Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
1.
ACS Omega ; 9(27): 29870-29883, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39005763

RESUMO

Idiopathic pulmonary fibrosis (IPF) affects an estimated global population of around 3 million individuals. IPF is a medical condition with an unknown cause characterized by the formation of scar tissue in the lungs, leading to progressive respiratory disease. Currently, there are only two FDA-approved small molecule drugs specifically for the treatment of IPF and this has created a demand for the rapid development of drugs for IPF treatment. Moreover, denovo drug development is time and cost-intensive with less than a 10% success rate. Drug repurposing currently is the most feasible option for rapidly making the drugs to market for a rare and sporadic disease. Normally, the repurposing of drugs begins with a screening of FDA-approved drugs using computational tools, which results in a low hit rate. Here, an integrated machine learning-based drug repurposing strategy is developed to significantly reduce the false positive outcomes by introducing the predock machine-learning-based predictions followed by literature and GSEA-assisted validation and drug pathway prediction. The developed strategy is deployed to 1480 FDA-approved drugs and to drugs currently in a clinical trial for IPF to screen them against "TGFB1", "TGFB2", "PDGFR-a", "SMAD-2/3", "FGF-2", and more proteins resulting in 247 total and 27 potentially repurposable drugs. The literature and GSEA validation suggested that 72 of 247 (29.14%) drugs have been tried for IPF, 13 of 247 (5.2%) drugs have already been used for lung fibrosis, and 20 of 247 (8%) drugs have been tested for other fibrotic conditions such as cystic fibrosis and renal fibrosis. Pathway prediction of the remaining 142 drugs was carried out resulting in 118 distinct pathways. Furthermore, the analysis revealed that 29 of 118 pathways were directly or indirectly involved in IPF and 11 of 29 pathways were directly involved. Moreover, 15 potential drug combinations are suggested for showing a strong synergistic effect in IPF. The drug repurposing strategy reported here will be useful for rapidly developing drugs for treating IPF and other related conditions.

2.
Mol Divers ; 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38227161

RESUMO

Endometrial cancer (EC) is the 6th most common cancer in women around the world. Alone in the United States (US), 66,200 new cases and 13,030 deaths are expected to occur in 2023 which needs the rapid development of potential therapies against EC. Here, a network-based drug-repurposing strategy is developed which led to the identification of 16 FDA-approved drugs potentially repurposable for EC as potential immune checkpoint inhibitors (ICIs). A network of EC-associated immune checkpoint proteins (ICPs)-induced protein interactions (P-ICP) was constructed. As a result of network analysis of P-ICP, top key target genes closely interacting with ICPs were shortlisted followed by network proximity analysis in drug-target interaction (DTI) network and pathway cross-examination which identified 115 distinct pathways of approved drugs as potential immune checkpoint inhibitors. The presented approach predicted 16 drugs to target EC-associated ICPs-induced pathways, three of which have already been used for EC and six of them possess immunomodulatory properties providing evidence of the validity of the strategy. Classification of the predicted pathways indicated that 15 drugs can be divided into two distinct pathway groups, containing 17 immune pathways and 98 metabolic pathways. In addition, drug-drug correlation analysis provided insight into finding useful drug combinations. This fair and verified analysis creates new opportunities for the quick repurposing of FDA-approved medications in clinical trials.

3.
Comput Struct Biotechnol J ; 21: 5186-5200, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37920815

RESUMO

In women, cervical cancer (CC) is the fourth most common cancer around the world with average cases of 604,000 and 342,000 deaths per year. Approximately 50% of high-grade CC are attributed to human papillomavirus (HPV) types 16 and 18. Chances of CC in HPV-positive patients are 6 times more than HPV-negative patients which demands timely and effective treatment. Repurposing of drugs is considered a viable approach to drug discovery which makes use of existing drugs, thus potentially reducing the time and costs associated with de-novo drug discovery. In this study, we present an integrative drug repurposing framework based on a systems biology-enabled network medicine platform. First, we built an HPV-induced CC protein interaction network named HPV2C following the CC signatures defined by the omics dataset, obtained from GEO database. Second, the drug target interaction (DTI) data obtained from DrugBank, and related databases was used to model the DTI network followed by drug target network proximity analysis of HPV-host associated key targets and DTIs in the human protein interactome. This analysis identified 142 potential anti-HPV repurposable drugs to target HPV induced CC pathways. Third, as per the literature survey 51 of the predicted drugs are already used for CC and 33 of the remaining drugs have anti-viral activity. Gene set enrichment analysis of potential drugs in drug-gene signatures and in HPV-induced CC-specific transcriptomic data in human cell lines additionally validated the predictions. Finally, 13 drug combinations were found using a network based on overlapping exposure. To summarize, the study provides effective network-based technique to quickly identify suitable repurposable drugs and drug combinations that target HPV-associated CC.

