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1.
Nat Commun ; 12(1): 5006, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408135

RESUMO

Obesity is a strong risk factor for cancer progression, posing obesity-related cancer as one of the leading causes of death. Nevertheless, the molecular mechanisms that endow cancer cells with metastatic properties in patients affected by obesity remain unexplored.Here, we show that IL-6 and HGF, secreted by tumor neighboring visceral adipose stromal cells (V-ASCs), expand the metastatic colorectal (CR) cancer cell compartment (CD44v6 + ), which in turn secretes neurotrophins such as NGF and NT-3, and recruits adipose stem cells within tumor mass. Visceral adipose-derived factors promote vasculogenesis and the onset of metastatic dissemination by activation of STAT3, which inhibits miR-200a and enhances ZEB2 expression, effectively reprogramming CRC cells into a highly metastatic phenotype. Notably, obesity-associated tumor microenvironment provokes a transition in the transcriptomic expression profile of cells derived from the epithelial consensus molecular subtype (CMS2) CRC patients towards a mesenchymal subtype (CMS4). STAT3 pathway inhibition reduces ZEB2 expression and abrogates the metastatic growth sustained by adipose-released proteins. Together, our data suggest that targeting adipose factors in colorectal cancer patients with obesity may represent a therapeutic strategy for preventing metastatic disease.


Assuntos
Tecido Adiposo/citologia , Reprogramação Celular , Neoplasias do Colo/fisiopatologia , Células-Tronco Neoplásicas/citologia , Nicho de Células-Tronco , Tecido Adiposo/metabolismo , Animais , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos SCID , MicroRNAs/genética , MicroRNAs/metabolismo , Metástase Neoplásica , Células-Tronco/citologia , Células-Tronco/metabolismo , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo
2.
Cancers (Basel) ; 13(15)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34359607

RESUMO

Organoids are revolutionizing approaches to cancer therapy and even diagnosis [...].

3.
Int J Mol Sci ; 22(8)2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33920318

RESUMO

Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics, such as oxaliplatin (L-OHP). The aim of the present work was to evaluate the potential beneficial effects of 2-pentadecyl-2-oxazoline (PEA-OXA) in a murine model of oxaliplatin-induced peripheral neuropathy (OIPN). OIPN was induced by an intraperitoneally injection of L-OHP in rats on five consecutive days (D0-4) for a final cumulative dose of 10 mg/kg. PEA-OXA and ultramicronized palmitoylethanolamide (PEAum), both 10 mg/kg, were given orally 15-20 min prior (L-OHP) and sacrifice was made on day 25. Our results demonstrated that PEA-OXA, more than PEAum, reduced the development of hypersensitivity in rats; this was associated with the reduction in hyperactivation of glia cells and the increased production of proinflammatory cytokines in the dorsal horn of the spinal cord, accompanied by an upregulation of neurotrophic factors in the dorsal root ganglia (DRG). Moreover, we showed that PEA-OXA reduced L-OHP damage via a reduction in NF-κB pathway activation and a modulation of Nrf-2 pathways. Our findings identify PEA-OXA as a therapeutic target in chemotherapy-induced painful neuropathy, through the biomolecular signaling NF-κB/Nrf-2 axis, thanks to its abilities to counteract L-OHP damage. Therefore, we can consider PEA-OXA as a promising adjunct to chemotherapy to reduce chronic pain in patients.


Assuntos
Fator 2 Relacionado a NF-E2/genética , Oxaliplatina/farmacologia , Oxazóis/farmacologia , Dor/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Animais , Modelos Animais de Doenças , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/patologia , Humanos , Camundongos , NF-kappa B/genética , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Oxaliplatina/efeitos adversos , Dor/induzido quimicamente , Dor/genética , Dor/patologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/genética , Doenças do Sistema Nervoso Periférico/patologia , Ratos , Transdução de Sinais/efeitos dos fármacos
4.
Cancers (Basel) ; 13(4)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578886

