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1.
Int J Mol Sci ; 25(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-39000134

RESUMO

Stem cells possess the ability to differentiate into different lineages and the ability to self-renew, thus representing an excellent tool for regenerative medicine. They can be isolated from different tissues, including the adipose tissue. Adipose tissue and human adipose-derived stem cells (hADSCs) are privileged candidates for regenerative medicine procedures or other plastic reconstructive surgeries. The cellular environment is able to influence the fate of stem cells residing in the tissue. In a previous study, we exposed hADSCs to an exhausted medium of a breast cancer cell line (MCF-7) recovered at different days (4, 7, and 10 days). In the same paper, we inferred that the medium was able to influence the behaviour of stem cells. Considering these results, in the present study, we evaluated the expression of the major genes related to adipogenic and osteogenic differentiation. To confirm the gene expression data, oil red and alizarin red colorimetric assays were performed. Lastly, we evaluated the expression of miRNAs influencing the differentiation process and the proliferation rate, maintaining a proliferative state. The data obtained confirmed that cells exposed to the medium maintained a stem and proliferative state that could lead to a risky proliferative phenotype.


Assuntos
Tecido Adiposo , Diferenciação Celular , Proliferação de Células , Osteogênese , Humanos , Diferenciação Celular/efeitos dos fármacos , Células MCF-7 , Proliferação de Células/efeitos dos fármacos , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Adipogenia/genética , Células-Tronco/metabolismo , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Meios de Cultura/farmacologia , Meios de Cultura/química
2.
Sci Rep ; 14(1): 14765, 2024 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926454

RESUMO

Adipose-derived stem cells (ADSCs) are promising in regenerative medicine. Their proliferation, survival and activation are influenced by specific signals within their microenvironment, also known as niche. The stem cell niche is regulated by complex interactions between multiple cell types. When transplanted in a specific area, ADSCs can secrete several immunomodulatory factors. At the same time, a tumor microenvironment can influence stem cell behavior, modulating proliferation and their ability to differentiate into a specific phenotype. Whitin this context, we exposed ADSCs to plasma samples derived from human patients diagnosed with prostate cancer (PC), or precancerous lesions (PL), or benign prostatic hyperplasia (BPH) for 4, 7 or 10 days. We then analyzed the expression of main stemness-related markers and cell-cycle regulators. We also measured cytokine production and polyamine secretion in culture medium and evaluated cell morphology and collagen production by confocal microscopy. The results obtained from this study show significant changes in the morphology of ADSCs exposed to plasma samples, especially in the presence of prostate cancer plasma, suggesting important implications in the use of ADSCs for the development of new treatments and application in regenerative medicine.


Assuntos
Hiperplasia Prostática , Neoplasias da Próstata , Células-Tronco , Masculino , Humanos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Hiperplasia Prostática/patologia , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/sangue , Células-Tronco/metabolismo , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Próstata/patologia , Próstata/metabolismo , Diferenciação Celular , Proliferação de Células , Citocinas/metabolismo , Citocinas/sangue , Células Cultivadas , Idoso , Pessoa de Meia-Idade
3.
Biometals ; 37(4): 803-817, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38347295

