The chemotherapeutics sorafenib and regorafenib inhibit shedding of MHC class I-related chain A (MICA) from hepatocellular carcinoma (HCC) cells by suppressing a disintegrin and metalloprotease 9 (ADAM9). MICA is a ligand for natural killer (NK) group 2 member D (NKG2D) and is expressed on tumor cells to elicit attack by NK cells. This study measured ADAM9 mRNA levels in blood samples of advanced HCC patients (n = 10). In newly diagnosed patients (n = 5), the plasma ADAM9 mRNA level was significantly higher than that in healthy controls (3.001 versus 1.00, p < 0.05). Among four patients treated with nivolumab therapy, two patients with clinical response to nivolumab showed significant decreases in fold changes of serum ADAM9 mRNA level from 573.98 to 262.58 and from 323.88 to 85.52 (p < 0.05); however, two patients with no response to nivolumab did not. Using the Cancer Genome Atlas database, we found that higher expression of ADAM9 in tumor tissues was associated with poorer survival of HCC patients (log-rank p = 0.00039), while ADAM10 and ADAM17 exhibited no such association. In addition, ADAM9 expression showed a positive correlation with the expression of inhibitory checkpoint molecules. This study, though small in sample size, clearly suggested that ADAM9 mRNA might serve as biomarker predicting clinical response and that the ADAM9-MICA-NKG2D system can be a good therapeutic target for HCC immunotherapy. Future studies are warranted to validate these findings.

A cancer-associated fibroblasts (CAFs) are the most important players that modulate tumor aggressiveness. In this study, we aimed to identify CAF-related genes in ovarian serous carcinomas (OSC) that account for the high incidence and mortality of ovarian cancers (OCs) and to develop therapeutic targets for tumor microenvironment modulation. Here, we performed a microarray analysis of CAFs isolated from three metastatic and three nonmetastatic OSC tissues and compared their gene expression profiles. Among the genes increased in metastatic CAFs (mCAFs), GLIS1 (Glis Family Zinc Finger 1) showed a significant increase in both the gene mRNA and protein expression levels. Knockdown of GLIS1 in mCAFs significantly inhibited migration, invasion, and wound healing ability of OC cells. In addition, an in vivo study demonstrated that knockdown of GLIS1 in CAFs reduced peritoneal metastasis. Taken together, these results suggest that CAFs support migration and metastasis of OC cells by GLIS1 overexpression. It also indicates GLIS1 in CAFs might be a potential therapeutic target to inhibit OC metastasis.

Plants produce a wide variety of natural volatile organic compounds (NVOCs), many of which are unique to each species. These compounds serve many purposes, such as fending off herbivores and adapting to changes in temperature and water supply. Interestingly, although NVOCs are synthesized to deter herbivores, many of these compounds have been found to possess several therapeutic qualities, such as promoting nerve stability, enhancing sleep, and suppressing hyperresponsiveness, in addition to acting as antioxidants and anti-inflammatory agents. Therefore, many NVOCs are promising drug candidates for disease treatment and prevention. Given their volatile nature, these compounds can be administered to patients through inhalation, which is often more comfortable and convenient than other administration routes. However, the development of NVOC-based drug candidates requires a careful evaluation of the molecular mechanisms that drive their therapeutic properties to avoid potential adverse effects. Furthermore, even compounds that appear generally safe might have toxic effects depending on their dose, and therefore their toxicological assessment is also critical. In order to enhance the usage of NVOCs this short review focuses not only on the biological activities and therapeutic mode of action of representative NVOCs but also their toxic effects.

Age-related macular degeneration (AMD) is related to central visual loss in elderly people and, based on the increment in the percentage of the aging population, the number of people suffering from AMD could increase. AMD is initiated by retinal pigment epithelium (RPE) cell death, finally leading to neovascularization in the macula lutea. AMD is an uncurable disease, but the symptom can be suppressed. The current therapy of AMD can be classified into four types: device-based treatment, anti-inflammatory drug treatment, anti-vascular endothelial growth factor treatment, and natural product treatment. All these therapies have adverse effects, however early AMD therapy used with products has several advantages, as it can prevent RPE cell apoptosis in safe doses. Cell death (apoptosis) is caused by various factors, such as oxidative stress, inflammation, carbonyl stress, and a deficiency in essential components for cells, and RPE cell death is related to oxidative stress, inflammation, and carbonyl stress. Some natural products have anti-oxidative effects, anti-inflammation effects, and/or anti-carbonylation effects. The AMD preventive mechanism of natural products varies, with some natural products activating one or more anti-apoptotic pathways, such as the Nrf2/HO-1 anti-oxidative pathway, the anti-inflammasome pathway, and the anti-carbonyl pathway. As AMD drug candidates from natural products effectively inhibit RPE cell death, they have the potential to be developed as drugs for preventing early (dry) AMD.

In 2016, obese patients represented 13% of the worldwide adult population, and by 2030, they are projected to make up 34%. Obesity is an incommunicable disease, but it can induce many health problems. The groups consisted of a control, a 65% high-fat group, and a 250 mg/kg P. erosus group. Several biomarkers, such as body weight gain, the presence of TC/LDL/HDL in the serum, the weight of fat tissue, and liver weight/morphology, were investigated to define the anti-obesity mechanisms of P. erosus, and the adipogenesis pathway was studied. P. erosus suppressed body weight gain, decreased TC and LDL, prevented fat tissue weight gain, and prevented liver weight gain by blocking lipid droplet accumulation. P. erosus effectively decreased the up-regulated levels of leptin, significantly controlled both C/EBPα and PPARγ levels, and prevented increased FAS expression levels. We concluded that P. erosus effectively controlled obesity by regulating leptin-C/EBPα-PPARγ and FAS and might be a promising AOM.