4.
Pharmaceuticals (Basel) ; 16(9)2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37765137

RESUMO

The objective of this study was to evaluate the effectiveness of organ-on-chip system investigating simultaneous cellular efficacy and real-time reactive oxygen species (ROS) occurrence of anticancer drug-loaded nanoparticles (NPs) using hepatocarcinoma cells (HepG2) chip system under static and hepatomimicking shear stress conditions (5 dyne/cm2). Then, the role of hepatomimetic shear stress exposed to HepG2 and drug solubility were compared. The highly soluble doxorubicin (DOX) and poorly soluble paclitaxel (PTX) were chosen. Fattigated NPs (AONs) were formed via self-assembly of amphiphilic albumin (HSA)-oleic acid conjugate (AOC). Then, drug-loaded AONs (DOX-AON or PTX-AON) were exposed to a serum-free HepG2 medium at 37 °C and 5% carbon dioxide for 24 h using a real-time ROS sensor chip-based microfluidic system. The cellular efficacy and simultaneous ROS occurrence of free drugs and drug-loaded AONs were compared. The cellular efficacy of drug-loaded AONs varied in a dose-dependent manner and were consistently correlated with real-time of ROS occurrence. Drug-loaded AONs increased the intracellular fluorescence intensity and decreased the cellular efficacy compared to free drugs under dynamic conditions. The half-maximal inhibitory concentration (IC50) values of free DOX (13.4 µg/mL) and PTX (54.44 µg/mL) under static conditions decreased to 11.79 and 38.43 µg/mL, respectively, under dynamic conditions. Furthermore, DOX- and PTX-AONs showed highly decreased IC50 values of 5.613 and 21.86 µg/mL, respectively, as compared to free drugs under dynamic conditions. It was evident that cellular efficacy and real-time ROS occurrence were well-correlated and highly dependent on the drug-loaded nanostructure, drug solubility and physiological shear stress.

5.
J Biomed Inform ; 142: 104373, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37120047

RESUMO

Cancer is the second leading cause of death globally, trailing only heart disease. In the United States alone, 1.9 million new cancer cases and 609,360 deaths were recorded for 2022. Unfortunately, the success rate for new cancer drug development remains less than 10%, making the disease particularly challenging. This low success rate is largely attributed to the complex and poorly understood nature of cancer etiology. Therefore, it is critical to find alternative approaches to understanding cancer biology and developing effective treatments. One such approach is drug repurposing, which offers a shorter drug development timeline and lower costs while increasing the likelihood of success. In this review, we provide a comprehensive analysis of computational approaches for understanding cancer biology, including systems biology, multi-omics, and pathway analysis. Additionally, we examine the use of these methods for drug repurposing in cancer, including the databases and tools that are used for cancer research. Finally, we present case studies of drug repurposing, discussing their limitations and offering recommendations for future research in this area.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Reposicionamento de Medicamentos/métodos , Biologia de Sistemas/métodos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Desenvolvimento de Medicamentos , Biologia Computacional/métodos
6.
J Med Virol ; 95(4): e28693, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36946499

RESUMO

Cancer management is major concern of health organizations and viral cancers account for approximately 15.4% of all known human cancers. Due to large number of patients, efficient treatments for viral cancers are needed. De novo drug discovery is time consuming and expensive process with high failure rate in clinical stages. To address this problem and provide treatments to patients suffering from viral cancers faster, drug repurposing emerges as an effective alternative which aims to find the other indications of the Food and Drug Administration approved drugs. Applied to viral cancers, drug repurposing studies following the niche have tried to find if already existing drugs could be used to treat viral cancers. Multiple drug repurposing approaches till date have been introduced with successful results in viral cancers and many drugs have been successfully repurposed various viral cancers. Here in this study, a critical review of viral cancer related databases, tools, and different machine learning, deep learning and virtual screening-based drug repurposing studies focusing on viral cancers is provided. Additionally, the mechanism of viral cancers is presented along with drug repurposing case study specific to each viral cancer. Finally, the limitations and challenges of various approaches along with possible solutions are provided.


Assuntos
Aprendizado Profundo , Neoplasias , Humanos , Reposicionamento de Medicamentos/métodos , Detecção Precoce de Câncer , Aprendizado de Máquina , Descoberta de Drogas/métodos , Neoplasias/tratamento farmacológico
7.
Biomed Pharmacother ; 161: 114408, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36841027

RESUMO

Antibody Drug Conjugate (ADC) is an emerging technology to overcome the limitations of chemotherapy by selectively targeting the cancer cells. ADC binds with an antigen, specifically over expressed on the surface of cancer cells, results decrease in bystander effect and increase in therapeutic index. The potency of an ideal ADC is entirely depending on several physicochemical factors such as site of conjugation, molecular weight, linker length, Steric hinderance, half-life, conjugation method, binding energy and so on. Inspite of the fact that there is more than 100 of ADCs are in clinical trial only 14 ADCs are approved by FDA for clinical use. However, to design an ideal ADC is still challenging and there is much more to be done. Here in this review, we have discussed the key components along with their significant role or contribution towards the efficacy of an ADC. Moreover, we also explained about the recent advancement in the conjugation method. Additionally, we spotlit the mode of action of an ADC, recent challenges, and future perspective regarding ADC. The profound knowledge regarding key components and their properties will help in the synthesis or production of different engineered ADCs. Therefore, contributes to develop an ADC with low safety concern and high therapeutic index. We hope this review will improve the understanding and encourage the practicing of research in anticancer ADCs development.


Assuntos
Antineoplásicos , Imunoconjugados , Imunoconjugados/uso terapêutico , Imunoconjugados/química , Antígenos/metabolismo , Antineoplásicos/farmacologia
8.
Life (Basel) ; 12(2)2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35207423

RESUMO

BACKGROUND: Plants have been considered a vital source of modern pharmaceutics since the paleolithic age. Contemporary chemotherapeutic drugs for cancer therapy are chemical entities sourced from plants. However, synthetic drugs or their derivatives come with severe to moderate side effects for human health. Hence, the quest to explore and discover plant-based novel anticancer drugs is ongoing. Anticancer activities are the primary method to estimate the potential and efficacy of an extract or compound for drug discovery. However, traditional in vitro anticancer activity assays often show poor efficacy due to the lack of in-vivo-like cellular environment. In comparison, the animal-based in vivo assays lack human genetic makeup and have ethical concerns. AIM: This study aimed to overcome the limitations of traditional cell-culture-based anticancer assays and find the most suitable assay for anticancer activity of plant extracts. We first reported utilizing a liver tumor microphysiological system in the anticancer effect assessment of plant extracts. METHODOLOGY: Methanolic extracts of Acer cappadocicum Gled were used to assess anticancer activity against liver tumor microphysiological system (MPS), and cell viability, liver function tests, and antioxidant enzyme activities were performed. Additionally, an embedded transepithelial electrical resistance sensor was utilized for the real-time monitoring of the liver tumor MPS. The results were also compared with the traditional cell culture model. RESULTS: The study demonstrated the superiority of the TEER sensor-based liver tumor MPS by its better anticancer activity based on cell viability and biomarker analysis compared to the traditional in vitro cell culture model. The anticancer effects of the plant extracts were successfully observed in real time, and methanolic extracts of Acer cappadocicum Gled increased the alanine transaminase and aspartate aminotransferase secretion, which may reveal the different mechanisms of these extracts and suggest a clue for the future molecular study of the anticancer pathways. CONCLUSION: Our results show that the liver tumor microphysiological system could be a better platform for plant-based anticancer activity assessment than traditional cell culture models.

9.
Life (Basel) ; 11(7)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34357028

RESUMO

The appearance of novel microbial resistance, diverse cancer ailment and several other morbidities such as appetite loss, hair loss, anemia, cell damage, etc., are among most critical situation that keeps the phytochemical quest on. Thus, this study characterized the antimicrobial, antioxidant, and anticancer potentials of a rarely accessed Acer cappadocicum gled (AC) population thriving in a remote Palas Valley in northern Pakistan. Leaf extracts of the plant were prepared in organic solvents with different polarities through maceration. Extracts were subjected to antimicrobial, antioxidant, and anticancer activities using agar well, DPPH and cell viability assays. A. cappadocicum methanolic extract (ACM) significantly inhibited bacterial growth, followed by n-butanolic extract (ACB) with the second-highest bacterial inhibition. Similar activity was observed against mycelial growth inhibition in plant-fungal pathogen by ACM and ACB. However, human pathogenic fungi did not affect much by extracts. In antioxidant assessment, the chloroform extract (ACC) showed strong scavenging activity and in cytotoxic evaluation, extracts restricted growth proliferation in cancer cells. The inhibitory evidence of extracts, potent scavenging ability, and low cell viability of human-derived cell lines supports the antimicrobial, antioxidant and anticancerous potential of A. cappadocicum. It advances our quest for natural product research.

10.
Nano Converg ; 8(1): 3, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33528697

RESUMO

Hepatic fibrosis is a foreshadowing of future adverse events like liver cirrhosis, liver failure, and cancer. Hepatic stellate cell activation is the main event of liver fibrosis, which results in excessive extracellular matrix deposition and hepatic parenchyma's disintegration. Several biochemical and molecular assays have been introduced for in vitro study of the hepatic fibrosis progression. However, they do not forecast real-time events happening to the in vitro models. Trans-epithelial electrical resistance (TEER) is used in cell culture science to measure cell monolayer barrier integrity. Herein, we explored TEER measurement's utility for monitoring fibrosis development in a dynamic cell culture microphysiological system. Immortal HepG2 cells and fibroblasts were co-cultured, and transforming growth factor ß1 (TGF-ß1) was used as a fibrosis stimulus to create a liver fibrosis-on-chip model. A glass chip-based embedded TEER and reactive oxygen species (ROS) sensors were employed to gauge the effect of TGF-ß1 within the microphysiological system, which promotes a positive feedback response in fibrosis development. Furthermore, albumin, Urea, CYP450 measurements, and immunofluorescent microscopy were performed to correlate the following data with embedded sensors responses. We found that chip embedded electrochemical sensors could be used as a potential substitute for conventional end-point assays for studying fibrosis in microphysiological systems.

11.
Plants (Basel) ; 11(1)2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-35009052

RESUMO

Medicinal plants are known for their diverse use in the traditional medicine of the Himalayan region of Pakistan. The present study is designed to investigate the anticancer and antimicrobial activities of Prunus cornuta and Quercus semicarpifolia. The anticancer activity was performed using cancerous human cell lines (HepG2, Caco-2, A549, MDA-MB-231, and NCI-H1437 carcinoma cells), while the antimicrobial activity was conducted with the agar-well diffusion method. Furthermore, toxicity studies were performed on alveolar and renal primary epithelial cells. Initially, different extracts were prepared by maceration techniques using n-hexane, chloroform, ethyl acetate, butanol, and methanol. The preliminary phytochemical screening showed the presence of secondary metabolites such as alkaloids, tannins, saponins, flavonoids, glycosides, and quinones. The chloroform extract of P. cornuta (PCC) exhibited significant inhibitory activity against Acinetobacter baumannii (16 mm) and Salmonella enterica (14.5 mm). The A. baumannii and S. enterica strains appeared highly susceptible to n-hexane extract of P. cornuta (PCN) with an antibacterial effect of 15 mm and 15.5 mm, respectively. The results also showed that the methanolic extracts of Quercus semecarpifolia (QSM) exhibited considerable antibacterial inhibitory activity in A. baumannii (18 mm), Escherichia coli (15 mm). The QSN and QSE extracts also showed good inhibition in A. baumannii with a 16 mm zone of inhibition. The Rhizopus oryzae strain has shown remarkable mycelial inhibition by PCM and QSN with 16 mm and 21 mm inhibition, respectively. Furthermore, the extracts of P. cornuta and Q. semicarpifolia exhibited prominent growth inhibition of breast (MDA-MB-231) and lung (A549) carcinoma cells with 19-30% and 22-39% cell viabilities, respectively. The gut cell line survival was also significantly inhibited by Q. semicarpifolia (24-34%). The findings of this study provide valuable information for the future development of new antibacterial and anticancer medicinal agents from P. cornuta and Q. semicarpifolia extracts.

