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1.
J Exp Clin Cancer Res ; 41(1): 278, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114510

RESUMO

Epithelial-mesenchymal transition (EMT) is a fundamental process for embryonic development during which epithelial cells acquire mesenchymal characteristics, and the underlying mechanisms confer malignant features to carcinoma cells such as dissemination throughout the organism and resistance to anticancer treatments. During the past decades, an entire class of molecules, called non-coding RNA (ncRNA), has been characterized as a key regulator of almost every cellular process, including EMT. Like protein-coding genes, ncRNAs can be deregulated in cancer, acting as oncogenes or tumor suppressors. The various forms of ncRNAs, including microRNAs, PIWI-interacting RNAs, small nucleolar RNAs, transfer RNA-derived RNA fragments, long non-coding RNAs, and circular RNAs can orchestrate the complex regulatory networks of EMT at multiple levels. Understanding the molecular mechanism underlying ncRNAs in EMT can provide fundamental insights into cancer metastasis and may lead to novel therapeutic approaches. In this review, we describe recent advances in the understanding of ncRNAs in EMT and provide an overview of recent ncRNA applications in the clinic.


Assuntos
MicroRNAs , Neoplasias , Transição Epitelial-Mesenquimal/genética , Humanos , MicroRNAs/genética , Neoplasias/genética , Neoplasias/patologia , RNA Circular , RNA não Traduzido/genética
2.
Pol J Radiol ; 87: e215-e219, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35582606

RESUMO

Purpose: Diffusion-weighted imaging as a noninvasive functional modality plays a valuable role in the evaluation of prostate cancer. However, there is still no agreement on the number and range of b-values to be used. Therefore, the purpose of this study is to investigate the influence of b-value choice on the diagnostic performance of apparent diffusion coefficient (ADC) values for prostate cancer detection. Material and methods: Fifty-nine consecutive patients with abnormal digital rectal examination findings and raised serum prostate-specific antigen were chosen for magnetic resonance imaging of the prostate before systematic 12-core trans-rectal ultrasound-guided prostate biopsies. ADC values for each ROI were calculated from different b-value combinations (0-1600 s/mm2) by a monoexponential model. Mann-Whitney and the paired-sample t-test were used to compare the mean ADC values for malignant lesions and noncancerous tissues. ROC curve analysis was used to evaluate the diagnostic performance of ADC values in distinguishing prostate cancer from normal-tissue ROIs. Results: The differences between mean ADC values of malignant lesions and contralateral healthy tissues were significant for all the pairs of b-value combinations. The pair of b-values 50 and 1200 provided the highest AUC (0.94), with a sensitivity of 90.2%, a specificity of 92.6%, and an accuracy of 91.2% at an ADC cut-off of 1.23 × 10-3 mm2/s. Conclusions: Our study showed that using a 1.5-Tesla MRI scanner the diagnostic performance of ADC values estimated from the b-value pair 50 and 1200 s/mm2 was highest. However, some other b-value pairs provided statically comparable diagnostic performance.

3.
Microb Pathog ; 166: 105552, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35469998

RESUMO

Helicobacter pylori is a significant human pathogen of the stomach's epithelial lining. This type of carcinogen is associated with gastric cancer, indigestion, peptic ulcers, and upper digestive diseases. Therefore, successful treatment and eradication of this bacterium are required to reduce the prevalence of these diseases, especially in high-risk individuals. Moreover, some concerns exist regarding the extensive use of elimination therapy, such as anti-microbial resistance and rising H. pylori-associated diseases. Since there is still no effective vaccine, finding alternative therapies would appear to be a worthwhile pursuit. In this regard, curcumin exhibits anti-inflammatory, anti-carcinogenic, anti-oxidant properties and is widely used as a natural product-derived medicine or nutraceutical. Furthermore, curcumin has been reported to have anti-bacterial activity. Therefore, curcumin might be an effective herbal-based medicine for preventing, managing, or treating H. pylori infection. This review discusses the anti-inflammatory, anti-cancer, and anti-bacterial properties of curcumin as it pertains to gastric cancer and H. pylori-associated diseases.


