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1.
Support Care Cancer ; 32(3): 190, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38400861

RESUMO

BACKGROUND: Highly emetogenic chemotherapy (HEC) is known to induce nausea and vomiting (CINV) in approximately 90% of cancer patients undergoing this regimen unless proper prophylactic antiemetics are administered. This study aimed to analyze the use of a three-drug prophylactic antiemetic regimen during the first cycle of chemotherapy and assess the compliance rate with the National Comprehensive Cancer Network (NCCN) guidelines. METHODS: This retrospective study utilized data from the National Inpatient Sample database from 2016 to 2020 provided by the Health Insurance Review and Assessment Service. The claims data encompassed 10 to 13% of inpatients admitted at least once each year. Patients with solid cancers treated with two HEC regimens, namely anthracycline + cyclophosphamide (AC) and cisplatin-based regimens, were selected as the study population. We evaluated the use of a three-drug prophylactic antiemetic regimen, including a neurokinin-1 receptor antagonist, a 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone and compliance with the NCCN guidelines. Multiple logistic regression was conducted to estimate the influence of variables on guideline adherence. RESULTS: A total of 3119 patients were included in the analysis. The overall compliance rate with the NCCN guidelines for prophylactic antiemetics was 74.3%, with higher rates observed in the AC group (87.9%) and lower rates in the cisplatin group (60.4%). The AC group had a 6.37 times higher likelihood of receiving guideline-adherent antiemetics than the cisplatin group. Further analysis revealed that, compared to 2016, the probability of complying with the guidelines in 2019 and 2020 was 0.72 times and 0.76 times lower, respectively. CONCLUSION: This study showed that a considerable proportion of HEC-treated patients received guideline-adherent antiemetic therapies. However, given the variations in adherence rates between different chemotherapy regimens (AC vs. cisplatin), efforts to improve adherence and optimize antiemetic treatment remain essential for providing the best possible care for patients experiencing CINV.


Assuntos
Antieméticos , Antineoplásicos , Neoplasias , Humanos , Antieméticos/uso terapêutico , Cisplatino , Estudos Retrospectivos , Náusea/induzido quimicamente , Náusea/prevenção & controle , Náusea/tratamento farmacológico , Vômito/induzido quimicamente , Vômito/prevenção & controle , Vômito/tratamento farmacológico , Neoplasias/tratamento farmacológico , Ciclofosfamida/efeitos adversos , Antraciclinas/efeitos adversos , República da Coreia , Antineoplásicos/efeitos adversos
2.
J Clin Neurosci ; 116: 60-66, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37633186

RESUMO

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disorder typically treated with dopamine replacement therapy and dopamine agonists (DAs) to alleviate symptoms and minimize dyskinesia. Optimal treatment strategies for patients newly diagnosed with PD have been a topic of debate for many years. METHODS: We conducted a 10-year descriptive study of drug prescription trends and factors affecting prescription choices for newly diagnosed drug-naïve PD patients using data from the National Health Insurance program in Korea. To identify statistically significant differences in yearly trends, we employed the Cochran-Armitage trend test. Additionally, we utilized multiple logistic regression analysis to investigate the factors associated with the selection of levodopa and DAs as initial anti-parkinsonian drugs. RESULTS: A total of 99,118 patients with PD who were prescribed levodopa or DAs alone as initial anti-parkinsonian drugs between 2011 and 2020 were eligible for inclusion in the analysis. The prescription rate of DAs increased until 2012, and then steadily decreased annually. The likelihood of levodopa prescription increased with age and at higher-level hospitals. In terms of comorbidities, patients with Alzheimer's disease and cerebrovascular diseases were more likely to be prescribed levodopa than those with peptic ulcer disease and dyslipidemia. CONCLUSION: The decline in levodopa prescriptions was reversed in 2012, and the prescription rate has continued to increase until recently. The odds ratio of levodopa prescription increased in elderly patients with Alzheimer's disease and decreased in patients with Medical aid insurance and peptic ulcer disease.