RESUMO

Organ-like cell clusters, so-called organoids, which exhibit self-organized and similar organ functionality as the tissue of origin, have provided a whole new level of bioinspiration for ex vivo systems. Microfluidic organoid or organs-on-a-chip platforms are a new group of micro-engineered promising models that recapitulate 3D tissue structure and physiology and combines several advantages of current in vivo and in vitro models. Microfluidics technology is used in numerous applications since it allows us to control and manipulate fluid flows with a high degree of accuracy. This system is an emerging tool for understanding disease development and progression, especially for personalized therapeutic strategies for cancer treatment, which provide well-grounded, cost-effective, powerful, fast, and reproducible results. In this review, we highlight how the organoid-on-a-chip models have improved the potential of efficiency and reproducibility of organoid cultures. More widely, we discuss current challenges and development on organoid culture systems together with microfluidic approaches and their limitations. Finally, we describe the recent progress and potential utilization in the organs-on-a-chip practice.

5.
Sci Rep ; 10(1): 21298, 2020 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-33277509

RESUMO

An increased incidence of thyroid cancer has been reported in the area close to Mount Etna, the largest volcano in Europe located in Northeastern Sicily. We tested the hypothesis that exposure to the emissions from the volcano is associated with thyroid cancer in 186 municipalities from three provinces surrounding the volcano (1.9 million inhabitants). We measured the angle between the bearing of the municipalities and each direction, with special focus on South-East, the prevalent direction of the plume, and conducted a regression analysis on 2003-2016 incidence rates of thyroid cancer, adjusting for distance from Mount Etna, population size, and income. A 10-degree increase in the angle with South-East was associated with a decrease in thyroid cancer rates in the whole population (- 0.67 cases/100,000, p = 0.002) and in women (- 1.54/100,000, p < 0.001), and were robust to several sensitivity analyses. Similar results were obtained for East-South-East direction. These results support the hypothesis of a potential role of exposure to the plume from Mount Etna in determining the high rates of thyroid cancer. The results need to be confirmed in analytical studies, in which information of exposure to chemicals originating from the volcano, as well as other possible causes, should be carefully measured, molecular characteristics of the tumors and taken into account.


Assuntos
Neoplasias da Glândula Tireoide/epidemiologia , Erupções Vulcânicas/efeitos adversos , Feminino , Humanos , Itália/epidemiologia , Masculino , Neoplasias da Glândula Tireoide/etiologia
6.
Cancers (Basel) ; 12(11)2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33126572

RESUMO

Nanosized extracellular vesicles (EVs) with dimensions ranging from 100 to 1000 nm are continuously secreted from different cells in their extracellular environment. They are able to encapsulate and transfer various biomolecules, such as nucleic acids, proteins, and lipids, that play an essential role in cell‒cell communication, reflecting a novel method of extracellular cross-talk. Since EVs are present in large amounts in most bodily fluids, challengeable hypotheses are analyzed to unlock their potential roles. Here, we review EVs by discussing their specific characteristics (structure, formation, composition, and isolation methods), focusing on their key role in cell biology. Furthermore, this review will summarize the biomedical applications of EVs, in particular those between 30 and 150 nm (like exosomes), as next-generation diagnostic tools in liquid biopsy for cancer and as novel drug delivery vehicles.

7.
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
8.
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.

9.
Andrology ; 8(6): 1935-1945, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33460247

RESUMO

BACKGROUND: The incretin hormone glucagon-like peptide-l (GLP-1) is an important regulator of post-prandial insulin secretion, acting through a G protein-coupled cell surface receptor (GLP-1R). In addition to its expression in pancreatic ß-cells, several studies suggested that GLP-1R is located in extra-pancreatic tissues. OBJECTIVES: In this study, we examined for the first time the testicular distribution of the GLP-1R, both in normal human and neoplastic testicular tissues as well as in rodent testis and rodent testicular cell lines. METHODS AND METHODS: The GLP-1R distribution in testicular section has been evaluated by immunohistochemistry, the specificity of IHC was validated by demonstrating a positive staining for GLP-1RmRNA by RISH technology. While GLP-1R expression in terms of protein was detected by western blot analysis, Moreover, mRNA levels were determined in human testis, in rodent Leydig, and Sertoli cell lines. RESULTS: Using immunohistochemistrya specific staining for GLP-1R was detected in Leydig cells. The specificity of IHC was validated by demonstrating a positive staining for GLP-1RmRNA only in these cell types. Species differences in the GLP-1R expression between humans and rodents were observed. Interestingly, a decreased expression of the receptor in rodent tumor Leydig cell line and an absence in human Leydig tumor samples was detected. DISCUSSION: It may be hypothesized that GLP-1R acts like an oncosuppressor in Leydig tumors. A role in regulation of hormone secretion by GLP-1 has been shown in other endocrine cells, therefore we hypothesized that GLP-1R is able to modulate somehow the Leydig cell function. CONCLUSION: In our findings, a careful evaluation of human testicular tissues and rodent testis revealed Leydig cells as a potential target for GLP-1. Collectively, an effect of GLP-1R in Leydig cell function may be presumed although future studies are needed to ascertain the GLP-1R's role both in normal and tumor Leydig cells.


Assuntos
Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Testículo/metabolismo , Animais , Linhagem Celular , Exenatida , Humanos , Masculino , Camundongos Endogâmicos C57BL
10.
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
12.
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
13.
Curr Cancer Drug Targets ; 18(5): 410-420, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29189158

RESUMO

The effectiveness of new personalized treatment procedures in oncology is based on the fact that certain tumors exhibit specific molecular features. More in detail, neoplastic tissues of patients should display a specific biomarker, most often a specific genetic alteration and/or under/overexpression of a definite protein, that could be the target of its respective drug. Immunohistochemical and molecular analyses, which usually include examination of nucleic acids from either tissues or fluids, are common tests to define the status of a tumor. This review focuses on the pathologist's role in carefully controlling pre- analytic procedures and standard operating procedures that are a crucial prerequisite to reach reliable and reproducible results. Six paradigmatic applications of targeted therapy, for which pathological diagnosis plays a fundamental role, are summarized. Traditional and next-generation sequencing are also addressed from the pathologist's perspective as well as the importance pathologists have in this shift to more accurate definition of disease risk and prognostication of therapy response in the personalized medicine era.


Assuntos
Antineoplásicos/uso terapêutico , Terapia de Alvo Molecular , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Patologistas , Humanos , Neoplasias/metabolismo , Medicina de Precisão , Prognóstico
14.
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.

15.
Sci Rep ; 7(1): 7110, 2017 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-28769083

RESUMO

Traumatic injury or surgical excision of diseased bone tissue usually require the reconstruction of large bone defects unable to heal spontaneously, especially in older individuals. This is a big challenge requiring the development of biomaterials mimicking the bone structure and capable of inducing the right commitment of cells seeded within the scaffold. In particular, given their properties and large availability, the human adipose-derived stem cells are considered as the better candidate for autologous cell transplantation. In order to evaluate the regenerative potential of these cells along with an osteoinductive biomaterial, we have used collagen/hydroxyapatite scaffolds to test ectopic bone formation after subcutaneous implantation in mice. The process was analysed both in vivo, by Fluorescent Molecular Tomography (FMT), and ex vivo, to evaluate the formation of bone and vascular structures. The results have shown that the biomaterial could itself be able of promoting differentiation of host cells and bone formation, probably by means of its intrinsic chemical and structural properties, namely the microenvironment. However, when charged with human mesenchymal stem cells, the ectopic bone formation within the scaffold was increased. We believe that these results represent an important advancement in the field of bone physiology, as well as in regenerative medicine.


Assuntos
Tecido Adiposo/citologia , Regeneração Óssea , Colágeno , Durapatita , Células-Tronco Mesenquimais/citologia , Tecidos Suporte , Animais , Materiais Biocompatíveis , Biomarcadores , Transplante Ósseo , Técnicas de Cultura de Células , Citometria de Fluxo , Imunofluorescência , Humanos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Camundongos , Neovascularização Fisiológica , Osteogênese , Engenharia Tecidual
16.
Future Oncol ; 13(11s): 5-10, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28481186

RESUMO

AIM: The halichondrin B analog, eribulin, exerts an anticancer effect, as reported by several clinical and real-life studies on metastatic breast cancer patients. Here, we evaluated efficacy and safety of eribulin, focusing on response to treatment per metastasis type. PATIENTS & METHODS: This monocentric, real-life study was conducted on 31 heavily pretreated patients with metastatic breast cancer. RESULTS: The median progression-free survival and overall survival were 2.0 and 5.5 months, respectively. All patients (12.9%) responding to eribulin were treated in fourth-line setting. Considering response per metastasis type, bone lesions (13.6%) responded more frequently than other metastases to eribulin. CONCLUSION: Eribulin exhibited a good overall response rate, with the highest response observed for bone metastases.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Furanos/uso terapêutico , Cetonas/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Biomarcadores Tumorais , Neoplasias da Mama/mortalidade , Progressão da Doença , Feminino , Furanos/administração & dosagem , Furanos/efeitos adversos , Humanos , Cetonas/administração & dosagem , Cetonas/efeitos adversos , Pessoa de Meia-Idade , Metástase Neoplásica , Retratamento , Resultado do Tratamento
17.
Biomed Rep ; 6(3): 314-318, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28451392

RESUMO

Stem cells are an important tool for the study of hematopoiesis. Despite developments in cryopreservation, post-thaw cell death remains a considerable problem. Cryopreservation protocol should limit cell damage due to freezing and ensure the recovery of the functional cell characteristics after thawing. Thus, the use of cryoprotectants is essential. In particular, the efficacy of trehalose has been reported for clinical purposes in blood stem cells. The aim of the current study was to establish an efficient method for biological research based on the use of trehalose, to cryopreserve pure peripheral blood stem cells. The efficacy of trehalose was assessed in vitro and the cell viability was evaluated. The data indicate that trehalose improves cell survival after thawing compared with the standard freezing procedure. These findings could suggest the potential for future trehalose application for research purposes in cell cryopreservation.

18.
Theranostics ; 7(5): 1333-1345, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28435469

RESUMO

Despite Imatinib (IM), a selective inhibitor of Bcr-Abl, having led to improved prognosis in Chronic Myeloid Leukemia (CML) patients, acquired resistance and long-term adverse effects is still being encountered. There is, therefore, urgent need to develop alternative strategies to overcome drug resistance. According to the molecules expressed on their surface, exosomes can target specific cells. Exosomes can also be loaded with a variety of molecules, thereby acting as a vehicle for the delivery of therapeutic agents. In this study, we engineered HEK293T cells to express the exosomal protein Lamp2b, fused to a fragment of Interleukin 3 (IL3). The IL3 receptor (IL3-R) is overexpressed in CML blasts compared to normal hematopoietic cells and thus is able to act as a receptor target in a cancer drug delivery system. Here we show that IL3L exosomes, loaded with Imatinib or with BCR-ABL siRNA, are able to target CML cells and inhibit in vitro and in vivo cancer cell growth.


Assuntos
Antineoplásicos/farmacocinética , Proliferação de Células/efeitos dos fármacos , Portadores de Fármacos/metabolismo , Exossomos/metabolismo , Mesilato de Imatinib/farmacocinética , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Receptores de Interleucina-3/metabolismo , Animais , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Modelos Animais de Doenças , Células HEK293 , Xenoenxertos , Humanos , Mesilato de Imatinib/administração & dosagem , Camundongos , Resultado do Tratamento
19.
Int J Oncol ; 50(5): 1767-1777, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28393181

RESUMO

MicroRNA (miRNA) expression is dysregulated in many human malignancies, and a growing number of studies are focused on their potential use as tumor biomarkers. To identify a miRNA signature for papillary thyroid carcinomas (PTC), we investigated miRNA expression profiles in two independent cohorts of PTCs, which included major histological subtypes [classical-type (PTC­CT), follicular-variant (PTC­FV), and tall-cell variant (PTC­TCV)] and cases with low or intermediate risk of recurrence. Using TaqMan® Array Human MicroRNA A+B Cards v3.0, we first performed microRNA profiling of normal and neoplastic thyroid tissues from 29 PTC patients. Promising candidates were then investigated in a second, independent cohort of 76 PTCs using Custom TaqMan® Array MicroRNA Cards. We identified a molecular signature of 11 miRNAs that were significantly upregulated (miR­146b-5p, miR­146b-3p, miR­221-3p, miR­222­5p, miR­222­3p) or downregulated (miR­1179, miR­486­5p, miR­204-5p, miR­7-2-3p, miR­144-5p, miR­140-3p) in PTC tissues vs. normal thyroid tissue. Upregulation of miR­146b-5p and miR­222­3p was also significantly associated with an increased risk of recurrence. Higher than normal expression of miR­146b-5p and miR­146b-3p characterized PTC­CT and PTC­TCV but not PTC­FV, whereas miR­21-5p was significantly upregulated only in PTC­TCV. When PTC­FV were subclassified as encapsulated (PTC­EFV) or infiltrative (PTC­IFV), miR­204-5p was downregulated in all histological subtypes except PTC­EFV, which displayed expression levels similar to those of normal thyroid tissues. These findings provide new insights into the molecular classification of PTC, showing that different miRNA expression profiles are associated with different histological types of PTC and different risks of recurrence.


Assuntos
Biomarcadores Tumorais/biossíntese , Carcinoma/genética , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/biossíntese , Neoplasias da Glândula Tireoide/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma/classificação , Carcinoma/patologia , Carcinoma Papilar , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , MicroRNAs/classificação , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico , Câncer Papilífero da Tireoide , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/classificação , Neoplasias da Glândula Tireoide/patologia
20.
Front Physiol ; 8: 50, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28210226

RESUMO

Recently, multipotent mesenchymal stem cells (MSCs) have attracted much attention in the field of regenerative medicine due to their ability to give rise to different cell types, including chondrocytes. Damaged articular cartilage repair is one of the most challenging issues for regenerative medicine, due to the intrinsic limited capability of cartilage to heal because of its avascular nature. While surgical approaches like chondral autografts and allografts provide symptoms and function improvement only for a short period, MSC based stimulation therapies, like microfracture surgery or autologous matrix-induced chondrogenesis demonstrate to be more effective. The use of adult chondrocytes, which are the main cellular constituent of cartilage, in medical practice, is indeed limited due to their instability in monolayer culture and difficulty to collect donor tissue (articular and nasal cartilage). The most recent cartilage engineering approaches combine cells, biomaterial scaffold and bioactive factors to promote functional tissue replacements. Many recent evidences demonstrate that scaffolds providing specific microenvironmental conditions can promote MSCs differentiation toward a functional phenotype. In the present work, the chondrogenic potential of a new Collagen I based 3D scaffold has been assessed in vitro, in combination with human adipose-derived MSCs which possess a higher chondrogenic potential compared to MSCs isolated from other tissues. Our data indicate that the scaffold was able to promote the early stages of chondrogenic commitment and that supplementation of specific soluble factors was able to induce the complete differentiation of MSCs in chondrocytes as demonstrated by the appearance of cartilage distinctive markers (Sox 9, Aggrecan, Matrilin-1, and Collagen II), as well as by the cartilage-specific Alcian Blue staining and by the acquisition of typical cellular morphology. Such evidences suggest that the investigated scaffold formulation could be suitable for the production of medical devices that can be beneficial in the field of articular cartilage engineering, thus improving the efficacy and durability of the current therapeutic options.

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