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1.
Lancet Oncol ; 22(2): 256-266, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33476595

RESUMO

BACKGROUND: The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery has been associated with encouraging survival results in some patients with colorectal peritoneal metastases who were eligible for complete macroscopic resection. We aimed to assess the specific benefit of adding HIPEC to cytoreductive surgery compared with receiving cytoreductive surgery alone. METHODS: We did a randomised, open-label, phase 3 trial at 17 cancer centres in France. Eligible patients were aged 18-70 years and had histologically proven colorectal cancer with peritoneal metastases, WHO performance status of 0 or 1, a Peritoneal Cancer Index of 25 or less, and were eligible to receive systemic chemotherapy for 6 months (ie, they had adequate organ function and life expectancy of at least 12 weeks). Patients in whom complete macroscopic resection or surgical resection with less than 1 mm residual tumour tissue was completed were randomly assigned (1:1) to cytoreductive surgery with or without oxaliplatin-based HIPEC. Randomisation was done centrally using minimisation, and stratified by centre, completeness of cytoreduction, number of previous systemic chemotherapy lines, and timing of protocol-mandated systemic chemotherapy. Oxaliplatin HIPEC was administered by the closed (360 mg/m2) or open (460 mg/m2) abdomen techniques, and systemic chemotherapy (400 mg/m2 fluorouracil and 20 mg/m2 folinic acid) was delivered intravenously 20 min before HIPEC. All individuals received systemic chemotherapy (of investigators' choosing) with or without targeted therapy before or after surgery, or both. The primary endpoint was overall survival, which was analysed in the intention-to-treat population. Safety was assessed in all patients who received surgery. This trial is registed with ClinicalTrials.gov, NCT00769405, and is now completed. FINDINGS: Between Feb 11, 2008, and Jan 6, 2014, 265 patients were included and randomly assigned, 133 to the cytoreductive surgery plus HIPEC group and 132 to the cytoreductive surgery alone group. After median follow-up of 63·8 months (IQR 53·0-77·1), median overall survival was 41·7 months (95% CI 36·2-53·8) in the cytoreductive surgery plus HIPEC group and 41·2 months (35·1-49·7) in the cytoreductive surgery group (hazard ratio 1·00 [95·37% CI 0·63-1·58]; stratified log-rank p=0·99). At 30 days, two (2%) treatment-related deaths had occurred in each group.. Grade 3 or worse adverse events at 30 days were similar in frequency between groups (56 [42%] of 133 patients in the cytoreductive surgery plus HIPEC group vs 42 [32%] of 132 patients in the cytoreductive surgery group; p=0·083); however, at 60 days, grade 3 or worse adverse events were more common in the cytoreductive surgery plus HIPEC group (34 [26%] of 131 vs 20 [15%] of 130; p=0·035). INTERPRETATION: Considering the absence of an overall survival benefit after adding HIPEC to cytoreductive surgery and more frequent postoperative late complications with this combination, our data suggest that cytoreductive surgery alone should be the cornerstone of therapeutic strategies with curative intent for colorectal peritoneal metastases. FUNDING: Institut National du Cancer, Programme Hospitalier de Recherche Clinique du Cancer, Ligue Contre le Cancer.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/patologia , Terapia Combinada/efeitos adversos , Procedimentos Cirúrgicos de Citorredução , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , França , Humanos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/secundário , Resultado do Tratamento
2.
BMC Surg ; 21(1): 35, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33435947

RESUMO

BACKGROUND: Guidelines do not recommend surgery for patients with oligometastatic disease from esophagogastric adenocarcinoma (EGAC), although some studies suggest a more favorable survival. We analyzed the outcome of oligometastatic EGAC receiving FLOT chemotherapy followed by surgery. METHODS: The data of patients with either pre-therapeutic, post-neoadjuvant or intraoperative clinical diagnosis of oligometastatic EGAC were extracted from a prospective database of the 2009-2018 treatment period. 48 consecutive patients were identified with oligometastatic disease, who underwent perioperative chemotherapy plus surgery. We retrospectively analyzed surgical outcome and overall survival. RESULTS: The overall 5-year survival was 18%. 12 patients (25%) with pre-therapeutic oligometastatic EGAC, who had no histologic vital tumor evidence of metastases after surgery had a survival rate of 48% compared to an 11% 5-year survival rate of 36 patients (75%), who had histologic vital tumor metastatic evidence after FLOT chemotherapy and surgical resection (p = 0.012). The survival rates after R0, R1 and R2 (non-resected metastases) resection were 21% (n = 33), 0% (n = 4) and 17% (n = 11), respectively (p = 0.273). CONCLUSION: Oligometastatic EGAC is associated with poor overall survival even after complete resection of all tumor manifestations. The subgroup of patients with a complete histologic response of metastatic lesions to neoadjuvant FLOT shows 5-year survival rates similar to non-metastatic EGAC. Trial registration Not applicable.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Terapia Neoadjuvante/métodos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Junção Esofagogástrica , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Taxoides/administração & dosagem , Resultado do Tratamento
3.
Int J Nanomedicine ; 16: 269-281, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33469286

