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1.
Int J Oral Maxillofac Implants ; 0(0): 1-24, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38941165

RESUMO

PURPOSE: As the population gets older, the prevalence of complete or partial tooth loss is increasing, significantly impacting people's quality of life. Scientific research demonstrates that implant-fixed complete dentures offer high levels of satisfaction. In certain cases, tooth loss can lead to significant bone atrophy, necessitating pre-implant bone reconstruction. We conducted a retrospective cohort study involving 43 arches, including or not bone grafts, rehabilitated using a stackable guided approach, which included an immediate loading protocol. The primary outcome measure was the survival rate of the implant at 4 months. MATERIAL AND METHODS: The digital workflow helps the design of the provisional prothesis before the implant surgery, which will be loaded immediately after the implant's placement. The stacked guides integrate both surgical and prosthetic considerations into a digital workflow. RESULT: A total of 284 implants were placed. After a 4-month follow-up period, 10 implants (3.5%) exhibited no osseointegration and were subsequently replaced, resulting in an overall success rate of 96.5%. After 1 year of follow-up, a prosthetic success rate of 100% was observed, with all patients being able to progress to the stages for the permanent fixed dentures. CONCLUSION: Our findings support the use of this protocol for all patients, whether they require bone grafts or not. However, a long-term follow-up is essential for a comprehensive evaluation of these treatment outcomes.

2.
Eur J Cancer ; 107: 124-132, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30562710

RESUMO

BACKGROUND: Atezolizumab (anti-programmed death-ligand 1 [PD-L1]) received approval from the US Food and Drug Administration and European Medicines Agency for previously treated advanced non-small-cell lung cancer based on OAK-a randomised, phase III trial that showed significantly improved survival with atezolizumab versus docetaxel regardless of PD-L1 expression. With longer follow-up, we summarised the characteristics of long-term survivors (LTSs). METHODS: In OAK (NCT02008227), patients were randomised 1:1 to receive atezolizumab or docetaxel until loss of clinical benefit or disease progression, respectively. Overall survival was evaluated after a 26-month minimum follow-up, including in patient subgroups defined by best overall response (BOR). LTSs were defined as patients who lived ≥24 months since randomisation. Non-LTSs died within 24 months, and patients censored before 24 months were excluded from the analysis. The baseline characteristics, including biomarkers, BOR, subsequent non-protocol therapy (NPT) and safety, are reported. RESULTS: Survival benefit with atezolizumab was observed across all patient subgroups defined by BOR. More atezolizumab-treated patients were LTSs versus those treated with docetaxel (28% versus 18%). Most atezolizumab responders were LTSs (77%) versus only 48% of docetaxel responders. However, 21% of atezolizumab-arm LTSs had progressive disease (PD) as BOR, and more atezolizumab-arm LTSs than non-LTSs continued treatment post-PD. Fifty-two percent of docetaxel-arm LTSs received immunotherapy as subsequent NPT. Despite extended treatment duration in atezolizumab-arm LTSs (median, 18 months), atezolizumab was well tolerated. CONCLUSIONS: After >2 years of follow-up, atezolizumab continued to provide durable survival benefit versus docetaxel, with tolerable safety. Atezolizumab-arm LTSs were enriched for patients with high PD-L1 expression and included PD-L1-negative patients. Long-term survival was not limited to responders.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/mortalidade , Neoplasias Pulmonares/mortalidade , Sobreviventes/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Docetaxel/administração & dosagem , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
3.
Br J Cancer ; 109(6): 1476-81, 2013 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-23942074

