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Omentum metastasis is a common occurrence in epithelial ovarian cancer (EOC), which is often accompanied by ascites that facilitates the spread of EOC cells. A subpopulation of fibroblasts-the cancer-associated fibroblasts (CAFs) are important promoters of tumor progression. We have shown previously that CAFs exist not only in omentum with EOC metastasis but also in omentum without metastasis. In the present study, using primary human fibroblasts isolated from normal omentum (NFs) and omentum with ovarian cancer metastasis (CAFs), we established in vitro coculture models and a 3D culture model mimicking human omentum structure for investigation of interactions between fibroblasts and cancer cells. We demonstrate that EOC cells activate NFs and promote their proliferation via transforming growth factor-β1 (TGF-β1) signaling, and the activated fibroblasts contribute to the invasion and adhesion of EOC cells. Moreover, EOC cells and NFs coculture led to overexpression of hepatocyte growth factor (HGF) and matrix metalloproteinase-2 (MMP-2) and adhesion and invasion of EOC cells could be partially suppressed by blocking the function of HGF or MMP-2. Additionally, mouse peritoneal dissemination models of EOC confirmed the activation of fibroblasts by cancer cells and the tumor growth- and metastasis-promoting effects of activated fibroblasts in vivo. Our findings indicate that activated fibroblasts in omentum form a congenial environment to promote EOC cells implantation. It is an intriguing concept that targeting the activation of omentum fibroblast through the inhibition of TGF-β1 signaling can be used as a new therapeutic strategy against ovarian cancer omentum metastases, which needs further study.

Development of multifunctional nanomaterials, one of the most interesting and advanced research areas in the field of nanotechnology, is anticipated to revolutionize cancer diagnosis and treatment. Gold nanoparticles (AuNPs) are now being widely utilized in bioimaging and phototherapy due to their tunable and highly sensitive optical and electronic properties (the surface plasmon resonance). As a new concept, termed “theranostics,” multifunctional AuNPs may contain diagnostic and therapeutic functions that can be integrated into one system, thereby simultaneously facilitating diagnosis and therapy and monitoring therapeutic responses. In this review, the important properties of AuNPs relevant to diagnostic and phototherapeutic applications such as structure, shape, optics, and surface chemistry are described. Barriers for translational development of theranostic AuNPs and recent advances in the application of AuNPs for cancer diagnosis, photothermal, and photodynamic therapy are discussed

Hepatocellular carcinoma (HCC) resistant to both chemotherapy and immunotherapy is among the deadliest malignancies. Doxorubicin widely used in transarterial chemotherapy in HCC can induce immunogenic cell death (ICD), but the resulting immunogenicity is still weak. We aim to seek a strategy for improving the efficacy of ICD in HCC based on an immunoregulatory drug called icaritin. Icaritin induced mitophagy and apoptosis to provoke ICD both in mouse Hepa1−6 and human Huh7 HCC cells. A combination of icaritin and doxorubicin with a molar ratio of 1:2 played a synergistic role in ICD induction. The poly lactic-co-glycolic acid (PLGA)-polyethylene glycol (PEG)-aminoethyl anisamide (AEAA) nanoparticle (NP) targeted codelivery of icaritin and doxorubicin remodeled the immunosuppressive tumor microenvironment and triggered a robust immune memory response, which efficiently improved anti-HCC effect at an early stage in mouse HCC model. In addition, the combo PLGA-PEG-AEAA NP together with lenvatinib significantly prolonged survival time of mice at the advanced stage of HCC. Collectively, our findings reveal an anti-HCC mechanism of icaritin on mitophagy and provide an effective immune-based therapeutic strategy for HCC.

miR-101 inhibits cell proliferation and invasion and enhances paclitaxel-induced apoptosis in NSCLC cells, at least in part, by directly repressing EZH2 expression. Therapeutic strategies to rescue miR-101 expression or silence EZH2 may be beneficial to patients with NSCLC in the future.

Sustained energy starvation leads to activation of AMP-activated protein kinase (AMPK), which coordinates energy status with numerous cellular processes including metabolism, protein synthesis, and autophagy. Here, we report that AMPK phosphorylates the histone methyltransferase EZH2 at T311 to disrupt the interaction between EZH2 and SUZ12, another core component of the polycomb repressive complex 2 (PRC2), leading to attenuated PRC2-dependent methylation of histone H3 at Lys27. As such, PRC2 target genes, many of which are known tumor suppressors, were upregulated upon T311-EZH2 phosphorylation, which suppressed tumor cell growth both in cell culture and mouse xenografts. Pathologically, immunohistochemical analyses uncovered a positive correlation between AMPK activity and pT311-EZH2, and higher pT311-EZH2 correlates with better survival in both ovarian and breast cancer patients. Our finding suggests that AMPK agonists might be promising sensitizers for EZH2-targeting cancer therapies.

Access to the full text of the published version may require a subscription. Rights AbstractGene silencing using RNA-interference, first described in mammalian systems almost a decade ago, is revolutionizing therapeutic target validation efforts both in vitro and in vivo. Moreover, the potential for using short interfering RNA (siRNA) as a therapy in its own right is also progressing at a significant pace. However, the widespread use of such approaches is contingent on having appropriate delivery systems to achieve clinically appropriate, safe, and efficient delivery of siRNA. There are many physicochemical and biological barriers to such delivery, and a growing emphasis on the design and characterisation of non-viral technologies that will overcome these barriers and expedite targeted delivery. This review discusses the considerations and challenges associated with use of siRNA-based therapeutics, including stability and off-target effects. Speculation is made on the properties of an ideal delivery system and the non-viral delivery approaches used to date, both in vitro and in vivo, are classified and discussed. Moreover, the ability of cyclodextrin-based delivery vectors to fulfil many of the criteria of an ideal delivery construct is also elaborated.3 Introduction: