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1.
Tob Control ; 32(e1): e95-e102, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-34615737

RESUMO

OBJECTIVES: Sensory methods use human senses to evaluate product attributes. This review provides an overview of the types of sensory methods used to evaluate the perception of flavour in tobacco and other nicotine-containing (ToNic) products and to discuss how sensory data could inform flavoured ToNic product policy. DATA SOURCES: PubMed, Embase and Web of Science. STUDY SELECTION: All peer-reviewed studies evaluating ToNic products using a sensory method published before 23 May 2020. DATA EXTRACTION: Two independent coders completed title/abstract and full-text screening to choose articles for inclusion (Cohen's kappa=0.85, strong agreement). Each coder completed data extraction on half the articles, recording relevant information (eg, sensory methods used, results). The coders categorised sensory methods and generated overarching themes. DATA SYNTHESIS: Of 110 articles identified, we included 29 articles containing 35 studies that used sensory methods to investigate ToNic products. The sensory methods included analytic methods such as discrimination and descriptive tests and hedonic methods such as liking tests. Six themes emerged regarding how sensory methods can be used to understand consumer perception and liking of ToNic products and to inform ToNic product policy. CONCLUSIONS: The identified studies highlight that sensory data can inform ToNic product policy. Analytic and sensory hedonic ratings can be used to assess a ToNic product's ability to promote addiction in the user (ie, abuse liability). Lastly, hedonic ratings can provide information to assess potential use behaviours.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Humanos , Nicotina , Nicotiana , Aromatizantes , Percepção
2.
Addict Behav ; 130: 107290, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35220150

RESUMO

INTRODUCTION: Flavored non-cigarette tobacco product use is widespread in the U.S. The availability of flavor options could be playing a role in recent increases in use, especially for non-cigarette tobacco products, among youth and young adults. Little is known about specific flavor preferences of youth and adult flavored tobacco product users, as well as how preferences may change over time. METHODS: This study analyzes PATH Study data from completed Wave 2 (2014-2015) and Wave 3 (2015-2016) youth (12-17 years), and adult (18 + years) interviews to estimate the prevalence of flavored non-cigarette tobacco product use. We assess flavor switching by examining changes between flavors and characteristics of those who changed flavors between waves. RESULTS: Across age groups, and at both waves, fruit-flavored products were the most frequently used flavor by past 30-day electronic nicotine delivery systems (ENDS), cigar, cigarillo, and hookah users. In the past 30 days, a higher proportion of youth and young adults used candy/sweets-flavored ENDS than adults. Among adult ENDS users, the odds of changing flavors were highest among younger users and decreased with increasing age. CONCLUSIONS: Flavored tobacco product use is prevalent across non-cigarette tobacco products. Stability in the number of flavors used, as well as specific flavors, is higher among adult tobacco users, while the use of multiple flavors, and change in specific flavor, is more prevalent among youth tobacco users. Additional longitudinal research can further examine the role flavors play in appeal, product trial, and switching.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Tabagismo , Adolescente , Aromatizantes , Humanos , Nicotiana , Adulto Jovem
3.
Toxicol Appl Pharmacol ; 434: 115813, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34838608

RESUMO

Serious adverse health effects have been reported with the use of vaping products, including neurologic disorders and e-cigarette or vaping product use-associated lung injury (EVALI). Vitamin E acetate, likely added as a diluent to cannabis-containing products, was linked to EVALI. Literature searches were performed on vitamin E and vitamin E acetate-associated neurotoxicity. Blood brain barrier (BBB) penetration potential of vitamin E and vitamin E acetate were evaluated using cheminformatic techniques. Review of the literature showed that the neurotoxic potential of inhalation exposures to these compounds in humans is unknown. Physico-chemical properties demonstrate these compounds are lipophilic, and molecular weights indicate vitamin E and vitamin E acetate have the potential for BBB permeability. Computational models also predict both compounds may cross the BBB via passive diffusion. Based on literature search, no experimental nonclinical studies and clinical information on the neurotoxic potential of vitamin E via inhalation. Neurotoxic effects from pyrolysis by-product, phenyl acetate, structurally analogous to vitamin E acetate, suggests vitamin E acetate has potential for central nervous system (CNS) impairment. Cheminformatic model predictions provide a theoretical basis for potential CNS permeability of these inhaled dietary ingredients suggesting prioritization to evaluate for potential hazard to the CNS.


