Vasculogenic mimicry (VM) is a brand-new tumour vascular paradigm independent of angiogenesis that describes the specific capacity of aggressive cancer cells to form vessel-like networks that provide adequate blood supply for tumour growth. A variety of molecule mechanisms and signal pathways participate in VM induction. Additionally, cancer stem cell and epithelial-mesenchymal transitions are also shown to be implicated in VM formation. As a unique perfusion way, VM is associated with tumour invasion, metastasis and poor cancer patient prognosis. Due to VM's important effects on tumour progression, more VM-related strategies are being utilized for anticancer treatment. Here, with regard to the above aspects, we make a review of advanced research on VM in cancer.

Background:Determining the somatic mutations of epidermal growth factor receptor (EGFR)-pathway networks is the key to effective treatment for non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors (TKIs).The somatic mutation frequencies and their association with gender, smoking history and histology was analysed and reported in this study.Methods:Five thousand one hundred and twenty-five NSCLC patients' pathology samples were collected, and EGFR, KRAS, BRAF and PIK3CA mutations were detected by multiplex testing. The mutation status of EGFR, KRAS, BRAF and PIK3CA and their association with gender, age, smoking history and histological type were evaluated by appropriate statistical analysis.Results:EGFR, KRAS, BRAF and PIK3CA mutation rates revealed 36.2%, 8.4%, 0.5% and 3.3%, respectively, across the 5125 pathology samples. For the first time, evidence of KRAS mutations were detected in two female, non-smoking patients, age 5 and 14, with NSCLC. Furthermore, we identified 153 double and coexisting mutations and 7 triple mutations. Interestingly, the second drug-resistant mutations, T790M or E545K, were found in 44 samples from patients who had never received TKI treatments.Conclusions:EGFR exons 19, 20 and 21, and BRAF mutations tend to happen in females and non-smokers, whereas KRAS mutations were more inclined to males and smokers. Activating and resistant mutations to EGFR-TKI drugs can coexist and ‘second drug-resistant mutations', T790M or E545K, may be primary mutations in some patients. These results will help oncologists to decide candidates for mutation testing and EGFR-TKI treatment.

Background: A number of studies have reported an association between the occurrence of immune-related adverse events (irAEs) and clinical efficacy in patients undergoing treatment with immune checkpoint inhibitors (ICIs), but the results remain controversial. Methods: Under the guidance of a predefined protocol and Preferred Reporting Items for Systematic Reviews and Meta-analyses statement, this meta-analysis included cohort studies investigating the association of irAEs and efficacy of ICIs in patients with cancer. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). Subgroup analyses involving the cancer type, class of ICIs, combination therapy, sample size, model, landmark analysis, and approach used to extract the data were performed. Specific analyses of the type and grade of irAEs were also performed. Results: This meta-analysis included 30 studies including 4971 individuals. Patients with cancer who developed irAEs experienced both an OS benefit and a PFS benefit from ICI therapy compared to patients who did not develop irAEs (OS: hazard ratio (HR), 0.54, 95% confidence interval (CI), 0.45-0.65; p < 0.001; PFS: HR, 0.52, 95% CI, 0.44-0.61, p < 0.001). Subgroup analyses of the study quality characteristics and cancer types recapitulated these findings. Specific analyses of endocrine irAEs (OS: HR, 0.52, 95% CI, 0.44-0.62, p < 0.001), dermatological irAEs (OS: HR, 0.45, 95% CI, 0.35-0.59, p < 0.001), and low-grade irAEs (OS: HR, 0.57, 95% CI, 0.43-0.75; p < 0.001) yielded similar results. The association between irAE development and a favorable benefit on survival was significant in patients with cancer who were undergoing treatment with programmed cell death-1 inhibitors (OS: HR, 0.51, 95% CI, 0.42-0.62; p < 0.001), but not cytotoxic T-lymphocyte antigen-4 inhibitors (OS: HR, 0.89, 95% CI, 0.49-1.61; p = 0.706).

Liang et al. find that the tumor suppressors TSC1 and TSC2, defects in which underlie the genetic disease Tuberous Sclerosis Complex (TSC), drive the mTOR-dependent autophagosomal destruction of the transcriptional activator YAP. Blocking YAP inhibited the abnormal proliferation of TSC1/2-deficient human cells and reversed TSC-like disease symptoms in mosaic Tsc1 mutant mice.

