RESUMEN
Colorectal cancer accounts for the second most common cancer-related lethality. Intestinal stem cells are responsible for enteric homeostasis maintenance that, once being transformed, become colorectal cancer stem cells. Arresting cancer stemness represents an innovative strategy for colorectal cancer management. Using intestinal stem cell organoids as the primary model, we screened common inflammatory cytokines to identify key players targeting cancer stemness. We also explored the downstream signaling that drives the functionalities of the identified cytokine through both experimental investigations and computational predictions. As the results, we identified IFNγ as the key cytokine capable of arresting intestinal stem cells via the IFNγ/IFNGR2/APC/TCF4/GPX4 axis, proposed its role in killing colorectal cancer stem cells via triggering GPX4-dependent ferroptosis, and demonstrated its synergistic anti-cancer effect with cold atmospheric plasma in killing colorectal cancer cells that is worthy to be experimentally validated.
Asunto(s)
Neoplasias Colorrectales , Ferroptosis , Neoplasias Primarias Secundarias , Humanos , Interferón gamma , Citocinas , Células Madre Neoplásicas , Factor de Transcripción 4RESUMEN
Exosomes, nano-sized extracellular vesicles for intercellular communications, are gaining rapid momentum as a novel strategy for the diagnosis and therapeutics of a spectrum of diseases including cancers. Secreted by various cell sources, exosomes pertain numerous functionalities from their parental cells and have enhanced stability that enable them with many features favorable for clinical use and commercialization. This paper focuses on the possible roles of exosomes in cancer therapeutics and reviews current exosome-based innovations toward enhanced cancer management and challenges that limit their clinical translation. Importantly, this paper casts insights on how cold atmospheric plasma, an emerging anticancer strategy, may aid in innovations on exosome-based onco-therapeutics toward improved control over cancers.
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Exosomas , Neoplasias , Transporte Biológico , Comunicación Celular , Sistemas de Liberación de Medicamentos , Exosomas/metabolismo , Humanos , Neoplasias/metabolismo , Neoplasias/terapiaRESUMEN
With the rapid advancement in sequencing technologies, the concept of omics has revolutionized our understanding of cellular behaviors. Conventional omics investigation approaches measure the averaged behaviors of multiple cells, which may easily hide signals represented by a small-cell cohort, urging for the development of techniques with enhanced resolution. Single-cell RNA sequencing, investigating cell transcriptomics at the resolution of a single cell, has been rapidly expanded to investigate other omics such as genomics, proteomics and metabolomics since its invention. The requirement for comprehensive understanding of complex cellular behavior has led to the integration of multi-omics and single-cell sequencing data with other layers of information such as spatial data and the CRISPR screening technique towards gained knowledge or innovative functionalities. The development of single-cell sequencing in both dimensions has rendered it a unique field that offers us a versatile toolbox to delineate complex diseases, including cancers.
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Genómica , Neoplasias , Genómica/métodos , Humanos , Metabolómica/métodos , Proteómica/métodos , TranscriptomaRESUMEN
Ovarian cancer (OC) causes more deaths than any other cancer of the female reproductive system due to its late presentation and malignant nature. Although significant progress has been made in the diagnosis and treatment of OC over the last decade, chemotherapeutic drug resistance and cancer recurrence remain serious challenges in OC management. In the field of cancer therapy, traditional Chinese herbal medicines and their active compounds have been widely reported to have favorable therapeutic effects on cancer. Recent studies have also revealed the protective effect of puerarin in cancer, but the exact role and underlying mechanism of puerarin in OC remain unclear. Here, we established in vivo and in vitro OC models to evaluate the anticancer effect of puerarin. It was found that puerarin significantly inhibited OC cell viability and proliferation and induced cell apoptosis. In OC model mice, puerarin treatment suppressed tumor formation and modulated the gut microbiome. In addition, the expression of tumor suppressor genes was activated by puerarin in vitro and in vivo. These findings add to the existing knowledge on the usefulness of herbal active ingredients for the prevention and treatment of OC and provide a new perspective regarding the therapeutic potential of puerarin in cancer.
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Microbioma Gastrointestinal , Neoplasias Ováricas , Animales , Carcinoma Epitelial de Ovario , Femenino , Genes Supresores de Tumor , Humanos , Isoflavonas , Ratones , Recurrencia Local de Neoplasia , Neoplasias Ováricas/tratamiento farmacológicoRESUMEN
Acetylation, a reversible epigenetic process, is implicated in many critical cellular regulatory systems including transcriptional regulation, protein structure, activity, stability, and localization. Lysine acetylation is the most prevalent and intensively investigated among the diverse acetylation forms. Owing to the intrinsic connections of acetylation with cell metabolism, acetylation has been associated with metabolic disorders including cancers. Yet, relatively little has been reported on the features of acetylation against the cancer hallmarks, even though this knowledge may help identify appropriate therapeutic strategies or combinatorial modalities for the effective treatment and resolution of malignancies. By examining the available data related to the efficacy of lysine acetylation against tumor cells and elaborating the primary cancer hallmarks and the associated mechanisms to target the specific hallmarks, this review identifies the intrinsic connections between lysine acetylation and cancer hallmarks and proposes novel modalities that can be combined with HDAC inhibitors for cancer treatment with higher efficacy and minimum adverse effects.
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Polygonatum sibiricum is a famous and well-known TCH (Traditional Chinese Herb) in China. In this paper, the complete chloroplast genome of P. sibiricum was studied and illustrated to add more genetic information and data. The chloroplast genome is 152,960 bp in length and a typical quadripartite structure, which exhibits a large single-copy region (LSC) of 81,471 bp, a small single-copy region (SSC) of 18,485 bp and a pair of inverted-repeat regions (IRs) of 26,502 bp in each. The overall nucleotide composition of chloroplast genome is: 30.7% A, 31.4% T, 19.3% C, 18.6% G and the total GC content 37.9%. A total of 136 genes were annotated that included 90 protein-coding genes (PCGs), 38 transfer RNA (tRNAs) and 8 ribosome RNA (rRNAs). The phylogenetic ML tree shown that P. sibiricum is closely related to P. cyrtonema on genetic position relationship by the Maximum-Likelihood (ML) method.
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CONTEXT: Colorectal cancer is the second leading cause of cancer deaths worldwide. DNA microarray-based technologies allow simultaneous analysis of expression of thousands of genes. AIM: To search for important molecular markers and pathways that hold great promise for further treatment of patients with colorectal cancer. MATERIALS AND METHODS: Here, we performed a comprehensive gene-level assessment of colorectal cancer using 35 colorectal cancer and 24 normal samples. RESULTS: It was shown that AURKA, MT1G, and AKAP12 had a high degree of response in colorectal cancer. Besides, we further explored the underlying molecular mechanism within these different genes. CONCLUSIONS: The results indicated calcium signaling pathway and vascular smooth muscle contraction pathway were the two significant pathways, giving hope to provide insights into the development of novel therapeutic targets and pathways.