Personalized neoantigen vaccines are a highly specific cancer treatment designed to induce a robust cytotoxic T-cell attack against a patient’s cancer antigens. In this study, we searched ClinicalTrials.gov for neoantigen vaccine clinical trials and systematically analyzed them, a total of 147 trials. Peptide vaccines are the largest neoantigen vaccine type, comprising up to 41% of the clinical trials. However, mRNA vaccines are a growing neoantigen vaccine group, especially in the most recent clinical trials. The most common cancer types in the clinical trials are glioma, lung cancer, and malignant melanoma, being seen in more than half of the clinical trials. Small-cell lung cancer and non-small-cell lung cancer are the largest individual cancer types. According to the results from the clinical trials, neoantigen vaccines work best when combined with other cancer treatments, and popular combination treatments include immune checkpoint inhibitors, chemotherapy, and radiation therapy. Additionally, half of the clinical trials combined neoantigen vaccines with an adjuvant to boost the immune effects, with poly-ICLC being the most recurrent adjuvant choice. This study clarifies the rapid clinical trial development of personalized neoantigen vaccines as an emerging class of cancer treatment with increasingly diversified opportunities in classes, indications, and combinatorial treatments.
Neurological diseases can significantly reduce the quality and duration of life. Stem cells provide a promising solution, not only due to their regenerative features but also for a variety of other functions, including reducing inflammation and promoting angiogenesis. Although only hematopoietic cells have been approved by the FDA so far, the number of trials continues to expand. We analyzed 492 clinical trials and illustrate the trends in stem cells origins, indications, and phase and status of the clinical trials. The most common neurological disorders treated with stem cells were injuries of brain, spinal cord, and peripheral nerves (14%), stroke (13%), multiple sclerosis (12%), and brain tumors (11%). Mesenchymal stem cells dominated (83%) although the choice of stem cells was highly dependent on the neurological disorder. Of the 492 trials, only two trials have reached phase 4, with most of all other trials being in phases 1 or 2, or transitioning between them (83%). Based on a comparison of the obtained results with similar works and further analysis of the literature, we discuss some of the challenges and future directions of stem cell therapies in the treatment of neurological diseases.
4-Methylbenzylidene camphor (4-MBC) is a photo-absorbing UV filter, which can be absorbed into the circulation and cause systemic effects. 4-MBC is found extensively in the environment and measurements suggest bioaccumulation in human tissues. 4-MBC is continued to be released in the environment despite the growing knowledge about its potential endocrine and reproductive disrupting effects. 4-MBC interfers with various processes, such as placental development, spermatogenesis, and inflammatory cascades. Previous reviews mention 4-MBC as one of the several UV filters but here we focus on 4-MBC only. We cover the potential effects on human health regarding systemic and molecular effects, with the focus on reproduction. We also cover the potential bioaccumulation and interactions with receptor systems, such as the estrogen receptors β and α, and progesterone receptor, and analyze 4-MBC´s effects on mRNA expression and protein expression. Furthermore, 4-MBC is reported to act with inflammatory pathways by activating p38 MAPK and NF-κB, leading to the production of inflammatory TNF-α and IL-6. In conclusion, 4-MBC has wide ranging effects in different models while there is more research warranted to detail the mechanism of action, long-term effects at low doses and the potential interaction with many pathways and other pollutants.
4‐Methylbenzylidene camphor (4‐MBC) is a photo‐absorbing UV filter prevalently used in cosmetics, which can be absorbed into circulation and cause systemic effects. 4‐MBC is continued to be released in the environment despite the growing knowledge about its bioaccumulation and endocrine disrupting effects. Previous reviews have mentioned UV‐filter together but this review considers 4‐MBC alone, due to its prevalence and concerning health effects. This review considers 4‐MBC's potential effects on human health regarding systemic and molecular effects, with the main focus on reproduction. Also, the potential bioaccumulation and interactions with receptor systems such as the oestrogen receptors β and α, and progesterone receptor are covered. Additionally, previous studies about 4‐MBC's effects on mRNA and protein expression, especially in the prostate and the brain are analysed. Furthermore, 4‐MBC is reported to act with inflammatory pathways by activating p38 MAPK and NF‐κB, leading to the production of inflammatory TNF‐α and IL‐6. 4‐MBC was also found to induce apoptosis and inhibit cell proliferation and DNA repair. In conclusion, 4‐MBC has wide‐ranging effects in many different models interacting with multiple pathways causing long‐term effects even at low doses and this knowledge can guide governmental risk assessment, regulation divisions and chemical industries.
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