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Research on different types of ionizing radiation's effects has been ongoing for years, revealing its efficacy in damaging cancer cells. Solid tumors comprise diverse cell types, each being able to respond differently to radiation. This study evaluated the radiobiological response of established (MDA-MB-231 (Triple negative breast cancer, TNBC), MCF-7 (Luminal A)) and patient-derived malignant cell lines, cancer-associated fibroblasts, and skin fibroblasts following proton IRR. All cell line types were irradiated with the proton dose of 2, 4, and 6 Gy. The radiobiological response was assessed using clonogenic assay, γH2AX, and p53 staining. It was noticeable that breast cancer lines of different molecular subtypes displayed no significant variations in their response to proton IRR. In terms of cancer-associated fibroblasts extracted from the tumor tissue, the line derived from a TNBC subtype tumor demonstrated higher resistance to ionizing radiation compared to lines isolated from luminal A tumors. Fibroblasts extracted from patients' skin responded identically to all doses of proton radiation. This study emphasizes that tumor response is not exclusively determined by the elimination of breast cancer cells, but also takes into account tumor microenvironmental variables and skin reactions.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Linhagem Celular Tumoral , Terapia com Prótons , Células MCF-7 , Prótons , Fibroblastos/efeitos da radiação , Fibroblastos/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/radioterapia , Histonas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Fibroblastos Associados a Câncer/efeitos da radiação , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Tolerância a Radiação , Radiação IonizanteRESUMO
Over the past few years, numerous bacterial strains have become resistant to selected drugs from various therapeutic groups. A potential tool in the fight against these strains is antimicrobial photodynamic therapy (APDT). APDT acts in a non-specific manner by generating reactive oxygen species and radicals, thereby inducing multidimensional intracellular effects. Importantly, the chance that bacteria will develop defense mechanisms against APDT is considered to be low. In our research, we performed the synthesis and physicochemical characterization of curcumin derivatives enriched with morpholine motifs. The obtained compounds were assessed regarding photostability, singlet oxygen generation, aggregation, and acute toxicity toward prokaryotic Aliivibrio fischeri cells in the Microtox® test. The impact of the compounds on the survival of eukaryotic cells in the MTT assay was also tested (WM266-4, WM115-melanoma, MRC-5-lung fibroblasts, and PHDF-primary human dermal fibroblasts). Initial studies determining the photocytotoxicity, and thus the potential APDT usability, were conducted with the following microbial strains: Candida albicans, Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa. It was noted that the exposure of bacteria to LED light at 470 nm (fluence: 30 J/cm2) in the presence of quaternized curcumin derivatives at the conc. of 10 µM led to a reduction in Staphylococcus aureus survival of over 5.4 log.
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Antibacterianos , Curcumina , Luz , Curcumina/farmacologia , Curcumina/química , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Testes de Sensibilidade Microbiana , Aliivibrio fischeri/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/síntese química , Sobrevivência Celular/efeitos dos fármacos , Oxigênio Singlete/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Fotoquimioterapia , Bactérias/efeitos dos fármacos , Luz AzulRESUMO
Background: Head and neck squamous carcinoma (HNSC) is the sixth most common neoplasm, with a 40-50% overall survival rate. HNSC standard treatment depends on tumor size, metastasis or human papillomavirus (HPV) status including surgery, chemotherapy, and radiotherapy. The last two may lead to defects in the tumor microenvironment and cancer cell biology as disorders in DNA damage repair systems. Here, we evaluate the correlation between single nucleotide polymorphism (SNP) rs2228001 in the XPC gene with the early and late adverse effects of radiotherapy, determine the distribution of the SNP and post-treatment follow-up in HNSC patients. Materials and methods: Head and neck cancer tissues and clinical data were obtained from 79 patients. The SNP of the XPC gene (rs2228001) was evaluated with polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP). The chi-square test was used to determine the correlation between mutation and adverse effects occurrence. Results/Conclusion: Single nucleotide polymorphism rs2228001 in the XPC gene is correlated with the early adverse effect of skin reaction and the late adverse effect of elevated C-reactive protein (CRP) levels in the HNSC patients.
