Lipidomic analysis of plant-derived extracellular vesicles for guidance of potential anti-cancer therapy.

Plant-derived extracellular vesicles (PEVs) have been regarded as a superior source for nanomedicine and drug delivery systems. Nevertheless, their clinical translation is hindered by the lack of clarity and even contradiction in their biomedical applications. Herein, we conducted a comprehensive compositional analysis of four commonly used PEVs to fully understand their functional lipid contents and assess their potential therapeutic applications.

Reversing Immune Checkpoint Inhibitor-Associated Cardiotoxicity via Bioorthogonal Metabolic Engineering-Driven Extracellular Vesicle Redirecting.

The cardiotoxicity induced by immune checkpoint inhibitors (ICIs) is associated with high mortality rates. T cells play an important role in ICI-induced cardiac injury. The inhibition of local T-cell activity is considered an effective strategy for alleviating ICI-related cardiotoxicity.

High-Lactate-Metabolizing Photosynthetic Bacteria Reprogram Tumor Immune Microenvironment.

The elevated levels of lactate in tumor tissue play a pivotal role in fostering an immunosuppressive microenvironment. Therefore, efficiently reducing lactate levels to reprogram tumor immune microenvironment (TIM) is considered a crucial step for boosted immunotherapy. Here, a high-lactate-metabolizing photosynthetic bacteria (LAB-1) is selectively screened for TIM reprogramming, which then improves the efficacy of tumor immunotherapy.

A transdermal drug delivery system based on dissolving microneedles for boron neutron capture therapy of melanoma.

Boron neutron capture therapy (BNCT) is a promising therapy for malignant tumors that requires selective and high concentrations of B accumulation in tumor cells. Despite ongoing developments in novel boron agents and delivery carriers, the progress and clinical application of BNCT is still restricted by the low B accumulation and tumor-to-normal tissue (T/N) ratio. Herein, a dissolving microneedle-based transdermal drug delivery system was specifically designed for BNCT in a mouse model of melanoma.

Role and clinical implication of autophagy in COVID-19.

The ongoing coronavirus disease 2019 (COVID-19) pandemic constitutes a serious public health concern worldwide. Currently, more than 6 million deaths have occurred despite drastic containment measures, and this number is still increasing. Currently, no standard therapies for COVID-19 are available, which necessitates identifying effective preventive and therapeutic agents against COVID-19.

Establishment of Sensitive Sandwich-Type Chemiluminescence Immunoassay for Interleukin-18 in Urinary Samples.

Interleukin-18 (IL-18), a member of IL-1 cytokine superfamily, is deemed as an important indicator of the kidney disease. Herein a sandwich chemiluminescence immunoassay integrated with magnetic beads was conducted to detect IL-18 in kidney disease. The detection limit and linear range were 0.

Chemiluminescence Immunoassay Method of Urinary Liver Fatty-acid-binding Protein as a Promising Candidate for Kidney Disease.

Liver fatty acid binding protein (L-FABP) is an intercellular lipid chaperone protein that selectively combines with unsaturated free fatty acids and transports them to mitochondria or peroxisomes. L-FABP is a promising biomarker for the early detection of renal diseases in humans. Herein a chemiluminescence method (CLIA) was demonstrated to measure the level of urinary L-FABP in the urinary samples.

RSK2 promotes melanoma cell proliferation and vemurafenib resistance upregulating cyclin D1.

BRAF inhibitors are commonly used in targeted therapies for melanoma patients harboring BRAF mutant. Despite the benefit of vemurafenib therapy, acquired resistance during or after treatment remains a major obstacle in BRAF mutant melanoma. Here we found that RSK2 is overexpressed in melanoma cells and the high expression of RSK2 indicates poor overall survival (OS) in melanoma patients.

Decoy Exosomes Offer Protection Against Chemotherapy-Induced Toxicity.

Cancer patients often face severe organ toxicity caused by chemotherapy. Among these, chemotherapy-induced hepatotoxicity and cardiotoxicity are the main causes of death of cancer patients. Chemotherapy-induced cardiotoxicity even creates a new discipline termed "cardio-oncology".

