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1.
Rinsho Ketsueki ; 60(10): 1455-1461, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31695007

RESUMO

A 64-year-old woman was diagnosed with diffuse large B-cell lymphoma (DLBCL) in 2013. After eight courses of R-CHOP therapy followed by local irradiation of the remaining retroperitoneal soft tissue shadow, complete response was confirmed on 18F-2-fluoro-2-deoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT). Early in 2016, patient's serum LDH and soluble IL-2 receptor levels elevated. With suspected recurrence of DLBCL, FDG-PET/CT was performed that showed no lymphadenopathy or abnormal FDG uptake. By the end of July 2016, the patient developed fever and night sweating. Intravascular large B-cell lymphoma (IVLBCL) was suspected, and the patient underwent random skin biopsies, which revealed large atypical cells infiltrating peripheral and intravascular regions of the subcutaneous adipose tissue. Cell morphology, immunostaining, and PCR analysis of the immunoglobulin heavy chain gene suggested the recurrence of DLBCL. Despite salvage chemotherapy and autologous peripheral stem cell transplantation with high-dose chemotherapy, approximately 15 months later, DLBCL recurred and involved the lungs. The patient again received chemotherapy and achieved a second remission. Because DLBCL may recur like intravascular lymphoma, the same tests used for IVLBCL diagnosis are required in cases of suspected recurrence of DLBCL based on clinical and laboratory findings.


Assuntos
Linfoma Difuso de Grandes Células B/diagnóstico , Neoplasias Vasculares/diagnóstico , Idoso , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Doxorrubicina , Feminino , Fluordesoxiglucose F18 , Humanos , Linfoma Difuso de Grandes Células B/terapia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Tomografia por Emissão de Pósitrons , Prednisona , Recidiva , Indução de Remissão , Terapia de Salvação , Transplante de Células-Tronco , Neoplasias Vasculares/terapia , Vincristina
2.
Anticancer Res ; 39(11): 6087-6095, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704836

RESUMO

BACKGROUND: RAS GTPase-activating protein-binding protein (G3BP1) is an RNA-binding protein that is essential for assembling stress granules. Many functions related to the survival and progression of cancer have been reported. The current study aimed to investigate the role of G3BP1 in radio-sensitisation of cancer cells. MATERIALS AND METHODS: Radiation sensitivity and chemosensitivity were analysed in A549 and H460 cells transfected with G3BP1 siRNAs, and N-acetyl-L-cysteine (NAC) was used to elucidate the involvement of reactive oxygen species (ROS). RESULTS: G3BP1 depletion sensitised lung cancer cell lines to radiation, and the effect was related to ROS. G3BP1 depletion impaired the intracellular ROS scavenging system and NAC abolished the radiation-sensitive phenotypes caused by G3BP1 depletion. CONCLUSION: The study suggested G3BP1 as a promising target for radio- and chemosensitisation of lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Dano ao DNA/efeitos da radiação , DNA Helicases/antagonistas & inibidores , Neoplasias Pulmonares/radioterapia , Estresse Oxidativo/efeitos da radiação , Proteínas de Ligação a Poli-ADP-Ribose/antagonistas & inibidores , RNA Helicases/antagonistas & inibidores , Proteínas com Motivo de Reconhecimento de RNA/antagonistas & inibidores , Tolerância a Radiação/efeitos dos fármacos , Antibióticos Antineoplásicos/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células , DNA Helicases/genética , DNA Helicases/metabolismo , Doxorrubicina/farmacologia , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Ligação a Poli-ADP-Ribose/genética , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , RNA Helicases/genética , RNA Helicases/metabolismo , Proteínas com Motivo de Reconhecimento de RNA/genética , Proteínas com Motivo de Reconhecimento de RNA/metabolismo , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismo , Células Tumorais Cultivadas
3.
J Environ Pathol Toxicol Oncol ; 38(2): 143-152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679277

