RESUMO
Mesenchymal stem cells (MSCs) have been extensively used in various therapeutic applications over the last two decades, particularly in regenerative medicine and cancer treatment. MSCs have the ability to differentiate into mesodermal and non-mesodermal lineages, which makes them a popular choice in tissue engineering and regenerative medicine. Studies have shown that MSCs have inherent tumor-suppressive properties and can affect the behavior of multiple cells contributing to tumor development. Additionally, MSCs possess a tumor tropism property and have a hypoimmune nature. The intrinsic features of MSCs along with their potential to undergo genetic manipulation and be loaded with various anticancer therapeutics have motivated researchers to use them in different cancer therapy approaches without considering their complex dynamic biological aspects. However, despite their desirable features, several reports have shown that MSCs possess tumor-supportive properties. These contradictory results signify the sophisticated nature of MSCs and warn against the potential therapeutic applications of MSCs. Therefore, researchers should meticulously consider the biological properties of MSCs in preclinical and clinical studies to avoid any undesirable outcomes. This manuscript reviews preclinical studies on MSCs and cancer from the last two decades, discusses how MSC properties affect tumor progression and explains the mechanisms behind tumor suppressive and supportive functions. It also highlights critical cellular pathways that could be targeted in future studies to improve the safety and effectiveness of MSC-based therapies for cancer treatment. The insights obtained from this study will pave the way for further clinical research on MSCs and development of more effective cancer treatments.
Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Neoplasias , Humanos , Medicina Regenerativa/métodos , Neoplasias/metabolismo , Transdução de SinaisRESUMO
The treatment of brain tumours remains a challenge despite progress in surgical techniques and radio/chemotherapy. The therapeutic outcomes for glioblastoma multiform (GBM) have not been satisfactory and result in median overall survival (12-18 months). GBM displays both intra- and inter-tumour heterogeneity, causing resistance and eventually tumour recurrence. In this review, we address molecular events responsible for the dysregulation of apoptosis and introduce newly discovered non-coding RNAs (MicroRNAs and Long non-coding RNAs) that regulate tumour growth and enhance therapeutic outcomes in GBM. The combinatory use of MicroRNAs and Long non-coding RNAs with chemotherapeutic compounds, as well as the induction of suicide genes, provide an innovative therapeutic approach for the management of GBM. The understanding of GBM pathogenesis, intrinsic drug resistance mechanism, and targetable oncogenic pathways could lead to establishing novel approaches and techniques to combat GBM.
Assuntos
Neoplasias Encefálicas , Glioblastoma , MicroRNAs , RNA Longo não Codificante , Apoptose , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
The bromodomain adjacent to the zinc finger domain 1B (BAZ1B) or Williams syndrome transcription factor (WSTF) are just two of the names referring the same protein that is encoded by the WBSCR9 gene and is among the 26-28 genes that are lost from one copy of 7q11.23 in Williams syndrome (WS: OMIM 194050). Patients afflicted by this contiguous gene deletion disorder present with a range of symptoms including cardiovascular complications, developmental defects as well as a characteristic cognitive and behavioral profile. Studies in patients with atypical deletions and mouse models support BAZ1B hemizygosity as a contributing factor to some of the phenotypes. Focused analysis on BAZ1B has revealed this to be a versatile nuclear protein with a central role in chromatin remodeling through two distinct complexes as well as being involved in the replication and repair of DNA, transcriptional processes involving RNA Polymerases I, II, and III as well as possessing kinase activity. Here, we provide a comprehensive review to summarize the many aspects of BAZ1B function including its recent link to cancer.
Assuntos
Fatores de Transcrição/genética , Síndrome de Williams/genética , Animais , Montagem e Desmontagem da Cromatina , Reparo do DNA , Humanos , Neurogênese , Fatores de Transcrição/metabolismo , Síndrome de Williams/metabolismoRESUMO
The influenza virus annually causes widespread damages to the health and economy of the global community. Vaccination is currently the most crucial strategy in reducing the number of patients. Genetic variations, the high diversity of pandemic viruses, and zoonoses make it challenging to select suitable strains for annual vaccine production. If new pandemic viruses emerge, it will take a long time to produce a vaccine according to the new strains. In the present study, intending to develop a universal influenza vaccine, new bicistronic DNA vaccines were developed that expressed NP or NPm antigen with one of modified IL-18/ IL-17A/ IL-22 cytokine adjuvants. NPm is a mutant form of the antigen that has the ability for cytoplasmic accumulation. In order to investigate and differentiate the role of each of the components of Th1, Th2, Th17, and Treg cellular immune systems in the performance of vaccines, Treg competent and Treg suppressed mouse groups were used. Mice were vaccinated with Foxp3-FC immunogen to produce Treg suppressed mouse groups. The potential of the vaccines to stimulate the immune system was assessed by IFN-γ/IL-17A Dual FluoroSpot. The vaccine's ability to induce humoral immune response was determined by measuring IgG1, IgG2a, and IgA-specific antibodies against the antigen. Kinetics of Th1, Th2, and Th17 cellular immune responses after vaccination, were assessed by evaluating the expression changes of IL-17A, IFN-γ, IL-18, IL-22, IL-4, and IL-2 cytokines by semi-quantitative real-time RT-PCR. To assess the vaccines' ability to induce heterosubtypic immunity, challenge tests with homologous and heterologous viruses were performed and then the virus titer was measured in the lungs of animals. Evaluation of the data obtained from this study showed that the DNA-vaccines coding NPm have more ability to induces a potent cross-cellular immune response and protective immunity than DNA-vaccines coding NP. Although the use of IL-18/ IL-17A/ IL-22 genetic adjuvants enhanced immune responses and protective immunity, Administration of NPm in combination with modified IL-18 (Igk-mIL18-IgFC) induced the most effective immunity in Treg competent mice group.
Assuntos
Citocinas/metabolismo , Vacinas contra Influenza/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Formação de Anticorpos/efeitos dos fármacos , Antígenos Virais/imunologia , Peso Corporal , Humanos , Imunização , Interferon gama/metabolismo , Interleucina-17 , Camundongos , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/virologia , Células Th1/imunologia , Células Th2/imunologia , Vacinas de DNA/imunologiaRESUMO
Salvia verticillata is one of the salvia species which possesses remarkable antioxidant activity. In the present study, we investigated the possible effects of hydro-alcoholic extract from Salvia verticillata plant (SVE) in various models of anxiety, depression and seizure in mice. Mice were randomly divided into control (saline), SVE-treated and standard treatment groups. The SVE-treated groups received oral administration of various doses of SVE. As a standard treatment, diazepam and imipramine were used orally for anxiety/seizure and depression tests, respectively. The results of the study revealed that the plant extract produced significant anticonvulsant activity in maximal electroshock and pentylenetetrazol induced seizure models. Moreover, in forced swim test and tail suspension test of depression, SVE produced significant antidepressant effect in mice compared to control group. However, SVE did not show any effects on anxiety-like behavior of mice in elevated plus maze and light-dark tests. These results suggest potential therapeutic effects of the plant extract in seizure and depression.