Yingjun Xie

Surgery is the main treatment for liver cancer in clinic owing to its low sensitivity to chemotherapy and radiotherapy, but this results in high mortality, recurrence, and metastasis rates. It is a feasible strategy to construct tumor microenvironments activated by nanotheranostics agents for the diagnosis and therapy of liver cancer. This study reports on a nanotheranostic agent (MONs@PDA-ICG) with manganese oxide nanoflowers (MONs) as core and polydopamine (PDA) as shell loading, with ICG as a photosensitizer and photothermal agent. MONs@PDA-ICG can not only produce ROS to kill cancer cells but also exhibit good photothermal performance for photothermal therapy (PTT). Importantly, O₂ generated by MONs decomposition can relieve the tumor hypoxia and further enhance the treatment effects of photodynamic therapy (PDT). In addition, the released Mn²⁺ ions make MONs@PDA-ICG serve as tumor microenvironments responsive to MRI contrast for highly sensitive and specific liver cancer diagnosis.

Microorganisms can help maintain homeostasis in humans by providing nutrition, maintaining hormone balance, and regulating inflammatory responses. In the case of imbalances, these microbes can cause various diseases, even malignancy. Pancreatic cancer (PC) is characterized by high tumor invasiveness, distant metastasis, and insensitivity to traditional chemotherapeutic drugs, and it is confirmed that PC is closely related to microorganisms. Recently, most studies based on clinical samples or case reports discussed the positive or negative relationships between microorganisms and PC. However, the specific mechanisms are blurry, especially the involved immunological pathways, and the roles of beneficial flora have usually been ignored. We reviewed studies published through September 2020 as identified using PubMed, MEDLINE, and Web of Science. We mainly introduced the traits of oral, gastrointestinal, and intratumoral microbes in PC and summarized the roles of these microbes in tumorigenesis and tumoral development through immunological pathways, in addition to illustrating the relationships between metabolic diseases with PC by microorganism. In addition, we identified microorganisms as biomarkers for early diagnosis and immunotherapy. This review will be significant for greater understanding the effect of microorganisms in PC and provide more meaningful guidance for future clinical applications.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and is associated with a high mortality rate and poor treatment efficacy. In an attempt to investigate the mechanisms involved in the pathogenesis of HCC, bioinformatic analysis and validation by qRT-PCR were performed. Three circRNA GEO datasets and one miRNA GEO dataset were selected for this purpose. Upon combined biological prediction, a total of 11 differentially expressed circRNAs, 15 differentially expressed miRNAs, and 560 target genes were screened to construct a circRNA-related ceRNA network. GO analysis and KEGG pathway analysis were performed for the 560 target genes. To further screen key genes, a protein-protein interaction network of the target genes was constructed using STRING, and the genes and modules with higher degree were identified by MCODE and CytoHubba plugins of Cytoscape. Subsequently, a module was screened out and subjected to GO enrichment analysis and KEGG pathway analysis. This module included eight genes, which were further screened using TCGA. Finally, UBE2L3 was selected as a key gene and the hsa_circ_0009910–miR-1261–UBE2L3 regulatory axis was established. The relative expression of the regulatory axis members was confirmed by qRT-PCR in 30 pairs of samples, including HCC tissues and adjacent nontumor tissues. The results suggested that hsa_circ_0009910, which was upregulated in HCC tissues, participates in the pathogenesis of HCC by acting as a sponge of miR-1261 to regulate the expression of UBE2L3. Overall, this study provides support for the possible mechanisms of progression in HCC.

Increasing evidence supports the association of microRNA with tumor occurrence and development. However, the expression of miR-6875-3p and its role in cell proliferation, invasion and metastasis in hepatocellular carcinoma (HCC) remains elusive. The expression of miR-6875-3p and BTG2 in HCC tissues and cell lines was detected by using in situ hybridization, immunohistochemistry and qRT-PCR, respectively. A western blot assay, qRT-PCR and Luciferase reporter assay were employed to study the interaction between miR-6875-3p and BTG2. Cell proliferation invasion and metastasis were measured by MTT, transwell and matrigel analyses in vitro. In vivo, tumorigenicity and metastasis assays were performed in nude mice. We found that miR-6875-3p were elevated expressed in HCC tissues and cell lines, and negatively correlated with BTG2 expression, while positively correlated with tumor staging, size, degree of differentiation, and vascular invasion of HCC. Moreover, in vitro and in vivo assays showed that miR-6875-3p regulates EMT and improve the proliferation, metastasis and stem cell-like properties of HCC cells. BTG2 was identified as a direct and functional target of miR-6875-3p via the 3’-UTR of BTG2. We also confirmed that miR-6875-3p plays its biological functions via the BTG2/FAK/Akt pathway. Our study provides evidence that high expression of miR-6875-3p can promote tumorigenesis of HCC in vitro and in vivo, so as to function as a novel oncogene in HCC. In mechanism, we found that miR-6875-3p plays its biological functions via the BTG2/FAK/Akt pathway.

Primary liver cancer is a common kind of digestive cancers with high malignancy, causing 745,500 deaths each year. Hepatocellular carcinoma is the major pathological type of primary liver cancer. Traditional treatment methods for patients with hepatocellular carcinoma have shown poor efficacy in killing residual cancer cells for a long time. In recent years, tumor immunotherapy has emerged as a promising method owing to its safety and efficacy with respect to delaying the progression of advanced tumors and protecting postoperative patients against tumor relapse and metastasis. Immune tolerance and suppression in tumor microenvironments are the theoretical basis of immunotherapy. Adoptive cell therapy functions by stimulating and cultivating autologous lymphocytes ex vivo and then reinfusing them into the patient to kill cancer cells. Cancer vaccination is performed using antigenic substances to activate tumor-specific immune responses. Immune checkpoint inhibitors can reactivate tumor-specific T cells and develop an antitumor effect by suppressing checkpoint-mediated signaling. Oncolytic viruses may selectively replicate in tumor cells and cause lysis without harming normal tissues. Here, we briefly introduce the mechanism of immunosuppression in hepatocellular carcinoma and summarize the rationale of the four major immunotherapeutic approaches with their current advances.

Hypoxia is prognostically important in colorectal cancer (CRC) therapy. Partial oxygen pressure (pO₂) is an important parameter of hypoxia. The correlation between pO₂ levels and expression levels of prognostic biomarkers was measured in CRC tissues. Human CRC tissues were collected and pO₂ levels were measured by OxyLite. Three methods for tissue fixation were compared, including formalin, Finefix, and Finefix‐plus‐microwave. Immunohistochemistry (IHC) staining was conducted by using the avidin‐biotin complex technique for detecting the antibodies to hypoxia inducible factor‐1 (HIF‐1) alpha, cytokeratin 20 (CK20), and cell proliferation factor Ki67. The levels of pO₂ were negatively associated with the size of CRC tissues. Finefix‐plus‐microwave fixation has the potential to replace formalin. Additionally, microwave treatment improved Finefix performance in tissue fixation and protein preservation. The percentage of positive cells and gray values of HIF‐1 alpha, CK20, and Ki67 were associated with CRC development (P < 0.05). The levels of pO₂ were positively related with the gray values of Ki67 and negatively related with the values of HIF‐1 alpha and CK20 (P < 0.05). Thus, the levels of microenvironmental pO₂ affect the expression of predictive biomarkers HIF‐1 alpha, CK20, and Ki67 in the development of CRC tissues.