RESUMO
Pulmonary injury is one of the key restricting factors for the therapy of malignancies with chemotherapy or following radiotherapy for chest cancers. The lung is a sensitive organ to some severely toxic antitumor drugs, consisting of bleomycin and alkylating agents. Furthermore, treatment with radiotherapy may drive acute and late adverse impacts on the lung. The major consequences of radiotherapy and chemotherapy in the lung are pneumonitis and fibrosis. Pneumonitis may arise some months to a few years behind cancer therapy. However, fibrosis is a long-term effect that appears years after chemo/or radiotherapy. Several mechanisms such as oxidative stress and severe immune reactions are implicated in the progression of pulmonary fibrosis. Epithelial-mesenchymal transition (EMT) is offered as a pivotal mechanism for lung fibrosis behind chemotherapy and radiotherapy. It seems that pulmonary fibrosis is the main consequence of EMT after chemo/radiotherapy. Several biological processes, consisting of the liberation of pro-inflammatory and pro-fibrosis molecules, oxidative stress, upregulation of nuclear factor of κB and Akt, epigenetic changes, and some others, may participate in EMT and pulmonary fibrosis behind cancer therapy. In this review, we aim to discuss how chemotherapy or radiotherapy may promote EMT and lung fibrosis. Furthermore, we review potential targets and effective agents to suppress EMT and lung fibrosis after cancer therapy.
Assuntos
Quimiorradioterapia , Transição Epitelial-Mesenquimal , Fibrose Pulmonar , Humanos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Fibrose Pulmonar/etiologia , Quimiorradioterapia/efeitos adversos , Animais , Estresse Oxidativo/efeitos dos fármacos , Lesão Pulmonar/etiologia , Lesão Pulmonar/patologia , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/metabolismoRESUMO
Objective: Dementia is a broad term referring to a decline in problem-solving abilities, language skills, memory, and other cognitive functions to a degree that it significantly disrupts everyday activities. The underlying cause of dementia is the impairment or loss of nerve cells and their connections within the brain. The particular symptoms experienced are contingent upon specific regions of the brain affected by this damage. In this research, we aimed to investigate the nonlinear dynamics of the mixed demented brain compared to healthy subjects using electroencephalogram (EEG) analysis. Method : For this purpose, EEG was recorded from 66 patients with mixed dementia and 65 healthy subjects during rest. After signal preprocessing, sample entropy and Katz fractal dimension analyses were applied to the preprocessed EEG data. Analysis of variance with repeated measures was utilized to compare the nonlinear dynamics of brain activity between dementia and healthy states and partial correlation analysis was employed to explore the relationship between EEG complexity measures and cognitive and neuropsychiatric symptoms of patients. Results: Based on repeated measures ANOVA, there was a significant main effect between groups for both Katz fractal dimension (F = 4.10, P = 0.01) and sample entropy (F = 4.81, P = 0.009) measures. Post hoc comparisons revealed that EEG complexity was significantly reduced in dementia mainly in the occipitoparietal and temporal areas (P < 0.05). MMSE scores were positively correlated with EEG complexity measures, while NPI scores were negatively correlated with EEG complexity measures, mainly in the occipitoparietal and temporal areas (P < 0.05). Moreover, using a KNN classifier, all significant complexity measures yielded the best classification performance with an accuracy of 98.05%, sensitivity of 97.03% and specificity of 99.16% in detecting dementia. Conclusion: This study demonstrated a unique dynamic system within the brain impacted by dementia that results in more predictable patterns of cortical activity mainly in the occipitoparietal and temporal areas. These abnormal patterns were associated with patients' cognitive capacity and neuropsychiatric symptoms.
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Cold tumors lack antitumor immunity and are resistant to therapy, representing a major challenge in cancer medicine. Because of the immunosuppressive spirit of the tumor microenvironment (TME), this form of tumor has a low response to immunotherapy, radiotherapy, and also chemotherapy. Cold tumors have low infiltration of immune cells and a high expression of co-inhibitory molecules, such as immune checkpoints and immunosuppressive molecules. Therefore, targeting TME and remodeling immunity in cold tumors can improve the chance of tumor repression after therapy. However, tumor stroma prevents the infiltration of inflammatory cells and hinders the penetration of diverse molecules and drugs. Nanoparticles are an intriguing tool for the delivery of immune modulatory agents and shifting cold to hot tumors. In this review article, we discuss the mechanisms underlying the ability of nanoparticles loaded with different drugs and products to modulate TME and enhance immune cell infiltration. We also focus on newest progresses in the design and development of nanoparticle-based strategies for changing cold to hot tumors. These include the use of nanoparticles for targeted delivery of immunomodulatory agents, such as cytokines, small molecules, and checkpoint inhibitors, and for co-delivery of chemotherapy drugs and immunomodulatory agents. Furthermore, we discuss the potential of nanoparticles for enhancing the efficacy of cancer vaccines and cell therapy for overcoming resistance to treatment.