Assuntos
Síndromes Neurotóxicas/patologia , Vaping , Vitamina E/administração & dosagem , Barreira Hematoencefálica/metabolismo , Humanos , Estrutura Molecular , Vitamina E/química , Vitamina E/metabolismo
6.
J Adolesc Health ; 66(1): 15-17, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31866055

RESUMO

PURPOSE: Electronic nicotine delivery systems (ENDS) use poses significant and avoidable health risks to young people. Until recently, seizures were most often associated with cases of liquid nicotine ingestion. METHODS: We examined 122 voluntary reports of seizures (n = 114) and neurological symptoms (syncope, n = 7; and tremor, n = 1) in 123 ENDS users (one report contained information on two users) received by the Food and Drug Administration between December 1, 2010, and June 30, 2019. RESULTS: The median age (interquartile range) of users was 20 years (17-27); 67% of reports were in youth and young adults aged 14-24 years. Fifty-one (41%) reported other underlying medical conditions, including previous history of anxiety (n = 11), attention deficit hyperactivity disorder (n = 7), seizure (n = 6), and depression (n = 5). Of the 79 reports with available information, 67 (85%) reported seizure occurred within 24 hours of last use; 49 (62%) reported seizure within 30 minutes. The potential impact of concomitant use of marijuana or cannabidiol oil could not be evaluated from the eight reports that mentioned concomitant use. CONCLUSIONS: Findings suggest an association between ENDS use and seizures. Additional information will help to clarify the relationship between ENDS use and seizures and to understand how product attributes such as nicotine content, formulation, quantity, and other ingredients or contaminants may contribute to seizures. It is important that health care providers ask about ENDS use when evaluating neurological symptoms and that users, parents, school personnel, and health care providers report adverse experiences involving tobacco products to Food and Drug Administration via the Safety Reporting Portal (www.safetyreporting.hhs.gov).


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Nicotina/efeitos adversos , Convulsões/induzido quimicamente , Vaping/efeitos adversos , Adolescente , Adulto , Cannabis , Humanos , Produtos do Tabaco , Adulto Jovem
7.
Tob Control ; 2016 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-26962042

RESUMO

BACKGROUND: Electronic nicotine delivery system (ENDS)-associated overheating, fire or explosion (OH/F/EXP) events have occurred since at least 2009. OBJECTIVE: To identify the number and nature of ENDS OH/F/EXP events in the USA. METHODS: Center for Tobacco Products (CTP) scientists searched for event reports among five US federal agencies, scientific literature and media outlets. FINDINGS: 100 reference sources identified 92 OH/F/EXP events in the USA, of which 45 (49%) injured 47 people, and 67 (73%) involved property damage beyond the product. Events were identified in media outlets (n=50; 54%) and reported to four agencies (n=42; 46%). The report rate peaked at an average of six reports per month in late 2013 with a smaller peak of three to four reports per month in the second quarter of 2015. All reports were incomplete and events exhibited variability. International events in three countries are mentioned, and international responses to events are summarised. CONCLUSIONS: The scope, causes and trajectory of ENDS OH/F/EXP events remain incompletely defined. Some events have resulted in life-threatening injury, permanent disfigurement or disability, and major property damage, suggesting the need for ongoing surveillance and risk mitigation. More comprehensive reporting could assist future analyses and may help to identify root causes and contributors to the OH/F/EXP events.

9.
Tob Control ; 23 Suppl 2: ii47-53, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24732164

RESUMO

OBJECTIVE: A systematic review was conducted to evaluate the impact of human factors (HF) on the risks associated with electronic cigarettes (e-cigarettes) and to identify research gaps. HF is the evaluation of human interactions with products and includes the analysis of user, environment and product complexity. Consideration of HF may mitigate known and potential hazards from the use and misuse of a consumer product, including e-cigarettes. METHODS: Five databases were searched through January 2014 and publications relevant to HF were incorporated. Voluntary adverse event (AE) reports submitted to the US Food and Drug Administration (FDA) and the package labelling of 12 e-cigarette products were analysed. RESULTS: No studies specifically addressing the impact of HF on e-cigarette use risks were identified. Most e-cigarette users are smokers, but data on the user population are inconsistent. No articles focused specifically on e-cigarette use environments, storage conditions, product operational requirements, product complexities, user errors or misuse. Twelve published studies analysed e-cigarette labelling and concluded that labelling was inadequate or misleading. FDA labelling analysis revealed similar concerns described in the literature. AE reports related to design concerns are increasing and fatalities related to accidental exposure and misuse have occurred; however, no publications evaluating the relationship between AEs and HF were identified. CONCLUSIONS: The HF impacting e-cigarette use and related hazards are inadequately characterised. Thorough analyses of user-product-environment interfaces, product complexities and AEs associated with typical and atypical use are needed to better incorporate HF engineering principles to inform and potentially reduce or mitigate the emerging hazards associated with e-cigarette products.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina/efeitos adversos , Medição de Risco , Humanos , Rotulagem de Produtos
10.
Proc Natl Acad Sci U S A ; 109(47): 19403-7, 2012 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-23129637

RESUMO

No conventional therapy exists for salivary hypofunction in surviving head and neck cancer patients with Radiation Therapy Oncology Group late grade 2-3 toxicity. We conducted a phase I clinical trial to test the safety and biologic efficacy of serotype 5, adenoviral-mediated aquaporin-1 cDNA transfer to a single previously irradiated parotid gland in 11 subjects using an open label, single-dose, dose-escalation design (AdhAQP1 vector; four dose tiers from 4.8 × 10(7) to 5.8 × 10(9) vector particles per gland). Treated subjects were followed at scheduled intervals. Multiple safety parameters were measured and biologic efficacy was evaluated with measurements of parotid salivary flow rate. Symptoms were assessed with a visual analog scale. All subjects tolerated vector delivery and study procedures well over the 42-d study period reported. No deaths, serious adverse events, or dose-limiting toxicities occurred. Generally, few adverse events occurred, and all were considered mild or moderate. No consistent changes were found in any clinical chemistry and hematology parameters measured. Objective responses were seen in six subjects, all at doses <5.8 × 10(9) vector particles per gland. Five of these six subjects also experienced subjective improvement in xerostomia. AdhAQP1 vector delivery to a single parotid gland was safe and transfer of the hAQP1 cDNA increased parotid flow and relieved symptoms in a subset of subjects.


Assuntos
Adenoviridae/genética , Aquaporina 1/genética , Aquaporina 1/uso terapêutico , DNA Complementar/genética , Terapia Genética , Lesões por Radiação/terapia , Doenças das Glândulas Salivares/terapia , Idoso , Citratos , Gálio , Terapia Genética/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/genética , Cintilografia , Doenças das Glândulas Salivares/diagnóstico por imagem , Doenças das Glândulas Salivares/etiologia , Doenças das Glândulas Salivares/fisiopatologia
11.
Otolaryngol Head Neck Surg ; 147(4): 744-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22597578

RESUMO

OBJECTIVE: To understand the audiologic and vestibular toxicities associated with adoptive cell immunotherapy (ACI) targeting pigment-pathway antigens on melanoma and to investigate the use of intratympanic steroid injections in the treatment of these toxicities. STUDY DESIGN: Prospective nonrandomized study. SETTING: Tertiary clinical research center. METHODS: Thirty-two patients with progressive metastatic melanoma who failed conventional therapy underwent ACI with T cells genetically modified to target MART-1 (n = 18) or gp100 (n = 14). All patients received serial audiometric testing. Vestibular testing was performed on patients with vestibular complaints. Patients with significant deficits received intratympanic steroid injections. RESULTS: Of 32 patients, 15 had no hearing change, 9 had mild hearing loss, and 8 had moderate hearing loss following treatment. Ten patients received intratympanic steroid injections for mild (n = 2) or moderate (n = 7) hearing loss or for significant imbalance (n = 1). Of those with mild hearing loss (n = 9), all but 1 recovered to pretreatment hearing levels. Four of 8 patients with moderate hearing loss recovered to baseline hearing levels, and 4 had partial recovery. All 7 patients with posttreatment vestibular complaints had demonstrable vestibular dysfunction. Three of these patients demonstrated recovery to normal vestibular function. The number of modified T cells infused for therapy correlated with the degree of audiovestibular deficit. CONCLUSION: Adoptive cell immunotherapy targeting pigment-pathway cell proteins, a novel therapy for melanoma, can induce hearing loss and vestibular dysfunction. The presumed mechanism of autoimmune attack on normal melanocytes in the cochlear stria vascularis and in the vestibular organs demonstrates the importance of melanocytes in normal inner ear function.


