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1.
Cancer Sci ; 109(12): 3953-3961, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30353607

RESUMO

The aim of this study was to evaluate whether a patented single-channel applicator, which was modified from the traditional tandem applicator and wrapped with an oval-shield alloy around the source channel, has the same clinical efficacy and safety as the standard Fletcher-type applicator in high dose rate (HDR) brachytherapy for carcinoma of the cervix. Between December 2011 and February 2017, 299 patients with pathologically confirmed International Federation of Gynecology and Obstetrics (2009) stage Ib2-IVa cervical cancer were recruited to the trial and finished the allocated intervention. Of the first 151 patients, 71 were allocated to the Fletcher group and 80 to the single-channel group, satisfying the criteria for a preliminary analysis. All but 3 patients were treated with concurrent cisplatin chemotherapy and external beam radiotherapy followed by HDR brachytherapy. The 2-year overall survival, progression-free survival, and locoregional failure-free survival was 80.3%, 77.5%, and 78.9%, respectively, for the Fletcher group, and 86.3%, 82.5%, and 83.8%, respectively, for the single-channel group. The seriousness of acute treatment-related toxicities was similar in the 2 groups. The cumulative rate of late rectal complications of grade 3-4 in the Fletcher group and the single-channel group was 2.8% and 2.5%, respectively. The cumulative rate of grade 3 bladder complications was 2.8% for the Fletcher group and 1.3% for the single-channel group. The preliminary results of our study show that the patented single-channel intracavitary applicator might be able to provide protection for the rectum and bladder and seems to have the same clinical efficacy as the standard Fletcher-type 3-channel applicator in HDR brachytherapy for carcinoma of the cervix. This trial was registered with the Chinese Clinical Trial Registry (registration no. ChiCTR-TRC-12002321).


Assuntos
Braquiterapia/instrumentação , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Cisplatino/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Dosagem Radioterapêutica , Análise de Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Adulto Jovem
2.
Int J Biol Macromol ; 267(Pt 1): 131428, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38583834

RESUMO

Breast cancer is the second leading cause of cancer-related deaths among women worldwide. Despite significant advancements in chemotherapy, its effectiveness is often limited by poor drug distribution and systemic toxicity caused by the weak targeting ability of conventional therapeutic agents. The hypoxic tumor microenvironment (TME) also plays a vital role in treatment outcomes. Oral anticancer therapeutic agents have gained popularity and show promising results due to their ease of repeated administration. This study introduces autopilot biohybrids (Bif@BDC-NPs) for the effective delivery of doxorubicin (DOX) to the tumor site. This hybrid combines albumin-encapsulated DOX nanoparticles (BD-NPs) coated with chitosan (CS) for breast cancer chemotherapy, along with anaerobic Bifidobacterium infantis (B. infantis, Bif) serving as self-propelled motors. Due to Bif's specific anaerobic properties, Bif@BDC-NPs precisely anchor hypoxic regions of tumor tissue and significantly increase drug accumulation at the tumor site, thereby promoting tumor cell death. In an in-situ mouse breast cancer model, Bif@BDC-NPs achieved 94 % tumor inhibition, significantly prolonging the median survival of mice to 62 days, and reducing the toxic side effects of DOX. Therefore, the new bacteria-driven oral drug delivery system, Bif@BDC-NPs, overcomes multiple physiological barriers and holds great potential for the precise treatment of solid tumors.


Assuntos
Neoplasias da Mama , Quitosana , Doxorrubicina , Nanopartículas , Quitosana/química , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/administração & dosagem , Animais , Feminino , Nanopartículas/química , Camundongos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Administração Oral , Humanos , Portadores de Fármacos/química , Linhagem Celular Tumoral , Microambiente Tumoral/efeitos dos fármacos , Sistemas de Liberação de Medicamentos
3.
Biomed Pharmacother ; 169: 115846, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37944443

RESUMO

Breast cancer is characterized by insidious onset, rapid progression, easy recurrence, and metastasis. Conventional monotherapies are usually ineffective due to insufficient drug delivery. Therefore, the combination of multimodal therapy with tumor microenvironment (TME)-responsive nanoplatforms is increasingly being considered for the targeted treatment of breast cancer. We synthesized bioactive hybrid nanoparticles for synergistic chemotherapy and photothermal therapy. Briefly, doxorubicin (DOX) and indocyanine green (ICG)-loaded nanoparticles (DI) of average particle size 113.58 ± 2.14 nm were synthesized, and their surface were modified with polydopamine (PDA) and attached to the anaerobic probiotic Bifidobacterium infantis (Bif). The bioactive Bif@DIP hybrid showed good photothermal conversion efficiency of about 38.04%. In addition, the self-driving ability of Bif allowed targeted delivery of the PDA-coated DI nanoparticles (DIP) to the hypoxic regions of the tumor. The low pH and high GSH levels in the TME stimulated the controlled release of DOX and ICG from the Bif@DIP hybrid, which then triggered apoptosis of tumor cells and induced immunogenic cell death (ICD), resulting in effective and sustained anti-tumor effect with minimum systemic toxicity. Thus, the self-driven Bif@DIP hybrid is a promising nanodrug for the targeted chemotherapy and photothermal therapy against solid cancers.


Assuntos
Neoplasias da Mama , Hipertermia Induzida , Nanopartículas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Verde de Indocianina , Terapia Fototérmica , Fototerapia/métodos , Doxorrubicina , Nanopartículas/química , Linhagem Celular Tumoral , Microambiente Tumoral
4.
J Inflamm (Lond) ; 20(1): 23, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37430327

RESUMO

BACKGROUND: To compare the severity of radiation-induced lung injury (RILI) after the right lung of SD rats received interstitial brachytherapy and stereotactic radiotherapy (SBRT). METHODS: RILI rat model was established using interstitial brachytherapy and SBRT methods, respectively. CT scan was performed to analyze the lung volume and the CT value difference between the left and right lungs in rats. Then the lung tissues were analyzed through H&E staining, peripheral blood was extracted to detect the expression levels of serum inflammatory cytokines, pro-fibrotic cytokines, and fibrotic-inhibiting cytokines by ELISA. RESULTS: The difference between right and left lung CT values was significantly elevated in the SBRT group when compared with the control group and the interstitial brachytherapy group (P < 0.05). The IFN-γ expression in the interstitial brachytherapy group was significantly different from that in the SBRT group at week 1, 4, 8 and 16. Besides, the expressions of IL-2, IL-6 and IL-10 in SBRT group were significantly higher than that of interstitial brachytherapy group (P < 0.05). The TGF-ß expression in interstitial brachytherapy group reached its peak with the increase of time from week 1 to week 16, and it was significantly lower than SBRT group (P < 0.05). The mortality rate in the SBRT group was 16.7%, which was significantly higher than that in the interstitial brachytherapy group. CONCLUSION: The treatment method of interstitial brachytherapy is considered as an effective and safe tool by reducing the side effects of radiotherapy and increasing the radiation dose of radiotherapy.

5.
Drug Deliv ; 29(1): 2713-2722, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35975331

RESUMO

Malignant ascites is a common complication of some advanced cancers. Although intraperitoneal (IP) administration of chemotherapy drugs is routinely used to treat cancerous ascites, conventional drugs have poor retention and therefore need to be administered frequently to maintain a sustained anti-tumor effect. In this study, a thermosensitive hydrogel composite loaded with norethindrone nanoparticles (NPs) and oxaliplatin (N/O/Hydrogel) was developed to inhibit ascites of hepatocellular carcinoma (HCC) through IP injection. N/O/Hydrogel induced apoptosis in the H22 cells in vitro, and significantly inhibited ascites formation, tumor cell proliferation and micro-angiogenesis in a mouse model of advanced HCC with ascites, and prolonged the survival of tumor-bearing mice. Histological examination of the major organs indicated that the hydrogel system is safe. Taken together, the N/O/Hydrogel system is a promising platform for in-situ chemotherapy of malignant ascites.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Neoplasias Peritoneais , Animais , Ascite/tratamento farmacológico , Ascite/patologia , Compostos Bicíclicos Heterocíclicos com Pontes , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Hidrogéis , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Camundongos , Oxaliplatina , Neoplasias Peritoneais/tratamento farmacológico
6.
Transl Oncol ; 14(8): 101118, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34020371

