beam. This technique can also be used to characterize other phase-structured illumination beams, and, in the future, will be able to be extended to other complex fields in the extreme ultraviolet or X-ray spectral regions, as well as to matter waves.
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BACKGROUND: The American Joint Committee on Cancer (AJCC) stage III classification of oral cavity squamous cell carcinoma (OCSCC) represents a heterogeneous group of patients with early local disease with regional metastases (T1N1 and T2N1) and advanced local disease with or without regional metastasis (T3N0 and T3N1). OBJECTIVE: The aim of this study was to evaluate prognostic heterogeneity in the stage III category. METHODS AND PATIENTS: An international retrospective multicenter study of 1815 patients who were treated for OCSCC from 2003 to 2011. RESULTS: Kaplan-Meier survival analysis and multivariate models of stage III patients revealed better overall survival (OS; HR 2.12, 95 % CI 1.03-4.15; p = 0.01) and disease-specific survival (DSS; HR 1.7, 95 % CI 1.16-4.12; p = 0.04) rates for patients with T1-2N1/T3N0 disease than for patients with T3N1 disease. The outcomes of patients with T3N1 and stage IVa disease were similar (p = 0.89 and p = 0.78 for OS and DSS, respectively). Modifying stage classification by transferring the T3N1 category to the stage VIa group resulted in a better prognostic performance [Harrell's concordance index, C index 0.76; Akaike's Information Criterion (AIC) 4131.6] compared with the AJCC 7th edition staging system (C index 0.65; AIC 4144.9) for OS. When DSS was assessed, the suggested staging system remained the best performing model (C index 0.71; AIC 1061.3) compared with the current AJCC 7th edition staging (C index 0.64; AIC 1066.2). CONCLUSIONS: The prognosis of T3N1 and stage IVa disease are similar in OCSCC, suggesting that these categories could be combined in future revisions of the nodal staging system to enhance prognostic accuracy.
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Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Estadiamento de Neoplasias/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Humanos , Agências Internacionais , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/cirurgia , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Estados Unidos , Adulto JovemRESUMO
Avian leukosis is an immunosuppressive neoplastic disease caused by avian leukosis viruses (ALV), which causes tremendous economic losses in the worldwide poultry industry. The susceptibility or resistance of chicken cells to subgroup A ALV and subgroup B, D, and E ALV are determined by the receptor genes tumor virus locus A (tva) and tumor virus locus B (tvb), respectively. Four genetic resistant loci (tva(r1), tva(r2), tva(r3), and tva(r4)) in tva receptor gene and a genetic resistant locus tvb(r) in the tvb receptor gene have been identified in inbred lines of White Leghorn. To evaluate the genetic resistance to subgroup A, B, D, and E ALV, genetic variations within resistant loci in tva and tvb genes were screened in Chinese local chicken breeds and commercial broiler lines. Here, the heterozygote tva(s1/r1) and the resistant genotype tva(r2/r2), tva(r3/r3), and tva(r4/r4) were detected in Chinese chickens by direct sequencing. The heterozygote tva(s1/r1) was detected in Huiyang Bearded chicken (HYBC), Rizhaoma chicken, and commercial broiler line 13 to 15 (CB13 to CB15), with the frequencies at 0.08, 0.18, 0.17, 0.25, and 0.15, respectively. The resistant genotype tva(r2/r2) was detected in Jiningbairi chicken (JNBRC), HYBC, and CB15, with the frequencies at 0.03, 0.08, and 0.06, respectively, whereas tva(r3/r3) and tva(r4/r4) were detected in 19 and 17 of the 25 Chinese chickens tested, with the average frequencies at 0.13 and 0.20, respectively. Furthermore, the resistant genotype tvb(r/r) was detected in JNBRC, CB07, CB12, CB14, and CB15 by pyrosequencing assay, with the frequencies at 0.03, 0.03, 0.11, 0.09, and 0.15, respectively. These results demonstrated that the potential for genetic improvement of resistance to subgroup A, B, D, and E ALV were great both in Chinese local chickens and commercial broilers. This study provides valuable insight into the selective breeding for chickens genetically resistant to ALV.