RESUMO

The current study evaluated the cardioprotective activity of genistein in cases of doxorubicin-(Dox) induced cardiac toxicity and a probable mechanism underlying this protection, such as an antioxidant pathway in cardiac tissues. Animals used in this study were categorized into four groups. The first group was treated with sodium carboxymethylcellulose (0.3%; CMC-Na) solution. The second group received Dox (3.0 mg/kg, i.p.) on days 6, 12, 18, and 24. The third and fourth groups received Dox (3 mg/kg, i.p.) on days 6, 12, 18, and 24 and received protective doses of genistein (100 [group 3] and 200 [group 4] mg/kg/day, p.o.) for 30 days. Treatment with genistein significantly improved the altered cardiac function markers and oxidative stress markers. This was coupled with significant improvement in cardiac histopathological features. Genistein enhanced the Nrf2 and HO-1 expression, which showed protection against oxidative insult induced by Dox. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed substantial inhibition of apoptosis by genistein in myocardia. The study showed that genistein has a strong reactive oxygen species scavenging property and potentially (P ≤ .001) decreases the lipid peroxidation as well as inhibits DNA damage in cardiac toxicity induced by Dox. In conclusion, the potential antioxidant effect of genistein may be because of its modulatory effect on Nrf2/HO-1 signalling pathway and by this means exhibits cardioprotective effects from Dox-induced oxidative injury.


Assuntos
Cardiotônicos/farmacologia , Cardiotoxinas/toxicidade , Doxorrubicina/toxicidade , Genisteína/farmacologia , Heme Oxigenase-1/genética , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Animais , Cardiotoxicidade/etiologia , Heme Oxigenase-1/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Ratos Wistar
4.
J Environ Pathol Toxicol Oncol ; 38(2): 153-163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679278

RESUMO

Chemobrain is a significant post-chemotherapy complication for which no approved treatments are available. We had previously identified that rutin inhibits doxorubicin (Dox-) -induced cognitive decline in healthy rats. However, it was important to also establish that it does so in rats with mammary carcinoma without compromising Dox's antitumor potential. Mammary carcinoma was induced in female rats by intraperitonial administration of N-methyl-N-nitrosourea (i.p.). Rats that developed mammary carcinoma were treated with Dox after pretreatment with vehicle or rutin. After Dox exposure (50 days), episodic and spatial memory was assessed using the novel object recognition task and the Morris water maze, respectively. Tumor progression was evaluated by measurement of tumor weight and volume and histological analysis. Blood samples were collected to estimate hematological parameters. Oxidative status and TNF-α levels were estimated in brain homogenates. Dox treatment significantly reduced tumor size and volume. Pretreatment with rutin did not significantly alter Dox's tumor suppression potential, suggesting that it does not influence Dox's anticancer activity. In addition, rutin ameliorated Dox-induced cognitive decline, myelosuppression, and brain oxidative stress. The present study indicates that rutin protects against Dox-induced cognitive decline and myelosuppression without affecting its antitumor potential.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/induzido quimicamente , Doxorrubicina/farmacologia , Metilnitrosoureia/toxicidade , Substâncias Protetoras/farmacologia , Rutina/farmacologia , Animais , Disfunção Cognitiva/induzido quimicamente , Doxorrubicina/toxicidade , Feminino , Ratos , Ratos Sprague-Dawley
5.
J Surg Oncol ; 120(7): 1220-1226, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31602673

RESUMO

BACKGROUND AND OBJECTIVES: Hyperthermic intrathoracic chemotherapy (HITOC) is used for the treatment of malignant pleural tumors. Although HITOC proved to be safe, postoperative renal failure due to nephrotoxicity of intrapleural cisplatin remains a concern. METHODS: This single-center study was performed retrospectively in patients who underwent pleural tumor resection and HITOC between September 2008 and December 2018. RESULTS: A total of 84 patients (female n = 33; 39.3%) with malignant pleural tumors underwent surgical cytoreduction with subsequent HITOC (60 minutes; 42°C). During the study period, we gradually increased the dosage of cisplatin (100-150 mg/m2 BSA n = 36; 175 mg/m2 BSA n = 2) and finally added doxorubicin (cisplatin 175 mg/m2 BSA/doxorubicin 65 mg; n = 46). All patients had perioperative fluid balancing. The last 54 (64.3%) patients also received perioperative cytoprotection. Overall 29 patients (34.5%) experienced renal insufficiency. Despite higher cisplatin concentrations, patients with cytoprotection showed significantly lower postoperative serum creatinine levels after 1 week (P = .006) and at discharge (P = .020). Also, they showed less intermediate and severe renal insufficiencies (5.6% vs 13.3%). CONCLUSIONS: Adequate perioperative fluid management and cytoprotection seem to be effective in protecting renal function. This allows the administration of higher intracavitary cisplatin doses without raising the rate of renal insufficiencies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Hipertermia Induzida/efeitos adversos , Mesotelioma/terapia , Néfrons/efeitos dos fármacos , Neoplasias Pleurais/terapia , Substâncias Protetoras/administração & dosagem , Insuficiência Renal Crônica/tratamento farmacológico , Amifostina/administração & dosagem , Cisplatino/administração & dosagem , Terapia Combinada , Creatinina/sangue , Citoproteção , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Mesotelioma/patologia , Pessoa de Meia-Idade , Neoplasias Pleurais/patologia , Cuidados Pós-Operatórios , Prognóstico , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Tiossulfatos/administração & dosagem , Cavidade Torácica/cirurgia
6.
Chem Commun (Camb) ; 55(87): 13082-13084, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31608901