RESUMO

The majority of the so-called heavy metals are suspected to be involved in a number of pathologies and play a role in human carcinogenesis. Some of them (i.e. arsenic (As), cadmium (Cd), chromium (Cr), lead (Pb), mercury (Hg) and nickel (Ni)) have been defined as carcinogens, increasing the susceptibility of tumor development and progression in humans. Moreover, Ni, Cr, Cd, Hg, and Pb together with zinc (Zn) and iron (Fe), may be capable of stimulating the progression of breast cancer and reducing a patient's sensitivity to treatment through alterations to DNA methylation. In patients with gastric cancers, levels of various heavy metals are augmented and hypothesized to amplify the expression of the human epidermal growth factor receptor type 2 gene. Cd may increase the risk of lung cancer development and have a negative impact on the overall survival of lung cancer patients. To investigate the relation between heavy metals in biological samples and risk, occurrence and survival cancer individuals, a comprehensive review work was performed, with a focus on breast, lung, prostate and gastric cancers. An extensive search strategy was devised to ensure relevant literature could be identified, with the PECO framework being adopted to facilitate this and identify key search terms. As evidenced in this review, there is substantial data to support the hypothesis that heavy metals influence tumor development and progression. Unluckily the number of papers dealing with the determination of metals directly in samples from cancer tissues is still rather limited, so we decided to expand the scope of this review also to analyses carried out on other biological samples, as urine, plasma, hair, nail, etc. The studies reviewed showed that several limitations and current knowledge gaps are present in the literature that require further investigation to improve our comprehension of the impact of different heavy metals on tumorigenesis.


Assuntos
Metais Pesados , Neoplasias , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias/patologia , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Feminino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Masculino , Cádmio/análise , Arsênio , Cromo
4.
Cancers (Basel) ; 16(4)2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38398215

RESUMO

Pancreatic ductal adenocarcinoma (PDAC), a neoplasm of the gastrointestinal tract, is the most common pancreatic malignancy (90%) and the fourth highest cause of cancer mortality worldwide. Surgery intervention is currently the only strategy able to offer an advantage in terms of overall survival, but prognosis remains poor even for operated patients. Therefore, the development of robust biomarkers for early diagnosis and prognostic stratification in clinical practice is urgently needed. In this work, we investigated deregulated microRNAs (miRNAs) in tissues from PDAC patients with high (G3) or low (G2) histological grade and with (N+) or without (N-) lymph node metastases. miRNA expression profiling was performed by a comprehensive PCR array and subsequent validation by RT-qPCR. The results showed a significant increase in miR-1-3p, miR-31-5p, and miR-205-5p expression in G3 compared to G2 patients (** p < 0.01; *** p < 0.001; *** p < 0.001). miR-518d-3p upregulation and miR-215-5p downregulation were observed in N+ compared to N- patients. A statistical analysis performed using OncomiR program showed the significant involvement (p < 0.05) of two miRNAs (miR-31 and miR-205) in the histological grade of PDAC patients. Also, an expression analysis in PDAC patients showed that miR-31 and miR-205 had the highest expression at grade 3 compared with normal and other tumor grades. Overall, survival plots confirmed that the overexpression of miR-31 and miR-205 was significantly correlated with decreased survival in TCGA PDAC clinical samples. A KEGG pathway analysis showed that all three miRNAs are involved in the regulation of multiple pathways, including the Hippo signaling, adherens junction and microRNAs in cancer, along with several target genes. Based on in silico analysis and experimental validation, our study suggests the potential role of miR-1-3p, miR-31-5p, and miR-205-5p as useful clinical biomarkers and putative therapeutic targets in PDAC, which should be further investigated to determine the specific molecular processes affected by their aberrant expression.

5.
Medicina (Kaunas) ; 59(12)2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38138227

RESUMO

Background and Objectives: The hemoglobin (Hb)/red cell distribution width (RDW) ratio has emerged as an accessible, repeatable, and inexpensive prognostic factor that may predict survival in cancer patients. The focus of this systematic review is to investigate the prognostic role of the Hb/RDW ratio in cancer and the implications for clinical practice. Materials and Methods: A literature search of PubMed, Scopus, and Web of Science databases was performed by an independent author between 18 March and 30 March 2023 to collect relevant literature that assessed the prognostic value of the Hb/RDW ratio in cancer. Overall survival (OS), progression-free survival (PFS), and the association of these with the Hb/RDW ratio were considered to be the main endpoints. Results: Thirteen retrospective studies, including 3818 cancer patients, were identified and involved in this review. It was observed that, when patients with a high vs. low Hb/RDW ratio were compared, those with a lower Hb/RDW ratio had significantly poorer outcomes (p < 0.05). In lung cancer patients, a one-unit increase in the Hb/RDW ratio reduces mortality by 1.6 times, whilst in esophageal squamous-cell carcinoma patients, a lower Hb/RDW ratio results in a 1.416-times greater risk of mortality. Conclusions: A low Hb/RDW ratio was associated with poor OS and disease progression in patients with cancer. This blood parameter should be considered a standard biomarker in clinical practice for predicting OS and PFS in cancer patients. Future searches will be necessary to determine and standardize the Hb/RDW cut-off value and to assess whether the Hb/RDW ratio is optimal as an independent prognostic factor or if it requires incorporation into risk assessment models for predicting outcomes in cancer patients.