Assuntos
Curcumina , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Curcumina/farmacologia , Curcumina/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/prevenção & controle
4.
Asian Pac J Cancer Prev ; 22(11): 3717-3722, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34837932

RESUMO

PURPOSE: CDK1A is one of the most important genes that have different key roles in cell lines. This gene has several transcript variants. Investigating of expression of each one actually can be so important because any one of them may have a separate unknown role in cancer cells so can be used to increase therapeutic efficacy. METHODS: A549, MDA-MB-231 and Hek-AD cell lines were used in this study. Firstly, three primers for variants of p21 gene were designed by Snapgene and BLAST software. Secondly, the variants expression was checked for each cell lines by RT-qPCR technique, separately. Then the variants that expressed in the cells were selected for more investigation. Finally 2 Gy irradiation was used to evaluate the effect of that on variants expression. RESULTS: The results show that for all cell lines, primer num1 and 3 expressed before any stimuli. After irradiation, for MDA-MB-231 and A549, the expression of primer num3 was decreased, while for Hek-AD no change was observed. The primer num1 expression after the irradiation was different for the cells, V1 expression was decreased in A549 by fold of 0.03 while expression of this for MDA-MB-231 cells was not changed after 2Gy irradiation. CONCLUSION: It is very necessary to pay attention to the function of each splice variant as well as the response to external stimuli. Understanding the role of each variant in a gene is critical and researchers can use that to improve radiotherapy as well.


Assuntos
Inibidor de Quinase Dependente de Ciclina p21/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Variação Genética/efeitos da radiação , Lesões por Radiação/genética , Radiação Ionizante , Linhagem Celular Tumoral , Primers do DNA/efeitos da radiação , Humanos
5.
Cancer Gene Ther ; 28(12): 1229-1255, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33432087

RESUMO

Gastrointestinal (GI) cancers comprise a heterogeneous group of complex disorders that affect different organs, including esophagus, stomach, gallbladder, liver, biliary tract, pancreas, small intestine, colon, rectum, and anus. Recently, an explosion in nucleic acid-based technologies has led to the discovery of long non-coding RNAs (lncRNAs) that have been found to possess unique regulatory functions. This class of RNAs is >200 nucleotides in length, and is characterized by their lack of protein coding. LncRNAs exert regulatory effects in GI cancer development by affecting different functions such as the proliferation and metastasis of cancer cells, apoptosis, glycolysis and angiogenesis. Over the past few decades, considerable evidence has revealed the important role of autophagy in both GI cancer progression and suppression. In addition, recent studies have confirmed a significant correlation between lncRNAs and the regulation of autophagy. In this review, we summarize how lncRNAs play a behind the scenes role in the pathogenesis of GI cancers through regulation of autophagy.


Assuntos
Autofagia/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Gastrointestinais/genética , RNA Longo não Codificante/metabolismo , Progressão da Doença , Humanos
6.
Adv Exp Med Biol ; 1328: 143-153, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34981476

RESUMO

Despite newer advances in cancer treatment, chemotherapy is still one of the most widely used treatment strategies in this field. However, this treatment strategy faces major challenges. Doxorubicin (Dox) is an effective chemotherapeutic agent used to treat various cancers. However, several studies have shown that the use of Dox in therapeutic concentrations is associated with serious side effects, such as cardiac toxicity. The use of natural products in combination with chemotherapeutic agents to reduce side effects is a novel approach, and several studies have shown promising results. In this regard, we examined the effect of Crocin on doxorubicin-induced cardiotoxicity in rat and H9c2 cell line. The in vitro model on H9C2 cells and the in vivo models on rats were treated with doxorubicin. Cell viability, DNA damage, and apoptosis were measured in H9C2 cell line in the presence and absence of Crocin. Oxidative stress and various inflammatory parameters, as well as cardiac function tests, also were assessed in doxorubicin-induced cardiotoxicity animal model in the presence and absence of Crocin. Our results showed that Crocin can significantly decrease apoptosis in H9C2 cell line through a reduction in ROS production and DNA damages. Moreover, evaluation of the effect of Crocin on doxorubicin-induced cardiotoxicity animal model showed that Crocin also can significantly reduce oxidative stress and inflammatory parameters in the serum of the animals. Assessment of cardiac function revealed that Crocin has a significant protective effect against doxorubicin-induced cardiotoxicity in the animal model. Our data indicate that Crocin significantly attenuated doxorubicin-induced cardiotoxicity. Hence, Crocin could be potentially used as an adjuvant treatment in combination with Dox to reduce cardiotoxicity.