RESUMO

The history of low-dose total-body irradiation (LTBI) as a means of radiotherapy for treating malignant tumors can be traced back to the 1920s. Despite this very low total dose, LTBI can induce long-term remissions. Tumor cells are known to change and maintain their own survival and development conditions through autocrine and paracrine signaling. LTBI can change the tumor microenvironment, enhance the infiltration of activated T cells, and trigger inflammatory processes. LTBI-mediated immune response can exert systemic long-term anti-tumor effects, and can induce tumor regression at the primary site and metastatic sites. With a continuous improvement in the anti-tumor immune microenvironment in the field of tumor therapy, LTBI provides more choices to comprehensively treat of tumors. The present study aimed to explore the experimental research mechanism of LTBI and immune microenvironment, and discuss the difficulties and development prospects of applying LTBI to tumor treatment.

7.
Mater Sci Eng C Mater Biol Appl ; 129: 112390, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34579909

RESUMO

Post-operative recurrence and metastasis is a major challenge for breast cancer treatment. Local chemotherapy is a promising strategy that can overcome this problem. In this study, we synthesized an injectable hyaluronic acid (HA)-based hydrogel loaded with paclitaxel (PTX) nanoparticles and epirubicin (EPB) (PPNPs/EPB@HA-Gel). PPNPs/EPB@HA-Gel steadily released the encapsulated drugs to achieve long-term inhibition of tumor recurrence and metastasis in a murine post-operative breast tumor model, which prolonged their survival without any systemic toxicity. The drug-loaded hydrogel inhibited the proliferation and migration of tumor cells in vitro, and significantly increased tumor cell apoptosis in vivo. Therefore, PPNPs/EPB@HA-Gel can be used as a local chemotherapeutic agent to prevent postoperative recurrence and metastasis of breast cancer.


Assuntos
Neoplasias da Mama , Nanopartículas , Animais , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Epirubicina/farmacologia , Epirubicina/uso terapêutico , Feminino , Humanos , Hidrogéis , Camundongos , Camundongos Endogâmicos BALB C , Paclitaxel/farmacologia
8.
J Cancer Res Clin Oncol ; 147(2): 411-422, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33130941

RESUMO

PURPOSE: The hypoxic microenvironments of solid tumours are complex and reduce the susceptibility of cancer cells to chemo- and radiotherapy. Conventional radiosensitisers have poor specificity, unsatisfactory therapeutic effects, and significant side effects. Anaerobic bacteria colonise and destroy hypoxic areas of the tumour and consequently enhance the effects of radiation. METHODS: In this study, we treated a Lewis lung carcinoma transplant mouse model with Bifidobacterium infantis (Bi) combined with its specific monoclonal antibody (mAb) and radiotherapy (RT) to investigate its ability to radiosensitise the tumour. The tumour metabolism and hypoxia in the tumour tissue were monitored by micro-18F-FDG and 18F-FMISO PET/CT imaging. Immunohistochemistry was used to detect phosphorylated histone (γ-H2AX), proliferation (Ki-67), platelet endothelial cell adhesion molecules (CD31), tumour necrosis factor-α (TNF-α), hypoxia-inducible factor-1α (HIF-1α), and glucose transporter 1 (Glut-1) levels. RESULTS: Tumour growth was slowed and survival time was markedly prolonged in mice subjected to the combination of B. infantis, specific antibody, and radiotherapy. Levels of HIF-1α, Glut-1, Ki-67, and CD31 expression, as well as uptake of FDG and FMISO, were the lowest in the combination-treated mice. In contrast, γ-H2AX and TNF-α expression levels were elevated and hypoxia in tumour tissue was reduced compared with controls. CONCLUSION: In conclusion, our data indicated that the curative effect of radiotherapy for lung cancer was enhanced by pre-treating mice with a combination of B. infantis and its specific monoclonal antibody.


Assuntos
Anticorpos Antibacterianos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Bifidobacterium longum subspecies infantis , Carcinoma Pulmonar de Lewis/radioterapia , Radiossensibilizantes/uso terapêutico , Animais , Bifidobacterium longum subspecies infantis/imunologia , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/mortalidade , Carcinoma Pulmonar de Lewis/patologia , Hipóxia Celular , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Glucose/metabolismo , Histonas/análise , Antígeno Ki-67/análise , Camundongos , Camundongos Endogâmicos C57BL , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
9.
Int J Biol Macromol ; 193(Pt A): 228-237, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34688683

RESUMO

Conventional chemotherapeutic drugs may cause serious side effects such as hepatotoxicity and renal toxicity due to lack of targeting, which affects therapy outcome and the prognosis of patients. Therefore, biomimetic nanoparticles with long blood circulation and active targeting have attracted increasing attention. In this work, we fabricated a biomimetic R-RBC@GEF-NPs nano-system by encapsulating gefitinib-loaded albumin nanoparticles (GEF-NPs) inside cRGD-modified red blood cell (RBC) membranes. The complete RBC membrane structure and membrane proteins enabled the NPs to escape phagocytosis by macrophages. In addition, the cRGD moiety significantly improved tumor cell targeting and uptake. R-RBC@GEF-NPs inhibited the growth of A549 cells in vitro in a dose- and time-dependent manner by inducing apoptosis and cell cycle arrest at the G1 phase. Likewise, the R-RBC@GEF-NPs also decreased tumor weight and volume in the mice injected with A549 cells and prolonged survival time. In addition, the 99Tc-labeled R-RBC@GEF-NPs selectively accumulated in the tumor tissues in vivo, and enabled real time tumor imaging. Finally, blood and histological analyses showed that R-RBC@GEF-NPs did not cause any obvious systemic toxicity. Taken together, the biomimetic R-RBC@GEF-NPs is a promising therapeutic formulation for the treatment of lung cancer.


Assuntos
Albuminas/química , Portadores de Fármacos , Gefitinibe/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/administração & dosagem , Células A549 , Animais , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Humanos , Camundongos , Camundongos Nus
10.
Int J Pharm ; 589: 119875, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32919003

RESUMO

Multi-drug chemotherapy has been one of the most popular strategies for the treatment of malignant tumors, and has achieved desirable therapeutic outcomes. The objective of the present study is to develop biodegradable PCEC nanoparticles (NPs) for the co-delivery of paclitaxel (PTX) and curcumin (CUR), and investigate the antitumor effect of the drug delivery system (DDS: PTX-CUR-NPs) against breast cancer both in vitro and in vivo. The prepared PTX-CUR-NPs had a small size of 27.97 ± 1.87 nm with a low polydispersity index (PDI, 0.197 ± 0.040). The results exhibited slow release of PTX and CUR from the DDS without any burst effect. Further, the PTX-CUR-NPs displayed a dose-dependent cytotoxicity in MCF-7 cells with a higher apoptosis rate (64.29% ± 1.97%) as compared to that of free drugs (PTX + CUR, 34.21% ± 0.81%). The cellular uptake study revealed that the drug loaded PCEC polymeric nanoparticles were more readily uptaken by tumor cells in vitro. To evaluate the in vivo anti-tumor effect, the PTX-CUR-NPs were intravenously administered to BALB/c nude mouse xenografted with MCF-7 cells and the results exhibited significant inhibition of tumor growth with prolonged survival time and reduced side effect when compared with free drugs (PTX + CUR). Moreover, the administration of PTX-CUR-NPs treatment led to lower Ki67 expression (p < 0.05), and enhanced TUNEL positivity (higher apoptosis, p < 0.01) in tumor cells as compared to other treatment groups, suggesting the therapeutic efficacy of the DDS. Altogether, the present study suggests that the DDS PTX-CUR-NPs could be employed for the effective treatment of breast cancers in near future.