Assuntos
Índices de Eritrócitos , Neoplasias Pulmonares , Humanos , Estudos Retrospectivos , Hemoglobinas , Prognóstico
6.
Medicina (Kaunas) ; 59(10)2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37893604

RESUMO

Minimal Residual Disease (MRD) detection has emerged as an independent factor in clinical and pathological cancer assessment offering a highly effective method for predicting recurrence in colorectal cancer (CRC). The ongoing research initiatives such as the DYNAMIC and CIRCULATE-Japan studies, have revealed the potential of MRD detection based on circulating tumor DNA (ctDNA) to revolutionize management for CRC patients. MRD detection represents an opportunity for risk stratification, treatment guidance, and early relapse monitoring. Here we overviewed the evolving landscape of MRD technology and its promising applications through the most up-to-date research and reviews, underscoring the transformative potential of this approach. Our primary focus is to provide a point-to-point perspective and address key challenges relating to the adoption of ctDNA-based MRD detection in the clinical setting. By identifying critical areas of interest and hurdles surrounding clinical significance, detection criteria, and potential applications of basic research, this article offers insights into the advancements needed to evaluate the role of ctDNA in CRC MRD detection, contributing to favorable clinical options and improved outcomes in the management of CRC.


Assuntos
Relevância Clínica , Neoplasias Colorretais , Humanos , Neoplasia Residual/diagnóstico , Japão , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Biomarcadores Tumorais/genética
7.
Microorganisms ; 11(9)2023 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-37764014

RESUMO

The aim is better to understand and critically explore and present the available data from observational studies on the pathogenetic role of the microbiome in the development of rheumatoid arthritis (RA). The electronic databases PubMed, Scopus, and Web of Science were screened for the relevant literature published in the last ten years. The primary outcomes investigated included the influence of the gut microbiome on the pathogenesis and development of rheumatoid arthritis, exploring the changes in microbiota diversity and relative abundance of microbial taxa in individuals with RA and healthy controls (HCs). The risk of bias in the included literature was assessed using the GRADE criteria. Ten observational studies were identified and included in the qualitative assessment. A total of 647 individuals with RA were represented in the literature, in addition to 16 individuals with psoriatic arthritis (PsA) and 247 HCs. The biospecimens comprised fecal samples across all the included literature, with 16S rDNA sequencing representing the primary method of biological analyses. Significant differences were observed in the RA microbiome compared to that of HCs: a decrease in Faecalibacterium, Fusicatenibacter, Enterococcus, and Megamonas and increases in Eggerthellales, Collinsella, Prevotella copri, Klebsiella, Escherichia, Eisenbergiella, and Flavobacterium. There are significant alterations in the microbiome of individuals with RA compared to HCs. This includes an increase in Prevotella copri and Lactobacillus and reductions in Collinsella. Collectively, these alterations are proposed to induce inflammatory responses and degrade the integrity of the intestinal barrier; however, further studies are needed to confirm this relationship.