Assuntos
Cardiotoxicidade , Doxorrubicina , Animais , Apoptose , Cardiotoxicidade/prevenção & controle , Carotenoides/metabolismo , Carotenoides/farmacologia , Doxorrubicina/toxicidade , Miócitos Cardíacos/metabolismo , Estresse Oxidativo , Ratos
7.
Curr Med Chem ; 28(8): 1549-1564, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32410550

RESUMO

Dendritic cells (DCs) are the most powerful antigen-presenting cells which link the innate and adaptive immune responses. Depending on the context, DCs initiate the immune responses or contribute to immune tolerance. Any disturbance in their phenotypes and functions may initiate inflammatory or autoimmune diseases. Hence, dysregulated DCs are the most attractive pharmacological target for the development of new therapies aiming at reducing their immunogenicity and at enhancing their tolerogenicity. Curcumin is the polyphenolic phytochemical component of the spice turmeric with a wide range of pharmacological activities. It acts in several ways as a modulator of DCs and converts them into tolerogenic DCs. Tolerogenic DCs possess anti-inflammatory and immunomodulatory activities that regulate the immune responses in health and disease. Curcumin by blocking maturation markers, cytokines and chemokines expression, and disrupting the antigen-presenting machinery of DCs render them non- or hypo-responsive to immunostimulants. It also reduces the expression of co-stimulatory and adhesion molecules on DCs and prevents them from both migration and antigen presentation but enhances their endocytosis capacity. Hence, curcumin causes DCs-inducing regulatory T cells and dampens CD4+ T helper 1 (Th1), Th2, and Th17 polarization. Inhibition of transcription factors such as NF-κB, AP-1, MAPKs (p38, JNK, ERK) and other intracellular signaling molecules such as JAK/STAT/SOCS provide a plausible explanation for most of these observations. In this review, we summarize the potential effects of curcumin on the phenotypes and functions of DCs as the key players in orchestration, stimulation, and modulation of the immune responses.


Assuntos
Curcumina , Curcumina/farmacologia , Células Dendríticas , Tolerância Imunológica , Fenótipo , Compostos Fitoquímicos
8.
Life Sci ; 257: 118087, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32702442

RESUMO

AIMS: Recent studies suggest that direct exposure of cells to fractionated radiotherapy might induce radioresistance. However, the effects of fractionated radiotherapy on the non-irradiated bystander cells remain unclear. We hypothesized that fractionated radiotherapy could enhance radioresistance and proliferation of bystander cells. MAIN METHODS: Human tumor cell lines, including A549 and HT29 were irradiated (2 Gy per day). The irradiated cells (either A549 or HT29) were co-cultured with non-irradiated cells of the same line using transwell co-culture system. Tumor cell proliferation, radioresistance and apoptosis were measured using MTT assay, clonogenic survival assay and Annexin-V in bystander cells, respectively. In addition, activation of Chk1 (Ser 317), Chk2 (Thr 68) and Akt (Ser473) were measured via western blot. KEY FINDINGS: Irradiated HT29 cells induced conventional bystander effects detected as modulation of clonogenic survival parameters (decreased area under curve, D10 and ED50 and increased α) and proliferation in recipient neighbors. While, irradiated A549 cells significantly enhanced the radioresistance and proliferation of bystander cells. These changes were accompanied with enhanced activation of Chk1, Chk2 and Akt in non-irradiated bystander A549 cells. Moreover, both bystander effects (damaging and protective) were mediated through secreted factors. SIGNIFICANCE: These findings suggest that fractionated radiotherapy could promote proliferation and radioresistance of bystander cells probably through survival and proliferation pathways.


