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1.
Cancer Med ; 10(21): 7475-7491, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34626092

RESUMO

BACKGROUND: We discovered that pure positive electrostatic charges (PECs) have an intrinsic suppressive effect on the proliferation and metabolism of invasive cancer cells (cell lines and animal models) without affecting normal tissues. METHODS: We interacted normal and cancer cell lines and animal tumors with PECs by connecting a charged patch to cancer cells and animal tumors. many biochemical, molecular and radiological assays were carried out on PEC treated and control samples. RESULTS: Correlative interactions between electrostatic charges and cancer cells contain critical unknown factors that influence cancer diagnosis and treatment. Different types of cell analyses prove PEC-based apoptosis induction in malignant cell lines. Flowcytometry and viability assay depict selective destructive effects of PEC on malignant breast cancer cells. Additionally, strong patterns of pyknotic apoptosis, as well as downregulation of proliferative-associated proteins (Ki67, CD31, and HIF-1α), were observed in histopathological and immunohistochemical patterns of treated mouse malignant tumors, respectively. Quantitative real-time polymerase chain reaction results demonstrate up/down-regulated apoptotic/proliferative transcriptomes (P21, P27, P53/CD34, integrin α5, vascular endothelial growth factor, and vascular endothelial growth factor receptor) in treated animal tumors. Expression of propidium iodide in confocal microscopy images of treated malignant tissues was another indication of the destructive effects of PECs on such cells. Significant tumor size reduction and prognosis improvement were seen in over 95% of treated mouse models with no adverse effects on normal tissues. CONCLUSION: We discovered that pure positive electrostatic charges (PECs) have an intrinsic suppressive effect on the proliferation and metabolism of invasive cancer cells (cell lines and animal models) without affecting normal tissues. The findings were statistically and observationally significant when compared to radio/chemotherapy-treated mouse models. As a result, this nonionizing radiation may be used as a practical complementary approach with no discernible side effects after passing future human model studies.


Assuntos
Proliferação de Células , Metástase Neoplásica/patologia , Metástase Neoplásica/terapia , Eletricidade Estática , Animais , Apoptose , Linhagem Celular Tumoral , Modelos Animais de Doenças , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Neoplasias Mamárias Experimentais/radioterapia , Necrose , Gradação de Tumores
2.
Biomater Sci ; 9(18): 6214-6226, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34357368

RESUMO

A new biosensor for detecting cancer involved sentinel lymph nodes has been developed via the electrochemical tracing of fatty acid oxidation as a distinct metabolism of malignant cells invading lymph nodes (LNs). The system included integrated platinum needle electrodes that were decorated by carbon nanotubes (as hydrophobic agents) through laser-assisted nanowelding. It was applied to record the dielectric spectroscopy data from LN contents via electrochemical impedance spectroscopy. The system was applied for dielectric spectroscopy of LN contents via electrochemical impedance approach. The reduced lipid content of involved LNs, due to fat metabolism by invasive cancer cells, would decrease the charge transfer resistance (RCT) of the LNs with respect to their normal counterparts. Multi-walled carbon nanotubes (MWCNTs) with superhydrophobic properties were used to enhance the interaction of Pt needle electrodes with the lipidic contents of lymph nodes. This is the first time that a fatty acid metabolism-based sensing approach has been introduced to detect involved LNs. Moreover, a novel electrode decorating method was applied to enhance the interfacial contact of this lipid detection probe (LDP). In order to avoid doubt about the biocompatibility of ferrocyanide, [Fe(CN)6]4- and ferricyanide, [Fe(CN)6]3-, a biocompatible injectable metal ion-based material, ferric carboxymaltose, was selected and applied as the electrolyte for the first time. Rabbit LNs were tested using the LDP in the animal model phase. The system was then used in vitro on 122 dissected human LNs in the operating room. Calibration of the results showed an excellent match between the dielectric response of the LDP (known as charge transfer resistance (RCT)) and the final pathological diagnoses. The LDP may have a promising future after further clinical investigations for intra-operative distinction between normal and cancerous LNs.


Assuntos
Técnicas Biossensoriais , Nanotubos de Carbono , Neoplasias , Animais , Técnicas Eletroquímicas , Eletrodos , Lasers , Linfonodos , Agulhas , Platina , Coelhos
3.
Biosens Bioelectron ; 142: 111566, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31404879

RESUMO

Cell free diagnosis of cancer is one of the crucial fields in new generation of medical technology. In this regard, cancer detection based on coastal fluids secreted from the tissues (named as secretome) has attracted a lot of attention. Lipids are important macromolecules could be found with much higher concentrations in secretome of cancer tissues vs. normal ones. On the other hand, lipids are the main dielectric components of the secretome with respect to proteins and ions. Here for the first time we introduced an electrochemical lipidomics based on electrical impedance spectroscopy (EIS) of the secretomes to detect the cancerous samples due to the lipidic content of their secretions. The EIS sensor was fabricated by multiwall carbon nanotube (MWCNT) arrays as conductive and super hydrophobic materials to have great interactive surface with the lipidic content of the solution. Results of the tests on the secretions of more than 100 human biopsied breast tissues showed the promising match between the charge transfer resistance (RCT) of samples' secretions and pathological states of the tissues with meaningful boundary (up to 8 kΩ for normal and more than 13 kΩ for cancer samples). Mass spectroscopic analyses confirmed the higher content of lipids in cancer secretomes. Electrical lipidomics of the secretome shed new lights in cell free cancer diagnosis and could be applied as a complementary clinical approach in all of biopsy based diagnoses in future.


Assuntos
Espectroscopia Dielétrica/instrumentação , Metabolismo dos Lipídeos , Lipidômica/instrumentação , Nanotubos de Carbono/química , Neoplasias/metabolismo , Microambiente Tumoral , Linhagem Celular Tumoral , Desenho de Equipamento , Humanos , Nanotubos de Carbono/ultraestrutura , Neoplasias/diagnóstico
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