Assuntos
Neoplasias da Mama , Curcumina , Nanopartículas , Animais , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Paclitaxel/uso terapêutico
11.
Drug Deliv ; 27(1): 1676-1685, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33251864

RESUMO

Skin repair remains a common problem in plastic surgery. Wound dressing plays an important role in promoting local skin healing and has been widely studied. This study aimed to manufacture a composite film (CPCF) containing curcumin nanoparticles, collagen, and polyvinyl alcohol (PVA) to effectively promote the healing of skin wounds. Sustained drug release from the composite film provides long-term protection and treatment for skin wounds. Both antibacterial property and good histocompatibility of the CPCF were examined by analyzing antibacterial activity and cytotoxicity to validate its applicability for wound management. Moreover, in vivo studies proved that the CPCF had a rapid healing rate of 98.03%±0.79% and mature epithelialization on day 15 after surgery. Obvious hair follicles and earlier re-epithelialization was also noticed in the CPCF group using H&E staining. The result of Masson's trichrome staining confirmed that CPCF could promote the formation of collagen fibers. In summary, CPCF may be promising as a wound dressing agent in wound management owing to its rapid wound-healing effects.


Assuntos
Colágeno/química , Curcumina/administração & dosagem , Curcumina/uso terapêutico , Álcool de Polivinil/química , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Bandagens , Materiais Biocompatíveis , Liberação Controlada de Fármacos , Epitélio/efeitos dos fármacos , Epitélio/crescimento & desenvolvimento , Escherichia coli/efeitos dos fármacos , Folículo Piloso/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana , Nanopartículas , Ratos , Ratos Sprague-Dawley , Pele/patologia , Staphylococcus aureus/efeitos dos fármacos
12.
J Biomed Nanotechnol ; 16(12): 1727-1739, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33485400

RESUMO

Malignant ascites indicate the presence of malignant cells in the peritoneal cavity that lower patient survival and reduce quality of life. Current chemotherapy regimens suffer from the dilution of ascites and rapid metabolism limiting their therapeutic efficacy. The storage and sustained release of drugs at the tumor site represents a promising strategy to improve drug efficacy. The aim of this study was to develop injectable hyaluronic acid hydrogel containing polymeric gemcitabine nanoparticles and cisplatin for the local treatment of malignant ascites through a dual sustained drug release pattern. Cell uptake assays showed that the drug-loaded nanoparticles readily entered tumor cells. Apoptosis and cell cycle analysis showed that the hydrogel system could enhance tumor cell apoptosis and arrest more cells in the G1 phase. In vivo experiments indicated that mice treated with the drug-loaded hydrogels manifested the most significant efficacy in ascites volume, tumor nodules, body weight, abdominal circumference, and survival. The expression of Ki-67 and CD31 also significantly decreased compared with other groups, indicative of anti-tumor activity. In addition, intraperitoneal administration of the hydrogel system led to no significant damage to vital organs. These findings confirm the clinical potential of the drug-loaded hydrogel system for the treatment of malignant ascites.


