Characteristics of clinical trials for non-small cell lung cancer therapeutic vaccines registered on ClinicalTrials.gov.

Background: Even after complete surgical treatment or chemotherapy, Non-Small Cell Lung Cancer (NSCLC) patients are also at substantial risk for recurrence and spread trend. Therapeutic cancer vaccination could increase the anti-tumor immune response and prevent tumor relapse. This study aimed to assess the characteristics of NSCLC therapeutic vaccines registered on ClinicalTrials.gov. Methods: We conducted a cross-sectional, descriptive study of clinical trials for Non-Small Cell Lung Cancer Therapeutic Vaccines Registered on ClinicalTrials.gov (https://clinicaltrials.gov/) through March 17, 2022. Results: This study encompassed 117 registered trials included for data analysis. The number of trials was significantly correlated with a beginning year (r = 0.504, P < 0.010). Of these trials, 45.30% were completed, 12.82% were terminated, and 8.55% were withdrawn. More than half of trials (52.99%) were funded by industry, and more than half of trials (52.14%) were located in economically developed North America. Regarding study designs of these trials, 27.35% were randomized, 52.14% were single group assignment, 83.76% were without masking, 35.90% were phase 1, and more than half of the trials (56.41%) recruited less than 50 participants. The highest proportion of vaccine types was protein/peptide vaccines (41.88%). Regarding TNM staging, the highest proportion of the trials is stage III-IV (26.50%). Conclusion: The number of clinical trials about the cancer therapeutic vaccines was sustained an increase in recent years. The main characteristic of clinical trials for NSCLC therapeutic vaccines is lack of randomized control, lack of mask, and recruiting less than 50 participants. In recent years, the protein/peptide vaccines for NSCLC active immunotherapy have been well studied.

The N-terminus of a Fusarium graminearum-secreted protein enhances broad-spectrum disease resistance in plants.

Fusarium head blight is a destructive disease caused by Fusarium species. Little is known about the pathogenic molecular weapons of Fusarium graminearum. The gene encoding a small secreted protein, Fg02685, in F. graminearum was found to be upregulated during wheat head infection. Knockout mutation of Fg02685 reduced the growth and development of Fusarium in wheat spikes. Transient expression of Fg02685 or recombinant protein led to plant cell death in a BAK1- and SOBIR1-independent system. Fg02685 was found to trigger plant basal immunity by increasing the deposition of callose, the accumulation of reactive oxygen species (ROS), and the expression of defence-related genes. The Fg02685 signal peptide was required for the plant's apoplast accumulation and induces cell death, indicating Fg02685 is a novel conserved pathogen-associated molecular pattern. Moreover, its homologues are widely distributed in oomycetes and fungal pathogens and induced cell death in tobacco. The conserved α-helical motif at the N-terminus was necessary for the induction of cell death. Moreover, a 32-amino-acid peptide, Fg02685 N-terminus peptide 32 (FgNP32), was essential for the induction of oxidative burst, callose deposition, and mitogen-activated protein kinase signal activation in plants. Prolonged exposure to FgNP32 enhanced the plant's resistance to Fusarium and Phytophthora. This study provides new approaches for an environment-friendly control strategy for crop diseases by applying plant immune inducers to strengthen broad-spectrum disease resistance in crops.

Organophosphate flame retardants induce oxidative stress and Chop/Caspase 3-related apoptosis via Sod1/p53/Map3k6/Fkbp5 in NCI-1975 cells.