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Background: RNA methyltransferase-like 3 (METTL3) is responsible for methyl group transfer in the progression of N 6-methyladenosine (m6A) modification. This epigenetic feature contributes to the structural and functional regulation of RNA and consequently may promote tumorigenesis, tumor progression, and cellular response to anticancer treatment (chemo-, radio-, and immunotherapy). In head and neck squamous cell carcinoma (HNSCC), the commonly used chemotherapy is cisplatin. Unfortunately, cisplatin resistance is still a major cause of tumor relapse and patients' death. Thus, this study aimed to investigate the role of METTL3 on cellular response to cisplatin in HNSCC in vitro models. Materials and methods: HNSCC cell lines (H103, FaDu, and Detroit-562) with stable METTL3 knockdown (sgMETTL3) established with CRISPR-Cas9 system were treated with 0.5 tolerable plasma level (TPL) and 1 TPL of cisplatin. Further, cell cycle distribution, apoptosis, CD44/CD133 surface marker expression, and cell's ability to colony formation were analyzed in comparison to controls (cells transduced with control sgRNA). Results: The analyses of cell cycle distribution and apoptosis indicated a significantly higher percentage of cells with METTL3 knockdown 1) arrested in the G2/S phase and 2) characterized as a late apoptotic or death in comparison to control. The colony formation assay showed intensified inhibition of a single cell's ability to grow into a colony in FaDu and Detroit-562 METTL3-deficient cells, while a higher colony number was observed in H103 METTL3 knockdown cells after cisplatin treatment. Also, METTL3 deficiency significantly increased cancer stem cell markers' surface expression in all studied cell lines. Conclusion: Our findings highlight the significant influence of METTL3 on the cellular response to cisplatin, suggesting its potential as a promising therapeutic target for addressing cisplatin resistance in certain cases of HNSCC.
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Hypoxia in the tumor core negatively affects the outcome of patients with head and neck squamous cell carcinoma (HNSCC). Nevertheless, its role in predicting treatment response requires further exploration. Typically, reduced oxygen levels in the tumor core correlate with diminished efficacy of radiotherapy, chemotherapy, and immunotherapy, which are commonly used for HNSCC patients' treatment. Understanding the mechanistic underpinnings of these varied treatment responses in HNSCC is crucial for enhancing therapeutic outcomes and extending patients' overall survival (OS) rates. Standard monolayer cell culture conditions have major limitations in mimicking tumor physiological features and the complexity of the tumor microenvironment. Three-dimensional (3D) cell cultures enable the recreation of the in vivo tumor attributes, encompassing oxygen and nutrient gradients, cellular morphology, and intracellular connections. It is vital to use the 3D model in treatment response studies to mimic the tumor microenvironment, as evidenced by the decreased sensitivity of 3D structures to anticancer therapy. Accordingly, the aim of the study was to delineate the utility of the 3D models of hypoxic head and neck tumors in drug screening and treatment response studies.
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BACKGROUND: One of the obstacles to autologous chondrocyte implantation (ACI) is obtaining a large quantity of chondrocytes without depletion of their properties. The conditioned medium (CM) from different subpopulations of stem cells (mesenchymal stromal cells (MSC) or induced pluripotent stem cells (iPSC)) could be a gamechanger. MSCs' potential is related to the donor's health and age, which could be omitted when, as a source, iPSCs are used. There is a lack of data regarding their use in the chondrocyte culture expansion. Thus, we wanted to verify whether iPSC-CM could be beneficial for the cell culture of primary chondrocyte cells. METHODS: We added the iPSC-CMs from GPCCi001-A and ND 41658*H cells to the culture of primary chondrocyte cell lines isolated from OA patients (n = 6) for other two passages. The composition of the CM was evaluated using Luminex technology. Then, we analysed the senescence, proliferation rate and using flow cytometry: viability, distribution of cell cycle phases, production of reactive oxygen species (ROS) and double-strand breaks. The cartilage-related markers were evaluated using Western blot and immunofluorescence. Additionally, a three-dimensional cell culture was used to determine the potential to form cartilage particles. RESULTS: iPSC-CM increased proliferation and diminished cell ROS production and senescence. CM influenced the cartilage-related protein expression and promoted the growth of cartilage particles. The cell exposed to CM did not lose the ECM proteins, suggesting the chondroprotective effect for prolonged culture time. CONCLUSION: Our preliminary results suggest a beneficial effect on maintaining chondrocyte biology during in vitro expansion.
