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1.
Mater Sci Eng C Mater Biol Appl ; 127: 112199, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34225852

RESUMO

Modern-day search for the novel agents (their preparation and consequent implementation) to effectively treat the cancer is mainly fuelled by the historical failure of the conventional treatment modalities. Apart from that, the complexities such as higher rate of cell mutations, variable tumor microenvironment, patient-specific disparities, and the evolving nature of cancers have made this search much stronger in the latest times. As a result of this, in about two decades, the theranostic nanoparticles (TNPs) - i.e., nanoparticles that integrate therapeutic and diagnostic characteristics - have been developed. The examples for TNPs include mesoporous silica nanoparticles, luminescence nanoparticles, carbon-based nanomaterials, metal nanoparticles, and magnetic nanoparticles. These TNPs have emerged as single and powerful cancer-treating multifunctional nanoplatforms, as they widely provide the necessary functionalities to overcome the previous/conventional limitations including lack of the site-specific delivery of anti-cancer drugs, and real-time continuous monitoring of the target cancer sites while performing therapeutic actions. This has been mainly possible due to the association of the as-developed TNPs with the already-available unique diagnostic (e.g., luminescence, photoacoustic, and magnetic resonance imaging) and therapeutic (e.g., photothermal, photodynamic, hyperthermia therapy) modalities in the biomedical field. In this review, we have discussed in detail about the recent developments on the aforementioned important TNPs without/with targeting ability (i.e., attaching them with ligands or tumor-specific antibodies) and also the strategies that are implemented to increase their tumor accumulation and to enhance their theranostic efficacies for effective biomedical cancer treatments.


Assuntos
Antineoplásicos , Hipertermia Induzida , Nanopartículas Metálicas , Nanopartículas , Neoplasias , Antineoplásicos/uso terapêutico , Humanos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Fototerapia , Medicina de Precisão , Nanomedicina Teranóstica , Microambiente Tumoral
2.
Molecules ; 26(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34201944

RESUMO

Photodynamic therapy (PDT) as a safe, non-invasive modality for cancer therapy, in which the low oxygen and high glutathione in the tumor microenvironment reduces therapeutic efficiency. In order to overcome these problems, we prepared a supramolecular photosensitive system of O2-Cu/ZIF-8@ZIF-8@WP6-MB (OCZWM), which was loaded with oxygen to increase the oxygen concentration in the tumor microenvironment, and the Cu2+ in the system reacted with glutathione (GSH) to reduce the GSH concentration to generate Cu+. It is worth noting that the generated Cu+ can produce the Fenton reaction, thus realizing the combination therapy of PDT and chemodynamic therapy (CDT) to achieve the purpose of significantly improving the anti-cancer efficiency.


Assuntos
Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes , Microambiente Tumoral/efeitos dos fármacos , Células Hep G2 , Humanos , Azul de Metileno/química , Neoplasias/metabolismo , Neoplasias/patologia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Compostos de Amônio Quaternário/química
3.
Int J Mol Sci ; 22(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208157

RESUMO

Advanced imaging techniques for diagnosis have increased awareness on the benefits of brain screening, facilitated effective control of extracranial disease, and prolonged life expectancy of metastatic renal cell carcinoma (mRCC) patients. Brain metastasis (BM) in patients with mRCC (RCC-BM) is associated with grave prognoses, a high degree of morbidity, dedicated assessment, and unresponsiveness to conventional systemic therapeutics. The therapeutic landscape of RCC-BM is rapidly changing; however, survival outcomes remain poor despite standard surgery and radiation, highlighting the unmet medical needs and the requisite for advancement in systemic therapies. Immune checkpoint inhibitors (ICIs) are one of the most promising strategies to treat RCC-BM. Understanding the role of brain-specific tumor immune microenvironment (TIME) is important for developing rationale-driven ICI-based combination strategies that circumvent tumor intrinsic and extrinsic factors and complex positive feedback loops associated with resistance to ICIs in RCC-BM via combination with ICIs involving other immunological pathways, anti-antiangiogenic multiple tyrosine kinase inhibitors, and radiotherapy; therefore, novel combination approaches are being developed for synergistic potential against RCC-BM; however, further prospective investigations with longer follow-up periods are required to improve the efficacy and safety of combination treatments and to elucidate dynamic predictive biomarkers depending on the interactions in the brain TIME.


Assuntos
Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/terapia , Carcinoma de Células Renais/patologia , Imunoterapia , Neoplasias Renais/patologia , Humanos , Imunossupressão , Microambiente Tumoral
4.
Nat Commun ; 12(1): 4091, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215748

RESUMO

Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation. Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Collectively, our results reveal a previously unappreciated spatial heterogeneity and an immune-escape mechanism of CTC, which may aid in designing new anti-metastasis therapeutic strategies in HCC.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Heterogeneidade Genética , Evasão da Resposta Imune , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Células Neoplásicas Circulantes/imunologia , Idoso , Animais , Biomarcadores Tumorais/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Quimiocina CCL5/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Metástase Neoplásica , Células Neoplásicas Circulantes/metabolismo , Prognóstico , RNA-Seq , Transcriptoma , Microambiente Tumoral
5.
Mater Sci Eng C Mater Biol Appl ; 127: 112200, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34225853

RESUMO

Self-assembling peptide hydrogels (SAPH) are a popular biomaterial due to their biocompatibility with a wide range of cell types, synthetic design, structural properties that provide a more accurate 3D microenvironment, and potential for cell- and/or drug-delivery system. Mimicking solid tumors in vitro using hydrogels is one method of testing anti-cancer drug efficacy and observing cancerous cell-ECM interactions within a 3D system. In this study, a SAPH, PeptiGel®Alpha1, was used to model in vitro the 3D breast tumor microenvironment. PeptiGel®Alpha1 is composed of entangled nanofibers with consistent diameter and mechanical properties similar to breast cancer that more accurately mimic the stiffness of breast tumor tissue than Matrigel® or collagen type I. PeptiGel®Alpha1 supported the viability and growth of the breast cancer cell lines MCF-7 and MDA-MB-231 and recapitulated key features of solid tumors such as hypoxia and invasion. MCF-7 cells in the hydrogels formed large spheroids resembling acini, while MDA-MB-231 remained dispersed. When treated with tamoxifen, PeptiGel®Alpha1 acted as a barrier, providing drug penetration geometry similar to that in vivo, providing better prediction of the drug effect. Finally, it was observed that MCF-7 cells engulfed the peptide matrix after 14 days, highlighting a potential use in drug delivery. PeptiGel®Alpha1 is a suitable platform for in vitro modeling of breast cancer.


Assuntos
Neoplasias da Mama , Hidrogéis , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Colágeno Tipo I , Progressão da Doença , Feminino , Humanos , Células MCF-7 , Peptídeos , Microambiente Tumoral
6.
Adv Exp Med Biol ; 1302: 15-24, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34286438

RESUMO

Cancer progression is driven, to a large extent, by the action of immune cells that have been recruited to tumor sites through interactions between chemokines and their receptors. Chemokines of the CXC subfamily are secreted by both tumor and non-tumor cells within the microenvironment of the tumor, where they induce either antitumor or protumor activity that fosters either clearance or progression of the tumor, respectively. Understanding the nature of these interactions is important to envisage novel approaches targeting the essential components of the tumor microenvironment, increasing the odds for favorable patient outcomes. In this chapter we describe the involvement of the chemokine (C-X-C motif) ligand 3 (CXCL3) in the human tumor microenvironment and its effects on immune and non-immune cells. Because of the limited data on the CXCL3 signaling in the tumor microenvironment, we extend the review to other members of the CXC subfamily of chemokines. This review also addresses the future trends or directions for therapeutic interventions that target signaling pathways used by these molecules in the tumor microenvironment.


Assuntos
Neoplasias , Microambiente Tumoral , Quimiocinas , Quimiocinas CXC/genética , Humanos , Neoplasias/genética , Transdução de Sinais
7.
Adv Exp Med Biol ; 1302: 1-14, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34286437

RESUMO

The C-C motif chemokine ligand 2 (CCL2) is a crucial mediator of immune cell recruitment during microbial infections and tissue damage. CCL2 is also frequently overexpressed in cancer cells and other cells in the tumor microenvironment, and a large body of evidence indicates that high CCL2 levels are associated with more aggressive malignancies, a higher probability of metastasis, and poorer outcomes in a wide range of cancers. CCL2 plays a role in recruiting tumor-associated macrophages (TAMs), which adopt a pro-tumorigenic phenotype and support cancer cell survival, facilitate tumor cell invasion, and promote angiogenesis. CCL2 also has direct, TAM-independent effects on tumor cells and the tumor microenvironment, including recruitment of other myeloid subsets and non-myeloid cells, maintaining an immunosuppressive environment, stimulating tumor cell growth and motility, and promoting angiogenesis. CCL2 also plays important roles in the metastatic cascade, such as creating a pre-metastatic niche in distant organs and promoting tumor cell extravasation across endothelia. Due to its many roles in tumorigenesis and metastatic processes, the CCL2-CCR2 signaling axis is currently being pursued as a potential therapeutic target for cancer.