8.
Plants (Basel) ; 12(12)2023 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-37375897

RESUMO

According to the WHO, the overall age-standardized cancer rate keeps declining, and the number of cases diagnosed each year increases, remaining among the leading causes of death in 91 out of 172 recorded countries. In this context, novel cancer prediction and therapeutic protocols are compulsory. The effect of a Stachys circinata L'Hér dichloromethane extract (ScDME) on cell redox homeostasis and tumor proliferation was investigated. HepG2 cell feedback mechanisms to oxidative stress exposure were evaluated by determining catalase (CAT) and reduced glutathione (GSH), following the supply with ScDME (0.0-5.7 µg/µL). Cytotoxicity of ScDME against the human umbilical vein endothelial cell (HUVEC) and two human cancer cell lines (breast: MCF7; liver: HepG2) was evaluated by the MTT assay. H2O2-stressed HepG2 cells supplied with the S. circinata extracts exhibited significantly increased CAT and GSH activity as compared to unsupplied ones. The anti-inflammatory activity of the extracts was evaluated by real time-qPCR on IL-1, IL-6 and TNF-α expression. As a result, this research points out that S. circinata dichloromethane extract owns anti-inflammatory and anti-proliferative properties against MCF7 and HepG2 cells and activates CAT and GSH of the HepG2 cells' antioxidant enzyme system.

9.
Biology (Basel) ; 12(4)2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37106758

RESUMO

BACKGROUND: Senescence is a cellular aging process in all multicellular organisms. It is characterized by a decline in cellular functions and proliferation, resulting in increased cellular damage and death. These conditions play an essential role in aging and significantly contribute to the development of age-related complications. Humanin is a mitochondrial-derived peptide (MDP), encoded by mitochondrial DNA, playing a cytoprotective role to preserve mitochondrial function and cell viability under stressful and senescence conditions. For these reasons, humanin can be exploited in strategies aiming to counteract several processes involved in aging, including cardiovascular disease, neurodegeneration, and cancer. Relevance of these conditions to aging and disease: Senescence appears to be involved in the decay in organ and tissue function, it has also been related to the development of age-related diseases, such as cardiovascular conditions, cancer, and diabetes. In particular, senescent cells produce inflammatory cytokines and other pro-inflammatory molecules that can participate to the development of such diseases. Humanin, on the other hand, seems to contrast the development of such conditions, and it is also known to play a role in these diseases by promoting the death of damaged or malfunctioning cells and contributing to the inflammation often associated with them. Both senescence and humanin-related mechanisms are complex processes that have not been fully clarified yet. Further research is needed to thoroughly understand the role of such processes in aging and disease and identify potential interventions to target them in order to prevent or treat age-related conditions. OBJECTIVES: This systematic review aims to assess the potential mechanisms underlying the link connecting senescence, humanin, aging, and disease.

10.
Int J Mol Sci ; 24(4)2023 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-36835065

RESUMO

Senescence is a cellular aging process in all multicellular organisms. It is characterized by a decay in cellular functions and proliferation, resulting in increased cellular damage and death. This condition plays an essential role in the aging process and significantly contributes to the development of age-related complications. On the other hand, ferroptosis is a systemic cell death pathway characterized by excessive iron accumulation followed by the generation of reactive oxygen species (ROS). Oxidative stress is a common trigger of this condition and may be induced by various factors such as toxins, drugs, and inflammation. Ferroptosis is linked to numerous disorders, including cardiovascular disease, neurodegeneration, and cancer. Senescence is believed to contribute to the decay in tissue and organ functions occurring with aging. It has also been linked to the development of age-related pathologies, such as cardiovascular diseases, diabetes, and cancer. In particular, senescent cells have been shown to produce inflammatory cytokines and other pro-inflammatory molecules that can contribute to these conditions. In turn, ferroptosis has been linked to the development of various health disorders, including neurodegeneration, cardiovascular disease, and cancer. Ferroptosis is known to play a role in the development of these pathologies by promoting the death of damaged or diseased cells and contributing to the inflammation often associated. Both senescence and ferroptosis are complex pathways that are still not fully understood. Further research is needed to thoroughly investigate the role of these processes in aging and disease, and to identify potential interventions to target such processes in order to prevent or treat age-related conditions. This systematic review aims to assess the potential mechanisms underlying the link connecting senescence, ferroptosis, aging, and disease, and whether they can be exploited to block or limit the decay of the physiological functions in elderly people for a healthy longevity.


