Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.326
Filtrar
1.
Int J Mol Sci ; 22(6)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808722

RESUMO

Chemo-radiotherapy, which combines chemotherapy with radiotherapy, has been clinically practiced since the 1970s, and various anticancer drugs have been shown to have a synergistic effect when used in combination with radiotherapy. In particular, cisplatin (CDDP), which is often the cornerstone of multi-drug combination cancer therapies, is highly versatile and frequently used in combination with radiotherapy for the treatment of many cancers. Therefore, the mechanisms underlying the synergistic effect of CDDP and radiotherapy have been widely investigated, although no definitive conclusions have been reached. We present a review of the combined use of CDDP and radiotherapy, including the latest findings, and propose a mechanism that could explain their synergistic effects. Our hypothesis involves the concepts of overlap and complementation. "Overlap" refers to the overlapping reactions of CDDP and radiation-induced excessive oxidative loading, which lead to accumulating damage to cell components, mostly within the cytoplasm. "Complementation" refers to the complementary functions of CDDP and radiation that lead to DNA damage, primarily in the nucleus. In fact, the two concepts are inseparable, but conceptualizing them separately will help us understand the mechanism underlying the synergism between radiation therapy and other anticancer drugs, and help us to design future radiosensitizers.


Assuntos
Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Neoplasias/terapia , Radiossensibilizantes/uso terapêutico , Radioterapia Adjuvante , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Estudos Clínicos como Assunto , Ensaios Clínicos como Assunto , Terapia Combinada , Avaliação Pré-Clínica de Medicamentos , Humanos , Neoplasias/diagnóstico , Neoplasias/etiologia , Neoplasias/mortalidade , Radiossensibilizantes/administração & dosagem , Radiossensibilizantes/efeitos adversos , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Resultado do Tratamento
2.
Carbohydr Polym ; 253: 117284, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33278950

RESUMO

High-efficient vectors for the co-delivery of photosensitizers and chemotherapeutics were urgently needed for the combination therapy. In this work, a redox-responsive micelle (PCL-SS-CMC-GA) was prepared for the co-delivery of doxorubicin (DOX) and pheophorbide A (PHA). Poly-ε-caprolactone was linked to carboxymethyl chitosan through a disulfide bond, which was easily broken in the reductive solution to release the payloads. The charge conversion property and glycyrrhetinic acid (GA) targeting ligand of the micelles effectively extended the average residence time (up to 18 times) in circulation and improved their intracellular uptake by HepG2 cells. The micelles exhibited an enhanced tumor accumulation and near infrared (NIR) imaging performance. More interestingly, this nanoplatform could fully exert the synergistic effect of DOX and PHA to improve the inhibition efficiency (with an inhibitory rate of 80.5 %) in vivo. With impressive photo-chemo theranostic and NIR imaging capability, PCL-SS-CMC-GA@DOX/PHA showed great potential in image-guided treatment of liver cancer.


Assuntos
Quitosana/análogos & derivados , Portadores de Fármacos/química , Raios Infravermelhos/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Micelas , Imagem Óptica/métodos , Fotoquimioterapia/métodos , Animais , Antibióticos Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Clorofila/administração & dosagem , Clorofila/análogos & derivados , Doxorrubicina/administração & dosagem , Combinação de Medicamentos , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Feminino , Células Hep G2 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanoestruturas/química , Oxirredução , Radiossensibilizantes/administração & dosagem , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Int J Mol Sci ; 21(24)2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33348549

RESUMO

Enhancing the effectiveness of colorectal cancer treatment is highly desirable. Radiation-based anticancer therapy-such as proton therapy (PT)-can be used to shrink tumors before subsequent surgical intervention; therefore, improving the effectiveness of this treatment is crucial. The addition of noble metal nanoparticles (NPs), acting as radiosensitizers, increases the PT therapeutic effect. Thus, in this paper, the effect of novel, gold-platinum nanocauliflowers (AuPt NCs) on PT efficiency is determined. For this purpose, crystalline, 66-nm fancy shaped, bimetallic AuPt NCs were synthesized using green chemistry method. Then, physicochemical characterization of the obtained AuPt NCs by transmission electron microscopy (TEM), selected area electron diffraction (SAED), energy dispersive X-ray spectroscopy (EDS), and UV-Vis spectra measurements was carried out. Fully characterized AuPt NCs were placed into a cell culture of colon cancer cell lines (HCT116, SW480, and SW620) and a normal colon cell line (FHC) and subsequently subjected to proton irradiation with a total dose of 15 Gy. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) test, performed after 18-h incubation of the irradiated cell culture with AuPt NCs, showed a significant reduction in cancer cell viability compared to normal cells. Thus, the radio-enhancing features of AuPt NCs indicate their potential application for the improvement in effectiveness of anticancer proton therapy.


Assuntos
Neoplasias do Colo/radioterapia , Ouro/química , Nanopartículas Metálicas/administração & dosagem , Platina/química , Terapia com Prótons/métodos , Radiossensibilizantes/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Neoplasias do Colo/patologia , Química Verde , Células HCT116 , Humanos , Nanopartículas Metálicas/química , Microscopia Eletrônica de Transmissão , Prótons , Radiossensibilizantes/química , Espectrometria por Raios X
4.
Int J Mol Sci ; 22(1)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33374960

RESUMO

To increase the efficiency of therapy via enhancing its selectivity, the usage of gold nanorods (GNR) as a factor sensitizing cancer cells to radiation was proposed. Due to gold nanoparticles' characteristics, the smaller doses of radiation would be sufficient in the treatment, protecting the healthy tissue around the tumor. The aim of this study was to investigate the effect of gold nanorods on cancer and normal prostate cells and the role of nanorods in the cell response to ionizing radiation. The effect was evaluated by measuring the toxicity, cell cycle, cell granularity, reactive oxygen species (ROS) level, and survival fractions. Nanorods showed a strong toxicity dependent on the concentration and incubation time toward all used cell lines. A slight effect of nanorods on the cycle distribution was observed. The results demonstrated that the administration of nanorods at higher concentrations resulted in an increased level of generated radicals. The results of cellular proliferation after irradiation are ambiguous; however, there are noticeable differences after the application of nanorods before irradiation. The obtained results lead to the conclusion that nanorods affect the physiology of both normal and cancer cells. Nanorods might become a potential tool used to increase the effectiveness of radiation treatment.


Assuntos
Ouro/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Radiação Ionizante , Radiossensibilizantes/administração & dosagem , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Ouro/química , Humanos , Masculino , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Microscopia Eletrônica de Transmissão , Nanotubos/química , Nanotubos/ultraestrutura , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Radiossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Fatores de Tempo
5.
Phys Med Biol ; 65(19): 195003, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32721936

RESUMO

The efficacy of dose-enhancing gold nanoparticles (AuNPs) is negatively impacted by low tumor uptake, low cell membrane penetration, limited diffusion distance, and short lifetime of radiation-induced secondary particles. To overcome these limitations, we have developed a novel AuNP system capable of radiation-triggered release of nitrite, a precursor of reactive nitrogen species, and report here on the in vivo characterization of this system. AuNPs were functionalized through PEGylation, cell-penetrating peptides (CPP; AuNP@CPP), and nitroimidazole (nIm; AuNP@nIm-CPP). Mice with subcutaneous 4T1 tumors received either AuNP@nIm-CPP or AuNP@CPP intraperitoneally. Tumor and normal tissue uptake were evaluated 24 h post AuNP administration. A separate cohort of mice was injected and irradiated to a single-fraction dose of 18 Gy in a 225 kVp small animal irradiator 24 h post NP administration. The mice were followed for two weeks to evaluate tumor response. The mean physical and hydrodynamic size of both NP systems were 5 and 13 nm, respectively. NP nIm-loading of 1 wt% was determined. Tumor accumulation of AuNP@nIm-CPP was significantly lower than that of AuNP@CPP (0.2% vs 1.2%, respectively). In contrast, AuNP@nIm-CPP showed higher accumulation compared to AuNP@CPP in liver (16.5% vs 6.6%, respectively) and spleen (10.8% vs 3.1%, respectively). With respect to tumor response, no differential response was found between non-irradiated mice receiving either saline or AuNP@nIm-CPP alone. The combination of AuNP@CPP+ radiation showed no differential response from radiation alone. In contrast, a significant delay in tumor regrowth was observed in mice receiving AuNP@nIm-CPP+ radiation compared to radiation alone. AuNP functionalized with both CPP and nIm exhibited an order of magnitude less tumor accumulation compared to the NP system without nIm yet resulted in a significantly higher therapeutic response. Our data suggest that by improving the biokinetics of AuNP@nIm-CPP, this novel NP system could be a promising radiosensitizer for enhanced therapeutic response following radiation therapy.


