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1.
Int J Mol Sci ; 25(13)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-39000420

RESUMO

Growth differentiation factor 15 (GDF-15) is a multifunctional cytokine that belongs to the transforming growth factor-beta (TGF-ß) superfamily. GDF-15 is involved in immune tolerance and is elevated in several acute and chronic stress conditions, often correlating with disease severity and patient prognosis in cancer172 and metabolic and cardiovascular disorders. Despite these clinical associations, the molecular mechanisms orchestrating its effects remain to be elucidated. The effects of GDF-15 are pleiotropic but cell-specific and dependent on the microenvironment. While GDF-15 expression can be stimulated by inflammatory mediators, its predominant effects were reported as anti-inflammatory and pro-fibrotic. The role of GDF-15 in the macrophage system has been increasingly investigated in recent years. Macrophages produce high levels of GDF-15 during oxidative and lysosomal stress, which can lead to fibrogenesis and angiogenesis at the tissue level. At the same time, macrophages can respond to GDF-15 by switching their phenotype to a tolerogenic one. Several GDF-15-based therapies are under development, including GDF-15 analogs/mimetics and GDF-15-targeting monoclonal antibodies. In this review, we summarize the major physiological and pathological contexts in which GDF-15 interacts with macrophages. We also discuss the major challenges and future perspectives in the therapeutic translation of GDF-15.


Assuntos
Fator 15 de Diferenciação de Crescimento , Macrófagos , Fator 15 de Diferenciação de Crescimento/metabolismo , Humanos , Macrófagos/metabolismo , Macrófagos/imunologia , Animais , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/imunologia
2.
Int J Mol Sci ; 25(13)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-39000421

RESUMO

This article provides an overview of the development, structure and activity of various metal complexes with anti-cancer activity. Chemical researchers continue to work on the development and synthesis of new molecules that could act as anti-tumor drugs to achieve more favorable therapies. It is therefore important to have information about the various chemotherapeutic substances and their mode of action. This review focuses on metallodrugs that contain a metal as a key structural fragment, with cisplatin paving the way for their chemotherapeutic application. The text also looks at ruthenium complexes, including the therapeutic applications of phosphorescent ruthenium(II) complexes, emphasizing their dual role in therapy and diagnostics. In addition, the antitumor activities of titanium and gold derivatives, their side effects, and ongoing research to improve their efficacy and reduce adverse effects are discussed. Metallization of host defense peptides (HDPs) with various metal ions is also highlighted as a strategy that significantly enhances their anticancer activity by broadening their mechanisms of action.


Assuntos
Antineoplásicos , Complexos de Coordenação , Neoplasias , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologia , Relação Estrutura-Atividade , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Animais , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/farmacologia , Rutênio/química , Rutênio/farmacologia , Peptídeos/química , Peptídeos/farmacologia
3.
Int J Mol Sci ; 25(13)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-39000444

RESUMO

The taurine transporter (TauT, SLC6A6) is a member of the solute carrier 6 (SLC6) family, which plays multiple physiological roles. The SLC6 family is divided into four subfamilies: GABA (γ-aminobutyric acid), monoamine, glycine and neutral amino acid transporters. Proteins from the GABA group, including the taurine transporter, are primarily considered therapeutic targets for treating central nervous system disorders. However, recent studies have suggested that inhibitors of SLC6A6 could also serve as anticancer agents. Overexpression of TauT has been associated with the progression of colon and gastric cancer. The pool of known ligands of this transporter is limited and the exact spatial structure of taurine transporter remains unsolved. Understanding its structure could aid in the development of novel inhibitors. Therefore, we utilized homology modelling techniques to create models of TauT. Docking studies and molecular dynamics simulations were conducted to describe protein-ligand interactions. We compared the obtained information for TauT with literature data on other members of the GABA transporter group. Our in silico analysis allowed us to characterize the transporter structure and point out amino acids crucial for ligand binding: Glu406, Gly62 and Tyr138. The significance of selected residues was confirmed through structural studies of mutants. These results will aid in the development of novel taurine transporter inhibitors, which can be explored as anticancer agents.


Assuntos
Proteínas da Membrana Plasmática de Transporte de GABA , Proteínas de Membrana Transportadoras , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Humanos , Proteínas da Membrana Plasmática de Transporte de GABA/metabolismo , Proteínas da Membrana Plasmática de Transporte de GABA/química , Proteínas da Membrana Plasmática de Transporte de GABA/genética , Proteínas de Membrana Transportadoras/química , Proteínas de Membrana Transportadoras/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/genética , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/antagonistas & inibidores , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Ligantes , Sequência de Aminoácidos , Ligação Proteica
4.
Int J Mol Sci ; 25(13)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-39000453

RESUMO

Regulatory T cells (Tregs) possess unique immunosuppressive activity among CD4-positive T cells. Tregs are ubiquitously present in mammals and function to calm excessive immune responses, thereby suppressing allergies or autoimmune diseases. On the other hand, due to their immunosuppressive function, Tregs are thought to promote cancer progression. The tumor microenvironment (TME) is a multicellular system composed of many cell types, including tumor cells, infiltrating immune cells, and cancer-associated fibroblasts (CAFs). Within this environment, Tregs are recruited by chemokines and metabolic factors and impede effective anti-tumor responses. However, in some cases, their presence can also improve patient's survival rates. Their functional consequences may vary across tumor types, locations, and stages. An in-depth understanding of the precise roles and mechanisms of actions of Treg is crucial for developing effective treatments, emphasizing the need for further investigation and validation. This review aims to provide a comprehensive overview of the complex and multifaceted roles of Tregs within the TME, elucidating cellular communications, signaling pathways, and their impacts on tumor progression and highlighting their potential anti-tumor mechanisms through interactions with functional molecules.


Assuntos
Progressão da Doença , Neoplasias , Linfócitos T Reguladores , Microambiente Tumoral , Humanos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Microambiente Tumoral/imunologia , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/metabolismo , Animais , Transdução de Sinais , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/imunologia , Fibroblastos Associados a Câncer/patologia
5.
Med Oncol ; 41(8): 202, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39008137

RESUMO

Proprotein convertase subtilisin/kexin type 9 (PCSK9), a well-known regulator of cholesterol metabolism and cardiovascular diseases, has recently garnered attention for its emerging involvement in cancer biology. The multifunctional nature of PCSK9 extends beyond lipid regulation and encompasses a wide range of cellular processes that can influence cancer progression. Studies have revealed that PCSK9 can modulate signaling pathways, such as PI3K/Akt, MAPK, and Wnt/ß-catenin, thereby influencing cellular proliferation, survival, and angiogenesis. Additionally, the interplay between PCSK9 and cholesterol homeostasis may impact membrane dynamics and cellular migration, further influencing tumor aggressiveness. The central role of the immune system in monitoring and controlling cancer is increasingly recognized. Recent research has demonstrated the ability of PCSK9 to modulate immune responses through interactions with immune cells and components of the tumor microenvironment. This includes effects on dendritic cell maturation, T cell activation, and cytokine production, suggesting a role in shaping antitumor immune responses. Moreover, the potential influence of PCSK9 on immune checkpoints such as PD1/PD-L1 lends an additional layer of complexity to its immunomodulatory functions. The growing interest in cancer immunotherapy has prompted exploration into the potential of targeting PCSK9 for therapeutic benefits. Preclinical studies have demonstrated synergistic effects between PCSK9 inhibitors and established immunotherapies, offering a novel avenue for combination treatments. The strategic manipulation of PCSK9 to enhance tumor immunity and improve therapeutic outcomes presents an exciting area for further investigations. Understanding the mechanisms by which PCSK9 influences cancer biology and immunity holds promise for the development of novel immunotherapeutic approaches. This review aims to provide a comprehensive analysis of the intricate connections between PCSK9, cancer pathogenesis, tumor immunity, and the potential implications for immunotherapeutic interventions.


Assuntos
Imunoterapia , Neoplasias , Pró-Proteína Convertase 9 , Humanos , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/metabolismo , Neoplasias/patologia , Pró-Proteína Convertase 9/imunologia , Pró-Proteína Convertase 9/metabolismo , Imunoterapia/métodos , Microambiente Tumoral/imunologia , Animais , Inibidores de PCSK9
6.
J Proteome Res ; 23(7): 2452-2473, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38965921

RESUMO

Cancer cachexia is an involuntary loss of body weight, mostly of skeletal muscle. Previous research favors the existence of a microbiota-muscle crosstalk, so the aim of the study was to evaluate the impact of microbiota alterations induced by antibiotics on skeletal muscle proteins expression. Skeletal muscle proteome changes were investigated in control (CT) or C26 cachectic mice (C26) with or without antibiotic treatment (CT-ATB or C26-ATB, n = 8 per group). Muscle protein extracts were divided into a sarcoplasmic and myofibrillar fraction and then underwent label-free liquid chromatography separation, mass spectrometry analysis, Mascot protein identification, and METASCAPE platform data analysis. In C26 mice, the atrogen mafbx expression was 353% higher than CT mice and 42.3% higher than C26-ATB mice. No effect on the muscle protein synthesis was observed. Proteomic analyses revealed a strong effect of antibiotics on skeletal muscle proteome outside of cachexia, with adaptative processes involved in protein folding, growth, energy metabolism, and muscle contraction. In C26-ATB mice, proteome adaptations observed in CT-ATB mice were blunted. Differentially expressed proteins were involved in other processes like glucose metabolism, oxidative stress response, and proteolysis. This study confirms the existence of a microbiota-muscle axis, with a muscle response after antibiotics that varies depending on whether cachexia is present.


Assuntos
Antibacterianos , Caquexia , Músculo Esquelético , Proteoma , Caquexia/metabolismo , Caquexia/microbiologia , Animais , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/efeitos adversos , Proteoma/metabolismo , Proteoma/análise , Camundongos , Neoplasias/metabolismo , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Proteínas Musculares/metabolismo , Masculino , Proteômica/métodos , Microbiota/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos
7.
Signal Transduct Target Ther ; 9(1): 170, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38965243

RESUMO

Cancer stem cells (CSCs), a small subset of cells in tumors that are characterized by self-renewal and continuous proliferation, lead to tumorigenesis, metastasis, and maintain tumor heterogeneity. Cancer continues to be a significant global disease burden. In the past, surgery, radiotherapy, and chemotherapy were the main cancer treatments. The technology of cancer treatments continues to develop and advance, and the emergence of targeted therapy, and immunotherapy provides more options for patients to a certain extent. However, the limitations of efficacy and treatment resistance are still inevitable. Our review begins with a brief introduction of the historical discoveries, original hypotheses, and pathways that regulate CSCs, such as WNT/ß-Catenin, hedgehog, Notch, NF-κB, JAK/STAT, TGF-ß, PI3K/AKT, PPAR pathway, and their crosstalk. We focus on the role of CSCs in various therapeutic outcomes and resistance, including how the treatments affect the content of CSCs and the alteration of related molecules, CSCs-mediated therapeutic resistance, and the clinical value of targeting CSCs in patients with refractory, progressed or advanced tumors. In summary, CSCs affect therapeutic efficacy, and the treatment method of targeting CSCs is still difficult to determine. Clarifying regulatory mechanisms and targeting biomarkers of CSCs is currently the mainstream idea.