RESUMO

Herein, a photoelectrochemical biosensor was successfully constructed on the basis of a sensitization strategy of doxorubicin sensitized graphitic carbon nitride for the ultrasensitive detection of microRNA-141 with the assistance of a target-activated enzyme-free DNA walker.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Técnicas Biossensoriais , DNA/efeitos dos fármacos , Doxorrubicina/farmacologia , Técnicas Eletroquímicas , Grafite/química , MicroRNAs/análise , Compostos de Nitrogênio/química , Antibióticos Antineoplásicos/química , Doxorrubicina/química , Processos Fotoquímicos
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1490-1496, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607303

RESUMO

OBJECTIVE: To investigate the efficacy of multiple protein expressions and clinical features on the threapeutic effect and prognosis of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical data of 68 DLBCL patients were collected and analyzed retrospectively. The clinical staging was performed according to Ann Arbor staging; the risk grading was performed by IPI index; the DLBCL typing (germinal center and non-germinal center) was performed according to B cell source; the expression of Ki67,BCL-2, BCL-6, C-MYC, MUM1 and CD10 protein was detected by immunohistochemistry method; the patients were divided into R-CHOP group(50 cases) and CHOP group(18 cases) according to chemotherapy regimen of using rituximab or not; finally, the related factors affecting the prognosis of patients(PFS and OS) were analysed statistically by using SPSS 22.0 software according to sex, age, erythrocyte sedimentation rate (ESR), lactate dehydrogenase(LDH) and use of rituximab or no, as well as the above-mentioned clinical indicators. RESULTS: IPI grade high-risk, elevated LDH, positive expression of BCL-2 protein and negative expression of BCL-6 protein were independent prognostic factors for progression-free survival (PFS); elevated LDH and negative expression of BCL-6 protein were independent prognostic factors for overall survival time (OS); multivariate analysis showed that elevated LDH and positive expression of BCL-2 protein were independent prognostic factors for progression-free survival (PFS). The overall survival time (OS) associated with ESR, IPI classification and BCL-6 protein expression. CONCLUSION: The expression of BCL-2 and BCL-6 protein and some clinical features can be used as predictors of clinical efficacy for DLBCL. Choosing the treatment regimen combined with ritu-ximab can further improve the survival and prognosis of DLBCL patients.


Assuntos
Linfoma Difuso de Grandes Células B , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Doxorrubicina , Humanos , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-6 , Estudos Retrospectivos
9.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(4): 615-618, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31642245