Assuntos
Doença de Alzheimer , Doença de Parkinson , Úlcera Péptica , Idoso , Humanos , Levodopa , Estudos de Coortes , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/epidemiologia , República da Coreia/epidemiologia
3.
ACS Appl Mater Interfaces ; 15(29): 34462-34474, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37438323

RESUMO

Natural phenolic compounds have antioxidant properties owing to their free radical-scavenging capability. The combined effect of a mixture of phenolic compounds has been studied; however, the detailed investigation for finding a correlation between single phenolic molecules and antioxidant activity has not been explored. Herein, we revealed that the number of phenolic hydroxyl groups in phenolics played a central role in their antioxidant capacity. Based on the finding, tannic acid showed the most effective antioxidant potential, e.g., 76% in tannic acid versus 22% in vitamin C as a standard antioxidant component. Because cancer progression is closely related to oxidative processes at the cellular level, we further applied the surface treatment of tannic acid drug-delivery nanocarriers. Tannic acid-loaded nanocarriers reduced reactive oxygen species of cancer cells as much as 41% of vehicle treatment and remodeled cytoskeletal network. By a gelatin degradation study, TA-loaded nanocarrier-treated cells induced 44.6% reduction of degraded area than vehicle-treated cells, implying a potential of blocking invasiveness of cancer cells.


Assuntos
Antioxidantes , Neoplasias , Antioxidantes/farmacologia , Fenóis/farmacologia , Oxirredução , Taninos/farmacologia , Espécies Reativas de Oxigênio
4.
Nano Converg ; 10(1): 26, 2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37296273

RESUMO

The understanding of the endocytosis process of internalized nanomedicines through membrane biomarker is essential for the development of molecular-specific nanomedicines. In various recent reports, the metalloproteases have been identified as important markers during the metastasis of cancer cells. In particular, MT1-MMP has provoked concern due to its protease activity in the degradation of the extracellular matrix adjacent to tumors. Thus, in the current work, we have applied fluorescent Au nanoclusters which present strong resistance to chemical quenching to the investigation of MT1-MMP-mediated endocytosis. We synthesized protein-based Au nanocluster (PAuNC) and MT1-MMP-specific peptide was conjugated with PAuNC (pPAuNC) for monitoring protease-mediated endocytosis. The fluorescence capacity of pPAuNC was investigated and MT1-MMP-mediated intracellular uptake of pPAuNC was subsequently confirmed by a co-localization analysis using confocal microscopy and molecular competition test. Furthermore, we confirmed a change in the intracellular lipophilic network after an endocytosis event of pPAuNC. The identical lipophilic network change did not occur with the endocytosis of bare PAuNC. By classification of the branched network between the lipophilic organelles at the nanoscale, the image-based analysis of cell organelle networking allowed the evaluation of nanoparticle internalization and impaired cellular components after intracellular accumulation at a single-cell level. Our analyses suggest a methodology to achieve a better understanding of the mechanism by which nanoparticles enter cells.

5.
Front Endocrinol (Lausanne) ; 14: 1172199, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37293506

RESUMO

Background: Approximately 30% of diabetic patients develop diabetic nephropathy, a representative microvascular complication. Although the etiological mechanism has not yet been fully elucidated, renal tubular damage by hyperglycemia-induced expression of transforming growth factor-ß (TGF-ß) is known to be involved. Recently, a new type of cell death by iron metabolism called ferroptosis was reported to be involved in kidney damage in animal models of diabetic nephropathy, which could be induced by TGF-ß. Bone morphogenetic protein-7 (BMP7) is a well-known antagonist of TGF-ß inhibiting TGF-ß-induced fibrosis in many organs. Further, BMP7 has been reported to play a role in the regeneration of pancreatic beta cells in diabetic animal models. Methods: We used protein transduction domain (PTD)-fused BMP7 in micelles (mPTD-BMP7) for long-lasting in vivo effects and effective in vitro transduction and secretion. Results: mPTD-BMP7 successfully accelerated the regeneration of diabetic pancreas and impeded progression to diabetic nephropathy. With the administration of mPTD-BMP7, clinical parameters and representative markers of pancreatic damage were alleviated in a mouse model of streptozotocin-induced diabetes. It not only inhibited the downstream genes of TGF-ß but also attenuated ferroptosis in the kidney of the diabetic mouse and TGF-ß-stimulated rat kidney tubular cells. Conclusion: BMP7 impedes the progression of diabetic nephropathy by inhibiting the canonical TGF-ß pathway, attenuating ferroptosis, and helping regenerate diabetic pancreas.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Ferroptose , Animais , Camundongos , Ratos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Pâncreas/metabolismo , Fator de Crescimento Transformador beta/metabolismo
6.
Curr Med Res Opin ; 39(2): 197-203, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36519289

RESUMO

OBJECTIVE: Ranitidine products contain unacceptable levels of N-nitrosodimethylamine. This study aimed to investigate changes in the treatment regimen and their influencing factors after the ranitidine recall. METHODS: This retrospective study used data from nationwide Korean claims from 2019. Patients with gastrointestinal disorders treated with ranitidine for at least a month on 25 September 2019, were selected for this study. Other histamine-2 receptor antagonists (H2RAs), proton pump inhibitors (PPIs), potassium-competitive acid blockers (PCABs), and prostaglandin E1 analogs were administered as alternatives to ranitidine. Kaplan-Meier survival and Cox proportional hazards regression analyses were performed to gauge the time until switching to alternative drugs and assess the influencing factors. RESULTS: In total, 7502 patients were included in this study, among which 5164 (68.8%) switched from ranitidine to an alternative drug. The most prescribed alternative drugs were H2RAs, followed by PPIs, PCABs, and prostaglandin E1 analogs. Increasing age; Medical Aid insurance (MedAid); and a history of hypertension, diabetes mellitus, asthma, and osteoarthritis were associated with a higher probability of switching treatments. Patients with concomitant gastroesophageal reflux disease and peptic ulcers were more likely to switch to alternative drugs than patients with gastritis. CONCLUSIONS: Approximately two-thirds of patients with gastrointestinal disorders switched from ranitidine to alternative drugs within 3 months after ranitidine withdrawal. The Cox regression analysis showed that age (>55 years); insurance type (MedAid); comorbidities, such as hypertension, diabetes mellitus, asthma, and osteoarthritis, and gastrointestinal disorder severity influenced the switch from ranitidine to alternative drugs.


Assuntos
Asma , Gastroenteropatias , Hipertensão , Osteoartrite , Humanos , Pessoa de Meia-Idade , Ranitidina/efeitos adversos , Estudos Retrospectivos , Estudos de Coortes , Alprostadil , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/epidemiologia , Inibidores da Bomba de Prótons/efeitos adversos , Antagonistas dos Receptores H2 da Histamina/efeitos adversos , Prescrições , Osteoartrite/tratamento farmacológico , Asma/tratamento farmacológico , Hipertensão/tratamento farmacológico
7.
Cell Rep ; 40(3): 111077, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35858554

RESUMO

Redox-active metal ions are pivotal for rapid metabolism, proliferation, and aggression across cancer types, and this presents metal chelation as an attractive cancer cell-targeting strategy. Here, we identify a metal chelator, KS10076, as a potent anti-cancer drug candidate. A metal-bound KS10076 complex with redox potential for generating hydrogen peroxide and superoxide anions induces intracellular reactive oxygen species (ROS). The elevation of ROS by KS10076 promotes the destabilization of signal transducer and activator of transcription 3, removes aldehyde dehydrogenase isoform 1-positive cancer stem cells, and subsequently induces autophagic cell death. Bioinformatic analysis of KS10076 susceptibility in pan-cancer cells shows that KS10076 potentially targets cancer cells with increased mitochondrial function. Furthermore, patient-derived organoid models demonstrate that KS10076 efficiently represses cancer cells with active KRAS, and fluorouracil resistance, which suggests clinical advantages.


Assuntos
Morte Celular Autofágica , Fator de Transcrição STAT3 , Família Aldeído Desidrogenase 1 , Apoptose , Linhagem Celular Tumoral , Quelantes , Humanos , Células-Tronco Neoplásicas/metabolismo , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT3/metabolismo , Superóxidos/metabolismo
8.
Am J Cancer Res ; 12(2): 763-778, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35261800

RESUMO

Bone morphogenetic protein-7 (BMP-7) antagonizes transforming growth factor-ß (TGF-ß), which is critically involved in liver fibrogenesis. Here, we designed a micelle formulation consisting of a protein transduction domain (PTD) fused BMP-7 polypeptide (mPTD-BMP-7) to enhance endocytic delivery, and investigated its ability to ameliorate liver fibrosis. The mPTD-BMP-7 formulation was efficiently delivered into cells via endocytosis, where it inhibited TGF-ß mediated epithelial-mesenchymal transition. After successfully demonstrating delivery of fluorescently labeled mPTD-BMP-7 into the murine liver in vivo, we tested the mPTD-BMP-7 formulation in a murine liver fibrosis model, developed by repeated intraperitoneal injection of hepatotoxic carbon tetrachloride, twice weekly from 4 to 16 weeks. mPTD-BMP-7 effects were tested by injecting the mPTD-BMP-7 formulation (or vehicle control) into the lateral tail at a dose of 50 (n=8) or 500 µg/kg (n=10), also twice per week from 4 to 16 weeks. Vehicle-treated control mice developed fibrous septa surrounding the liver parenchyma and marked portal-to-portal bridging with occasional nodules, whereas mice treated with mPTD-BMP-7 showed only fibrous expansion of some portal areas, with or without short fibrous septa. Using the Ishak scoring system, we found that the fibrotic burden was significantly lower in mPTD-BMP-7 treated mice than in control mice (all P<0.001). Treatment with mPTD-BMP-7 protected tight junctions between hepatocytes and reduced extracellular matrix protein levels. It also significantly decreased mRNA levels of collagen 1A, smooth muscle α-actin, and connective tissue growth factor compared with that in control mice (all P<0.001). Collectively, out results indicate that mPTD-BMP-7, a prodrug formulation of BMP-7, ameliorates liver fibrosis by suppressing the TGF-ß signaling pathway in a murine liver fibrosis model.

9.
Anticancer Res ; 42(1): 589-598, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34969768

RESUMO

BACKGROUND/AIM: We previously identified KS40008 (4-(3-(4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)benzene-1,2-diol), a novel inhibitor of dual-specificity tyrosine phosphorylation-regulated kinase family (DYRK) 1A/B, which exhibited high enzymatic activity and cell proliferation-inhibitory effects in colorectal cancer (CRC) cell lines. In the present study, we aimed to elucidate the antitumor mechanisms of KS40008. MATERIALS AND METHODS: To assess the cytotoxicity of KS40008, we utilized a human cell line and organoid model and performed a CCK-8 assay and real-time cell analysis. Mitochondrial function was determined through mitochondrial staining, mito-stress test, and glycolysis test. In addition, we investigated the mechanisms of cancer cell death induced by KS40008 through immunoblotting, real-time quantitative polymerase chain reaction, reactive oxygen species staining, and immunofluorescence staining. RESULTS: KS40008 exhibited significant cytotoxicity in CRC and non-CRC cell lines, and organoid models compared to 5-fluorouracil, a conventional chemotherapeutic drug. Moreover, KS40008-induced inhibition of DYRK1A/B led to mitochondrial dysfunction and endoplasmic reticulum stress, promoting autophagic cancer cell death. CONCLUSION: KS40008 exerts antitumor activity through the inhibition of DYRK1A/B. Here, we demonstrated a mechanism by which KS40008 affects endoplasmic reticulum stress-mediated autophagy through the induction of mitochondrial stress, leading to cytotoxicity in CRC.


Assuntos
Morte Celular Autofágica/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Tirosina Quinases/genética , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Reprogramação Celular/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/genética , Fluoruracila/farmacologia , Glicólise/efeitos dos fármacos , Humanos , Redes e Vias Metabólicas/efeitos dos fármacos , Camundongos , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Quinases Dyrk
10.
J Chemother ; 34(8): 534-542, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34870568

RESUMO

Docetaxel/cyclophosphamide (TC) is a widely used adjuvant chemotherapy regimen, especially in patients with node-negative or low-risk node-positive breast cancer. Guidelines recommend the use of prophylactic granulocyte colony-stimulating factor (G-CSF) to prevent febrile neutropenia. In this study, we aimed to explore the use of G-CSF as a primary prophylactic and determine the factors influencing its use. This retrospective study used nationwide claims data from the National Inpatient Sample compiled by the Health Insurance Review and Assessment Service in South Korea from 2018. The claims data included 10% of inpatients admitted at least once in 2018 and 1% of outpatients who were not admitted. Female patients with breast cancer who received an adjuvant TC regimen after surgery were selected. Primary prophylactic G-CSF was defined as G-CSF prescribed within two days of the first cycle of TC. The factors influencing its utilisation were investigated using the chi-square test and a multiple logistic regression model. A total of 229 patients were included in the analysis. The proportion of patients who received primary prophylactic G-CSF treatment after the first cycle of TC was 55.5%. The factors positively influencing G-CSF utilization were patients' age ≥65 years, location (i.e. metropolitan areas), and the type of healthcare facility (i.e. non-tertiary hospitals). The use of prophylactic G-CSF in patients with breast cancer who received the adjuvant TC regimen was insufficient. The use of primary G-CSF prophylaxis should be emphasised to reduce the risk of febrile neutropenia among patients receiving a myelosuppressive TC regimen.