Assuntos
Neoplasias da Mama/terapia , Raios gama , Ouro/química , Nanopartículas Metálicas/administração & dosagem , Nitritos/metabolismo , Radiossensibilizantes/administração & dosagem , Espécies Reativas de Nitrogênio/metabolismo , Animais , Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células , Terapia Combinada , Feminino , Humanos , Nanopartículas Metálicas/química , Camundongos , Camundongos Nus , Radiossensibilizantes/química , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Biochim Biophys Acta Rev Cancer ; 1874(1): 188381, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32492470

RESUMO

The United States Food and Drug Administration has permitted number of therapeutic agents for cancer treatment. Most of them are expensive and have some degree of systemic toxicity which makes overbearing in clinical settings. Although advanced research continuously applied in cancer therapeutics, but drug resistance, metastasis, and recurrence remain unanswerable. These accounts to an urgent clinical need to discover natural compounds with precisely safe and highly efficient for the cancer prevention and cancer therapy. Gambogic acid (GA) is the principle bioactive and caged xanthone component, a brownish gamboge resin secreted from the of Garcinia hanburyi tree. This molecule showed a spectrum of biological and clinical benefits against various cancers. In this review, we document distinct biological characteristics of GA as a novel anti-cancer agent. This review also delineates specific molecular mechanism(s) of GA that are involved in anti-cancer, anti-metastasis, anti-angiogenesis, and chemo-/radiation sensitizer activities. Furthermore, recent evidence, development, and implementation of various nanoformulations of gambogic acid (nanomedicine) have been described.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Nanomedicina/métodos , Neoplasias/terapia , Radiossensibilizantes/administração & dosagem , Xantonas/administração & dosagem , Animais , Antineoplásicos Fitogênicos/economia , Quimiorradioterapia/economia , Quimiorradioterapia/métodos , Ensaios Clínicos Fase II como Assunto , Relação Dose-Resposta a Droga , Portadores de Fármacos/química , Custos de Medicamentos , Garcinia/química , Humanos , Nanomedicina/economia , Nanopartículas/química , Neoplasias/economia , Radiossensibilizantes/economia , Resinas Vegetais/química , Resultado do Tratamento , Xantonas/economia , Ensaios Antitumorais Modelo de Xenoenxerto
7.
J Photochem Photobiol B ; 205: 111827, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32120183

RESUMO

5-iodo-2-deoxyuridine (IUdR) has been demonstrated to induce an appreciable radiosensitizing effect on glioblastoma patients, but due to the short circulation half-life times and failure to pass through the blood-brain barrier (BBB), its clinical use is limited. Accordingly, in this study, we used magnetic graphene oxide (NGO/SPIONs) nanoparticles coated with PLGA polymer as a dynamic nanocarrier for IUdR and, evaluated its sensitizing enhancement ratio in combination with a single dose X-ray at clinically megavoltage energies for treatment of C6 glioma rats. Nanoparticles were characterized using Zetasizer and TEM microscopy, and in vitro biocompatibility of nanoparticles was assessed with MTT assay. IUdR/MNPs were intravenously administered under a magnetic field (1.3 T) on day 13 after the implantation of C6 cells. After a day following the injection, rats exposed with radiation (8 Gy). ICP-OES analysis data indicated an effective magnetic targeting, leading to remarkably improved penetration through the BBB. In vivo release analysis with HPLC indicated sustained release of IUdR and, prolonged the lifespan in plasma (P < .01). In addition, our findings revealed a synergistic effect for IUdR/MNPs coupled with radiation, which significantly inhibited the tumor expansion (>100%), prolonged the survival time (>100%) and suppressed the anti-apoptotic response of glioma rats by increasing Bax/Bcl-2 ratio (2.13-fold) in compared with the radiation-only. In conclusion, besides high accumulation in targeted tumor sites, the newly developed IUdR/MNPs, also exhibited the ability of IUdR/MNPs to significantly enhance radiosensitizing effect, improve therapeutic efficacy and increase toxicity for glioma-bearing rats.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Grafite/administração & dosagem , Idoxuridina/administração & dosagem , Nanopartículas/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Radiossensibilizantes/administração & dosagem , Animais , Encéfalo/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Glioma/metabolismo , Glioma/patologia , Grafite/química , Grafite/farmacocinética , Concentração de Íons de Hidrogênio , Idoxuridina/farmacocinética , Fenômenos Magnéticos , Masculino , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacocinética , Coelhos , Radiossensibilizantes/farmacocinética , Ratos Wistar , Carga Tumoral/efeitos dos fármacos
8.
Mol Biol Rep ; 47(1): 129-139, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31781916

