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1.
AAPS PharmSciTech ; 21(2): 57, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31912318

RESUMO

The aim of this study was to examine the effectiveness of alanine-proline-arginine-proline-glycine (APRPG) peptide-conjugated PEGylated cationic liposomes-encapsulated zoledronic acid (ZOL) (APRPG-PEG-ZOL-CLPs) in achieving vascular normalization. Cisplatin (diamminedichloroplatinum, DDP) was used to improve anticancer efficacy. The present study showed that APRPG-PEG-ZOL-CLPs increased anticancer efficacy, which was regarded as vascular normalization. Our results demonstrated that the viability, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were evidently repressed by APRPG-PEG-ZOL-CLPs. Moreover, APRPG-PEG-ZOL-CLPs could decrease vessel density, as well as hypoxia-inducible factor 1α (HIF-1α), and increase thrombospondin 1 (TSP-1) expression of tumors. Therefore, the anticancer efficacy of APRPG-PEG-ZOL-CLPs combined with DDP was superior to that of PEG-ZOL-CLP or ZOL treatment combined with DDP schemes, as demonstrated by the obviously evident reduction in tumor volume. These results indicated that APRPG-PEG-ZOL-CLPs were most effective in normalizing tumor vasculature to elevate the therapeutic effect of antitumor drugs.

2.
Drug Deliv Transl Res ; 10(1): 93-107, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31418132

RESUMO

The metronomic administration of a low-dose cytotoxic agent with no prolonged drug-free breaks is an anti-angiogenic cancer treatment method. The use of nano-formulations in this manner enhances anti-tumor efficacy and reduces toxicity by inhibiting angiogenic activity, reduces adverse effects, and changes the biodistribution of TP in the body, steering TP away from potentially endangering healthy tissues. The present study uses liposomes and Asn-Gly-Arg (NGR) peptide conjugated aminopeptidase N(APN)-targeted liposomes for triptolide (TP), as a model for the investigation of targeted metronomic administration and subsequent effects on the toxicity profile and efficacy of the chemotherapeutic agent. Metronomic NGR-PEG-TP-LPs have been found to have enhanced anti-tumor activity, a phenomenon that is attributed to an increase in angiogenic inhibition properties. In vitro experiments demonstrate that the viability, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) are obviously suppressed in comparison with that of other treatment groups. In vivo experiments also demonstrate that the anti-tumor efficacy of targeted metronomic administration is superior to that of liposome-administered treatments given at maximum tolerated dose (MTD) schemes, as is evidenced by markedly decreased tumor volume, vessel density, and the volume of circulating endothelial progenitor cells (CEPCs) in serum. Moreover, we observed that the metronomic administration of NGR-PEG-TP-LPs could elevate thrombospondin-1 (TSP-1) expression in tumors, a finding that is consistent with the promotion of TSP-1 secretion specifically from HUVECs. Additionally, metronomic NGR-PEG-TP-LPs have minimal drug-associated toxicity (weight loss, hepatotoxicity and nephrotoxicity in mice). Our research demonstrates the significance of targeted metronomic administration using liposomes for anti-angiogenic cancer therapy.

3.
J Cancer Res Ther ; 14(Supplement): S656-S660, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30249883

RESUMO

Objective: To investigate the prevalence and characteristics of gemcitabine-based chemotherapy-induced thrombocytopenia in Chinese patients with nonsmall cell lung cancer (NSCLC). Materials and Methods: Medical records of 197 patients with histologically proven NSCLC received gemcitabine-based chemotherapy from June 2011 to June 2013 in our hospital were collected. The relative risk factors were identified and evaluated by univariate and multivariate analyses. Results: The incidence of gemcitabine-based chemotherapy-induced thrombocytopenia in these NSCLC patients was 85.8%. Between thrombocytopenia and nonthrombocytopenia patients, in patients with thrombocytopenia and thrombocytopenia, we found Stage III/IV patients got more probabilities for thrombocytopenia (P < 0.01). In addition, patients who received gemcitabine and cisplatin (GP) regimen resulted in more thrombocytopenia than gemcitabine and carboplatin (GC) and other regimens (P < 0.001). In addition, majority of the thrombocytopenia patients presented thrombocytopenia in their first cycle (P < 0.001). Whereas, other potential risk factors such as age, gender, performance status value, diabetes mellitus or not, and other underlying disease (hypertension and hepatopathy) were not showed such significance in this study. Further, the multivariate analysis revealed that stage (odds ratio [OR] 7.113, P < 0.01) and chemotherapy cycles (OR 0.543, P < 0.01) were also statistically significant independent risk factors for gemcitabine-based chemotherapy-induced thrombocytopenia. Conclusion: This study shows that thrombocytopenia is common in Chinese NSCLC patients receiving gemcitabine-based regimens. Chemotherapy cycles and stage might be the important factors influencing the occurrence of gemcitabine-based regimens-induced thrombocytopenia.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/efeitos adversos , Desoxicitidina/análogos & derivados , Trombocitopenia/patologia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , China/epidemiologia , Cisplatino/uso terapêutico , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Feminino , Humanos , Masculino , Registros Médicos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores de Risco , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologia , Resultado do Tratamento
4.
Oncotarget ; 8(48): 84248-84257, 2017 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-29137420

RESUMO

Zoledronic acid (ZOL) has been used as an adjuvant therapy for breast cancer. It is suggested that ZOL might be associated with inhibition of macrophages, which in turn reduces tumor growth, metastasis and tumor angiogenesis. Moreover, metronomic therapy can inhibit tumor angiogenesis and tumor immune cells. Previously we developed ZOL based cationic liposomes that allowed a higher intratumor delivery of drug compared with free ZOL in vivo. Therefore, in this study, Asn-Gly-Arg (NGR) and PEG2000 were used as ligands to modify the surface of liposomes (NGR-PEG-LP-ZOL) in metronomic therapy to clear the tumor-associated macrophages (TAMs) and inhibit the formation of tumor angiogenesis, achieving the purpose of anti-tumor growth. Our data showed that NGR-PEG-LP-ZOL metronomic therapy has the strongest inhibitory effect on tumor growth. Further, NGR-PEG-LP-ZOL metronomic therapy could significantly impair TAMs by inhibiting the expression of CD206 antibody in tumor tissues, decreasing the expression of cytokine related gene expression of TAMs, as well as reducing the percentage of TAMs in tumor tissues. In addition, NGR-PEG-LP-ZOL metronomic therapy could significantly inhibit the expression of tumor neovascular specific antibody CD31 and reduce the microvessel density. In conclusion, our study demonstrated that NGR-PEG-LP-ZOL metronomic therapy could impair TAMs by inhibiting tumor angiogenesis and enhance the antitumor effect of ZOL.

5.
Onco Targets Ther ; 9: 3147-52, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27307756

RESUMO

OBJECTIVE: To evaluate the expressions of circulating angiogenic factors affected by pamidronic acid (PA) intravenous infusion in bone metastatic breast cancer patients and the impact on their prognosis. METHODS: Peripheral blood of ten bone metastatic breast cancer patients was collected for serum insulin-like growth factor-1 (IGF-1) and platelet endothelial cell adhesion molecule-1 expression detection just before and 2 days after PA infusion. RESULTS: Both IGF-1 and platelet endothelial cell adhesion molecule-1 concentrations decreased after PA treatment for 48 hours (P<0.05). Modification was defined as >20% decrease recorded 2 days after PA administration. The decrease of IGF-1 was more significant in breast cancer patients who had received previous hormonotherapy. Moreover, the progression-free survival of first-line chemotherapy treatment of IGF-1 modified patients was longer than that of IGF-1 unmodified patients (P=0.009). CONCLUSION: PA treatment could suppress circulating serum IGF-1 and platelet endothelial cell adhesion molecule-1 concentrations; moreover, the prognosis of patients in IGF-1 unmodified group was relatively poor.

6.
Oncotarget ; 7(21): 31299-310, 2016 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-27121317

RESUMO

Blood-tumor barrier (BTB) reduce the permeability for drugs into tumor tissues. We found that histamine might serve as an essential regulator of BTB function. Further, we aim to determine the role of H2 receptor expression in BTB permeability, and elucidate the underlying mechanisms thereof. Transmission electron microscopy showed that histamine disrupted the integrity of tight junctions (TJ) and increased the number of pinosomes in the cytoplasm. Horseradish peroxidase (HRP) and trans-endothelial resistance detection (TEER) assays revealed that histamine could open BTB and this action was inhibited by cimetidine. Western blot and immunofluorescence assays showed that histamine decreased the expression of tight junction proteins zonula occluden-1(ZO-1), occludin, and claudin-5. Further, quantitative RT-PCR assay showed that the expression of H2 receptor could represent and predicted histamine-induced BTB permeability. In conclusion, histamine opened BTB by down-regulating the TJ-associated proteins. The levels of H2 receptor expression was correlated with the histamine-induced BTB permeability.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Histamina/farmacologia , Junções Íntimas/efeitos dos fármacos , Animais , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/fisiopatologia , Western Blotting , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Células Cultivadas , Técnicas de Cocultura , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Glioma/irrigação sanguínea , Glioma/metabolismo , Glioma/patologia , Microscopia Eletrônica de Transmissão , Permeabilidade/efeitos dos fármacos , Ratos Sprague-Dawley , Receptores Histamínicos H2/metabolismo , Junções Íntimas/metabolismo , Junções Íntimas/ultraestrutura , Proteína da Zônula de Oclusão-1/metabolismo
7.
J Cancer Res Ther ; 11 Suppl 1: C84-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26323932