Assuntos
Doenças Cardiovasculares , Ferroptose , Humanos , Idoso , Doenças Cardiovasculares/patologia , Envelhecimento/metabolismo , Senescência Celular/fisiologia , Inflamação
11.
J Cancer Res Clin Oncol ; 149(7): 3951-3963, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36030436

RESUMO

PURPOSE: Triple negative breast cancer (TNBC) is an aggressive clinical tumor, accounting for about 25% of breast cancer (BC) related deaths. Chemotherapy is the only therapeutic option to treat TNBC, hence a detailed understanding of the biology and its categorization is required. To investigate the clinical relevance of BCL11A in TNBC subtype, we focused on gene and protein expression and its mutational status in a large cohort of this molecular subtype. METHODS: Gene expression profiling of BCL11A and its isoforms (BCL11A-XL, BCL11A-L and BCL11A-S) has been determined in Luminal A, Luminal B, HER2-enriched and TNBC subtypes. BCL11A protein expression has been analyzed by immunohistochemistry (IHC) and its mutational status by Sanger sequencing. RESULTS: In our study, BCL11A was significantly overexpressed in TNBC both at transcriptional and translational levels compared to other BC molecular subtypes. A total of 404 TNBCs were selected and examined showing a high prevalence of BCL11A-XL (37.3%) and BCL11A-L (31.4%) isoform expression in TNBC, associated with a 26% of BCL11A protein expression levels. BCL11A protein expression predicts scarce LIV (HR = 0.52; 95% CI, 0.29-0.92, P = 0.03) and AR downregulation (HR = 0.37; 95% CI, 0.16-0.88; P = 0.02), as well as a higher proliferative index in TNBC cells. BCL11A-L expression is associated with more aggressive TNBC histological types, such as medullary and metaplastic carcinoma. CONCLUSION: Our finding showed that BCL11A protein expression acts as an unfavorable prognostic factor in TNBC patients, especially in non luminal TNBCs subgroups. These results may yield a better treatment strategy by providing a new parameter for TNBC classification.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias da Mama/patologia , Relevância Clínica , Mama/patologia , Fatores de Transcrição , Imuno-Histoquímica , Prognóstico , Proteínas Repressoras/genética
12.
Biomedicines ; 10(11)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36359261

RESUMO

Cancer is a complex disease including approximately 200 different entities that can potentially affect all body tissues. Among the conventional treatments, radiotherapy and chemotherapy are most often applied to different types of cancers. Despite substantial advances in the development of innovative antineoplastic drugs, cancer remains one of the most significant causes of death, worldwide. The principal pitfall of successful cancer treatment is the intrinsic or acquired resistance to therapeutic agents. The development of more effective or synergistic therapeutic approaches to improve patient outcomes and minimize toxicity has become an urgent issue. Inula viscosa is widely distributed throughout Europe, Africa, and Asia. Used as a medicinal plant in different countries, I. viscosa has been characterized for its complex chemical composition in order to identify the bioactive compounds responsible for its biological activities, including anticancer effects. Sesquiterpene lactones (SLs) are natural, biologically active products that have attracted considerable attention due to their biological activities. SLs are alkylating agents that form covalent adducts with free cysteine residues within enzymes and key proteins favoring cancer cell cytotoxicity. They are effective inducers of apoptosis in several cancer cell types through different molecular mechanisms. This review focuses on recent advances in the cytotoxic effects of I. viscosa and SLs in the treatment of neoplastic diseases, with a special emphasis on their proapoptotic molecular mechanisms.

