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1.
Med Pharm Rep ; 97(2): 132-142, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38746025

RESUMO

We have examined genomic and transcriptomic abnormalities in human and canine samples to evaluate the canine model's validity for breast cancer research, emphasizing similarities and differences. Both species commonly utilize serum tumor markers and noncoding microRNAs. Immunohistochemistry and immunocytochemistry were employed to illustrate and compare results based on histological diagnoses. In addition to these factors, similarities exist in spontaneous tumor occurrence, age of onset, hormonal influences, and disease progression, including tumor size, clinical stage, and lymph node involvement. Molecular traits such as hormone receptor status, Epidermal Growth Factor Receptor (EGFR), and proliferation markers (Ki67) further endorse the canine model's utility in breast cancer studies. The advancement of technologies facilitates the identification of new cancer-associated molecules, both coding and non-coding genes, underscoring their potential as prognostic/diagnostic biomarkers and therapeutic targets.

2.
Stem Cell Rev Rep ; 20(3): 656-671, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38279054

RESUMO

Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNAs (ncRNAs) which unlike linear RNAs, have a covalently closed continuous loop structure. circRNAs are found abundantly in human cells and their biology is complex. They feature unique expression to different types of cells, tissues, and developmental stages. To the present, the functional roles of circular RNAs are not fully understood. They reportedly act as microRNA (miRNA) sponges, therefore having key regulatory functions in diverse physiological and pathological processes. As for dentistry field, lines of evidence indicate that circRNAs play vital roles in the odontogenic and osteogenic differentiation of dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs). Abnormal expression of circRNAs have been found in other areas of pathology frequently reflected also in the oral environment, such as inflammation or bone and soft tissue loss. Therefore, circRNAs could be of significant importance in various fields in dentistry, especially in bone and soft tissue engineering and regeneration. Understanding the molecular mechanisms occurring during the regulation of oral biological and tissue remodeling processes could augment the discovery of novel diagnostic biomarkers and therapeutic strategies that will improve orthodontic and other oral therapeutic protocols.


Assuntos
MicroRNAs , RNA Circular , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Osteogênese/fisiologia , MicroRNAs/genética , MicroRNAs/metabolismo , Diferenciação Celular/genética , Células-Tronco/metabolismo
3.
Vet J ; 303: 106055, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38097103

RESUMO

Despite all clinical progress recorded in the last decades, human breast cancer (HBC) remains a major challenge worldwide both in terms of its incidence and its management. Canine mammary tumors (CMTs) share similarities with HBC and represent an alternative model for HBC. The utility of the canine model in studying HBC relies on their common features, include spontaneous development, subtype classification, mutational profile, alterations in gene expression profile, and incidence/prevalence. This review describes the similarities between CMTs and HBC regarding genomic landscape, microRNA expression alteration, methylation, and metabolomic changes occurring during mammary gland carcinogenesis. The primary purpose of this review is to highlight the advantages of using the canine model as a translational animal model for HBC research and to investigate the challenges and limitations of this approach.


Assuntos
Neoplasias da Mama , Doenças do Cão , Neoplasias Mamárias Animais , Humanos , Animais , Cães , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/veterinária , Neoplasias Mamárias Animais/metabolismo , Transcriptoma , Carcinogênese , Modelos Animais , Doenças do Cão/genética , Doenças do Cão/metabolismo
4.
Biomedicines ; 11(12)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38137519

RESUMO

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) as the most common type. In addition, NSCLC has a high mortality rate and an overall adverse patient outcome. Although significant improvements have been made in therapeutic options, effectiveness is still limited in late stages, so the need for a better understanding of the genomics events underlying the current therapies is crucial to aid future drug development. Vinorelbine (VRB) is an anti-mitotic chemotherapy drug (third-generation vinca alkaloid) used to treat several malignancies, including NSCLC. However, despite its widespread clinical use, very little is known about VRB-associated genomic alterations in different subtypes of NSCLC. This article is an in vitro investigation of the cytotoxic effects of VRB on three different types of NSCLC cell lines, A549, Calu-6, and H1792, with a closer focus on post-treatment genetic alterations. Based on the obtained results, VRB cytotoxicity produces modifications on a cellular level, altering biological processes such as apoptosis, autophagy, cellular motility, cellular adhesion, and cell cycle, but also at a genomic level, dysregulating the expression of some coding genes, such as EGFR, and long non-coding RNAs (lncRNAs), including CCAT1, CCAT2, GAS5, MALAT1, NEAT1, NORAD, XIST, and HOTAIR, that are implicated in the mitogen-activated protein kinase (MAPK) signaling pathway. Therefore, although extensive validation is required, these results pave the way towards a better understanding of the cellular and genomic alterations underlying the cytotoxicity of VRB.

5.
Med Pharm Rep ; 96(4): 392-399, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37970200

RESUMO

Background and aims: In the context of the novelty of personalized medicine and biobanking in Romania, there is an acute need to analyze the degree of knowledge of the key actors in the domain. The present study sought to investigate the understanding of 'biobanking' and 'personalized medicine' in three categories of participants in the development of a biobank - health professionals (clinicians/diagnosticians), scientific researchers, and patients, in order to identify possible faults regarding the level of information. The secondary objective of this study was to identify key elements and relevant data that should be detailed in the clinical dataset that accompanies a biological sample. Methods: A total of 120 participants were included in this study that were divided into three categories that represent key actors in the development and management of a cancer biobank - clinicians (n=40), scientific researchers (n=40), and oncology patients (n=40). Results: The survey indicated that the terms 'biobank' and 'personalized medicine' are unknown only in a proportion of patients, while for the other two groups, these terms are already known. The second questionnaire allowed the arrangement of a recommended clinical dataset to be filled when a biological sample is provided to be included in a cancer biobank. Conclusions: The trust of patients and healthcare professionals in building biobanks that adhere to ethical and operational standards in Romania is important, as the development of artificial intelligence and databases allows advanced knowledge and connection of findings from different databases and, therefore, brings the concept of personalized medicine closer to the clinical practice. The information included in this dataset will be integrated and constitutes a comprehensive biobank database. All these aspects are meant to increase the utility of the specimens in cancer research, as clearly annotated samples, along with prospective data, bring valuable knowledge that helps scientific researchers and clinicians make the clinical connection between the molecular alterations and the phenotype of particular patients or a disease.

6.
Med Pharm Rep ; 96(3): 235-245, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37577017

RESUMO

Background/Aim: A biobank is an organization that gathers, refines, preserves and provides access to biospecimens along with relevant clinical data that can be used in applied or clinical research. Biobanking is a critical component of the scientific foundation for personalized medicine; this implies the accessibility of high-quality human biospecimens, such as blood, tissue, and other body fluids, along with the patient clinical data that goes with them. Methods: This paper summarizes the function of biobanks in oncology and the requirements for biobank development in translational and clinical research. Results: Biobanks raise numerous ethical issues that government agencies address by enacting particular laws. To develop personalized medicine, biobanks are crucial, given that the availability of an extensive collection of patient samples with thoroughly annotated clinical and pathological data is an essential necessity. Also, data related to biobanking raises complex ethical, legal, and social issues, particularly concerning the protection of donor privacy and the appropriate use of collected samples. International standards have been developed to address these issues to ensure biobanking practices' quality, safety, and integrity. Conclusions: Biobanking is vital in advancing biomedical research, supporting clinical applications, and enhancing our understanding of human health and disease. Using real-world data and biobanking can accelerate medical research, support personalized medicine initiatives, and improve patient care.

7.
Med Pharm Rep ; 96(3): 310-317, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37577021

RESUMO

Background/Aim: Squamous cell carcinoma (SCC) is the most frequent cancer of the head and neck area in the oral cavity. Epigenetic alterations in oral and maxillofacial area cancers are urgently needed to be investigated, as the observed changes might have crucial diagnostic value for personalized medicine. Methods: Our study aimed to identify the most frequently hypermethylated tumor suppressor gene promoters in OSCC, followed by correlation analysis with the patients' survival. We evaluated the methylation status of the promoters in a panel of 22 tumor suppressor genes in Romanian (n=9) and Bulgarian (n=12) patient groups suffering from oral and maxillofacial area cancers. The extracted DNA was further digested through EpiTect Methyl II PCR Array System containing methylation-sensitive and methylation-dependent restriction enzymes, followed by specific amplification of the products obtained by qPCR and data analysis using the online platform provided by the producer. Results: Different methylation patterns were observed in the tumor suppressor genes' promoters. Among them, the methylation profile of Cccnd2, Chd1, Cdh13, Cdkn1c, Neurog1, Gstp1, and Runx3 genes further correlated with overall survival rates. Conclusions: Our data emphasize that epigenetic alterations are responsible for the clinical heterogeneity of oral and maxillofacial area cancers and significantly impact on patient survival. Additional investigation on a larger patient cohort should validate these potential biomarkers.

8.
J Gastrointestin Liver Dis ; 32(3): 356-366, 2023 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-37494555

RESUMO

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is a common hepatic condition that can progress to hepatocellular carcinoma (HCC) in non-cirrhotic livers. To better understand the development of NAFLD-associated HCC, we performed an integrated morphological and molecular analysis to identify new insights that can improve the follow-up of NAFLD patients. METHODS: Our study included a cohort of 14 NAFLD-associated HCC and 41 NAFLD patients. We analyzed clinical parameters, a four-microRNA (miRNA) panel (miR-21-5p, miR-34a-5p, miR-130a-3p, and miR-155-3p) panel and their relationship with p53 and ß-catenin expression. RESULTS: In the study cohort, the NAFLD-associated HCC patients were predominantly male, older, had significantly altered hepatic function, and a higher incidence of hypertension, type 2 diabetes, and dyslipidemia. Morphologically, the NAFLD-HCC group had substantially higher steatosis, ballooning, and fibrosis grades than the NAFLD group. The ß-catenin expression was higher in both adjacent non-tumoral liver tissue (ANT) from NAFLD-associated HCC patients and in HCC tissue com-pared with NAFLD samples. The 4 miRNAs panel showed a dysregulated expression profile between NAFLD, ANT and HCC samples. CONCLUSIONS: This study provides important insights regarding the molecular mechanisms underlying HCC progression in NAFLD patients, allowing for the development of better screening strategies for the early detection of NAFLD-associated HCC.


Assuntos
Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Neoplasias Hepáticas , MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Humanos , Masculino , Feminino , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/epidemiologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/complicações , MicroRNAs/genética , beta Catenina/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Imuno-Histoquímica
9.
Expert Rev Mol Med ; 25: e18, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-37154101

RESUMO

BACKGROUND: Glioblastoma (GBM) is the most frequent type of primary brain cancer, having a median survival of only 15 months. The current standard of care includes a combination of surgery, radiotherapy (RT) and chemotherapy with temozolomide, but with limited results. Moreover, multiple studies have shown that tumour relapse and resistance to classic therapeutic approaches are common events that occur in the majority of patients, and eventually leading to death. New approaches to better understand the intricated tumour biology involved in GBM are needed in order to develop personalised treatment approaches. Advances in cancer biology have widen our understanding over the GBM genome and allowing a better classification of these tumours based on their molecular profile. METHODS: A new targeted therapeutic approach that is currently investigated in multiple clinical trials in GBM is represented by molecules that target various defects in the DNA damage repair (DDR) pathway, a mechanism activated by endogenous and exogenous factors that induce alteration of DNA, and is involved for the development of chemotherapy and RT resistance. This intricate pathway is regulated by p53, two important kinases ATR and ATM and non-coding RNAs including microRNAs, long-non-coding RNAs and circular RNAs that regulate the expression of all the proteins involved in the pathway. RESULTS: Currently, the most studied DDR inhibitors are represented by PARP inhibitors (PARPi) with important results in ovarian and breast cancer. PARPi are a class of tumour agnostic drugs that showed their efficacy also in other localisations such as colon and prostate tumours that have a molecular signature associated with genomic instability. These inhibitors induce the accumulation of intracellular DNA damage, cell cycle arrest, mitotic catastrophe and apoptosis. CONCLUSIONS: This study aims to provide an integrated image of the DDR pathway in glioblastoma under physiological and treatment pressure with a focus of the regulatory roles of ncRNAs. The DDR inhibitors are emerging as an important new therapeutic approach for tumours with genomic instability and alterations in DDR pathways. The first clinical trials with PARPi in GBM are currently ongoing and will be presented in the article. Moreover, we consider that by incorporating the regulatory network in the DDR pathway in GBM we can fill the missing gaps that limited previous attempts to effectively target it in brain tumours. An overview of the importance of ncRNAs in GBM and DDR physiology and how they are interconnected is presented.


Assuntos
Glioblastoma , Masculino , Humanos , Glioblastoma/terapia , Glioblastoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Dano ao DNA , RNA não Traduzido/genética , Biomarcadores , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Instabilidade Genômica , DNA , Reparo do DNA/genética
10.
Life Sci ; 318: 121499, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36775114

RESUMO

Semaphorins are regulatory molecules that are linked to the modulation of several cancer processes, such as angiogenesis, cancer cell invasiveness and metastasis, tumor growth, as well as cancer cell survival. Semaphorin (SEMA) activity depends on the cancer histotypes and their particularities. In broad terms, the effects of SEMAs result from their interaction with specific receptors/co-receptors - Plexins, Neuropilins and Integrins - and the subsequent effects upon the downstream effectors (e.g. PI3K/AKT, MAPK/ERK). The present article serves as an integrative review work, discussing the broad implications of semaphorins in cancer, focusing on cell proliferation/survival, angiogenesis, invasion, metastasis, stemness, and chemo-resistance/response whilst highlighting their heterogeneity as a family. Herein, we emphasized that semaphorins are largely implicated in cancer progression, interacting with the tumor microenvironment components. Whilst some SEMAs (e.g. SEMA3A, SEMA3B) function widely as tumor suppressors, others (e.g. SEMA3C) act as pro-tumor semaphorins. The differences observed in terms of the biological structure of SEMAs and the particularities of each cancer histotypes require that each semaphorin be viewed as a unique entity, and its roles must be researched accordingly. A more in-depth and comprehensive view of the molecular mechanisms that promote and sustain the malignant behavior of cancer cells is of utmost importance.


Assuntos
Neoplasias , Semaforinas , Humanos , Fosfatidilinositol 3-Quinases , Neoplasias/patologia , Neuropilinas/química , Semaforina-3A , Microambiente Tumoral
11.
Antioxidants (Basel) ; 12(2)2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36829966

RESUMO

Melanoma is the most aggressive type of skin cancer. Although different anti-melanoma treatments are available, their efficacy is still improvable, and the number of deaths continues to increase worldwide. A promising source of antitumor agents could be presented by polyphenols-natural plant-based compounds. Over the past decades, many studies have described multiple anticancer effects of polyphenols in melanoma, presenting their potential interactions with targeted molecules from different signaling pathways. However, to our knowledge, there is no comprehensive review on polyphenols-regulated mechanisms in melanoma cells available in the literature. To fulfill this gap, this article aims to summarize the current knowledge of molecular mechanisms of action regulated by polyphenols involved in melanoma initiation and progression. Here, we focus on in vitro and in vivo effects of polyphenol treatments on tumor-essential cellular pathways, such as cell proliferation, apoptosis, autophagy, inflammation, angiogenesis, and metastasis. Moreover, emerging studies regarding the well-marked role of polyphenols in the regulation of microRNAs (miRNAs), highlighting their contribution to melanoma development, are also epitomized. Finally, we hope this review will provide a firm basis for developing polyphenol-based therapeutic agents in melanoma treatment.

12.
Int J Mol Sci ; 23(20)2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36293225

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver pathology worldwide. Meanwhile, liver cancer represents the sixth most common malignancy, with hepatocellular carcinoma (HCC) as the primary, most prevalent subtype. Due to the rising incidence of metabolic disorders, NAFLD has become one of the main contributing factors to HCC development. However, although NAFLD might account for about a fourth of HCC cases, there is currently a significant gap in HCC surveillance protocols regarding noncirrhotic NAFLD patients, so the majority of NAFLD-related HCC cases were diagnosed in late stages when survival chances are minimal. However, in the past decade, the focus in cancer genomics has shifted towards the noncoding part of the genome, especially on the microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), which have proved to be involved in the regulation of several malignant processes. This review aims to summarize the current knowledge regarding some of the main dysregulated, noncoding RNAs (ncRNAs) and their implications for NAFLD and HCC development. A central focus of the review is on miRNA and lncRNAs that can influence the progression of NAFLD towards HCC and how they can be used as potential screening tools and future therapeutic targets.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Hepatopatia Gordurosa não Alcoólica , RNA Longo não Codificante , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/diagnóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Progressão da Doença
13.
Cells ; 11(18)2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36139356

RESUMO

The increasing burden on human malignant diseases became a major concern for healthcare practitioners, that must deal with tumor relapse and the inability to efficiently treat metastasis, in addition to side effects. Throughout the decades, many therapeutic strategies have been employed to improve the clinical outcomes of cancer patients and great efforts have been made to develop more efficient and targeted medicines. The malignant cell is characterized by genetic and epigenetic modifications, therefore targeting those specific drivers of carcinogenesis is highly desirable. Among the genome editing technologies, CRISPR/Cas9 stood as a promising candidate for cancer treatment alternatives, due to its low complexity design. First described as a defense mechanism of bacteria against invading foreign DNA, later it was shown that CRISPR components can be engineered to target specific DNA sequences in a test tube, a discovery that was awarded later with the Nobel Prize in chemistry for its rapid expansion as a reliable genome editing tool in many fields of research, including medicine. The present paper aims of describing CRISPR/Cas9 potential targets for malignant disorders, and the approaches used for achieving this goal. Aside from preclinical studies, we also present the clinical trials that use CRISPR-based technology for therapeutic purposes of cancer. Finally, a summary of the presented studies adds a more focused view of the therapeutic value CRISPR/Cas9 holds and the associated shortcomings.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Sistemas CRISPR-Cas/genética , DNA , Epigênese Genética , Humanos , Recidiva Local de Neoplasia/genética
14.
Int J Mol Sci ; 23(18)2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36142135

RESUMO

Acute ischemic stroke (AIS) represents an important cause of disability and death. Since only a minor percentage of patients with AIS are eligible for acute therapy, the management of risk factors is mandatory. An important risk factor of AIS is hyperlipemia. The current guidelines recommend a strict correction of it. Statins are recommended as the first-line treatment, while proprotein convertase subtilin/kexin type 9 (PCSK-9) inhibitors are administered as a second or even third option when the goal for a low-density lipoprotein cholesterol (LDL-C) level is not achieved. PCSK-9 inhibitors effectively decrease the LDL-C levels through the inhibition of PCSK-9-LDL-receptor complex formation. The in-depth understanding of the PCSK-9 protein mechanism in the metabolism of LDL-C led to the development of effective targeted approaches. Furthermore, a better understanding of the LDL-C metabolic pathway led to the development of newer approaches, which increased the therapeutic options. This article aims to offer an overview of the PCSK-9 inhibitors and their mechanism in reducing the LDL-C levels. Moreover, we will present the main indications of the current guidelines for patients with hyperlipemia and for those who have suffered an acute ischemic stroke, as well as the importance of LDL-C reduction in decreasing the rate of a recurrence.


Assuntos
Anticolesterolemiantes , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipidemias , AVC Isquêmico , Acidente Vascular Cerebral , Anticolesterolemiantes/efeitos adversos , Bacteriocinas , LDL-Colesterol/metabolismo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , AVC Isquêmico/tratamento farmacológico , Pró-Proteína Convertases , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/tratamento farmacológico
16.
Sci Rep ; 12(1): 10874, 2022 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-35760972

RESUMO

A variety of medical procedures are classified as aerosol generating. However there is no consensus on whether some procedures such as nasopharyngeal swabbing can generate aerosols. During specimen collection, the contact of the nasopharyngeal swab with the respiratory mucosa often triggers defense reflexes such as sneezing and coughing, which generate airborne particles. The accumulation and persistence of a viral load from infectious aerosols for hours after their generation can represent a threat for increased spread of infection. Prospective observational cohort study in individuals tested for RT-PCR SARS-CoV-2 from July to October 2020. Participants were evaluated for the prevalence of aerosol generating events (AGEs) triggered by the nasopharyngeal swabbing. We used descriptive statistics to analyze the data set and the chi-square test for AGE comparison between sexes. Among 1239 individuals, we reported 264 in which AGEs were triggered by the specimen collection. 97 individuals tested positive for SARS-CoV-2, of which 20 presented AGEs. There were no significant differences in the occurrence of AGEs by age, but significant differences have been identified between sex and the occurrence of AGEs both in the SARS-CoV-2 negative and SARS-CoV-2 positive individuals. The prevalence of coughing or sneezing triggered by the nasopharyngeal swabbing was high among tested individuals. Testing facilities should ensure adequate availability of personal protective equipment (PPE) for the testing personnel, ensure appropriate ventilation of the rooms, and develop additional strategies to limit the risk of contamination of other participants to the testing session from potentially infectious and persistent aerosols.


Assuntos
COVID-19 , Pandemias , Aerossóis , COVID-19/diagnóstico , COVID-19/epidemiologia , Tosse/etiologia , Humanos , Nasofaringe , Estudos Prospectivos , SARS-CoV-2 , Espirro
17.
Genes (Basel) ; 13(4)2022 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-35456400

RESUMO

Oral cancer is one of the leading causes of death worldwide, with a reported 5-year survival rate of around 50% after treatment. Epigenetic modifications are considered to have a key role in oral carcinogenesis due to histone modifications, aberrant DNA methylation, and altered expression of miRNAs. MicroRNAs (miRNAs) are small non-coding RNAs that have a key role in cancer development by regulating signaling pathways involved in carcinogenesis. MiRNA deregulation identified in oral cancer has led to the idea of using them as potential biomarkers for early diagnosis, prognosis, and the development of novel therapeutic strategies. In recent years, a key role has been observed for risk factors in preventing and treating this malignancy. The purpose of this review is to summarize the recent knowledge about the altered mechanisms of oral cancer due to risk factors and the role of miRNAs in these mechanisms.


Assuntos
MicroRNAs , Neoplasias Bucais , Carcinogênese/genética , Metilação de DNA/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Bucais/genética , Fatores de Risco
18.
J Pers Med ; 12(3)2022 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-35330454

RESUMO

Background: Lung cancer remains one of the most diagnosed malignancies, being the second most diagnosed cancer, while still being the leading cause of cancer-related deaths. Late diagnosis remains a problem, alongside the high mutational burden encountered in lung cancer. Methods: We assessed the genetic profile of cancer genes in lung cancer using The Cancer Genome Atlas (TCGA) datasets for mutations and validated the results in a separate cohort of 32 lung cancer patients using tumor tissue and whole blood samples for next-generation sequencing (NGS) experiments. Another separate cohort of 32 patients was analyzed to validate some of the molecular alterations depicted in the NGS experiment. Results: In the TCGA analysis, we identified the most commonly mutated genes in each lung cancer dataset, with differences among the three histotypes analyzed. NGS analysis revealed TP53, CSF1R, PIK3CA, FLT3, ERBB4, and KDR as being the genes most frequently mutated. We validated the c.1621A>C mutation in KIT. The correlation analysis indicated negative correlation between adenocarcinoma and altered PIK3CA (r = −0.50918; p = 0.0029). TCGA survival analysis indicated that NRAS and IDH2 (LUAD), STK11 and TP53 (LUSC), and T53 (SCLC) alterations are correlated with the survival of patients. Conclusions: The study revealed differences in the mutational landscape of lung cancer histotypes.

19.
Pharmgenomics Pers Med ; 15: 177-193, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35300057

RESUMO

Prostate cancer biology is complex, and needs to be deciphered. The latest evidence reveals the significant role of non-coding RNAs, particularly microRNAs (miRNAs), as key regulatory factors in cancer. Therefore, the identification of altered miRNA patterns involved in prostate cancer will allow them to be used for development of novel diagnostic and prognostic biomarkers. PATIENTS AND METHODS: We performed a miRNAs transcriptomic analysis, using microarray (10 matched pairs tumor tissue versus normal adjacent tissue, selected based on inclusion criteria), followed by overlapping with TCGA data. A total of 292 miRNAs were differentially expressed, with 125 upregulated and 167 downregulated in TCGA patients' cohort with PRAD (prostate adenocarcinoma), respectively for the microarray experiments; 16 upregulated and 44 downregulated miRNAs were found in our cohort. To confirm our results obtained for tumor tissue, we performed validation with qRT-PCR at the tissue and plasma level of two selected transcripts, and finally, we focused on the identification of altered miRNAs involved in key biological processes. RESULTS: A common signature identified a panel of 12 upregulated and 1 downregulated miRNA, targeting and interconnected in a network with the TP53, AGO2, BIRC5 gene and EGFR as a core element. Among this signature, the overexpressed transcripts (miR-20b-5p, miR-96-5p, miR-183-5p) and the downregulated miR-542-5p were validated by qRT-PCR in an additional patients' cohort of 34 matched tumor and normal adjacent paired samples. Further, we performed the validation of the expression level for miR-20b-5p, miR-96-5p, miR-183-5p plasma, on the same patients' cohort versus a healthy control group, confirming the overexpression of these transcripts in the PRAD group, demonstrating the liquid biopsy as a potential investigational tool in prostate cancer. CONCLUSION: In this pilot study, we provide evidence on miRNA dysregulation and its association with key functional components of the PRAD landscape, where an important role is acted by miR-20b-5p, miR-542-5p, or the oncogenic cluster miR-183-96-182.

20.
Genes (Basel) ; 12(12)2021 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-34946878

RESUMO

Non melanoma skin cancer (NMSC) is one of the most common types of skin cancer. It has a number of subtypes, which include basal cell carcinoma, cutaneous squamous cell carcinoma and Merkel cell carcinoma. MicroRNAs are short, non-coding RNA (ribonucleic acid) molecules, capable of regulating gene expression at a post transcriptional level. They play a pivotal role in a variety of physiologic cellular functions and pathologies, including malignant diseases. The development of miRNAs represents an important study field, which has been extensively exploited in melanoma for almost a decade with promising results, therefore we consider it a stepstone for further research projects also in non-melanoma skin cancers. The aim of our study was to explore the current literature in order to present the role of the different miRNAs in some of the most frequent types of NMSC pertaining to oncogenesis, evolution and therapy. The most relevant and accurate available data from the literature were evaluated. Our study concluded that there are almost 100 miRNAs which can be upregulated or downregulated and can play a role in oncogenesis. They can be easily identified in circulation, are stable and they can be important diagnosis/prognosis and therapy monitoring markers.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/prevenção & controle , Biomarcadores Tumorais/genética , Carcinogênese/genética , Carcinoma Basocelular/genética , Carcinoma de Célula de Merkel/genética , Carcinoma de Células Escamosas/genética , Progressão da Doença , Humanos , RNA Neoplásico
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