Simple Summary Previous clinical studies have suggested a relationship between obstructive sleep apnea and some types of cancer. This relationship is very heterogeneous, however. This heterogeneity probably depends on the complex pathophysiological pathways activated. It seems that the hypoxia inducible transcription factor, a molecule expressed in situations of hypoxemia such as obstructive sleep apnea, is a key factor. In recent years, however, some new pathophysiological pathways have been shown to be involved, including a large number of biomarkers, pathways related to immune cell dysfunction, exosomes, genetics, and even microbiome alterations. Furthermore, there is an array of tumor cell lines, each with a different capacity to respond to intermittent hypoxia. Both clinical and murine model studies suggest that tumors, such as melanoma and some histological types of breast and lung cancer, could respond in different ways from cancer cell lines in the prostate or the liver. Abstract Several epidemiological and clinical studies have suggested a relationship between obstructive sleep apnea (OSA) and a higher incidence or severity of cancer. This relationship appears to be dependent on a myriad of factors. These include non-modifiable factors, such as age and gender; and modifiable or preventable factors, such as specific comorbidities (especially obesity), the use of particular treatments, and, above all, the histological type or location of the cancer. Heterogeneity in the relationship between OSA and cancer is also related to the influences of intermittent hypoxemia (a hallmark feature of OSA), among others, on metabolism and the microenvironment of different types of tumoral cells. The hypoxia inducible transcription factor (HIF-1α), a molecule activated and expressed in situations of hypoxemia, seems to be key to enabling a variety of pathophysiological mechanisms that are becoming increasingly better recognized. These mechanisms appear to be operationally involved via alterations in different cellular functions (mainly involving the immune system) and molecular functions, and by inducing modifications in the microbiome. This, in turn, may individually or collectively increase the risk of cancer, which is then, further modulated by the genetic susceptibility of the individual. Here, we provide an updated and brief review of the different pathophysiological pathways that have been identified and could explain the relationship between OSA and cancer. We also identify future challenges that need to be overcome in this intriguing field of research.

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Potential Pathophysiological Pathways in the Complex Relationships between OSA and Cancer

Applying multi‐omics toward tumor microbiome research

Colorectal cancer (CRC) is one of the most common malignant tumor types occurring in the digestive system. The incidence of CRC has exhibits yearly increases and the mortality rate among patients with CRC is high. The Wnt/β-catenin signaling pathway, which is associated with carcinogenesis, is abnormally activated in CRC. Most patients with CRC have adenomatous polyposis coli mutations, while half of the remaining patients have β-catenin gene mutations. Therefore, targeting the Wnt/β-catenin signaling pathway for the treatment of CRC is of clinical value. In recent years, with in-depth research on the Wnt/β-catenin signaling pathway, inhibitors have been developed that are able to suppress or hinder the development and progression of CRC. In the present review, the role of the Wnt/β-catenin signaling pathway in CRC is summarized, the research status on Wnt/β-catenin pathway inhibitors is outlined and potential targets for inhibition of this pathway are presented.

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Blocking the Wnt/β-catenin signaling pathway to treat colorectal cancer: Strategies to improve current therapies (Review)

Admission systolic blood pressure and effect of endovascular treatment in patients with ischaemic stroke: an individual patient data meta-analysis

Forkhead box M1 (FOXM1), a vital member of the Forkhead box family of transcription factors, helps in mediating oncogenesis. However, limited knowledge exists regarding the mechanistic insights into the FOXM1 gene regulation. p68, an archetypal member of the DEAD-box family of RNA helicases, shows multifaceted action in cancer progression by arbitrating RNA metabolism and transcriptionally coactivating transcription factors. Here, we report a novel mechanism of alliance between p68 and the Wnt/β-catenin pathway in regulating FOXM1 gene expression and driving colon carcinogenesis. Initial bioinformatic analyses highlighted elevated expression levels of FOXM1 and p68 in colorectal cancer datasets. Immunohistochemical assays confirmed that FOXM1 showed a positive correlation with p68 and β-catenin in both normal and colon carcinoma patient samples. Overexpression of p68 and β-catenin increased the protein and mRNA expression profiles of FOXM1, and the converse correlation occurred during downregulation. Mechanistically, overexpression and knockdown of p68 and β-catenin elevated and diminished FOXM1 promoter activity respectively. Additionally, Chromatin immunoprecipitation assay demonstrated the occupancy of p68 and β-catenin at the TCF4/LEF binding element (TBE) sites on the FOXM1 promoter. Thiostrepton delineated the effect of FOXM1 inhibition on cell proliferation and migration. Colony formation assay, migration assay, and cell cycle data reveal the importance of the p68/β-catenin/FOXM1 axis in oncogenesis. Collectively, our study mechanistically highlights the regulation of FOXM1 gene expression by p68 and β-catenin in colorectal cancer.