Assuntos
Cisplatino , Nanopartículas , Animais , Ascite/tratamento farmacológico , Linhagem Celular Tumoral , Desoxicitidina/análogos & derivados , Humanos , Ácido Hialurônico , Hidrogéis , Camundongos , Camundongos Endogâmicos BALB C , Qualidade de Vida , Gencitabina
13.
Int J Biol Macromol ; 152: 718-726, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32126201

RESUMO

Colorectal peritoneal carcinomatosis (CRPC) is an advanced stage of colorectal cancer (CRC), which significantly decreases patient survival and quality of life. Here, the naturally occurring polysaccharide hyaluronic acid (HA) was used to prepare an injectable hydrogel and simultaneously deliver 5-fluorouracil (5-FU), cisplatin (DDP) and paclitaxel (PTX) microspheres for intraperitoneal CRPC chemotherapy. The drug-loaded HA hydrogel released the drugs in a sustained manner, and showed low toxicity both in vitro and in a mouse model of CRPC. Furthermore, direct injection of the drug-loaded HA hydrogel in the abdominal cavity of tumor-bearing mice significantly decreased tumor growth and liver/lung metastasis, along with decreasing the volume of ascites and inhibiting local intestinal infiltration of the tumor cells. Therefore, this novel multi-drug hydrogel delivery system may effectively clear CRPC tumors without any adverse effects when used in intraperitoneal chemotherapy.


Assuntos
Antineoplásicos/administração & dosagem , Materiais Biocompatíveis/química , Carcinoma/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Ácido Hialurônico/administração & dosagem , Hidrogéis/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Feminino , Humanos , Injeções Intraperitoneais/métodos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Sprague-Dawley
14.
Int J Pharm ; 582: 119334, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32305362

RESUMO

Ascites constitutes the most frequent decompensating event in patients with advanced liver cancer and is associated with poor quality of life and high mortality. Intraperitoneal chemotherapy appears to be a reliable treatment strategy for advanced liver cancer ascites. However, the rapid metabolism of drugs and ascites dilution limits the efficacy of chemotherapeutics. Therefore, the present study aimed to develop a novel thermosensitive hydrogel drug system for targeted therapy of advanced hepatocellular carcinoma (HCC) ascites through intraperitoneal administration. The system was prepared by blending resveratrol (RES) microspheres and cisplatin (DDP) into thermosensitive Pluronic F127 hydrogel. The in vitro anti-tumor activity against H22 cells indicated that the prepared drug system could initiate apoptosis and induce cell cycle arrest at the G1 phase. The mice model of ascites with advanced HCC was established to validate the therapeutic potential of the F127 hydrogel drug system in vivo. The results revealed that intraperitoneal administration of F127 hydrogel drug could significantly inhibit the number of ascites, the proliferation of tumor cells, micro-angiogenesis, and prolong the survival of mice, thus, augmenting the efficacy of intraperitoneal chemotherapy. Moreover, immunohistochemical staining revealed that the F127 hydrogel drug system was safe and presented low toxicity to major vital organs. Collectively, this study highlights the clinical application potential of the F127 hydrogel drug delivery system.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Ascite/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico , Cisplatino/farmacologia , Portadores de Fármacos , Neoplasias Hepáticas/tratamento farmacológico , Poloxâmero/química , Resveratrol/farmacologia , Polímeros Responsivos a Estímulos/química , Temperatura , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/química , Ascite/etiologia , Ascite/patologia , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Cisplatino/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Feminino , Células Hep G2 , Humanos , Hidrogéis , Cinética , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Camundongos , Microesferas , Poloxâmero/toxicidade , Resveratrol/química , Polímeros Responsivos a Estímulos/toxicidade
15.
Drug Deliv ; 27(1): 876-887, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32516033

RESUMO

Dihydroartemisinin (DHA) is a potent anti-cancer drug that has limited clinical applications due to poor water solubility and low bioavailability. We designed a biodegradable poly(ethylene glycol) methyl ether-poly(ε-caprolactone) (MPEG-PCL) micelle carrier for DHA using the self-assembly method. The DHA/MPEG-PCL nanoparticles were spherical with an average particle size of 30.28 ± 0.27 nm, and released the drug in a sustained manner in aqueous solution. The drug-loaded nanoparticles showed dose-dependent toxicity in HeLa cells by inducing cycle arrest and apoptosis. Furthermore, compared to free DHA, the DHA/MPEG-PCL nanoparticles showed higher therapeutic efficacy and lower toxicity in vivo, and significantly inhibited tumor growth and prolonged the survival of tumor-bearing nude mice. In addition, the tumor tissues of the DHA/MPEG-PCL-treated mice showed a marked decline in the in situ expression of proliferation and angiogenesis markers. Taken together, the self-assembled DHA/MPEG-PCL nanoparticles are a highly promising delivery system for targeted cancer treatment.