Assuntos
Neoplasias , Células-Tronco Neoplásicas , Humanos , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/metabolismo , Neoplasias/terapia , Neoplasias/genética , Neoplasias/patologia , Neoplasias/metabolismo , Transdução de Sinais , Resistencia a Medicamentos Antineoplásicos/genética
8.
Mol Med Rep ; 30(3)2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38994757

RESUMO

Cancer incidence is increasing globally, presenting a growing public health challenge. While anticancer drugs are crucial in treatment, their limitations, including poor targeting ability and high toxicity, hinder effectiveness and patient safety, requiring relentless scientific research and technological advancements to develop safer and more effective therapeutics. Cinnamaldehyde (CA), an active compound derived from the natural plant cinnamon, has garnered attention in pharmacological research due to its diverse therapeutic applications. CA has potential in treating a wide array of conditions, including cardiovascular diseases, diabetes, inflammatory disorders and various forms of cancer. The present review comprehensively summarizes the physicochemical and pharmacokinetic profiles of CA, and delves into the latest advancements in elucidating its potential mechanisms and targets across various cancer types. CA and its derivatives have antitumor effects, which encompass inhibiting cell proliferation, arresting the cell cycle, inducing apoptosis, limiting cell migration and invasion, and suppressing angiogenesis. Additionally, the present review explores targeted formulations of CA, laying a scientific foundation for further exploration of its implications in cancer prevention and treatment strategies.


Assuntos
Acroleína , Antineoplásicos , Neoplasias , Acroleína/análogos & derivados , Acroleína/química , Acroleína/farmacologia , Acroleína/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Animais , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos
9.
Front Immunol ; 15: 1434118, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38994361

RESUMO

The suppressive tumour microenvironment significantly hinders the efficacy of immunotherapy in treating solid tumors. In this context, stromal cells, such as tumour-associated fibroblasts, undergo changes that include an increase in the number and function of immunosuppressive cells. Adenosine, a factor that promotes tumour growth, is produced from ATP breakdown and is markedly elevated in the tumour microenvironment. It acts through specific binding to adenosine receptors, with A2A and A2B adenosine receptor being primary drivers of immunosuppression. This paper presents the roles of various adenosine receptors in different tumour microenvironments. This review focus on the function of adenosine receptors in the stromal cells and non-cellular components of the tumour microenvironment. Additionally, we summarize and discuss recent advances and potential trends in using adenosine receptor antagonists combined with immunotherapy.


Assuntos
Neoplasias , Receptores Purinérgicos P1 , Microambiente Tumoral , Microambiente Tumoral/imunologia , Humanos , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/terapia , Receptores Purinérgicos P1/metabolismo , Receptores Purinérgicos P1/imunologia , Animais , Imunoterapia/métodos , Adenosina/metabolismo , Adenosina/imunologia , Antagonistas de Receptores Purinérgicos P1/farmacologia , Antagonistas de Receptores Purinérgicos P1/uso terapêutico
11.
Front Immunol ; 15: 1428920, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39015566

