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Tratamento odontológico realizado em pacientes com diagnóstico de câncer atendidos no Serviço de Odontologia Oncológica do UNACON do Hospital Geral de Palmas/Tocantins, no período de abril de 2011 a dezembro de 2016 / Dental treatment performed in patients diagnosed with cancer attended at the UNACON Oncology Dentistry Service of the General Hospital of Palmas / Tocantins, from april 2011 to december 2016Tosin, Daniela Carvalho 20 February 2018 (has links)
No Brasil, o Sistema de Saúde é Universalista, com o tratamento integral gratuito ao paciente com câncer, cujo direito é assegurado por Lei e regulamentado pelo Ministério da Saúde / Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA), por meio de Decreto Presidencial e Portarias. A habilitação e credenciamento de Hospitais em Unidades ou Centros de Alta Complexidade em Oncologia segue critérios rígidos, que determina como sendo obrigatória a presença do Cirurgião-Dentista na equipe multiprofissional e multidisciplinar na oncoterapia. O tratamento odontológico é compulsório e imprescindível na terapia antineoplásica, para prevenir e tratar as complicações orais: hemorragia, infecção, mucosite oral, xerostomia, cárie de radiação, trismo, alterações periodontais, osteonecrose avascular, osteorradionecrose; que podem levar à interrupção da oncoterapia, acarretando um aumento considerável nos custos da terapia implementada, a piora da qualidade de vida, e em alguns casos, podendo levar o paciente a óbito. O protocolo de cuidados orais na oncoterapia é normatizado e padronizado pelo INCA. Desta forma, foi realizado estudo do tratamento odontológico em pacientes com diagnóstico de câncer atendidos no Serviço de Odontologia Oncológica do UNACON do Hospital Geral de Palmas/Tocantins, no período de abril de 2011 a dezembro de 2016. Os dados foram obtidos de forma individualizada e estruturados segundo Variáveis Demográficas (VD), Procedimento Odontológico (PO), Procedimento Odontológico por Dente (POD) e Outras Variáveis de Interesse (OVI). O impacto financeiro de PO e POD foi avaliado pela comparação entre a tabela SIGTAP do Sistema Único de Saúde (SUS) e a tabela VRPO/SOESP (Valores Referenciais para Procedimentos Odontológicos/Sindicato dos Odontologistas do Estado de São Paulo). A maior incidência de pacientes foi observada na 5ª década de vida, com tendência à proporção homem/mulher de 1:1. Foram realizados 910 procedimentos preventivos/profilaxia/atividade educativa; 1826 raspagens supra e subgengival e aplicação tópica de flúor por hemiarcada; 932 restaurações de uma e duas faces com resina fotopolimerizável; 909 exodontias; 2746 sessões de laserterapia de baixa potência. O impacto financeiro mostrou uma defasagem significativa da Tabela SIGTAP/SUS. O estudo realizado revela a importância de uma base de dados estruturada para o registro do tratamento odontológico realizado em pacientes com diagnóstico de câncer atendidos no Sistema Único de Saúde; para que com isso seja possível fomentar, nos Sistemas de Saúde no Mundo, a elaboração e padronização de protocolo de cuidados orais na terapia antineoplásica, e o planejamento dos recursos humanos e financeiros destinados ao tratamento odontológico nos pacientes oncológicos. / In Brazil, the Health System is Universalist, with free comprehensive treatment for the cancer patient, whose right is guaranteed by Law and regulated by the Ministry of Health / National Cancer Institute José Alencar Gomes da Silva (INCA), through a Presidential Decree and Ordinances. The accreditation of Hospitals in Units or Centers of High Complexity in Oncology follows rigid criteria, which determines as mandatory the presence of the Dentist in the multiprofessional and multidisciplinary team in oncotherapy. Dental treatment is compulsory and essential in antineoplastic therapy to prevent and treat oral complications: hemorrhage, infection, oral mucositis, xerostomia, radiation caries, trismus, periodontal changes, avascular osteonecrosis, osteorradionecrosis; which can lead to interruption of oncotherapy, leading to a considerable increase in the costs of the therapy implemented, worsening of quality of life, and in some cases, leading to death. The protocol of oral care in oncotherapy is standardized by INCA. In this way, a study of the dental treatment was carried out in patients diagnosed with cancer attended at the UNACON Oncological Dentistry Service of the General Hospital of Palmas / Tocantins, from april 2011 to december 2016. Data were obtained