Assuntos
Neoplasias da Mama , Neutropenia Febril , Fator Estimulador de Colônias de Granulócitos , Idoso , Feminino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/efeitos adversos , Ciclofosfamida/efeitos adversos , Docetaxel/efeitos adversos , Docetaxel/uso terapêutico , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/tratamento farmacológico , Neutropenia Febril/prevenção & controle , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Estudos Retrospectivos
11.
Diagnostics (Basel) ; 11(5)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067713

RESUMO

Sentinel lymph node (SLN) biopsy has gained attention as a method of minimizing the extent of neck dissection with a similar survival rate as elective neck dissection in oral cancer. Indocyanine green (ICG) imaging is widely used in the field of surgical oncology. Real-time ICG-guided SLN imaging has been widely used in minimally invasive surgeries for various types of cancers. Here, we provide an overview of conventional SLN biopsy and ICG-guided SLN mapping techniques for oral cancer. Although ICG has many strengths, it still has limitations regarding its potential use as an ideal compound for SLN mapping. The development of novel fluorophores and imaging technology is needed for accurate identification of SLNs, which will allow precision surgery that would reduce morbidities and increase patient survival.

12.
Front Pharmacol ; 11: 591275, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33364962

RESUMO

Tubulointerstitial renal fibrosis is a chronic disease process affecting chronic kidney disease (CKD). While the etiological role of transforming growth factor-beta (TGF-ß) is well known for epithelial-mesenchymal transition (EMT) in chronic kidney disease, effective therapeutics for renal fibrosis are largely limited. As a member of the TGF-ß superfamily, bone morphogenetic protein-7 (BMP-7) plays an important role as an endogenous antagonist of TGF-ß, inhibiting fibrotic progression in many organs. However, soluble rhBMP-7 is hardly available for therapeutics due to its limited pharmacodynamic profile and rapid clearance in clinical settings. In this study, we have developed a novel therapeutic approach with protein transduction domain (PTD) fused BMP-7 in micelle (mPTD-BMP-7) for long-range signaling in vivo. Contrary to rhBMP-7 targeting its cognate receptors, the nano-sized mPTD-BMP-7 is transduced into cells through an endosomal pathway and secreted to the exosome having active BMP-7. Further, transduced mPTD-BMP-7 successfully activates SMAD1/5/8 and inhibits the TGF-ß-mediated epithelial-mesenchymal transition process in vitro and in an in vivo unilateral ureter obstruction model. To determine the clinical relevance of our strategy, we also developed an intra-arterial administration of mPTD-BMP-7 through renal artery in pigs. Interestingly, mPTD-BMP-7 through renal artery intervention effectively delivered into Bowman's space and inhibits unilateral ureter obstruction-induced renal fibrosis in pigs. Our results provide a novel therapeutic targeting TGF-ß-mediated renal fibrosis and other organs as well as a clinically available approach for kidney.

13.
Langmuir ; 36(9): 2271-2277, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-32013441

RESUMO

Flow lithography (FL), a versatile technique used to synthesize anisotropic multifunctional microparticles, has attracted substantial interest, given that the resulting particles with complex geometries and multilayered biochemical functionalities can be used in a wide variety of applications. However, after this process, there are double bonds remaining from the cross-linkable groups of monomers. The unreacted cross-linkable groups can affect the particles' biochemical properties. Here, we verify that the microparticles produced by FL contain a significant number of unreacted acrylate double bonds (UADBs), which could cause irreversible biochemical changes in the particle and pernicious effects to biological systems. We also confirm that the particles contain a considerable number of UADBs, regardless of the various synthetic (lithographic) conditions that can be used in a typical FL process. We present an effective way to eliminate a substantial amount of UADBs after synthesis by linking biochemically inert poly(ethylene glycol) based on click chemistry. We verify that eliminating UADBs by using this click chemistry approach can efficiently resolve problems, such as the occurrence of random reactions and the cytotoxicity of UADBs.

