In the fields of medicine and public health, when randomized controlled trials are impractical, observational studies serve as a key alternative approach. However, the results of observational studies are often susceptible to bias. Target trial emulation (TTE) enhances the reliability and interpretability of results through structured design, rigorous analytical methods, and adjustment for confounding factors. The absence of a unified reporting guideline, however, has somewhat limited the reliability and reproducibility of TTE results. To address this gap, an international collaborative team developed the Transparent Reporting of Observational Studies Emulating a Target Trial (TARGET) reporting guideline, which aims to improve the transparency and methodological rigor of TTE. This study presents a Chinese translation and interpretation of the TARGET reporting guideline, with the goal of promoting its adoption and application in China.
Precision medicine is a new strategy that aims at preventing and treating human diseases by focusing on individual variations in people's genes, environment and lifestyle. Precision medicine has been used for cancer diagnosis and treatment and shows evident clinical efficacy. Rapid developments in molecular biology, genetics and sequencing technologies, as well as computational technology, has enabled the establishment of "big data", such as the Human Genome Project, which provides a basis for precision medicine. Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with a high incidence rate and low survival rate. Current therapies are often aggressive and carry considerable side effects. Much research now indicates that precision medicine can be used for HNSCC and may achieve improved results. From this perspective, we present an overview of the current status, potential strategies, and challenges of precision medicine in HNSCC. We focus on targeted therapy based on cell the surface signaling receptors epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and human epidermal growth factor receptor-2 (HER2), and on the PI3K/AKT/mTOR, JAK/STAT3 and RAS/RAF/MEK/ERK cellular signaling pathways. Gene therapy for the treatment of HNSCC is also discussed.
Interleukin 23 (IL-23) is an inflammatory cytokine which plays a vital role in autoimmune diseases as well as in tumorigenesis. However, the role of IL-23 in tumor procession is still controversial and the underlying mechanism remains unclear. Here we established a stable cell line overexpressing IL-23 to prove that IL-23 promoted tumor growth and pulmonary metastasis through induction of tumor-related inflammation and absence of immune surveillance. IL-23 promotes tumor-associate inflammatory response such as infiltration of M2 macrophages, neutrophils and their elevated secretions of immunosuppressive cytolcines transforming growth factor-beta (TGF-beta), IL-10 and vascular endothelial growth factor (VEGF) into tumor tissues, meanwhile the increase of the matrix metalloprotease MMP9. In addition, IL-23 increases the expression of the endothelial marker CD31 and proliferative marker Ki67 in tumors. Moreover, IL23 induces immunosuppression though reducing the infiltration of CD4(+) and CD8(+)T cells into tumor tissues. In conclusion, IL-23 is a considerable molecular in tumor progression, which simultaneously facilitates processes of pro-tumor inflammation, such as angiogenesis, immunosuppressive cytolcines as well as infiltrations of M2 macrophages and neutrophils, and suppresses antitumor immune responses through reduction of CD4(+) T cells and CD8(+) T cells. (C) 2016 Elsevier Inc. All rights reserved.
Epirubicin (EPI) is one of the most widely used anticarcinogens; however, serious side effects, including cardiomyopathy and congestive heart failure, limit its long-term administration. To overcome this problem, the HAIYPRH peptide ligand was used with EPI in the synthesis of a HAIYPRH-EPI conjugate. The anticancer activity and cellular uptake of the conjugate were measured and evaluated. The results of the present study indicated that the cytotoxicity of HAIYPRH-EPI was correlated with the expression of the cell surface transferrin receptor (TfR). The conjugate exerted high cytotoxicity and proapoptotic function when in an LN229 glioma cell line, which overexpresses surface TfR. It was hypothesized that transferrin (Tf) can promote cytotoxicity. Conversely, the conjugate exhibited very low cytotoxicity and proapoptotic function in a U87 glioma cell line, in which surface TfR expression was undetectable. In addition, fluorescence microscopy and flow cytometry methods were used to evaluate cellular uptake, and the results of these methods were consistent with the present hypotheses. The conjugate cellular uptake of the conjugate in LN229 cells was markedly higher compared with that in U87 cells, and it was hypothesized that Tf can enhance the uptake in LN229 cells. The cytotoxicity of HAIYPRH-EPI was dependent upon the expression of surface TfR. Considering that the majority of cancer cells have high rates of iron uptake and surface TfR is generally overexpressed on cancer cells, it was speculated by the authors that HAIYPRH-EPI may form part of an effective strategy for increasing the selectivity of EPI for cancer cells, as well as reducing its systemic toxicity. To confirm the hypothesis, the effects of HAIYPRH-EPI on non-cancerous cell lines were investigated. A future study will examine the side effects of HAIYPRH-EPI, using a suitable delivery system in an animal model.
Cordycepin, a main active composition extracted from Cordyceps militaris, has been reported to exert anti-tumor activity in a broad spectrum of cancer types. However, the function of cordycepin on human non-small cell lung cancer cells is still obscure. Our present work showed that cordycepin inhibited cell growth by inducing apoptosis and autophagy in human NSCLC cells. Further study revealed that cordycepin triggered extrinsic apoptosis associated with down-regulation of c-FLIPL which suppresses the activity of caspase-8. And ectopic expression of c-FLIPL dramatically prevented cordycepin-caused apoptosis. Meanwhile, cordycepin stimulated autophagy through suppressing mTOR signaling pathway in lung cancer cells. When autophagy was blocked by Atg5 siRNA or PI3K inhibitor LY294002, the levels of apoptosis caused by cordycepin were obviously attenuated. In addition, suppression of autophagy could also elevate the level of c-FLIPL which indicated cordycepin-triggered autophagy promoted the degradation of c-FLIPL. Therefore, we conclude that cordycepin induces apoptosis through autophagy-mediated downregulation of c-FLIPL in human NSCLC cells. Taken together, our findings provide a novel prospect on the anti-tumor property of cordycepin, which may further prompt cordycepin to serve as a promising therapeutic approach in NSCLC treatment.