ABSTRACT
Objective@#More than 75% of ovarian cancer patients are diagnosed at advanced stages and die of tumor cell metastasis. This study aimed to identify new epigenetic and transcriptomic alterations associated with ovarian cancer metastasis. @*Methods@#Two cell sublines with low- and high-metastasis potentials were derived from the ovarian cancer cell line A2780. Genome-wide DNA methylome and transcriptome profiling were carried out in these two sublines by Reduced Representation Bisulfite Sequencing and RNA-seq technologies. Cell-based assays were conducted to support the clinical findings. @*Results@#There are distinct DNA methylation and gene expression patterns between the two cell sublines with low- and high-metastasis potentials. Integrated analysis identified 33 methylation-induced genes potentially involved in ovarian cancer metastasis. The DNA methylation patterns of two of them (i.e., SFRP1 and LIPG) were further validated in human specimens, indicating that they were hypermethylated and downregulated in peritoneal metastatic ovarian carcinoma compared to primary ovarian carcinoma. Patients with lower SFRP1 and LIPG expression tend to have a worse prognosis. Functionally, knockdown of SFRP1 and LIPG promoted cell growth and migration, whereas their overexpression resulted in the opposite effects. In particular, knockdown of SFRP1 could phosphorylate GSK3β and increase β-catenin expression, leading to deregulated activation of the Wnt/β-catenin signaling. @*Conclusion@#Many systemic and important epigenetic and transcriptomic alterations occur in the progression of ovarian cancer. In particular, epigenetic silencing of SFRP1 and LIPG is a potential driver event in ovarian cancer metastasis. They can be used as prognostic biomarkers and therapeutic targets for ovarian cancer patients.
ABSTRACT
Malignant tumor is a persistent disease that perplexes public health. Traditional treatment appears ineffective for patients with advanced metastasis. In recent years, immune checkpoint inhibitor therapy has developed rapidly and has great potential, but the overall clinical efficiency is still low. Carcinoma changes the tumor microenvironment through various mechanisms, resulting in immune resistance, which greatly reduces the efficacy of immune checkpoint inhibitors. Hyperthermia can not only play the anti-tumor advantage of thermal effect, but also play a direct and indirect immune sensitization effect through a variety of ways, transforming" cold tumor" into" hot tumor" , to enhance the impact of immune checkpoint inhibitors in many patterns. Numerous basic experiments have proved that hyperthermia combined with immune checkpoint inhibitors has achieved a classy impression in mice. Presently, some ongoing clinical trials of hyperthermia combined with immune checkpoint inhibitors have gained promising progress. In this paper, the merits of combination therapy were analyzed from three aspects: immune checkpoint inhibitors, hyperthermia, hyperthermia combined with immune checkpoint inhibitors, and the future research directions of hyperthermia combined with immune checkpoint inhibitors were prospected.
ABSTRACT
Myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are bone marrow disorders characterized by cytopenias and progression to acute myeloid leukemia. Hypomethylating agents (HMAs) are Food and Drug Administration-approved therapies for MDS and MDS/MPN patients. HMAs have improved patients’ survival and quality of life when compared with other therapies. Although HMAs are effective in MDS and MDS/MPN patients, they are associated with significant toxicities that place a large burden on patients. Our goal is to develop a safer and more effective HMA from natural products. We previously reported that black raspberries (BRBs) have hypomethylating effects in the colon, blood, spleen, and bone marrow of mice. In addition, BRBs exert hypomethylating effects in patients with colorectal cancer and familial adenomatous polyposis. In the current study, we conducted a pilot clinical trial to evaluate the hypomethylating effects of BRBs in patients with low-risk MDS or MDS/MPN. Peripheral blood mononuclear cells (PBMCs) were isolated before and after three months of BRB intervention. CD45 + cells were isolated from PBMCs for methylation analysis using a reduced-representation bisulfite sequencing assay. Each patient served as their own matched control, with their measurements assessed before intervention providing a baseline for post-intervention results. Clinically, our data showed that BRBs were well-tolerated with no side effects. When methylation data was combined, BRBs significantly affected methylation levels of 477 promoter regions. Pathway analysis suggests that BRB-induced intragenic hypomethylation drives leukocyte differentiation. A randomized, placebo-controlled clinical trial of BRB use in low-risk MDS or MDS/ MPN patients is warranted.
ABSTRACT
@#Objective The article described the design and building of a virtual reality technology-based rehabilitation system for patients with cognitive deficits, including overall idea, design and structure of the system, the key technology, such as formal description of the training data, man-machine interactive control, controlling simulation of the training process and virtual environment module development to achieve system implementation. The system is suitable for our country and military. It will create a new way for the cognitive rehabilitation and help to promote the application of virtual reality technology in rehabilitation