Anticancer Effects of BAF312 (Siponimod) in Epithelial Ovarian Cancer.

Background/aim: Epithelial ovarian cancer (EOC) is a lethal disease that is the fifth leading cause of cancer-related death in women. BAF312 (siponimod) is a potent and selective sphingosine-1-phosphate (S1P) receptor modulator that has been approved as a treatment for multiple sclerosis. In addition to its immunomodulatory action, BAF312 shows preclinical antitumor effects in several cancer types.

The mA writer RBM15 drives the growth of triple-negative breast cancer cells through the stimulation of serine and glycine metabolism.

N-adenosine methylation (mA) is critical for controlling cancer cell growth and tumorigenesis. However, the function and detailed mechanism of how mA methyltransferases modulate mA levels on specific targets remain unknown. In the current study, we identified significantly elevated levels of RBM15, an mA writer, in basal-like breast cancer (BC) patients compared to nonbasal-like BC patients and linked this increase to worse clinical outcomes.

KRG and its major ginsenosides do not show distinct steroidogenic activities examined by the OECD test guideline 440 and 456 assays.

Background: Ginseng has been used as a traditional medicine for treatment of many diseases and for general health maintenance. Previously, we showed that ginseng did not demonstrate estrogenic property in ovariectomized mouse model. However, it is still possible that disruption of steroidogenesis leading to indirect hormonal activity.

Enhancement of anticancer immunity by immunomodulation of apoptotic tumor cells using annexin A5 protein-labeled nanocarrier system.

Chemotherapy promotes phosphatidylserine (PS) externalization in tumors undergoing apoptosis, forms an immunosuppressive tumor microenvironment (TME), and inhibits dendritic cell (DC) maturation and antigen presentation by binding PS receptors expressed in DCs, thereby limiting naive T cell education and activation. In this study, we demonstrate a selective nanocarrier system composed of annexin A5-labeled poly (lactide-co-glycolide) nanoparticles (PLGA_NPs) encapsulating tumor specific antigen or neoantigen, to target apoptotic tumor cells expressing PS as an innate immune checkpoint inhibitor (ICI) that induces active cancer immunotherapy. Moreover, PLGA_NPs enhanced tumor-specific antigen-based cytotoxic T cell immunity via the original function of DCs by converting the tumor antigen-rich environment.

Korean Red Ginseng attenuates Di-(2-ethylhexyl) phthalate-induced inflammatory response in endometrial cancer cells and an endometriosis mouse model.

Background: Di-(2-ethylhexyl) phthalate (DEHP) is the most common endocrine disrupting chemical used as a plasticizer. DEHP is associated with the development of endometrium-related diseases through the induction of inflammation. The major therapeutic approaches against endometrial cancer and endometriosis involve the suppression of inflammatory response.

Improvement of STING-mediated cancer immunotherapy using immune checkpoint inhibitors as a game-changer.

Various cancer therapies, such as surgery, radiotherapy, chemotherapy, and immunotherapy, have been used to treat cancer. Among cancer immunotherapies, stimulators of interferon genes (STING) activate various immune cells and induce them to attack cancer cells. However, the secretion of type I interferon (IFN α and β) increases after stimulation of the immune cell as a side effect of STING agonist, thereby increasing the expression of programmed death-ligand 1 (PD-L1) in the tumor microenvironment (TME).

Hypoxic induction of apoptosis occurs through HIF-1α and accompanies mammalian sterile 20-like kinase 2 cleavage in human endometrial adenocarcinoma Ishikawa cells.

The incidence of endometrial cancer is increasing worldwide. One of the main causes of this cancer is a hormone imbalance; progesterone derivatives have been used for treatment. However, reports have shown that hypoxia plays important and possibly beneficial roles in endometrial function.

Immune checkpoint silencing using RNAi-incorporated nanoparticles enhances antitumor immunity and therapeutic efficacy compared with antibody-based approaches.

Background: Cytotoxic CD8 T cell-based cancer immunotherapy has been extensively studied and applied, however, tumor cells are known to evade immune responses through the expression of immune checkpoints, such as programmed death ligand 1 (PD-L1). To overcome these issues, antibody-based immune checkpoint blockades (eg, antiprogrammed cell death 1 (anti-PD-1) and anti-PD-L1) have been revolutionized to improve immune responses. However, their therapeutic efficacy is limited to 15%-20% of the overall objective response rate.

A novel form of immunotherapy using antigen peptides conjugated on PD-L1 antibody.

Immune checkpoint inhibitors (ICIs), including programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 have shown promising cancer clinical outcomes. However, IC therapy has low patient response rates (10%-15%). Thus, ICIs and sufficient antigen combinations into the tumor microenvironment (TME) is important to produce strong tumor-specific adaptive immune responses.

NIR irradiation-controlled drug release utilizing injectable hydrogels containing gold-labeled liposomes for the treatment of melanoma cancer.

Drug-based chemotherapy is associated with serious side effects. We developed a chemotherapeutic system comprising a chitosan hydrogel (CH-HG) containing gold cluster-labeled liposomal doxorubicin (DOX) (CH-HG-GL) as an injectable drug depot system. CH-HG-GL can be directly injected into tumor tissue without a surgical procedure, allowing this system to act as a reservoir for liposomal DOX.