Background Effective treatment of hypertension requires careful self-management. With the ongoing development of mobile technologies and the scarcity of health care resources, mobile health (mHealth)–based self-management has become a useful treatment for hypertension, and its effectiveness has been assessed in many trials. However, there is a paucity of comprehensive summaries of the studies using both qualitative and quantitative methods. Objective This systematic review aimed to measure the effectiveness of mHealth in improving the self-management of hypertension for adults. The outcome measures were blood pressure (BP), BP control, medication adherence, self-management behavior, and costs. Methods A systematic search was conducted using 5 electronic databases. The snowballing method was used to scan the reference lists of relevant studies. Only peer-reviewed randomized controlled trials (RCTs) published between January 2010 and September 2019 were included. Data extraction and quality assessment were performed by 3 researchers independently, adhering to the validation guideline and checklist. Both a meta-analysis and a narrative synthesis were carried out. Results A total of 24 studies with 8933 participants were included. Of these, 23 studies reported the clinical outcome of BP, 12 of these provided systolic blood pressure (SBP) and diastolic blood pressure (DBP) data, and 16 articles focused on change in self-management behavior and medication adherence. All 24 studies were included in the narrative synthesis. According to the meta-analysis, a greater reduction in both SBP and DBP was observed in the mHealth intervention groups compared with control groups, −3.78 mm Hg (P<.001; 95% CI −4.67 to −2.89) and −1.57 mm Hg (P<.001; 95% CI −2.28 to −0.86), respectively. Subgroup analyses showed consistent reductions in SBP and DBP across different frequencies of reminders, interactive patterns, intervention functions, and study duration subgroups. A total of 16 studies reported better medication adherence and behavioral change in the intervention groups, while 8 showed no significant change. Six studies included an economic evaluation, which drew inconsistent conclusions. However, potentially long-term financial benefits were mentioned in all economic evaluations. All studies were assessed to be at high risk of bias. Conclusions This review found that mHealth self-management interventions were effective in BP control. The outcomes of this review showed improvements in self-management behavior and medication adherence. The most successful mHealth intervention combined the feature of tailored messages, interactive communication, and multifaceted functions. Further research with longer duration and cultural adaptation is necessary. With increasing disease burden from hypertension globally, mHealth offers a potentially effective method for self-management and control of BP. mHealth can be easily integrated into existing health care systems. Trial Registration PROSPERO CRD42019152062; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=152062

Supplemental Table 1. Detailed results from the mixed-effected models with interaction terms between the treatment effect and time Outcomes Variables Coefficient (95%CI) P Value 6MWD (m) Intervention 52.7 (22.9 to 82.6) 0.001

Vasculogenic mimicry ( VM ) is a vascular‐like structure which can mimic the embryonic vascular network pattern to nourish the tumour tissue. As a unique perfusion way, VM is correlated with tumour progression, invasion, metastasis and lower 5‐year survival rate. Notably, epithelial‐mesenchymal transition ( EMT ) regulators and EMT ‐related transcription factors are highly up‐regulated in VM ‐forming tumour cells, which demonstrated that EMT may play a crucial role in VM formation. Therefore, the up‐regulation of EMT ‐associated adhesion molecules and other factors can also make a contribution in VM ‐forming process. Depending on these discoveries, VM and EMT can be utilized as therapeutic target strategies for anticancer therapy. The purpose of this article is to explore the advance research in the relationship of EMT and VM and their corresponding mechanisms in tumorigenesis effect.

DEP-domain containing 5 (DEPDC5), encoding a repressor of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway, has recently emerged as a major gene mutated in familial focal epilepsies and focal cortical dysplasia. Here we established a global knockout rat using TALEN technology to investigate in vivo the impact of Depdc5-deficiency. Homozygous Depdc5(-/-) embryos died from embryonic day 14.5 due to a global growth delay. Constitutive mTORC1 hyperactivation was evidenced in the brains and in cultured fibroblasts of Depdc5(-/-) embryos, as reflected by enhanced phosphorylation of its downstream effectors S6K1 and rpS6. Consistently, prenatal treatment with mTORC1 inhibitor rapamycin rescued the phenotype of Depdc5(-/-) embryos. Heterozygous Depdc5(+/-) rats developed normally and exhibited no spontaneous electroclinical seizures, but had altered cortical neuron excitability and firing patterns. Depdc5(+/-) rats displayed cortical cytomegalic dysmorphic neurons and balloon-like cells strongly expressing phosphorylated rpS6, indicative of mTORC1 upregulation, and not observed after prenatal rapamycin treatment. These neuropathological abnormalities are reminiscent of the hallmark brain pathology of human focal cortical dysplasia. Altogether, Depdc5 knockout rats exhibit multiple features of rodent models of mTORopathies, and thus, stand as a relevant model to study their underlying pathogenic mechanisms.