Brain metastasis often has a poor prognosis in patients with advanced non-small cell lung cancer (NSCLC). Therefore, it is urgent to identify factors associated with lung cancer brain metastasis. ...Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) also known as noncoding nuclear-enriched abundant transcript 2 is a long noncoding RNA, which is highly conserved amongst mammals. It has been shown to be increased in a variety of tumors including NSCLC and regulate the expression of metastasis-associated genes. However, the role of MALAT1 in lung cancer brain metastasis has not been investigated. In this study, we examined the level of MALAT1 in 78 cases of NSCLC samples with 19 brain metastasis and 59 non-brain metastasis by qRT-PCR. We observed that the level of MALAT1 was significantly higher in brain metastasis than that of non brain metastasis samples (
P
< 0.001). The level of MALAT1 was associated with patients’ survival. To investigate the role of MALAT1 in brain metastasis, we established a highly invasive and metastatic cell subline using the brain metastasis lung cancer cell H1915. We found that MALAT1 is increased in highly invasive subline of brain metastasis lung cancer cells. Further functional studies indicate that silencing MALAT1 inhibits highly invasive subline of brain metastasis lung cancer cell migration and metastasis by inducing epithelial-mesenchymal transition (EMT). Therefore, increased level of long noncoding RNA MALAT1 promotes lung cancer brain metastasis by inducing EMT, which may be a promising prognosis factor and therapeutic target to treat lung cancer brain metastasis in future.
The applications of liquid biopsy have attracted much attention in biomedical research in recent years. Circulating cell-free DNA (cfDNA) in the serum may serve as a unique tumor marker in various ...types of cancer. Circulating tumor DNA (ctDNA) is a type of serum cfDNA found in patients with cancer and contains abundant information regarding tumor characteristics, highlighting its potential diagnostic value in the clinical setting. However, the diagnostic value of cfDNA as a biomarker, especially circulating HPV DNA (HPV cDNA) in cervical cancer remains unclear. Here, we performed a meta-analysis to evaluate the applications of HPV cDNA as a biomarker in cervical cancer. A systematic literature search was performed using PubMed, Embase, and WANFANG MED ONLINE databases up to March 18, 2019. All literature was analyzed using Meta Disc 1.4 and STATA 14.0 software. Diagnostic measures of accuracy of HPV cDNA in cervical cancer were pooled and investigated. Fifteen studies comprising 684 patients with cervical cancer met our inclusion criteria and were subjected to analysis. The pooled sensitivity and specificity were 0.27 (95% confidence interval CI, 0.24-0.30) and 0.94(95% CI, 0.92-0.96), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 6.85 (95% CI, 3.09-15.21) and 0.60 (95% CI, 0.46-0.78), respectively. The diagnostic odds ratio was 15.25 (95% CI, 5.42-42.94), and the area under the summary receiver operating characteristic curve was 0.94 (95% CI, 0.89-0.99). There was no significant publication bias observed. In the included studies, HPV cDNA showed clear diagnostic value for diagnosing and monitoring cervical cancer. Our meta-analysis suggested that detection of HPV cDNA in patients with cervical cancer could be used as a noninvasive early dynamic biomarker of tumors, with high specificity and moderate sensitivity. Further large-scale prospective studies are required to validate the factors that may influence the accuracy of cervical cancer diagnosis and monitoring.
Tripartite motif‑containing 27 (TRIM27) belongs to the TRIM protein family, which is closely related to the progression of some certain human cancers. Nevertheless, the biological function of TRIM27 ...in esophageal squamous cell carcinoma (ESCC) is still not clear. The aim of present research is to examine the function of TRIM27 in ESCC cells.
In the present study, RNA interference (RNAi) and lentiviral vector were used to knockdown and overexpression of TRIM27 in ESCC cells respectively. qRT-PCR and western blot were used to examine the expression of TRIM27 in ESCC cells. Cell counting kit-8 (CCK-8) assay was performed to determine the proliferation of cells.
Our analyses indicated that TRIM27 was a pro-proliferation factor in ESCC cells. Moreover, overexpression of TRIM27 deeply suppressed the apoptosis of ESCC cells and accelerated its glucose uptake. In addition, an AKT inhibitor LY294002 was used to determine the connection between TRIM27 and AKT in ESCC cells. Our results demonstrated that TRIM27 has involved in the PI3/AKT signaling pathway. Moreover, TRIM27 interacted with PTEN and mediated its poly-ubiquitination in ESCC cells. Importantly, the glycolysis inhibitor 3-BrPA also inhibited the effect of TRIM27 on ESCC cells. Hence, TRIM27 also participated in the regulation of energy metabolism in ESCC cells.