RESUMO

Background: Rapamycin is a promising agent for treating tumors, but clinical applications of rapamycin are limited due to its poor water solubility and low bioavailability. This paper constructs a liposome delivery system for rapamycin to improve the effect in treating colorectal cancer. Methods: We prepared the rapamycin liposomes using the ethanol injection method. The cellular uptake and biodistribution were detected by LC-MS and in vivo imaging system. MTT assay, transwell migration experiment, flow cytometry, and Western blot analysis evaluated the antitumor effect of rapamycin liposomes in vitro. Furthermore, HCT-116 tumor-bearing mice were used to assess the therapeutic efficacy of rapamycin liposomes in vivo. Results: The prepared rapamycin liposomes had a particle size of 100±5.5 nm and with a narrow size distribution. In vitro cellular uptake experiments showed that the uptake of rapamycin liposomes by colorectal cells was higher than that of free rapamycin. Subsequently, in vivo imaging experiments also demonstrated that rapamycin liposomes exhibited higher tumor accumulation. Therefore, the ability of rapamycin liposomes to inhibit tumor proliferation, migration and to induce tumor apoptosis is superior to that of free rapamycin. We also demonstrated in vivo good antitumor efficacy of the rapamycin liposomes in HCT-116 xenograft mice. In addition, rapamycin liposomes and 5-FU can synergistically improve the efficacy of colorectal cancer via the Akt/mTOR and P53 pathways. Conclusion: Collectively, rapamycin liposomes are a potential treatment for colorectal cancer, as it not only improves rapamycin's antitumor effect but also synergistically enhances 5-FU's chemotherapy effect.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/uso terapêutico , Sirolimo/administração & dosagem , Sirolimo/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/patologia , Sinergismo Farmacológico , Fluoruracila/administração & dosagem , Fluoruracila/farmacologia , Humanos , Concentração Inibidora 50 , Lipossomos , Camundongos , Tamanho da Partícula , Transdução de Sinais/efeitos dos fármacos , Sirolimo/farmacologia , Distribuição Tecidual , Ensaio Tumoral de Célula-Tronco , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Notas enferm. (Córdoba) ; 20(36): 70-77, nov.2020.
Artigo em Espanhol | LILACS, BDENF - Enfermagem, BINACIS, UNISALUD | ID: biblio-1140731

RESUMO

Introducción. Este espacio es acerca del empleo de bombas elastoméricas en la administración de citostáticos de infusión continua con pacientes oncológicos que reciben tratamiento endovenoso, de infusión continua en el domicilio, mejorando así la calidad de vida del paciente, (esta experiencia es sólo en relación a aplicación de 5 fluorouracilo).Material y método: Al inicio, la primera dosis de quimioterapia, se realiza en el internado común para observar la tolerancia a la medicación, y en la segunda o tercera aplicación se realiza la misma en el hospital de día la primera parte del esquema, y luego se realiza la conexión de la bomba elastomérica que infundirá durante 46hs con el 5 fluorouracilo. El paciente asistirá al hospital oncológico para realizar la desconexión. Nuestro rol enfermero de contención y capacitación es necesario y así poder asegurar el buen manejo del dispositivo y brindar seguridad a los pacientes, para que logren un cuidado autónomo, seguro y eficaz. Para tal fin se les provee un instructivo. Poseer catéter implantable es requisito obligatorio para esta modalidad. Beneficios encontrados: es portátil y ergonómico, Mejora la movilidad y autocuidado, tasa de infusión exacta. Características de seguridad, que incluyan la protección del reservorio frente a posibles daños; Descomprimimos las internaciones, reducimos la espera de camas para internación de pacientes. Reducimos el uso de bombas comunes eléctricas del internado quedando a disponibilidad para otros pacientes hospitalizados. Dificultades halladas: Desconocimiento del paciente sobre el insumo (bomba). Inseguridad del paciente al encontrarse en el hogar por primera vez. Trámites burocráticos para autorización de la bomba. Conclusión: esta implementación innovadora requiere aún más aprendizaje, contamos con el apoyo del Departamento de Enfermería y la jefatura del servicio del Hospital de Día Oncológico, para el uso de las bombas. Para esta experiencia se utilizaron 10 bombas elastoméricas. Experiencia práctica, positiva para el paciente, además él mismo se compromete con su autocuidado y tratamiento, se logra evitar las exposiciones nosocomiales minimizando así los riesgos de contagios. Reducimos el uso de bombas comunes eléctricas del internado quedando a disposición para otros pacientes que lo requieran. Descomprimimos el internado común permitiendo así contar con más camas y mayor fluidez para satisfacer la demanda de internación de pacientes con otras patologías[AU]


Introduction. This space is about the use of elastomeric pumps in the administration of cytostatics of continuous infusion with cancer patients who receive intravenous treatment, of continuous infusion of qmt at home, thus improving the quality of life of the patient, (this experience is only in relation to to application of 5 fluorouracil). Material and method: At the beginning, the first dose of chemotherapy is carried out in the common boarding school to observe the tolerance to the medication, and in the second or third application it is carried out in the day hospital the first part of the scheme, and then the elastomeric pump is connected, which will infuse for 46 hours with 5 fluorouracil. The patient will attend the cancer hospital at hour 46 to perform the disconnection. Our nursing role of containment and training is necessary in order to ensure the proper handling of the device and provide safety to patients, so that they achieve autonomous, safe and effective care. For this purpose, an instruction manual is provided. Having an implantable catheter is a mandatory requirement for this modality; Benefits found: It is portable and ergonomic, Improves mobility and self-care, exact infusion rate. Safety features, including protection of the reservoir against possible damage; We decompressed hospitalizations, we reduced the wait for beds for patient admission. We reduced the use of common electric pumps in the internship, making them available for other hospitalized patients. Difficulties encountered: Lack of knowledge of the patient about the input (pump). Patient insecurity when being at home for the first time. Bureaucratic procedures for authorization of the pump. Conclusion. This innovative implementation requires even more learning, we have the support of the Nursing Department and the head of the Oncology Day Hospital service, for the use of the pumps. For this experiment 10 elastomeric pumps were used. Practical experience, positive for the patient, he also commits himself to self-care and treatment, it is possible to avoid nosocomial exposures, thus minimizing the risks of contagion. We reduce the use of common electric pumps in the internship by being available for other patients who require it. We decompress the common boarding school, thus allowing us to have more beds and greater fluidity to satisfy the demand for hospitalization of patients with other pathologies[AU]