14.
Small ; 15(21): e1900434, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30997745

RESUMO

Microcapsules with molecule-selective permeation are appealing as microreactors, capsule-type sensors, drug and cell carriers, and artificial cells. To accomplish molecular size- and charge-selective permeation, regular size of pores and surface charges have been formed in the membranes. However, it remains an important challenge to provide advanced regulation of transmembrane transport. Here, smart microcapsules are designed that provide molecular polarity- and temperature-dependent permeability. With capillary microfluidic devices, water-in-oil-in-water (W/O/W) double-emulsion drops are prepared, which serve as templates to produce microcapsules. The oil shell is composed of two monomers and dodecanol, which turns to a polymeric framework whose continuous voids are filled with dodecanol upon photopolymerization. One of the monomers provides mechanical stability of the framework, whereas the other serves as a compatibilizer between growing polymer and dodecanol, preventing macrophase separation. Above melting point of dodecanol, molecules that are soluble in the molten dodecanol are selectively allowed to diffuse across the shell, where the rate of transmembrane transport is strongly influenced by partition coefficient. The rate is drastically lowered for temperatures below the melting point. This molecular polarity- and temperature-dependent permeability renders the microcapsules potentially useful as drug carriers for triggered release and contamination-free microreactors and microsensors.


Assuntos
Cápsulas/química , Portadores de Fármacos/química , Emulsões/química , Permeabilidade , Polímeros/química , Temperatura
15.
Nanotechnology ; 30(24): 245101, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-30836350

RESUMO

Polydiacetylene-based nanoparticles have been developed as nanocarriers for various bio-applications. However, how nanocarriers enter the cell environment and affect cell viability has not yet been considerably explored. In this study, polydiacetylene-based nanoliposomes (nanosomes) were electrostatically complexed with rhodamine fluorophores. Based on real-time cell imaging and cell viability assessment, the most highly polymerized nanosomes were found to be less toxic to cells. Moreover, it was revealed that the rhodamine/polydiacetylene nanosome complex dissociates at cell environment, the polydiacetylene nanosome penetrates into cells, as suggested by the fluorescence observed in confocal microscopy images.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Nanopartículas/administração & dosagem , Polímero Poliacetilênico/administração & dosagem , Linhagem Celular Tumoral , Humanos , Lipossomos/administração & dosagem , Lipossomos/química , Nanopartículas/química , Polímero Poliacetilênico/química
16.
Exp Mol Med ; 51(1): 1-14, 2019 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-30700700

RESUMO

Epidermal growth factor receptor (EGFR) overexpression is common in head and neck squamous cell carcinoma. Targeted therapy specifically directed towards EGFR has been an area of keen interest in head and neck cancer research, as EGFR is potentially an integration point for convergent signaling. Despite the latest advancements in cancer diagnostics and therapeutics against EGFR, the survival rates of patients with advanced head and neck cancer remain disappointing due to anti-EGFR resistance. This review article will discuss recent multilateral efforts to discover and validate actionable strategies that involve signaling pathways in heterogenous head and neck cancer and to overcome anti-EGFR resistance in the era of precision medicine. Particularly, this review will discuss in detail the issue of cancer metabolism, which has recently emerged as a novel mechanism by which head and neck cancer may be successfully controlled according to different perspectives.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Animais , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Inibidores de Proteínas Quinases/uso terapêutico , Transdução de Sinais
17.
Carbohydr Polym ; 203: 26-34, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30318212

RESUMO

Recently, Near-infrared (NIR)-induced photothermal killing of pathogenic bacteria has received considerable attention due to the increase in antibiotic resistant bacteria. In this paper, we report a simple aqueous solution-based strategy to construct an effective photothermal nanocomposite composed of poly(3,4-ethylenedioxythiophene):poly(styrene-sulfonate) (PEDOT:PSS) and agarose with thermo-processability, light triggered self-healing, and excellent antibacterial activity. Our experiments revealed that PEDOT:PSS/agarose was easily coated on both a 2D glass substrate and 3D cotton structure. Additionally, PEDOT:PSS/agarose can be designed into free-standing objects of diverse shape as well as restored through an NIR light-induced self-healing effect after damage. Taking advantage of strong NIR light absorption, PEDOT:PSS/agarose exhibited a sharp temperature increase of 24.5 °C during NIR exposure for 100 s. More importantly, we demonstrated that the temperature increase on PEDOT:PSS/agarose via photothermal conversion resulted in the rapid and effective killing of nearly 100% of the pathogenic bacteria within 2 min of NIR irradiation.