individually and structured according to Demographics Variables (VD), Dental Procedure (PO), Dental Procedure by Tooth (POD) and Other Variables of Interest (OVI). The financial impact of PO and POD was evaluated by comparing the SIGTAP table of the Unified Health System (SUS) and the VRPO / SOESP table (Reference Values for Dental Procedures / Union of Dental Practitioners of the State of São Paulo). The highest incidence of patients was observed in the 5th decade of life, with a tendency to male to female ratios of 1: 1. Nine hundred and ten (910) preventive procedures / prophylaxis / educational activity were carried out; 1826 supra and subgingival scaling and topical application of fluoride by hemiarcate; 932 single and double sided restorations with photopolymerizable resin; 909 exodontia; 2746 sessions of low power laser therapy. The financial impact showed a significant lag in the SIGTAP / SUS Table. The study reveals the importance of a structured database for the registry of dental treatment performed in patients diagnosed with cancer treated in the Unified Health System; so that it is possible to promote, in the World Health Systems, the elaboration and standardization of oral care protocol in antineoplastic therapy, and the planning of human and financial resources for dental treatment in cancer patients.
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Sinais e sintomas vestibulares em pacientes que receberam tratamento com drogas derivadas da platina / Vestibular signs and symptoms in patients after platinum based chemotherapySandra Maria Deutschmann 02 August 2016 (has links)
A toxicidade vestibular pode ser definida como danos que uma substância química causa sobre a estrutura e a função vestibular. Entre as drogas que podem causar a vestibulotoxicidade estão os agentes antineoplásicos como os derivados da platina. OBJETIVO: Identificar a frequência de ocorrência de alteração vestibular em pacientes oncológicos tratados com derivados da platina, os sinais e sintomas vestibulares nestes pacientes, e se a alteração vestibular pré-existente exacerba os sintomas eméticos durante a quimioterapia com derivados da platina. METODOLOGIA: Amostra foi composta por pacientes adultos com câncer que realizaram tratamento com drogas derivadas da platina. O protocolo para o monitoramento vestibular foi composto pelo questionário Dizziness Handicap Inventory (DHI) Brasileiro, Testes da Função Vestibular (manobra de Dix-Hallpike e vecto-eletronistagmografia) e pela descrição de sintomas eméticos e tontura durante a quimioterapia e avaliação vestibular. RESULTADOS: Quarenta e oito pacientes realizaram a avaliação vestibular pré-quimioterapia, sendo que 23 (48%) apresentaram avaliação vestibular dentro da normalidade. Dezesseis pacientes submeteram-se ao monitoramento vestibular com avaliação antes e após tratamento, sendo que após o tratamento dois pacientes (12,5%) apresentaram avaliação vestibular dentro da normalidade e 14 (87,5%) apresentaram algum tipo de alteração vestibular, evidenciada somente pela prova calórica. Nenhum paciente referiu queixas vestibulares ao DHI na avaliação pré-tratamento, assim como quase todos os pacientes, exceto um, na avaliação pós tratamento. Apenas um (6,3%) com avaliação vestibular alterada pós-tratamento apresentou grau leve no DHI. A dose de cisplatina entre os pacientes que mostraram piora do quadro vestibular variou entre 160 e 400 mg/m² e dois pacientes foram tratados com carboplatina com dose de 2306 mg/m² e 1801 mg/m². Não houve diferença de manifestação dos sintomas eméticos/tontura durante a avaliação vestibular ou após quimioterapia entre os pacientes com e sem alteração vestibular prévia. Entretanto, os pacientes que referiram sintomas eméticos durante os ciclos de quimioterapia foram aqueles que manifestaram maior desconforto na PC, independente da dose de quimioterapia ou da alteração vestibular. CONCLUSÃO: Alteração vestibular ou a modificação do quadro vestibular ocorreu em 50% dos pacientes com câncer tratados com derivados da platina. O sinal mais frequente de alteração nos testes vestibulares foi a hiporreflexia à prova calórica, sem sintomas vestibulares relatados na vida diária destes pacientes. As alterações vestibulares pré-existentes não exacerbaram os sintomas eméticos durante a quimioterapia / Vestibular toxicity may be defined as a damage that chemical substances cause on the structure and the function of the vestibular system. Among the drugs that may cause vestibulotoxicity there are antineoplastic agents, such as those derived from platinum. OBJECTIVE: To identify the frequency of occurrence of vestibular alterations in cancer patients treated with platinum-based chemotherapy; the vestibular signs and symptoms in these patients, and whether the pre-existing vestibular alterations exacerbate emetic symptoms during chemotherapy with platinum-based drugs. METHODS: The sample was composed of adults who were treated of the cancer with platinum-based chemotherapy. The vestibular monitoring protocol involved the Brazilian Dizziness Handicap Inventory (DHI), Vestibular Function Tests (positioning nystagmus with Dix-Hallpike maneuver and vectoelectronystagmography) and the description of emetic symptoms and dizziness during chemotherapy and vestibular evaluation. RESULTS: Forty-eight subjects performed the pre-treatment vestibular evaluation, and 23 of them (48%) presented vestibular assessment within the normal range. Sixteen patients underwent the vestibular monitoring evaluation before and after treatment: after the treatment two patients (12.5%) showed normal vestibular assessment while 14 (87.5%) showed a vestibular disorder, basically in the caloric tests, but the alteration was considered a modification in their baseline stage in eight patients (50%). None of the patients reported complaints in the pre-treatment assessment, with a DHI scores within the normal range, as well as all the patients, except one, in the post treatment assessment (81,3%). Only one patient (6.3%) had a score above normal (mild complaint) with altered vestibular evaluation in the post treatment assessment. The dose of cisplatin among these patients who had a modification in the vestibular function varied from 160 to 400 mg/m² and two patients were treated with carboplatin with do of 2306 mg/m² and 1801 mg/m². There was no difference of emetic symptoms/dizziness during the chemotherapy or the vestibular evaluation among patients with or without previous vestibular alterations. However, patients who reported more emetic symptoms during chemotherapy cycles were those who showed greater discomfort in the caloric test, regardless of the dosage of chemotherapy or vestibular alteration. CONCLUSION: Vestibular alterations or modification of the baseline alteration were found in 50% of cancer patients treated with platinum-based chemotherapy. The most common sign of vestibular alteration in the vestibular tests was the hiporeflexia at the caloric test with no reported symptoms in their daily life. The preexisting vestibular alterations did not exacerbate emetic symptoms during chemotherapy
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Investigation of unique marine environments for microbial natural productsThornburg, Christopher C. 25 March 2013 (has links)
Metagenomics has revealed that the marine microbial biosphere is immensely more diverse than originally considered, and is an almost untapped reservoir for the potential discovery of microbial natural products. Despite numerous advances in culturing, biosynthetic engineering and genomic-based screening efforts to uncover much of this diversity in relatively accessible environments, a high rediscovery rate has resulted in the investigation of unique, relatively unexplored ecosystems harboring phylogenetically diverse communities of marine organisms. The focus of this research was to establish a culture repository of microorganisms collected from the Red Sea and from deep-sea hydrothermal vents, and to assess their biosynthetic potential for the production of new chemical scaffolds. Cultivation of marine cyanobacteria from the Red Sea has led to the identification of five new cyclic depsipeptides, apratoxin H, grassypeptolides D and E, Ibu-epidemethoxylyngbyastin 3 and leptochelin, the latter possessing a unique chemical scaffold capable of binding metals. A collection of deep-sea hydrothermal vent sediment and microbial mat samples led to the isolation of 64 unique bacterial strains, with eight assigned as members of the order Actinomycetales. Importantly, these isolates, along with a collection of deep-vent invertebrates and microbes, have led to the development of methods for the collection, culturing and biological screening of organisms from this extreme environment for future natural products research. / Graduation date: 2013
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Head and neck cancer : factors affecting tumour growth /Sundelin, Kaarina, January 2007 (has links) (PDF)
Diss. (sammanfattning) Linköping : Linköpings universitet, 2007. / Härtill 4 uppsatser.
