Non-small cell lung cancer (NSCLC) is the leading cause of death by cancer worldwide. Despite developments in therapeutic approaches for the past few decades, the 5-year survival rate of patients with NSCLC remains low. NSCLC tumor is a complex, heterogeneous microenvironment, comprising blood vessels, cancer cells, immune cells, and stroma cells. Vascular endothelial growth factors (VEGFs) are a major mediator to induce tumor microvasculature and are associated with the progression, recurrence, and metastasis of NSCLC. Current treatment medicines targeting VEGF/VEGF receptor (VEGFR) pathway, including neutralizing antibodies to VEGF or VEGFR and receptor tyrosine kinase inhibitors, have shown good treatment efficacy in patients with NSCLC. VEGF is not only an important angiogenic factor but also an immunomodulator of tumor microenvironment (TME). VEGFs can suppress antigen presentation, stimulate activity of regulatory T (Treg) cells, and tumor-associated macrophages, which in turn promote an immune suppressive microenvironment in NSCLC. The present review focuses on the angiogenic and non-angiogenic functions of VEGF in NSCLC, especially the interaction between VEGF and the cellular components of the TME. Additionally, we discuss recent preclinical and clinical studies to explore VEGF/VEGFR-targeted compounds and immunotherapy as novel approaches targeting the TME for the treatment of NSCLC.
Over the past decade, immunotherapy, especially cell-based immunotherapy, has provided new strategies for cancer therapy. Recent clinical studies demonstrated that adopting cell transfer of tumor-infiltrating lymphocytes (TILs) for advanced solid tumors showed good efficacy. TIL therapy is a type of cell-based immunotherapy using the patient’s own immune cells from the microenvironment of the solid tumor to kill tumor cells. In this review, we provide a comprehensive summary of the current strategies and challenges in TIL isolation and generation. Moreover, the current clinical experience of TIL therapy is summarized and discussed, with an emphasis on lymphodepletion regimen, the use of interleukin-2, and related toxicity. Furthermore, we highlight the clinical trials where TIL therapy is used independently and in combination with other types of therapy for solid cancers. Finally, the limitations, future potential, and directions of TIL therapy for solid tumor treatment are also discussed.
1 January 2017 in Oxidative Medicine and Cellular Longevity
Over the past two decades, obesity has been one of the major public health concerns in most countries. In the search for new molecules that could be used for the treatment of obesity, good perspectives have been opened up for polyphenols, a class of natural bioactive phytochemicals. Experimental and limited clinical trial evidence supports that some polyphenols such as quercetin, curcumin, and resveratrol have potential benefit functions on obesity treatment. This brief review focuses on the main functions of the above‐named polyphenols on adipose tissue. These polyphenols may play beneficial effects on adipose tissue under obese condition by alleviating intracellular oxidative stress, reducing chronic low‐grade inflammation, inhibiting adipogenesis and lipogenesis, and suppressing the differentiation of preadipocytes to mature adipocytes.
Gene expression can be posttranscriptionally regulated by a complex network of proteins. N1-methyladenosine (m1A) is a newly validated RNA modification. However, little is known about both its influence and biogenesis in tumor development. This study analyzed TCGA data of patients with five kinds of gastrointestinal (GI) cancers. Using data from cBioPortal, molecular features of the nine known m1A-related enzymes in GI cancers were investigated. Using a variety of bioinformatics approach, the impact of m1A regulators on its downstream signaling pathway was studied. To further confirm this regulation, the effect of m1A writer ALKBH3 knockdown was studied using RNA-seq data from published database. Dysregulation and multiple types of genetic alteration of putative m1A-related enzymes in tumor samples were observed. The ErbB and mTOR pathways with ErbB2, mTOR, and AKT1S1 hub genes were identified as being regulated by m1A-related enzymes. The expression of both ErbB2 and AKT1S1 was decreased after m1A writer ALKBH3 knockdown. Furthermore, Gene Ontology analysis revealed that m1A downstream genes were associated with cell proliferation, and the results showed that m1A genes are reliably linked to mTOR. This study demonstrated for the first time the dysregulation of m1A regulators in GI cancer and its signaling pathways and will contribute to the understanding of RNA modification in cancer.