Introdução. Este espaço trata da utilização de bombas elastoméricas na administração de citostáticos de infusão contínua em pacientes oncológicos que recebem tratamento intravenoso, de infusão contínua de qmtem casa, melhorando assim a qualidade de vida do paciente, (esta experiência é apenas emrelação a aplicação de 5 fluorouracil). Material e método: No início, a primeira dose de quimioterapia é realizada no colégio interno comum para observar a tolerânciaao medicamento, e na segunda ou terceira aplicação é realizada em hospital dia a primeira parte do esquema, e em seguida, a bomba elastomérica é conectada, que fará a infusão de 5 fluorouracil por 46 horas. O paciente comparecerá ao hospital oncológico na hora 46 para realizar o desligamento. Nosso papel de enfermagem de contenção e treinamento é necessário a fim de garantir o correto manuseio do dispositivo e dar segurançaaos pacientes, para que alcancem um cuidado autônomo, seguro e eficaz. Para tal, é fornecido um manual de instruções. Ter Um catéter implantável é requisito obrigatório para esta modalidade; Benefícios encontrados: É portátil e ergonômico, melhora a mobilidade e o autocuidado, taxa de infusão exata. Recursos de segurança, incluindo proteção do reservatório contra possíveis danos; Descomprimimos internações, reduzimos a espera por leitos para admissão de pacientes .Reduzimos o uso de bombas elétricas comuns no internato, disponibilizando-as para outros pacientes internados. Dificuldades encontradas: Falta de conhecimento do paciente sobre o insumo (bomba). Insegurança do paciente ao estar em casa pela primeira vez. Procedimentos burocráticos para autorização da bomba. Conclusão. Esta implementação inovadora exige ainda mais aprendizagem, contamos com o apoio do Departamento de Enfermagem e do chefe do serviço de Oncologia-Dia Hospital, para utilização das bombas. Para esta experiencia foram utilizadas 10 bombas elastoméricas. Experiência prática, positiva para o paciente, ele também se compromete com o autocuidado e o tratamento, sendo possível evitar exposições nosocomiais, minimizando assim os riscos de contágio. Reduzimos o uso de bombas elétricas comuns no estágio, disponibilizando para outros pacientes que necessitem. Descomprimimos o internato comum, permitindo assim ter Mais leitos e maior fluidez para atender a demanda de internação de pacientes como utras patologias[AU]


Assuntos
Humanos , Autocuidado , Bombas de Infusão , Citostáticos/administração & dosagem , Assistência Ambulatorial , Fluoruracila/administração & dosagem
6.
J Vasc Interv Radiol ; 31(10): 1600-1608, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32861569

RESUMO

PURPOSE: To compare survival after CT-guided percutaneous irreversible electroporation (IRE) and folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) chemotherapy versus FOLFIRINOX only in patients with locally advanced pancreatic cancer (LAPC). MATERIALS AND METHODS: A post hoc comparison was performed of data derived from a prospective IRE-FOLFIRINOX cohort and a retrospective FOLFIRINOX-only cohort. All patients received a minimum of 3 cycles of FOLFIRINOX for LAPC and were considered eligible for CT-guided percutaneous IRE. Endpoints included overall survival (OS), local and distant progression-free survival, and time to progression (TTP) and were compared using stratified Kaplan-Meier analysis. Patients who received > 8 cycles of FOLFIRINOX before IRE and who had tumors > 6 cm in the FOLFIRINOX-only group were excluded. RESULTS: Of 103 patients with a diagnosis of LAPC, 52 were deemed eligible (n = 30 IRE-FOLFIRINOX and n = 22 FOLFIRINOX-only). Patients in the FOLFIRINOX-only arm had larger tumors (53 mm ± 19 vs 38 mm ± 7, P = .340), had more locoregional lymph node metastases (23% vs 7%, P = .622), and more often received radiotherapy (7 patients vs 2 patients, P = .027); all other baseline characteristics were comparable. Median OS was 17.0 months (range, 5-35 mo; SD = 6) for IRE-FOLFIRINOX versus 12.4 months (range, 3-22 mo; SD = 6) for FOLFIRINOX-only (P = .038). After sensitivity analyses, median OS was 17.2 months (range, 6-27 mo; SD = 6) versus 12.4 months (range, 7-32 mo; SD = 10) (P = .05). Median TTP was longer in the IRE-FOLFIRINOX group: 14.2 months (range, 5-25 mo; SD = 4) versus 5.2 months (range, 2-22; SD = 6) (P = .0001). CONCLUSIONS: In patients with LAPC after FOLFIRINOX chemotherapy, CT-guided percutaneous IRE may improve OS and TTP. This study may facilitate the design of randomized controlled trials to compare survival after IRE-FOLRINOX versus FOLFIRINOX-only.