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Rb-Raf-1 interaction as a therapeutic target for proliferative disordersKinkade, Rebecca. January 2008 (has links)
Dissertation (Ph.D.)--University of South Florida, 2008. / Title from PDF of title page. Document formatted into pages; contains 181 pages. Includes bibliographical references.
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Clinical studies on adrenocortical tumours using [11C]-metomidate positron emission tomographyHennings, Joakim, January 2009 (has links)
Diss. (sammanfattning) Uppsala : Uppsala universitet, 2009.
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Tratamento odontológico realizado em pacientes com diagnóstico de câncer atendidos no Serviço de Odontologia Oncológica do UNACON do Hospital Geral de Palmas/Tocantins, no período de abril de 2011 a dezembro de 2016 / Dental treatment performed in patients diagnosed with cancer attended at the UNACON Oncology Dentistry Service of the General Hospital of Palmas / Tocantins, from april 2011 to december 2016Daniela Carvalho Tosin 20 February 2018 (has links)
No Brasil, o Sistema de Saúde é Universalista, com o tratamento integral gratuito ao paciente com câncer, cujo direito é assegurado por Lei e regulamentado pelo Ministério da Saúde / Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA), por meio de Decreto Presidencial e Portarias. A habilitação e credenciamento de Hospitais em Unidades ou Centros de Alta Complexidade em Oncologia segue critérios rígidos, que determina como sendo obrigatória a presença do Cirurgião-Dentista na equipe multiprofissional e multidisciplinar na oncoterapia. O tratamento odontológico é compulsório e imprescindível na terapia antineoplásica, para prevenir e tratar as complicações orais: hemorragia, infecção, mucosite oral, xerostomia, cárie de radiação, trismo, alterações periodontais, osteonecrose avascular, osteorradionecrose; que podem levar à interrupção da oncoterapia, acarretando um aumento considerável nos custos da terapia implementada, a piora da qualidade de vida, e em alguns casos, podendo levar o paciente a óbito. O protocolo de cuidados orais na oncoterapia é normatizado e padronizado pelo INCA. Desta forma, foi realizado estudo do tratamento odontológico em pacientes com diagnóstico de câncer atendidos no Serviço de Odontologia Oncológica do UNACON do Hospital Geral de Palmas/Tocantins, no período de abril de 2011 a dezembro de 2016. Os dados foram obtidos de forma individualizada e estruturados segundo Variáveis Demográficas (VD), Procedimento Odontológico (PO), Procedimento Odontológico por Dente (POD) e Outras Variáveis de Interesse (OVI). O impacto financeiro de PO e POD foi avaliado pela comparação entre a tabela SIGTAP do Sistema Único de Saúde (SUS) e a tabela VRPO/SOESP (Valores Referenciais para Procedimentos Odontológicos/Sindicato dos Odontologistas do Estado de São Paulo). A maior incidência de pacientes foi observada na 5ª década de vida, com tendência à proporção homem/mulher de 1:1. Foram realizados 910 procedimentos preventivos/profilaxia/atividade educativa; 1826 raspagens supra e subgengival e aplicação tópica de flúor por hemiarcada; 932 restaurações de uma e duas faces com resina fotopolimerizável; 