RESUMO

OBJECTIVE: To investigate the predictors and impact of cytotoxic second-line chemotherapy for stage IIIa-IV nonsmall cell lung cancer (NSCLC) patients in China. METHODS: Medical records of 132 patients who underwent chemotherapy from January 2008 to December 2010 in our hospital were retrospectively reviewed. The response of first-line gemcitabine (GEM) and platinum doublets chemotherapy was evaluated, and the overall survival (OS) of all patients was followed. Further, risk factors of receipt cytotoxic second-line chemotherapy or not were identified and evaluated by univariate analyses. RESULTS: Sixty-six cases have undergone cytotoxic second-line chemotherapy for lung cancer. The OS between patients received first-line GEM plus platinum doublets chemotherapy and patients without cytotoxic second chemotherapy had no statistical difference (P = 0.73). Smoking or not might be a meaningful predictor for cytotoxic second-line therapy among these patients in this investigation (P < 0.05). Other factors, such as age (≥ 65 or < 65), gender, alcohol use, hypertension, diabetes mellitus, histology type, number of cycles of first-line chemotherapy, and response of first-line chemotherapy had no statistical difference between patients received first-line GEM plus platinum doublets chemotherapy and patients received cytotoxic second chemotherapy (P > 0.05). In the sub-analysis, we found that the OS between patients received first-line GEM plus platinum doublets chemotherapy and patients without cytotoxic second chemotherapy had statistical difference in the population whose OS < 540 days (P = 0.019). Moreover, in these patients, the blood type was found to be a selected factor in receiving cytotoxic second-line chemotherapy or not (P < 0.05). Whereas other factors were not shown their selected effect (P > 0.05). CONCLUSION: This study demonstrated that though the essentiality of cytotoxic second-line chemotherapy for stage IIIa-IV EGFR mutation indefinite NSCLC is unclear, patients who are blood type AB with poor prognosis and short OS might be a dominant population for cytotoxic second-line chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Retratamento , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
8.
Asian Pac J Cancer Prev ; 15(7): 3071-4, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24815449

RESUMO

BACKGROUND: To investigate the related risk factors of postoperative nosocomial pneumonia (POP) in patients with I-IIIa lung cancer. METHODS: Medical records of 511 patients who underwent resection for lung cancer between January 2012 to December 2012 were retrospectively reviewed. Risk factors of postoperative pneumonia were identified and evaluated by univariate and multivariate analyses. RESULTS: The incidence of postoperative pneumonia in these lung cancer patients was 2.9% (15 cases). Compared with 496 patients who had no pneumonia infection after operation, older age (>60), histopathological type of squamous cell carcinoma and longer surgery time (>3h) were significant risk factors by univariate analysis. Other potential risk factors such as alcohol consumption, history of smoking, hypersensitivity, hypertension, diabetes mellitus and so on were not showed such significance in this study. Further, the multivariate analysis revealed that old age (>60 years) (OR 5.813, p=0.018) and histopathological type of squamous cell carcinoma (OR 5.831, p<0.001) were also statistically significant independent risk factors for postoperative pneumonia. CONCLUSIONS: This study demonstrated that being old aged (>60 years) and having squamous cell carcinoma histopathological type might be important factors in determining the risk of postoperative pneumonia in lung cancer patients after surgery.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Envelhecimento , Infecção Hospitalar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonia/mortalidade , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Fatores de Risco
9.
Cytotechnology ; 63(4): 319-23, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21720796

RESUMO

In past years with the advances of chemistry and material sciences, the development of nanotechnology brought generations of nanomaterials with specific biomedical properties. These include the nanoparticle-based drug delivery, nanosized drugs, and nanomaterials for tissue engineering. The present article focuses on the use of nanomaterials in controlled drug release. The applications of nanomaterials with nano-enabled drug release characteristics brought many benefits when compared to the traditional (bulk) materials. We discuss the current advances and propose some future directions for the technology development.

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