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Leucose Aviária/genética , Proteínas Aviárias/genética , Galinhas/genética , Polimorfismo de Nucleotídeo Único , Doenças das Aves Domésticas/genética , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Receptores Virais/genética , Animais , Leucose Aviária/virologia , Vírus da Leucose Aviária/fisiologia , Proteínas Aviárias/metabolismo , China , Resistência à Doença/genética , Reação em Cadeia da Polimerase/veterinária , Doenças das Aves Domésticas/virologia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Receptores Virais/metabolismoRESUMO
BACKGROUND: Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed to validate the concept of LND in OSCC. METHODS: The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan-Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis. RESULTS: The OS was 49% for patients with LNDîº0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LNDîº0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures. CONCLUSION: This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.
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Carcinoma de Células Escamosas/patologia , Linfonodos/patologia , Neoplasias Bucais/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/cirurgia , Análise Multivariada , Metástase Neoplásica , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: We aimed to study the importance of clinical N classification (cN) in a subgroup of patients with oral cavity squamous cell carcinoma (OSCC) and pathologically negative neck nodes (pN-). METHODS: A total of 2,258 patients from 11 cancer centers who underwent neck dissection for OSCC (1990-2011) had pN- disease. The median follow-up was 44 months. 5-year overall survival (OS), disease-specific survival (DSS), disease free survival, local control, locoregional control, and distant metastasis rates were calculated by the Kaplan-Meier method. cN classification and tumor, node, metastasis classification system staging variables were subjected to multivariate analysis. RESULTS: A total of 345 patients were preoperatively classified as cN+ and 1,913 were classified as cN-. The 5-year OS and DSS of cN- patients were 73.6 and 82.2 %, respectively. The 5-year OS and DSS of cN+ patients were 64.9 and 76.9 %, respectively (p < 0.0001 each). A cN+ classification was a significant predictor of worse OS (p = 0.03) and DSS (p = 0.016), regardless of treatment, depth of invasion, or extent of neck dissection. cN classification was associated with recurrence-free survival (p = 0.01) and locoregional (neck and primary tumor) control (p = 0.004), but not with local (p = 0.19) and distant (p = 0.06) recurrence rates. CONCLUSIONS: Clinical evidence of neck metastases is an independent predictor of outcome, even in patients with pN- nodes.
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Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Linfonodos/patologia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Esvaziamento Cervical/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Agências Internacionais , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
OBJECTIVE: The infection of human papilloma virus (HPV) has been reported in head and neck cancer; however, the clinical significance of HPV infection on the pathogenesis of oral cavity squamous cell carcinoma (OSCC) is still uncertain. MATERIALS AND METHODS: The study recruited 103 patients with pathological early-stage OSCC between March 1997 and December 2003 from Chang Gung Memorial Hospital, Taiwan. Tumor specimens were HPV-genotyped by the EasychipVR HPV Blot method. Clinical association study was performed by using chi-square, Kaplan-Meier, and logrank tests. RESULTS: Thirty-one patients (30.1%) were positive for HPV infection. The most frequent HPV types were types 16 (16 patients, 51.6%) and 18 (seven patients, 22.6%). HPV infection was not associated with tumor aggressiveness (pathological tumor stage or differentiation status), risk exposure (alcohol, cigarette, or areca quid chewing habit), or the treatment outcome (disease-free survival or overall survival). However, infection with HPV-18 was associated with the occurrence of a second primary cancers (P = 0.033), indicating the infection of HPV in OSCC enhances the susceptibility of developing secondary malignancy. CONCLUSIONS: There are 30% of the patients with OSCC infected with HPV, with most high-risk types. HPV-18 infection may enhance the susceptibility of second primary tumors. Large scale of validation study will be needed to confirm this result.
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Alphapapillomavirus/fisiologia , Carcinoma de Células Escamosas/virologia , Neoplasias Bucais/virologia , Segunda Neoplasia Primária/virologia , Infecções por Papillomavirus/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas , Alphapapillomavirus/classificação , Areca , Suscetibilidade a Doenças , Intervalo Livre de Doença , Feminino , Seguimentos , Papillomavirus Humano 16/fisiologia , Papillomavirus Humano 18/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Retrospectivos , Fumar , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Midline and paramedian mandibulotomies both have distinct anatomical and surgical strengths. A retrospective study was performed at Chang Gung Memorial Hospital, Linkou Branch between 2014 and 2019 to investigate how the osteotomy site (midline (n = 221) or paramedian (n = 44)) and type (straight, notched, or stair-stepped) affect postoperative and post-radiotherapy complications in patients undergoing wide excision of tongue cancer with flap reconstruction. Midline mandibulotomies were predominantly of the straight osteotomy type, while paramedian mandibulotomies were mostly notched type (P < 0.001). Comparably low elective tooth extraction rates were found in both approaches (P = 0.556). Paramedian mandibulotomy showed a higher osteoradionecrosis rate (P = 0.026), but there was no significance in the sub-analysis of individual types. Paramedian sites were associated with more early infection (P = 0.036) and plate exposure (P = 0.036) than midline sites with the straight osteotomy type, but complication rates did not differ significantly for the notched and stair-stepped types. Paramedian sites (P = 0.020) and notched types (P = 0.006) were associated with higher odds of osteoradionecrosis in the univariable logistic regression analysis, but only the notched type remained significant in the multivariable analysis (P = 0.048). In conclusion, paramedian sites increased the rate of osteoradionecrosis, and correlation with the osteotomy type resulted in more osteoradionecrosis in notched types and more complications in straight paramedian mandibulotomies.