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Proliferação de Células , Condrócitos , Células-Tronco Pluripotentes Induzidas , Condrócitos/metabolismo , Condrócitos/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Meios de Cultivo Condicionados/farmacologia , Meios de Cultivo Condicionados/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , Secretoma/metabolismo , Linhagem Celular , Células Cultivadas , Técnicas de Cultura de Células/métodos , Espécies Reativas de Oxigênio/metabolismo , Senescência CelularRESUMO
Hypoxia-inducible factor 1-alpha (HIF1A) is a key transcription factor aiding tumor cells' adaptation to hypoxia, regulated by the prolyl hydroxylase family (EGLN1-3) by directing toward degradation pathways. DNA methylation potentially influences EGLN and HIF1A levels, impacting cellular responses to hypoxia. We examined 96 HNSCC patients and three cell lines, analyzing gene expression of EGLN1-3, HIF1A, CA9, VEGF, and GLUT1 at the mRNA level and EGLN1 protein levels. Methylation levels of EGLNs and HIF1A were assessed through high-resolution melting analysis. Bioinformatics tools were employed to characterize associations between EGLN1-3 and HIF1A expression and methylation. We found significantly higher mRNA levels of EGLN3, HIF1A, GLUT1, VEGF, and CA9 (p = 0.021; p < 0.0001; p < 0.0001; p = 0.004, and p < 0.0001, respectively) genes in tumor tissues compared to normal ones and downregulation of the EGLN1 mRNA level in tumor tissues (p = 0.0013). In HNSCC patients with hypermethylation of HIF1A in normal tissue, we noted a reduction in HIF1A mRNA levels compared to tumor tissue (p = 0.04). In conclusion, the differential expression of EGLN and HIF1A genes in HNSCC tumors compared to normal tissues influences patients' overall survival, highlighting their role in tumor development. Moreover, DNA methylation could be responsible for HIF1A suppression in the normal tissues of HNSCC patients.
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Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço , Subunidade alfa do Fator 1 Induzível por Hipóxia , Prolina Dioxigenases do Fator Induzível por Hipóxia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Feminino , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Masculino , Linhagem Celular Tumoral , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Pessoa de Meia-Idade , Prolil Hidroxilases/metabolismo , Prolil Hidroxilases/genética , Idoso , Carcinogênese/genética , AdultoRESUMO
The tumor microenvironment (TME) is a complex ecosystem of cells, signaling molecules, and extracellular matrix components that profoundly influence cancer progression. Among the key players in the TME, cancer-associated fibroblasts (CAFs) have gained increasing attention for their diverse and influential roles. CAFs are activated fibroblasts found abundantly within the TME of various cancer types. CAFs contribute significantly to tumor progression by promoting angiogenesis, remodeling the extracellular matrix, and modulating immune cell infiltration. In order to influence the microenvironment, CAFs engage in cross-talk with immune cells, cancer cells, and other stromal components through paracrine signaling and direct cell-cell interactions. This cross-talk can result in immunosuppression, tumor cell proliferation, and epithelial-mesenchymal transition, contributing to disease progression. Emerging evidence suggests that CAFs play a crucial role in therapy resistance, including resistance to chemotherapy and radiotherapy. CAFs can modulate the tumor response to treatment by secreting factors that promote drug efflux, enhance DNA repair mechanisms, and suppress apoptosis pathways. This paper aims to understand the multifaceted functions of CAFs within the TME, discusses cross-talk between CAFs with other TME cells, and sheds light on the contibution of CAFs to therapy resistance. Targeting CAFs or disrupting their cross-talk with other cells holds promise for overcoming drug resistance and improving the treatment efficacy of various cancer types.
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In recent decades, significant progress has been made in understanding the molecular characteristics of cancer and its microenvironment, leading to the development of life-saving treatments. However, patients often experience side effects from standard therapies, highlighting the need for personalized medicine. Personalized medicine aims to customize drug therapy and preventive care based on individual patients' specific requirements. The heterogeneity within tumors and among patients necessitates personalized medicine approaches. Patient-derived organoids (PDOs), xenografts (PDXs), and explants (PDEs) have emerged as valuable models for studying tumor behaviour and drug response. This paper aims to summarize the latest advancements in patient-derived explants, focusing on their potential utility in the clinic. Different methods for culturing PDEs, including the free-floating approach, the grid method, and sponge scaffolds, are discussed. These approaches provide opportunities for long-term viability, oxygen and nutrient supply, and maintenance of tissue integrity. Additionally, various solid tumor models using PDEs are highlighted, together with assays to study PDE viability, characteristics, and response to drug treatment.