RESUMO

OBJECTIVE: To evaluate the clinical effect of bortezomib with different dose-frequency in the treatment of multiple myeloma. METHODS: 86 patients with multiple myeloma in our hospital from February 2011 to February 2017 were included in the study. The patients were randomly divided into the experimental group (43 cases) and the control group (43 cases). The patients in the control group were treated with high dose bortezomib (1.6 mg/m2) on day 1, day 8, day 15 and day 22, with 35 d as a chemotherapy cycle. The patients in experimental group was treated with low dose bortezomib (1.0-1.3 mg/m2) on day 1, day 4, day 8 and day 11, with 21 d as a chemotherapy cycle. The patients in both groups were given dexamethasone(40 mg/d) and doxorubicin (10 mg/m2) from day 1 to day 4, and thalidomide was given orally at the intervals of 6 chemotherapy cycles. The clinical effect and the incidence of adverse drug reactions were compared between the two groups. RESULTS: The overall response rate (ORR) and disease control rate (DCR) were 88.37% and 95.35% respectively in the experimental group, while those of the control group were 81.40% and 90.70% respectively. There was no significant difference in ORR and DCR between the two groups. In the incidence of leukopenia, thrombocytopenia and neutropenia showed no significant difference between the two groups. The incidences of grade Ⅲ to grade Ⅳ peripheral neuropathy, herpes zoster, fatigue and abdominal distension in the experimental group were 2.33%, 4.65%, 13.95% and 2.33% respectively, while those of the control group were 16.28%, 27.91%, 34.88% and 18.60% respectively. The differences of the above incidences between the two groups were significant (P < 0.05). All the patients were followed up for 24 months. There was no significant difference in the overall survival (OS) rate, progression-free survival (PFS) rate and cumulative recurrence rate between the two groups. CONCLUSIONS: The effect of bortezomib in the treatment of multiple myeloma was similar at different dose-frequency group. The patients treated with low dose bortezomib (day 1, day 4, day 8 and day 11) had the better tolerance and lower incidences of adverse drug reactions.


Assuntos
Bortezomib/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Dexametasona/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Humanos , Recidiva Local de Neoplasia , Resultado do Tratamento
10.
Beijing Da Xue Xue Bao Yi Xue Ban ; 51(5): 791-796, 2019 Oct 18.
Artigo em Chinês | MEDLINE | ID: mdl-31624379

RESUMO

OBJECTIVE: p53 gene, as "the guardian of the genome", is the most widely studied tumor suppressor gene. Previous studies have shown that about 50 percent of tumors have P53 dysfunction. This article aims to retrospectively analyze the correlation between p53 rs1625895 polymorphism and the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: PCR combined with Sanger sequencing were used to detect rs1625895 genotype in 384 DLBCL patients. The relationship between rs1625895 polymorphisms and the clinical characteristics, first-line therapeutic effects and the prognosis of the patients were analyzed. RESULTS: Among all the patients, 2 (0.5%) patients with AA genotype, 34 (8.9%) patients with AG genotype and 348 (90.6%) patients with GG genotype were identified. The patients with different rs1625895 genotypes did not have any difference in terms of age, gender, B symptoms (developing any of the following symptoms: unexplained recurrent fever (often above 38 °C), night sweats, and unexplained weight loss of 10% within 6 months ), erythrocyte sedimentation rate (ESR), international prognostic index (IPI) and molecular subtype (P>0.05). The overall response rate (ORR) was 82.9% and 82.8% in AA/AG and GG, respectively. There was no significant difference between the first-line therapeutic effects of the two groups (P>0.05). And there was also no difference between A allele carriers and homozygous G allele carriers for the 5-year progressionfree survival rate (PFS) (71.8% vs. 62.3%, χ2=1.351, P=0.245) and 5-year overall survival rate (OS) (72.2% vs. 64.1%, χ2=1.267, P=0.260). But in the subgroup with Germinal Center B-cell (GCB) type, the patients carrying A allele for rs1625895 had an obviously longer PFS (91.7% vs. 72.7%, χ2=4.493, P=0.034) and OS (91.7% vs. 76.7%, χ2=4.246, P=0.039) compared with the patients homozygous for the G allele. As for the patients with non-GCB subtype, there was no significant difference in PFS and OS between different rs1625895 genotypes (P>0.05). According to whether the first-line regimen contained rituximab or not, the patients were divided into two groups treated with cyclophosphoramide, doxorubicin, vincristine and prednisone (CHOP) or with rituximab and CHOP (R-CHOP). But in both subgroups, there was no significant difference in the 5-year PFS and OS between the AA/AG and GG patients, too (P>0.05). CONCLUSION: For DLBCL patients receiving CHOP regimen chemotherapy in the first line, p53 rs1625895 cannot predict the clinical efficacy and prognosis of the patients, but in the patients with GCB subtype, this polymorphism may be a prognostic indicator.