18.
Small ; 14(41): e1803000, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30350552

RESUMO

Biophysical properties are intimately connected to metastatic functions and aggressiveness in cancers. Especially, cellular stiffness is regarded as a biomarker for the understanding of metastatic potential and drug sensitivity. Here, protease-mediated changes of cortical stiffness are identified due to the deformation of cytoskeleton alignment at a cortex. For the past few decades, membrane type 1-matrix metalloproteinase (MT1-MMP) has been well known as a kernel protease enriched in podosomes during metastasis for extracellular matrix degradation. However, the biophysical significance of MT1-MMP expressing cancer cells is still unknown. Therefore, the nanomechanics of cancer cells is analyzed by a nanoindentation using a microsphere-attached cantilever of atomic force microscopy (AFM). In conclusion, the results suggest that MT1-MMP has contributed as a key regulator in cytoskeletal deformation related with cancer metastasis. Particularly, the AFM-based nanoindentation system for the monitoring of cortical nanomechanics will be crucial to understand molecular networks in cancers.


Assuntos
Metaloproteinase 14 da Matriz/química , Microesferas , Citoesqueleto/química , Microscopia de Força Atômica
19.
Nanoscale Res Lett ; 13(1): 288, 2018 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-30229394

RESUMO

The aim of this study was the development of a human epidermal growth factor receptor 2 (HER2)-targetable contrast agent for magnetic resonance imaging (MRI) with a high magnetic sensitivity. An anti-HER2 aptamer-modified magnetic nanosensitizer (AptHER2-MNS) was prepared by conjugation with 5'-thiol-modified aptamers and maleimidylated magnetic nanocrystals (MNCs). The physicochemical characteristics and targeting ability of AptHER2-MNS were confirmed, and the binding affinity (Kd) onto HER2 protein of AptHER2-MNS was 0.57 ± 0.26 nM. In vivo MRI contrast enhancement ability was also verified at HER2+ cancer cell (NIH3T6.7)-xenograft mouse models (n = 3) at 3T clinical MRI instrument. The control experiment was carried out using non-labeled MNCs. The results indicated that up to 150% contrast enhancement was achieved at the tumor region in the T2-weighted MR images after the injection of the AptHER2-MNS agent in mice that received the NIH3T6.7 cells.

20.
Sci Rep ; 8(1): 13683, 2018 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-30209277

RESUMO

Gold nanorods (GNRs) are of great interest in cancer therapy given their ability to ablate tumor cells using deep tissue-penetrating near-infrared light. GNRs coated with tumor-specific moieties have the potential to target tumor tissue to minimize damage to normal tissue. However, perfect targeting is difficult to achieve given that nanoparticles could be broadly dispersed inside the body. Moreover, interaction between targeting groups and biological molecules could lower targeting abilities, resulting in off-target accumulation which might produce nanotoxicity. Here we introduce GNR-encapsulated microcubes (GNR@MCs) that can be utilized as implantable photothermal agents. GNR@MCs are created by encapsulating GNRs in polymeric networks via stop flow lithography (SFL), a one-phase synthesis technique which allows for creation of surfactant-free, uniform particles, and injection of GNR@MCs into the body after a simple rinse step. GNRs are highly packed and firmly encapsulated inside MCs, and entrapped GNRs exhibit optical properties comparable to that of unbound GNRs and photothermal efficiency (58%) in line with that of nano-sized agents (51-95%). Photothermal ablation in murine models is achieved using GNR@MCs stably implanted into the tumor tissue, which suggests that GNR@MCs can be a safe and effective platform for cancer therapy.


Assuntos
Ouro/farmacologia , Fototerapia/métodos , Animais , Linhagem Celular Tumoral , Camundongos , Nanotubos
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