13.
Diagnostics (Basel) ; 12(9)2022 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-36140552

RESUMO

Lymphomas represent a heterogeneous and widely diversified group of neoplastic diseases rising from a variety of lymphoid subsets at heterogeneous differentiation stages. These lymphoproliferative disorders lead to the clinicopathological complexity of the classification of lymphoid neoplasms, describing to date more than 40 categories of non-Hodgkin's lymphoma (NHL) and 5 categories of Hodgkin's lymphoma (HL). Inflammation has been shown to play a key role in the evolution of cancer diseases, and it might be interesting to understand their role also in the context of lymphoid neoplasms. Among circulating biomarkers, the role of polyamines belonging to the arginine and lysine metabolism is relevant. Through modern analytical methods, such as mass spectrometry (MS), we are enabled to increase knowledge and improve our understanding of cancer metabolism. In this study, high-resolution mass spectrometry was used in combination with high-performance liquid chromatography (LC-HRMS) to measure serum levels of polyamines and identify possible diagnostic circulating biomarkers, potentially allowing a more accurate assessment of the diagnostic stratification of lymphoma patients and robust comparisons between different patient groups.

14.
J Mol Diagn ; 24(11): 1171-1180, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35835374

RESUMO

miRNAs are short noncoding RNAs able to regulate specific mRNA stability, thus influencing target gene expression. Disrupted levels of several miRNAs have been associated with prostate cancer (PC), the leading cause of cancer death among men and the fifth leading cause of death worldwide. Herein, we investigated whether miR-145, miR-148, and miR-185 circulating levels in plasma could be used as molecular biomarkers, to allow distinguishing between individuals with benign prostatic hyperplasia, precancerous lesions, and PC. One-hundred and seventy urological clinic patients with suspected PC who underwent prostate biopsy were recruited. Total RNA was isolated from plasma, and TaqMan MicroRNA assays were used to analyze miR-145, miR-185, and miR-148 expression. First, differential miRNA expression among patient groups was evaluated. Then, miRNA levels were combined with clinical assessment outcomes, including results from invasive tests, using multivariate analysis to examine their ability in discriminating among the three patient groups. Our results suggest that miRNA is a promising molecular tool for clinical management of at-risk patients.


Assuntos
MicroRNAs , Neoplasias da Próstata , Masculino , Humanos , MicroRNAs/genética , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Próstata/patologia , Biomarcadores , Biópsia , Biomarcadores Tumorais/genética
15.
Int J Mol Sci ; 23(12)2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35743278

RESUMO

MicroRNAs (miRNA) are key regulators of gene expression, controlling different biological processes such as cellular development, differentiation, proliferation, metabolism, and apoptosis. The relationships between miRNA expression and the onset and progression of different diseases, such as tumours, cardiovascular and rheumatic diseases, and neurological disorders, are well known. A nanotechnology-based approach could match miRNA delivery and detection to move beyond the proof-of-concept stage. Different kinds of nanotechnologies can have a major impact on the diagnosis and treatment of miRNA-related diseases such as cancer. Developing novel methodologies aimed at clinical practice represents a big challenge for the early diagnosis of specific diseases. Within this context, nanotechnology represents a wide emerging area at the forefront of research over the last two decades, whose potential has yet to be fully attained. Nanomedicine, derived from nanotechnology, can exploit the unique properties of nanometer-sized particles for diagnostic and therapeutic purposes. Through nanomedicine, specific treatment to counteract only cancer-cell proliferation will be improved, while leaving healthy cells intact. In this review, we dissect the properties of different nanocarriers and their roles in the early detection and treatment of cancer.