Assuntos
Linfoma Difuso de Grandes Células B/diagnóstico , Proteína Supressora de Tumor p53/metabolismo , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Intervalo Livre de Doença , Doxorrubicina , Humanos , Prednisona , Prognóstico , Estudos Retrospectivos , Vincristina
11.
Int J Nanomedicine ; 14: 6901-6915, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564860

RESUMO

Background: Smart materials capable of responding to external stimuli are noteworthy candidates in designing drug delivery systems. In many of the recent research, temperature and pH have been recognized as the main stimulating factors in designing systems for anti-cancer drugs delivery systems. Purpose: In this study, thermo and pH-responsive character of a nano-carrier drug delivery platform based on lysine modified poly (vinylcaprolactam) hydrogel conjugated with doxorubicin was assessed. Methods: Poly (vinylcaprolactam) cross-linked with poly (ethyleneglycol) diacrylate was prepared via RAFT polymerization, and the prepared structure was linked with lysine through ring-opening. The anti-cancer drug doxorubicin, was linked to lysine moiety of the prepared structure via Schiff-base reaction. The prepared platform was characterized by 1HNMR and FT-IR, while molecular weight characterization was performed by size exclusion chromatography. The temperature-responsive activity was evaluated using differential scanning calorimetry and dynamic light scattering. In vitro release pattern in simulated physiologic pH at 37°C was compared with acidic pH attributed to tumor site and elevated temperature. The anticancer efficiency of the drug-conjugated structure was evaluated in breast cancer cell line MCF-7 in 24 and 48 h, and cell uptake assay was performed on the same cell line. Conclusion: According to the results, well-structure defined smart pH and temperature responsive nano-hydrogel was prepared. The enhanced release rates are observed at acidic pH and elevated temperature. We have concluded that the doxorubicin-conjugated nanoparticle results in higher cellular uptakes and more cytotoxicity.


Assuntos
Caprolactama/análogos & derivados , Sistemas de Liberação de Medicamentos , Hidrogéis/química , Lisina/química , Nanopartículas/química , Polímeros/química , Temperatura Ambiente , Caprolactama/síntese química , Caprolactama/química , Morte Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Humanos , Hidrogéis/síntese química , Concentração de Íons de Hidrogênio , Células MCF-7 , Peso Molecular , Nanopartículas/ultraestrutura , Transição de Fase , Polímeros/síntese química , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Testes de Toxicidade
12.
Int J Nanomedicine ; 14: 7017-7038, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564863

RESUMO

Background: Fabrication of a smart drug delivery system that could dramatically increase the efficiency of chemotherapeutic drugs and reduce the side effects is still a challenge for pharmaceutical researchers. By the emergence of nanotechnology, a huge window was opened towards this goal, and a wide type of nanocarriers were introduced for delivering the chemotherapeutic to the cancer cells, among them are cyclodextrins with the ability to host different types of hydrophobic bioactive molecules through inclusion complexation process. Aim: The aim of this study is to design and fabricate a pH-responsive theranostic nanocapsule based on cyclodextrin supramolecular nano-structure. Materials and methods: This nanostructure contains iron oxide nanoparticles in the core surrounded with three polymeric layers including polymeric ß-cyclodextrin, polyacrylic acid conjugated to sulfadiazine, and polyethylenimine functionalized with ß-cyclodextrin. Sulfadiazine is a pH-responsive hydrophobic component capable of making inclusion complex with ß-cyclodextrin available in the first and third layers. Doxorubicin, as an anti-cancer drug model, was chosen and the drug loading and release pattern were determined at normal and acidic pH. Moreover, the biocompatibility of the nanocapsule (with/without drug component) was examined using different techniques such as MTT assay, complement activation, coagulation assay, and hemolysis. Results: The results revealed the successful preparation of a spherical nanocapsule with mean size 43±1.5 nm and negatively charge of -43 mV that show 160% loading efficacy. Moreover, the nanocapsule has an on/off switching release pattern in response to pH that leads to drug released in low acidic pH. The results of the biocompatibility tests indicated that this nano drug delivery system had no effect on blood and immune components while it could affect cancer cells even at very low concentrations (0.3 µg mL-1). Conclusion: The obtained results suggest that this is a "switchable" theranostic nanocapsule with potential application as an ideal delivery system for simultaneous cancer diagnosis and therapy.


Assuntos
Nanocápsulas/química , Polietilenoimina/química , Nanomedicina Teranóstica , beta-Ciclodextrinas/química , Animais , Doxorrubicina/química , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Compostos Férricos/química , Hemólise/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Camundongos , Nanocápsulas/ultraestrutura , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Eletricidade Estática , Compostos de Sulfidrila/síntese química , Compostos de Sulfidrila/química , Difração de Raios X , beta-Ciclodextrinas/síntese química
13.
Int J Nanomedicine ; 14: 7141-7153, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564870

RESUMO

Background: Theranostics, elaborately integrating both therapeutic and diagnostic functions into a nanoplatform holds great potential for precision cancer medicine. Methods: Herein, a biodegradable theranostic nanoplatform with hyperthermia-induced bubble ability for highly efficient ultrasound (US) imaging-guided chemo-photothermal therapy of breast tumors was developed. The prepared nanoparticles consisted of polydopamine (PDA)-modified hollow mesoporous organosilica nanoparticles (HMONs) with approximately 75 nm in diameter for doxorubicin (DOX) loading and perfluoropentane (PFP) filling. In addition, the pH-sensitive PDA coating served as both gatekeeper controlling DOX release and photothermal agent for inducing hyperthermia. Results: Such nanoplatform (PDA@HMONs-DOX/PFP, PHDP) provides efficient loading (328 mg/g) and controllable stimuli-responsive release of DOX for chemotherapy. The incorporated disulfide bonds in the framework of HMONs endowed nanoparticles with intrinsic glutathione-responsive biodegradability and improved biocompatibility. Benefiting from the hyperthermia upon an 808-nm laser irradiation of PDA, the liquid-gas phase transition of the loaded PFP was induced, resulting in the generation of the nanobubbles, followed by the coalescence into microbubbles. This conversation could enhance the tumor cell uptake of nanoparticles, as well as intensify the US imaging signals. In addition, a synergistic therapeutic effect of our fabricated nanoplatform on cells/tumor growth effect has been systematically evaluated both in vitro and in vivo. Conclusion: Therefore, such "all-in-one" PHDP nanoparticles with satisfactory biocompatibility and biodegradability, hyperthermia-induced bubble ability and simultaneous US imaging performance hold great potential for cancer nanotheranostics.


Assuntos
Hipertermia Induzida , Microbolhas , Nanopartículas/química , Fototerapia , Nanomedicina Teranóstica , Ultrassonografia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Endocitose/efeitos dos fármacos , Feminino , Humanos , Indóis/química , Cinética , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/ultraestrutura , Polímeros/química , Distribuição Tecidual/efeitos dos fármacos
15.
Eur J Pharm Biopharm ; 145: 65-75, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31628997

RESUMO

With a very poor prognosis and no clear etiology, glioma is the most aggressive cancer in the brain. Thanks to its versatility, nanomedicine is a promising option to overcome the limitations on chemotherapy imposed by the blood brain barrier (BBB). The objective of this paper was to obtain monitored tumor-targeted therapeutic nanoparticles (NPs). To that end, theranostic surfactant-coated polymer poly-Lactic-co-Glycolic Acid (PLGA) nanoplatform encapsulating doxorubicin hydrochloride (DOX) and superparamagnetic iron oxide NPs (SPIONs) were developed. Different non-ionic surfactants known as BBB crossing enhancers (Tween 80, Brij-35, Pluronic F68 or Vitamin E-TPGS) were used to develop 4 types of theranostic nanoplatforms, which were characterized in terms of size and morphology by DLS, TEM and STEM-HAADF analyses. Moreover, the 3-month stability test, the therapeutic efficacy against different glioma cell lines (U87-MG, 9L/LacZ and patient derived-neuronal stem cells) and the Magnetic Resonance Imaging (MRI) relaxivity were studied. Results showed that the synthesised nanoplatforms were stable at 4 °C after their lyophilization, being that of paramount importance to ensure a long-term stability in a future in vivo application. Furthermore, the theranostic nanoplatforms were efficient in the in vitro treatment of glioma cells, proving to have imaging efficacy as MRI contrast agents. Our results show an efficient loading of drugs and good value of the relaxivity. Therefore, the efficient theranostic hybrid nanoplatform developed here could be used to perform MRI-guided delivery of hydrophobic drugs.