Assuntos
Artemisininas/farmacologia , Nanopartículas/uso terapêutico , Poliésteres/farmacologia , Polietilenoglicóis/farmacologia , Animais , Antimaláricos/farmacologia , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis/farmacologia , Ciclo Celular/efeitos dos fármacos , Portadores de Fármacos/farmacologia , Sistemas de Liberação de Medicamentos , Feminino , Células HeLa , Humanos , Camundongos , Camundongos Nus , Resultado do Tratamento , Neoplasias do Colo do Útero/tratamento farmacológico
16.
ACS Biomater Sci Eng ; 5(3): 1580-1588, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33405631

RESUMO

Postoperative adhesions are the most common complications of peri-abdominal surgery; they not only affect the patient's quality of life but also increase the risk of a subsequent surgery. The use of implantable dressings to physically block surgical wounds is the primary solution to prevent postoperative adhesions. In this study, we prepared naproxen nanoparticles that were loaded with chitosan hydrogel (CS/Nap hydrogel) to prevent postoperative adhesions. Our data confirmed that the prepared CS/Nap hydrogel was thermosensitive and suitable for injection. The efficacy of anti-adhesion in a rat model revealed that the hydrogel effectively separated from the wounds of the abdominal wall and cecum. On day 7 postsurgery, the wounds were completely covered by a new epithelial layer, whereas wounds in the negative control group were glued together. Additionally, the in vivo toxicity study showed that the CS/Nap hydrogel had fewer toxic and side effects on major tissues and organs, including the liver, spleen, heart, lung, and kidney. We showed that a drug delivery system based on CS/Nap hydrogel has the potential not only to prevent postoperative abdominal adhesions and relieve pain but also to contribute to the administration of the hydrophobic drug naproxen.

17.
Int J Nanomedicine ; 13: 8461-8472, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30587971

RESUMO

BACKGROUND: Poly (ADP-ribose) polymerase (PARP) is a key enzyme in the repair process of DNA strand breaks (DSBs). Olaparib (Ola) is a PARP inhibitor that is involved in arresting PARP release from radiotherapy (RT)-induced damaged DNA to potentiate the effect of RT. Although the underlying mechanisms for the radiosensitization effects of Ola are well understood in vitro, the radiosensitization effects in vivo are still unclear. Moreover, poor water solubility and severe toxicity are two major impediments for the clinical success of Ola. MATERIALS AND METHODS: Here, we developed olaparib nanoparticles (Ola-NPs) and investigated their radiosensitization mechanisms and toxicity using human non-small-cell lung cancer xenograft models in mice. RESULTS: The prepared Ola-NPs showed a mean size of 31.96±1.54 nm and a lower polydispersity index of about 0.126±0.014. In addition, the sensitization enhancement ratio of Ola-NPs (3.81) was much higher than that of free Ola (1.66). The combination of Ola-NPs and RT (Ola-NPs + RT) significantly inhibited tumor growth and prolonged survival in mice. The mechanism of enhanced antitumor efficacy might be related to the inhibition of DSB repair and the promotion of cell apoptosis in vivo. No additional toxicity caused by Ola-NPs was observed. CONCLUSION: This study demonstrated the principle of using Ola-NPs as a potent radiosensitizer to improve the therapeutic effect of RT relative to free Ola (P<0.05 in all cases).