Assuntos
Imunidade Adaptativa , Perda Auditiva/etiologia , Imunoterapia/efeitos adversos , Melanoma/imunologia , Melanoma/terapia , Adulto , Audiometria de Tons Puros , Distribuição de Qui-Quadrado , Progressão da Doença , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunoterapia/métodos , Interleucina-2/uso terapêutico , Antígeno MART-1/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Testes de Função Vestibular , Antígeno gp100 de Melanoma/imunologia
12.
ORL Head Neck Nurs ; 30(1): 6-15, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22474919

RESUMO

This is a companion paper to two previous publications on recommended practices for cleaning and reprocessing flexible endoscopes used in Otolaryngology (Burlingame, Arcilla, & McDermott, 2008; Adams & Baker, 2010). In this paper we capture and expand upon the audience question and answer session in which the Society of Otorhinolaryngology and Head-Neck Nurse (SOHN)--endorsed the Association of periOperative Registered Nurses (AORN) recommended practices were presented to the SOHN membership (Adams & Waddington, September, 2010). We include additional background information to assist readers in understanding some of the science behind the recommendations and share successful implementation strategies from Otorhinolaryngology (ORL) outpatient nurses and published references.


Assuntos
Desinfecção/normas , Endoscópios/microbiologia , Contaminação de Equipamentos/prevenção & controle , Controle de Infecções/métodos , Otolaringologia/instrumentação , Guias de Prática Clínica como Assunto , Biofilmes , Reutilização de Equipamento , Humanos , Otorrinolaringopatias/enfermagem , Sociedades de Enfermagem
13.
PLoS One ; 6(10): e26639, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22066003

RESUMO

We investigated auditory perception and cognitive processing in individuals with chronic tinnitus or hearing loss using functional magnetic resonance imaging (fMRI). Our participants belonged to one of three groups: bilateral hearing loss and tinnitus (TIN), bilateral hearing loss without tinnitus (HL), and normal hearing without tinnitus (NH). We employed pure tones and frequency-modulated sweeps as stimuli in two tasks: passive listening and active discrimination. All subjects had normal hearing through 2 kHz and all stimuli were low-pass filtered at 2 kHz so that all participants could hear them equally well. Performance was similar among all three groups for the discrimination task. In all participants, a distributed set of brain regions including the primary and non-primary auditory cortices showed greater response for both tasks compared to rest. Comparing the groups directly, we found decreased activation in the parietal and frontal lobes in the participants with tinnitus compared to the HL group and decreased response in the frontal lobes relative to the NH group. Additionally, the HL subjects exhibited increased response in the anterior cingulate relative to the NH group. Our results suggest that a differential engagement of a putative auditory attention and short-term memory network, comprising regions in the frontal, parietal and temporal cortices and the anterior cingulate, may represent a key difference in the neural bases of chronic tinnitus accompanied by hearing loss relative to hearing loss alone.


Assuntos
Discriminação Psicológica , Perda Auditiva/fisiopatologia , Rede Nervosa/fisiopatologia , Análise e Desempenho de Tarefas , Zumbido/fisiopatologia , Audiometria de Tons Puros , Comportamento , Demografia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
14.
Clin Cancer Res ; 17(17): 5755-64, 2011 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-21750205