Assuntos
Apoptose/efeitos da radiação , Efeito Espectador/efeitos da radiação , Proliferação de Células/efeitos da radiação , Tolerância a Radiação/efeitos da radiação , Células A549 , Sobrevivência Celular/efeitos da radiação , Técnicas de Cocultura , Células HT29 , Humanos
9.
Adv Healthc Mater ; 9(7): e1901695, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32142225

RESUMO

Despite all of the efforts in the field of cancer therapy, the heterogeneous properties of tumor cells induce an insufficient therapeutic outcome when treated with conventional monotherapies, necessitating a shift in cancer treatment from monotherapy to combination therapy for complete cancer treatment. Multifunctional bismuth (Bi)-based nanomaterials (NMs) with therapeutic functions hold great promise for the fields of cancer diagnosis and therapy based on their low toxicity, X-ray sensitive capabilities, high atomic number, near-infrared driven semiconductor properties, and low cost. Herein, a comprehensive review of recent advances in various medicinal aspects of Bi-based NMs is presented including: evaluation of in-tumor site accumulation, tumor targeting, and therapeutic performance, as well as the characteristics, benefits, and shortcomings of Bi-based NM-mediated major monotherapies. In addition, the cooperative enhancement mechanisms between two or more of these monotherapies are described in detail to address common challenges in cancer therapy, such as multidrug resistance, hypoxia, and metastasis. Finally, this review opens new insights into the design of multimodal synergistic therapies for potential future clinical applications of Bi-based NMs.


Assuntos
Nanoestruturas , Neoplasias , Bismuto , Terapia Combinada , Humanos , Nanoestruturas/uso terapêutico , Neoplasias/tratamento farmacológico , Fototerapia
10.
Molecules ; 25(3)2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32041140

RESUMO

Todays, nano-pharmaceutics is emerging as an important field of science to develop and improve efficacy of different drugs. Although nutraceuticals are currently being utilized in the prevention and treatment of various chronic diseases such as cancers, a number of them have displayed issues associated with their solubility, bioavailability, and bio-degradability. In the present review, we focus on curcumin, an important and widely used polyphenol, with diverse pharmacological activities such as anti-inflammatory, anti-carcinogenic, anti-viral, etc. Notwithstanding, it also exhibits poor solubility and bioavailability that may compromise its clinical application to a great extent. Therefore, the manipulation and encapsulation of curcumin into a nanocarrier formulation can overcome these major drawbacks and potentially may lead to a far superior therapeutic efficacy. Among different types of nanocarriers, biological and biopolymer carriers have attracted a significant attention due to their pleiotropic features. Thus, in the present review, the potential protective and therapeutic applications of curcumin, as well as different types of bio-nanocarriers, which can be used to deliver curcumin effectively to the different target sites will be discussed.


Assuntos
Curcumina/administração & dosagem , Curcumina/química , Nanopartículas/química , Animais , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Polifenóis/química
11.
Cancer Res ; 80(2): 139-150, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31767626

RESUMO

The ataxia-telangiectasia mutated (ATM) protein kinase is widely known for its function as a chief mobilizer of the DNA damage response (DDR) upon DNA double-strand breaks. ATM orchestrates the DDR by modulating the expression of various miRNAs through several mechanisms. On the other hand, a set of miRNAs contribute to tight regulation of ATM by directly targeting the 3'-untranslated region of ATM mRNA. This review addresses the therapeutic application and molecular mechanisms that underlie the intricate interactions between miRNAs and ATM. It also describes therapeutic delivery of miRNAs in different environments such as hypoxic tumor microenvironments.


Assuntos
Antineoplásicos/farmacologia , Proteínas Mutadas de Ataxia Telangiectasia/genética , Quimiorradioterapia/métodos , MicroRNAs/metabolismo , Neoplasias/terapia , Tolerância a Radiação/genética , Regiões 3' não Traduzidas/genética , Antagomirs/farmacologia , Antagomirs/uso terapêutico , Antineoplásicos/uso terapêutico , Hipóxia Celular/genética , Hipóxia Celular/efeitos da radiação , Terapia Combinada/métodos , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/efeitos da radiação , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Neoplasias/genética , Tolerância a Radiação/efeitos dos fármacos , Transdução de Sinais/genética , Transdução de Sinais/efeitos da radiação , Microambiente Tumoral/genética , Microambiente Tumoral/efeitos da radiação
12.
Int J Biol Macromol ; 145: 282-300, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31870872