Assuntos
MicroRNAs , Neoplasias , Humanos , MicroRNAs/metabolismo , Nanomedicina , Nanotecnologia/métodos , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/terapia
16.
Biomolecules ; 12(4)2022 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-35454104

RESUMO

Prostate cancer is the most frequent malignant tumour among males (19%), often clinically silent and of difficult prognosis. Although several studies have highlighted the diagnostic and prognostic role of circulating biomarkers, such as PSA, their measurement does not necessarily allow the detection of the disease. Within this context, many authors suggest that the evaluation of circulating polyamines could represent a valuable tool, although several analytical problems still counteract their clinical practice. In particular, agmatine seems particularly intriguing, being a potential inhibitor of polyamines commonly derived from arginine. The aim of the present work was to evaluate the potential role of agmatine as a suitable biomarker for the identification of different classes of patients with prostate cancer (PC). For this reason, three groups of human patients-benign prostatic hyperplasia (BPH), precancerous lesion (PL), and prostate cancer (PC)-were recruited from a cohort of patients with suspected prostate cancer (n = 170), and obtained plasma was tested using the LC-HRMS method. Statistics on the receiver operating characteristics curve (ROC), and multivariate analysis were used to examine the predictive value of markers for discrimination among the three patient groups. Statistical analysis models revealed good discrimination using polyamine levels to distinguish the three classes of patients. AUC above 0.8, sensitivity ranging from 67% to 89%, specificity ranging from 74% to 89% and accuracy from 73% to 86%, considering the validation set, were achieved. Agmatine plasma levels were measured in PC (39.9 ± 12.06 ng/mL), BPH (77.62 ± 15.05 ng/mL), and PL (53.31 ± 15.27 ng/mL) patients. ROC analysis of the agmatine panel showed an AUC of 0.959 and p ≤ 0.001. These results could represent a future tool able to discriminate patients belonging to the three different clinical groups.


Assuntos
Agmatina , Hiperplasia Prostática , Neoplasias da Próstata , Biomarcadores , Biomarcadores Tumorais , Humanos , Masculino , Poliaminas , Antígeno Prostático Específico , Hiperplasia Prostática/diagnóstico , Neoplasias da Próstata/patologia
17.
Int J Mol Sci ; 23(3)2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-35163550

RESUMO

MicroRNAs (miRNAs) are small non-coding RNA molecules that play a role in cancer linked to the regulation of important cellular processes and pathways involving tumorigenesis, cell proliferation, differentiation, and apoptosis. A lot of human miRNA sequences have been identified which are linked to cancer pathogenesis. MicroRNAs, in prostate cancer (PC), play a relevant role as biomarkers, show a specific profile, and have been used as therapeutic targets. Prostate cancer (PC) is the most frequently diagnosed cancer in men. Clinical diagnoses among the gold standards for PC diagnosis and monitoring are prostate-specific antigen (PSA) testing, digital rectal examination, and prostate needle biopsies. PSA screening still has a large grey area of patients, which leads to overdiagnosis. Therefore, new biomarkers are needed to improve existing diagnostic tools. The miRNA expression profiles from tumour versus normal tissues are helpful and exhibit significant differences not only between cancerous and non-cancerous tissues, but also between different cancer types and subtypes. In this review, we focus on the role of miRNAs-145, 148, and 185 and their correlation with stem cells in prostate cancer pathogenesis. MiR-145, by modulating multiple oncogenes, regulates different cellular processes in PC, which are involved in the transition from localised to metastatic disease. MiR-148 is downregulated in high-grade tumours, suggesting that the miR-148-3 family might act as tumour suppressors in PC as a potential biomarker for detecting this disease. MiR-185 regulation is still unclear in being able to regulate tumour processes in PC. Nevertheless, other authors confirm the role of this miRNA as a tumour suppressor, suggesting its potential use as a suitable biomarker in disease prognosis. These three miRNAs are all involved in the regulation of prostate cancer stem cell behaviour (PCSCs). Within this contest, PCSCs are often involved in the onset of chemo-resistance in PC, therefore strategies for targeting this subset of cells are strongly required to control the disease. Hence, the relationship between these two players is interesting and important in prostate cancer pathogenesis and in PCSC stemness regulation, in the attempt to pave the way for novel therapeutic targets in prostate cancer.