12.
Arch Pharm Res ; 43(5): 503-513, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32472315

RESUMO

One of the key problems that have hindered the development and approval of anticancer nanoparticle drug delivery systems is the limited predictability of 2D cell culture and animal models. Here, we describe a biomimetic alveolus-epithelium-on-a-chip (AEOC) model with in-built sensors for monitoring and evaluating pH-responsive zinc oxide quantum dots (QDs)-loaded human serum albumin nanoparticles. This AEOC model closely represents the cancerous alveolus epithelium, which comprises lung cancer cells, as well as stromal cells, such as fibroblasts along with extracellular matrix (ECM) in the form of collagen. ZnO QDs were encapsulated in the HSA nanoparticles with a diameter of 60 nm. The physicochemical properties, quantum dots release, in vitro cytotoxicity, and cellular uptake of HSA-ZnO were evaluated. HSA-ZnO showed higher ZnO loading and encapsulation efficacy. TEER and pH sensors were used to monitor the cells over three days, and real-time data with and without nanoparticle treatment were obtained. Cell viability after treatment with 10 and 50 µg/mL of HSA-ZnO nanoparticles and confocal imaging data confirmed the significant internalization of the nanoparticles under co-culture cellular conditions in the AEOC model. Our designed organ-on-a-chip model has potentially expanded the capabilities of cell culture in biomimetic conditions, and therefore, can provide a low-cost alternative to expensive and tedious animal models for the evaluation of nanomedicines.


Assuntos
Dispositivos Lab-On-A-Chip , Pulmão/efeitos dos fármacos , Modelos Biológicos , Nanopartículas/química , Albumina Sérica Humana/química , Óxido de Zinco/farmacologia , Células A549 , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Relação Dose-Resposta a Droga , Liberação Controlada de Fármacos , Epitélio/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Pontos Quânticos/química , Óxido de Zinco/química
13.
Mater Sci Eng C Mater Biol Appl ; 111: 110760, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32279783

RESUMO

Nanoparticle-protein interactions under conditions mimicking physiology determine how nanoparticles (NPs) will behave inside blood vessels and, therefore, the overall outcome of the drug-delivery system. Here, for the first time, we explore the effects of bio-mimicking shear stress and protein corona conditions on novel active targeting of clickable fattigation nanoparticles (NPs) for cancer therapy. Active targeting dibenzocyclooctyne-functionalized biocompatible gelatin-oleic NPs (GON-DBCOs) via a bioorthogonal click reaction were prepared by the desolvation method for delivery of docetaxel (DTX) to lung and breast cancer models. The effect of shear stress (5 dyne/cm2) and human serum albumin (HSA) protein corona on the cellular behavior of NPs was explored under a dynamic microfluidic system in lung (A549) and breast (MCF-7) cancer cell lines. The developed drug-loaded NPs had a particle size of 300 nm, a narrow size distribution, positive zeta potential, high encapsulation efficacy (72.4%), and spherical morphology. The particle size of the protein corona-coated NPs increased to 341 nm with a negative zeta potential. The inhibitory dose (IC50) increased approximately 3- and 42-fold in A549 and MCF-7 cells, respectively, under dynamic microfluidic conditions compared to static conditions. Cellular uptake was significantly decreased in the presence of shear stress and a protein corona, compared with static conditions, in both lung (A549, **p < 0.01) and breast (MCF-7, *p < 0.05) cancer cell lines. Clathrin-and energy-dependent pathways were found to be involved in the cellular uptake of NPs. This study could serve as a vital tool for the evaluation of NPs under aggressive bio-mimicking conditions comprising shear stress and a protein corona to predict the in vivo performance of NPs and support the preclinical and clinical translation of NP drug delivery systems.


Assuntos
Docetaxel/química , Portadores de Fármacos/química , Gelatina/química , Nanopartículas/química , Coroa de Proteína/química , Materiais Biocompatíveis/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Química Click , Docetaxel/metabolismo , Docetaxel/farmacologia , Liberação Controlada de Fármacos , Humanos , Microscopia Confocal , Tamanho da Partícula , Albumina Sérica Humana/química , Resistência ao Cisalhamento
14.
Mater Sci Eng C Mater Biol Appl ; 92: 477-488, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30184773