RESUMO

Ferroptosis induces significant changes in mitochondrial morphology, including membrane condensation, volume reduction, cristae alteration, and outer membrane rupture, affecting mitochondrial function and cellular fate. Recent reports have described the intrinsic cellular iron metabolism and its intricate connection to ferroptosis, a significant kind of cell death characterized by iron dependence and oxidative stress regulation. Furthermore, updated molecular insights have elucidated the significance of mitochondria in ferroptosis and its implications in various cancers. In the context of cancer therapy, understanding the dual role of anastasis and ferroptosis in chemoresistance is crucial. Targeting the molecular pathways involved in anastasis may enhance the efficacy of ferroptosis inducers, providing a synergistic approach to overcome chemoresistance. Research into how DNA damage response (DDR) proteins, metabolic changes, and redox states interact during anastasis and ferroptosis can offer new insights into designing combinatorial therapeutic regimens against several cancers associated with stemness. These treatments could potentially inhibit anastasis while simultaneously inducing ferroptosis, thereby reducing the likelihood of cancer cells evading death and developing resistance to chemotherapy. The objective of this study is to explore the intricate interplay between anastasis, ferroptosis, EMT and chemoresistance, and immunotherapeutics to better understand their collective impact on cancer therapy outcomes. We searched public research databases including google scholar, PubMed, relemed, and the national library of medicine related to this topic. In this review, we discussed the interplay between the tricarboxylic acid cycle and glycolysis implicated in modulating ferroptosis, adding complexity to its regulatory mechanisms. Additionally, the regulatory role of reactive oxygen species (ROS) and the electron transport chain (ETC) in ferroptosis has garnered significant attention. Lipid metabolism, particularly involving GPX4 and System Xc- plays a significant role in both the progression of ferroptosis and cancer. There is a need to investigate the intricate interplay between anastasis, ferroptosis, and chemoresistance to better understand cancer therapy clinical outcomes. Integrating anastasis, and ferroptosis into strategies targeting chemoresistance and exploring its potential synergy with immunotherapy represent promising avenues for advancing chemoresistant cancer treatment. Understanding the intricate interplay among mitochondria, anastasis, ROS, and ferroptosis is vital in oncology, potentially revolutionizing personalized cancer treatment and drug development.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Ferroptose , Mitocôndrias , Neoplasias , Espécies Reativas de Oxigênio , Ferroptose/efeitos dos fármacos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Mitocôndrias/metabolismo , Animais , Metástase Neoplásica
12.
Int J Mol Sci ; 25(13)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-39000443

RESUMO

The advent of comprehensive genomic profiling using next-generation sequencing (NGS) has unveiled an abundance of potentially actionable genetic aberrations that have shaped our understanding of the cancer biology landscape. Isocitrate dehydrogenase (IDH) is an enzyme present in the cytosol (IDH1) and mitochondria (IDH2 and IDH3). In the mitochondrion, it catalyzes the irreversible oxidative decarboxylation of isocitrate, yielding the production of α-ketoglutarate and nicotinamide adenine dinucleotide phosphate (NADPH) as well as carbon dioxide (CO2). In the cytosol, IDH catalyzes the decarboxylation of isocitrate to α-ketoglutarate as well as the reverse reductive carboxylation of α-ketoglutarate to isocitrate. These rate-limiting steps in the tricarboxylic acid cycle, as well as the cytoplasmic response to oxidative stress, play key roles in gene regulation, cell differentiation, and tissue homeostasis. Mutations in the genes encoding IDH1 and IDH2 and, less commonly, IDH3 have been found in a variety of cancers, most commonly glioma, acute myeloid leukemia (AML), chondrosarcoma, and intrahepatic cholangiocarcinoma. In this paper, we intend to elucidate the theorized pathophysiology behind IDH isomer mutation, its implication in cancer manifestation, and discuss some of the available clinical data regarding the use of novel IDH inhibitors and their role in therapy.


Assuntos
Isocitrato Desidrogenase , Terapia de Alvo Molecular , Neoplasias , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/antagonistas & inibidores , Isocitrato Desidrogenase/metabolismo , Humanos , Neoplasias/genética , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Mutação , Animais , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia
13.
J Extracell Vesicles ; 13(7): e12449, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39001708

RESUMO

Hypoxia is a common feature of solid tumours and activates adaptation mechanisms in cancer cells that induce therapy resistance and has profound effects on cellular metabolism. As such, hypoxia is an important contributor to cancer progression and is associated with a poor prognosis. Metabolic alterations in cells within the tumour microenvironment support tumour growth via, amongst others, the suppression of immune reactions and the induction of angiogenesis. Recently, extracellular vesicles (EV) have emerged as important mediators of intercellular communication in support of cancer progression. Previously, we demonstrated the pro-angiogenic properties of hypoxic cancer cell derived EV. In this study, we investigate how (hypoxic) cancer cell derived EV mediate their effects. We demonstrate that cancer derived EV regulate cellular metabolism and protein synthesis in acceptor cells through increased activation of mTOR and AMPKα. Using metabolic tracer experiments, we demonstrate that EV stimulate glucose uptake in endothelial cells to fuel amino acid synthesis and stimulate amino acid uptake to increase protein synthesis. Despite alterations in cargo, we show that the effect of cancer derived EV on recipient cells is primarily determined by the EV producing cancer cell type rather than its oxygenation status.


