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The Chemical Functional Ontology (ChemFOnt), located at https://www.chemfont.ca, is a hierarchical, OWL-compatible ontology describing the functions and actions of >341 000 biologically important chemicals. These include primary metabolites, secondary metabolites, natural products, food chemicals, synthetic food additives, drugs, herbicides, pesticides and environmental chemicals. ChemFOnt is a FAIR-compliant resource intended to bring the same rigor, standardization and formal structure to the terms and terminology used in biochemistry, food chemistry and environmental chemistry as the gene ontology (GO) has brought to molecular biology. ChemFOnt is available as both a freely accessible, web-enabled database and a downloadable Web Ontology Language (OWL) file. Users may download and deploy ChemFOnt within their own chemical databases or integrate ChemFOnt into their own analytical software to generate machine readable relationships that can be used to make new inferences, enrich their omics data sets or make new, non-obvious connections between chemicals and their direct or indirect effects. The web version of the ChemFOnt database has been designed to be easy to search, browse and navigate. Currently ChemFOnt contains data on 341 627 chemicals, including 515 332 terms or definitions. The functional hierarchy for ChemFOnt consists of four functional 'aspects', 12 functional super-categories and a total of 173 705 functional terms. In addition, each of the chemicals are classified into 4825 structure-based chemical classes. ChemFOnt currently contains 3.9 million protein-chemical relationships and â¼10.3 million chemical-functional relationships. The long-term goal for ChemFOnt is for it to be adopted by databases and software tools used by the general chemistry community as well as the metabolomics, exposomics, metagenomics, genomics and proteomics communities.
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Bases de Dados de Compostos Químicos , Software , Bases de Dados Factuais , Ontologia Genética , Genômica , ProteômicaRESUMO
SYNGAP1 is a neuronal Ras and Rap GTPase-activating protein with important roles in regulating excitatory synaptic plasticity. While many SYNGAP1 missense and nonsense mutations have been associated with intellectual disability, epilepsy, schizophrenia, and autism spectrum disorder (ASD), whether and how they contribute to individual disease phenotypes is often unknown. Here, we characterize 57 variants in seven assays that examine multiple aspects of SYNGAP1 function. Specifically, we used multiplex phospho-flow cytometry to measure variant impact on protein stability, pERK, pGSK3ß, pp38, pCREB, and high-content imaging to examine subcellular localization. We find variants ranging from complete loss-of-function (LoF) to wild-type (WT)-like in their regulation of pERK and pGSK3ß, while all variants retain at least partial ability to dephosphorylate pCREB. Interestingly, our assays reveal that a larger proportion of variants located within the disordered domain of unknown function (DUF) comprising the C-terminal half of SYNGAP1 exhibited higher LoF, compared to variants within the better studied catalytic domain. Moreover, we find protein instability to be a major contributor to dysfunction for only two missense variants, both located within the catalytic domain. Using high-content imaging, we find variants located within the C2 domain known to mediate membrane lipid interactions exhibit significantly larger cytoplasmic speckles than WT SYNGAP1. Moreover, this subcellular phenotype shows both correlation with altered catalytic activity and unique deviation from signaling assay results, highlighting multiple independent molecular mechanisms underlying variant dysfunction. Our multidimensional dataset allows clustering of variants based on functional phenotypes and provides high-confidence, multi-functional measures for making pathogenicity predictions.
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GTP Fosfo-Hidrolases/genética , Mutação/genética , Transdução de Sinais/genética , Proteínas Ativadoras de ras GTPase/genética , Transtorno do Espectro Autista/genética , Linhagem Celular , Epilepsia/genética , Células HEK293 , Humanos , Deficiência Intelectual/genética , Transtornos do Neurodesenvolvimento/genética , Fenótipo , Estabilidade ProteicaRESUMO
PathBank (www.pathbank.org) is a new, comprehensive, visually rich pathway database containing more than 110 000 machine-readable pathways found in 10 model organisms (Homo sapiens, Bos taurus, Rattus norvegicus, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, Saccharomyces cerevisiae, Escherichia coli and Pseudomonas aeruginosa). PathBank aims to provide a pathway for every protein and a map for every metabolite. This resource is designed specifically to support pathway elucidation and pathway discovery in transcriptomics, proteomics, metabolomics and systems biology. It provides detailed, fully searchable, hyperlinked diagrams of metabolic, metabolite signaling, protein signaling, disease, drug and physiological pathways. All PathBank pathways include information on the relevant organs, organelles, subcellular compartments, cofactors, molecular locations, chemical structures and protein quaternary structures. Each small molecule is hyperlinked to the rich data contained in public chemical databases such as HMDB or DrugBank and each protein or enzyme complex is hyperlinked to UniProt. All PathBank pathways are accompanied with references and detailed descriptions which provide an overview of the pathway, condition or processes depicted in each diagram. Every PathBank pathway is downloadable in several machine-readable and image formats including BioPAX, SBML, PWML, SBGN, RXN, PNG and SVG. PathBank also supports community annotations and submissions through the web-based PathWhiz pathway illustrator. The vast majority of PathBank's pathways (>95%) are not found in any other public pathway database.
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Bases de Dados Factuais , Genômica/métodos , Redes e Vias Metabólicas , Metabolômica/métodos , Software , Animais , Arabidopsis , Caenorhabditis elegans , Bovinos , Drosophila , Humanos , Camundongos , Ratos , Saccharomyces cerevisiaeRESUMO
Owing to the constraints of time and space complexity, network intrusion detection systems (NIDSs) based on support vector machines (SVMs) face the "curse of dimensionality" in a large-scale, high-dimensional feature space. This study proposes a joint training model that combines a stacked autoencoder (SAE) with an SVM and the kernel approximation technique. The training model uses the SAE to perform feature dimension reduction, uses random Fourier features to perform kernel approximation, and then random Fourier mapping is explicitly applied to the sub-sample to generate the random feature space, making it possible to apply a linear SVM to uniformly approximate to the Gaussian kernel SVM. Finally, the SAE performs joint training with the efficient linear SVM. We studied the effects of an SAE structure and a random Fourier feature on classification performance, and compared that performance with that of other training models, including some without kernel approximation. At the same time, we compare the accuracy of the proposed model with that of other models, which include basic machine learning models and the state-of-the-art models in other literatures. The experimental results demonstrate that the proposed model outperforms the previously proposed methods in terms of classification performance and also reduces the training time. Our model is feasible and works efficiently on large-scale datasets.
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BACKGROUND: Local recurrence is the major cause of treatment failure in patients who undergo surgical salvage of recurrent nasopharyngeal carcinoma (NPC) after radiotherapy. The authors investigated the role of Epstein-Barr virus (EBV)-encoded Bam HI-A rightward transcript 7 microRNA (BART7) status in resection margins in the identification of a subgroup of patients who may benefit from adjuvant reradiation after surgery. METHODS: One hundred two consecutive patients who had histologically clear resection margins after undergoing nasopharyngectomy for recurrent NPC were studied. The status of EBV microRNA BART7 in resection margins was investigated and correlated with the pattern of subsequent disease recurrence. RESULTS: After a median follow-up of 64 months, 20 patients (19.6%) developed local recurrence after surgery despite histologically uninvolved margins. The risk of local recurrence in patients with histologically close (<5 mm) and clear (≥5 mm) margins was 31.6% and 12.5%, respectively. In patients with clear histologic margins, those with margins that were positive for EBV microRNA BART7 has a significantly higher chance of developing local tumor recurrence (P = .016) than those with negative molecular margins. The difference was not significant when the histologic clearance at the resection margins was <5 mm. CONCLUSIONS: Tissue EBV microRNA BART7 is useful for identifying a subgroup of patients with histologically clear margins who are at increased risk of subsequent local tumor recurrence. Postoperative adjuvant treatment is warranted for these patients.
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Proteínas de Transporte/genética , Procedimentos Cirúrgicos Nasais , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/cirurgia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/cirurgia , Faringectomia , Terapia de Salvação/métodos , Adulto , Idoso , Carcinoma , Feminino , Herpesvirus Humano 4 , Humanos , Masculino , MicroRNAs , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/virologia , Recidiva Local de Neoplasia/virologia , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Fatores de TranscriçãoAssuntos
Infecções por Coronavirus/prevenção & controle , Desinfecção , Meato Acústico Externo/lesões , Contaminação de Equipamentos , Controle de Infecções/métodos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Estetoscópios/efeitos adversos , Betacoronavirus , COVID-19 , Humanos , SARS-CoV-2RESUMO
INTRODUCTION: Curative resection of malignant tumours of the skull base is increasingly undertaken endoscopically. Hitherto the diverse histology, rarity and long natural history have made it difficult to accrue statistically robust cohorts for comparison with conventional craniofacial resection. It is now possible to make such a comparison in a large personal cohort. METHOD: Data on all cases of sinonasal malignancy undergoing endoscopic resection with curative intent over an eighteen year period were collected prospectively and analysed for survival and prognostic factors. RESULTS: There were 140 cases, 68 men and 72 women, aged 20-92 years (mean 63 yrs). Follow-up ranged from 6-184 months (mean 60 months). Eighteen different histopathologies were represented with olfactory neuroblastoma (36), malignant melanoma (33) and adenocarcinoma (19) being the commonest. Additional radiotherapy was given in 95 cases and chemotherapy in 49. Overall survival is 84% at 5 years and 69% at 10 years. Overall disease-free survival was 77% at 5 years and 56% at ten. Overall and disease-free survival at 5 (and 10) years is, respectively, 97% and 90% for olfactory neuroblastoma, 79% and 68% for adenocarcinoma and 56% and 39% for malignant melanoma. CONCLUSION: These results show that endoscopic resection is an alternative to conventional craniofacial resection in selected cases.
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Carcinoma/cirurgia , Endoscopia , Estesioneuroblastoma Olfatório/cirurgia , Melanoma/cirurgia , Neoplasias Nasais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Carcinoma/patologia , Estudos de Coortes , Feminino , Humanos , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Cavidade Nasal , Neoplasias Nasais/mortalidade , Neoplasias Nasais/patologia , Seios Paranasais , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: Radiotherapy has been the mainstay treatment for nasopharyngeal carcinoma (NPC) and has achieved good disease control. However, irradiation is associated with potential complications such as osteoradionecrosis (ORN) and infection. There is sparse description in the literature of such complications and how they are best managed. The objectives of the study are: (1) to describe the complications at the cervical spine after surgical and radiotherapy treatment for NPC (2) to identify key principles in the diagnosis and treatment of these complications. METHODS: A retrospective review of all patients with cervical spine complications after radiation treatment and surgery for NPC treated in a tertiary referral center, since 1990. RESULTS: Fourteen patients with cervical spine ORN and infections were found with an average duration to diagnosis of 8.6 years. All 14 patients had mucosal and deep biopsies and none had tumor recurrence. Four patients had ORN, eight had osteomyelitis and two patients had both ORN and osteomyelitis. CONCLUSIONS: Radiotherapy complications usually have delayed and subtle presentations. ORN progresses slowly and can often be treated conservatively. Infections should be treated aggressively with surgical debridement and the results are generally good. Patients should be regularly followed-up with transoral examination to assess the integrity of the posterior pharyngeal wall and imaging to assess for ORN. Pharyngeal defects raise concern for cervical spine infections. Coverage of pharyngeal defects in these patients is important to prevent recurrent infection.
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Carcinoma/terapia , Vértebras Cervicais/patologia , Neoplasias Nasofaríngeas/terapia , Osteomielite/etiologia , Osteorradionecrose/etiologia , Radioterapia/efeitos adversos , Adulto , Biópsia , Carcinoma/radioterapia , Carcinoma/cirurgia , Vértebras Cervicais/cirurgia , Desbridamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/cirurgia , Osteomielite/patologia , Osteorradionecrose/patologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
To study the role of surgery for symptom palliation in patients with advanced head and neck malignancy. Between 2000 and 2011, patients with locoregionally advanced cancer in the head and neck region, who chose surgical palliation for symptom control, were studied retrospectively. During the study period, 52 patients were included. The index tumour included carcinoma of the maxilla (23.1 %), tongue (19.2 %), larynx/hypopharynx (15.4 %), post-radiation sarcoma (11.5 %), primary sarcoma (11.5 %), carcinoma of the lower alveolus (11.5 %), nasal mucosal melanoma (3.9 %) and metastatic tumour in the head and neck region (3.9 %). The major symptoms included bleeding (53.9 %), tumour pain (19.2 %), dysphagia (11.5 %), non-healing ulcerations (7.7 %), airway obstruction (5.8 %) and pathological fracture of the mandible (1.9 %). Ligation of the carotid artery was performed in 10 patients, complete resection of tumour in 35, and surgical debulking of the tumour in 7 patients. Mean survival of the patients was 5.6 months. The majority of the patients achieved satisfactory and persistent control of symptoms. One patient died from pneumonia during the hospital stay, and the rest were discharged after a mean duration of 16.4 days. In selected patients, surgery is effective in palliating symptoms which are otherwise difficult to manage. Detailed planning and good communication is the key to success in improving the quality of dying.
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Neoplasias de Cabeça e Pescoço/cirurgia , Cuidados Paliativos , Assistência Terminal , Obstrução das Vias Respiratórias/etiologia , Transtornos de Deglutição/etiologia , Feminino , Fraturas Espontâneas/etiologia , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/mortalidade , Hemorragia/etiologia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Taxa de SobrevidaRESUMO
Objective: To compare gender compositions in the leadership of the top 25 medical schools in North America with the leadership of their affiliated university senior leadership and other faculties. Materials and Methods: This retrospective cross-sectional observational study used publicly available gender data from 2018 to 2019 of universities drawn from the U.S. News Best Global Universities for Clinical Medicine Ranking report. Gender compositions in eight leadership tiers from senior leadership to medical school department directors were analyzed. Data analysis included gender compositions by leadership tier and faculty. Results: Male representation is greater at higher leadership tiers, with the largest imbalance being at the level of medical school department heads. The faculty of medicine has more men in leadership positions than the average of the other faculties (p = 0.02), though similar to schools of engineering, business, dentistry, and pharmacy. Across the eight leadership tiers, a significant trend exists between tier and proportions, indicating that male representation was greater at higher tiers (p < 0.001). No correlation was found between a university's leadership gender composition and its ranking. Conclusion: The under-representation of women is greater in medical school leadership than the leadership of their affiliated universities. The faculty of medicine has greater male over-representation than the average of the other faculties.
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OBJECTIVE: The lifelong risks of cardiovascular disease following hypertensive disorders of pregnancy are well described. Awareness of these risks and associated health-seeking behaviours among affected individuals remains unclear. We aimed to assess participants' knowledge of their cardiovascular disease risk and relevant health-seeking behaviours following a pregnancy affected by preeclampsia or gestational hypertension. METHODS: We undertook a single-site, cross-sectional cohort study. The target population included individuals who birthed at a large tertiary referral centre in Melbourne, Australia, between 2016 and 2020, and were diagnosed with gestational hypertension or pre-eclampsia. Participants completed a survey assessing pregnancy details, medical comorbidities, knowledge of future risks and health-seeking behaviours post-pregnancy. RESULTS: 1526 individuals met inclusion criteria and 438 (28.6%) completed the survey. Of these, 62.6% (n=237) were unaware of their increased risk of cardiovascular disease following a hypertensive disorder of pregnancy. Participants who reported awareness of their increased risk were more likely to have annual blood pressure monitoring (54.6% vs 38.1%, p<0.01), and at least one assessment of blood cholesterol (p<0.01), blood glucose (p=0.03) and renal function (p=0.01). Participants who were aware were more likely to be taking antihypertensive medication (24.5% vs 6.6%, p<0.01) since pregnancy, compared with those who were unaware. There were no differences between groups in diet, exercise or smoking habits. CONCLUSION: Among our study cohort, risk awareness was associated with increased health-seeking behaviours. Participants who were aware of their increased risk of cardiovascular disease were more likely to have regular cardiovascular risk factor assessments. They were also more likely to be taking antihypertensive medication.
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Doenças Cardiovasculares , Hipertensão Induzida pela Gravidez , Pré-Eclâmpsia , Complicações Cardiovasculares na Gravidez , Gravidez , Feminino , Humanos , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/tratamento farmacológico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Hipertensão Induzida pela Gravidez/diagnóstico , Hipertensão Induzida pela Gravidez/epidemiologia , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Estudos Transversais , Complicações Cardiovasculares na Gravidez/epidemiologia , Fatores de Risco , Fatores de Risco de Doenças Cardíacas , Aceitação pelo Paciente de Cuidados de SaúdeRESUMO
Carbapenem-hydrolyzing class D ß-lactamases (CHDLs) represent an emerging antibiotic resistance mechanism encountered among the most opportunistic Gram-negative bacterial pathogens. We report here the substrate kinetics and mechanistic characterization of a prominent CHDL, the OXA-58 enzyme, from Acinetobacter baumannii. OXA-58 uses a carbamylated lysine to activate the nucleophilic serine used for ß-lactam hydrolysis. The deacylating water molecule approaches the acyl-enzyme species, anchored at this serine (Ser-83), from the α-face. Our data show that OXA-58 retains the catalytic machinery found in class D ß-lactamases, of which OXA-10 is representative. Comparison of the homology model of OXA-58 and the recently solved crystal structures of OXA-24 and OXA-48 with the OXA-10 crystal structure suggests that these CHDLs have evolved the ability to hydrolyze imipenem, an important carbapenem in clinical use, by subtle structural changes in the active site. These changes may contribute to tighter binding of imipenem to the active site and removal of steric hindrances from the path of the deacylating water molecule.
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Acinetobacter baumannii/enzimologia , Antibacterianos/química , Proteínas de Bactérias/química , Farmacorresistência Bacteriana/fisiologia , Imipenem/química , beta-Lactamases/química , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Catálise , Hidrólise , Imipenem/farmacologia , Estrutura Terciária de Proteína , Homologia Estrutural de Proteína , beta-Lactamases/metabolismoRESUMO
BACKGROUND: The objective of this study was to examine the quality of life (QOL) of patients who underwent salvage nasopharyngectomy for residual or recurrent nasopharyngeal carcinoma and to justify the value of the procedure. METHODS: A self-reported, health-related QOL questionnaire was used to assess the QOL of patients after salvage nasopharyngectomy. The effects of potential complications after surgery also were evaluated. RESULTS: Between 2003 and 2011, 185 patients underwent salvage nasopharyngectomy using the maxillary swing approach. Curative resection was achieved in 80% of patients. There were no significant changes in mean global health system scores after surgery, except after palliative resection requiring postoperative adjuvant chemoradiation. Social functioning scores were the lowest of the 5 functioning scales in all patient groups. Palatal fistula significantly affected social eating and weight loss, and osteoradionecrosis caused more pain and nasal discharge, severely affecting the social life of patients. CONCLUSIONS: The QOL of patients after maxillary swing salvage nasopharyngectomy was good. The current results indicated that attention must be paid to the factors that adversely affect QOL after surgery, such as palliative resection, and complications like trismus, palatal fistula and osteoradionecrosis.
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Neoplasias Nasofaríngeas/psicologia , Neoplasias Nasofaríngeas/cirurgia , Faringectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/cirurgia , Neoplasia Residual/cirurgia , Faringectomia/efeitos adversos , Prognóstico , Qualidade de Vida , Terapia de Salvação/métodos , Adulto JovemRESUMO
Squamous cell carcinoma (SCC) of tongue is an aggressive head and neck cancer with high propensity of regional spreading and invasion. Tongue carcinoma cells treated with curcumin, the major curcuminoid of the turmeric, demonstrated reduction in adhesion, migration, and invasion ability. High-throughput microarray analysis indicated that curcumin treatment suppressed matrix metallopeptidase 10 (MMP10) expression. MMP10 is overexpressed in tongue carcinoma tissues in comparison with the normal epithelia. Curcumin treatment on tongue carcinoma cell lines suppressed MMP10 expression at both mRNA and protein levels. Our results suggested that curcumin is a promising inhibitor to tongue cancer cells migration and invasion.
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Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/patologia , Metaloproteinase 10 da Matriz/metabolismo , Neoplasias da Língua/enzimologia , Neoplasias da Língua/patologia , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/farmacologia , Regulação para Baixo , Humanos , Neoplasias da Língua/tratamento farmacológicoRESUMO
OBJECTIVE: To assess the long-term audiological outcome and otological complications of nasopharyngeal carcinoma patients who have received intensity-modulated radiotherapy (IMRT) versus conventional two-dimensional radiotherapy (2 DRT). STUDY DESIGN: Prospective study on the audiological outcome and otological complications 5-9 years after radiotherapy. METHODOLOGY: Patients had pure-tone audiogram before radiotherapy and 5 years after radiotherapy. Otological examination was performed 5-9 years after radiotherapy by an otolaryngologist. RESULTS: There is a significant deterioration of the hearing threshold 5 years after radiotherapy but there is no statistically significant difference in the deterioration of hearing between IMRT and 2 DRT. Six patients in the 2 DRT group and 1 patient in the IMRT group had osteoradionecrosis of the external auditory canal (p = 0.042). CONCLUSION: There are fewer incidences of osteoradionecrosis of the external auditory canal in patients treated with IMRT. There is no difference in bone conduction threshold in patients treated with IMRT or 2 DRT.
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Perda Auditiva Neurossensorial/diagnóstico , Audição/efeitos da radiação , Neoplasias Nasofaríngeas/radioterapia , Osteorradionecrose/complicações , Lesões por Radiação/diagnóstico , Radioterapia Conformacional/efeitos adversos , Adulto , Idoso , Carcinoma , Feminino , Perda Auditiva Neurossensorial/etiologia , Testes Auditivos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/complicações , Estudos Prospectivos , Lesões por Radiação/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: We have previously reported our early experience in robotic-assisted nasopharyngectomy. The current case series is a report of our experience in 33 robotic-assisted nasopharyngectomy. METHODS: Prospective series of patients who underwent robotic-assisted nasopharyngectomy for local recurrent nasopharyngeal carcinoma from January 2010 to March 2019. RESULTS: Thirty-one patients underwent robotic-assisted nasopharyngectomy with two additional second procedure for positive margin. Median age is 55 years (29-85). Twenty-five patients had rT1 disease and six patients had tumor invaded sphenoid floor (rT3). Median operative time was 227 min and median blood loss was 200 ml. The median follow-up period for all patients were 38 months. Four patients had local recurrence. Five-year local control rate, overall survival, and disease-free survival are 85.1%, 55.7%, and 69.1%, respectively. CONCLUSION: Robotic-assisted nasopharyngectomy for recurrent nasopharyngectomy was showed to have a high local control rate. The operating time was comparable to open surgery.
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Neoplasias Nasofaríngeas , Procedimentos Cirúrgicos Robóticos , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/cirurgia , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/patologia , Faringectomia/métodos , Estudos Prospectivos , Terapia de Salvação/métodos , Taxa de SobrevidaRESUMO
Chimeric antigen receptor-engineered T (CAR-T) cells have shown promising efficacy in patients with relapsed/refractory B cell acute lymphoblastic leukemia (R/R B-ALL). However, challenges remain including long manufacturing processes that need to be overcome. We presented the CD19-targeting CAR-T cell product GC007F manufactured next-day (FasTCAR-T cells) and administered to patients with R/R B-ALL. A total of 21 patients over 14 years of age with CD19+ R/R B-ALL were screened, enrolled and infused with a single infusion of GC007F CAR-T at three different dose levels. The primary objective of the study was to assess safety, secondary objectives included pharmacokinetics of GC007F cells in patients with R/R B-ALL and preliminary efficacy. We were able to demonstrate in preclinical studies that GC007F cells exhibited better proliferation and tumor killing than conventional CAR-T (C-CAR-T) cells. In this investigator-initiated study all 18 efficacy-evaluable patients achieved a complete remission (CR) (18/18, 100.00%) by day 28, with 17 of the patients (94.4%) achieving CR with minimal residual disease (MRD) negative. Fifteen (83.3%) remained disease free at the 3-month assessment, 14 patients (77.8%) maintaining MRD negative at month 3. Among all 21 enrolled patients, the median peak of CAR-T cell was on day 10, with a median peak copy number of 104899.5/µg DNA and a median persistence period of 56 days (range: 7-327 days). The incidence of cytokine release syndrome (CRS) was 95.2% (n = 20), with severe CRS occurring in 52.4% (n = 11) of the patients. Six patients (28.6%) developed neurotoxicity of any grade. GC007F demonstrated superior expansion capacity and a less exhausted phenotype as compared to (C-CAR-T) cells. Moreover, this first-in-human clinical study showed that the novel, next-day manufacturing FasTCAR-T cells was feasible with a manageable toxicity profile in patients with R/R B-ALL.
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Linfoma de Células B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Antígenos Quiméricos , Doença Aguda , Proteínas Adaptadoras de Transdução de Sinal , Antígenos CD19 , Humanos , Imunoterapia Adotiva/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos Quiméricos/genética , Indução de Remissão , Linfócitos TRESUMO
BACKGROUND: Pharyngo-laryngo-esophagectomy (PLE) has been regarded as a standard treatment for cervical esophageal cancer, but the morbidity and mortality rates associated with PLE are substantial. Chemoradiation (CTRT) is widely used to treat esophageal cancer; however, its role in managing cervical esophageal cancer has not been fully elucidated. It was hypothesized that up-front CTRT could be an effective alternative treatment option to PLE. The purpose of this study was to compare the outcomes of patients with cervical esophageal cancer treated with these two methods. METHODS: Patients with cervical esophageal cancer from 1995 to 2008 were studied. Three main groups were identified: those treated with PLE, those managed with up-front concurrent chemoradiation, and those not suitable for either PLE or chemoradiation but to whom palliative treatment was offered. The demographics, management strategies, and outcomes of these patients were studied and analyzed. RESULTS: A total of 107 patients were studied: 87 (81.3%) were men, and the median age was 64 years (range 17-92 years). There were 62 patients who underwent PLE as the primary treatment, 21 had up-front chemoradiation, and the others had palliative treatment. In the PLE group, curative resection was achieved in 37 (59.7%) patients, 20 of whom had either adjuvant chemoradiation or radiotherapy. The hospital mortality rate was 7.1%. In the chemoradiation group, 10 (47.6%) had tumor down-staging, 6 of whom achieved a clinically complete response. Among the 11 patients with poor response, 5 required salvage PLE for palliation. Chemoradiation-associated morbidities included oral mucositis, bilateral vocal cord palsy, esophageal stricture, carotid artery blowout, and permanent hypothyroidism and hypoparathyroidism. The median survival durations of patients in the PLE and chemoradiation groups were 20 and 25 months respectively (P = 0.39). CONCLUSIONS: Up-front chemoradiation can be an alternative therapeutic strategy to PLE. However, this method is not without drawbacks. A significant proportion also requires salvage surgery. Both PLE and chemoradiation have significant curative as well as palliative role in the management of cervical esophageal cancer and treatment should be individualized.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Cuidados Paliativos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Estudos de Coortes , Terapia Combinada , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Laringectomia/métodos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Cuidados Paliativos/métodos , Faringectomia/métodos , Prognóstico , Radioterapia/métodos , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Schwannoma is a type of benign nerve sheath tumour arising from the Schwann cell. Because of the close relationship between the tumour and the nerve of origin (NOO), the operation of extracranial head and neck schwannoma may lead to palsy of major nerve. For this reason, an accurate diagnosis of schwannoma with the identification of the NOO is crucial to the management. The aim of this review was to find out the distribution of the NOO and the usefulness of the investigations in the diagnosis of schwannoma. Medical records of the patients who underwent operation of the extracranial head and neck schwannoma in our division were reviewed. Between January 2000 and December 2009, 30 cases of extracranial head and neck schwannoma were operated. Sympathetic trunk (10, 33%) and vagus nerve (6, 20%) were the two most common NOOs. In five (17%) cases, the NOO was not found to be arising from any major nerve. For these 30 patients, 20 received fine needle aspiration cytology (FNAC) and 26 underwent imaging studies (computed tomography or magnetic resonance imaging) before operation. The specificity of FNAC and imaging studies in making the diagnosis of schwannoma was 20 and 38%, respectively. For the patients who had nerve palsies on presentation, their deficits remained after operation. The rate of nerve palsy after tumour excision with division of NOO and intracapsular enucleation was 100 and 67%, respectively. The diagnosis of schwannoma is suggested by clinical features and supported by investigations. Most of the time, the diagnosis can only be confirmed on the histological study of the surgical specimen. Sympathetic trunk and vagus nerve are the two common NOOs. MRI is the investigation of choice in the diagnosis of schwannoma and the identification of NOO.
Assuntos
Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Neurilemoma/patologia , Neurilemoma/cirurgia , Adolescente , Adulto , Idoso , Biópsia por Agulha Fina , Estudos de Coortes , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neurilemoma/diagnóstico , Neurilemoma/mortalidade , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Nervo Trigêmeo/patologia , Nervo Vago/patologia , Adulto JovemRESUMO
Second primary squamous cell carcinoma (SCC) in the skin of a flap used for reconstruction of floor of mouth is rare. A case of SCC arising in the pectoralis major myocutaneous flap that was used to reconstruct the floor of mouth 12 years after subtotal glossectomy and resection of the floor of mouth is reported. The tumour is a second primary SCC arises in the skin of a myocutaneous flap without any obvious risk factors. Review of the literature reveals four previous similar reports and the findings are summarized. In summary, squamous epithelium of the skin flap after prolonged exposure to non-physiological stimuli may lead to metaplasia and possible carcinoma formation. Long-term follow up and awareness of this complication are needed for head and neck cancer patients after resection and reconstruction.