RESUMO

Most cancer patients die as a consequence of distant metastases, which are frequently unresponsive to cancer therapy. This study focuses on the anti-tumorigenic and anti-metastatic properties of tangeretin-zinc oxide quantum dots (Tan-ZnO QDs) against the NCI-H358 cell line. Tan-ZnO QDs are pH-sensitive and capitalize on the acidic pH maintained in the tumor microenvironment; therefore, targeted drug delivery is directed specifically to cancer cells, leaving the normal cells less affected. Tan was loaded into synthesized ZnO QDs, and drug loading was analyzed using Fourier transform infrared (FTIR) spectroscopy and ultraviolet-visible (UV-Vis) spectrometry. Crystalline phase and particle size were measured using transmission electron microscopy (TEM) and X-ray diffraction (XRD). Drug release was evaluated in buffered solutions with differing pH for up to 15 h. The results confirmed stable drug release (80%) in an acidic pH. Tan-ZnO QDs induced significant cytotoxicity in NCI-H358 metastatic cells, while not markedly affecting HK-2 human normal cells. Morphology of treated H358 cells analyzed via atomic force microscopy (AFM) showed an increased surface roughness and pores. Further, the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells increased after treatment with Tan-ZnO QDs. DNA fragmentation was also induced after treatment with increasing concentrations of Tan-ZnO QDs in H358 cells. We also confirmed regulation of apoptosis via expression levels of Bax and Bcl-2 proteins; G2/M phase cell cycle arrest was observed. Additionally, cell proliferation and migration drastically decreased, and cell invasion and migration, hallmarks of metastasis, were significantly inhibited in H358 cells. Matrix metalloproteinase (MMP)2 and MMP9, markers of metastasis, as well as vascular endothelial growth factor (VEGF), a marker of angiogenesis, were significantly downregulated upon treatment with Tan-ZnO QDs. In conclusion, our novel formulation destabilized H358 cells by using its acidic tumor microenvironment, thereby regulating cell apoptosis, proliferation, and metastatic properties.


Assuntos
Apoptose/efeitos dos fármacos , Flavonas , Neoplasias Pulmonares/tratamento farmacológico , Pontos Quânticos , Óxido de Zinco , Linhagem Celular Tumoral , Fragmentação do DNA/efeitos dos fármacos , Flavonas/química , Flavonas/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Metástase Neoplásica , Pontos Quânticos/química , Pontos Quânticos/uso terapêutico , Óxido de Zinco/química , Óxido de Zinco/farmacologia
15.
Mater Sci Eng C Mater Biol Appl ; 81: 551-560, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28888009

RESUMO

Current trends in therapeutic research are the application of nanomaterial carriers for cancer therapy. One such molecule, ZnO, originally used in diagnosis and as a drug carrier, is gaining importance for its biological properties. Here, we report for the first time, the scope of ZnO QDs for enhanced cytotoxicity against MCF-7 and metastatic MDA-MB-231 human breast cancer cells. Unlike other ZnO nanostructures, ZnO QDs are dispersed and small sized (8-10nm) which is believed to greatly increase the cellular uptake. Furthermore, the acidic tumor microenvironment attracts ZnO QDs enhancing targeted therapy while leaving normal cells less affected. Results from MTT assay demonstrated that ZnO QDs induced cytotoxicity to MCF-7 and metastatic MDA-MB-231 breast cancer cells at very low concentrations (10 and 15µg/ml) as compared to other reported ZnO nanostructures. HEK-293 cells showed less toxicity at these concentrations. Confocal microscope images from DAPI staining and TUNEL assay demonstrated that ZnO QDs induced nuclear fragmentation and apoptosis in MCF-7 and MDA-MB-231. FACS results suggested ZnO QDs treatment induced cell cycle arrest at the G0/G1 phase in these cells. ZnO QDs drastically decreased the proliferation and migration of MCF-7 and MDA-MB-231 as seen from the results of the clonogenic and wound healing assays respectively. Furthermore, our data suggested that ZnO QDs regulated apoptosis via Bax and Bcl-2 proteins as validated by immunofluorescence and western blot. Taken together, our findings demonstrate that these ultra-small sized ZnO QDs destabilize cancer cells by using its acidic tumor microenvironment thereby inducing apoptosis and controlling the cell proliferation and migration at low dosages.


Assuntos
Neoplasias da Mama , Pontos Quânticos , Antineoplásicos , Apoptose , Linhagem Celular Tumoral , Humanos , Óxido de Zinco
16.
Sci Rep ; 7(1): 5802, 2017 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-28725015

RESUMO

Immunosensors are used to detect the presence of certain bio-reagents mostly targeted at the diagnosis of a condition or a disease. Here, a general purpose electrical immunosensor has been fabricated for the quantitative detection of multiple bio-reagents through the formation of an antibody-antigen pair. The sensors were fabricated using all printing approaches. 2D transition metal dichalcogenide (TMDC) MoS2 thin film was deposited using Electrohydrodynamic atomization (EHDA) on top of an interdigitated transducer (IDT) electrode fabricated by reverse offset printing. The sensors were then treated with three different types of antibodies that were immobilized by physisorption into the highly porous multi-layered structure of MoS2 active layer. BSA was used as blocking agent to prevent non-specific absorption (NSA). The sensors were then employed for the targeted detection of the specific antigens including prostate specific antigen (PSA), mouse immunoglobulin-G (IgG), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). IgG was then selected to test the sensors for point of care (POC) diagnosis through a specially designed electronic readout system for sensors and interfacing it with a smartphone using Bluetooth connection. The sensors showed promising performance in terms of stability, specificity, repeatability, sensitivity, limit of detection (LoD), and range of detection (RoD).


Assuntos
Técnicas Biossensoriais/instrumentação , Dissulfetos/química , Molibdênio/química , Sistemas Automatizados de Assistência Junto ao Leito , Impressão , Smartphone , Anticorpos Imobilizados/metabolismo , Antígenos/metabolismo , Humanos , Imunoglobulina G/metabolismo , Indicadores e Reagentes , NF-kappa B/metabolismo , Antígeno Prostático Específico/metabolismo , Reprodutibilidade dos Testes
17.
J Korean Med Sci ; 31(7): 1105-13, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27366010

RESUMO

It is important to assess psychological distress after a diagnosis for cancer survivors, a population with a high risk for psychological distress. The aim of this study is to assess psychological distress among cancer survivors and to clarify the associated factors. In this cross-sectional analysis, data were obtained from standardized questionnaires administered to 1,163 cancer survivors and 49,243 non-cancer survivors who participated in the Fourth and Fifth Korea National Health and Nutrition Examination Survey (2007-2012). We identified the adjusted rates for psychological distress and assessed factors associated with this kind of distress using multivariate logistic regression. Cancer survivors tended to have a higher adjusted rate of psychological distress than the general population. The current depressive symptom rate for cancer survivors was 16.69%, and the adjusted rate for history of depression in cancer survivors was 15.61%. The adjusted rate for higher level of stress was 25.51% in cancer survivors. Among the cancer survivors, younger subjects, female subjects, and those with limited social support were more prone to psychological distress. In addition, current smokers or risky drinkers, those with chronic diseases, and those with a poor self-perception of their health status were also identified as a high-risk group for psychological distress. As the number of cancer survivors has increased, the importance of assessing psychological distress after a cancer diagnosis should be emphasized among all cancer survivors. Further, psychological supportive care interventions for cancer survivors are needed to improve the survival rate and improve their quality of life.


Assuntos
Neoplasias/diagnóstico , Estresse Psicológico , Sobreviventes/psicologia , Idoso , Estudos Transversais , Depressão/etiologia , Feminino , Nível de Saúde , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/mortalidade , Inquéritos Nutricionais , Qualidade de Vida , Apoio Social , Fatores Socioeconômicos , Inquéritos e Questionários
18.
BMC Public Health ; 16: 492, 2016 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-27286953

RESUMO

BACKGROUND: This study investigated whether the prevalence, awareness, treatment, and control of hypertension and diabetes differed by residential areas. In addition, the rate of good hypertension or diabetes control was examined separately in men and women, and in urban and rural areas. METHODS: This study used Korea National Health and Nutrition Examination V (2010-2012) data, a nationwide cross-sectional survey of general South Korean population. Residential areas were categorized into urban and rural areas. To examine differences between the residential areas in terms of prevalence, awareness, treatment, and control of hypertension and diabetes we performed a multivariate logistic regression adjusting for age, body mass index, physical activity, alcohol use, smoking, marital status, monthly income, and educational level. To investigate control of hypertension or diabetes within each residential area, we performed a subgroup analysis in both urban and rural areas. RESULTS: The prevalence of hypertension is higher among men in urban areas than among those in rural areas (OR = 0.80; 95 % CI = 0.67-0.96, reference group = urban areas). However, the subgroups did not differ in terms of diabetes prevalence, awareness, treatment, and control. Regardless of both sex and residential area, participants in good control of their hypertension and diabetes were younger. Inequality in good control of hypertension was observed in men who lived in urban (≤Elementary school, OR 0.74, 95 % CI 0.60-0.92) and rural areas (≤Elementary school, OR 0.67, 95 % CI 0.46-0.99). Inequality in health status was found in women who resided in urban areas (≤Elementary school, OR 0.53, 95 % CI 0.37-0.75). Good control of diabetes also showed inequalities in health status for both men (≤Elementary school, OR 0.61, 95 % CI 0.40-0.94; Middle/High school, OR 0.69, 95 % CI 0.49-0.96) and women in urban areas (≤1 million won, OR 0.56, 95 % CI 0.33-0.93) (Reference group = '≥College' for education and '>3 million' Korean won for income). CONCLUSIONS: After correction for individual socioeconomic status, differences by residential area were not observed. However, when the participants with good disease control were divided by region, inequality was confirmed in urban residents. Therefore, differentiated health policies to resolve individual and regional health inequalities are necessary.