RESUMO

Paclitaxel (PTX) and docetaxel (DTX) are key members of taxanes with high anti-tumor activity against various cancer cells. These chemotherapeutic agents suffer from a number of drawbacks and it seems that low solubility in water is the most important one. Although much effort has been made in improving the bioavailability of PTX and DTX, the low bioavailability and minimal accumulation at tumor sites are still the challenges faced in PTX and DTX therapy. As a consequence, bio-based nanoparticles (NPs) have attracted much attention due to unique properties. Among them, chitosan (CS) is of interest due to its great biocompatibility. CS is a positively charged polysaccharide with the capability of interaction with negatively charged biomolecules. Besides, it can be processed into the sheet, micro/nano-particles, scaffold, and is dissolvable in mildly acidic pH similar to the pH of the tumor microenvironment. Keeping in mind the different applications of CS in the preparation of nanocarriers for delivery of PTX and DTX, in the present review, we demonstrate that how CS functionalized-nanocarriers and CS modification can be beneficial in enhancing the bioavailability of PTX and DTX, targeted delivery at tumor site, image-guided delivery and co-delivery with other anti-tumor drugs or genes.


Assuntos
Antineoplásicos Fitogênicos/farmacocinética , Quitosana/administração & dosagem , Docetaxel/farmacocinética , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Paclitaxel/farmacocinética , Animais , Antineoplásicos Fitogênicos/farmacologia , Disponibilidade Biológica , Quitosana/química , Quitosana/metabolismo , Docetaxel/farmacologia , Portadores de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Terapia de Alvo Molecular/métodos , Nanopartículas/química , Neoplasias/metabolismo , Neoplasias/patologia , Oxirredução , Paclitaxel/farmacologia , Solubilidade , Eletricidade Estática , Nanomedicina Teranóstica/métodos
13.
Mutat Res ; 816-818: 111679, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31715522

RESUMO

Glioblastoma (GBM) is the most lethal type of primary brain tumor. Currently, even with optimal and multimodal cancer therapies, the survival rate of GBM patients remains poor. One reason for inadequate response of GBM tumors to radiotherapy is radioresistance (RR). Thus, there is a critical need for new insights about GBM treatment to increase the chance of treatment. microRNAs (miRNAs) are important regulatory molecules that can effectively control GBM radiosensitivity (RS) by affecting radiation-related signal transduction pathways such as apoptosis, proliferation, DNA repair and cell cycle regulation. miRNAs provide new clinical perspectives for developing effective GBM treatments. A growing body of literature has demonstrated that GBM RS can be modified by modulating the expression of miRNAs such as miR-7, miR-10b, miR-124, miR-128, miR-320, miR-21, miR-203, and miR-153. This paper highlights the miRNAs and the underlying molecular mechanisms that are involved in the RS of GBM. Besides highlighting the role of miRNAs in different signaling pathways, we explain the mechanisms that affect RS of GBM for modulating radiation response at the clinical level.


Assuntos
Neoplasias Encefálicas/genética , Glioblastoma/genética , MicroRNAs/genética , Tolerância a Radiação/genética , Transdução de Sinais/genética , Animais , Neoplasias Encefálicas/radioterapia , Proliferação de Células/genética , Proliferação de Células/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Glioblastoma/radioterapia , Humanos , Tolerância a Radiação/efeitos da radiação , Transdução de Sinais/efeitos da radiação
14.
Biomolecules ; 9(10)2019 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31557936

RESUMO

Autophagy modulation is considered to be a promising programmed cell death mechanism to prevent and cure a great number of disorders and diseases. The crucial step in designing an effective therapeutic approach is to understand the correct and accurate causes of diseases and to understand whether autophagy plays a cytoprotective or cytotoxic/cytostatic role in the progression and prevention of disease. This knowledge will help scientists find approaches to manipulate tumor and pathologic cells in order to enhance cellular sensitivity to therapeutics and treat them. Although some conventional therapeutics suffer from poor solubility, bioavailability and controlled release mechanisms, it appears that novel nanoplatforms overcome these obstacles and have led to the design of a theranostic-controlled drug release system with high solubility and active targeting and stimuli-responsive potentials. In this review, we discuss autophagy modulators-related signaling pathways and some of the drug delivery strategies that have been applied to the field of therapeutic application of autophagy modulators. Moreover, we describe how therapeutics will target various steps of the autophagic machinery. Furthermore, nano drug delivery platforms for autophagy targeting and co-delivery of autophagy modulators with chemotherapeutics/siRNA, are also discussed.


Assuntos
Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Animais , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Transdução de Sinais/efeitos dos fármacos
15.
Infect Genet Evol ; 76: 104003, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31425784

RESUMO

Apoptosis is a universal cellular defense mechanism against senescent, damaged, genetically mutated, or virally-infected cells. It also is critical for the maintenance of liver health. Fas and FasL system act as a major death pathway that triggers apoptosis cascade in the liver. In this systematic review and meta-analysis, we aimed to investigate the relationship between four major polymorphisms of Fas and FasL genes with susceptibility to or clearance of HBV infection. All the eligible studies were extracted from PubMed and Scopus with no date and language restriction. ORs with 95% CIs were used to evaluate the strength of the association based on the following genetic models: (1) the allelic, (2) the homozygote, (3) the dominant, and (4) the recessive models. Totally 7 related articles were included in this meta-analysis; 5 studies of 7 related articles investigated FasL -844C/T (rs763110) polymorphism, 4 studies investigated FasL IVS2nt-124, 6 studies investigated Fas -670 A/G (rs1800682), and 4 studies investigated Fas -1377 A/G (rs2234767) polymorphism. This meta-analysis showed that there is no statistically significant association between the risk or clearance of HBV infection and four studied Fas and FasL polymorphisms in their allelic comparison or genetic models. Fas -670, Fas -1377, FasL -124, and FasL -844 polymorphisms did not show any significant association with the clearance or risk of HBV infection. Therefore, it seems that susceptibility to HBV infection or clearance of it is not affected by Fas and FasL genetic polymorphisms. But, to reach a definitive conclusion, further studies with a larger sample size of different ethnicity are still needed.


Assuntos
Proteína Ligante Fas/genética , Hepatite B/genética , Polimorfismo de Nucleotídeo Único , Receptor fas/genética , Predisposição Genética para Doença , Hepatite B/virologia , Vírus da Hepatite B/isolamento & purificação , Homozigoto , Humanos , Razão de Chances , Regiões Promotoras Genéticas
16.
Pathol Res Pract ; 215(10): 152556, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31358480

RESUMO

Curcumin is a natural non-toxic phenol which is isolated from Curcumin longa L. Mounting evidence has revealed the anticancer properties of curcumin in various tumors, but the underlying molecular mechanisms of this suppression in cervical cancer is still remained unclear. Here we assessed the antitumor effects of curcumin compared with 5-Fluorouracil in Hella cells in spheroids models and monolayer cell cultures. The anti-proliferative effects of curcumin and 5-Fluorouracil were as examined in spheroid and monolayer models. The expression levels of Wnt/ß-catenin and NF-kB pathways as well as the influence of the cell cycle were evaluated. Curcumin inhibited cell growth in Hella cells through the regulation of NF-kB and Wnt pathways. Also, cells developed a G2/M cell cycle arrest followed by sub-G1 apoptosis with 5-Fluorouracil and curcumin. It was also shown that curcumin either considerably affects the Wnt/ß-catenin and NF-kB pathways. We showed that curcumin inhibits invasion and proliferation of cervical cancer cells via impairment of NF-kB and Wnt/ß-catenin pathways, proposing further studies on the potential impacts of this compound on cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Curcumina/farmacologia , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , beta Catenina/metabolismo , Apoptose/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Feminino , Fluoruracila/farmacologia , Células HeLa , Humanos , Neoplasias do Colo do Útero/metabolismo , Proteínas Wnt/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos
17.
J Cell Biochem ; 120(5): 8601-8610, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30485518