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Gold nanoparticles (AuNPs), as an agent enhancing radiosensitivity, play a key role in the potential treatment of breast cancer (BC). Assessing and understanding the kinetics of modern drug delivery systems is a crucial element that allows the implementation of AuNPs in clinical treatment. The main objective of the study was to assess the role of the properties of gold nanoparticles in the response of BC cells to ionizing radiation by comparing 2D and 3D models. In this research, four kinds of AuNPs, different in size and PEG length, were used to sensitize cells to ionizing radiation. The in vitro viability, uptake, and reactive oxygen species generation in cells were investigated in a time- and concentration-dependent manner using 2D and 3D models. Next, after the previous incubation with AuNPs, cells were irradiated with 2 Gy. The assessment of the radiation effect in combination with AuNPs was analyzed using the clonogenic assay and γH2AX level. The study highlights the role of the PEG chain in the efficiency of AuNPs in the process of sensitizing cells to ionizing radiation. The results obtained imply that AuNPs are a promising solution for combined treatment with radiotherapy.
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BACKGROUND: The approaches currently used in osteoarthritis (OA) are mainly short-term solutions with unsatisfactory outcomes. Cell-based therapies are still controversial (in terms of the sources of cells and the results) and require strict culture protocol, quality control, and may have side-effects. A distinct population of stromal cells has an interesting secretome composition that is underrated and commonly ends up as biological waste. Their unique properties could be used to improve the existing techniques due to protective and anti-ageing properties. SCOPE OF REVIEW: In this review, we seek to outline the advantages of the use of conditioned media (CM) and exosomes, which render them superior to other cell-based methods, and to summarise current information on the composition of CM and their effect on chondrocytes. MAJOR CONCLUSIONS: CM are obtainable from a variety of mesenchymal stromal cell (MSC) sources, such as adipose tissue, bone marrow and umbilical cord, which is significant to their composition. The components present in CMs include proteins, cytokines, growth factors, chemokines, lipids and ncRNA with a variety of functions. In most in vitro and in vivo studies CM from MSCs had a beneficial effect in enhance processes associated with chondrocyte OA pathomechanism. GENERAL SIGNIFICANCE: This review summarises the information available in the literature on the function of components most commonly detected in MSC-conditioned media, as well as the effect of CM on OA chondrocytes in in vitro culture. It also highlights the need to standardise protocols for obtaining CM, and to conduct clinical trials to transfer the effects obtained in vitro to human subjects.
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Células-Tronco Mesenquimais , Osteoartrite , Humanos , Meios de Cultivo Condicionados/farmacologia , Meios de Cultivo Condicionados/metabolismo , Osteoartrite/terapia , Condrócitos , Citocinas/metabolismoRESUMO
Cancer-associated fibroblasts are a highly heterogeneous group of cells whose phenotypes and gene alterations are still under deep investigation. As a part of tumor microenvironment, they are the focus of a growing number of studies. Cancer-associated fibroblasts might become a new target of breast cancer therapy, but still more tests and analyses are needed to understand mechanisms and interactions between them and breast cancer cells. The study aimed to isolate cancer associated fibroblasts from breast cancer tissue and to phenotype the isolated cell lines. We focused on various cancer-associated fibroblast characteristic biomarkers and those that might differentiate various cancer-associated fibroblasts' subtypes. Patients with a histological diagnosis of invasive breast cancer (diameter ≤15 mm) and qualified for primary surgical treatment were enrolled in the study. Cell lines were isolated from breast cancer biopsy. For the phenotyping, we used flow cytometry, immunofluorescence and RT-qPCR analysis. Based on our study, there was no indication of a clear pattern in the cancer-associated fibroblasts' classification. Results of cancer-associated fibroblasts expression were highly heterogeneous, and specific subtypes were not defined. Moreover, comparing cancer-associated fibroblasts divided into groups based on BC subtypes from which they were isolated also did not allow to notice of any clear pattern of expressions. In the future, a higher number of analyzed cancer-associated fibroblast cell lines should be investigated to find expression schemes.