Assuntos
Técnicas de Ablação , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Eletroporação , Neoplasias Pancreáticas/terapia , Radiografia Intervencionista , Tomografia Computadorizada por Raios X , Técnicas de Ablação/efeitos adversos , Técnicas de Ablação/mortalidade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos como Assunto , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Irinotecano/administração & dosagem , Irinotecano/efeitos adversos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Estudos Prospectivos , Radiografia Intervencionista/efeitos adversos , Radiografia Intervencionista/mortalidade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X/efeitos adversos , Tomografia Computadorizada por Raios X/mortalidade , Resultado do Tratamento
7.
Int J Nanomedicine ; 15: 5417-5432, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801697

RESUMO

Introduction: Green-based materials have been increasingly studied to circumvent off-target cytotoxicity and other side-effects from conventional chemotherapy. Materials and Methods: Here, cellulose fibers (CF) were isolated from rice straw (RS) waste by using an eco-friendly alkali treatment. The CF network served as an anticancer drug carrier for 5-fluorouracil (5-FU). The physicochemical and thermal properties of CF, pure 5-FU drug, and the 5-FU-loaded CF (CF/5-FU) samples were evaluated. The samples were assessed for in vitro cytotoxicity assays using human colorectal cancer (HCT116) and normal (CCD112) cell lines, along with human nasopharyngeal cancer (HONE-1) and normal (NP 460) cell lines after 72-hours of treatment. Results: XRD and FTIR revealed the successful alkali treatment of RS to isolate CF with high purity and crystallinity. Compared to RS, the alkali-treated CF showed an almost fourfold increase in surface area and zeta potential of up to -33.61 mV. SEM images illustrated the CF network with a rod-shaped structure and comprised of ordered aggregated cellulose. TGA results proved that the thermal stability of 5-FU increased within the drug carrier. Based on UV-spectroscopy measurements for 5-FU loading into CF, drug loading encapsulation efficiency was estimated to be 83 ±0.8%. The release media at pH 7.4 and pH 1.2 showed a maximum drug release of 79% and 46%, respectively, over 24 hours. In cytotoxicity assays, CF showed almost no damage, while pure 5-FU killed most of the both normal and cancer cells. Impressively, the drug-loaded sample of CF/5-FU at a 250 µg/mL concentration demonstrated a 58% inhibition against colorectal cancer cells, but only a 23% inhibition against normal colorectal cells. Further, a 62.50 µg/mL concentration of CF/5FU eliminated 71% and 39% of nasopharyngeal carcinoma and normal nasopharyngeal cells, respectively. Discussion: This study, therefore, showed the strong potential anticancer activity of the novel CF/5-FU formulations, warranting their further investigation.


Assuntos
Celulose/química , Portadores de Fármacos/química , Fluoruracila/administração & dosagem , Fluoruracila/farmacologia , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Fluoruracila/farmacocinética , Células HCT116 , Humanos , Neoplasias Nasofaríngeas/tratamento farmacológico , Oryza/química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Difração de Raios X
8.
Int J Nanomedicine ; 15: 5445-5458, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801699

RESUMO

5-Fluorouracil (5-FU) has become one of the most widely employed antimetabolite chemotherapeutic agents in recent decades. It is considered a first line antineoplastic agent for the treatment of colorectal cancer. Unfortunately, chemotherapy with 5-FU has several limitations, including its short half-life, high cytotoxicity and low bioavailability. In order to overcome the drawbacks of 5-FU and enhance its therapeutic efficiency, many scientific groups have focused on designing a new delivery system to successfully deliver 5-FU to tumor sites. We provide a comprehensive review on different strategies to design effective delivery systems, including nanoformulations, drug-conjugate formulations and other strategies for the delivery of 5-FU to colorectal cancer. Furthermore, co-delivery of 5-FU with other therapeutics is discussed. This review critically highlights the recent innovations in and literature on various types of carrier system for 5-FU.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Fluoruracila/administração & dosagem , Animais , Antimetabólitos Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Disponibilidade Biológica , Portadores de Fármacos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fluoruracila/farmacocinética , Humanos , Nanoestruturas/administração & dosagem , Nanoestruturas/química
9.
Anticancer Res ; 40(8): 4263-4270, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727753

RESUMO

BACKGROUND/AIM: Enzymatic variants involved in fluoropyrimidine metabolism have been associated with adverse events (AEs). We assessed the association between C677T (rs1801133) and A1298 (rs1801131) methylenetetrahydrofolate reductase (MTHFR) polymorphisms and AEs in patients with first-line fluoropyrimidine-based chemotherapy. PATIENTS AND METHODS: Fifty patients with metastatic colorectal cancer were prospectively followed-up during the first 4 cycles of fluoropyrimidine-based treatment to assess AEs. Germline DNA was analyzed to determine the C677T and A1298C MTHFR polymorphisms. The associations between MTHFR polymorphisms and toxicity were examined. RESULTS: Individuals carrying at least one mutant allele of the MTHFR C677T polymorphism had increased risk to experience anemia (OR=1.69, 95% CI=1.13-2.53, p=0.005), neutropenia (OR=2.27, 95% CI=1.47-3.42, p<0.001) thrombocytopenia (OR=1.91, 95% CI=1.30-2.70, p<0.001), neuropathy (OR=1.77, 95% CI=1.16-2.70, p=0.02), diarrhea (OR=1.69, 95% CI=1.13-2.53, p=0.005), and hand-foot syndrome (OR=1.56, 95% CI=1.08-2.27, p=0.013), compared to patients carrying the wild type alleles. The presence of the mutant allele C of the MTHFR A1298C polymorphism was associated with increased risk of anemia (OR=2.75, 95% CI=1.01-7.48, p=0.02) and thrombocytopenia (OR=3.14, 95% CI=1.01-9.78, p=0.03); however, the prevalence of this allele in the sample was quite low (20%). CONCLUSION: MTHFR C677T and A1298C polymorphisms predicted toxicity in a subset of Mestizo patients with colorectal adenocarcinoma.