909 exodontias; 2746 sessões de laserterapia de baixa potência. O impacto financeiro mostrou uma defasagem significativa da Tabela SIGTAP/SUS. O estudo realizado revela a importância de uma base de dados estruturada para o registro do tratamento odontológico realizado em pacientes com diagnóstico de câncer atendidos no Sistema Único de Saúde; para que com isso seja possível fomentar, nos Sistemas de Saúde no Mundo, a elaboração e padronização de protocolo de cuidados orais na terapia antineoplásica, e o planejamento dos recursos humanos e financeiros destinados ao tratamento odontológico nos pacientes oncológicos. / In Brazil, the Health System is Universalist, with free comprehensive treatment for the cancer patient, whose right is guaranteed by Law and regulated by the Ministry of Health / National Cancer Institute José Alencar Gomes da Silva (INCA), through a Presidential Decree and Ordinances. The accreditation of Hospitals in Units or Centers of High Complexity in Oncology follows rigid criteria, which determines as mandatory the presence of the Dentist in the multiprofessional and multidisciplinary team in oncotherapy. Dental treatment is compulsory and essential in antineoplastic therapy to prevent and treat oral complications: hemorrhage, infection, oral mucositis, xerostomia, radiation caries, trismus, periodontal changes, avascular osteonecrosis, osteorradionecrosis; which can lead to interruption of oncotherapy, leading to a considerable increase in the costs of the therapy implemented, worsening of quality of life, and in some cases, leading to death. The protocol of oral care in oncotherapy is standardized by INCA. In this way, a study of the dental treatment was carried out in patients diagnosed with cancer attended at the UNACON Oncological Dentistry Service of the General Hospital of Palmas / Tocantins, from april 2011 to december 2016. Data were obtained individually and structured according to Demographics Variables (VD), Dental Procedure (PO), Dental Procedure by Tooth (POD) and Other Variables of Interest (OVI). The financial impact of PO and POD was evaluated by comparing the SIGTAP table of the Unified Health System (SUS) and the VRPO / SOESP table (Reference Values for Dental Procedures / Union of Dental Practitioners of the State of São Paulo). The highest incidence of patients was observed in the 5th decade of life, with a tendency to male to female ratios of 1: 1. Nine hundred and ten (910) preventive procedures / prophylaxis / educational activity were carried out; 1826 supra and subgingival scaling and topical application of fluoride by hemiarcate; 932 single and double sided restorations with photopolymerizable resin; 909 exodontia; 2746 sessions of low power laser therapy. The financial impact showed a significant lag in the SIGTAP / SUS Table. The study reveals the importance of a structured database for the registry of dental treatment performed in patients diagnosed with cancer treated in the Unified Health System; so that it is possible to promote, in the World Health Systems, the elaboration and standardization of oral care protocol in antineoplastic therapy, and the planning of human and financial resources for dental treatment in cancer patients.
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Estudo de fase I/II de Erlotinib (OZI-774) combinado com radioterapia e cisplatina em pacientes com carcinoma epidermóide de cabeça e pescoço, localmente avançado / Phase I/II study of erlotinib combined with cisplatin and radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neckDaniel Herchenhorn 19 October 2009 (has links)
Propósito: Erlotinib, um inibidor oral da Tirosina Quinase posicionada junto ao domínio intracelular do EGFR, é uma droga ativa contra Carcinoma de Células Escamosas de Cabeça e Pescoço (CECCP) avançado e possivelmente possui sinergismo com a quimioterapia e radioterapia. O objetivo deste trabalho foi avaliar a dose adequada, a segurança e eficácia do Erlotinib associado à combinação padrão de quimioterapia e radioterapia no CECCP localmente avançado. Pacientes e Métodos: Pacientes com CECCP localmente avançado são o fundamento deste ensaio clínico de FaseI/II, cujo tratamento consistiu da combinação de Cisplatina 100mg/m² intra-venoso (iv), administrada nos dias 8, 29 e 50 do tratamento; e radioterapia na dose de 70.2Gy administrada em 39 frações a partir do Dia 8. Durante a fase I do estudo a dose de Erlotinib foi escalonada (50 mg, 100mg e 150mg por via oral, tomado uma vez ao dia) em consecutivas coortes de três pacientes. Toxicidade dose limitante (TDL) foi avaliada pelos critérios do CTCAE e do RTOG e foi definida como qualquer evento grau 4 que requeresse interrupção da radioterapia. A fase II do estudo foi iniciada 8 semanas após o último registro de paciente na fase I. Resultados: Nove pacientes foram recrutados na fase I e 28 na fase II; todos foram avaliados para análise de segurança e eficácia. Nenhuma TDL ocorreu durante o escalonamento na fase I e foi recomendada para fase II a dose de 150mg ao dia de erlotinib. As toxicidades não hematológicas observadas mais freqüentes foram náusea e vômitos, disfagia, estomatite, xerostomia, dermatite no campo de radiação, rash acneiforme, e diarréia. Dos 31 pacientes que usaram Erlotinib na dose de 150mg/dia, 23 (74%, 95% CI 56,8% - 86,3%) obtiveram resposta completa, 3 apresentaram doença residual que foi resgatada imediatamente com cirurgia e ficaram sem evidência de doença, 4 permaneceram com doença residual inoperável, e 1 morreu de sepse durante o tratamento. Com seguimento médio de 37 meses, a sobrevida livre de progressão em 3 anos (SLP) e sobrevida global (SG) foram de 61 e 72%, respectivamente. Embora sem significância estatística, análise de subgrupo estratificando pacientes pela presença do rash acneiforme demonstrou uma tendência a maior SG naqueles com rash (SG em 3 anos 50 versus 79%, p=0.061). Conclusão: A combinação de erlotinib/ cisplatina/ radioterapia parece ser segura e tem atividade encorajadora em CECCP localmente avançado. Esses dados serão confirmados em estudos randomizados já iniciados / Purpose: Erlotinib, an oral tyrosine-kinase inhibitor, is active against squamous cell carcinoma of the head and neck (HNSCC) and possibly has a synergistic interaction with chemotherapy and radiotherapy. We investigated the safety and efficacy of erlotinib added to cisplatin and radiotherapy in locally advanced HNSCC. Patients and Methods: Phase I/II trial of cisplatin 100 mg/m2 on days 8, 29 and 50; and radiotherapy 70 Gy starting on day 8. During the phase I, erlotinib dose was escalated (50 mg, 100 mg and 150 mg) in consecutive cohorts of three patients, starting on day 1 and continued during radiotherapy. Dose-limiting toxicity (DLT) was defined as any grade 4 event requiring radiotherapy interruptions. Phase II initiated 8 weeks after the last phase I enrollment. Results: Nine patients were accrued in the phase I and 28 in the phase II; all were evaluable for efficacy and safety. No DLT occurred in the phase I and the recommended phase II dose was 150mg. The most frequent non-hematological toxicities were nausea/vomiting, dysphagia, stomatitis, xerostomia and in-field dermatitis, acneiform rash, and diarrhea. Of the 31 patients in the erlotinib 150 mg daily dose, 23 (74%, 95% CI 56.8% 86.3%) had a complete response, 3 were disease-free after salvage surgery, 4 had an inoperable residual disease, and 1 died of sepsis during treatment. With a median 37 months follow-up, the 3-year progression-free and overall survival were 61 and 72% respectively. Conclusion: This combination appears safe, has encouraging activity and deserves further studies in locally advanced HNSCC
