Explore the vast range of titles available.

Despite the promise of cold atmospheric plasma (CAP) for cancer treatment, the challenges associated with the treatment of solid tumors and penetration depth limitations remain, restricting its clinical application. Here, biological evidence is provided that the killing effect of CAP treatment is confined to less than 500 µm subcutaneously and the actual biological dose decreased gradually with depth for the first time, indicating that the limited penetration depth has become an urgent problem that demands immediate solutions. Significantly, it is showed that different from high‐dose treatments, CAP decreased the doses to the low‐dose range but still exhibited anti‐tumor effects via mitotic catastrophe. Unlike radiotherapy or chemotherapy, low‐dose CAP treatment induces mitochondrial structural damage and dysfunction, disrupts energy metabolism and redox balance, and results in mitotic catastrophe. Collectively, these findings suggest that better understanding and taking full advantage of the dose‐response gradient effect of CAP is a potential strategy to prompt its clinical application beyond improving CAP penetration. This study focuses on the limited cold atmospheric plasma (CAP) penetration, a major challenge for its clinical application, in vivo and the results show the depth‐dependent biological effect of CAP treatment for the first time. Mitochondria damage and dysfunction induced by low dose CAP suppress microtubule assemble and spindle bipolar, and ultimately result in mitotic catastrophe to suppress tumor growth.

Bioactive peptides with potent antitumor activity are attractive therapeutic agents. The present study aimed to prepare renal cell peptides (RCPs) from fetal rats to test their antitumor activities in vitro. Candidate peptides were characterized by capillary HPLC and MS and their bioactivity was predicted using PeptideRanker. The predicted top 10 bioactive peptides were synthesized and tested for their cytotoxicity against different types of tumor cells by cell counting kit‐8 assays and their half maximal inhibitory concentration values were calculated. Protease‐digested < 3 kDa protein products reduced the viability of Michigan Cancer Foundation (MCF)‐7 cells in a dose‐dependent manner. Functionally, many candidate peptides were predicted to have antitumor activity and the top ten peptides (RCPs 1–10) were synthesized. Interestingly, RCP1, 5 and 6 displayed preferable cytotoxicity against human cancer MCF‐7, A549, HCT‐116, Hela, HepG2 and SGC‐7901 cells and their cytotoxicity was dose‐dependent. RCPs prepared from fetal rats displayed potent cytotoxicity preferably against different types of cancer cells in vitro in a dose‐dependent manner which may be valuable for the treatment of malignant tumors. This study aimed to prepare renal cells (RCs) from fetal rats which were digested by enzymes. Candidate peptides RCPs were characterized by capillary HPLC and MS and their bioactivity was predicted using peptideranker. The predicted top 10 bioactive peptides were synthesized. Interestingly, RCP1, 5 and 6 displayed preferable cytotoxicity against different types of cancer cells in vitro in a dose‐dependent manner.

Background Acute myeloid leukemia (AML) is a highly aggressive form of cancer that is frequently diagnosed in adults and small molecule inhibitors have gained significant attention as a potential treatment option for AML. Methods The up‐regulated genes in AML were identified through bioinformatics analysis. Potential candidate agents were selected through pharmacogenomics analysis. Proteomic experiments were conducted to determine the molecular mechanism after inhibitor treatment. To evaluate drug synergy, both cellular functional experiments and an AML mouse model were used. Results Through bioinformatics analysis, we conducted a screening for genes that are highly expressed in AML, which led to the identification of nine small‐molecule inhibitors. Among these inhibitors, the PI3K/mTOR inhibitor VS‐5584 demonstrated significant effectiveness in inhibiting AML cell proliferation at low concentrations. Further testing revealed that VS‐5584 induced apoptosis and cycle arrest of AML cells in a dose‐ and time‐dependent manner. Proteomics analysis showed significant changes in protein expression profiles of AML cells after VS‐5584 treatment, with 287 proteins being down‐regulated and 71 proteins being up‐regulated. The proteins that exhibited differential expression were primarily involved in regulating the cell cycle and apoptosis, as determined by GO analysis. Additionally, KEGG analysis indicated that the administration of VS‐5584 predominantly affected the P53 and SIRT2 signaling pathways. The use of SIRT2 inhibitor SirReal2 alongside VS‐5584 caused a significant reduction in the half‐maximal inhibitory concentration (IC50) of VS‐5584 on AML cells. In vivo, experiments suggested that VS‐5584 combined with SirReal2 suppressed tumor growth in the subcutaneous model and extended the survival rate of mice injected with tumor cells via tail vein. Conclusions Taken together, the PI3K/mTOR inhibitor VS‐5584 was effective in suppressing AML cell proliferation. PI3K/mTOR inhibitor combined with SIRT2 inhibitor exhibited a synergistic inhibitory effect on AML cells. Our findings offer promising therapeutic strategies and drug candidates for the treatment of AML.

Immune checkpoint inhibitor (ICI) clinically benefits cancer treatment. However, the ICI responses are only achieved in a subset of patients, and the underlying mechanisms of the limited response remain unclear. 160 patients with non‐small cell lung cancer treated with anti‐programmed cell death protein‐1 (anti‐PD‐1) or anti‐programmed death ligand‐1 (anti‐PD‐L1) are analyzed to understand the early determinants of response to ICI. It is observed that high levels of intracellular adhesion molecule‐1 (ICAM‐1) in tumors and plasma of patients are associated with prolonged survival. Further reverse translational studies using murine syngeneic tumor models reveal that soluble ICAM‐1 (sICAM‐1) is a key molecule that increases the efficacy of anti‐PD‐1 via activation of cytotoxic T cells. Moreover, chemokine (CXC motif) ligand 13 (CXCL13) in tumors and plasma is correlated with the level of ICAM‐1 and ICI efficacy, suggesting that CXCL13 might be involved in the ICAM‐1‐mediated anti‐tumor pathway. Using sICAM‐1 alone and in combination with anti‐PD‐1 enhances anti‐tumor efficacy in anti‐PD‐1‐responsive tumors in murine models. Notably, combinatorial therapy with sICAM‐1 and anti‐PD‐1 converts anti‐PD‐1‐resistant tumors to responsive ones in a preclinical study. These findings provide a new immunotherapeutic strategy for treating cancers using ICAM‐1. Soluble intracellular adhesion molecule‐1 (sICAM‐1) is a co‐stimulatory molecule that activates CD4+ T cells and cytotoxic CD8+ T cells by interacting with lymphocyte function‐associated antigen‐1. sICAM‐1 induces anti‐tumor responses, reinvigorating the efficacy of anti‐programmed cell death protein‐1 (anti‐PD‐1) in cancers not responding to the anti‐PD‐1 single treatment. It suggests a therapeutic potential of sICAM‐1 in treating cancers.

Chemokines are a group of cytokines involved in the mobilization of leukocytes, which play a role in host defense and a variety of pathological conditions, including cancer. Interferon (IFN)-inducible chemokines C-X-C motif ligand 9 (CXCL), CXCL10, and CXCL11 are anti-tumor chemokines; however, the differential anti-tumor effects of IFN-inducible chemokines are not completely understood. In this study, we investigated the anti-tumor effects of IFN-inducible chemokines by transferring chemokine expression vectors into a mouse squamous cell carcinoma cell line, SCCVII, to generate a cell line stably expressing chemokines and transplanted it into nude mice. The results showed that CXCL9- and CXCL11-expressing cells markedly inhibited tumor growth, whereas CXCL10-expressing cells did not inhibit growth. The NH2-terminal amino acid sequence of mouse CXCL10 contains a cleavage sequence by dipeptidyl peptidase 4 (DPP4), an enzyme that cleaves the peptide chain of chemokines. IHC staining indicated DPP4 expression in the stromal tissue, suggesting CXCL10 inactivation. These results suggest that the anti-tumor effects of IFN-inducible chemokines are affected by the expression of chemokine-cleaving enzymes in tumor tissues.

Docosahexaenoic acid (DHA) has a variety of anti-tumor activities. The present study examined the anti-tumor activity of DHA in renal cancer cells and its underlying mechanisms of action. The effects of DHA on the viability and proliferation of the human renal cancer cell lines Caki-1 and 786-O were examined by an MTS assay and cell counting. In addition, cell cycle distribution and cell apoptosis were analyzed by flow cytometry and Annexin V staining, and modulation of cell mobility and invasiveness was assessed by wound healing and Matrigel invasion assays. Effects of DHA on intracellular signaling pathways were also analyzed by western blotting. It was observed that DHA significantly reduced the viability and proliferation of Caki-1 and 786-O cells (P<0.01). Specifically, there were increases in the sub-G1 and G2/M cell populations, as well as the percentages of cells exhibiting Annexin-positive and propidium-iodide-negative staining. In addition, the covered area in a wound and the number of cells invading through a Matrigel chamber decreased when Caki-1 or 786-O cells were treated with DHA. Phosphorylation of epidermal growth factor receptor was also upregulated following DHA treatment, while phosphorylation of signal transducer and activator of transcription 3 and Akt was downregulated. Collectively, these data suggest that DHA may be useful in the treatment of renal cell carcinoma.