Assuntos
Antimetabólitos Antineoplásicos/toxicidade , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Grupos Étnicos/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Idoso , Neoplasias Colorretais/patologia , Costa Rica , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Estudos Prospectivos
10.
Anticancer Res ; 40(8): 4655-4661, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727789

RESUMO

In recent years, therapeutic drug monitoring (TDM) of intravenous administration of 5-fluorouracil (5-FU) has resulted in reduced toxicity and improved efficacy. Prodrugs of 5-FU were developed to reduce toxicity, extend the duration of action, and increase tumour selectivity of 5-FU. These drugs are important in daily practice because of their ease of administration. Dose adjustment of 5-FU prodrugs by TDM is expected to reduce its toxicity and improve its efficacy. This review focuses on data from a recent study of personalized treatment using TDM of 5-FU and its prodrugs.


Assuntos
Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Pró-Fármacos/administração & dosagem , Pró-Fármacos/efeitos adversos , Monitoramento de Medicamentos/métodos , Humanos , Neoplasias/tratamento farmacológico
11.
Dermatol Online J ; 26(3)2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-32609455

RESUMO

Keratoacanthomas are rapidly growing neoplasms of squamous epithelium. Despite their benign nature, they are often difficult to distinguish from squamous cell carcinoma and require excision. In cases in which excision is not successful or not desired, intralesional treatments may be considered. However, limited research exists on individual therapeutic efficacy. We present a 68-year-old man who developed multiple eruptive keratoacanthomas around the wound edge of a previous keratoacanthoma excision. Considering previous excisional failure, intralesional 5-fluorouracil was used as a treatment modality. Injections every 3-4 weeks over a course of 12 weeks induced clinical keratoacanthoma clearance with excellent cosmetic results. This case showcases that weekly intralesional 5-fluorouracil injections, as was the standard mode of treatment in previous case reports, may not be necessary. This less frequent injection strategy is more convenient for the patient and may lead to fewer treatments and less medication necessary. Although a case-by-case basis is needed for any alternative approach to keratoacanthoma treatment, this report is useful for the practicing clinician in showing that 5-fluorouracil may be efficacious in these difficult-to-treat patients.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Fluoruracila/administração & dosagem , Ceratoacantoma/tratamento farmacológico , Idoso , Braço/cirurgia , Humanos , Injeções Intralesionais , Ceratoacantoma/cirurgia , Masculino , Recidiva
12.
Lancet Oncol ; 21(9): 1147-1154, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32717180

RESUMO

BACKGROUND: Diagnosis and treatment of colorectal peritoneal metastases at an early stage, before the onset of signs, could improve patient survival. We aimed to compare the survival benefit of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC), with surveillance, in patients at high risk of developing colorectal peritoneal metastases. METHODS: We did an open-label, randomised, phase 3 study in 23 hospitals in France. Eligible patients were aged 18-70 years and had a primary colorectal cancer with synchronous and localised colorectal peritoneal metastases removed during tumour resection, resected ovarian metastases, or a perforated tumour. Patients were randomly assigned (1:1) to surveillance or second-look surgery plus oxaliplatin-HIPEC (oxaliplatin 460 mg/m2, or oxaliplatin 300 mg/m2 plus irinotecan 200 mg/m2, plus intravenous fluorouracil 400 mg/m2), or mitomycin-HIPEC (mitomycin 35 mg/m2) alone in case of neuropathy, after 6 months of adjuvant systemic chemotherapy with no signs of disease recurrence. Randomisation was done via a web-based system, with stratification by treatment centre, nodal status, and risk factors for colorectal peritoneal metastases. Second-look surgery consisted of a complete exploration of the abdominal cavity via xyphopubic incision, and resection of all peritoneal implants if resectable. Surveillance after resection of colorectal cancer was done according to the French Guidelines. The primary outcome was 3-year disease-free survival, defined as the time from randomisation to peritoneal or distant disease recurrence, or death from any cause, whichever occurred first, analysed by intention to treat. Surgical complications were assessed in the second-look surgery group only. This study was registered at ClinicalTrials.gov, NCT01226394. FINDINGS: Between June 11, 2010, and March 31, 2015, 150 patients were recruited and randomly assigned to a treatment group (75 per group). After a median follow-up of 50·8 months (IQR 47·0-54·8), 3-year disease-free survival was 53% (95% CI 41-64) in the surveillance group versus 44% (33-56) in the second-look surgery group (hazard ratio 0·97, 95% CI 0·61-1·56). No treatment-related deaths were reported. 29 (41%) of 71 patients in the second-look surgery group had grade 3-4 complications. The most common grade 3-4 complications were intra-abdominal adverse events (haemorrhage, digestive leakage) in 12 (23%) of 71 patients and haematological adverse events in 13 (18%) of 71 patients. INTERPRETATION: Systematic second-look surgery plus oxaliplatin-HIPEC did not improve disease-free survival compared with standard surveillance. Currently, essential surveillance of patients at high risk of developing colorectal peritoneal metastases appears to be adequate and effective in terms of survival outcomes. FUNDING: French National Cancer Institute.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Adolescente , Adulto , Idoso , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Hipertermia Induzida/métodos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Oxaliplatina/administração & dosagem , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/secundário , Fatores de Risco , Cirurgia de Second-Look/métodos , Adulto Jovem
13.
Tumour Biol ; 42(6): 1010428320925237, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32484056