Assuntos
Receptores CCR2 , Microambiente Tumoral , Linhagem Celular Tumoral , Quimiocina CCL2/genética , Quimiocinas , Ligantes , Receptores CCR2/genética
8.
Adv Exp Med Biol ; 1302: 25-39, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34286439

RESUMO

The tumor microenvironment represents a dynamic and complex cellular network involving intricate communications between the tumor and highly heterogeneous groups of cells, including tumor-supporting immune and inflammatory cells, cancer-associated fibroblasts, endothelial cells, tumor-associated macrophages, adipose cells, and pericytes. Associated with a variety of growth factors, chemokines, cytokines, and other signaling molecules, the interaction between the tumor microenvironment and the tumor cells empowers aggressiveness of tumor by enhancing its survivability. CXCL8 (also known as Interleukin 8), a multifunctional proinflammatory chemokine that was initially classified as a neutrophil chemoattractant, recently has been found to be a key contributor in tumorigenesis. The upregulation of CXCL8 at the tumor invasion front in several human cancers suggests its interplay between the tumor and its microenvironment rendering tumor progression by enhancing angiogenesis, tumor genetic diversity, survival, proliferation, immune escape, metastasis, and multidrug resistance. The autocrine and paracrine modulation of CXCL8 via the chemokine receptors CXCR1/2 promotes several intracellular signaling cascades that fosters tumor-associated inflammation, reprogramming, epithelial-mesenchymal transition, and neovascularization. Hence, decrypting the regulatory/signaling cascades of CXCL8 and its downstream effects may harbor prognostic clinical prospects of a tumor microenvironment-oriented cancer therapeutics.


Assuntos
Interleucina-8 , Microambiente Tumoral , Células Endoteliais , Humanos , Receptores de Interleucina-8A , Receptores de Interleucina-8B
9.
Adv Exp Med Biol ; 1302: 41-50, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34286440

RESUMO

CXCL11 which can bind to two different chemokine receptors, CXCR3 and CXCR7, has found a prominent place in current tumor research. In this chapter, we mainly discuss the current evidence on the role of the immune response of CXCL11 in tumor microenvironment (TME). The diverse functions of CXCL11 include inhibiting angiogenesis, affecting the proliferation of different cell types, playing a role in fibroblast directed carcinoma invasion, increasing adhesion properties, suppressing M2 macrophage polarization, and facilitating the migration of certain immune cells. In addition, we discussed the application of CXCL11 as an adjuvant to various mainstream anti-cancer therapies and the future challenges in the application of CXCL11 targeted therapies.


Assuntos
Neoplasias , Microambiente Tumoral , Quimiocina CXCL10 , Quimiocina CXCL11/genética , Humanos , Neoplasias/tratamento farmacológico , Neovascularização Patológica , Receptores CXCR3 , Transdução de Sinais
10.
Adv Exp Med Biol ; 1302: 91-98, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34286443

RESUMO

Chemokines with their network play an important role in cancer growth, metastasis, and host-tumor interactions. Of many chemokines, C-C motif chemokine ligand 24 (CCL24) has been shown to contribute to tumorigenesis as well as inflammatory diseases like asthma, allergies, and eosinophilic esophagitis. CCL24 is expressed in some tumor cells such as colon cancer, hepatocellular carcinoma, and cutaneous T cell lymphoma. CCL24 can be used as a potential biomarker in several cancers including colon cancer, non-small cell cancer, and nasopharyngeal carcinoma as the plasma level of CCL24 is increased. The various functions of CCL24 contribute to the biology of cancer by M2 macrophage polarization, angiogenesis, invasion and migration, and recruitment of eosinophils.


Assuntos
Neoplasias Hepáticas , Microambiente Tumoral , Quimiocina CCL24 , Eosinófilos , Humanos , Transdução de Sinais
11.
Adv Exp Med Biol ; 1302: 71-90, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34286442

RESUMO

Chemokines have emerged as important players in tumorigenic process. An extensive body of literature generated over the last two or three decades strongly implicate abnormally activated or functionally disrupted chemokine signaling in liaising most-if not all-hallmark processes of cancer. It is well-known that chemokine signaling networks within the tumor microenvironment are highly versatile and context-dependent: exert both pro-tumoral and antitumoral activities. The C-X-C motif chemokine ligand 13 (CXCL13), and its cognate receptor CXCR5, represents an emerging example of chemokine signaling axes, which express the ability to modulate tumor growth and progression in either way. Collateral evidence indicate that CXCL13-CXCR5 axis may directly modulate tumor growth by inducing proliferation of cancer cells, as well as promoting invasive phenotypes and preventing their apoptosis. In addition, CXCL13-CXCR5 axis may also indirectly modulate tumor growth by regulating noncancerous cells, particularly the immune cells, within the tumor microenvironment. Here, we review the role of CXCL13, together with CXCR5, in the human tumor microenvironment. We first elaborate their patterns of expression, regulation, and biological functions in normal physiology. We then consider how their aberrant activity, as a result of differential overexpression or co-expression, may directly or indirectly modulate the growth of tumors through effects on both cancerous and noncancerous cells.


Assuntos
Neoplasias , Microambiente Tumoral , Apoptose , Quimiocina CXCL13/genética , Humanos , Neoplasias/genética , Receptores CXCR5 , Transdução de Sinais
12.
Adv Exp Med Biol ; 1302: 51-70, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34286441

RESUMO

Tumor microenvironment (TME) is the local environment of tumor, composed of tumor cells and blood vessels, extracellular matrix (ECM), immune cells, and metabolic and signaling molecules. Chemokines and their receptors play a fundamental role in the crosstalk between tumor cells and TME, regulating tumor-related angiogenesis, specific leukocyte infiltration, and activation of the immune response and directly influencing tumor cell growth, invasion, and cancer progression. The chemokine CXCL12 is a homeostatic chemokine that regulates physiological and pathological process such as inflammation, cell proliferation, and specific migration. CXCL12 activates CXCR4 and CXCR7 chemokine receptors, and the entire axis has been shown to be dysregulated in more than 20 different tumors. CXCL12 binding to CXCR4 triggers multiple signal transduction pathways that regulate intracellular calcium flux, chemotaxis, transcription, and cell survival. CXCR7 binds with high-affinity CXCL12 and with lower-affinity CXCL11, which binds also CXCR3. Although CXCR7 acts as a CXCL12 scavenger through ligand internalization and degradation, it transduces the signal mainly through ß-arrestin with a pivotal role in endothelial and neural cells. Recent studies demonstrate that TME rich in CXCL12 leads to resistance to immune checkpoint inhibitors (ICI) therapy and that CXCL12 axis inhibitors sensitize resistant tumors to ICI effect. Thus targeting the CXCL12-mediated axis may control tumor and tumor microenvironment exerting an antitumor dual action. Herein CXCL12 physiology, role in cancer biology and in composite TME, prognostic role, and the relative inhibitors are addressed.


Assuntos
Neoplasias , Microambiente Tumoral , Linhagem Celular Tumoral , Proliferação de Células , Quimiocina CXCL12 , Humanos , Neovascularização Patológica , Transdução de Sinais
13.
Adv Exp Med Biol ; 1302: 99-111, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34286444

RESUMO

Multiple checkpoint mechanisms are overridden by cancer cells in order to develop into a tumor. Neoplastic cells, while constantly changing during the course of cancer progression, also craft their surroundings to meet their growing needs. This crafting involves changing cell surface receptors, affecting response to extracellular signals and secretion of signals that affect the nearby cells and extracellular matrix architecture. This chapter briefly comprehends the non-cancer cells facilitating the cancer growth and elaborates on the notable role of the CCR9-CCL25 chemokine axis in shaping the tumor microenvironment (TME), directly and via immune cells. Association of increased CCR9 and CCL25 levels in various tumors has demonstrated the significance of this axis as a tool commonly used by cancer to flourish. It is involved in attracting immune cells in the tumor and determining their fate via various direct and indirect mechanisms and, leaning the TME toward immunosuppressive state. Besides, elevated CCR9-CCL25 signaling allows survival and rapid proliferation of cancer cells in an otherwise repressive environment. It modulates the intra- and extracellular protein matrix to instigate tumor dissemination and creates a supportive metastatic niche at the secondary sites. Lastly, this chapter abridges the latest research efforts and challenges in using the CCR9-CCL25 axis as a cancer-specific target.


Assuntos
Receptores CCR , Microambiente Tumoral , Transdução de Sinais
14.
Adv Exp Med Biol ; 1302: 113-132, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34286445

RESUMO

Chemokines are a group of small proteins which play an important role in leukocyte migration and invasion. They are also involved in the cellular proliferation and migration of tumor cells.Chemokine CCL27 (cutaneous T cell-attracting chemokine, CTACK) is mainly expressed by keratinocytes of the normal epidermis. It is well known that this chemokine plays an important role in several inflammatory diseases of the skin, such as atopic dermatitis, contact dermatitis, and psoriasis. Moreover, several studies have shown an association between CCL27 expression and a variety of neoplasms including skin cancer.In this chapter, we address the role of chemokine CCL27 in the tumor microenvironment in the most relevant cancers of the skin and other anatomical locations. We also make a brief comment on future perspectives and the potential relation of CCL27 with different immunotherapeutic modalities.


Assuntos
Quimiocina CCL27 , Microambiente Tumoral , Quimiocina CCL27/genética , Quimiocinas CC , Queratinócitos , Pele
15.
Int J Mol Sci ; 22(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200243

RESUMO

Hepatocellular carcinoma (HCC) exerts huge effects on the health burden of the world because of its high mortality and poor prognosis. HCC is often clinically detected late in patients. If HCC could be detected and treated earlier, the survival rate of patients will be greatly improved. Therefore, identifying specific biomarkers is urgent and important for HCC. The liver is also recognized as an immune organ. The occurrence of HCC is related to exacerbation of immune tolerance and/or immunosurveillance escape. The host immune system plays an important role in the recognition and targeting of tumor cells in cancer immunotherapy, as can be seen from the clinical success of immune checkpoint inhibitors and chimeric antigen receptor (CAR) T cells. Thus, there is a pressing medical need to discover immunodiagnostic biomarkers specific to HCC for understanding the pathological mechanisms of HCC, especially for immunotherapy targets. We have reviewed the existing literature to summarize the immunodiagnostic markers of HCC, including autoantibodies against tumor-associated antigens (TAAs) and exosomes, to provide new insights into HCC and early detection of this deadly cancer.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Imunoterapia/métodos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Animais , Carcinoma Hepatocelular/imunologia , Humanos , Neoplasias Hepáticas/imunologia , Microambiente Tumoral/imunologia
16.
Int J Mol Sci ; 22(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200679

RESUMO

Lymphocyte migration to and sequestration in specific microenvironments plays a crucial role in their differentiation and survival. Lymphocyte trafficking and homing are tightly regulated by signaling pathways and is mediated by cytokines, chemokines, cytokine/chemokine receptors and adhesion molecules. The production of cytokines and chemokines is largely controlled by transcription factors in the context of a specific epigenetic landscape. These regulatory factors are strongly interconnected, and they influence the gene expression pattern in lymphocytes, promoting processes such as cell survival. The epigenetic status of the genome plays a key role in regulating gene expression during many key biological processes, and it is becoming more evident that dysregulation of epigenetic mechanisms contributes to cancer initiation, progression and drug resistance. Here, we review the signaling pathways that regulate lymphoma cell migration and adhesion with a focus on Mantle cell lymphoma and highlight the fundamental role of epigenetic mechanisms in integrating signals at the level of gene expression throughout the genome.


Assuntos
Linfócitos B/patologia , Adesão Celular , Movimento Celular , Epigênese Genética , Linfoma de Célula do Manto/patologia , Microambiente Tumoral/imunologia , Animais , Humanos , Linfoma de Célula do Manto/imunologia , Transdução de Sinais
17.
Int J Mol Sci ; 22(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200790

RESUMO

Exosomes released from tumor cells are instrumental in shaping the local tumor microenvironment to allow cancer progression. Recently, it has been shown that tumor exosomes carry large fragments of dsDNA, which may reflect the mutational status of parental cells. Although it has been described that a stressful microenvironment can influence exosomal cargo, the effects on DNA packing and its transfer into recipient cells have yet to be investigated. Here, we report that exosomes derived from SW480 (human colorectal adenocarcinoma cell line) cells can carry dsDNA fragments containing the entire coding sequence of both TP53 and KRAS genes, harboring the SW480-related TP53 c.818G > A and KRAS c.35G > T typical mutations. We also report the following: that cell stimulation with lipopolysaccharides (LPS) promotes the selective packaging of the TP53 gene, but not the KRAS gene; that exosomes secreted by SW480 cells efficiently transfer the mutated sequences into normal CCD841-CoN colon epithelial and THLE-2 hepatic cells; that this mechanism is more efficient when the cells had been previously incubated with pro-inflammatory cytokines; that the TP53 gene appears actively transcribed in both recipient cells; and that mutated mRNA levels are not influenced by cytokine treatment. Our data strongly suggest that pro-inflammatory stimulation promotes the horizontal transfer of an oncogene by exosomes, although this remains a rare event. Further studies are needed to assess the impact of the oncogenic transfer by exosomes in malignant transformation and its role in tumor progression.


Assuntos
Transformação Celular Neoplásica/patologia , Neoplasias Colorretais/patologia , Exossomos/genética , Mediadores da Inflamação/imunologia , Mutação , Microambiente Tumoral/imunologia , Proteína Supressora de Tumor p53/genética , Transformação Celular Neoplásica/genética , Neoplasias Colorretais/genética , Humanos , Células Tumorais Cultivadas
18.
Int J Mol Sci ; 22(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200849

RESUMO

Nitric oxide (NO) has been identified and described as a dual mediator in cancer according to dose-, time- and compartment-dependent NO generation. The present review addresses the different epigenetic mechanisms, such as histone modifications and non-coding RNAs (ncRNAs), miRNA and lncRNA, which regulate directly or indirectly nitric oxide synthase (NOS) expression and NO production, impacting all hallmarks of the oncogenic process. Among lncRNA, HEIH and UCA1 develop their oncogenic functions by inhibiting their target miRNAs and consequently reversing the inhibition of NOS and promoting tumor proliferation. The connection between miRNAs and NO is also involved in two important features in cancer, such as the tumor microenvironment that includes key cellular components such as tumor-associated macrophages (TAMs), cancer associated fibroblasts (CAFs) and cancer stem cells (CSCs).


Assuntos
Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Neoplasias/patologia , Células-Tronco Neoplásicas/patologia , Óxido Nítrico/metabolismo , RNA Longo não Codificante/genética , Microambiente Tumoral , Animais , Fibroblastos Associados a Câncer/patologia , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Transdução de Sinais
19.
Int J Mol Sci ; 22(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200820

RESUMO

Colorectal carcinoma (CRC) is one of the most frequently diagnosed carcinomas and one of the leading causes of cancer-related death worldwide. Metabolic reprogramming, a hallmark of cancer, is closely related to the initiation and progression of carcinomas, including CRC. Accumulating evidence shows that activation of oncogenic pathways and loss of tumor suppressor genes regulate the metabolic reprogramming that is mainly involved in glycolysis, glutaminolysis, one-carbon metabolism and lipid metabolism. The abnormal metabolic program provides tumor cells with abundant energy, nutrients and redox requirements to support their malignant growth and metastasis, which is accompanied by impaired metabolic flexibility in the tumor microenvironment (TME) and dysbiosis of the gut microbiota. The metabolic crosstalk between the tumor cells, the components of the TME and the intestinal microbiota further facilitates CRC cell proliferation, invasion and metastasis and leads to therapy resistance. Hence, to target the dysregulated tumor metabolism, the TME and the gut microbiota, novel preventive and therapeutic applications are required. In this review, the dysregulation of metabolic programs, molecular pathways, the TME and the intestinal microbiota in CRC is addressed. Possible therapeutic strategies, including metabolic inhibition and immune therapy in CRC, as well as modulation of the aberrant intestinal microbiota, are discussed.


Assuntos
Reprogramação Celular , Neoplasias Colorretais/patologia , Microbioma Gastrointestinal/imunologia , Imunoterapia/métodos , Microambiente Tumoral/imunologia , Animais , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/terapia , Humanos
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