RESUMO

Tumor environmental cytokines, such as IL-6, has a major role in the outcome of radiation and chemotherapy. In this study, we hypothesized that IL-6 mediates its effects via SIRT1 as a protein deacetylase and activator of phosphatidylinositol-3 kinase pathways. In the present study, we evaluated the effects of the novel dual inhibitor of phosphatidylinositol-3 kinase/mammalian target of rapamycin, NVP-BEZ235, and SIRT1 inhibitor and activator plus radiotherapy in breast cancer cells treated with IL-6. Here, IL-6 untreated/pretreated human breast cancer cells were cultured with single or combination of NVP-BEZ235 and/or SIRT1 activator (SRT1720)/inhibitor (EX-527) under radiotherapy condition. After all treatments, the MTT assay and flow cytometry assay were used to explore cell viability and the ability of our treatments in altering cancer stem cells (CSCs) population or cellular death (apoptosis + necrosis) induction. Simultaneous exposure to NVP-BEZ235 and SRT1720 sensitized breast cancer cells to radiotherapy but elevated CSCs. Treatment with IL-6 for 2 weeks significantly decreased CSCs population. Activation of SIRT1 via SRT1720 in combination with NVP-BEZ235 significantly decreased breast cancer cells viability in IL-6 pretreatment cultures. Inhibition of SIRT1 via EX-527 diminished the beneficial effects of IL-6 pretreatment. The combination of NVP-BEZ235 and SRT1720 as a SIRT1 activation could effectively decrease breast cancer cells population and augments the efficacy of radiotherapy.


Assuntos
Neoplasias da Mama/patologia , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Imidazóis/farmacologia , Interleucina-6/farmacologia , Quinolinas/farmacologia , Radiossensibilizantes/farmacologia , Sirtuína 1/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Carbazóis/administração & dosagem , Carbazóis/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Humanos , Imidazóis/administração & dosagem , Células MCF-7 , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Quinolinas/administração & dosagem , Radiossensibilizantes/administração & dosagem
9.
Int J Radiat Oncol Biol Phys ; 106(3): 564-570, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31678634

RESUMO

PURPOSE: Activation of the PI3K/mTOR signaling pathway is common in head and neck squamous cell carcinoma (HNSCC). BYL719 is an α-specific PI3K inhibitor that is synergistic and efficacious when combined with cetuximab, a Food and Drug Administration-approved radiosensitizing agent in the treatment of HNSCC. The agent independently has been shown to enhance radiosensitivity. This study evaluates the addition of BYL719 to cetuximab and radiation in the treatment of locally advanced HNSCC. METHODS AND MATERIALS: This is a single-institution, phase 1 study. Patients with American Joint Committee on Cancer seventh edition stage III to IVB HNSCC received standard cetuximab (400 mg/m2 intravenous loading dose) before intensity modulated radiation therapy (IMRT) followed by 250 mg/m2 weekly infusions during IMRT. BYL719 was given orally during IMRT in 3 dose levels: (1) 200 mg/d, (2) 250 mg/d, or (3) 300 mg/d in a standard 3 + 3 dose-escalation design. RESULTS: Eleven patients were evaluable. Dose level 2 was the maximum tolerated dose for BYL719. Two patients on dose level 3 had dose-limiting toxicities of oral mucositis that required a dose reduction of BYL719. One patient on dose level 2 had a dose-limiting toxicity of nausea that led to withdrawal of on-study treatment. Related grade 3 or higher adverse events consisted of decreased lymphocyte count, oral mucositis, dysphagia, hyperglycemia, maculopapular rash, and palmar-plantar erythrodysesthesia syndrome. All 11 patients had a complete response on posttreatment imaging, and 10 remain disease free. Of the 8 patients with mutational analysis, 1 had an activating PIK3CA mutation associated with a rapid response on serial intratreatment magnetic resonance imaging scans. CONCLUSIONS: The recommended phase 2 dose of BYL719 is 250 mg/d in combination with cetuximab and IMRT in patients with locally advanced HNSCC. Further evaluation of the addition of BYL719 to the platinum-sparing regimen of cetuximab and IMRT in the treatment of locally advanced HNSCC is warranted.