This research not only gained a deep insight into the biological function of TRIM27 but also elucidated its potential target and signaling pathway in human ESCC cells.
Guanylate binding proteins (GBPs), a family of interferon-inducible large GTPase, play a pivotal role in cell-autonomous immunity and tumor malignant transformation. Glioblastoma (GBM) is the most ...prevalent and lethal primary brain tumor in adults. Here we show that GBP5 was highly expressed in GBM cell lines and in clinical samples, especially in the mesenchymal subtype. The expression levels of GBP5 were negatively correlated with the prognosis of GBM patients. Overexpression of GBP5 promoted the proliferation, migration, and invasion of GBM cells in vitro and in vivo. In contrast, silencing GBP5 by RNA interference exhibited the opposite effects. Consequently, targeting GBP5 in GBM cells resulted in impaired tumor growth and prolonged survival time of mice with GBM tumors. We further identified that the Src/ERK1/2/MMP3 axis was essential for GBP5-promoted GBM aggressiveness. These findings suggest that GBP5 may represent a novel target for GBM intervention.
Gastric cancer is one of the top causes of cancer‐related death around the world, and poor prognosis of gastric cancer is due to the lack of early detection and effective treatment especially in ...male. Here, we first revealed the role of histone lysine‐specific demethylase 5D (KDM5D) in gastric cancer in male. KDM5D was associated with the metastasis of gastric cancer because of its critical role in the epithelial‐mesenchymal transition of gastric cancer cells. Downregulation of KDM5D in gastric cancer cells significantly increase the number of migrated or invaded cells due to the increasing expressions of mesenchymal markers. Downregulation of KDM5D also promotes tumor formation of gastric cancer cell in vivo. For mechanism, downregulation of KDM5D could inhibit the demethylation in the promoter of CUL4A, which lead to the increasing expression of ZEB1 and decreasing expressions of p21 and p53. Collectively, KDM5D performed its role in metastasis of gastric cancer through demethylation in the promoter of CUL4A, and it suggested us a novel target in gastric cancer treatment in male.
Histone lysine‐specific demethylase 5D (KDM5D) performs its role in metastasis of gastric cancer through the demethylation in the promoter of Cul4A and KDM5D
Gastric cancer (GC) is one of the most common malignancies in the world, and the fourth most frequent malignancy worldwide. YTHDF2 (YTH domain family 2, YTHDF2) binds to mRNA containing m6A, thereby ...regulating the localization and stability of the bound mRNA. YTHDF2 was shown to be associated with some cancer patient prognosis. However, the effect of YTHDF2 on gastric cancer and the molecular mechanism of this effect have not been documented.
To conduct this research, YTHDF2 expression levels in public databases and gastric cancer patient samples were analyzed. The effects of YTHDF2 on the growth of gastric cancer cells were detected
and
RNA-seq was used to analyze the signal pathways regulated by YTHDF2, and experiments were carried out for verification.
In our study, we found that YTHDF2 has lower expression in GC tissues and GC cells, and inhibits the growth of GC cells. In addition, the analysis of clinical data found that the expression level of YTHDF2 is closely related to the stage of GC and the survival of patients with GC. RNA sequencing results showed that overexpression of YTHDF2 significantly reduced protein expression in the FOXC2 (Forkhead box protein C2, FOXC2) signaling pathway. Finally, we found that knockout of FOXC2 reversed the inhibitory effect of YTHDF2 on GC cells.
In summary, YTHDF2 inhibits the growth of GC cells by negatively regulating FOXC2 and may serve as a prognostic marker in GC.
Abstract
Background
Regulatory T cells (Tregs) play an important role in regulation of immune response and immunologic tolerance in cancer. Gastrointestinal cancer is still a leading cause of ...cancer-related death in the world. This study aimed to detect Tregs in patients with gastrointestinal cancer.