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Osteorradionecrose , Neoplasias da Língua , Humanos , Mandíbula/cirurgia , Osteotomia Mandibular , Osteorradionecrose/cirurgia , Complicações Pós-Operatórias , Estudos Retrospectivos , Neoplasias da Língua/cirurgiaRESUMO
OBJECTIVES: Previous studies have demonstrated a relationship between elevated serum C-reactive protein (CRP) levels and shorter survival in cancer patients. Few studies, however, have investigated the role of serum CRP levels in oral squamous cell carcinoma. The present study was conducted to analyze the relationship between preoperative CRP levels, clinicopathologic factors, and prognosis in oral squamous cell carcinoma patients. DESIGN: Retrospective clinical study. SETTING: University teaching hospital. PARTICIPANTS: Eighteen oral cavity leukoplakia and 59 oral squamous cell carcinoma patients between November 2006 and November 2009 from the Chang Gung Memorial Hospital. OUTCOME MEASURES: Clinicopathologic parameters, disease-free survival and overall survival were correlated with CRP levels. METHODS: Serum CRP levels were measured preoperatively, and all oral cavity cancer patients underwent curative intent radical surgery with or without postoperative adjuvant therapy. RESULTS: The CRP levels in leukoplakia patients were used to analyze if factors (including diabetes and liver cirrhosis, smoking, alcohol drinking and areca quid chewing) influence CRP levels, and the results demonstrated they were not associated with CRP elevation (> 5.0 mg/L) (P > 0.05). In oral cancer patients, elevated CRP levels were associated with tumor status (P = 0.005), tumor stage (P = 0.054), bone invasion (P = 0.033), lymph node metastasis (P = 0.004) and lymph node extra-capsular spread (P = 0.018). Patients with higher CRP levels showed poorer disease-free survival (log rank test, P < 0.001) and overall survival (log rank test, P = 0.013). CONCLUSIONS: Preoperative serum CRP levels are associated with advanced tumor stage, bone invasion, lymph node metastasis, lymph node extra-capsular spread and patients' survival. CRP is thus potentially a prognostic indicator, but studies with longer follow-up will be needed to confirm its reliability.
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Biomarcadores Tumorais/análise , Proteína C-Reativa/análise , Carcinoma de Células Escamosas/patologia , Leucoplasia Oral/patologia , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/patologia , Adulto , Idoso , Areca/efeitos adversos , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Leucoplasia Oral/mortalidade , Leucoplasia Oral/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Neoplasias Bucais/cirurgia , Esvaziamento Cervical , Estadiamento de Neoplasias , Lesões Pré-Cancerosas/mortalidade , Lesões Pré-Cancerosas/cirurgia , Prognóstico , Estudos Retrospectivos , Estatística como Assunto , Análise de Sobrevida , Taiwan , Tomografia Computadorizada por Raios XRESUMO
Intermediate precision is one of the most important characteristics for evaluation of precision in assay validation. The current methods for evaluation of within-device precision recommended by the Clinical Laboratory Standard Institute (CLSI) guideline EP5-A2 are based on the point estimator. On the other hand, in addition to point estimators, confidence intervals can provide a range for the within-device precision with a probability statement. Therefore, we suggest a confidence interval approach for assessment of the within-device precision. Furthermore, under the two-stage nested random-effects model recommended by the approved CLSI guideline EP5-A2, in addition to the current Satterthwaite's approximation and the modified large sample (MLS) methods, we apply the technique of generalized pivotal quantities (GPQ) to derive the confidence interval for the within-device precision. The data from the approved CLSI guideline EP5-A2 illustrate the applications of the confidence interval approach and comparison of results between the three methods. Results of a simulation study on the coverage probability and expected length of the three methods are reported. The proposed method of the GPQ-based confidence intervals is also extended to consider the between-laboratories variation for precision assessment.