Although immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for patients with many advanced malignancies, only 15–60% of patients respond, leaving a broad swath of patients who do not derive benefit. Identifying biomarkers to optimally identify patients who will benefit from ICIs is a major research focus for the oncology community. Thus far, predictive biomarker research has focused on tumor signatures such as microsatellite instability, programmed death-ligand 1 (PD-L1) expression and tumor mutational burden; clinical biomarkers have been far less studied. One potential clinical biomarker for ICI response in patients is immune-related adverse event (IRAE) onset.IRAEs are thought to represent bystander effects from activated T-cells and it is plausible that patients responding to ICIs would have greater likelihood of autoimmune toxicities (e.g. due to a more competent/treatment-responsive immune system, or cross-reactivity between tumor and host tissue). Earlier studies in melanoma patients however, suggested no association between IRAE onset and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody efficacy. In contrast, a growing body of literature suggests IRAE onset is predictive of anti-programmed cell death protein 1 (PD-1) and anti-PD-L1 antibody response across a variety of solid tumors. Most of these studies report that patients who experienced IRAEs demonstrate marked improvements in progression-free survival, overall survival and overall response rate compared to those lacking toxicity.Key questions regarding the association between IRAE onset and ICI efficacy remain. The most pertinent of these involve whether the association is only relevant for patients treated with anti-PD-1 and anti-PD-L1 antibodies and whether IRAE site, severity, timing of onset and management influence ICI efficacy. Herein, we discuss the seminal studies which have begun to address these questions and have shaped the narrative about the predictive value of IRAE onset for patients on ICIs, in this review.

Malignant cancer cells engage in a dynamic reciprocity with the tumor microenvironment (TME) that promotes tumor growth, development, and resistance to therapy. Early embryonic blastocyst microenvironments can reverse the tumorigenic phenotype of malignant cancer cells via ameliorating of TME. It is potential to apply embryonic stem cell (ESC) microenvironment to suppress the malignant behaviors of cancer cells. This study aimed to investigate a better method and the mechanism of ESC microenvironment supplied by ESCs on suppressing the malignancy of cutaneous melanoma cells. Cutaneous melanoma cell line A2058 were cultured and divided into four groups: (a) A2058‐only (Control); (b) A2058 and ESCs continuously co‐cultured (Group One); (c) A2058 co‐cultured with daily refreshed ESCs (Group two); (d) Group one with VO‐Ohpic, inhibitor of PTEN (VO‐Ohpic Group). The results showed that, compared to control group, A2058 cells in group one exhibited decreased cellular proliferation, migration, invasiveness and vasculogenic mimicry concomitant with an increase in cell apoptosis, accompanied by down‐regulation of PI3K/AKT pathway. Besides, the above mentioned anti‐tumor effects on A2058 cells were significantly enhanced in group two but statistically weakened after administration of VO‐Ohpic compared to group one. We demonstrate that ESC microenvironment reduces the malignancy of A2058 by down‐regulating PI3K/AKT pathway. Notably, such anti‐tumor effects can be enhanced by appropriately increasing the quality and quantity of ESCs in co‐culture system. Our results suggest that ESC microenvironment could be an effective and safe approach to treating cancer. We firstly demonstrate that embryonic stem cell (ESC) microenvironment supplied by ESCs inhibits malignant behaviors of cutaneous melanoma cells by down‐regulation of the PI3K/AKT pathway. Moreover, appropriate increase in the quality and quantity of ESCs in direct co‐culture system can enhance the above mentioned anti‐tumor effects.

Metformin is the most commonly prescribed drug for type 2 diabetes mellitus. In recent years, in addition to glucose lowering, several studies have presented evidence suggesting some potential role for metformin, such as antitumor effect, antiaging effect, cardiovascular protective effect, neuroprotective effect or an optional treatment for polycystic ovary syndrome. This paper will critically review the role of metformin to provide reference for doctors and researchers.

The scientific interest in the beneficial properties of natural substances has been recognized for decades, as well as the growing attention in extracellular vesicles (EVs) released by different organisms, in particular from animal cells. However, there is increasing interest in the isolation and biological and functional characterization of these lipoproteic structures in the plant kingdom. Similar to animal vesicles, these plant-derived extracellular vesicles (PDEVs) exhibit a complex content of small RNAs, proteins, lipids, and other metabolites. This sophisticated composition enables PDEVs to be therapeutically attractive. In this review, we report and discuss current knowledge on PDEVs in terms of isolation, characterization of their content, biological properties, and potential use as drug delivery systems. In conclusion, we outline controversial issues on which the scientific community shall focus the attention shortly.