RESUMO

The KCNB1 gene variants were differentially associated with cancers. However, their association with colorectal cancer has not yet been explored. We investigated the contribution of the KCNB1 gene variants rs3331, rs1051295, and indel (insertion/deletion) rs11468831 Polymorphism as predictors of the treatment response in colorectal cancer patients. A retrospective study, which involved 291 Tunisian colorectal cancer patients (aged 60.0 ± 13.1 years), who were stratified into responder and non-responder groups, according to TNM stages and their responsiveness to chemotherapy based on fluorouracil. KCNB1 genotyping was performed with amplification-refractory mutation system-polymerase chain reaction, and was confirmed by Sanger sequencing. Sex-specific response was found and colorectal cancer females are less likely to achieve a positive response during the chemotherapy strategy, compared to males. Weight and body mass index, tumor size, and tumor localization are considered as predictive factors to treatment responsiveness. Carriage of rs11468831 Ins allele was significantly associated with successful therapy achievement (p adjusted < 0.001). Stratification of colorectal cancer patients' response according to tumor localization and TNM stages reveals negative association of rs3331 Major allele to treatment response among the patients with advanced cancer stages (subgroup G2). The presence of rs3331 (homozygous minor) C/C genotype was positively associated with decline in carcino-embryonic antigen (p = 0.043) and CA19-9 (p = 0.014) serum levels. On the other hand, the presence of rs1051295 (homozygous minor) A/A genotype was correlated with marked decline in CA19-9 serum levels. KCNB1 haplotype did not reveal any association between haplotypes and treatment response. The results obtained suggest that gender-specific strategies for screening treatment and prevention protocols as well as KCNB1 variants may constitute an effective model for ongoing personalization medicine.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/tratamento farmacológico , Estudos de Associação Genética , Canais de Potássio Shab/genética , Antígenos Glicosídicos Associados a Tumores/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Genótipo , Humanos , Mutação INDEL/genética , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Polimorfismo de Nucleotídeo Único/genética , Medicina de Precisão , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Caracteres Sexuais , Resultado do Tratamento
14.
Oncology ; 98(9): 637-642, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32474564

RESUMO

BACKGROUND: FOLFIRI plus bevacizumab have been widely used as first-line treatment for metastatic colorectal cancer (mCRC). Pharmacokinetics and pharmacodynamics suggested a low dose of irinotecan given as a long-term infusion is expected to enhance antitumor activity. We conducted a randomized phase II study to compare oral S-1 with a 24-h infusion of irinotecan plus bevacizumab versus FOLFIRI plus bevacizumab. METHODS: The subjects comprised 120 chemotherapy-naïve patients with mCRC. The study group received a 24-h infusion of irinotecan at a dose of 125 mg/m2 on days 1 and 15, combined with oral S-1 80 mg/m2 on days 1-14 (24h-SIRI/B). The FOLFIRI/B group received irinotecan at a dose of 150 mg/m2, 5-fluorouracil given at a dose of 400 mg/m2 as a bolus injection and at a dose of 2,400 mg/m2 as a 46-h infusion, and 200 mg/m2 leucovorin on days 1 and 15. Bevacizumab was given at a dose of 5.0 mg/kg on days 1 and 15 in both groups. Treatment was repeated every 4 weeks. The primary endpoint was 1-year progression-free survival (PFS). Secondary endpoints were PFS, response rates (RR), overall survival (OS), and adverse events (AEs). RESULTS: From December 2013 through January 2018, 120 patients were randomly assigned, 61 patients to the 24h-SIRI/B and 59 patients to the FOLFIRI/B. The median follow-up period was 22.8 months. The 1-year PFS rate was 43.14% in the 24h-SIRI/B arm and 19.15% in the FOLFIRI/B arm (HR = 0.312 [95%CI 0.13-0.78], p = 0.01). The median PFS was 10.2 months (95%CI 8.8-14.3) and 10.0 months (95%CI 7.4-11.0), and the median OS was 29.7 months (95%CI 22.9-43.9) and 28.8 months (95%CI 18.4-ND), respectively (p = 0.3758, p = 0.8234). The overall RR was 86.3 and 61.7%, respectively (p = 0.0053). AEs were similar. CONCLUSIONS: Our results show that the 24h-SIRI/B regimen is an effective and reasonably well-tolerated regimen for the first-line treatment of mCRC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Administração Oral , Adulto , Idoso , Bevacizumab/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Esquema de Medicação , Combinação de Medicamentos , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intravenosas , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Ácido Oxônico/administração & dosagem , Intervalo Livre de Progressão , Taxa de Sobrevida , Tegafur/administração & dosagem , Adulto Jovem
15.
Medicine (Baltimore) ; 99(21): e20026, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481270