RESUMO

Despite the fact that radiotherapy is a main therapeutic modality in cancer treatment, recent evidence suggests that fractionated radiotherapy (FR) might confer radioresistance through epithelial-mesenchymal transition (EMT). Nevertheless, the effects of FR on EMT phenotype and the potential link between EMT induction and radioresistance development yet to be clarified. The aim of this study was to assess whether FR could promote EMT, and to elucidate if induction of EMT contributes to the acquisition of radioresistance. To this end, two human cancer cell lines (A549 and HT-29) were irradiated (2 Gy/day) and analyzed using wound healing, transwell migration and invasion assays, real-time polymerase chain reaction (for E-cadherin, N-cadherin, Vimentin, CD44, CD133, Snail, and Twist), clonogenic assay, Annexin V/PI, and 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Irradiation of A549 (for 5 or 10 consecutive days) resulted in morphological changes including elongation of cytoplasm and nuclei and pleomorphic nuclei. Also, irradiation-enhanced migratory and invasive potential of A549. These phenotypic changes were in agreement with decreased expression of the epithelial marker (E-cadherin), enhanced expression of mesenchymal markers (N-cadherin, Vimentin, Snail, and Twist) and increased stemness factors (CD44 and CD133). Moreover, induction of EMT phenotype was accompanied with enhanced radioresistance and proliferation of irradiated A549. However, FR (for 5 consecutive days) did not increase HT-29 motility. Furthermore, molecular alterations did not resemble EMT phenotype (downregulation of E-cadherin, Vimentin, ALDH, CD44, CD133, and Snail). Eventually, FR led to enhanced radiosensitivity and decreased proliferation of HT-29. Altogether, our findings suggest that FR might induce EMT and confer radioresistance in a cell context-dependent manner.

18.
Rev Med Virol ; 29(1): e2016, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30378208

RESUMO

Enteroviruses are members of Pichornaviridae family consisting of human enterovirus group A, B, C, and D as well as nonhuman enteroviruses. Hand, foot, and mouth disease (HFMD) is a serious disease which is usually seen in the Asia-Pacific region in children. Enterovirus 71 and coxsackievirus A16 are two important viruses responsible for HFMD which are members of group A enterovirus. IFN α and ß are two cytokines, which have a major activity in the innate immune system against viral infections. Most of the viruses have some weapons against these cytokines. EV71 has two main proteases called 2A and 3C, which are important for polyprotein processing and virus maturation. Several studies have indicated that they have a significant effect on different cellular pathways such as interferon production and signaling pathway. The aim of this study was to investigate the latest findings about the interaction of 2A and 3C protease of EV71 and IFN production/signaling pathway and their inhibitory effects on this pathway.


Assuntos
Cisteína Endopeptidases/metabolismo , Enterovirus Humano A/patogenicidade , Doença de Mão, Pé e Boca/virologia , Evasão da Resposta Imune , Fatores Imunológicos/antagonistas & inibidores , Interferon Tipo I/antagonistas & inibidores , Proteínas Virais/metabolismo , Proteases Virais 3C , Ásia/epidemiologia , Enterovirus Humano A/enzimologia , Doença de Mão, Pé e Boca/epidemiologia , Humanos
19.
Tumour Biol ; 37(6): 7007-19, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26880587

RESUMO

Twist1 (also known as Twist) is a transcription factor that belongs to the family of basic helix-loop-helix (bHLH) proteins. It functions as a negative regulator of epithelial gene expression and a positive regulator of mesenchymal gene expression, thereby leading to induction of the epithelial mesenchymal transition (EMT), a process in which epithelial cells acquire the motile and migratory characteristics of mesenchymal cells. In addition to regulating the expression of protein-coding genes, Twist1 regulates the expression of microRNAs (miRNAs), adding a regulatory layer to EMT induction. Interestingly, the mRNA of Twist1 represents a downstream target of miRNAs, indicating an intricate network between miRNAs and Twist1. This network was shown to play multiple roles in cancer cell migration, invasion, and metastasis. The network can induce angiogenesis, protect cells from oncogene-induced apoptosis and senescence, enhance cancer cell resistance to conventional therapies, and increase cancer stem cell (CSC) populations. Recently, miRNAs have attracted considerable attention as potential promising tools in cancer therapies. Thus, this systematic review was conducted to clarify the reciprocal link between Twist1 and miRNAs in order to provide potential candidate miRNAs for diagnostic and therapeutic approaches in cancer treatment.


Assuntos
Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias/patologia , Proteínas Nucleares/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , Animais , Humanos , Invasividade Neoplásica , Neoplasias/genética , Neoplasias/metabolismo , Proteínas Nucleares/genética , Proteína 1 Relacionada a Twist/genética
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