Assuntos
Proteínas Quinases Ativadas por AMP , Vesículas Extracelulares , Glicólise , Neoplasias , Biossíntese de Proteínas , Serina-Treonina Quinases TOR , Humanos , Serina-Treonina Quinases TOR/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Vesículas Extracelulares/metabolismo , Neoplasias/metabolismo , Células Endoteliais/metabolismo , Glucose/metabolismo , Linhagem Celular Tumoral , Microambiente Tumoral , Células Endoteliais da Veia Umbilical Humana/metabolismo
14.
Mol Cancer ; 23(1): 134, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951879

RESUMO

Natural killer (NK) cells are important immune cells in the organism and are the third major type of lymphocytes besides T cells and B cells, which play an important function in cancer therapy. In addition to retaining the tumor cell killing function of natural killer cells, natural killer cell-derived exosomes cells also have the characteristics of high safety, wide source, easy to preserve and transport. At the same time, natural killer cell-derived exosomes are easy to modify, and the engineered exosomes can be used in combination with a variety of current cancer therapies, which not only enhances the therapeutic efficacy, but also significantly reduces the side effects. Therefore, this review summarizes the source, isolation and modification strategies of natural killer cell-derived exosomes and the combined application of natural killer cell-derived engineered exosomes with other antitumor therapies, which is expected to accelerate the clinical translation process of natural killer cell-derived engineered exosomes in cancer therapy.


Assuntos
Exossomos , Células Matadoras Naturais , Neoplasias , Humanos , Relevância Clínica , Exossomos/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Neoplasias/terapia , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/patologia
15.
Nanoscale ; 16(28): 13386-13398, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38967103

RESUMO

Mechanical properties, as crucial physical properties, have a significant impact on the occurrence, development, and metastasis of tumors. Regulating the mechanical properties of tumors to enhance their sensitivity to radiotherapy and chemotherapy has become an important strategy in the field of cancer treatment. Over the past few decades, nanomaterials have made remarkable progress in cancer therapy, either based on their intrinsic properties or as drug delivery carriers. However, the investigation of nanomaterials of mechanical regulation in tumor therapy is currently in its initial stages. The mechanical properties of nanomaterials themselves, drug carrier targeting, and regulation of the mechanical environment of tumor tissue have far-reaching effects on the efficient uptake of drugs and clinical tumor treatment. Therefore, this review aims to comprehensively summarize the applications and research progress of nanomaterials in tumor therapy based on the regulation of mechanical properties, in order to provide strong support for further research and the development of treatment strategies in this field.


Assuntos
Nanoestruturas , Neoplasias , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo , Humanos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Animais , Portadores de Fármacos/química , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Sistemas de Liberação de Medicamentos
16.
FASEB J ; 38(13): e23802, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38979944

RESUMO

Intercellular adhesion molecule 1 (ICAM1) is a cell surface adhesion glycoprotein in the immunoglobulin supergene family. It is associated with several epithelial tumorigenesis processes, as well as with inflammation. However, the function of ICAM1 in the prognosis of tumor immunity is still unclear. This study aimed to examine the immune function of ICAM1 in 33 tumor types and to investigate the prognostic value of tumors. Using datasets from the Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), Cancer Cell Lines Encyclopedia (CCLE), Human Protein Atlas (HPA), and cBioPortal, we investigated the role of ICAM1 in tumors. We explored the potential correlation between ICAM1 expression and tumor prognosis, gene mutations, microsatellite instability, and tumor immune cell levels in various cancers. We observed that ICAM1 is highly expressed in multiple malignant tumors. Furthermore, ICAM1 is negatively or positively associated with different malignant tumor prognoses. The expression levels of ICAM1 were correlated with the tumor mutation burden (TMB) in 11 tumors and with MSI in eight tumors. ICAM1 is a gene associated with immune infiltrating cells, such as M1 macrophages and CD8+ T cells in gastric and colon cancer. Meanwhile, the expression of ICAM1 is associated with several immune-related functions and immune-regulation-related signaling pathways, such as the chemokine signaling pathway. Our study shows that ICAM1 can be used as a prognostic biomarker in many cancer types because of its function in tumorigenesis and malignant tumor immunity.