https://www.biorxiv.org/content/biorxiv/early/2022/10/28/2022.10.28.514256.full.pdf

The DEAD-box protein p68 and β-catenin: the crucial regulators of FOXM1 gene expression in arbitrating colorectal cancer

Intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke (ENCHANTED2/MT): a multicentre, open-label, blinded-endpoint, randomised controlled trial

As one of the most common malignancies worldwide, gastric cancer contributes to cancer death with a high mortality rate partly responsible for its out-of-control progression as well as limited diagnosis. DNA methylation, one of the epigenetic events, plays an essential role in the carcinogenesis of many cancers, including gastric cancer. Long non-coding RNAs have emerged as the significant factors in the cancer progression functioned as the oncogene genes, the suppressor genes and regulators of signaling pathways over the decade. Intriguingly, increasing reports, recently, have claimed that abnormal DNA methylation regulates the expression of lncRNAs as tumor suppressor genes in gastric cancer and lncRNAs as regulators could exert the critical influence on tumor progression through acting on DNA methylation of other cancer-related genes. In this review, we summarized the DNA methylation-associated lncRNAs in gastric cancer which play a large impact on tumor progression, such as proliferation, invasion, metastasis and so on. Furthermore, the underlying molecular mechanism and signaling pathway might be developed as key points of gastric cancer range from diagnosis to prognosis and treatment in the future. 

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Regulatory function of DNA methylation mediated lncRNAs in gastric cancer

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Colorectal cancer (CRC) ranks third in terms of global incidence and second in terms of death toll among malignant tumors. Gut microbiota are involved in the formation, development, and responses to different treatments of CRC. Under normal physiological conditions, intestinal microorganisms protect the intestinal mucosa, resist pathogen invasion, and regulate the proliferation of intestinal mucosal cells via a barrier effect and inhibition of DNA damage. The composition of gut microbiota and the influences of diet, drugs, and gender on the composition of the intestinal flora are important factors in the early detection of CRC and prediction of the results of CRC treatment. Regulation of gut microbiota is one of the most promising new strategies for CRC treatment, and it is essential to clarify the effect of gut microbiota on CRC and its possible mechanisms to facilitate the prevention and treatment of CRC. This review discusses the role of gut microbiota in the pathogenesis of CRC, the potential of gut microbiota as biomarkers for CRC, and therapeutic approaches to CRC based on the regulation of gut microbiota. It might provide new ideas for the use of gut microbiota in the prevention and treatment of CRC in the near future and thus reduce the incidence of CRC.

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Therapeutic approaches to colorectal cancer via strategies based on modulation of gut microbiota

Management of antibiotic-resistant bacteria-induced skin infections for rapid healing remains a critical clinical challenge. Photothermal therapy, which uses mediated hyperthermia to combat such problems, has recently been recognised as a promising approach to take. In this study, bacterial cellulose-based photothermal membranes were designed and developed to combat bacterial infections and promote rapid wound healing. Polydopamine was incorporated into gold nanoparticles to produce superior dual-photothermal behaviour. The in vitro antibacterial efficacy of the prepared composite membranes against S. aureus, E. coli and methicillin-resistant Staphylococcus aureus (MRSA) could reach 99% under near-infrared (NIR) irradiation. In addition, the synthesised nanocomposite exhibited good biocompatibility in vitro as demonstrated by a cell survival ratio of >85%. The effectiveness of the composite membranes on wound healing was further investigated in a murine model of MRSA-infected wounds, focusing on the effect of photothermal temperature. According to the detailed therapeutic mechanism study undertaken, the composite membranes cause bacterial killing initially and promote the transition from the inflammatory phase to proliferation by suppressing pro-inflammatory cytokine production, promoting collagen deposition, and stimulating angiogenesis. Considering their remarkable effectiveness and facile fabrication process, it is expected that these novel materials could serve as competitive multifunctional dressings in the management of infectious wounds and accelerate the regeneration of damaged tissues related to abnormal immune responses.

Maohua Chen

Papers

Intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke (ENCHANTED2/MT): a multicentre, open-label, blinded-endpoint, randomised controlled trial

Regulatory function of DNA methylation mediated lncRNAs in gastric cancer

Regulatory function of DNA methylation mediated lncRNAs in gastric cancer

Therapeutic approaches to colorectal cancer via strategies based on modulation of gut microbiota

Dual photothermal nanocomposites for drug-resistant infectious wound management.