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Nucleic acid vaccines (NAVs) have the potential to be economical, safe, and efficacious. Furthermore, just the chosen antigen in the pathogen is the target of the immune responses brought on by NAVs. Triple-negative breast cancer (TNBC) treatment shows great promise for nucleic acid-based vaccines, such as DNA (as plasmids) and RNA (as messenger RNA [mRNA]). Moreover, cancer vaccines offer a compelling approach that can elicit targeted and long-lasting immune responses against tumor antigens. Bacterial plasmids that encode antigens and immunostimulatory molecules serve as the foundation for DNA vaccines. In the 1990s, plasmid DNA encoding the influenza A nucleoprotein triggered a protective and targeted cytotoxic T lymphocyte (CTL) response, marking the first instance of DNA vaccine-mediated immunity. Similarly, in vitro transcribed mRNA was first successfully used in animals in 1990. At that point, mice were given an injection of the gene encoding the mRNA sequence, and the researchers saw the production of a protein. We begin this review by summarizing our existing knowledge of NAVs. Next, we addressed NAV delivery, emphasizing the need to increase efficacy in TNBC.
Assuntos
Neoplasias de Mama Triplo Negativas , Vacinas de DNA , Humanos , Camundongos , Animais , Vacinas Baseadas em Ácido Nucleico , Neoplasias de Mama Triplo Negativas/terapia , Neoplasias de Mama Triplo Negativas/patologia , Imunoterapia , DNA , RNA Mensageiro/genéticaRESUMO
Ovarian cancer continues to be a difficult medical issue that affects millions of individuals worldwide. Important platforms for cancer immunotherapy include checkpoint inhibitors, chimeric antigen receptor T cells, bispecific antibodies, cancer vaccines, and other cell-based treatments. To avoid numerous infectious illnesses, conventional vaccinations based on synthetic peptides, recombinant subunit vaccines, and live attenuated and inactivated pathogens are frequently utilized. Vaccine manufacturing processes, however, are not entirely safe and carry a significant danger of contaminating living microorganisms. As a result, the creation of substitute vaccinations is required for both viral and noninfectious illnesses, including cancer. Recently, there has been testing of nucleic acid vaccines, or NAVs, as a cancer therapeutic. Tumor antigens (TAs) are genetically encoded by DNA and mRNA vaccines, which the host uses to trigger immune responses against ovarian cancer cells that exhibit the TAs. Despite being straightforward, safe, and easy to produce, NAVs are not currently thought to be an ideal replacement for peptide vaccines. Some obstacles to this strategy include selecting the appropriate therapeutic agents (TAs), inadequate immunogenicity, and the immunosuppressive characteristic of ovarian cancer. We focus on strategies that have been employed to increase NAVs' effectiveness in the fight against ovarian cancer in this review.
Assuntos
Vacinas Anticâncer , Neoplasias Ovarianas , Humanos , Feminino , Vacinas Baseadas em Ácido Nucleico , Neoplasias Ovarianas/tratamento farmacológico , Antígenos de Neoplasias , Vacinas Anticâncer/uso terapêuticoRESUMO
Head and neck cancer (HNC) refers to the epithelial malignancies of the upper aerodigestive tract. HNCs have a constant yet slow-growing rate with an unsatisfactory overall survival rate globally. The development of new blood vessels from existing blood conduits is regarded as angiogenesis, which is implicated in the growth, progression, and metastasis of cancer. Aberrant angiogenesis is a known contributor to human cancer progression. Representing a promising therapeutic target, the blockade of angiogenesis aids in the reduction of the tumor cells oxygen and nutrient supplies. Despite the promise, the association of existing anti-angiogenic approaches with severe side effects, elevated cancer regrowth rates, and limited survival advantages is incontrovertible. Exosomes appear to have an essential contribution to the support of vascular proliferation, the regulation of tumor growth, tumor invasion, and metastasis, as they are a key mediator of information transfer between cells. In the exocrine region, various types of noncoding RNAs (ncRNAs) identified to be enriched and stable and contribute to the occurrence and progression of cancer. Mounting evidence suggest that exosome-derived ncRNAs are implicated in tumor angiogenesis. In this review, the characteristics of angiogenesis, particularly in HNC, and the impact of ncRNAs on HNC angiogenesis will be outlined. Besides, we aim to provide an insight on the regulatory role of exosomes and exosome-derived ncRNAs in angiogenesis in different types of HNC.