Assuntos
Biomarcadores Tumorais , Molécula 1 de Adesão Intercelular , Neoplasias , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Molécula 1 de Adesão Intercelular/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Prognóstico , Neoplasias/imunologia , Neoplasias/genética , Neoplasias/metabolismo , Mutação , Regulação Neoplásica da Expressão Gênica , Instabilidade de Microssatélites , Microambiente Tumoral/imunologia
17.
Nat Commun ; 15(1): 5694, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38972873

RESUMO

Tumor-associated myeloid-derived cells (MDCs) significantly impact cancer prognosis and treatment responses due to their remarkable plasticity and tumorigenic behaviors. Here, we integrate single-cell RNA-sequencing data from different cancer types, identifying 29 MDC subpopulations within the tumor microenvironment. Our analysis reveals abnormally expanded MDC subpopulations across various tumors and distinguishes cell states that have often been grouped together, such as TREM2+ and FOLR2+ subpopulations. Using deconvolution approaches, we identify five subpopulations as independent prognostic markers, including states co-expressing TREM2 and PD-1, and FOLR2 and PDL-2. Additionally, TREM2 alone does not reliably predict cancer prognosis, as other TREM2+ macrophages show varied associations with prognosis depending on local cues. Validation in independent cohorts confirms that FOLR2-expressing macrophages correlate with poor clinical outcomes in ovarian and triple-negative breast cancers. This comprehensive MDC atlas offers valuable insights and a foundation for futher analyses, advancing strategies for treating solid cancers.


Assuntos
Glicoproteínas de Membrana , Células Mieloides , Neoplasias , Receptores Imunológicos , Análise de Célula Única , Microambiente Tumoral , Humanos , Análise de Célula Única/métodos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Células Mieloides/metabolismo , Células Mieloides/patologia , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Prognóstico , Neoplasias/genética , Neoplasias/patologia , Neoplasias/metabolismo , Feminino , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética
18.
Front Immunol ; 15: 1424909, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39007129

RESUMO

The study of immunometabolism, which examines how immune cells regulate their metabolism to maintain optimal performance, has become an important area of focus in cancer immunology. Recent advancements in this field have highlighted the intricate connection between metabolism and immune cell function, emphasizing the need for further research. MicroRNAs (miRNAs) have gained attention for their ability to post-transcriptionally regulate gene expression and impact various biological processes, including immune function and cancer progression. While the role of miRNAs in immunometabolism is still being explored, recent studies have demonstrated their significant influence on the metabolic activity of immune cells, such as macrophages, T cells, B cells, and dendritic cells, particularly in cancer contexts. Disrupted immune cell metabolism is a hallmark of cancer progression, and miRNAs have been linked to this process. Understanding the precise impact of miRNAs on immune cell metabolism in cancer is essential for the development of immunotherapeutic approaches. Targeting miRNAs may hold potential for creating groundbreaking cancer immunotherapies to reshape the tumor environment and improve treatment outcomes. In summary, the recognition of miRNAs as key regulators of immune cell metabolism across various cancers offers promising potential for refining cancer immunotherapies. Further investigation into how miRNAs affect immune cell metabolism could identify novel therapeutic targets and lead to the development of innovative cancer immunotherapies.