RESUMO

BACKGROUND: The association between tumour measurements and survival has been studied extensively in early-stage and locally advanced non-small cell lung cancer (NSCLC). We analysed these factors in patients with advanced NSCLC. METHODS: Data were derived from the E4599 trial of paclitaxel-carboplatin±bevacizumab. Associations between the Response Evaluation Criteria in Solid Tumors (RECIST) baseline sum longest diameter (BSLD), response rate, progression-free survival (PFS) and overall survival (OS) were evaluated using univariate and multivariable Cox regression models. RESULTS: A total of 759 of the 850 patients (89%) in the E4599 trial had measurable diseases and were included in this analysis. The median BSLD was 7.5 cm. BSLD predicted OS (hazard ratio (HR) 1.41; P<0.001) and had a trend towards association with PFS (HR 1.14; P=0.08). The median OS was 12.6 months for patients with BSLD <7.5 cm compared with 9.5 months for BSLD ≥ 7.5 cm. This association persisted in a multivariable model controlling multiple prognostic factors, including the presence and sites of extrathoracic disease (HR 1.24; P=0.01). There was no association between BSLD and response rate. CONCLUSION: Tumour measurements are associated with survival in the E4599 trial. If validated in other populations, this parameter may provide important prognostic information to patients and clinicians.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab , Carboplatina/administração & dosagem , Feminino , Humanos , Masculino , Invasividade Neoplásica , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida , Resultado do Tratamento
4.
Ann Oncol ; 24(1): 20-30, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23180113

RESUMO

BACKGROUND: Previous studies have demonstrated the efficacy and safety of bevacizumab in the treatment of non-small-cell lung cancer (NSCLC). METHODS: Summary data from randomised trials comparing first-line bevacizumab plus platinum-based chemotherapy with chemotherapy alone for inoperable locally advanced, recurrent or metastatic NSCLC were meta-analysed. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and pooled odds ratio (OR) for adverse events were calculated. The chi-squared tests evaluated interactions between treatment effects, and prognostic factors and patient characteristics. RESULTS: Data of 2194 patients (1313 bevacizumab; 881 controls) from four phase II and III trials: AVF-0757g, JO19907,ECOG 4599 and AVAiL, were analysed. Compared with chemotherapy alone, bevacizumab significantly prolonged OS(HR 0.90; 95% confidence interval [CI] 0.81, 0.99; P=0.03), and PFS (0.72; 95% CI 0.66, 0.79; P<0.001). Bevacizumab showed a significantly greater effect on OS in patients with adenocarcinoma versus other histologies (P=0.03), and patients with body weight loss ≤5% versus >5% (P=0.04). Bevacizumab significantly increased the risk of grade ≥3 proteinuria, hypertension,haemorrhagic events, neutropenia, and febrile neutropenia [corrected]. CONCLUSIONS: Bevacizumab significantly prolonged OS and PFS when added to first-line platinum-based chemotherapy in patients with advanced NSCLC; no unexpected toxicity was evident.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Neoplasias Pulmonares/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Feminino , Humanos , Masculino , Compostos Organoplatínicos/administração & dosagem , Análise de Sobrevida
5.
Lung Cancer ; 76(3): 410-5, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22266041

RESUMO

BACKGROUND: The impact of age on prognosis in advanced stage non-small cell lung cancer (NSCLC) may differ by sex. PATIENTS AND METHODS: Eligible patients (N=1590) from E1594, a 4-arm platinum-based chemotherapy trial, and E4599 (carboplatin/paclitaxel ± bevacizumab) chemotherapy arm were divided into male and female cohorts and separated into age groups of <60 or ≥60 years old. Eligible E4599 patients (N=850) were similarly separated by age and sex and by treatment (± bevacizumab). Survival was calculated separately for each cohort. RESULTS: The median survival time (MST) for women ≥60 years old treated with chemotherapy alone on E1594 and E4599 was 11.6 months versus 9.0 months for women <60 (p=0.03). MST was 7.4 and 8.3 months for men ≥60 and <60 years old respectively (NS). In E4599 the age <60 by bevacizumab treatment interaction was statistically significant (p=0.03) for women (younger had greater benefit), with no age effect in men. CONCLUSIONS: In this unplanned, exploratory subgroup analysis of advanced stage NSCLC ECOG trials, women ≥60 years old treated with chemotherapy live longer than men and younger women. In contrast, bevacizumab survival benefit was more pronounced in men of any age and in younger women on E4599.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Adulto , Fatores Etários , Idoso , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Bevacizumab , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Fatores Sexuais
6.
Br J Cancer ; 105(9): 1295-301, 2011 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-21979421

RESUMO

BACKGROUND: Plasma is an ionised gas that is typically generated in high-temperature laboratory conditions. However, recent progress in atmospheric plasmas has led to the creation of cold plasmas with ion temperature close to room temperature. METHODS: Both in-vitro and in-vivo studies revealed that cold plasmas selectively kill cancer cells. RESULTS: We show that: (a) cold plasma application selectively eradicates cancer cells in vitro without damaging normal cells; and (b) significantly reduces tumour size in vivo. It is shown that reactive oxygen species metabolism and oxidative stress responsive genes are deregulated. CONCLUSION: The development of cold plasma tumour ablation has the potential of shifting the current paradigm of cancer treatment and enabling the transformation of cancer treatment technologies by utilisation of another state of matter.


Assuntos
Melanoma Experimental/terapia , Gases em Plasma/uso terapêutico , Neoplasias da Bexiga Urinária/terapia , Animais , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Transplante de Neoplasias , Transdução de Sinais , Temperatura Cutânea , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
7.
Minerva Anestesiol ; 77(4): 468-9, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21483392

RESUMO

Clindamycin in a commonly used antibiotic, considered safe for oral, intravenous and intra-arterial use. We present a case of a patient that received an inadvertent injection clindamycin 600 mg in 4 mL through a radial arterial line. The patient presented signs and symptoms of vascular occlusion and despite aggressive pharmacological and medical treatment developed massive and severe tissue injury.


Assuntos
Antibacterianos/efeitos adversos , Clindamicina/efeitos adversos , Lesões do Sistema Vascular/induzido quimicamente , Idoso , Antibacterianos/administração & dosagem , Clindamicina/administração & dosagem , Dedos/irrigação sanguínea , Humanos , Infusões Intra-Arteriais , Isquemia/induzido quimicamente , Isquemia/patologia , Neoplasias Laríngeas/cirurgia , Laringectomia , Masculino , Dor/etiologia , Fluxo Sanguíneo Regional/fisiologia , Lesões do Sistema Vascular/patologia
8.
Clin Neuropathol ; 27(2): 78-82, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18402386

RESUMO

Ependymoblastomas are distinct embryonal tumors of the central nervous system reported only rarely in the literature. Most examples arise in young children under the age of 2 years, in the supratentorial compartment, and may or may not be related to the ventricular system. We report the case of a one-day-old infant who presented with a 6.4 x 5.6 x 3.5 cm ruptured buttock mass. Ultrasound demonstrated a solid mass at the base of the spine that displaced the bladder anteriorly with resultant hydronephrosis. Magnetic resonance images confirmed the presence of a solid mass surrounding the lower sacrum with an internal component partially encircling and deviating the rectum. Histopathological evaluation confirmed the diagnosis of ependymoblastoma. Of note, immunohistochemical analysis revealed diffuse staining with vimentin and patchy expression of synaptophysin, glial fibrillary acidic protein, neurofilament proteins, neuron-specific enolase, CD99 and nestin. On the 42nd day of life, chemotherapy was initiated with a modified Children's Oncology Group (COG) AGCT-01P1 (cyclophosphamide, cisplatin, 70% etoposide, no bleomycin) regimen. The authors describe their experience and review the literature, emphasizing that ependymoblastomas should be considered in the differential diagnosis of sacral masses in the newborn.


Assuntos
Tumores Neuroectodérmicos Primitivos/congênito , Tumores Neuroectodérmicos Primitivos/patologia , Região Sacrococcígea/anormalidades , Neoplasias de Tecidos Moles/congênito , Neoplasias de Tecidos Moles/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Imuno-Histoquímica , Recém-Nascido , Tumores Neuroectodérmicos Primitivos/terapia , Neoplasias de Tecidos Moles/terapia
9.
Child Care Health Dev ; 34(1): 104-10, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18171451

RESUMO

BACKGROUND: This study examined short-term efficacy, side effects and acceptability of a placebo treatment procedure designed to maintain children with attention deficit hyperactivity disorder (ADHD) on 50% of their usual stimulant dose. METHODS: An open-label prospective crossover trial was conducted in 26 children with ADHD, ages 7-15 years, stable on stimulant therapy, followed at a community-based developmental paediatrics ADHD clinic. Subjects were randomly assigned to one of two orders of experimental conditions: (1) baseline (100%) dose (1 week), then 50% dose (1 week), then 50% dose + placebo (1 week), or (2) baseline (100%), then 50% dose + placebo, then 50% dose. The inert nature of the placebo was fully disclosed to parent and child. Treatment was open-label for child, parents and physician, but single blind for teachers. Main outcome measures included weekly IOWA Conners parent and teacher rating scales, the Pittsburgh side effects rating scale (PSERS) and the Clinical Global Impressions (CGI) scale. RESULTS: Parent IOWA showed ADHD behaviour tended to remain the same when the dose of stimulant medication was reduced with placebo but to deteriorate when the dose was reduced without placebo. There were no significant differences between conditions on the Teacher IOWA. PSERS scores were higher at baseline than on 50% dose. On the CGI, there was a significant difference (P = 0.004) between the 50% dose and the 50% + placebo conditions. Individual subject analysis showed that eight subjects met criteria for responder. CONCLUSIONS: Results indicate that the open-label placebo treatment was acceptable and efficacious in the short term for some children.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Metilfenidato/uso terapêutico , Placebos/uso terapêutico , Adolescente , Criança , Estudos Cross-Over , Preparações de Ação Retardada/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Satisfação do Paciente , Projetos Piloto , Efeito Placebo , Estudos Prospectivos
10.
Child Care Health Dev ; 34(1): 111-20, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18171452

RESUMO

BACKGROUND: The purpose of this study was to examine the efficacy and acceptability of an open-label conditioned placebo dose reduction (CPDR) treatment in 70 children with attention deficit hyperactivity disorder (ADHD). This paper focuses on the qualitative data from the study. METHODS: Following a double-blind, crossover dose finding procedure to determine each subject's optimal dose of stimulant medication, subjects were randomized to the CPDR treatment or one of two control groups. Outcome measures included parent and teacher ratings of ADHD behaviours and stimulant side effects. Qualitative assessments were based on open-ended interviews of children and parents. Positive responders to CPDR and controls were followed for 3 months to assess persistence of treatment benefits. RESULTS: Children randomized to CPDR showed an excellent treatment response, well maintained over time. Parents and children were generally accepting of the treatment. Most parents reported treatment benefits and 80% of the children found the placebo to be useful. Full disclosure of the placebo to parents and children did not appear to negate the placebo's effectiveness. Participation effects and changes in caregiver behaviour may have contributed to positive treatment outcomes. CONCLUSIONS: Open-label use of placebos as part of CPDR treatment may represent an innovative, ethical way of harnessing the power of placebos in clinical therapeutics.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Metilfenidato/uso terapêutico , Satisfação do Paciente , Placebos/uso terapêutico , Adulto , Criança , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Relações Pais-Filho , Pais/psicologia , Efeito Placebo , Inquéritos e Questionários
11.
Apoptosis ; 11(1): 15-24, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16374545

RESUMO

Caspase 8 is a key apoptotic factor in the receptor/ligand apoptosis-signaling cascade. Absent caspase 8 expression is shown to correlate with poor prognosis in neuroblastoma. Paradoxically, the caspase 8 gene can produce as plice variant and novel inhibitor of itself-caspase 8l. The presence of caspase 8 alone in tumors may not necessarily portend a good prognosis. We sought to determine whether caspase 8l is present in neuroblastoma and whether over-expression of this protein could inhibit caspase 8-dependent apoptosis. Six of 6 histologically undifferentiated and 2 of 5 differentiated neuroblastoma tumors expressed the caspase 8l isoform, whereas caspase 8l was absent in 3 of 3 ganglioneuromas. Seven human neuroblastoma cell lines were surveyed. Two of the 5 cell lines that expressed caspase 8 also expressed the caspase 8l isoform and both were of a less differentiated neuronal phenotype. Over-expression of caspase 8l in cell lines afforded protection against TRAIL, but not against etoposide induced apoptosis. Conversely, blockade of Caspase 8l in cells that express this splice variant made them more sensitive to apoptosis induced cell death. We demonstrate the caspase 8l isoform is present in neuroblastoma and appears to be associated with undifferentiated cell lines and tumors. Furthermore, it suppresses caspase 8-dependent apoptosis.


Assuntos
Caspase 8/metabolismo , Neuroblastoma/enzimologia , Processamento Alternativo , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Sequência de Bases , Caspase 8/genética , Inibidores de Caspase , Diferenciação Celular , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Clonagem Molecular , Primers do DNA/genética , Expressão Gênica , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/genética , Isoenzimas/metabolismo , Neuroblastoma/genética , Neuroblastoma/patologia , Fenótipo , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Transfecção
12.
Neurology ; 62(6): 851-63, 2004 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-15037681

RESUMO

OBJECTIVE: The Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society develop practice parameters as strategies for patient management based on analysis of evidence. For this parameter the authors reviewed available evidence on the assessment of a child suspected of having cerebral palsy (CP), a nonprogressive disorder of posture or movement due to a lesion of the developing brain. METHODS: Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a four-tiered scheme of evidence classification. RESULTS: CP is a common problem, occurring in about 2 to 2.5 per 1,000 live births. In order to establish that a brain abnormality exists in children with CP that may, in turn, suggest an etiology and prognosis, neuroimaging is recommended with MRI preferred to CT (Level A). Metabolic and genetic studies should not be routinely obtained in the evaluation of the child with CP (Level B). If the clinical history or findings on neuroimaging do not determine a specific structural abnormality or if there are additional and atypical features in the history or clinical examination, metabolic and genetic testing should be considered (Level C). Detection of a brain malformation in a child with CP warrants consideration of an underlying genetic or metabolic etiology. Because the incidence of cerebral infarction is high in children with hemiplegic CP, diagnostic testing for coagulation disorders should be considered (Level B). However, there is insufficient evidence at present to be precise as to what studies should be ordered. An EEG is not recommended unless there are features suggestive of epilepsy or a specific epileptic syndrome (Level A). Because children with CP may have associated deficits of mental retardation, ophthalmologic and hearing impairments, speech and language disorders, and oral-motor dysfunction, screening for these conditions should be part of the initial assessment (Level A). CONCLUSIONS: Neuroimaging results in children with CP are commonly abnormal and may help determine the etiology. Screening for associated conditions is warranted as part of the initial evaluation.


Assuntos
Paralisia Cerebral/diagnóstico , Técnicas de Diagnóstico Neurológico/normas , Algoritmos , Encefalopatias Metabólicas/diagnóstico , Paralisia Cerebral/complicações , Paralisia Cerebral/genética , Criança , Diagnóstico Diferencial , Eletroencefalografia/normas , Epilepsia/complicações , Epilepsia/diagnóstico , Oftalmopatias/diagnóstico , Oftalmopatias/etiologia , Transtornos da Audição/diagnóstico , Transtornos da Audição/etiologia , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/etiologia , Transtornos da Linguagem/diagnóstico , Transtornos da Linguagem/etiologia , Imageamento por Ressonância Magnética/normas , Distúrbios da Fala/diagnóstico , Distúrbios da Fala/etiologia , Tomografia Computadorizada por Raios X/normas
13.
J Pediatr Surg ; 36(12): 1785-91, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11733907

RESUMO

BACKGROUND/PURPOSE: Apoptotic factors inducing or preventing cell death may intrinsically govern the behavior of some tumors. Survivin is a recently described member of the inhibitor of apoptosis protein (IAP) family, that is expressed in a cell cycle-dependent manner and is found in tumors of unfavorable histology. This study examines the presence of several apoptotic factors, including survivin, in neuroblastoma (NB) tumors. Clues to survivin's function in NB are provided by examining its association with behavior and cell dynamics in tumors and cell lines. METHODS: Expression of a panel of apoptosis factors were quantified in 15 NB and related tumors before chemotherapy and in 3 NB cell lines (NB7, NB10, and NB16). Survivin and other apoptotic factors, as well N-myc amplification in primary tumors was correlated with recurrent disease and outcome. Proliferation rate, apoptosis assays, cell cycle analysis, and drug- or immune-mediated cell death were assessed in cell lines and evaluated in the context of differential survivin and apoptosis gene expression. RESULTS: All 7 tumors that went on to recur expressed survivin, whereas expression was absent in all 8 tumors that went into remission. N-myc was amplified in 4 (57.1%) of the 7 recurrent tumors. Of the 8 tumors that were cured, Fas was expressed in 3 (38%), TRAIL-R1 in 6 (75%) and tumor necrosis factor (TNF)-R1 in 8 (100%), whereas these pro-apoptotic receptors were present in only 1 (14%), 1 (14%), and 4 (57%) of the 7 tumors that went on to recur, respectively. Of the 3 cell lines, NB10 expressed the least survivin, displayed the lowest proliferation index, and had the fewest number of cells in the G2/M (mitotic) phase of the cell cycle. Furthermore, NB10 also was most sensitive to TNF-related apoptosis-inducing ligand (TRAIL) or etoposide-induced cell death. CONCLUSIONS: In primary NB tumors, survivin expression was associated with tumors of high risk and unfavorable prognosis, whereas pro-apoptotic receptor expression was more abundant in tumors of favorable prognosis. In this small series, survivin expression appeared to be more predictive of recurrent disease than N-myc amplification. In cell lines, survivin expression was cell cycle dependent, and its expression was associated with greater proliferation rates and greater resistance to drug- or immune-mediated cell death. Survivin expression may become a useful prognostic marker in NB and could be a potential target for the treatment of this tumor. J Pediatr Surg 36:1785-1791.


Assuntos
Apoptose/genética , Proteínas Cromossômicas não Histona/antagonistas & inibidores , Proteínas Cromossômicas não Histona/biossíntese , Inibidores de Cisteína Proteinase/biossíntese , Neoplasias Renais/patologia , Proteínas Associadas aos Microtúbulos , Neuroblastoma/patologia , Proteínas Reguladoras de Apoptose , Biomarcadores Tumorais , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Inibidores de Cisteína Proteinase/metabolismo , Etoposídeo/farmacologia , Expressão Gênica , Humanos , Proteínas Inibidoras de Apoptose , Neoplasias Renais/diagnóstico , Neoplasias Renais/metabolismo , Glicoproteínas de Membrana/farmacologia , Proteínas de Neoplasias , Neuroblastoma/diagnóstico , Neuroblastoma/metabolismo , RNA Mensageiro/metabolismo , Survivina , Ligante Indutor de Apoptose Relacionado a TNF , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/farmacologia
14.
Cancer ; 92(10): 2639-47, 2001 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-11745199

RESUMO

BACKGROUND: Eastern Cooperative Oncology Group (ECOG) Study E1594 compared paclitaxel and cisplatin with three newer chemotherapy doublets in the treatment of patients with advanced nonsmall cell lung carcinoma (NSCLC). The accrual of patients with an ECOG performance status (PS) of 2 was discontinued due to a perceived rate of unacceptable toxicity. METHODS: Patients were stratified by PS and randomized to one of the following treatments: 1) paclitaxel (135 mg/m2) over 24 hours with cisplatin (75 mg/m2) on a 21-day cycle; 2) cisplatin (100 mg/m2) with gemcitabine (1 g/m2) on Days 1, 8, and 15 on a 28-day cycle; 3) cisplatin (75 mg/m2) with docetaxel (75 mg/m2) on a 21-day cycle; and 4) paclitaxel (225 mg/m2) over 3 hours with carboplatin (area under the curve, 6). All tests of statistical significance were two-sided. RESULTS: Sixty-eight patients with an ECOG PS of 2 were enrolled, and 64 patients were evaluable for toxicity and response. Fifty-six percent of 64 evaluable patients were male, and 81% had Stage IV disease. Grade 3-4 hematologic toxicities occurred in > 50% of the patients in each treatment group. Nonhematologic Grade 3-4 toxicities occurred significantly less often in the paclitaxel and carboplatin arm (P = 0.0032). The overall rate of toxicity did not differ significantly from the rate of toxicity in the PS-0 or PS-1 cohorts. There were 5 deaths (7.35%) among 68 patients with a PS of 2 during therapy; however, only 2 of those deaths were attributed to therapy. The overall response rate for the 64 evaluable patients was 14%. The overall median survival of all 68 patients with a PS of 2, as determined by an intent-to-treat analysis, was 4.1 months. CONCLUSIONS: Patients with advanced NSCLC and a PS of 2 experienced a large number of adverse reactions and overall poor survival. A comparison with patients with a PS of 0-1 suggests that these events and the shorter survival were related to disease process rather than treatment. Alternative strategies need to be explored with therapy specifically tailored for this group of patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/análogos & derivados , Índice de Gravidade de Doença , Taxoides , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Progressão da Doença , Docetaxel , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Seleção de Pacientes , Prognóstico , Fatores de Risco , Análise de Sobrevida , Gencitabina
15.
Mt Sinai J Med ; 68(6): 406-9, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11687871

RESUMO

A 36-year-old man with recent onset of unilateral peripheral 7th nerve paresis presented ten days later with involvement of the other side of his face. Physical examination was otherwise normal, and since blood tests and imaging were also normal, he was considered to have bilateral Bell's palsy. However, unexpected headaches and worsening of the paresis led to a gallium-67 scan which revealed uptake in the mediastinum. A repeat lumbar puncture revealed cells which were identified as lymphoblasts. T-cell acute lymphoblastic leukemia (T-ALL) was diagnosed, although the peripheral blood smear was normal. The differential diagnosis of bilateral 7th nerve palsy and of mononuclear cerebrospinal fluid pleocytosis is discussed, as well as this rare central nervous system presentation of acute leukemia.


Assuntos
Paralisia de Bell/complicações , Paralisia Facial/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Adulto , Diagnóstico Diferencial , Humanos , Masculino
16.
J Pediatr Surg ; 36(11): 1725-7, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11685713

RESUMO

PURPOSE: This study evaluates the multistaged extrathoracic esophageal elongation procedure performed on 12 babies with long gap esophageal atresia over 15 years. METHODS: Eight babies had pure esophageal atresia, 2 had proximal tracheoesophageal fistula (TEF), and 2 had distal TEF. The gaps ranged between 2 and 7 vertebral bodies. Proximal esophagostomy, TEF ligation, and gastrostomy were performed initially. The proximal esophagus is elongated 2 to 3 cm each time by translocating the esophagostomy distally along the anterior chest wall at 2- to 3-month intervals. Sham-fed milk is collected in an ostomy bag and refed via the gastrostomy. The definitive esophageal reconstruction is performed at 5 to 24 months of age. RESULTS: Only one elongation was required in 4 babies, 2 were needed in 5, 3 in 2, and 5 in 1 patient. All patients tolerated sham feeding well. After esophageal restoration, 3 patients had minor leakage. All (12 of 12) patients had anastomotic stenosis requiring multiple dilatations, of which, 3 needed resection of stricture. Eleven patients had gastroesophageal reflux that required fundoplication. Follow-up was possible in 11 patients for 4 months to 14 years after esophageal restoration. Seven early patients are eating normally. CONCLUSION: Multistaged extrathoracic esophageal elongation is effective in stretching the proximal esophagus to bridge 2 to 7 vertebral bodies.


Assuntos
Atresia Esofágica/cirurgia , Esôfago/cirurgia , Fístula Traqueoesofágica/cirurgia , Pré-Escolar , Esofagostomia , Feminino , Gastrostomia , Humanos , Lactente , Masculino , Reoperação
17.
Gynecol Oncol ; 83(1): 138-42, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11585426

RESUMO

BACKGROUND: Primitive neuroectodermal tumors (PNETs) are rare and potentially aggressive malignancies. CASE: A 24-year-old woman in her eighth week of pregnancy presented with a cervical mass. Tissue biopsy demonstrated poorly differentiated carcinosarcoma with neuroendocrine features. Immunohistochemical studies confirmed the diagnosis of PNET. Treatment included alternating courses of cyclophosphamide, adriamycin, vincristine (CAV) and ifosfamide, etoposide (IE). A radical hysterectomy with bilateral ovarian transposition and periaortic lymphadenectomy was performed with postoperative chemotherapy and radiotherapy. The patient remains disease free 2 years from therapy. CONCLUSION: This is a rare case of cervical PNET occurring in a pregnant patient. A review of the literature indicates that cervical PNET is distinguishable from uterine PNET. This tumor affects younger women and may have a different histogenesis. Pregnancy should not delay diagnosis of this potentially aggressive tumor.