Assuntos
MicroRNAs/genética , Células-Tronco Neoplásicas/patologia , Neoplasias da Próstata/patologia , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Gradação de Tumores , Células-Tronco Neoplásicas/química , Prognóstico , Neoplasias da Próstata/genética
18.
Int J Mol Sci ; 24(1)2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36613539

RESUMO

Colorectal cancer (CRC) is one of the major public health and socio-economic problems, which management demands the development of non-invasive screening tests. Assessment of circulating polyamines could be a valuable tool, although analytical problems still preclude its clinical practice. We exploited ultra-high-resolution liquid chromatography and mass spectrometry, as a highly sensitive and innovative method, to profile eleven polyamines, including spermine and spermidine with their acetylated forms. These data together with an evaluation of the inflammatory indexes might represent suitable biomarkers for the identification of CRC patients. The statistical models revealed good discrimination in distinguishing CRC patients from healthy subjects. The plasma assessment of ornithine and acetylspermine, as well as lymphocyte/platelet ratio, revealed helpful information on the progression of CRC. The combined profiles of circulating polyamines and inflammatory indexes, together with the application of an innovative technology, could represent a valuable tool for discriminating patients from different clinical groups.


Assuntos
Neoplasias Colorretais , Poliaminas , Humanos , Poliaminas/análise , Espermidina , Espermina , Cromatografia Líquida/métodos , Neoplasias Colorretais/diagnóstico
19.
Cells ; 10(7)2021 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-34359925

RESUMO

Human adipose tissue-derived stem cells (hADSCs) are highly suitable for regeneration therapies being easily collected and propagated in vitro. The effects of different external factors and culturing conditions are able to affect hADSC proliferation, senescence, differentiation, and migration, even at the molecular level. In the present paper, we exposed hADSCs to an exhausted medium from the breast cancer cell line (MCF-7) to evaluate whether the soluble factors released by these cells may be able to induce changes in stem cell behavior. In particular, we investigated the expression of stemness-related genes (OCT4; Sox 2; Nanog), the cell-cycle regulators p21 (WAF1/CIP1) p53, epigenetic markers (DNMT1 and Sirt1), and autophagy-related proteins. From our results, we can infer that the exhausted medium from MCF-7 is able to influence the hADSCs behavior increasing the expression of stemness-related genes, cell proliferation, and autophagy. Polyamines detectable in MCF-7 exhausted medium could be related to the higher proliferation capability observed in hADSCs, suggesting direct crosstalk between these molecules and the observed changes in stem cell potency.


Assuntos
Tecido Adiposo/citologia , Células-Tronco/citologia , Autofagossomos/metabolismo , Autofagia/genética , Bromodesoxiuridina/metabolismo , Proliferação de Células , Forma Celular , Sobrevivência Celular , Meios de Cultura , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Epigênese Genética , Humanos , Células MCF-7 , Pessoa de Meia-Idade , Poliaminas/metabolismo , Células-Tronco/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo
20.
Semin Cancer Biol ; 76: 27-37, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34153434

RESUMO

Gold nanoparticles (AuNPS) represent one of the most studied classes of nanomaterials for biomedical applications, especially in the field of cancer research. In fact, due to their unique properties and high versatility, they can be exploited under all aspects connected to cancer management, from early detection to diagnosis and treatment. AuNPs have thus been tested with amazing results as biosensors, contrast agents, therapeutics. Their importance as potent theranostics is undoubted, but the translation to clinical practice has been hampered by a series of aspects, such as the unclear toxicity in humans and the lack of thorough studies on reliable animal models. Still, their potential action is so appealing and the results so impressive that an outstanding number of papers is being published every year, with the consequence that any review on this topic becomes obsolete within a few months. Here we would like to report the latest findings on AuNPs research addressing all their functions as theranostic agents.


Assuntos
Ouro , Nanopartículas Metálicas , Neoplasias/diagnóstico , Neoplasias/terapia , Nanomedicina Teranóstica/tendências , Animais , Humanos , Nanomedicina Teranóstica/métodos
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