Organophosphate flame retardants (OPFRs) have been ubiquitously detected in dust and air which could cause damage to human health through inhalation. Currently the understanding of their adverse effects and potential mechanisms on the lung are still limited. In this study, human non-small cell lung cancer cell line NCI-H1975 was used to investigate the cytotoxicity, oxidative stress, cellular apoptosis of 9 typical OPFRs with concentrations varied from 0 to 200 µM, and their toxic mechanism associated with molecular structure was compared. After 72 h, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) displayed the highest cytotoxicity, followed by 2-ethylhexyl diphenyl phosphate (EHDPP), tris(2-butoxyethyl) phosphate (TBOEP) and tris(2-chloroisopropyl) phosphate (TCIPP), while tris(2-chloroethyl) phosphate (TCEP) and tris(2-ethylhexyl) phosphate (TEHP) exhibited the least suppression on cell viability. These results indicated that the variation of cytotoxicity on OPFRs could only be partially explained by their ester linkage. Moreover, the overexpression of intracellular reactive oxygen species (ROS), free Ca2+ and cellular apoptosis suggested that exposure to OPFRs can lead to apoptosis related to oxidative stress. Six genes associated with oxidative stress and apoptosis were upregulated dramatically compared with the control, demonstrating OPFRs induced Chop/Caspase 3-related apoptosis by activating Sod1/p53/Map3k6/Fkbp5 expression in NCI-H1975 cells. This is the first study to investigate cytotoxicity and related mechanism on commonly-used OPFRs in NCI-H1975 cells.

Correction: Preparation of electrospray ALG/PDA-PVP nanocomposites and their application in cancer therapy.

Correction for 'Preparation of electrospray ALG/PDA-PVP nanocomposites and their application in cancer therapy' by Yangjie Xu et al., Soft Matter, 2020, 16, 132-141.

Preparation of electrospray ALG/PDA-PVP nanocomposites and their application in cancer therapy.

In this study, sodium alginate (ALG)/poly dopamine (PDA)-polyvinylpyrrolidone (PVP) nanocomposites was synthesized via a one-step electrostatic spraying method. The spinning solution of ALG and dopamine was electrostatically sprayed into an alkaline solution of PVP, calcium chloride and tris buffer (pH = 8.5), in which the gelation of ALG and the polymerization of dopamine could be simultaneously triggered. PDA hence produced possesses a high photothermal conversion efficiency, while the PVP that was facilely conjugated onto the surface of nanocomposites improves the colloidal stability and compatibility of the material. Moreover, the ALG renders the nanocomposite excellent drug (doxorubicine, DOX) loading capacity. Promisingly, the temperature increment during the PTT process could promote the DOX release, thus enhancing its therapeutic effect. The in vitro/in vivo biosafety and tumor treatment experiments further corroborate that the ALG/PDA-PVP nanocomposites have remarkable biocompatibility and synergism for tumor hyperthermia and chemotherapy. Consequently, such a one-step electrospray strategy provides a new way for designing nanomaterials and is expected to significantly promote the development of organic photothermal therapeutic agents with excellent bio-compatibility.

Curcumin reverses irinotecan resistance in colon cancer cell by regulation of epithelial-mesenchymal transition.

The objective of this study was to investigate the effect and the mechanism by which curcumin reverses irinotecan-induced chemotherapy resistance in colon cancer. Construction of irinotecan-resistant colon cancer model LoVo/CPT-11R cells was performed by increasing drug concentration. The Cell Counting Kit-8 assay was used to detect inhibition of proliferation; cell morphology was observed by an optical microscope. Quantitative RT-PCR and western blotting were performed to detect molecular marker expressions during epithelial-mesenchymal transition (EMT); drug-resistant cells were treated with curcumin at different concentrations and Cell Counting Kit-8 was reperformed to detect cell proliferation after treatments. Drug-resistant cells were then divided into four groups: control group, irinotecan group, curcumin group, and irinotecan+curcumin group; quantitative RT-PCR and western blotting were performed to detect molecular marker expressions during epithelial-mesenchymal transition. Flow cytometry was used to detect cell apoptosis after grouping, and apoptosis-related protein was detected by western blotting. LoVo/CPT-11R cells could survive in culture medium containing irinotecan at 60 µg/ml and the drug-resistance index was 5.69; the drug-resistant cells had a larger volume than normal cells and were poorly connected to each other. E-cadherin expression was downregulated, whereas vimentin and N-cadherin expressions were upregulated. After curcumin treatment, drug-resistant cell proliferation was significantly inhibited; in the curcumin+irinotecan treatment group, E-cadherin expression was upregulated, whereas vimentin and N-cadherin expressions were downregulated. Curcumin could significantly increase cell apoptosis. EMT is involved in the development of irinotecan resistance and curcumin can reverse this drug resistance through reversion of the EMT process.