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1.
Med Pharm Rep ; 97(2): 132-142, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38746025

RESUMEN

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.
Med Pharm Rep ; 97(2): 184-195, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38746032

RESUMEN

Background and aims: The carcinogenic effect of arsenic is a subject of controversy in relation to breast cancer. In our current research, we aimed to simulate the effects of chronic low-level arsenic exposure on breast cells by intoxicating MCF-10A and MCF-7 cells with 1 µM Arsenic trioxide (As2O3) for 3 weeks (3w) and 6 weeks (6w), respectively. Methods: We assessed the cellular responses to As2O3 through various assays, including confocal fluorescence microscopy, flow cytometry for cell cycle analysis, Transwell invasion assay, scratch assay, and colony assay. Additionally, we analyzed the mutation burden in all the exposed cells by using the next generation sequencing technology. Results: Our findings indicate that As2O3 has a minor carcinogenic effect in normal cells, with no definitive evidence of malignant transformation observed after 6 weeks of exposure. In the case of breast cancer cells, As2O3 exhibits a dual effect, both inhibitory and stimulatory. It leads to reduced colony formation ability at 6 weeks, while enhancing the cells' ability for invasion. The mutations triggered by As2O3 exposure are distributed across genes with both tumor-suppressive and oncogenic functions. Five mutations are common to both cell lines, involving the following genes: Kinase Insert Domain Receptor (KDR) (c.798+54G>A), Colony Stimulating Factor 1 Receptor (CSF1R) (c.*37AC>C, c.*35C>TC), SWI/SNF-Related Matrix-Associated Actin-Dependent Regulator of Chromatin Subfamily B Member 1 (SMARCB1) (c.1119-41C>T), and Fms-like Tyrosine Kinase 3 (FLT3) (c.1310-3T>C). Additionally, Human Epidermal Growth Factor Receptor 4 (ERBB4/HER4) (c.421+58A>G) and Human Epidermal Growth Factor Receptor 2 (HER2/ERBB2) (c.2307+46A>G) mutations were exclusively found in MCF-10A cells exposed to As2O3. Furthermore, MCF-7 cells exhibited unique mutations in the KIT Proto-Oncogene (KIT) (c.1594G>A) and TP53 (c.215C>G). Conclusion: In summary, our study reveals that a 6-weeks exposure to arsenic has a limited carcinogenic effect in normal breast cells and a dual role in breast cancer cells.

3.
Med Pharm Rep ; 97(2): 222-233, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38746034

RESUMEN

Maxillary lateral sinus floor elevation, or external sinus lift, is a widespread surgical intervention in the dental field. Insertion of implants in the posterior region of the maxilla often requires reconstruction of the remaining native bone that has insufficient volume. Background and aims: Much of the research published involves using artificial products, like xenografts and resorbable collagen membranes, after a prior Cone Beam Computer Tomography (CBCT) investigation. Nowadays, more accessible access, less financial costs, a biological approach, and faster healing are objectives that surround this procedure. Leucocytes and platelets rich in Fibrin (L-PRF) are a natural component with a high concentration of growth factors. Due to its regenerative properties and lack of complications, it is used in several medical fields, like orthopedics, dermatology, and oral surgery. This retrospective study aims to compare results in bone height and volume obtained through external sinus lift, either by using xenografts or autologous plasma rich in fibrin, by evaluating the quantity of new bone formation from a radiological point of view. Methods: Fifty-eight Caucasian patients were included in this retrospective study; 48 were submitted to xenograft procedure, and 10 were selected for L-PRF grafting material with simultaneous implant placement. Lack of clinical and histological studies performed on patients with L-PRF surgeries limited us in choosing a larger group for the radiological analysis. CBCT evaluation was performed before surgery and 6 months after. All patients selected for the study presented good general and oral health, acute oral and sinus infections excluded; smoking and periodontal disease were also criteria of exclusion. Two operators performed the measurements in pre-established landmarks in different time frames. The two independent groups were compared with the Wilcoxon rank-sum test for quantitative data. Qualitative characteristics were described as counts and percentages. All analyses were performed in an R environment for statistical computing and graphics. Results: Mean bone height gain in the xenograft group in the regions was as follows: 7.44 for the anterior landmark, 12.14 for the median and 8.28 for the distal. The mean group height gained for the L-PRF group was 0.1 anteriorly, -0.18 for the median measurement, and 0.23 distally. We obtained excellent overall reliability for all the height measurements between the two operators. Conclusions: Further studies must be conducted to establish new sets of surgical protocols in case L-PRF alone is found to be a reliable, stable, biological alternative to the well-documented xenografts in external sinus lifts. Radiological results, although promising, must be further applied in long term clinical survival of the implants in the grafted sites. Also, studies combining L-PRF in conjunction with xenograft might bring improved clinical results in terms of reduced postoperative complications and accelerated healing.

4.
Transl Oncol ; 44: 101951, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38564933

RESUMEN

Lung cancer remains one of the leading causes of cancer-related deaths worldwide. It is classified into two main histological groups: non-small cell lung cancer (NSCLC) and small cell lung cancer. Improving the outcome of cancer patients could be possible by enhancing the early diagnosis. In the current study, we evaluated the levels of three microRNAs - miR-21-5p, miR-155-5p, and miR-181a-5p in tumor (TT) vs adjacent normal tissue (NT), as well as their expression levels in plasma and extracellular vesicles (EVs) from plasma in lung squamous cell carcinoma (LUSC) male patients vs healthy individuals as means to identify a panel of miRNAs that could serve as novel biomarkers for the diagnosis of LUSC in male patients. Matched paired tissue samples from male LUSC (n=40) patients were used for miRNA expression analysis. MiR-21-5p and miR-155-5p in tumor tissue were overexpressed, while underexpression of miR-181a-5p was observed in LUSC TT vs NT. These results were further validated in the TCGA LUSC dataset, considering 279 male samples. These alterations of miR-21-5p, miR-181a-5p, and miR-155-5p in tumor tissue are also present in plasma and plasma extracellular vesicles in LUSC male patients. In addition, ROC curves were performed to assess the sensitivity and specificity of different combinations of these miRNAs, confirming a high diagnostic accuracy for LUSC of up to 88 % in male subjects. The expression levels in tissue samples and the abundance in plasma and plasma EVs of the three miRNAs combined - miR-21-5p, miR-155-5p and miR-181a-5p - could be considered for further studies on biomarkers for the early detection of LUSC in male subjects.

5.
Int J Mol Sci ; 25(6)2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38542322

RESUMEN

Previous studies have shown that inorganic arsenic (iAs) exposure may be associated with genotoxic and cytotoxic effects. The aim of this study was to evaluate the relationship between several polymorphisms in AS3MT and APOE genes and urinary As and the relationship between these polymorphisms and pregnancy loss. We determined urinary As concentrations and performed genotyping analysis in 50 cases of spontaneous pregnancy loss and 50 controls, matched to cases on gestational age. The most frequently identified AS3MT polymorphisms in both cases and controls were in rs10748835 (80% cases and 68% controls), rs3740400 (78% cases and 64% controls), rs7085104 (74% cases and 48% controls), and rs1046778 (62% cases and 54% controls). We identified 30 different haplotypes in AS3MT SNPs, with four predominant haplotypes (>8%). Cases with Haplotype 1 had four-fold higher urinary DMA and two-fold higher MMA concentration than those without this haplotype, the MMA levels were lower in cases and controls with Haplotype 4 compared to Haplotype 1, and the DMA levels were significantly lower in cases with Haplotype 4 compared to Haplotype 3. Cases with Haplotype 1 had higher levels of all analyzed biomarkers, suggesting that Haplotype 1 may be associated with greater exposure to iAs and tobacco smoke. Our results suggest the importance of the AS3MT gene in iAs metabolism among pregnant women with low-level drinking water iAs exposure.


Asunto(s)
Aborto Espontáneo , Arsénico , Arsenicales , Agua Potable , Humanos , Femenino , Embarazo , Arsénico/toxicidad , Arsénico/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , Mujeres Embarazadas , Rumanía , Polimorfismo de Nucleótido Simple , Apolipoproteínas E/genética
7.
Food Chem Toxicol ; 186: 114523, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38382870

RESUMEN

The carcinogenic role of cadmium (Cd2+) in breast cancer is still debatable. Current data points to duration of exposure as the most important element. In our study, we designed an in vitro model to investigate the effects of 3 weeks versus 6 weeks of low-level CdCl2 exposure on MCF10A cells. Our results demonstrated that after 3 weeks of CdCl2 exposure the cells displayed significant changes in the DNA integrity, but there was no development of malignant features. Interestingly, after 6 weeks of exposure, the cells significantly increased their invasion, migration and colony formation capacities. Additionally, MCF10A cells exposed for 6 weeks to CdCl2 had many dysregulated genes (4905 up-regulated and 4262 down-regulated). As follows, Cd-induced phenotypical changes are accompanied by a profound modification of the transcriptomic landscape. Furthermore, the molecular alterations driving carcinogenesis in MCF10A cells exposed to CdCl2 were found to be influenced by the duration of exposure, as in the case of MEG8. This long non-coding RNA was down-regulated at 3 weeks, but up-regulated at 6 weeks of exposure. In conclusion, even very low levels of Cd (0.5 µM) can have significant carcinogenic effects on breast cells in the case of subchronic exposure.


Asunto(s)
Neoplasias de la Mama , Cadmio , Humanos , Femenino , Cadmio/toxicidad , Células Epiteliales , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Carcinógenos/toxicidad , Perfilación de la Expresión Génica , Cloruro de Cadmio/toxicidad
8.
Cancers (Basel) ; 16(4)2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38398137

RESUMEN

This research investigated the serum levels of three interleukins (IL8, IL17A, and IL33) and the possible relationships between them in healthy people and colon cancer patients at different stages. This study involved 82 participants, 42 of whom had colon cancer and 40 were healthy individuals. The cancer patients were classified into four groups according to the TNM staging classification of colon and rectal cancer. Serum levels of the interleukins were measured by the ELISA test. The data were analyzed statistically to compare the demographic characteristics, the interleukin levels across cancer stages, and the correlation between interleukins in both groups. The results showed that women had more early-stage colon cancer diagnoses, while men had more advanced-stage cancer diagnoses. Stage two colon cancer was more common in older people. Younger people, men, and those with early-stage colon cancer had higher levels of interleukins. The levels of IL8 and IL17A were higher in the cancer group, while the level of IL33 was higher in the healthy group. There was a strong correlation between IL8 and IL17A levels in both groups (p = 0.001). IL17A influenced the level of IL33 in the cancer group (p = 0.007). This study suggested that cytokine variation profiles could be useful for detecting colon cancer and predicting its outcome.

9.
Stem Cell Rev Rep ; 20(3): 656-671, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38279054

RESUMEN

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.


Asunto(s)
MicroARNs , ARN Circular , Humanos , ARN Circular/genética , ARN Circular/metabolismo , Osteogénesis/fisiología , MicroARNs/genética , MicroARNs/metabolismo , Diferenciación Celular/genética , Células Madre/metabolismo
10.
Biomedicines ; 12(1)2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38255241

RESUMEN

Recent research has revealed the importance of miRNAs in the diagnosis and clinical evolution of papillary thyroid cancer (PTC). We aim to identify a specific miRNA profile that could differentiate between specific subtypes of PTC. METHODS: In this cross-sectional study, total RNA was extracted from paraffin-embedded tissues of 43 patients, 17 with an infiltrative follicular variant of PTC (iFVPTC) and 26 with a conventional variant of PTC (cPTC). Nine miRNAs were evaluated using qRT-PCR technology and specific miRNA assays. RESULTS: We found specific patterns for cPTC and iFVPTC, such as miRNA altered in both types of tumours (miR-146b-5p, miR-181a-5p, miR-221-3p, miR-21-5p and miR-222-3p) and two miRNAs significantly expressed only in cPTC (miR-20b-5p, miR-21-5p). The iFVPTC group presented strong and moderate correlations between miRNA expression and clinical data. miR-221-3p, miR-195-5p, miR-181-5p, miR-146b-5p and miR-222 were correlated with age, tumour size (TS) or lymph node metastases (N), while only miR-20b-5p, miR-195-5p and miR-181-5p were correlated with TS, N and age in the cPTC group. CONCLUSIONS: The present study allowed the identification of a signature of two miRNAs to confirm miRNA differences between the two histological subtypes of TC. Our results provide advances in the molecular diagnosis of TC and could help to improve the diagnostic performance of already existing molecular classifiers.

11.
Am J Rhinol Allergy ; 38(2): 92-101, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38192070

RESUMEN

BACKGROUND: Despite advances in surgical techniques, recurrence rates after endoscopic sinus surgery (ESS) for chronic rhinosinusitis with nasal polyps (CRSwNP) remain high and difficult to predict. OBJECTIVE: This study aimed to evaluate the potential role of microRNA 125b (miR-125b) in predicting disease evolution following ESS. METHODS: We conducted a prospective study including patients undergoing first ESS for CRSwNP in our department between January 2020 and November 2021. We determined miR-125b levels from nasal polyps and pursued a standardized follow-up for at least 18 months for each patient. RESULTS: A total of 86 patients were included in the study. Higher postoperative endoscopy scores were associated with more severe disease at presentation on computed tomography scan, presence of concomitant asthma, and higher values of miR-125b. Even after multivariate repeated measures analysis and adjustments for confounders, miR-125b remained statistically significant. Moreover, miR-125 was the most important factor in predicting disease evolution at 18 months. CONCLUSION: A clear, robust relation between nasal polyp control evaluated through objective measures and miR-125b values was observed. This finding indicates the potential role of miR-125b in predicting the course of the disease following ESS.


Asunto(s)
MicroARNs , Pólipos Nasales , Rinitis , Rinosinusitis , Sinusitis , Humanos , Pólipos Nasales/complicaciones , Estudios Prospectivos , Rinitis/cirugía , Sinusitis/cirugía , Endoscopía/métodos , Enfermedad Crónica , Resultado del Tratamiento
12.
Biomol Biomed ; 24(1): 125-137, 2024 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-37622179

RESUMEN

Clinical application of chemotherapy in lung cancer is constrained by side effects, notably cardiotoxicity, the mechanisms of which remain elusive. This study assessed the potential of specific miRNAs as biomarkers for chemotherapy-induced cardiotoxicity in lung cancer. We employed two lung adenocarcinoma cell lines (Calu6 and H1792) and ventricular normal human cardiac fibroblasts (NHCF-V) in single and co-culture experiments. Functional tests were conducted using 100 µM carboplatin and 1µM vinorelbine doses. The effects of carboplatin and vinorelbine, both individually and in combination, were evaluated at cellular and molecular levels 48h post-therapy for both mono- and co-cultures. miR-205-5p, miR-21-5p, and miR-30a-5p, modulated by anticancer treatments and influencing cardiotoxicity, were analyzed. Vinorelbine and carboplatin treatment promoted apoptosis and autophagy in lung cancer cells and cardiac fibroblasts more than in controls. Western blot analyses revealed BCL2 and p53 protein upregulation. Using qRT-PCR, we investigated the expression dynamics of miR-21-5p, miR-30c-5p, and miR-205-5p in co-cultured cardiomyocytes and lung cancer cells, revealing altered miRNA patterns from vinorelbine and carboplatin treatment. Our findings underscore the intricate relationship between chemotherapy, miRNA regulation, and cardiotoxicity, highlighting the importance of cardiac health in lung cancer treatment decisions.


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , Humanos , Cardiotoxicidad/genética , Técnicas de Cocultivo , Vinorelbina , Carboplatino/efectos adversos , Regulación Neoplásica de la Expresión Génica , Carcinoma de Pulmón de Células no Pequeñas/genética , MicroARNs/genética , Neoplasias Pulmonares/tratamiento farmacológico , Antineoplásicos/efectos adversos
13.
Stem Cell Rev Rep ; 20(1): 206-217, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37922107

RESUMEN

Strategies to improve hematopoietic stem and progenitor cell (HSPC) mobilization from the bone marrow can have a pivotal role in addressing iatrogenic bone-marrow insufficiency from chemo(radio)therapy and overcoming peripheral blood stem cell transplantation (PBSCT) limitations such as insufficient mobilization. Granulocyte-colony stimulating factor (G-CSF) represents the standard mobilization strategy for HSPC and has done so for more than three decades since its FDA approval. Its association with non-G-CSF agents is often employed for difficult HSPC mobilization. However, obtaining a synergistic effect between the two classes is limited by different timing and mechanisms of action. Based on our previous in vitro results, we tested the mobilization potential of human chorionic gonadotropin (HCG), alone and in combination with G-CSF in vivo in a murine study. Our results show an improved mobilization capability of the combination, which seems to act synergistically in stimulating hematopoiesis. With the current understanding of the dynamics of HSPCs and their origins in more primitive cells related to the germline, new strategies to employ the mobilization of hematopoietic progenitors using chorionic gonadotropins could soon become clinical practice.


Asunto(s)
Trasplante de Células Madre de Sangre Periférica , Humanos , Animales , Ratones , Factor Estimulante de Colonias de Granulocitos/farmacología , Modelos Animales de Enfermedad , Células Madre Hematopoyéticas/metabolismo , Gonadotropina Coriónica/farmacología
14.
Vet J ; 303: 106055, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38097103

RESUMEN

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.


Asunto(s)
Neoplasias de la Mama , Enfermedades de los Perros , Neoplasias Mamarias Animales , Humanos , Animales , Perros , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/veterinaria , Neoplasias Mamarias Animales/metabolismo , Transcriptoma , Carcinogénesis , Modelos Animales , Enfermedades de los Perros/genética , Enfermedades de los Perros/metabolismo
15.
Biomedicines ; 11(12)2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38137519

RESUMEN

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.

16.
J Clin Med ; 12(24)2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38137606

RESUMEN

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a disease of real interest for researchers due to its heterogenicity and complex pathophysiological mechanisms. Identification of the factors that ensure success after treatment represents one of the main challenges in CRSwNP research. No consensus in this direction has been reached so far. Biomarkers for poor outcomes have been noted, but nonetheless, their prognostic value has not been extensively investigated, and needs to be sought. We aimed to evaluate the correlation between potential prognostic predictors for recalcitrant disease in patients with CRSwNP. METHODS: The study group consisted of CRSwNP patients who underwent surgical treatment and nasal polyp (NP) tissue sampling. The preoperative workup included Lund-Mackay assessment, nasal endoscopy, eosinophil blood count, asthma, and environmental allergy questionnaire. Postoperatively, in subjects with poor outcomes, imagistic osteitis severity was evaluated, and IL-33 expression was measured. RESULTS: IL-33 expression in NP was positively and significantly correlated with postoperative osteitis on CT scans (p = 0.01). Furthermore, high osteitis CT scores were related to high blood eosinophilia (p = 0.01). A positive strong correlation was found between postoperative osteitis and the Lund-Mackay preoperative score (p = 0.01), as well as the nasal endoscopy score (p = 0.01). CONCLUSIONS: Our research analyzed the levels of polyp IL-33, relative to blood eosinophilia, overall disease severity score, and osteitis severity, in patients with CRSwNP. These variables are prognostic predictors for poor outcomes and recalcitrant disease. Considering the importance of bone involvement in CRSwNP, this research aims to provide a better insight into the correlations of osteitis with clinical and biological factors.

17.
Int J Mol Sci ; 24(22)2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-38003512

RESUMEN

Glioblastoma (GBM) is a primary brain tumor arising from glial cells. The tumor is highly aggressive, the reason for which it has become the deadliest brain tumor type with the poorest prognosis. Like other cancers, it compromises molecular alteration on genetic and epigenetic levels. Epigenetics refers to changes in gene expression or cellular phenotype without the occurrence of any genetic mutations or DNA sequence alterations in the driver tumor-related genes. These epigenetic changes are reversible, making them convenient targets in cancer therapy. Therefore, we aim to review critical epigenetic dysregulation processes in glioblastoma. We will highlight the significant affected tumor-related pathways and their outcomes, such as regulation of cell cycle progression, cell growth, apoptosis, angiogenesis, cell invasiveness, immune evasion, or acquirement of drug resistance. Examples of molecular changes induced by epigenetic modifications, such as DNA epigenetic alterations, histone post-translational modifications (PTMs), and non-coding RNA (ncRNA) regulation, are highlighted. As understanding the role of epigenetic regulators and underlying molecular mechanisms in the overall pro-tumorigenic landscape of glioblastoma is essential, this literature study will provide valuable insights for establishing the prognostic or diagnostic value of various non-coding transcripts, including miRNAs.


Asunto(s)
Glioblastoma , MicroARNs , Humanos , Glioblastoma/metabolismo , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , Epigénesis Genética
18.
Med Pharm Rep ; 96(4): 384-391, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37970196

RESUMEN

Background and aims: Prostate adenocarcinoma (PRAD) is a complex disease that can be driven by alterations in both coding and noncoding genes. Recent research has identified coding and non-coding genes that are considered to play important roles in prostate cancer evolution and which may be used as biomarkers for disease diagnosis, prognosis, and treatment. TP53 is a critical hub gene in prostate cancer. Advanced studies have demonstrated the crosstalk between coding and non-coding RNAs, particularly microRNAs (miRNAs). Methods: In this study, we investigated the roundabout of TP53 and their regulatory miRNAs (miR-15a-5p, miR-34a-5p, and miR-141-3p) based on the TCGA data set. We validated an additional patient cohort of 28 matched samples of patients with PRAD at tissue and plasma level. Results: Therefore, using the UALCAN online database, we evaluated the expression level in PRAD of these genes revealing overexpression of TP53. qRT-PCR validation step endorsed the expression level for these genes. Additionally, we evaluated the expression level of the four key miRNAs (miR-15a-5p, miR-34a-5p, and miR-141-3p) interconnected as a network at tissue and plasma levels. Conclusions: Through these results, we demonstrated the essential function of TP53 and its associated miRNAs that play a significant role in tumor control, highlighting miRNAs' potential as future therapeutic targets and biomarkers with important implications in managing prostate cancer.

19.
Med Pharm Rep ; 96(4): 392-399, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37970200

RESUMEN

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.

20.
Vet Sci ; 10(11)2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37999477

RESUMEN

Canine mammary tumors represent one of the leading malignant pathologies in female dogs, displaying the importance of efficient therapeutic findings, besides the golden-standard surgery, able to limit the development of the disease. Studies in human cancers demonstrated that Doxorubicin presents a good effect in different biological processes like apoptosis, autophagy, the cell cycle, cell invasion, and the epithelial-to-mesenchymal transition. This study followed the effects of Doxorubicin on two canine mammary cancer cell lines P114 and CMT-U27. Doxorubicin treatment in both cell lines shows an inhibitory effect in cell proliferation and an alteration in expression of the EMT-related genes. The obtained results provide valuable information for revealing the link between Doxorubicin, phenotypic changes, and proliferation dynamics in canine mammary tumor models.

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