Assuntos
Diabetes Mellitus/epidemiologia , Disparidades em Assistência à Saúde , Hipertensão/epidemiologia , Adulto , Estudos Transversais , Diabetes Mellitus/prevenção & controle , Feminino , Inquéritos Epidemiológicos , Humanos , Hipertensão/prevenção & controle , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , República da Coreia/epidemiologia , População Rural , Classe Social
19.
J Korean Med Sci ; 29(8): 1061-8, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25120314

RESUMO

Influenza vaccination is important for cancer survivors, a population with impaired immunity. This study was designed to assess influenza vaccination patterns among Korean cancer survivors. In this cross-sectional analysis, data were obtained from standardized questionnaires from 943 cancer survivors and 41,233 non-cancer survivors who participated in the Fourth and Fifth Korea National Health and Nutrition Examination Surveys (2007-2011). We identified the adjusted influenza vaccination rates and assessed factors associated with influenza vaccination using multivariate logistic regression. Cancer survivors tended to have a higher adjusted influenza vaccination rate than the general population. The rates for influenza vaccination in specific cancer types such as stomach, hepatic, colon, and lung cancers were significantly higher than non-cancer survivors. Among all cancer survivors, those with chronic diseases, elderly subjects, and rural dwellers were more likely to receive influenza vaccination; those with cervical cancer were less likely to receive influenza vaccination. Cancer survivors were more likely to receive influenza vaccinations than non-cancer survivors, but this was not true for particular groups, especially younger cancer survivors. Cancer survivors represent a sharply growing population; therefore, immunization against influenza among cancer survivors should be concerned as their significant preventative healthcare services.


Assuntos
Vacinas contra Influenza/uso terapêutico , Influenza Humana/mortalidade , Influenza Humana/prevenção & controle , Vacinação em Massa/estatística & dados numéricos , Neoplasias/mortalidade , Sobreviventes/estatística & dados numéricos , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Suscetibilidade a Doenças/mortalidade , Escolaridade , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Fatores de Risco , Distribuição por Sexo , Classe Social , Taxa de Sobrevida
20.
Asian Pac J Cancer Prev ; 14(8): 4743-50, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24083737

RESUMO

BACKGROUND: Identifying and managing osteoporosis among cancer survivors is an important issue, yet little is known about the bone health of cancer survivors in Korea. This study was designed to measure the prevalence of osteoporosis and to assess related factors among Korean cancer survivors. MATERIALS AND METHODS: This study was designed as a cross-sectional analysis. Data were obtained from dual energy X-ray absorptiometry measurement of the lumbar vertebrae and femoral neck, and from standardized questionnaires among 556 cancer survivors and 17,623 non-cancer controls who participated in the Fourth and Fifth Korea National Health and Nutrition Examination Surveys (2008-2011). We calculated adjusted proportions of osteoporosis in non-cancer controls vs. cancer survivors, and we performed multivariate logistic regression analysis. RESULTS: The prevalence of osteoporosis among cancer survivors was significant higher than that of the non-cancer controls after adjusting for related factors. Furthermore, osteoporosis among cancer survivors was higher in elderly subjects (60-69 years : adjusted odds ratio (aOR) 3.04, 95% CI : 1.16-8.00, ≥70 years : aOR 6.60, 95% CI 2.20-19.79), in female cancer survivors (aOR: 7.03, 95% CI: 1.88-26.28), and in a group with lower monthly income (aOR: 3.38, 95% CI: 1.31-8.71). In male cancer survivors, underweight and lower calcium intake were risk factors. CONCLUSIONS: These data suggest that the osteoporosis among cancer survivors varies according to non-oncologic and oncologic factors. Effective screening should be applied, and a sufficient and comprehensive management should be matched to individual cancer survivors early after cancer treatment.


Assuntos
Inquéritos Nutricionais , Osteoporose/epidemiologia , Sobreviventes/estatística & dados numéricos , Absorciometria de Fóton , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/etiologia , Prevalência , Prognóstico , República da Coreia/epidemiologia , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA