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1.
Int J Mol Sci ; 22(21)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34769212

RESUMO

Brain tumors are particularly aggressive and represent a significant cause of morbidity and mortality in adults and children, affecting the global population and being responsible for 2.6% of all cancer deaths (as well as 30% of those in children and 20% in young adults). The blood-brain barrier (BBB) excludes almost 100% of the drugs targeting brain neoplasms, representing one of the most significant challenges to current brain cancer therapy. In the last decades, carbon dots have increasingly played the role of drug delivery systems with theranostic applications against cancer, thanks to their bright photoluminescence, solubility in bodily fluids, chemical stability, and biocompatibility. After a summary outlining brain tumors and the current drug delivery strategies devised in their therapeutic management, this review explores the most recent literature about the advances and open challenges in the employment of carbon dots as both diagnostic and therapeutic agents in the treatment of brain cancers, together with the strategies devised to allow them to cross the BBB effectively.

2.
Int J Mol Sci ; 22(19)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34639030

RESUMO

During the cell cycle, DNA suffers several lesions that need to be repaired prior to entry into mitosis to preserve genome integrity in daughter cells. Toward this aim, cells have developed complex enzymatic machinery, the so-called DNA damage response (DDR), which is able to repair DNA, temporarily stopping the cell cycle to provide more time to repair, or if the damage is too severe, inducing apoptosis. This DDR mechanism is considered the main source of resistance to DNA-damaging therapeutic treatments in oncology. Recently, cancer stem cells (CSCs), which are a small subset of tumor cells, were identified as tumor-initiating cells. CSCs possess self-renewal potential and persistent tumorigenic capacity, allowing for tumor re-growth and relapse. Compared with cancer cells, CSCs are more resistant to therapeutic treatments. Wee1 is the principal gatekeeper for both G2/M and S-phase checkpoints, where it plays a key role in cell cycle regulation and DNA damage repair. From this perspective, Wee1 inhibition might increase the effectiveness of DNA-damaging treatments, such as radiotherapy, forcing tumor cells and CSCs to enter into mitosis, even with damaged DNA, leading to mitotic catastrophe and subsequent cell death.


Assuntos
Biomarcadores Tumorais , Proteínas de Ciclo Celular/genética , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas Tirosina Quinases/genética , Tolerância a Radiação/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/metabolismo , Terapia Combinada , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Terapia de Alvo Molecular , Família Multigênica , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Especificidade de Órgãos/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/metabolismo
3.
Cancers (Basel) ; 13(14)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34298658

RESUMO

Glioblastoma (GB) is the most aggressive tumor of the central nervous system (CNS), characterized by excessive proliferation, necrosis and invasiveness. The survival rate for patients with GB still remains low. Angiogenesis and apoptosis play a key role in the development of GB. Thus, the modulation of angiogenesis and apoptosis processes represent a possible strategy to counteract GB progression. This study aimed to investigate the potential effect of KYP-2047, an inhibitor of the prolyl-oligopeptidase (POP), known to modulate angiogenesis, in an in vivo U87-xenograft model and in an in vitro study on human GB cells. Our results showed that KYP-2047 at doses of 2.5 mg/kg and 5 mg/kg was able to reduce tumor burden in the xenograft-model. Moreover, KYP-2047 significantly reduced vascular endothelial-growth-factor (VEGF), angiopoietins (Ang) and endothelial-nitric-oxide synthase (eNOS) expression. In vitro study revealed that KYP-2047 at different concentrations reduced GB cells' viability. Additionally, KYP-2047 at the concentrations of 50 µM and 100 µM was able to increase the pro-apoptotic protein Bax, p53 and caspase-3 expression whereas Bcl-2 expression was reduced. Thus, KYP-2047 could represent a potential therapeutic treatment to counteract or reduce GB progression, thanks its abilities to modulate angiogenesis and apoptosis pathways.

4.
Cancers (Basel) ; 13(9)2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33919096

RESUMO

Carbon Dots (CDs) are the latest members of carbon-based nanomaterials, which since their discovery have attracted notable attention due to their chemical and mechanical properties, brilliant fluorescence, high photostability, and good biocompatibility. Together with the ease and affordable preparation costs, these intrinsic features make CDs the most promising nanomaterials for multiple applications in the biological field, such as bioimaging, biotherapy, and gene/drug delivery. This review will illustrate the most recent applications of CDs in the biomedical field, focusing on their biocompatibility, fluorescence, low cytotoxicity, cellular uptake, and theranostic properties to highlight above all their usefulness as a promising tool for cancer diagnosis and therapy.

5.
Thorac Cancer ; 12(9): 1489-1492, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33811459

RESUMO

The presence of calcified or inflammatory lymph nodes between the target bronchus and pulmonary artery is a huge challenge when performing thoracoscopic lobectomy as it may frequently result in tearing of the vessel, and massive bleeding. Herein, we describe a simple strategy in which thoracoscopic lobectomy was safely completed in similar cases. After fissure dissection, the target pulmonary artery was exposed by more than two-thirds of its circumference. A needle was passed across the nodes and the target vessel was closed with a proximal and distal suture. After dissection of lymphadenopathies, the target bronchus was exposed, and stapled. This strategy was applied with success to complete right lower lobectomies for cancer in three patients. No complications occurred during the operation. Only one patient had persistent air leaks that spontaneously ceased 11 days later. Final pathology showed pN0 disease in all cases.

6.
Thorac Cancer ; 12(5): 567-579, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33544445

RESUMO

Thoracoscopic lobectomy has become the preferred approach for surgical management of early stage lung cancer, but the potential higher operative costs limit its widespread use. Theoretically, higher direct costs may be significantly counterbalanced by lower indirect costs, resulting in lower overall costs for thoracoscopic than for open lobectomy. To support this hypothesis, we reviewed the literature until May 2020, analyzing all papers comparing the cost of thoracoscopic versus open lobectomy.A total of 20 studies provided the most applicable evidence to evaluate this issue. In all the studies apart from one, thoracoscopic lobectomy was associated with higher operative costs due to the increased use of disposable instruments, and prolonged operative time. By contrast, in 17 studies the increased operative costs were significantly offset by indirect costs which were lower in thoracoscopic than in open lobectomy due to fewer postoperative complications, faster recovery, and lower readmission rates. It translated into lower overall costs for thoracoscopic than for open lobectomy in 10 studies, similar costs in seven, and higher in three, despite the lower hospitalization costs. The low bed fees and high prices of disposable instruments in these three studies may explain the discordance. The careful use of disposable instruments, and the minimizing hospitalization costs can reduce the total costs of thoracoscopic lobectomy to levels similar or to below those of open lobectomy. The worry that video-assisted thoracoscopic surgery lobectomy (VATSL) might be associated with an increased overal cost is thus not warranted, and should not be used as an excuse against the use of VATS in surgery for early stage lung cancers.


Assuntos
Custos Hospitalares/tendências , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida/métodos , Feminino , Humanos , Masculino
7.
Cancers (Basel) ; 12(12)2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33297488

RESUMO

Neo-adjuvant radiotherapy is frequently employed in the therapeutic management of locally advanced rectal cancer (LARC). Radiotherapy can both reduce local recurrence and improve the success of surgical procedures by reducing tumor mass size. However, some patients show a poor response to treatment, which results in primary resistance or relapse after apparent curative surgery. In this work, we report in vitro and in vivo models based on patient-derived cancer stem cells (CSCs); these models are able to predict individual responses to radiotherapy in LARC. CSCs isolated from colorectal cancer biopsies were subjected to in vitro irradiation with the same clinical protocol used for LARC patients. Animal models, generated by CSC xenotransplantation, were also obtained and treated with the same radiotherapy protocol. The results indicate that CSCs isolated from rectal cancer needle biopsies possess an intrinsic grade of sensitivity to treatment, which is also maintained in the animal model. Notably, the specific CSCs' in vitro and in vivo sensitivity values correspond to patients' responses to radiotherapy. This evidence suggests that an in vitro radiotherapy response predictivity assay could support clinical decisions for the management of LARC patients, thus avoiding radiation toxicity to resistant patients and reducing the treatment costs.

8.
Regen Biomater ; 7(5): 461-469, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33149935

RESUMO

Nanotechnology plays a key role in the development of innovative scaffolds for bone tissue engineering (BTE) allowing the incorporation of nanomaterials able to improve cell proliferation and differentiation. In this study, Mg-HA-Coll type I scaffolds (Mg-HA-based scaffolds) were nanofunctionalized with gold nanorods (Au NRs), palladium nanoparticles (Pd NPs) and maghemite nanoparticles (MAG NPs). Nanofunctionalized Mg-HA-based scaffolds (NF-HA-Ss) were tested for their ability to promote both the proliferation and the differentiation of adipose-derived mesenchymal stem cells (hADSCs). Results clearly highlight that MAG nanofunctionalization substantially improves cell proliferation up to 70% compared with the control (Mg-HA-based scaffold), whereas both Au NRs and Pd NPs nanofunctionalization induce a cell growth inhibition of 94% and 89%, respectively. Similar evidences were found for the osteoinductive properties showing relevant calcium deposits (25% higher than the control) for MAG nanofunctionalization, while a decreasing of cell differentiation (20% lower than the control) for both Au NRs and Pd NPs derivatization. These results are in agreement with previous studies that found cytotoxic effects for both Pd NPs and Au NRs. The excellent improvement of both osteoconductivity and osteoinductivity of the MAG NF-HA-S could be attributed to the high intrinsic magnetic field of superparamagnetic MAG NPs. These findings may pave the way for the development of innovative nanostructured scaffolds for BTE.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32982967

RESUMO

Thyroid tumors are extremely heterogeneous varying from almost benign tumors with good prognosis as papillary or follicular tumors, to the undifferentiated ones with severe prognosis. Recently, several models of thyroid carcinogenesis have been described, mostly hypothesizing a major role of the thyroid cancer stem cell (TCSC) population in both cancer initiation and metastasis formation. However, the cellular origin of TCSC is still incompletely understood. Here, we review the principal epigenetic mechanisms relevant to TCSC origin and maintenance in both well-differentiated and anaplastic thyroid tumors. Specifically, we describe the alterations in DNA methylation, histone modifiers, and microRNAs (miRNAs) involved in TCSC survival, focusing on the potential of targeting aberrant epigenetic modifications for developing novel therapeutic approaches. Moreover, we discuss the bidirectional relationship between TCSCs and immune cells. The cells of innate and adaptive response can promote the TCSC-driven tumorigenesis, and conversely, TCSCs may favor the expansion of immune cells with protumorigenic functions. Finally, we evaluate the role of the tumor microenvironment and the complex cross-talk of chemokines, hormones, and cytokines in regulating thyroid tumor initiation, progression, and therapy refractoriness. The re-education of the stromal cells can be an effective strategy to fight thyroid cancer. Dissecting the genetic and epigenetic landscape of TCSCs and their interactions with tumor microenvironment cells is urgently needed to select more appropriate treatment and improve the outcome of patients affected by advanced differentiated and undifferentiated thyroid cancers.


Assuntos
Metástase Neoplásica/patologia , Células-Tronco Neoplásicas/patologia , Neoplasias da Glândula Tireoide/patologia , Metilação de DNA , Histonas/genética , Histonas/metabolismo , Humanos , MicroRNAs/genética , Metástase Neoplásica/genética , Células-Tronco Neoplásicas/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Microambiente Tumoral
10.
Cancers (Basel) ; 12(8)2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32707760

RESUMO

Multiple myeloma (MM) is a B-cell malignancy requiring inflammatory microenvironment signals for cell survival and proliferation. Despite improvements in pharmacological tools, MM remains incurable mainly because of drug resistance. The present study aimed to investigate the implication of Toll-like receptor 4 (TLR4) as the potential mechanism of bortezomib (BTZ) resistance. We found that TLR4 activation induced mitochondrial biogenesis and increased mitochondrial mass in human MM cell lines. Moreover, TLR4 signaling was activated after BTZ exposure and was increased in BTZ-resistant U266 (U266-R) cells. A combination of BTZ with TAK-242, a selective TLR4 inhibitor, overcame drug resistance through the generation of higher and extended oxidative stress, strong mitochondrial depolarization and severe impairment of mitochondrial fitness which in turn caused cell energy crisis and activated mitophagy and apoptosis. We further confirmed the efficacy of a TAK-242/BTZ combination in plasma cells from refractory myeloma patients. Consistently, inhibition of TLR4 increased BTZ-induced mitochondrial depolarization, restoring pharmacological response. Taken together, these findings indicate that TLR4 signaling acts as a stress-responsive mechanism protecting mitochondria during BTZ exposure, sustaining mitochondrial metabolism and promoting drug resistance. Inhibition of TLR4 could be therefore be a possible target in patients with refractory MM to overcome BTZ resistance.

11.
Cancers (Basel) ; 12(6)2020 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-32486505

RESUMO

Although improvement in early diagnosis and treatment ameliorated life expectancy of cancer patients, metastatic disease still lacks effective therapeutic approaches. Resistance to anticancer therapies stems from the refractoriness of a subpopulation of cancer cells-termed cancer stem cells (CSCs)-which is endowed with tumor initiation and metastasis formation potential. CSCs are heterogeneous and diverge by phenotypic, functional and metabolic perspectives. Intrinsic as well as extrinsic stimuli dictated by the tumor microenvironment (TME)have critical roles in determining cell metabolic reprogramming from glycolytic toward an oxidative phenotype and vice versa, allowing cancer cells to thrive in adverse milieus. Crosstalk between cancer cells and the surrounding microenvironment occurs through the interchange of metabolites, miRNAs and exosomes that drive cancer cells metabolic adaptation. Herein, we identify the metabolic nodes of CSCs and discuss the latest advances in targeting metabolic demands of both CSCs and stromal cells with the scope of improving current therapies and preventing cancer progression.

12.
Cells ; 9(2)2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32028592

RESUMO

Stem cell therapy and tissue engineering represent a promising approach for cartilage regeneration. However, they present limits in terms of mechanical properties and premature de-differentiation of engineered cartilage. Cycloastragenol (CAG), a triterpenoid saponin compound and a hydrolysis product of the main ingredient in Astragalus membranaceous, has been explored for cartilage regeneration. The aim of this study was to investigate CAG's ability to promote cell proliferation, maintain cells in their stable active phenotype, and support the production of cartilaginous extracellular matrix (ECM) in human adipose-derived mesenchymal stem cells (hAMSCs) in up to 28 days of three-dimensional (3D) chondrogenic culture. The hAMSC pellets were cultured in chondrogenic medium (CM) and in CM supplemented with CAG (CAG-CM) for 7, 14, 21, and 28 days. At each time-point, the pellets were harvested for histological (hematoxylin and eosin (H&E)), histochemical (Alcian-Blue) and immunohistochemical analysis (Type I, II, and X collagen, aggrecan, SOX9, lubricin). After excluding CAG's cytotoxicity (MTT Assay), improved cell condensation, higher glycosaminoglycans (sGAG) content, and increased cell proliferation have been detected in CAG-CM pellets until 28 days of culture. Overall, CAG improved the chondrogenic differentiation of hAMSCs, maintaining stable the active chondrocyte phenotype in up to 28 days of 3D in vitro chondrogenic culture. It is proposed that CAG might have a beneficial impact on cartilage regeneration approaches.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Sapogeninas/farmacologia , Agrecanas/metabolismo , Morte Celular/efeitos dos fármacos , Células Cultivadas , Colágeno/metabolismo , Feminino , Glicoproteínas/metabolismo , Glicosaminoglicanos/metabolismo , Humanos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Fatores de Transcrição SOX9/metabolismo , Fatores de Tempo
13.
J Nanobiotechnology ; 17(1): 119, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801555

RESUMO

The functional preservation of the central nervous system (CNS) is based on the neuronal plasticity and survival. In this context, the neuroinflammatory state plays a key role and involves the microglial cells, the CNS-resident macrophages. In order to better understand the microglial contribution to the neuroprotection, microglia-derived extracellular vesicles (EVs) were isolated and molecularly characterized to be then studied in neurite outgrowth assays. The EVs, mainly composed of exosomes and microparticles, are an important cell-to-cell communication process as they exhibit different types of mediators (proteins, lipids, nucleic acids) to recipient cells. The medicinal leech CNS was initially used as an interesting model of microglia/neuron crosstalk due to their easy collection for primary cultures. After the microglia-derived EV isolation following successive methods, we developed their large-scale and non-targeted proteomic analysis to (i) detect as many EV protein markers as possible, (ii) better understand the biologically active proteins in EVs and (iii) evaluate the resulting protein signatures in EV-activated neurons. The EV functional properties were also evaluated in neurite outgrowth assays on rat primary neurons and the RNAseq analysis of the microglia-derived EVs was performed to propose the most representative miRNAs in microglia-derived EVs. This strategy allowed validating the EV isolation, identify major biological pathways in EVs and corroborate the regenerative process in EV-activated neurons. In parallel, six different miRNAs were originally identified in microglia-derived EVs including 3 which were only known in plants until now. The analysis of the neuronal proteins under the microglial EV activation suggested possible miRNA-dependent regulation mechanisms. Taken together, this combination of methodologies showed the leech microglial EVs as neuroprotective cargos across species and contributed to propose original EV-associated miRNAs whose functions will have to be evaluated in the EV-dependent dialog between microglia and neurons.


Assuntos
Vesículas Extracelulares/genética , MicroRNAs/genética , Microglia/citologia , Animais , Fracionamento Celular , Células Cultivadas , Cromatografia em Gel , Sanguessugas/citologia , Sanguessugas/genética , Microglia/metabolismo , Neuroproteção , Ratos , Ratos Wistar , Transcriptoma , Ultracentrifugação
14.
Int J Surg Oncol ; 2019: 2715260, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737363

RESUMO

Background: Despite a large amount of data, the optimal surgical management of differentiated thyroid cancer remains controversial. Current guidelines recommend total thyroidectomy if primary thyroid cancer is >4 cm, while for tumors that are between 1 and 4 cm in size, either a bilateral or a unilateral thyroidectomy may be appropriate as surgical treatment. In general, total thyroidectomy would seem to be preferable because subtotal resection can be correlated with a higher risk of local recurrences and cervical lymph node metastases; on the other hand, total thyroidectomy is associated with more complications. Methods: This is a retrospective study conducted on 359 patients with differentiated thyroid cancer, subjected to total thyroidectomy. Our aim was to correlate clinical and pathological features (extrathyroid tumor growth, bilaterality, nodal and distant metastasis) with patient (gender and age) and tumor (size and histotype) characteristics. Moreover, we recorded postoperative complications, including hypoparathyroidism and laryngeal nerve damage. Results: In our study, we found a high occurrence of pathological features indicating cancer aggressiveness (bilaterality, nodal metastases, and extrathyroid invasion). On the other hand, total thyroidectomy was associated with relatively low postsurgical complication rates. Conclusions: Our data support the view that total thyroidectomy remains the first choice for the routine treatment of differentiated thyroid cancer.


Assuntos
Neoplasias da Glândula Tireoide/patologia , Tireoidectomia , Adenocarcinoma Folicular/patologia , Adenocarcinoma Folicular/cirurgia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Complicações Pós-Operatórias , Estudos Retrospectivos , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia
15.
Int J Mol Sci ; 20(9)2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31064152

RESUMO

A reduction in BCR-ABL1/ABL1IS transcript levels to <10% after 3 months or <1% after 6 months of tyrosine kinase inhibitor therapy are associated with superior clinical outcomes in chronic myeloid leukemia (CML) patients. In this study, we investigated the reliability of multiple BCR-ABL1 thresholds in predicting treatment outcomes for 184 subjects diagnosed with CML and treated with standard-dose imatinib mesylate (IM). With a median follow-up of 61 months, patients with concordant BCR-ABL1/ABL1IS transcripts below the defined thresholds (10% at 3 months and 1% at 6 months) displayed significantly superior rates of event-free survival (86.1% vs. 26.6%) and deep molecular response (≥ MR4; 71.5% vs. 16.1%) compared to individuals with BCR-ABL1/ABL1IS levels above these defined thresholds. We then analyzed the outcomes of subjects displaying discordant molecular transcripts at 3- and 6-month time points. Among these patients, those with BCR-ABL1/ABL1IS values >10% at 3 months but <1% at 6 months fared significantly better than individuals with BCR-ABL1/ABL1IS <10% at 3 months but >1% at 6 months (event-free survival 68.2% vs. 32.7%; p < 0.001). Likewise, subjects with BCR-ABL1/ABL1IS at 3 months >10% but <1% at 6 months showed a higher cumulative incidence of MR4 compared to patients with BCR-ABL1/ABL1IS <10% at 3 months but >1% at 6 months (75% vs. 18.2%; p < 0.001). Finally, lower BCR-ABL1/GUSIS transcripts at diagnosis were associated with BCR-ABL1/ABL1IS values <1% at 6 months (p < 0.001). Our data suggest that when assessing early molecular responses to therapy, the 6-month BCR-ABL1/ABL1IS level displays a superior prognostic value compared to the 3-month measurement in patients with discordant oncogenic transcripts at these two pivotal time points.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Proteínas de Fusão bcr-abl/genética , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Feminino , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Proteínas de Fusão bcr-abl/metabolismo , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Resultado do Tratamento
16.
Int J Mol Sci ; 20(5)2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30841521

RESUMO

The diagnostic approach to thyroid cancer is one of the most challenging issues in oncology of the endocrine system because of its high incidence (3.8% of all new cancer cases in the US) and the difficulty to distinguish benign from malignant non-functional thyroid nodules and establish the cervical lymph node involvement during staging. Routine diagnosis of thyroid nodules usually relies on a fine-needle aspirate biopsy, which is invasive and often inaccurate. Therefore, there is an urgent need to identify novel, accurate, and non-invasive diagnostic procedures. Liquid biopsy, as a non-invasive approach for the detection of diagnostic biomarkers for early tumor diagnosis, prognosis, and disease monitoring, may be of particular benefit in this context. Extracellular vesicles (EVs) are a consistent source of tumor-derived RNA due to their prevalence in circulating bodily fluids, the well-established isolation protocols, and the fact that RNA in phospholipid bilayer-enclosed vesicles is protected from blood-borne RNases. Recent results in other types of cancer, including our recent study on plasma EVs from glioblastoma patients suggest that information derived from analysis of EVs from peripheral blood plasma can be integrated in the routine diagnostic tumor approach. In this review, we will examine the diagnostic and prognostic potential of liquid biopsy to detect tumor-derived nucleic acids in circulating EVs from patients with thyroid carcinoma.


Assuntos
Biomarcadores Tumorais/metabolismo , Vesículas Extracelulares/patologia , Neoplasias da Glândula Tireoide/patologia , Vesículas Extracelulares/metabolismo , Humanos , Neoplasias da Glândula Tireoide/metabolismo
17.
Onco Targets Ther ; 12: 9571-9583, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32009794

RESUMO

Background: MicroRNAs (miRNAs) are endogenous, single-stranded, non-coding RNAs acting as negative regulators of gene expression involved in a number of physiological processes. MiRNAs' expression is commonly dysregulated in many types of human tumor diseases and cancers, including thyroid cancers, and is often involved in tumor initiation and progression. miR-19a, a member of miR-17-92 cluster, has been demonstrated to promote cell growth in anaplastic thyroid cancer (ATC), the most advanced and aggressive thyroid cancer. Purpose: In this work, we investigate the potential contribution of miR-19a in thyroid cancer cells poor prognosis and de-differentiation. Methods: We directly modulated the expression of miR-19a in papillary (PTC) and anaplastic thyroid carcinoma cell lines through transfection of specific miR-19a mimic or inhibitor. Further, we performed gene expression analysis of specific genes to evaluate miR-19a association with cell cycle, differentiation, and poor prognosis. Results: Our data indicate that miR-19a overexpression in PTC cells significantly promotes cell growth, decreases the expression of differentiation genes and activates poor prognosis genes. Its inhibition in ATC cells reduces cell proliferation and the expression of genes related to poor prognosis but does not affect differentiation. Conclusion: Our findings reveal the existence of functional associations between miR-19a expression and thyroid cancer progression and malignancy suggesting miR-19a as a novel candidate therapeutic target for ATC.

18.
Eur Phys J C Part Fields ; 78(11): 932, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30881210

RESUMO

We compute the total cross-section for Z boson production in bottom-quark fusion, applying to this case the method we previously used for Higgs production in bottom fusion. Namely, we match, through the FONLL procedure, the next-to-next-to-leading-log five-flavor scheme result, in which the b quark is treated as a massless parton, with the next-to-leading-order O ( α s 3 ) four-flavor scheme computation in which bottom is treated as a massive final-state particle. Also, we add to our formalism the possibility of varying the heavy quark matching scale. The results obtained with the FONLL formalism can thus be compared directly to recent results obtained in various approximations, and used as a proxy to assess and discuss the issues of scale dependence and treatment of heavy quarks. Finally, We use our results in order to improve the prediction for the total Z production cross-section.

19.
Eur Phys J C Part Fields ; 78(5): 408, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30996667

RESUMO

We present a determination of the strong coupling constant α s ( m Z ) based on the NNPDF3.1 determination of parton distributions, which for the first time includes constraints from jet production, top-quark pair differential distributions, and the Z p T distributions using exact NNLO theory. Our result is based on a novel extension of the NNPDF methodology - the correlated replica method - which allows for a simultaneous determination of α s and the PDFs with all correlations between them fully taken into account. We study in detail all relevant sources of experimental, methodological and theoretical uncertainty. At NNLO we find α s ( m Z ) = 0.1185 ± 0 . 0005 (exp) ± 0 . 0001 (meth) , showing that methodological uncertainties are negligible. We conservatively estimate the theoretical uncertainty due to missing higher order QCD corrections (N 3 LO and beyond) from half the shift between the NLO and NNLO α s values, finding Δ α s th = 0.0011 .

20.
Front Physiol ; 8: 984, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29238307

RESUMO

Injured articular cartilage has a limited innate regenerative capacity, due to the avascular nature and low cellularity of the tissue itself. Although several approaches have been proposed to repair the joint cartilage, none of them has proven to be effective. The absence of suitable therapeutic options has encouraged tissue-engineering approaches combining specific cell types and biomaterials. In the present work, we have evaluated the potential of a cell-free Collagen I-based scaffold to promote the augmentation of cartilage-like phenotype after subcutaneous implantation in the mouse. Forty female mice were grafted subcutaneously with scaffolds, while four additional mice without scaffold were used as negative controls. The effects of scaffold were evaluated at 1, 2, 4, 8, or 16 weeks after implantation. Immunohistochemical analysis shows the expression of typical cartilage markers, including type-II Collagen, Aggrecan, Matrilin-1 and Sox 9. These data are also confirmed by qRT-PCR that further show that both COL2A1 and COL1A1 increase over time, but the first one increases more rapidly, thus suggesting a typical cartilage-like address. Histological analysis shows the presence of some pericellular lacunae, after 8 and 16 weeks. Results suggest that this scaffold (i) is biocompatible in vivo, (ii) is able to recruit host cells (iii) induce chondrogenic differentiation of host cells. Such evidences suggest that this cell-free scaffold is promising and represents a potential approach for cartilage regeneration.

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