Brusatol improves the efficacy of an anti-mouse-PD-1 antibody via inhibiting programmed cell death 1 ligand 1 expression in a murine head and neck squamous cell carcinoma model.

Objective: Combing PD-1/PD-L1 immune checkpoint inhibitors with natural products has exhibited better efficacy than monotherapy. Hence, the purpose of this research was to examine the anti-cancer effects of brusatol, a natural quassinoid-terpenoid derived from Brucea javanica, when used in conjunction with an anti-mouse-PD-1 antibody in a murine head and neck squamous cell carcinoma (HNSCC) model and elucidate underlying mechanisms.

Design: A murine HNSCC model and an SCC-15 cell xenograft nude mouse model were established to investigate the anti-cancer effects of brusatol and anti-PD-1 antibody.

HMGB1 Signaling-Mediated Tumor Immunity in Cancer Progress.

Tumor immunity is a cycle that begins with the release of antigens from tumor cells and ends with the destruction of tumor cells. High mobility group box 1 (HMGB1) is a nonhistone protein widely present in the nucleus of mammalian cells and can be released by immune cells or tumor cells. As a proinflammatory mediator or alarm protein, the activity and function of HMGB1 are determined by the environment, binding receptors, redox status and posttranslational modifications (PTMs), and HMGB1 plays a key role in inflammation and tumor immune processes.

Knockdown of HMGB1 inhibits the crosstalk between oral squamous cell carcinoma cells and tumor-associated macrophages.

Tumor-associated macrophages (TAMs), the major component of the tumor microenvironment (TME), play distinctly different roles in different tumors. High mobility group box 1 (HMGB1), a nonhistone protein in the nucleus, can perform functions during inflammation and cancers. However, the role of HMGB1 in the crosstalk between oral squamous cell carcinoma (OSCC) cells and TAMs remains unclear.

Chemoprevention of 4NQO-Induced Mouse Tongue Carcinogenesis by AKT Inhibitor through the MMP-9/RhoC Signaling Pathway and Autophagy.

Oral cancer (OC), the most common cancer in the head and neck, which has a poor prognosis, histopathologically follows a stepwise pattern of hyperplasia, dysplasia, and cancer. Blocking the progression of OC in the precancer stage could greatly improve the survival and cure rates. AKT protein plays a critical role in the signal transduction of cancer cells, and we found that AKT was overexpressed in human OC samples through analysis of TCGA database.

MMP-9 Knockdown Inhibits Oral Squamous Cell Carcinoma Lymph Node Metastasis in the Nude Mouse Tongue-Xenografted Model through the RhoC/Src Pathway.

Oral squamous cell carcinoma (OSCC) is one of the most common types of cancers in developing countries. A major contributor to the high mortality rate of OSCC is the tendency of oral cancer cells to metastasize to lymph nodes around the head and neck during the early stages of cancer development. Matrix metalloproteinase 9 (MMP-9), an endopeptidase, can degrade the extracellular matrix and basement membrane and plays a key role in tumor invasion and metastasis.

Knockdown of RhoC Inhibits Oral Squamous Cell Carcinoma Cell Invasion and Metastasis via Regulation of HMGA2.

Ras homolog family member C (RhoC) is an important component of intracellular signal transduction and its overexpression has been reported to be involved in regulating tumor proliferation, invasion, and metastasis in various malignant tumors. However, its role and underlying mechanism in oral squamous cell carcinoma (OSCC) still remain obscure. In our study, RhoC expression, its relation with clinical stages, and survival rate in OSCC were analyzed using datasets from The Cancer Genome Atlas (TCGA).

Knockdown of Matrix Metallopeptidase 9 Inhibits Metastasis of Oral Squamous Cell Carcinoma Cells in a Zebrafish Xenograft Model.

Destruction of extracellular matrix (ECM) is one of the basic steps of tumor invasion and metastasis. Matrix metalloproteinase (MMP) 9, a kind of zinc-ion-dependent endopeptidase, can degrade almost all protein components in the ECM, destroy the histological barrier of tumor cell invasion, and play a key role in tumor invasion and metastasis. The role of MMP-9 in tumor invasion and metastasis has attracted increasing attention and is considered the main proteolytic enzyme in this process.

High‑dose folic acid improves endothelial function by increasing tetrahydrobiopterin and decreasing homocysteine levels.

The aim of this study was to investigate the effect of folic acid (FA) on tetrahydrobiopterin (BH4), neopterin, nitric oxide (NO) and homocysteine (Hcy) levels in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were cultured in vitro in the presence or absence of Hcy. The effect of various doses of FA on Hcy, BH4, neopterin and NO concentrations in HUVECs was then assessed.