Assuntos
MicroRNAs , Neoplasias , Humanos , MicroRNAs/genética , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/terapia , Animais , Microambiente Tumoral/imunologia , Regulação Neoplásica da Expressão Gênica , Imunoterapia/métodos , Macrófagos/imunologia , Macrófagos/metabolismo , Metabolismo Energético , Células Dendríticas/imunologia , Células Dendríticas/metabolismo
19.
Int J Mol Sci ; 25(13)2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-39000555

RESUMO

Among the non-coding RNAs, the aberrant expression of microRNAs (miRNAs) is well described in the oncology field. It is clear that the altered expression of miRNAs is crucial for a variety of processes such as proliferation, apoptosis, motility, angiogenesis and metastasis insurgence. Considering these aspects, RNA-based therapies and the use of miRNAs as non-invasive biomarkers for early diagnosis are underlined as promising opportunities against cancer death. In the era of precision medicine, significant progress in next-generation sequencing (NGS) techniques has broadened knowledge regarding the miRNAs expression profile in cancer tissues and in the blood of cancer patients. In this scenario, pre-clinical and clinical studies suggested that the members of the miR-584 family, i.e., miR-584-5p and -3p, are prominent players in cancer development and progression. Under some conditions, these miRNAs are under-expressed in cancer tissues acting as tumor suppressors, while in other conditions, they are overexpressed, acting as oncogenes increasing the aggressive behavior of cancer cells. The aim of this review is to provide a comprehensive and up-to-date overview on the expression, upstream genes, molecular targets and signaling pathways influenced by the miR-584 family (i.e., miR-584-3p and -5p) in various human solid and hematological cancers. To achieve this goal, 64 articles on this topic are discussed. Among these articles, 55 are focused on miR-584-5p, and it is outlined how this miRNA could be used in future applications as a potential new therapeutic strategy and diagnostic tool.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs , Neoplasias , Humanos , MicroRNAs/genética , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Biomarcadores Tumorais/genética , Transdução de Sinais/genética , Animais
20.
Int J Mol Sci ; 25(13)2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-39000565

RESUMO

The incidence and mortality of cancer are increasing, making it a leading cause of death worldwide. Conventional treatments such as surgery, radiotherapy, and chemotherapy face significant limitations due to therapeutic resistance. Autophagy, a cellular self-degradation mechanism, plays a crucial role in cancer development, drug resistance, and treatment. This review investigates the potential of autophagy inhibition as a therapeutic strategy for cancer. A systematic search was conducted on Embase, PubMed, and Google Scholar databases from 1967 to 2024 to identify studies on autophagy inhibitors and their mechanisms in cancer therapy. The review includes original articles utilizing in vitro and in vivo experimental methods, literature reviews, and clinical trials. Key terms used were "Autophagy", "Inhibitors", "Molecular mechanism", "Cancer therapy", and "Clinical trials". Autophagy inhibitors such as chloroquine (CQ) and hydroxychloroquine (HCQ) have shown promise in preclinical studies by inhibiting lysosomal acidification and preventing autophagosome degradation. Other inhibitors like wortmannin and SAR405 target specific components of the autophagy pathway. Combining these inhibitors with chemotherapy has demonstrated enhanced efficacy, making cancer cells more susceptible to cytotoxic agents. Clinical trials involving CQ and HCQ have shown encouraging results, although further investigation is needed to optimize their use in cancer therapy. Autophagy exhibits a dual role in cancer, functioning as both a survival mechanism and a cell death pathway. Targeting autophagy presents a viable strategy for cancer therapy, particularly when integrated with existing treatments. However, the complexity of autophagy regulation and the potential side effects necessitate further research to develop precise and context-specific therapeutic approaches.


Assuntos
Antineoplásicos , Autofagia , Neoplasias , Humanos , Autofagia/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Hidroxicloroquina/uso terapêutico , Hidroxicloroquina/farmacologia
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