Assuntos
Cetuximab/administração & dosagem , Neoplasias de Cabeça e Pescoço/terapia , Inibidores de Fosfoinositídeo-3 Quinase/administração & dosagem , Radiossensibilizantes/administração & dosagem , Radioterapia de Intensidade Modulada , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Tiazóis/administração & dosagem , Adulto , Idoso , Quimiorradioterapia/métodos , Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Mutação , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Serina-Treonina Quinases TOR/metabolismo , Tiazóis/efeitos adversos
10.
Int J Cancer ; 146(4): 1075-1085, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31283004

RESUMO

Radiotherapy is one of the most used treatment approaches for head and neck squamous cell carcinoma (HNSCC). Targeted inhibition of DNA repair machinery has the potential to improve treatment response by tailoring treatment to cancer cells lacking specific DNA repair pathways. Human papillomavirus (HPV)-negative and HPV-positive HNSCCs respond differently to radiotherapy treatment, suggesting that different approaches of DNA repair inhibition should be employed for these HNSCC groups. Here, we searched for optimal radiosensitization approaches for HPV-positive and HPV-negative HNSCCs by performing a targeted CRISPR-Cas9 screen. We found that inhibition of base excision repair resulted in a better radiotherapy response in HPV-positive HNSCC, which is correlated with upregulation of genes involved in base excision repair. In contrast, inhibition of nonhomologous end-joining and mismatch repair showed strong effects in both HNSCC groups. We validated the screen results by combining radiotherapy with targeted inhibition of DNA repair in several preclinical models including primary and recurrent patient-derived HNSCC xenografts. These findings underline the importance of stratifying HNSCC patients for combination treatments.


Assuntos
Neoplasias de Cabeça e Pescoço/terapia , Recidiva Local de Neoplasia/terapia , Infecções por Papillomavirus/terapia , Radiossensibilizantes/administração & dosagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Animais , Benzimidazóis/administração & dosagem , Sistemas CRISPR-Cas/genética , Linhagem Celular Tumoral , Quimiorradioterapia/métodos , Cromonas/administração & dosagem , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/efeitos da radiação , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Morfolinas/administração & dosagem , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/virologia , Papillomaviridae/efeitos dos fármacos , Papillomaviridae/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Dosagem Radioterapêutica , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Sci Rep ; 9(1): 17120, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31745177

RESUMO

Metal nanoparticles have significant interaction cross-sections with electromagnetic waves due to their large surface area-to-volume ratio, which can be exploited in cancer radiotherapy to locally enhance the radiation dose deposition in tumors. We developed a new type of silver nanoparticle composite, PEGylated graphene quantum dot (GQD)-decorated Silver Nanoprisms (pGAgNPs), that show excellent in vitro intracellular uptake and radiosensitization in radiation-sensitive HCT116 and relatively radiation-resistant HT29 colorectal cancer cells. Furthermore, following biodistribution analysis of intravenously injected nanoparticles in nude mice bearing HCT116 tumors radiosensitization was evaluated. Treatment with nanoparticles and a single radiation dose of 10 Gy significantly reduces the growth of colorectal tumors and increases the survival time as compared to treatment with radiation only. Our findings suggest that these novel nanoparticles offer a promising paradigm for enhancing colorectal cancer radiation therapy efficacy.


Assuntos
Neoplasias Colorretais/radioterapia , Grafite/química , Nanopartículas Metálicas/administração & dosagem , Radiossensibilizantes/administração & dosagem , Prata/química , Animais , Apoptose , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Raios gama , Humanos , Masculino , Nanopartículas Metálicas/química , Camundongos , Pontos Quânticos , Radiossensibilizantes/química , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Biomater Sci ; 7(12): 5143-5149, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31577285

RESUMO

Photodynamic therapy has attracted significant attention due to its localized treatment advantage. However, the non-specific distribution of photosensitizers and the subsequent potential toxicity caused by sunshine exposure hinder its wide adoption in cancer treatment. To minimize these unwanted effects and improve its efficacy, we developed a bioactivatable self-quenched nanogel, which remains in its inactive state in healthy tissues. Anti-EGFR Affibody decorated nanogels can effectively target head and neck cancer and release activated pheophorbide A in a reducing environment, such as in the tumor stroma and cytoplasm. Consequently, the EGFR targeted nanogel coupled with NIR irradiation alleviates tumor burden by 94.5% while not inducing systemic toxicity.


Assuntos
Clorofila/análogos & derivados , Neoplasias de Cabeça e Pescoço/terapia , Radiossensibilizantes/administração & dosagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Clorofila/administração & dosagem , Clorofila/química , Clorofila/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Células HeLa , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Ligantes , Camundongos , Terapia de Alvo Molecular , Nanogéis/química , Fotoquimioterapia , Radiossensibilizantes/química , Radiossensibilizantes/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
PLoS One ; 14(10): e0223760, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31613929

RESUMO

The current study aimed to identify the radiosensitizing effect of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, in combination with radiotherapy in non-small-cell lung cancer (NSCLC) cells. The combination of celecoxib potentiated radiation-induced apoptosis; however, no changes in cell cycle distribution and number of phosphorylated histone H2AX foci were detected, indicating a DNA damage-independent mechanism. In an in vivo mouse model, the tumor size was significantly decreased in the group combining celecoxib with radiation compared with the radiation only group. Phosphorylation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR), as well as expression of COX-2 were significantly downregulated in cells treated with the combination of celecoxib and radiation compared with the radiation only group. The result indicated that celecoxib exhibits radiosensitizing effects through COX-2 and Akt/mTOR-dependent mechanisms. Induction the Akt/mTOR signaling pathway promotes radioresistance in various cancers, including NSCLC. Therefore, the current study suggested the therapeutic potential of combination therapy of celecoxib and radiation in the prevention of radioresistance.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Celecoxib/administração & dosagem , Ciclo-Oxigenase 2/metabolismo , Neoplasias Pulmonares/terapia , Radiossensibilizantes/administração & dosagem , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Celecoxib/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Radiossensibilizantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Int J Mol Sci ; 20(21)2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31652849

RESUMO

The improvement of diagnostic techniques and the efficacy of new therapies in clinical practice have allowed cancer patients to reach a higher chance to be cured together with a better quality of life. However, tumors still represent the second leading cause of death worldwide. On the contrary, chemotherapy and radiotherapy (RT) still lack treatment plans which take into account the biological features of tumors and depend on this for their response to treatment. Tumor cells' response to RT is strictly-connected to their radiosensitivity, namely, their ability to resist and to overcome cell damage induced by ionizing radiation (IR). For this reason, radiobiological research is focusing on the ability of chemical compounds to radiosensitize cancer cells so to make them more responsive to IR. In recent years, the interests of researchers have been focused on natural compounds that show antitumoral effects with limited collateral issues. Moreover, nutraceuticals are easy to recover and are thus less expensive. On these bases, several scientific projects have aimed to test also their ability to induce tumor radiosensitization both in vitro and in vivo. The goal of this review is to describe what is known about the role of nutraceuticals in radiotherapy, their use and their potential application.


Assuntos
Suplementos Nutricionais , Neoplasias/radioterapia , Radiossensibilizantes/administração & dosagem , Radioterapia/métodos , Animais , Humanos
16.
Cancer Lett ; 467: 9-18, 2019 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-31563561

RESUMO

Radiation sensitizers that can selectively act on cancer cells hold great promise to patients who receive radiation therapy. We developed a novel targeted therapy and radiation sensitizer for non-small cell lung cancer (NSCLC) based on cetuximab conjugated nanoparticle that targets epidermal growth factor receptor (EGFR) and delivers small interfering RNA (siRNA) against polo-like kinase 1 (PLK1). EGFR is overexpressed in 50% of lung cancer patients and a mediator of DNA repair, while PLK1 is a key mitotic regulator whose inhibition enhances radiation sensitivity. The nanoparticle construct (C-siPLK1-NP) effectively targets EGFR + NSCLC cells and reduces PLK1 expression, leading to G2/M arrest and cell death. Furthermore, we show a synergistic combination between C-siPLK1-NP and radiation, which was confirmed in vivo in A549 flank tumors. We also demonstrate the translational potential of C-siPLK1-NP as a systemic therapeutic in an orthotopic lung tumor model, where administration of C-siPLK1-NP reduced tumor growth and led to prolonged survival. Our findings demonstrate that C-siPLK1-NP is effective as a targeted therapy and as a potent radiation sensitizer for NSCLC. Potential application to other EGFR + cancer types such as colorectal and breast cancer is also demonstrated.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Cetuximab/administração & dosagem , Neoplasias Pulmonares/terapia , RNA Interferente Pequeno/administração & dosagem , Radiossensibilizantes/administração & dosagem , Células A549 , Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas de Ciclo Celular/antagonistas & inibidores , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cetuximab/farmacologia , Receptores ErbB/antagonistas & inibidores , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Neoplasias Pulmonares/genética , Masculino , Terapia de Alvo Molecular , Nanopartículas , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , RNA Interferente Pequeno/farmacologia , Radiossensibilizantes/farmacologia , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Int J Mol Sci ; 20(18)2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31540386

RESUMO

Ultrasmall polyaminocarboxylate-coated gold nanoparticles (NPs), Au@DTDTPA and Au@TADOTAGA, that have been recently developed exhibit a promising potential for image-guided radiotherapy. In order to render the radiosensitizing effect of these gold nanoparticles even more efficient, the study of their localization in cells is required to better understand the relation between the radiosensitizing properties of the agents and their localization in cells and in tumors. To achieve this goal, post-functionalization of Au@DTDTPA nanoparticles by near-infrared (NIF) organic dyes (aminated derivative of cyanine 5, Cy5-NH2) was performed. The immobilization of organic Cy5-NH2 dyes onto the gold nanoparticles confers to these radiosensitizers fluorescence properties which can be exploited for monitoring their internalization in cancerous cells, for determining their localization in cells by fluorescence microscopy (a common and powerful imaging tool in biology), and for following up on their accumulation in tumors after intravenous injection.


Assuntos
Carbocianinas/análise , Corantes Fluorescentes/análise , Ouro/análise , Nanopartículas Metálicas/análise , Neoplasias/diagnóstico por imagem , Radiossensibilizantes/análise , Animais , Carbocianinas/administração & dosagem , Linhagem Celular Tumoral , Feminino , Corantes Fluorescentes/administração & dosagem , Ouro/administração & dosagem , Humanos , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/ultraestrutura , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia de Fluorescência/métodos , Imagem Óptica/métodos , Poliaminas/análise , Radiossensibilizantes/administração & dosagem
18.
Curr Oncol ; 26(4): e433-e438, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31548811

RESUMO

Background: Gliomas are the most dreaded primary brain tumour because of their dismal cure rates. Ketogenic-type diets (kds) are high-fat, low-protein, and low-carbohydrate diets; the modified Atkins diet (mad) is a less-stringent version of a kd that still generates serum ketones in patients. The purpose of the present study was to retrospectively examine the feasibility of attaining ketosis and the safety of the mad in patients undergoing radiation and chemotherapy treatment for glioma. The rate of pseudoprogression (psp) after treatment was also assessed as a marker of radiation sensitization. To our knowledge, this dataset is the largest published relating to patients with glioma undergoing kd during radiation and chemotherapy. Methods: We retrospectively studied 29 patients with grades ii-iv astrocytoma following the mad during standard radiation and chemotherapy. Feasibility of attaining ketosis was assessed though levels of beta hydroxybutyrate in blood. Pre- and post-radiation magnetic resonance images were evaluated for psp by a neuroradiologist blinded to patient data. Results: In the 29 patients who started the mad during radiation, ketosis was achieved in all 29 (100%). No serious adverse events occurred secondary to the mad. Of those 29 patients, 19 had glioblastoma multiforme. Of the latter 19 patients, 11 (58%) showed psp after mad and radiation and temozolomide therapy. Conclusions: A modified Atkins diet is feasible and safe for glioma patients during radiation and chemotherapy treatment. The mad and resulting ketosis could play a role as a radiation sensitizer.


Assuntos
Neoplasias Encefálicas/terapia , Dieta Cetogênica/métodos , Glioma/terapia , Radiossensibilizantes/administração & dosagem , Ácido 3-Hidroxibutírico/sangue , Adulto , Idoso , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/patologia , Estudos de Viabilidade , Feminino , Glioma/sangue , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Radioterapia , Estudos Retrospectivos , Resultado do Tratamento
19.
Mol Cancer Ther ; 18(11): 2063-2073, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31413177

RESUMO

Sustained locoregional control of disease is a significant issue in patients with inflammatory breast cancer (IBC), with local control rates of 80% or less at 5 years. Given the unsatisfactory outcomes for these patients, there is a clear need for intensification of local therapy, including radiation. Inhibition of the DNA repair protein PARP1 has had little efficacy as a single agent in breast cancer outside of studies restricted to patients with BRCA mutations; however, PARP1 inhibition (PARPi) may lead to the radiosensitization of aggressive tumor types. Thus, this study investigates inhibition of PARP1 as a novel and promising radiosensitization strategy in IBC. In multiple existing IBC models (SUM-149, SUM-190, MDA-IBC-3), PARPi (AZD2281-olaparib and ABT-888-veliparib) had limited single-agent efficacy (IC50 > 10 µmol/L) in proliferation assays. Despite limited single-agent efficacy, submicromolar concentrations of AZD2281 in combination with RT led to significant radiosensitization (rER 1.12-1.76). This effect was partially dependent on BRCA1 mutational status. Radiosensitization was due, at least in part, to delayed resolution of double strand DNA breaks as measured by multiple assays. Using a SUM-190 xenograft model in vivo, the combination of PARPi and RT significantly delays tumor doubling and tripling times compared with PARPi or RT alone with limited toxicity. This study demonstrates that PARPi improves the effectiveness of radiotherapy in IBC models and provides the preclinical rationale for the opening phase II randomized trial of RT ± PARPi in women with IBC (SWOG 1706, NCT03598257).


Assuntos
Neoplasias Inflamatórias Mamárias/terapia , Ftalazinas/efeitos adversos , Piperazinas/efeitos adversos , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Radiossensibilizantes/administração & dosagem , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Neoplasias Inflamatórias Mamárias/metabolismo , Camundongos , Ftalazinas/farmacologia , Piperazinas/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Radiossensibilizantes/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Int J Mol Sci ; 20(16)2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31416237

RESUMO

We fabricated poly (ethylene glycol)-block-polycaprolactone (PEG-b-PCL) nanoemulsion for drug delivery and photodynamic therapy. PEG-b-PCL effectively stabilized the interface between water and soybean oil, and the resulting nanoemulsion was about 220.3 nm in diameter with spherical shape. For photodynamic therapy (PDT), chlorin e6 (Ce6) was loaded into the nanoemulsion as a photosensitizer (PS). These chlorin e6-loaded PEG-PCL nanoemulsions (Ce6-PCL-NEs) showed efficient cellular uptake and, upon laser irradiation, generated singlet oxygen to kill tumor cells. Particularly, Ce6-PCL-NEs showed prolonged blood circulation and about 60% increased tumor accumulation compared to free Ce6 after intravenous injection to 4T1 tumor-bearing mice. These results demonstrate the promising potential of Ce6-PCL-NEs for efficient PDT and in vivo drug delivery to tumor tissue.


Assuntos
Portadores de Fármacos/química , Emulsões , Lactonas/química , Nanopartículas , Polietilenoglicóis/química , Porfirinas/administração & dosagem , Radiossensibilizantes/administração & dosagem , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Emulsões/química , Camundongos , Modelos Animais , Nanopartículas/química , Nanopartículas/ultraestrutura , Fotoquimioterapia , Porfirinas/química , Porfirinas/farmacocinética , Radiossensibilizantes/química , Distribuição Tecidual
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...