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Oncolytic viruses cancer therapyZeicher, Marc 21 October 2008 (has links)
Wild-type viruses with intrinsic oncolytic capacity in human includes DNA viruses like some autonomous parvoviruses and many RNA viruses. Recent advances in molecular biology have allowed the design of several genetically modified viruses, such as adenovirus and herpes simplex virus that specifically replicate in, and kill tumor cells. However, still several hurdles regarding clinical limitations and safety issues should be overcome before this mode of therapy can become of clinical relevance. It includes limited virus spread in tumor masses, stability of virus in the blood, trapping within the liver sinusoids, transendothelial transfer, and/or vector diffusion of viral particles to tumor cells, limited tumor transduction, immune-mediated inactivation or destruction of the virus. For replication-competent vectors without approved antiviral agents, suicide genes might be used as fail-safe mechanism. Cancer stem cells are a minor population of tumor cells that possess the stem cell property of self-renewal. Therefore, viruses that target the defective self-renewal pathways in cancer cells might lead to improved outcomes.<p>In this thesis, data we generated in the field of oncolytic autonomous parvoviruses are presented.<p>We replaced capsid genes by reporter genes and assessed expression in different types of human cancer cells and their normal counterparts, either at the level of whole cell population, (CAT ELISA) or at the single cell level, (FACS analysis of Green Fluorescent Protein). Cat expression was substantial (up to 10000 times background) in all infected tumor cells, despite variations according to the cell types. In contrast, no gene expression was detected in similarly infected normal cells, (with the exception of an expression slightly above background in fibroblasts.). FACS analysis of GFP expression revealed that most tumor cells expressed high level of GFP while no GFP positive normal cells could be detected with the exception of very few (less than 0.1%) human fibroblast cells expressing high level of GFP. We also replace capsid genes by genes coding for the costimulatory molecules B7-1 and B7-2 and show that, upon infection with B7 recombinant virions, only tumor cells display the costimulatory molecules and their immunogenicity was increased without any effect on normal cells. Using a recombinant MVM containig the Herpes Simplex thymidine kinase gene, we could get efficient killing of most tumor cell types in the presence of ganciclovir, whithout affecting normal proliferating cells. We also produced tetracycline inducible packaging cell lines in order to improve recombinant vectors yields. The prospects and limitations of these different strategies will be discussed.<p>An overview is given of the general mechanisms and genetic modifications by which oncolytic viruses achieve tumor cell-specific replication and antitumor efficacy. However, as their therapeutic efficacy in clinical trials is still not optimal, strategies are evaluated that could further enhance the oncolytic potential of conditionally replicating viruses in conjunction with other standard therapies. <p>Another exciting new area of research has been the harnessing of naturally tumor-homing cells as carrier cells to deliver oncolytic viruses to tumors. The trafficking of these tumor-homing cells (stem cells, immune cells and cancer cells), which support proliferation of the viruses, is mediated by specific chemokines and cell adhesion molecules and we are just beginning to understand the roles of these molecules. Finally, we will explore some ways deserving further study in order to be able to utilize various oncolytic viruses for effective cancer treatment. <p><p> / Doctorat en sciences, Spécialisation biologie moléculaire / info:eu-repo/semantics/nonPublished
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Estudo de fase I/II de Erlotinib (OZI-774) combinado com radioterapia e cisplatina em pacientes com carcinoma epidermóide de cabeça e pescoço, localmente avançado / Phase I/II study of erlotinib combined with cisplatin and radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neckHerchenhorn, Daniel 19 October 2009 (has links)
Propósito: Erlotinib, um inibidor oral da Tirosina Quinase posicionada junto ao domínio intracelular do EGFR, é uma droga ativa contra Carcinoma de Células Escamosas de Cabeça e Pescoço (CECCP) avançado e possivelmente possui sinergismo com a quimioterapia e radioterapia. O objetivo deste trabalho foi avaliar a dose adequada, a segurança e eficácia do Erlotinib associado à combinação padrão de quimioterapia e radioterapia no CECCP localmente avançado. Pacientes e Métodos: Pacientes com CECCP localmente avançado são o fundamento deste ensaio clínico de FaseI/II, cujo tratamento consistiu da combinação de Cisplatina 100mg/m² intra-venoso (iv), administrada nos dias 8, 29 e 50 do tratamento; e radioterapia na dose de 70.2Gy administrada em 39 frações a partir do Dia 8. Durante a fase I do estudo a dose de Erlotinib foi escalonada (50 mg, 100mg e 150mg por via oral, tomado uma vez ao dia) em consecutivas coortes de três pacientes. Toxicidade dose limitante (TDL) foi avaliada pelos critérios do CTCAE e do RTOG e foi definida como qualquer evento grau 4 que requeresse interrupção da radioterapia. A fase II do estudo foi iniciada 8 semanas após o último registro de paciente na fase I. Resultados: Nove pacientes foram recrutados na fase I e 28 na fase II; todos foram avaliados para análise de segurança e eficácia. Nenhuma TDL ocorreu durante o escalonamento na fase I e foi recomendada para fase II a dose de 150mg ao dia de erlotinib. As toxicidades não hematológicas observadas mais freqüentes foram náusea e vômitos, disfagia, estomatite, xerostomia, dermatite no campo de radiação, rash acneiforme, e diarréia. Dos 31 pacientes que usaram Erlotinib na dose de 150mg/dia, 23 (74%, 95% CI 56,8% - 86,3%) obtiveram resposta completa, 3 apresentaram doença residual que foi resgatada imediatamente com cirurgia e ficaram sem evidência de doença, 4 permaneceram com doença residual inoperável, e 1 morreu de sepse durante o tratamento. Com seguimento médio de 37 meses, a sobrevida livre de progressão em 3 anos (SLP) e sobrevida global (SG) foram de 61 e 72%, respectivamente. Embora sem significância estatística, análise de subgrupo estratificando pacientes pela presença do rash acneiforme demonstrou uma tendência a maior SG naqueles com rash (SG em 3 anos 50 versus 79%, p=0.061). Conclusão: A combinação de erlotinib/ cisplatina/ radioterapia parece ser segura e tem atividade encorajadora em CECCP localmente avançado. Esses dados serão confirmados em estudos randomizados já iniciados / Purpose: Erlotinib, an oral tyrosine-kinase inhibitor, is active against squamous cell carcinoma of the head and neck (HNSCC) and possibly has a synergistic interaction with chemotherapy and radiotherapy. We investigated the safety and efficacy of erlotinib added to cisplatin and radiotherapy in locally advanced HNSCC. Patients and Methods: Phase I/II trial of cisplatin 100 mg/m2 on days 8, 29 and 50; and radiotherapy 70 Gy starting on day 8. During the phase I, erlotinib dose was escalated (50 mg, 100 mg and 150 mg) in consecutive cohorts of three patients, starting on day 1 and continued during radiotherapy. Dose-limiting toxicity (DLT) was defined as any grade 4 event requiring radiotherapy interruptions. Phase II initiated 8 weeks after the last phase I enrollment. Results: Nine patients were accrued in the phase I and 28 in the phase II; all were evaluable for efficacy and safety. No DLT occurred in the phase I and the recommended phase II dose was 150mg. The most frequent non-hematological toxicities were nausea/vomiting, dysphagia, stomatitis, xerostomia and in-field dermatitis, acneiform rash, and diarrhea. Of the 31 patients in the erlotinib 150 mg daily dose, 23 (74%, 95% CI 56.8% 86.3%) had a complete response, 3 were disease-free after salvage surgery, 4 had an inoperable residual disease, and 1 died of sepsis during treatment. With a median 37 months follow-up, the 3-year progression-free and overall survival were 61 and 72% respectively. Conclusion: This combination appears safe, has encouraging activity and deserves further studies in locally advanced HNSCC
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