Interactions between tumor-derived proteins and Toll-like receptors.

Damage-associated molecular patterns (DAMPs) are danger signals (or alarmins) alerting immune cells through pattern recognition receptors (PRRs) to begin defense activity. Moreover, DAMPs are host biomolecules that can initiate a noninflammatory response to infection, and pathogen-associated molecular pattern (PAMPs) perpetuate the inflammatory response to infection. Many DAMPs are proteins that have defined intracellular functions and are released from dying cells after tissue injury or chemo-/radiotherapy.

Chloroquine reverses chemoresistance via upregulation of p21 and autophagy inhibition in ovarian cancer.

Overcoming drug-resistance is a big challenge to improve the survival of patients with epithelial ovarian cancer (EOC). In this study, we investigated the effect of chloroquine (CQ) and its combination with cisplatin (CDDP) in drug-resistant EOC cells. We used the three EOC cell lines CDDP-resistant A2780-CP20, RMG-1 cells, and CDDP-sensitive A2780 cells.

Nucleoporin 210 Serves a Key Scaffold for SMARCB1 in Liver Cancer.

The roles of chromatin remodelers and their underlying mechanisms of action in cancer remain unclear. In this study, SMARCB1, known initially as a bona fide tumor suppressor gene, was investigated in liver cancer. SMARCB1 was highly upregulated in patients with liver cancer and was associated with poor prognosis.

Efficacy of Combination Therapy with Linalool and Doxorubicin Encapsulated by Liposomes as a Two-in-One Hybrid Carrier System for Epithelial Ovarian Carcinoma.

Background: Epithelial ovarian cancer (EOC) is a fatal gynecologic malignancy that is usually treated with chemotherapy after surgery. However, patients who receive chemotherapy experience severe side effects because of the inherent toxicity and high dose of chemotherapeutics. To overcome these issues, we suggest a combination therapeutic strategy using liposomes encapsulating linalool nanoemulsions (LN-NEs) and doxorubicin (DOX), a chemotherapeutic drug, to increase their synergistic antitumor efficacy and reduce the incidence of side effects from chemotherapeutics for EOC.

Improvement of DC-based vaccines using adjuvant TLR4-binding 60S acidic ribosomal protein P2 and immune checkpoint inhibitors.

Cancer immunotherapy has fewer side effects and higher efficiency than conventional methods. Dendritic cell (DC)-based vaccine, a cancer immunotherapeutic, is prepared by processing mature DCs and pulsing with tumor antigen peptide ex vivo, to induce the activation of tumor-specific T lymphocytes followed by tumor clearance in vivo. Unfortunately, clinical trials of this method mostly failed due to low patient response, possibly due to the absence of novel adjuvants that induce DC maturation through Toll-like receptor (TLR) signals.

MST2 silencing induces apoptosis and inhibits tumor growth for estrogen receptor alpha-positive MCF-7 breast cancer.

Mammalian sterile 20-like kinase 1/2 (MST1/2) plays an important role in cell growth and apoptosis and functions as a tumor suppressor. Previously, we showed that MST2 overexpression activates Estrogen receptor alpha (ERα) in human breast cancer MCF-7 cells in the absence of a ligand. Here, we examined the role of MST2 in the growth of ER-positive MCF-7 cells.

RNA-binding protein NONO contributes to cancer cell growth and confers drug resistance as a theranostic target in TNBC.

Breast cancer (BC) is one of the most common cancers in women. TNBC (Triple-negative breast cancer) has limited treatment options and still lacks viable molecular targets, leading to poor outcomes. Recently, RNA-binding proteins (RBPs) have been shown to play crucial roles in human cancers, including BC, by modulating a number of oncogenic phenotypes.

Selective Tumor-Specific Antigen Delivery to Dendritic Cells Using Mannose-Labeled Poly(d, l-lactide-co-glycolide) Nanoparticles for Cancer Immunotherapy.

A key issue in dendritic cell (DC)-based cancer immunotherapy is the effective delivery of tumor-specific antigens to DCs. To deliver antigens, non-viral vaccine system has been used in ex vivo manipulation. However, manipulation is time-consuming, lacks quality control of DCs, and demonstrates low antigen delivery efficiency, which implicates that there are serious problems in therapeutic DC preparations.

Preclinical assessment of the VEGFR inhibitor axitinib as a therapeutic agent for epithelial ovarian cancer.

Axitinib, small molecule tyrosine kinase inhibitor, demonstrates anti-cancer activity for various solid tumors. We investigated anti-cancer effect of axitinib in epithelial ovarian cancer (EOC). We treated EOC cells (A2780, HeyA8, RMG1, and HeyA8-MDR) with axitinib to evaluate its effects on cell viabilty, apoptosis and migration.

CDK7 is a reliable prognostic factor and novel therapeutic target in epithelial ovarian cancer.

Objective: Cyclin-dependent kinase 7 (CDK7) engages tumor growth by acting as a direct link between the regulation of transcription and the cell cycle. Here, we investigated the clinical significance of CDK7 expression and its potential as a therapeutic target in epithelial ovarian cancer (EOC).

Methods: CDK7 expression was examined in 436 ovarian tissues including normal to metastatic ovarian tumors using immunohistochemistry, and its clinical implications were analyzed.