RESUMO

RATIONALE: Cutaneous metastases from colorectal cancer are extremely rare and generally appear several years after diagnosis or resection of the primary colorectal tumor. Although cutaneous metastasis is unusual, it often indicates a poor prognosis. PATIENT CONCERNS: We treated a 62-year-old woman with multiple cutaneous metastatic nodules on the chest, back, and armpit 7 months after resection of ascending colon cancer. DIAGNOSES: The patient was diagnosed with cutaneous metastasis of ascending colon cancer with BRAF V600E mutation. INTERVENTIONS: After 6 cycles of fluorouracil, leucovorin, oxaliplatin, cetuximab, and emurafenib, most of the metastatic lesions had begun to shrink, and no new metastases were observed. Serum tests showed that the levels of several tumor markers were decreased. OUTCOMES: The patient responded well to treatment and survived for 6.5 months after presentation with skin metastasis. LESSONS: Cutaneous metastasis of colorectal cancer with BRAF V600E mutation is a rare but important phenomenon that should not be ignored. Cutaneous metastasis of colorectal cancer frequently indicates advanced disease and poor prognosis. The SWOG 1406 program is one of the treatment options, but this needs further exploration.


Assuntos
Adenocarcinoma/patologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/secundário , Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Evolução Fatal , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas B-raf , Neoplasias Cutâneas/tratamento farmacológico
16.
Bull Cancer ; 107(7-8): 792-799, 2020.
Artigo em Francês | MEDLINE | ID: mdl-32591138

RESUMO

Anal canal cancer is a rare disease that accounts for 2.5% of digestive cancers. Squamous cell carcinomas are the most common histological form. Their incidence is in progression, probably due to the increase in Human Papilloma Virus infections. Metastatic forms account for 20% of anal canal cancers considering synchronous forms or metastatic recurrence of an initially localised disease. Their prognosis remains poor with an estimated 5-year survival rate of 30%. The first-line therapeutic standard based on the combination of cisplatin with 5-Fluorouracil has recently been challenged by carboplatin - paclitaxel and docetaxel, cisplatin and 5-Fluorouracil regimens which are becoming new treatment options. In second-line setting, there is no international consensus. Anti-EGFRs and immunotherapy in combination or not with other molecules are promising but these results need to be confirmed. In this review, we report current and future data in the management of squamous cell carcinomas of the anal canal in unresectable locoregional recurrence or at metastatic stage.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias do Ânus/mortalidade , Carboplatina/administração & dosagem , Carcinoma de Células Escamosas/mortalidade , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Receptores ErbB/antagonistas & inibidores , Fluoruracila/administração & dosagem , Humanos , Imunoterapia/métodos , Paclitaxel/administração & dosagem , Prognóstico , Taxa de Sobrevida
17.
Int J Nanomedicine ; 15: 2765-2776, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32425520

RESUMO

Purpose: Over the past decades, quantum dots (QDs) have shown the broad application in diverse fields, especially in intracellular probing and drug delivery, due to their high fluorescence intensity, long fluorescence lifetime, strong light-resistant bleaching ability, and strong light stability. Therefore, we explore a kind of therapeutic potential against cancer with fluorescent imaging. Methods: In the current study, a new type of QDs (QDs@L-Cys-TAEA-5-FUA) capped with L-cysteine (L-Cys) and tris(2-aminoethyl)amine (TAEA) ligands, and conjugated with 5-fluorouracil-1-acetic acid (5-FUA) has been synthesized. Ligands were characterized by electrospray ionization mass spectrometry and H-nuclear magnetic resonance (1H NMR) spectroscopy. The modified QDs were characterized by transmission electron microscopy, ultraviolet and visible spectrophotometry (UV-Vis), and fluorescence microscopy. And the biological activity of modified QDs was explored by using MTT assay with HeLa, SMMC-7721 HepG2, and QSG-7701 cells. The fluorescence imaging of modified QDs was obtained by fluorescence microscope. Results: The modified QDs are of controllable sizes in the range of 4-5 nm and they possess strong optical emission properties. UV-Vis and fluorescence spectra demonstrated that the L-Cys-TAEA-5-FUA was successfully incorporated into QD nanoparticles. The MTT results demonstrated that L-Cys-TAEA-5-FUA modified QDs could efficiently inhibit the proliferation of cancer cells as compared to the normal cells, illustrating their antitumor efficacy. The mechanistic studies revealed that the effective internalization of modified QDs inside cancer cells could inhibit their proliferation, through excessive production of intracellular reactive oxygen species, leading to apoptosis process. Conclusion: The present study suggests that modified QDs can enter cells efficiently and could be employed as therapeutic agents for the treatment of various types of cancers with fluorescent imaging.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Fluoruracila/farmacologia , Pontos Quânticos/química , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Cisteína/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Etilenodiaminas/química , Fluoruracila/administração & dosagem , Fluoruracila/química , Células HeLa , Células Hep G2 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Pontos Quânticos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Espectrofotometria Ultravioleta
18.
Int J Clin Oncol ; 25(8): 1515-1522, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32409917