Methods
In this study, 45 gastric cancer patients, 50 colorectal cancer patients and 50 healthy controls were enrolled. Flow cytometry was used to detect CD4
+
CD25
hi
CD127
low
Tregs, CD4
+
CD25
hi
, and CD4
+
cells in peripheral blood. Cytokine interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) in peripheral blood and in the supernatant of Tregs cultures were measured by enzyme linked immunosorbent assay.
Results
Compared with healthy controls, the levels of CD4
+
CD25
hi
CD127
low
Tregs and CD4
+
CD25
hi
cells increased significantly in patients with gastrointestinal cancer. Patients with gastrointestinal cancer also showed a significantly increased levels of IL-10 and TGF-β1 in both peripheral blood and CD4
+
CD25
hi
CD127
low
Tregs culture medium.
Conclusion
The present study firstly demonstrated that gastrointestinal patients have a compromised immune status where the CD4
+
CD25
hi
CD127
low
Tregs, as well as levels of IL-10 and TGF-β1 are elevated. The data offered new information for understanding the immunological features of gastrointestinal patients, as well as provided new insights into approaches to develop new immunotherapies for patients with gastrointestinal cancer.
Rezivertinib (BPI-7711) is a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). This phase IIa study was part of a phase I/IIa study (NCT03386955), aimed ...to evaluate the efficacy and safety of rezivertinib as the first-line treatment for patients with locally advanced or metastatic/recurrent EGFR mutated non-small cell lung cancer (NSCLC).
Patients received the first-line treatment of 180 mg rezivertinib orally once daily until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety.
From Jun 12, 2019, to Oct 17, 2019, 43 patients were enrolled. At the data cutoff date on Dec 23, 2021, the ORR by BICR was 83.7% (95% CI: 69.3-93.2%). The median DoR was 19.3 (95% CI: 15.8-25.0) months. The median PFS by BICR was 20.7 (95% CI: 13.8-24.8) months and 22.0 (95% CI: 16.8-26.3) months by investigators. Data on OS was immature. Totally, 40 (93.0%) patients had at least one treatment-related adverse event while 4 (9.3%) of them were grade ≥ 3.
Rezivertinib (BPI-7711) showed promising efficacy and a favorable safety profile for the treatment among the locally advanced or metastatic/recurrent NSCLC patients with EGFR mutation in the first-line setting.
ClinicalTrials.gov, NCT03386955.
...there is an urgent need to better characterize ICI-cardiotoxicity in patients with GI cancer. Compared with a non-cardiotoxicity group, a cardiotoxicity group appeared to have a higher prevalence ...of comorbidities and concomitant medication. ...a significantly higher prevalence of previous mediastinal radiation was observed in patients with esophageal cancer in the cardiotoxicity group (80% (4/5) vs. 27.5% (44/160), P = 0.04). PD-L1 was found to be enriched in cardiomyocytes and the endothelium to help regulate self-tolerance, and cardiomyopathy mediated by autoimmunity developed in PD-1-deficient mice. ...patients with a history of autoimmune disease appear to be predisposed to radiation toxicities. Du et al8 previously showed that a combination of PD-1 blockade and radiation increased the cardiac toxicity caused by cardiac radiation via CD8+ T cell-mediated myocarditis with associated fibrosis. ...due to the relatively early onset of radiation-induced cardiotoxicity and the potential synergistic effect of PD-1 blockade and radiation, esophageal cancer patients who received prior mediastinal radiation might be more susceptible to ICI-induced cardiac inflammation.
By extracting and simplifying the characteristics of commercial streets with arcades (Qilou) in Nanning, the tissue map of Qilou streets which reflects the urban morphology, including the road ...network form, block scale, building scale and other characteristics in a hot and humid area is obtained. In addition, the sunshine simulation is performed by using sunshine design software in an environment comprising streets with arcades to simulate street sunlight environments under various conditions. The relationship among street height-to-width ratio, sunshine hours, and street orientation angle is achieved by nonlinear fitting analysis. Then, a model is established to adjust the street height-to-width ratio based on sunshine requirement and street orientation. The finding indicated that when the street is north–south, it is suggested that the street height-to-width ratio is 0.95–1.13 to reduce sunshine hours effectively, and when the street is east–west, it is proposed that one side of the street should have a recessed space to improve the thermal conditions. The results of this study can serve as the specific guidelines that can be adopted in the redesign and reformation of commercial streets with arcades to achieve thermal comfort of Qilou streets in hot and humid areas.
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