CHMFL-BMX-078, a BMX inhibitor, overcomes the resistance of melanoma to vemurafenib via inhibiting AKT pathway.

Our recent study demonstrated eIF3a loss contributes to vemurafenib resistance in melanoma by activating ERK. However, overexpression of eIF3a in the clinic is not feasible to produce vemurafenib re-sensitization, and ERK inhibitors combined with vemurafenib still exhibit limited effectiveness in the treatment of melanoma. Here, using the human receptor tyrosine kinase phosphorylation antibody array, we observed that silencing eIF3a could activate BMX, a tyrosine kinase.

DNA Repair Pathways in Cancer Therapy and Resistance.

DNA repair pathways are triggered to maintain genetic stability and integrity when mammalian cells are exposed to endogenous or exogenous DNA-damaging agents. The deregulation of DNA repair pathways is associated with the initiation and progression of cancer. As the primary anti-cancer therapies, ionizing radiation and chemotherapeutic agents induce cell death by directly or indirectly causing DNA damage, dysregulation of the DNA damage response may contribute to hypersensitivity or resistance of cancer cells to genotoxic agents and targeting DNA repair pathway can increase the tumor sensitivity to cancer therapies.

Inhibition of AXL enhances chemosensitivity of human ovarian cancer cells to cisplatin via decreasing glycolysis.

Anexelekto (AXL), a member of the TYRO3-AXL-MER (TAM) family of receptor tyrosine kinases (RTK), is overexpressed in varieties of tumor tissues and promotes tumor development by regulating cell proliferation, migration and invasion. In this study, we investigated the role of AXL in regulating glycolysis in human ovarian cancer (OvCa) cells. We showed that the expression of AXL mRNA and protein was significantly higher in OvCa tissue than that in normal ovarian epithelial tissue.

RSK2 protects human breast cancer cells under endoplasmic reticulum stress through activating AMPKα2-mediated autophagy.

Autophagy can protect stressed cancer cell by degradation of damaged proteins and organelles. However, the regulatory mechanisms behind this cellular process remain incompletely understood. Here, we demonstrate that RSK2 (p90 ribosomal S6 kinase 2) plays a critical role in ER stress-induced autophagy in breast cancer cells.

UCH-L1-mediated Down-regulation of Estrogen Receptor α Contributes to Insensitivity to Endocrine Therapy for Breast Cancer.

: To determine the role of UCH-L1 in regulating ERα expression, and to evaluate whether therapeutic targeting of UCH-L1 can enhance the efficacy of anti-estrogen therapy against breast cancer with loss or reduction of ERα. : Expressions of UCH-L1 and ERα were examined in breast cancer cells and patient specimens. The associations between UCH-L1 and ERα, therapeutic response and prognosis in breast cancer patients were analyzed using multiple databases.

Correction: Sirt3-mediated mitophagy protects tumor cells against apoptosis under hypoxia.

[This corrects the article DOI: 10.18632/oncotarget.9717.

Anticancer strategies based on the metabolic profile of tumor cells: therapeutic targeting of the Warburg effect.

Tumor cells rely mainly on glycolysis for energy production even in the presence of sufficient oxygen, a phenomenon termed the Warburg effect, which is the most outstanding characteristic of energy metabolism in cancer cells. This metabolic adaptation is believed to be critical for tumor cell growth and proliferation, and a number of onco-proteins and tumor suppressors, including the PI3K/Akt/mTOR signaling pathway, Myc, hypoxia-inducible factor and p53, are involved in the regulation of this metabolic adaptation. Moreover, glycolytic cancer cells are often invasive and impervious to therapeutic intervention.

Sirt3-mediated mitophagy protects tumor cells against apoptosis under hypoxia.

Sirt3, a mitochondrial deacetylase, participates in the regulation of multiple cellular processes through its effect on protein acetylation. The objective of this study was to explore the role of Sirt3 in the mitochondrial autophagy (mitophagy), a process of the specific autophagic elimination of damaged mitochondria. We found that silencing of Sirt3 expression in human glioma cells by RNA interference blunted the hypoxia-induced the localization of LC3 on the mitochondria, and the degradation of mitochondria.