RESUMO

BACKGROUND: Chemotherapy in relapsed colorectal cancer patients treated with oxaliplatin as adjuvant chemotherapy is under debate. REACT study aimed to investigate the efficacy of reintroducing modified FOLFOX6 (mFOLFOX6) or CAPOX with or without bevacizumab in recurrent colorectal cancer patients after oxaliplatin adjuvant chemotherapy. METHODS: Patients that participated in this trial had a medical history of adjuvant chemotherapy, including oxaliplatin with a cumulative dose greater than 400 mg/m2, and recurrence that was diagnosed more six months post adjuvant chemotherapy. Primary endpoints were response rate (RR) and disease control rate (DCR), while key secondary endpoints were time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: A total of 31 patients were enrolled between October 2012 and October 2016. Of the 29 eligible patients, 7 received mFOLFOX6 and 22 received CAPOX. The RR was 62.1% (95% confidence interval 42.3-79.3) and the DCR was 82.8% (95% confidence interval 64.2-94.2). The RR for oxaliplatin-free interval was 100.0% in months 6-12 and 56.0% after 12 months. Median TTF, PFS, and OS were 6.3, 10.8, and 28.7 months, respectively. Grade 3 or worse peripheral sensory neuropathy developed in 6.5%. Allergic reactions occurred in 12.9% of the patients, with one (3.2%) grade 3 episode. There were no other severe treatment-related adverse events. CONCLUSION: Reintroduction of oxaliplatin was feasible and achieved high RR or DCR in patients after more than 6 months post oxaliplatin adjuvant chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Capecitabina/administração & dosagem , Quimioterapia Adjuvante , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina/administração & dosagem , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento
19.
Radiol Med ; 125(12): 1216-1224, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32410063

RESUMO

PURPOSE: To determine whether MRI T2-weighted sequences-based texture analysis (TA) can predict histopathological tumor regression grade (TRG) in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemo-radiotherapy (nCRT). METHODS: Data on patients undergoing curative-intent surgery for LARC were collected. Patients with a complete pathological response, or TRG1 according to Mandard's system were classified as responders, while patients with TRG ≥ 2 were classified as non-responders. Tumor TA was performed on each patient's paraxial T2w MRI in both pre- and post-nCRT scans, in order to extract histograms, gray-level co-occurrence matrix (GLCM) and run-length matrix (RLM) texture parameters. For features that showed a significant difference between the two groups, a receiver operating characteristic (ROC) curve was drawn. RESULTS: Overall, 62 patients with LARC, treated with nCRT and resective surgery at our institution between 2013 and 2019 were identified. Only post-nCRT GLCM maximum probability showed a significant difference between the two groups (2909 ± 4479 in responders vs. 6515 ± 8990 in non- responders; p = 0.039); at the ROC curve, Youden index showed a sensitivity of 14% and a specificity of 100% for this parameter. CONCLUSIONS: MRI T2-weighted sequences-based TA was not effective in predicting pathological complete response to nCRT in patients with LARC. Further studies are needed to thoroughly investigate the potential of MRI TA in this setting.


Assuntos
Quimiorradioterapia Adjuvante , Imagem por Ressonância Magnética/métodos , Terapia Neoadjuvante/métodos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia , Adulto , Antimetabólitos Antineoplásicos/administração & dosagem , Capecitabina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Dosagem Radioterapêutica , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento
20.
Int J Nanomedicine ; 15: 2777-2787, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368054

RESUMO

Background: Owing to its combined effects, the co-delivery of different therapeutics is a promising option for the treatment of cancer. In the present study, tumor-targeting poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) nanoparticles were developed for the transportation of two molecules, namely chemotherapeutic drug 5-fluorouracil (5Fu) and radionuclide iodine-131 (131I), in a single platform. Methods: The obtained nanoparticles (Cetuximab [Cet]-PEG-PLA-5Fu-131I) were spherical (diameter approximately 110 nm) and pH-sensitive. The targeting effect of nanoparticles via Cet was confirmed in colorectal cancer cells using a fluorescent assay. The combined effects of Cet-PEG-PLA-5Fu-131I on cell viability and apoptosis were evaluated in colorectal cancer cells by Cell Counting Kit-8 and flow cytometry assays. Results: Blank nanoparticles (Cet-PEG-PLA) showed good biocompatibility, and Cet-PEG-PLA-5Fu-131I nanoparticles were the most effective in terms of inhibition of cell viability and induction of apoptosis compared with monotherapy using Cet-PEG-PLA-5Fu or Cet-PEG-PLA-131I. In the xenograft mouse model, compared with using Cet-PEG-PLA-5Fu or Cet-PEG-PLA-131I alone, Cet-PEG-PLA-5Fu-131I nanoparticles exhibited prolonged circulation in the blood and accumulation in the tumor, thus resulting in enhanced antitumor efficacy. Additionally, combined radio-chemotherapy with Cet-PEG-PLA-5Fu-131I nanoparticles was associated with smaller tumor sizes than monotherapy, revealing the superior antitumor effects of Cet-PEG-PLA-5Fu-131I nanoparticles. These effects were further evidenced by histological and immunohistochemical analyses. Conclusion: The multifunctional Cet-PEG-PLA-5Fu-131I nanoparticles are promising candidates for the co-delivery of 5Fu-mediated chemotherapy and 131I-mediated radiotherapy.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/administração & dosagem , Nanopartículas Multifuncionais/química , Animais , Antimetabólitos Antineoplásicos/farmacologia , Circulação Sanguínea , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cetuximab/química , Neoplasias Colorretais/patologia , Sistemas de Liberação de Medicamentos/métodos , Fluoruracila/farmacologia , Humanos , Radioisótopos do Iodo/química , Radioisótopos do Iodo/farmacocinética , Camundongos Endogâmicos BALB C , Nanopartículas Multifuncionais/uso terapêutico , Polietilenoglicóis , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
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