Assuntos
Antineoplásicos/química , Doxorrubicina/química , Portadores de Fármacos/química , Glioma/tratamento farmacológico , Nanopartículas de Magnetita/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Antineoplásicos/administração & dosagem , Linhagem Celular , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Humanos , Tamanho da Partícula , Ratos , Tensoativos/química
16.
Eur J Pharm Biopharm ; 145: 54-64, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31654712

RESUMO

To achieve enhanced cancer therapy, a sequentially dynamic polymeric drug delivery system (ortho ester-linked PEGylated poly(disulfide)s-based micelle-doxorubicin (PS-g-OEMPEG-DOX)) is successfully constructed. The PEGylated micelle can keep stable in sodium dodecyl sulfate (SDS) solution at pH 7.4, but be prone to DePEGylation and dynamic size changes via the hydrolysis of ortho ester linkages in side chains at tumoral extracellular pH value (6.5). Moreover, the micelle can rapidly release DOX via the cleavage of poly(disulfide)s in backbone at intracellular reductive milieu (10 mmol/L of dithiothreitol (DTT)). The dynamic micelle with detachable PEGylation achieves the stable blood circulation, improved cellular uptake and cytotoxicity, stronger in vitro penetration and inhibition of tumoral multicellular spheroids, and significant in vivo tumor accumulation and inhibition while decreasing side effects. Thus, the sequentially dynamic polymeric micelle with detachable PEGylation can be considered as a promising and effective drug delivery system in cancer therapy.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/química , Neoplasias/tratamento farmacológico , Polietilenoglicóis/química , Polímeros/química , Animais , Linhagem Celular Tumoral , Ditiotreitol/administração & dosagem , Ditiotreitol/química , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Hidrólise/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Micelas , Dodecilsulfato de Sódio/química
17.
Rinsho Ketsueki ; 60(9): 1193-1198, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597843

RESUMO

In 2018 the practical guidelines for hematological malignancies, edited by Japanese Society of Hematology, underwent major revision for the first time in five years. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) remains the standard treatment for diffuse large B-cell lymphoma (DLBCL) in line with the prior 2013 guidelines. R-CHOP has been considered as the standard treatment for DLBCL since early 2000s, when a 20% improvement in survival was observed when adding rituximab to CHOP. Following this, several clinical trials were conducted, but most attempts to exceed R-CHOP have failed. Moreover, this evidence has raised further research questions. In this report, the current evidence and the problems associated with DLBCL treatments have been reviewed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos como Assunto , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Prednisona/uso terapêutico , Rituximab , Resultado do Tratamento , Vincristina/uso terapêutico
18.
Anticancer Res ; 39(10): 5703-5707, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570470

RESUMO

BACKGROUND/AIM: Anthracyclines, such as doxorubicin, though widely used in anticancer therapy, they are associated with cardiotoxic side-effects. The aim of this trial was to investigate long-term follow-up cardiotoxicity findings in patients treated with doxorubicin and concomitant metoprolol or enalapril 10 years earlier. PATIENTS AND METHODS: Overall, 147 patients were randomized into the treatment arms. A total of 125 patients treated with doxorubicin without evidence of heart disease at the start of chemotherapy were analyzed. They were followed-up for up to 10 years after treatment start. RESULTS AND CONCLUSION: A total of 47 patients completed the follow-up and 21 patients died, none due to cardiotoxicity events. Clinical signs of heart failure were not seen in any patients and no statistically significant differences between baseline and 10-year findings were seen for echocardiographic variables. No evidence of long-term cardiotoxicity was seen and nor metoprolol or enalapril offered an additional benefit.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Cardiotoxicidade/prevenção & controle , Doxorrubicina/efeitos adversos , Enalapril/uso terapêutico , Linfoma/tratamento farmacológico , Metoprolol/uso terapêutico , Adolescente , Antraciclinas/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Cardiotoxicidade/etiologia , Doxorrubicina/uso terapêutico , Ecocardiografia/métodos , Feminino , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Masculino , Estudos Prospectivos
19.
Int J Nanomedicine ; 14: 7609-7624, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571866

RESUMO

Background: Iron oxide nanoparticles (IONs) have been increasingly utilized in a wide spectrum of biomedical applications. Surface coatings of IONs can bestow a number of exceptional properties, including enhanced stability of IONs, increased loading of drugs or their controlled release. Methods: Using two-step sonochemical protocol, IONs were surface-coated with polyoxyethylene stearate, polyvinylpyrrolidone or chitosan for a loading of two distinct topo II poisons (doxorubicin and ellipticine). The cytotoxic behavior was tested in vitro against breast cancer (MDA-MB-231) and healthy epithelial cells (HEK-293 and HBL-100). In addition, biocompatibility studies (hemotoxicity, protein corona formation, binding of third complement component) were performed. Results: Notably, despite surface-coated IONs exhibited only negligible cytotoxicity, upon tethering with topo II poisons, synergistic or additional enhancement of cytotoxicity was found in MDA-MB-231 cells. Pronounced anti-migratory activity, DNA fragmentation, decrease in expression of procaspase-3 and enhancement of p53 expression were further identified upon exposure to surface-coated IONs with tethered doxorubicin and ellipticine. Moreover, surface-coated IONs nanoformulations of topo II poisons exhibited exceptional stability in human plasma with no protein corona and complement 3 binding, and only a mild induction of hemolysis in human red blood cells. Conclusion: The results imply a high potential of an efficient ultrasound-mediated surface functionalization of IONs as delivery vehicles to improve therapeutic efficiency of topo II poisons.


Assuntos
Materiais Revestidos Biocompatíveis/química , DNA Topoisomerases Tipo II/metabolismo , Liberação Controlada de Fármacos , Compostos Férricos/química , Nanopartículas/química , Sonicação/métodos , Inibidores da Topoisomerase II/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Humanos , Cinética , Masculino , Eletricidade Estática , Propriedades de Superfície , Cicatrização/efeitos dos fármacos
20.
Int J Nanomedicine ; 14: 7627-7642, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571868

RESUMO

Purpose: Focused ultrasound-mediated chemotherapy, as a non-invasive therapeutic modality, has been extensively explored in combating deep tumors for predominant penetration performance. However, the generally used high-intensity focused ultrasound (HIFU) inevitably jeopardizes normal tissue around the lesion for hyperthermal energy. To overcome this crucial issue, low-intensity focused ultrasound (LIFU) was introduced to fulfill precisely controlled imaging and therapy in lieu of HIFU. The objective of this study was to develop a facile and versatile nanoplatform (DPP-R) in response to LIFU and provide targeted drug delivery concurrently. Methods: Multifunctional DPP-R was fabricated by double emulsion method and carbodiimide method. Physicochemical properties of DPP-R were detected respectively and the bio-compatibility and bio-safety were evaluated by CCK-8 assay, blood analysis, and histologic section. The targeted ability, imaging function, and anti-tumor effect were demonstrated in vitro and vivo. Results: The synthetic DPP-R showed an average particle size at 367 nm, stable physical-chemical properties in different media, and high bio-compatibility and bio-safety. DPP-R was demonstrated to accumulate at the tumor site by active receptor/ligand reaction and passive EPR effect with intravenous administration. Stimulated by LIFU at the tumor site, phase-transformable PFH was vaporized in the core of the integration offering contrast-enhanced ultrasound imaging. The stimuli led to encapsulated DOX's initial burst release and subsequent sustained release for anti-tumor therapy which was verified to be more effective and have less adverse effects than free DOX. Conclusion: DPP-R combined with LIFU provides a novel theranostic modality for GC treatment with potent therapeutic effect, including prominent performance of targeting, ultrasound imaging, and accurate drug release.


Assuntos
Doxorrubicina/uso terapêutico , Composição de Medicamentos , Nanopartículas/química , Transição de Fase , Neoplasias Gástricas/terapia , Nanomedicina Teranóstica , Ultrassonografia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Feminino , Fluorcarbonetos/química , Humanos , Concentração de Íons de Hidrogênio , Camundongos Nus , Oligopeptídeos/química , Imagem Óptica , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Neoplasias Gástricas/tratamento farmacológico , Distribuição Tecidual/efeitos dos fármacos
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