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Bioensaio/estatística & dados numéricos , Modelos Estatísticos , Animais , Glicemia/análise , Distribuição de Qui-Quadrado , Simulação por Computador , Intervalos de Confiança , Interpretação Estatística de Dados , Humanos , Método de Monte Carlo , Variações Dependentes do Observador , Probabilidade , Reprodutibilidade dos TestesRESUMO
To identify genes that could potentially serve as molecular therapeutic markers for human head and neck cancer (HNC), we employed differential display analysis to compare the gene expression profiles between HNC and histopathologically normal epithelial tissues. Using reverse transcription-polymerase chain reaction and Western blot analysis, desmoglein 3 (DSG3) was identified as being differentially expressed at both the RNA and protein levels. Of 56 patients assayed, 34 (61%) had overexpression of DSG3, which correlated statistically with T stage (P=0.009), N stage (P=0.047), overall stage (P=0.011), tumor depth (P=0.009) and extracapsular spread in lymph nodes (P=0.044), suggesting that DSG3 participates in carcinogenesis of HNC. Consistent with the clinical findings, inhibition of DSG3 by RNA interference (RNAi) significantly reduced cell growth and colony formation to 57-21% in three HNC cell lines. Use of an in vitro wound healing and Matrigel invasion assays, we found that cell migration and invasive ability were also inhibited to 30-48% in three cell lines tested. An in vivo xenograft study showed that administration of DSG3-RNAi plasmid significantly inhibited tumor growth for 2 months in BALB/C nude mice. In conclusion, DSG3 is identified overexpressed in HNC, with the degree of overexpression associated with clinicopathologic features of the tumor. Inhibition of DSG3 significantly suppresses carcinogenic potential in cellular and in vivo animal studies. These findings suggest that DSG3 is a potential molecular target in the development of adjuvant therapy for HNC.
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Desmogleína 3/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias Bucais/patologia , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular , Colágeno/metabolismo , Desmogleína 3/antagonistas & inibidores , Desmogleína 3/genética , Combinação de Medicamentos , Perfilação da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Células KB/transplante , Laminina/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Bucais/metabolismo , Invasividade Neoplásica/patologia , Plasmídeos , Proteoglicanas/metabolismo , RNA Interferente Pequeno/farmacologia , Taxa de Sobrevida , Ensaio Tumoral de Célula-Tronco , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: To assess the outcome of and determine prognostic factors for locally recurrent nasopharyngeal carcinoma (NPC) in patients treated with a second course of radiotherapy (RT). MATERIALS AND METHODS: From 1982 to 1995, 186 NPC patients, who had initially been treated in the Department of Radiation Oncology, Chang Gung Memorial Hospital-Linkou, developed local recurrence in the nasopharynx and were re-treated with RT (>/=20 Gy). The time from the initial RT to re-treatment ranged from 8 to 136 months (median: 23 months). All patients were treated with external RT and conformal radiotherapy was used in 35 patients after 1993. Fifteen received radiosurgery as a boost treatment. The RT dose at the nasopharyngeal tumor area ranged from 20 to 67.2 Gy (median 50 Gy). Eighty-two patients received one to eight courses of cisplatin-based chemotherapy in addition to RT. RESULTS: The 1-, 3- and 5-year survival was 54.9, 22. 1 and 12.4%, respectively. Patients whose tumor relapsed later than 2 years after the first treatment had a better survival than those with earlier relapse (3-year survival: 30.1 vs. 10.8%; P=0.015), but the difference became insignificant in patients who received >/=50 Gy. Patients without evidence of intracranial invasion or cranial nerve palsy had better survival than those with such lesions (3-year survival: 30.9 vs. 3.7%; P=0.006). A re-treatment dose >/=50 Gy yielded better survival (3-year survival: 22.8 vs. 18.5%; P=0.003). Addition use of radiosurgery may improve survival. The use of chemotherapy did not improve survival. Conformal radiotherapy resulted in significantly fewer severe complications than conventional RT. CONCLUSIONS: A repeat course of RT for locally recurrent NPC successfully prolongs survival in a significant number of patients. Intracranial invasion and/or cranial nerve palsy and re-treatment dose affect the prognosis, with a dose of >/=50 Gy significantly improving survival. Radiosurgery boost may also improve survival. Our preliminary data indicates that conformal radiotherapy may decrease the severity of radiation-induced complications. However; longer follow-up and larger sample size is necessary to document the findings.