Assuntos
Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/química , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Radiossensibilizantes/uso terapêutico , Células A549 , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Liberação Controlada de Fármacos , Feminino , Fluordesoxiglucose F18/química , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/ultraestrutura , Ftalazinas/efeitos adversos , Ftalazinas/farmacologia , Piperazinas/efeitos adversos , Piperazinas/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radiossensibilizantes/efeitos adversos , Radiossensibilizantes/farmacologia
18.
J Cancer Res Ther ; 12(1): 209-14, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27072239

RESUMO

BACKGROUND: The aim of this study was to investigate medical-related reasons for misdiagnosis of nasopharyngeal carcinoma. (NPC) patients presenting with headaches alone or accompanied by other symptoms. PATIENTS AND METHODS: Two-hundred and nineteen NPC cases describing headaches as one of the initial symptoms during primary treatment were selected for this prospective study. Medical records were carefully collected and all data were summarized for final analyses. RESULT: Distributions of NPC stage in the patients were: Stage II, 1.4%; stage III, 46.6%; stage IVA, 36.1%; stage IVB, 7.7%; and stage IVC, 8.2%. The ratio of men to women was 2.42:1 (155/64 cases). The total misdiagnosis rate was 43.4%. Patients that only complained of headaches had the highest misdiagnosis rate of 86.4% (19/22 cases). The lowest misdiagnosis rate of 10.9% (5/46 cases) was observed in patients with both headaches and epistaxis. The misdiagnosis rate in rural hospitals was more than two times that in provincial hospitals. Neurosurgery departments had a 100% misdiagnosis rate. CONCLUSION: Frequently, headaches are the only prominent symptom of NPC. Due to the various clinical manifestations, NPC patients encounter a high misdiagnosis rate, which leads to unsatisfactory treatment outcomes. Improved awareness of the various nonspecific symptoms of NPC by nonspecialist physicians will be a pivotal step in decreasing the misdiagnosis rate. Mini Abstract: The misdiagnosis rate of nasopharyngeal carcinoma (NPC) patients with headaches was 43.4%. Improved awareness of the various nonspecific symptoms of NPC is a pivotal step in decreasing the misdiagnosis rate.


Assuntos
Erros de Diagnóstico , Cefaleia/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Adulto , Idoso , Carcinoma , Feminino , Cefaleia/complicações , Cefaleia/diagnóstico por imagem , Cefaleia/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/complicações , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/fisiopatologia , Estadiamento de Neoplasias , Tomografia Computadorizada por Raios X
19.
Colloids Surf B Biointerfaces ; 122: 90-98, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25033428

RESUMO

In this study, an in situ gel-based dual drug delivery system (PEG-PCL-PEG/DDP+MPEG-PCL/PTX, abbreviated as PDMP) was prepared through the combination of a cisplatin (DDP)-containing thermosensitive hydrogel (PEG-PCL-PEG/DDP, PECE/DDP) and paclitaxel (PTX)-loaded polymeric micelles (average diameter of 20.1nm). PDMP is a free-flowing solution at room temperature and forms a stationary gel at body temperature, allowing it to serve as a drug depot for the in situ treatment of lung cancer. For in vivo experiments, the xenografted lung cancer model was used to evaluate the anti-tumor efficacy of the PDMP. The results suggested that PDMP is effective at inhibiting tumor growth and prolonging the survival time of tumor-bearing BALB/c nude mice. The survival time of the PDMP-treated group (53 days) is significantly higher than that of other groups (40 days from the free DDP+PTX group, 26 days from the blank PECE group, 25 days from the normal saline group, p<0.05). Immunohistochemical analysis revealed that tumors in the PDMP group had fewer microvessels and lower proliferation activity compared with those of the control group. Thus, PDMP may have great potential for in situ treatment of lung cancer by minimally invasive injection methods.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Hidrogéis , Neoplasias Pulmonares/tratamento farmacológico , Micelas , Paclitaxel/administração & dosagem , Antineoplásicos Fitogênicos/química , Proliferação de Células , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/patologia , Neovascularização Patológica/tratamento farmacológico , Paclitaxel/química , Tamanho da Partícula
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