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1.
Med Oncol ; 40(1): 52, 2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36527530

RESUMO

Low-dose chemotherapy in advanced stages of cancer does not give a positive response in treatment. The use of high-dose antineoplastic drugs creates significant side effects. The limiting situation in treatment creates a need for new generation drugs with less side effects and new treatment methods that will enable low-dose drug use. Electroporation (EP), a phenomenon, is a technique in which the membrane permeability is increased by the establishment of hydrophilic pores in the cell membrane with short and high-voltage electrical pulses. In the present investigation study, we aimed to inspect the effects of EP plus bleomycin, cisplatin, and calcium administration (CaEP) on cell viability, apoptotic activity, gene expression p53, Bax/Bcl-2 rate mitochondrial membrane potential (ΔΨm), and cell cycle in HeLa cervical cancer cell line. The permeabilization of the membrane was evaluated in flow cytometry with the PI method, and cell viability was measured in an ELISA reader with the WST-8 method. For bleomycin and cisplatin doses applied to HeLa cells, the concentration values (IC50) that inhibited 50% of the cells were found to be 214.11 ± 4.7 µM and 35.16 ± 3.3 µM, respectively. The IC50 values of the groups administered together with EP were calculated as 0.44 ± 0.3 µM for bleomycin and 20.55 ± 4.3 µM for cisplatin. There was no change in cell viability in calcium alone application, but a statistically notable reduction in cell vitality was observed in CaEP application. An increase in ΔΨm was found in bleomycin and CaEP exposure with EP. It was determined that EP exposure caused G0/G1 arrest in the cell cycle at all electric field intensities. It was determined that EP application in HeLa cells increased bleomycin cytotoxicity 487 times and cisplatin cytotoxicity 1.71 times, and CaEP could be an alternative treatment method.


Assuntos
Antineoplásicos , Eletroquimioterapia , Neoplasias do Colo do Útero , Feminino , Humanos , Eletroquimioterapia/métodos , Cisplatino/farmacologia , Bleomicina/farmacologia , Cálcio , Neoplasias do Colo do Útero/tratamento farmacológico , Células HeLa , Antineoplásicos/farmacologia , Eletroporação/métodos
2.
Med Oncol ; 40(1): 60, 2022 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-36565382

RESUMO

In this study, we have investigated the chemotherapeutic potential of titanium dioxide (TiO2) nanoparticles on skin and breast cancer cells. The cells have treated with a 75 µg/ml concentration of titanium dioxide because it is a recommended dose with proven effectiveness in vitro studies and then the cells were exposed to UV-A radiation. The combined effects of titanium dioxide and UV-A radiation on cell viability, cell cycle, plasma membrane, mitochondrial membrane potentials and apoptotic activity of the cells were investigated. The viability of SK-MEL 30 cells was measured by MTT assay and apoptotic activity of cells was determined by Annexin-V FITC/PI staining. As a result of the research, an increase was observed in the viability of cells treated with 75 µg/ml titanium dioxide concentration, while a significant decrease in cell viability was observed for both cell types when UV-A radiation and TiO2 were applied together. The results also showed that the percentage of apoptotic cells increased as a result of UV + TiO2 exposure. Accordingly, it can be said that TiO2 nanoparticles may research as potential chemotherapeutic agents for skin and breast cancers, especially in the presence of UV radiation.


Assuntos
Nanopartículas , Neoplasias Cutâneas , Humanos , Raios Ultravioleta , Titânio/farmacologia
3.
Toxicol Appl Pharmacol ; 433: 115780, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34756876

RESUMO

Ischemia/Reperfusion (I/R) injury is clinically important in many surgical practice including kidney transplantation. It is known that mitochondria have a key role in the intracellular and extracellular signaling pathways of ischemia and reperfusion injury. In this respect, we pointed to explore the probable effects of isolated mitochondria transplantation from MSCs (mesenchymal stem cells), to alleviate ischemia/reperfusion-induced renal injury. Experiments were held on the 48 male Sprague Dawley rats. Groups were divided as Control (C1), I/R-Control (C2), Vehicle-1 (V1), Vehicle-2 (V2), Transplantation-1 (T1) and Transplantation-2 (T2) group. Unilaterally nephrectomy was performed in all groups. In the groups except the control, the left kidneys ischemized for 45 min and then reperfusion was carried out. According to the study groups, isolated mitochondria or vehicle infused into the renal cortex and rats were monitored for 48 h. Following that mentioned procedure, animals were sacrificed and biological samples were taken for physiological, histological and biochemical examinations. The results of present study show that mitochondrial transplantation promoted proliferation and regeneration of tubular cells after renal injury. Moreover, mitochondrial transplantation reduced mitochondrial dynamics-DRP-1 fission protein of tubular cells and reversed renal deficits. Mitochondrial transplantation diminished apoptotic markers including TUNEL and Caspase-3 levels in injured renal cells. Our results provide a direct link between mitochondria dysfunction and ischemia/reperfusion-induced renal injury and suggest a therapeutic effect of transplanting isolated mitochondria obtained from MSCs against renal injury.


Assuntos
Proliferação de Células , Nefropatias/prevenção & controle , Rim/patologia , Transplante de Células-Tronco Mesenquimais , Mitocôndrias/transplante , Dinâmica Mitocondrial , Regeneração , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose , Caspase 3/metabolismo , Células Cultivadas , Dinaminas/metabolismo , GTP Fosfo-Hidrolases , Rim/metabolismo , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Proteínas Mitocondriais , Estresse Oxidativo , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
4.
Life Sci ; 279: 119669, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34081988

RESUMO

AIMS: Acetaminophen (APAP) toxicity is one of the leading causes of acute liver injury-related death and liver failure worldwide. In many studies, mitochondrial dysfunction has been identified as an important cause of damage in APAP toxicity. Therefore, our study aimed to investigate the possible effects of mitochondrial transplantation on liver damage due to APAP toxicity. MAIN METHODS: APAP toxicity model was implemented by administering a toxic dose of APAP. To demonstrate the efficiency of mitochondria transplantation, it was compared with N-acetylcysteine (NAC) application, which is now clinically accepted. Mitochondrial transplantation was carried out by delivering mitochondria to the liver via the portal circulation, which was injected into the spleen. In our study, the rats were randomly divided into 6 groups as Sham, APAP, Control 1, APAP+mito, Control 2, and APAP+NAC. In the end of the experiment, histological and biochemical analysis were performed and the biodistribution of the transplanted mitochondria to target cells were also shown. KEY FINDINGS: Successful mitochondrial transplantation was confirmed and mitochondrial transplantation improved the liver histological structure to a similar level with healthy rats. Moreover, plasma ALT levels, apoptotic cells, and total oxidant levels were decreased. It was also observed that NAC treatment increased GSH levels to the highest level among the groups. However, mitochondrial transplantation was more effective than NAC application in terms of histological and functional improvement. SIGNIFICANCE: It has been evaluated that mitochondrial transplantation can be used as an important alternative or adjunctive treatment method in liver damage caused by toxic dose APAP intake.


Assuntos
Acetaminofen/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/terapia , Glutationa/metabolismo , Peroxidação de Lipídeos , Mitocôndrias/transplante , Analgésicos não Narcóticos/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Masculino , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley
5.
Balkan Med J ; 33(2): 173-80, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27403386

RESUMO

BACKGROUND: Historically, sexual assault is a common issue in Turkey. As doctors are one of the steps to help sexually assaulted women, medical students should have basic knowledge of and sensitivity regarding this subject. Another common women's public health issue is induced abortion. In countries where access to abortion is restricted, there is a tendency towards unhealthy abortion. AIMS: The aims of this study are: (1) to determine the attitudes and opinions of Marmara University Medical Faculty students about sexual assault against women and induced abortion and (2) to propose an educational program for medical students about sexual assault and abortion. STUDY DESIGN: Cross-sectional study. METHODS: The questionnaires were self-administered and the data were analyzed using SPSS v.15.0. First, the descriptive statistics were analyzed, followed by Chi-square for contingency tests assessing differences in attitudes toward sexual assault and induced abortion by factors such as gender and educational term. Differences were considered statistically significant at p<0.05. RESULTS: About 89.6% of the participants (n=266) reported that they had never been sexually assaulted and about 11.5% of the women (n=19) had been sexually assaulted. There was no significant relationship between previous sexual assault and gender (p>0.05). Although there was no significant difference regarding the extent of punishment by victim's status as a virgin, 21.3% (n=63) agreed that punishment should be more severe when the victim was a virgin. About 40.7% (n=120) agreed that the legal period of abortion in Turkey (10 weeks) should be longer. The majority (86.1%, n=255) agreed that legally prohibiting abortions causes an increase in unhealthy abortions. CONCLUSION: An educational program on these issues should be developed for medical students.

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