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Antineoplásicos/uso terapêutico , Neoplasias Nasofaríngeas/terapia , Recidiva Local de Neoplasia/terapia , Radiocirurgia , Radioterapia Conformacional , Adulto , Idoso , Biópsia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/mortalidade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios XRESUMO
The promoter -10 binding region of the Bacillus subtilis sigma(A) factor forms an amphiphilic alpha-helix with three conserved isoleucines located at four-residue intervals. To investigate the structural and functional roles of the three isoleucine residues, we constructed a series of sigA mutants with single and double Ile-to-Ala substitutions on the hydrophobic face of this alpha-helix and isolated intragenic revertants with either same-site or second-site suppressor that partially restores the structural stability and transcription activity of the mutant sigma(A) factors. Our data show that the three conserved isoleucine residues (Ile-194, Ile-198, and Ile-202) are involved in the hydrophobic core packing of sigma(A); they affect differentially and additively the structure and function of sigma(A), with the central isoleucine residue (Ile-198) playing the most important role. By analogy with the crystal structure of a sigma(70) peptide, it is apparent that interdigital interactions exist between the three conserved isoleucine residues and certain hydrophobic amino acids in region 2. 1 of sigma(A). They include at least the van der Waals contacts between Ile-194 and both Leu-145 and Ile-149, between Ile-198 and both Ile-149 and Tyr-153, as well as between Ile-202 and Tyr-153. The same-site suppressors, Val-194 and Val-198, restore the structural stability and transcription activity of sigma(A) by repacking the hydrophobic core of sigma(A). The second-site suppressor (S291F) appears to be allele-specific, but it is not as effective as the same-site suppressors in restoring sigma(A) structure and function.
Assuntos
Bacillus subtilis/enzimologia , RNA Polimerases Dirigidas por DNA/metabolismo , Isoleucina/metabolismo , Regiões Promotoras Genéticas , Fator sigma/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Sítios de Ligação , DNA Bacteriano , RNA Polimerases Dirigidas por DNA/química , RNA Polimerases Dirigidas por DNA/genética , Isoleucina/química , Dados de Sequência Molecular , Mutação , Fator sigma/química , Fator sigma/genética , Relação Estrutura-Atividade , Transcrição GênicaRESUMO
Two Bacillus subtilis sigA mutants with amino acid substitutions tending to disrupt the structure of the promoter -10 binding helix of B. subtilis sigma A factor were constructed. B. subtilis DB1001 which contained an A197P substitution was very sensitive to temperature elevation. B. subtilis DB1002 had a T199G substitution and was low in growth potential at the elevated temperature. Degradation of sigma A in B. subtilis DB1001 (t(1/2)=63.2 min) and DB1002 (t(1/2)=186.0 min) occurred readily even at 37 degrees C; however, sigma A in B. subtilis DB2 (wild-type) was fairly stable at the same temperature. The activities of both DB1001 and DB1002 sigma A factors on groE promoter (sigma A-type) were lower than those of the wild-type counterpart at both permissive and restrictive temperatures. The failure of a higher sigma A concentration to suppress the Ts phenotype of DB1001 indicated that the temperature sensitivity of B. subtilis DB1001 was due to altered function, rather than insufficient concentration, of sigma A in the cells. Taken together, our results suggest that the helicity of the promoter -10 binding helix is essential to the packing interaction in the hydrophobic core region of sigma A, which helps to maintain the stable and functional sigma A structure.
Assuntos
Bacillus subtilis/enzimologia , Bacillus subtilis/genética , Proteínas de Bactérias/química , Proteínas de Ligação a DNA/química , RNA Polimerases Dirigidas por DNA/química , Regiões Promotoras Genéticas , Estrutura Secundária de Proteína , Fator sigma/química , Substituição de Aminoácidos/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Chaperoninas , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Ativação Enzimática , Proteínas de Escherichia coli , Genes Bacterianos , Proteínas de Choque Térmico/genética , Temperatura Alta , Mutagênese , Plasmídeos/síntese química , Fator sigma/genética , Fator sigma/metabolismo , Transcrição GênicaRESUMO
Most patients with hypopharyngeal carcinomas show advanced disease, either at the primary site or in the neck, at the time of diagnosis. Despite intensive therapy, a great number of recurrences and distant metastases can be observed. The most common metastatic sites are the lung and bone, and only in autopsy cases has peritoneum carcinomatosis been mentioned as a metastatic site. Since January 1992, two of 78 patients (2.3%) with advanced hypopharyngeal squamous cell carcinomas (SCCs) treated initially by chemotherapy in our department developed clinical peritoneal carcinomatosis during their natural courses. Both patients were man patients with advanced locoregional disease at stage T4N3. Their clinical peritoneal carcinomatosis appeared during chemotherapy, with good disease control above the clavicle. Both patients eventually died of sepsis within 1 month after diagnosis of the peritoneal carcinomatosis. The authors suggest that peritoneal carcinomatosis is not as rare as previously believed, and should be included in the differential diagnosis in patients with advanced hypopharyngeal SCC with abdominal symptoms. Peritoneal carcinomatosis appears to be refractory to chemotherapy, and carried a poor prognosis in patients in the present study.
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Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/secundário , Carcinoma/secundário , Neoplasias Hipofaríngeas/tratamento farmacológico , Neoplasias Hipofaríngeas/patologia , Neoplasias Peritoneais/secundário , Antineoplásicos/uso terapêutico , Carcinoma/patologia , Carcinoma de Células Escamosas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/patologiaRESUMO
In Southeast Asia and Taiwan, betel quid chewing is prevalent. Patients with head and neck cancer who chewed betel quid habitually seem to experience more severe chemotherapy-induced mucositis in our clinical practice. To validate this issue, patients with untreated head and neck cancer who received cisplatin (cDDP) plus a 5-fluorouracil (5-FU)-based neoadjuvant chemotherapy were included in this analysis. Information on the consumption of betel quid, tobacco, and alcohol were recorded before chemotherapy. Oral submucous fibrosis (OSF) was diagnosed clinically according to the fibrotic appearance of the mucosa and trismus. Mucositis was scored according to the World Health Organization criteria, and the mucositis score of the first course of chemotherapy was used for analysis. From December 1993 to April 1996, 120 patients were enrolled in this trial. Neither the betel quid chewing nor the cancer of the oral cavity was to be a significant factor for mucositis. However, clinically diagnosed OSF was found to display a significant correlation with more severe mucositis (p = 0.02). We concluded that in betel quid chewing-prevalent areas, OSF was a risk factor of more severe mucositis in head and neck cancer patients treated by CDDP and 5-FU-based regimens.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Areca/efeitos adversos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Fibrose Oral Submucosa/complicações , Plantas Medicinais , Estomatite/induzido quimicamente , Adulto , Idoso , Sudeste Asiático/etnologia , Cisplatino/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Terapia Neoadjuvante , Fibrose Oral Submucosa/etiologia , Estomatite/complicações , Estomatite/epidemiologia , Taiwan/epidemiologiaRESUMO
Secondary soft-tissue deficits may develop following a microsurgical reconstruction in the head and neck region because of inadequate planning or chronic effects of radiotherapy. Although most cases could be managed with alternative methods, free flaps might be necessary in difficult cases. Herein are described 11 cases of microsurgical head and neck reconstruction in which secondary soft-tissue deficits required transfer of another soft-tissue free flap. All patients had malignant tumors treated with surgical resection, and their defects were reconstructed with free flaps. Seven patients received either preoperative or postoperative adjunctive radiotherapy. These patients gradually developed signs and symptoms of soft-tissue deficiency in the reconstructed area, and a soft-tissue free flap transfer was required for treatment within an average of 21.5 months of their initial reconstruction. Five rectus abdominis, one rectus femoris, one latissimus dorsi, one tensor fasciae latae myocutaneous, one radial forearm, one medial arm, and one dorsalis pedis flap were used for this purpose. All flaps survived completely. The average follow-up time was 32 months. Significant improvement was achieved in all cases, and no further major surgical procedures were required. Secondary soft-tissue deficits that could not be predicted or prevented during the initial microsurgical reconstruction may be treated successfully by a subsequent free soft-tissue transfer in selected cases.
Assuntos
Face/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Microcirurgia , Procedimentos de Cirurgia Plástica/métodos , Complicações Pós-Operatórias/cirurgia , Retalhos Cirúrgicos , Adulto , Tecido Conjuntivo/cirurgia , Comportamento Alimentar , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Radioterapia Adjuvante/efeitos adversos , Reoperação , Estudos RetrospectivosRESUMO
Radiation-induced hearing loss was evaluated in 21 patients with unilateral malignant parotid tumors treated with surgery and radiotherapy. The contralateral ear was used as a control. Eight patients (38%) were found to have a reduction in static compliance of the tympanic membrane (type B tympanogram) in the irradiated ear. By audiometry, significant hearing loss was found in 9 patients (43%). These hearing losses were mainly sensorineural, as shown by a similar reduction in both air and bone conduction, although mixed-type hearing loss existed in some patients. A statistically significant difference in incidence of 67% versus 0% (p = .0085) was noted for patients with a cochlear dose of greater than or equal to 60 Gy, in comparison to those receiving doses of less than 60 Gy. A type B tympanogram was also found to be a prognostic factor for significant sensorineural hearing loss. Patients with type B tympanograms had a much higher incidence of significant sensorineural hearing loss than those with type A tympanograms (88% versus 15%, p = .02). This study clearly shows that radiotherapy can induce significant hearing impairment, especially when the cochlear doses are higher than 60 Gy.
Assuntos
Perda Auditiva Neurossensorial/etiologia , Neoplasias Parotídeas/radioterapia , Lesões por Radiação/complicações , Radioterapia/efeitos adversos , Testes de Impedância Acústica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Audiometria de Tons Puros/métodos , Feminino , Perda Auditiva Neurossensorial/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
From March 1977 to October 1989, 85 patients with early stage glottic cancer were treated with either radiotherapy or surgery at Chang Gung Memorial Hospital (CGMH). Patients were excluded from the analysis of local control if they died or remained disease-free with a follow-up period of less than two years. Of the 26 patients treated with definitive radiotherapy, initial control of the primary lesions was achieved in 100% of stage T1s, 76% of T1, and 57% of T2 patients. Surgical salvage of radiation failure was achieved in 83% of the patients, giving the ultimate local control of 100% for T1s, 94% for T1, 86% for T2 patients. Of the 44 patients treated with definitive surgery, initial control of the primary lesions was achieved in 100% for T1s, 95% for T1, and 78% for T2 patients. Salvage of the surgical failure was 50%, giving the ultimate control in this group of 100% for T1s, 95% for T1, 83% for T2. There was no difference in either initial or ultimate control of T1 and T2 lesions between patients treated with primary radiotherapy and primary surgery. Voice preservation rates were 73% and 34% in the radiotherapy and surgery group, respectively. When divided into two groups according to the times they were being treated, we found that surgery preserved a comparable number of larynges as radiotherapy did after 1988 (60% vs 77%, p = 0.33). It is concluded that radiotherapy and surgery could achieve the same good local control results and long-term survival and comparable functional results of early stage glottic cancer, if conservative surgery is carefully selected for each patient.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Glote , Neoplasias Laríngeas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/radioterapia , Neoplasias Laríngeas/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
The present study was designed to examine whether different p53 haplotypes of exon 4-intron 3-intron 6 affect the frequency of mutations and loss of heterozygosity (LOH) of the p53 gene in male oral squamous cell carcinomas (OSCCs) in Taiwan. We found that individuals without two Pro-W-G alleles had significantly higher frequency of p53 mutations than those with two Pro-W-G alleles (odds ratio (OR) = 1.98; 95% confidence interval (CI), 1.10-3.56). Out of the 172 p53 gene exon 4 informative male OSCCs, 72 (41.9%) showed LOH. Among these 72 OSCCs with LOH, the frequency of Pro allele loss was 73.6% (53/72). It is notable that alcohol drinking increased the frequency of Arg allele loss (OR = 10.56; 95% CI, 1.23-234.94) in OSCCs from patients who both smoked cigarettes and chewed areca quid (AQ). The frequency of LOH of p53 was not different between p53-mutated OSCCs and p53-normal OSCCs. Thus, the present study revealed that (a) the Arg allele is associated with p53 mutations, (b) the Pro allele is preferentially lost in OSCCs associated with cigarette smoking and AQ chewing, while the frequency of Arg allele loss is increased with alcohol drinking, and (c) haploinsufficiency of p53 is in itself likely to contribute to tumour progression in Taiwanese OSCCs.