Assuntos
Tumores Neuroectodérmicos Primitivos Periféricos/patologia , Complicações Neoplásicas na Gravidez/patologia , Neoplasias do Colo do Útero/patologia , Adulto , Terapia Combinada , Feminino , Humanos , Tumores Neuroectodérmicos Primitivos Periféricos/tratamento farmacológico , Tumores Neuroectodérmicos Primitivos Periféricos/cirurgia , Gravidez , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Complicações Neoplásicas na Gravidez/cirurgia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/cirurgia
18.
Invest New Drugs ; 19(3): 229-31, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11561679

RESUMO

Thirty patients with advanced renal cell carcinoma were treated on a phase 11 trial with altretamine. Altretamine was administered orally at a dosage of 260 mg/m2 days 1 through 14 with cycles repeated every 28 days. Nausea and vomiting were the most common toxicities. Ten percent (3 of 30) experienced Grade 3 gait abnormalities. None of the thirty evaluable patients achieved a complete or partial response. In summary, altretamine did not show antitumor activity in the treatment of advanced renal cell carcinoma.


Assuntos
Altretamine/uso terapêutico , Antineoplásicos Alquilantes/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Adulto , Idoso , Altretamine/efeitos adversos , Antineoplásicos Alquilantes/efeitos adversos , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento
19.
J Clin Anesth ; 13(1): 11-5, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11259888

RESUMO

STUDY OBJECTIVE: To determine the optimum time of administration of diclofenac in patients undergoing ambulatory knee arthroscopy: either preoperatively or postoperatively. DESIGN: Randomized, double-blind study. SETTING: Ambulatory surgical unit in a tertiary referral hospital. PATIENTS: 127 ASA physical status I and II patients undergoing ambulatory knee arthroscopy. INTERVENTIONS: Patients were randomized into three groups. The Preop group received 50 mg of potassium diclofenac orally 1 hour preoperatively and a placebo 30 minutes postoperatively. The Pre+postop group received 25 mg of potassium diclofenac 1 hour preoperatively and 25 mg diclofenac 30 minutes postoperatively. The Postop group received a placebo 1 hour before surgery and 50 mg of potassium diclofenac 30 minutes postoperatively. MEASUREMENTS AND MAIN RESULTS: The Postop group received a placebo 1 hour preoperatively and 50 mg of potassium diclofenac 30 min postoperatively. Postoperatively, patients used intravenous patient-controlled analgesia (PCA) with fentanyl. Total fentanyl consumption was recorded. During the recovery period, pain was assessed using a visual analog scale (VAS) at 30-minute intervals. Pain was assessed in both legs at rest, on flexion, and extension of the knee. There were no significant differences in pain scores either at rest or on movement of the operative knee among the Preop, Pre+postop, and Postop groups. The consumption of fentanyl via PCA showed no significant differences among the groups. CONCLUSIONS: There is no difference in pain relief whether diclofenac is given preoperatively or postoperatively in patients undergoing unilateral ambulatory knee arthroscopy. Preoperative and postoperative treatment with diclofenac potassium is equally effective.


Assuntos
Procedimentos Cirúrgicos Ambulatórios , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Diclofenaco/administração & dosagem , Diclofenaco/uso terapêutico , Dor Pós-Operatória/prevenção & controle , Adulto , Artroscopia , Feminino , Humanos , Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/psicologia , Período Pós-Operatório , Cuidados Pré-Operatórios
20.
Chest Surg Clin N Am ; 11(1): 133-64, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11253595

RESUMO

The management of advanced NSCLC remains a daunting challenge; however, new tools are available for treating this malignancy, and continued progress is likely. The future is bright, with a myriad of opportunities to exploit our ever-expanding knowledge of tumor biology. What is perhaps most needed, however, is development of new methods to prevent children and young adults from ever taking up the use of tobacco. In addition, clinicians need new techniques to assist those who are already addicted to escape from tobacco's death grip. Sadly, most users of tobacco still fail to recognize the dangers of their habit. This needs to change.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Animais , Terapia Genética , Humanos , Metástase Neoplásica , Seleção de Pacientes
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