RESUMO

PURPOSE: A phase I clinical trial and molecular correlative studies were conducted to evaluate preclinical evidence for combinatorial activity of the proteasome inhibitor bortezomib, the epidermal growth factor receptor (EGFR) inhibitor cetuximab, and radiation therapy. EXPERIMENTAL DESIGN: Patients with radiotherapy-naive stage IV or recurrent squamous cell carcinoma of the head and neck (SCCHN) were studied. Escalating doses of bortezomib (0.7, 1.0, and 1.3 mg/m²) were given intravenously twice weekly on days 1, 4, 8, and 11, every 21 days, with weekly cetuximab beginning 1 week prior and concurrently with intensity-modulated radiotherapy, delivered in 2 Gy fractions to 70 to 74 Gy. Molecular effects were examined in serial serum and SCCHN tumor specimens and the cell line UMSCC-1. RESULTS: Seven patients were accrued before the study was terminated when five of six previously untreated patients with favorable prognosis oropharyngeal SCCHN progressed within 1 year (progression-free survival = 4.8 months; 95% CI, 2.6-6.9). Three patients each received bortezomib 0.7 or 1.0 mg/m², without dose-limiting toxicities; one patient treated at 1.3 mg/m² was taken off study due to recurring cetuximab infusion reaction and progressive disease (PD). Expected grade 3 toxicities included radiation mucositis (n = 4), dermatitis (n = 4), and rash (n = 1). SCCHN-related cytokines increased in serial serum specimens of patients developing PD (P = 0.029). Bortezomib antagonized cetuximab- and radiation-induced cytotoxicity, degradation of EGFR, and enhanced prosurvival signal pathway activation in SCCHN tumor biopsies and UMSCC-1. CONCLUSIONS: Combining bortezomib with cetuximab and radiation therapy showed unexpected early progression, evidence for EGFR stabilization, increased prosurvival signaling, and SCCHN cytokine expression, warranting avoidance of this combination.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ácidos Borônicos/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Pirazinas/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose , Biomarcadores Tumorais/análise , Ácidos Borônicos/administração & dosagem , Bortezomib , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Cetuximab , Terapia Combinada/efeitos adversos , Citocinas/biossíntese , Citocinas/sangue , Progressão da Doença , Receptores ErbB/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Proteases/administração & dosagem , Inibidores de Proteases/efeitos adversos , Pirazinas/administração & dosagem , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Fatores de Transcrição/biossíntese , Resultado do Tratamento
15.
Int J Radiat Oncol Biol Phys ; 77(2): 447-54, 2010 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-19879702

RESUMO

PURPOSE: Epidermal growth factor receptor (EGFR) overexpression in head-and-neck squamous cell carcinoma (HNSCC) stimulates tumor cell proliferation, inhibits apoptosis, and increases chemotherapy and radiation resistance. We examined the toxicity, safety and the effects on EGFR signaling in tumor biopsy samples from patients with locally advanced HNSCC treated with the EGFR signaling inhibitor gefitinib (GEF) combined with weekly intravenous paclitaxel (PAC) and radiation therapy (RT). METHODS AND MATERIALS: This was a pilot Phase I dose-escalation study. Eligibility included Stage III to IVB HNSCC, age >or=18 years, no prior RT or chemotherapy, adequate organ function, and informed consent. Endpoints included determination of maximum tolerated dose (MTD) and analysis of treatment effect on EGFR signaling, tumor cell proliferation, and apoptosis in biopsy samples. RESULTS: Ten patients were treated. The MTD of this combination was GEF 250 mg/d with PAC 36 mg/m(2) intravenously weekly x 6 with concurrent RT. Grade 3/4 toxicities included prolonged (>8 weeks) stomatitis (7 patients), infection (2 patients), and interstitial pneumonitis (1 patient). There were five complete responses (CR) and two partial responses (PR). Of 7 patients undergoing serial biopsies, only 1 patient demonstrated a reduction in phosphorylated EGFR, decreased downstream signaling, and reduced cellular proliferation after initiating GEF. CONCLUSIONS: Inhibition of EGFR by GEF was observed in only one of seven tumors studied. The addition of GEF to PAC and RT did not appear to improve the response of locally advanced HNSCC compared with our prior experience with PAC and RT alone. This treatment appeared to delay recovery from stomatitis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Receptores ErbB/antagonistas & inibidores , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Apoptose , Carcinoma de Células Escamosas/patologia , Proliferação de Células , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/metabolismo , Feminino , Gefitinibe , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Infecções/etiologia , Doenças Pulmonares Intersticiais/etiologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Projetos Piloto , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Dosagem Radioterapêutica , Indução de Remissão , Estomatite/etiologia
16.
Blood ; 114(3): 535-46, 2009 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-19451549

RESUMO

Gene therapy of human cancer using genetically engineered lymphocytes is dependent on the identification of highly reactive T-cell receptors (TCRs) with antitumor activity. We immunized transgenic mice and also conducted high-throughput screening of human lymphocytes to generate TCRs highly reactive to melanoma/melanocyte antigens. Genes encoding these TCRs were engineered into retroviral vectors and used to transduce autologous peripheral lymphocytes administered to 36 patients with metastatic melanoma. Transduced patient lymphocytes were CD45RA(-) and CD45RO(+) after ex vivo expansion. After infusion, the persisting cells displayed a CD45RA(+) and CD45RO(-) phenotype. Gene-engineered cells persisted at high levels in the blood of all patients 1 month after treatment, responding patients with higher ex vivo antitumor reactivity than nonresponders. Objective cancer regressions were seen in 30% and 19% of patients who received the human or mouse TCR, respectively. However, patients exhibited destruction of normal melanocytes in the skin, eye, and ear, and sometimes required local steroid administration to treat uveitis and hearing loss. Thus, T cells expressing highly reactive TCRs mediate cancer regression in humans and target rare cognate-antigen-containing cells throughout the body, a finding with important implications for the gene therapy of cancer. This trial was registered at www.ClinicalTrials.gov as NCI-07-C-0174 and NCI-07-C-0175.


Assuntos
Antígenos de Neoplasias/imunologia , Terapia Genética/métodos , Melanoma/terapia , Receptores de Antígenos de Linfócitos T/administração & dosagem , Transferência Adotiva/efeitos adversos , Transferência Adotiva/métodos , Adulto , Animais , Autoantígenos/imunologia , Feminino , Vetores Genéticos , Perda Auditiva/etiologia , Humanos , Transfusão de Linfócitos/efeitos adversos , Transfusão de Linfócitos/métodos , Linfócitos/metabolismo , Masculino , Melanócitos/imunologia , Melanoma/complicações , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Especificidade do Receptor de Antígeno de Linfócitos T , Transdução Genética , Transplante Autólogo , Resultado do Tratamento , Uveíte/etiologia
17.
Int J Radiat Oncol Biol Phys ; 74(4): 1040-6, 2009 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-19117692

RESUMO

PURPOSE: To report the long-term outcomes and toxicity of a regimen of infusion paclitaxel delivered concurrently with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Between 1995 and 1999, 35 patients with nonmetastatic, Stage III or IV squamous cell carcinoma of the head and neck were treated with three cycles of paclitaxel as a 120-h continuous infusion beginning on Days 1, 21, and 42, concurrent with radiotherapy. The initial 16 patients received 105 mg/m(2)/cycle, and the subsequent 19 patients received 120 mg/m(2)/cycle. External beam radiotherapy was delivered to a dose of 70.2-72 Gy at five fractions weekly. Patients were followed to evaluate the disease outcomes and late toxicity of this regimen. RESULTS: The median follow-up for all patients was 56.5 months. The median survival was 56.5 months, and the median time to local recurrence was not reached. Of the 35 patients, 15 (43%) developed hypothyroidism. Of the 33 patients who underwent percutaneous endoscopic gastrostomy tube placement, 11 were percutaneous endoscopic gastrostomy tube dependent until death or their last follow-up visit. Also, 5 patients (14%) required a tracheostomy until death, and 3 (9%) developed a severe esophageal stricture. All evaluated long-term survivors exhibited salivary hypofunction. Fibrosis in the radiation field occurred in 24 patients (69%). CONCLUSION: The results of our study have shown that concurrent chemoradiotherapy with a 120-h infusion of paclitaxel provides long-term local control and survival in patients with squamous cell carcinoma of the head and neck. Xerostomia, hypothyroidism, esophageal and pharyngeal complications, and subcutaneous fibrosis were common long-term toxicities; however, the vast majority of toxicities were grade 1 or 2.


Assuntos
Antineoplásicos Fitogênicos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Paclitaxel , Adulto , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Terapia Combinada/métodos , Esquema de Medicação , Estudos de Viabilidade , Feminino , Fibrose , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Estudos Prospectivos , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Pele/efeitos da radiação , Taxa de Sobrevida , Resultado do Tratamento
18.
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