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Wound healing and skin tissue regeneration remain the most critical challenges faced by medical professionals. Titanium(IV) oxide-based materials were proposed as components of pharmaceutical formulations for the treatment of difficult-to-heal wounds and unsightly scarring. A gallic acid-functionalized TiO2 nanomaterial (TiO2-GA) was obtained using the self-assembly technique and characterized using the following methods: scanning electron microscopy (SEM), transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), X-ray powder diffraction (XRPD), infrared spectroscopy (IR), Raman spectroscopy and thermogravimetry (TG). Additionally, physicochemical and biological tests (DPPH assay, Microtox® acute toxicity test, MTT assay) were performed to assess antioxidant properties as well as to determine the cytotoxicity of the novel material against eukaryotic (MRC-5 pd19 fibroblasts) and prokaryotic (Staphylococcus aureus, Escherichia coli, Candida albicans, Aliivibrio fischeri) cells. To determine the photocytotoxicity of the material, specific tests were carried out with and without exposure to visible light lamps (425 nm). Following the results, the TiO2-GA material could be considered an additive to dressings and rinsing suspensions for the treatment of difficult-to-heal wounds that are at risk of bacterial infections.
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The development of induced pluripotent stem cells has brought unlimited possibilities to the field of regenerative medicine. This could be ideal for treating osteoarthritis and other skeletal diseases, because the current procedures tend to be short-term solutions. The usage of induced pluripotent stem cells in the cell-based regeneration of cartilage damages could replace or improve on the current techniques. The patient's specific non-invasive collection of tissue for reprogramming purposes could also create a platform for drug screening and disease modelling for an overview of distinct skeletal abnormalities. In this review, we seek to summarise the latest achievements in the chondrogenic differentiation of pluripotent stem cells for regenerative purposes and disease modelling.
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Cartilagem Articular , Células-Tronco Pluripotentes Induzidas , Diferenciação Celular , Condrogênese , Humanos , Medicina RegenerativaRESUMO
Primary cancer cell lines are ex vivo cell cultures originating from resected tissues during biopsies and surgeries. Primary cell cultures are objects of intense research due to their high impact on molecular biology and oncology advancement. Initially, the patient-derived specimen must be subjected to dissociation and isolation. Techniques for tumour dissociation are usually reliant on the organisation of connecting tissue. The most common methods include enzymatic digestion (with collagenase, dispase, and DNase), chemical treatment (with ethylene diamine tetraacetic acid and ethylene glycol tetraacetic acid), or mechanical disaggregation to obtain a uniform cell population. Cells isolated from the tissue specimen are cultured as a monolayer or three-dimensional culture, in the form of multicellular spheroids, scaffold-based cultures (i.e., organoids), or matrix-embedded cultures. Every primary cell line must be characterised to identify its origin, purity, and significant features. The process of characterisation should include different assays utilising specific (extra- and intracellular) markers. The most frequently used approaches comprise immunohistochemistry, immunocytochemistry, western blot, flow cytometry, real-time polymerase chain reaction, karyotyping, confocal microscopy, and next-generation sequencing. The growing body of evidence indicates the validity of the usage of primary cancer cell lines in the formulation of novel anti-cancer treatments and their contribution to drug development.
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RNA methylation at the nitrogen sixth of adenosine (m6A, N6-methyladenosine) is the most abundant RNA modification which plays a crucial role in all RNA metabolic aspects. Recently, m6A modification has been assigned to mediate the biological processes of cancer cells, but their significance in HNSCC development is still poorly described. Thus, the main aim of this study was to globally quantify m6A modification by the mass spectrometry approach and determine the mRNA expression level of selected m6A RNA methyltransferase (METTL3), demethylase (FTO), and m6A readers (YTHDF2, YTHDC2) in 45 HNSCC patients and 4 cell lines (FaDu, Detroit 562, A-253 and SCC-15) using qPCR. In the results, we have not observed differences in the global amount of m6A modification and the mRNA level of the selected genes between the cancerous and paired-matched histopathologically unchanged tissues from 45 HNSCC patients. However, we have found a positive correlation between selected RNA methylation machinery genes expression and m6A abundance on total RNA and characterized the transcript level of those genes in the HNSCC cell lines. Moreover, the lack of global m6A differences between cancerous and histopathologically unchanged tissues suggests that m6A alterations in specific RNA sites may specifically influence HNSCC tumorigenesis.
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RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Carcinogênese/genética , Feminino , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias de Cabeça e Pescoço/genética , Humanos , Masculino , Espectrometria de Massas/métodos , Metilação , Metiltransferases/genética , Metiltransferases/metabolismo , Pessoa de Meia-Idade , Polônia , RNA/genética , RNA Helicases/genética , Processamento Pós-Transcricional do RNA/genética , Processamento Pós-Transcricional do RNA/fisiologia , RNA Mensageiro/análise , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , tRNA Metiltransferases/metabolismoRESUMO
Ovarian cancer is the most deadly gynecologic malignancy worldwide. Although the primary response to chemotherapy is high, the majority of patients will develop resistance against applied treatment. In this study, we focused on resistance to cisplatin, a first-line drug used for the treatment of ovarian cancer. The mechanism of the resistance development process is widely described, but there is a lack of information about the involvement of members of small heat shock proteins (HSPs) and their transport via exosomes. In this study, we used two cell lines: A2780 and SKOV3, and their cisplatin-resistance variants: A2780 CDDP and SKOV3 CDDP. We have shown that the expression of three small HSPs (HSPB5, HSPB6, and HSPB8) in cisplatin-resistant cell lines differs from their sensitive counterparts. Further, we isolated exosomes and determined the small HSPs in their cargo. In A2780 WT we observed a low amount of HSPB5 and HSPB6. We did not observe the expression of small HSPs in the SKOV3 cell line in both sensitive and resistant variants. Our data suggest the involvement of small HSPs in drug resistance of ovarian cancer and their presence is not related to exosomal transport. Analysis of the biological consequences of the imbalance of small HSPs expression in cisplatin resistance needs further investigation.
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The toxicity of radiotherapy is a key issue when analyzing the eligibility criteria for patients with breast cancer. In order to obtain better results, proton therapy is proposed because of the more favorable distribution of the dose in the patient's body compared with photon radiotherapy. Scientific groups have conducted extensive research into the improved efficacy and lower toxicity of proton therapy for breast cancer. Unfortunately, there is no complete insight into the potential reasons and prospects for avoiding undesirable results. Cardiotoxicity is considered challenging; however, researchers have not presented any realistic prospects for preventing them. We compared the clinical evidence collected over the last 20 years, providing the rationale for the consideration of proton therapy as an effective solution to reduce cardiotoxicity. We analyzed the parameters of the dose distribution (mean dose, Dmax, V5, and V20) in organs at risk, such as the heart, blood vessels, and lungs, using the following two irradiation techniques: whole breast irradiation and accelerated partial breast irradiation. Moreover, we presented the possible causes of side effects, taking into account biological and technical issues. Finally, we collected potential improvements in higher quality predictions of toxic cardiac effects, like biomarkers, and model-based approaches to give the full background of this complex issue.
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Ovarian cancer (OvCa) is one of the most lethal gynaecological malignancies. It is diagnosed mostly in advanced stages. Due to a lack of appropriate early detection markers and non-ambiguous symptoms, the five-year survival rate is significantly reduced. Despite a primary good response to platinum-based therapy, approximately 70% of patients will develop a chemoresistance phenotype. The activation of the NF-κB signalling pathway plays a crucial role in this process. It is responsible for increasing cell viability, cell cycle progression and induces growth and migration of neoplastic cells. A few independent studies have yet suggested a high correlation between activation of NF-κB and poor outcome in OvCa patients. Thus, developing inhibitors of the NF-κB pathway has become a new target of cancer therapies. One of the promising compounds is DHMEQ (dehydroxymethylepoxyquinomicin). Our preliminary studies indicated that DHMEQ combined with cisplatin (CDDP) or carboplatin (CBP) enhanced apoptosis in the A2780 cell line and caused cell cycle arrest in the G2/M phase in the SKOV3 cell line, but not in the normal cell line MRC-5 pd19. Moreover, the combination of those agents caused decreased motility of cells, especially with the CBP. However, the invasion of cells was not changed significantly. The analysis of drug interactions using CompuSyn software has revealed that observed effect of the doses used in the study was antagonistic, but the DRI guidelines and in vitro observation of biological response indicate that a combination of DHMEQ with CDDP or CBP could be a novel proposal in ovarian cancer treatment.
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Head and neck squamous carcinoma (HNSCC) constitutes the sixth most prevalent cancer worldwide. The molecular pathogenesis of HNSCC includes disorders in cell cycle, intercellular signaling, proliferation, squamous cell differentiation and apoptosis. In addition to the genetic mutations, changes in HNSCC are also characterized by the accumulation of epigenetic alterations such as DNA methylation, histone modifications, non-coding RNA activity and RNA methylation. In fact, some of them may promote cancer formation and progression by controlling the gene expression machinery, hence, they could be used as biomarkers in the clinical surveillance of HNSCC or as targets for therapeutic strategies. In this review, we focus on the current knowledge regarding epigenetic modifications observed in HNSCC and its predictive value for cancer development.