Expression of cytoskeleton-associated protein 4 is associated with poor prognosis and metastasis in nasopharyngeal carcinoma.

Cytoskeleton-associated protein 4 (CKAP4) acts as a key transmembrane protein that connects the endoplasmic reticulum (ER) to microtubule dynamics. Researchers have not examined the roles of CKAP4 in nasopharyngeal carcinoma (NPC). The study aimed at evaluating the prognostic value and metastasis-regulating effect of CKAP4 in NPC. CKAP4 protein could be observed in 86.36% of 557 NPC specimens but not in normal nasopharyngeal epithelial tissue. According to immunoblot assays, NPC cell lines presented high CKAP4 expression relative to NP69 immortalized nasopharyngeal epithelial cells. Moreover, CKAP4 was highly expressed at the NPC tumor front and in matched liver, lung, and lymph node metastasis samples. Furthermore, high CKAP4 expression reported poor overall survival (OS) and presented a positive relevance to tumor (T) classification, recurrence, and metastasis. According to multivariate analysis, CKAP4 could independently and negatively predict patients' prognosis. Stable knockdown of CKAP4 expression in NPC cells inhibited cell migration, invasion and metastasis in vitro and in vivo. Moreover, CKAP4 promoted epithelial-mesenchymal transition (EMT) in NPC cells. CKAP4 knockdown was followed by the downregulation of the interstitial marker vimentin, and upregulation of the epithelial marker E-cadherin. In NPC tissues, high CKAP4 expression exhibited a positive relevance to vimentin expression and a negative relevance to E-cadherin expression. In conclusion, CKAP4 is an independent predictor of NPC, and CKAP4 might contribute NPC progression and metastasis, which may be involved in EMT with vimentin and E-cadherin.

Identification and Validation of a Necroptosis-Related Prognostic Signature for Kidney Renal Clear Cell Carcinoma.

Background: Necroptosis is progressively becoming an important focus of research because of its role in the pathogenesis of cancer and other inflammatory diseases. Our study is designed to anticipate the survival time of kidney renal clear cell carcinoma (KIRC) by constructing a prognostic signature of necroptosis-related genes. Materials: Clinical information and RNA-seq data were acquired from Renal Cell Cancer-European Union (RECA-EU) and The Cancer Genome Atlas- (TCGA-) KIRC, respectively. ConsensusClusterPlus was used to identify molecular subtypes, and the distribution of immune cell infiltration, anticancer drug sensitivity, and somatic gene mutations was studied in these subtypes. Subsequently, LASSO-Cox regression and univariate Cox regression were also carried out to construct a necroptosis-related signature. Cox regression, survival analysis, clinicopathological characteristic correlation analysis, nomogram, cancer stem cell analysis, and receiver operating characteristic (ROC) curve were some tools employed to study the prognostic power of the signature. Results: Based on the expression patterns of 66 survival-related necroptosis genes, we classified the KIRC into three subtypes (C1, C2, and C3) that are associated with necroptosis, which had significantly different tumor stem cell components. Among these, C2 patients had a longer survival time and enhanced immune status and were more sensitive to conventional chemotherapeutic drugs. Moreover, in order to predict the prognosis of KIRC patients, five genes (BMP8A, TLCD1, CLGN, GDF7, and RARB) were used to develop a necroptosis-related prognostic signature, which had an acceptable predictive potency. The results from Cox regression and stratified survival analysis revealed that the signature was an independent prognostic factor, whereas the nomogram and calibration curve demonstrated satisfactory survival time prediction based on the risk score. Conclusions: Three molecular subtypes and five necroptosis-related genes were discovered in KIRC using data from TCGA-KIRC and RECA-EU. Thus, a new biomarker and a potentially effective therapeutic approach for KIRC patients were provided in the current study.

Identification of Molecular Subtypes and Potential Small-Molecule Drugs for Esophagus Cancer Treatment Based on m6A Regulators.

BACKGROUND: Esophagus cancer (ESCA) is the sixth most frequent cancer in males, with 5-year overall survival of 15%-25%. RNA modifications function critically in cancer progression, and m6A regulators are associated with ESCA prognosis. This study further revealed correlations between m6A and ESCA development. METHODS: Univariate Cox regression analysis and consensus clustering were applied to determine molecular subtypes. Functional pathways and gene ontology terms were enriched by gene set enrichment analysis. Protein-protein interaction (PPI) analysis on differentially expressed genes (DEGs) was conducted for hub gene screening. Public drug databases were employed to study the interactions between hub genes and small molecules. RESULTS: Three molecular subtypes related to ESCA prognosis were determined. Based on multiple analyses among molecular subtypes, 146 DEGs were screened, and a PPT network of 15 hub genes was visualized. Finally, 8 potential small-molecule drugs (BMS-754807, gefitinib, neratinib, zuclopenthixol, puromycin, sulfasalazine, and imatinib) were identified for treating ESCA. CONCLUSIONS: This study applied a new approach to analyzing the relation between m6A and ESCA prognosis, providing a reference for exploring potential targets and drugs for ESCA treatment.

Expression of Programmed Death Ligand-2 is associated with Prognosis in Nasopharyngeal Carcinoma Microenviroment.

Background: Although immune checkpoint inhibitors have opened a new mode of treatment for solid tumors, their efficacy in nasopharyngeal carcinoma (NPC) needs to be further investigated. Inhibitors of the PD-1/PD-L1 immune checkpoint are one of the hot topics in tumor immunotherapy. Programmed death ligand-2 (PD-L2) is a less studied ligand of PD-1 and has not yet been fully explored, especially in NPC. Understanding the clinical significance of PD-L2 expression, together with immune cell infiltration, might provide clues for biomarker screening in NPC immunotherapy. This study aimed to evaluate the role of PD-L2 as a prognostic factor for NPC patients as well as its role in immune regulation. Methods: Immunohistochemistry (IHC) was performed on a tissue microarray including 557 NPC specimens using PD-L2 antibody. The immune cell markers CD4, FOXP3 and CD68 were also stained and quantified. The expression of PD-L2 exhibited different spatial patterns among NPC tumor and stromal tissues. Results: A total of 90.8% of the cases showed membranous PD-L2 expression in tumors, and 80.8% showed membranous PD-L2 expression in stromal tissue. High stromal expression of PD-L2 predicted favorable overall and disease-free survival of NPC patients and was negatively correlated with tumor size, recurrence or metastasis and clinical stage. In contrast, high tumor abundance of PD-L2 correlated with poor disease-free survival, but had no obvious correlation with clinicopathological parameters. Multivariate analysis indicated that stromal PD-L2 was an independent and favorable prognostic factor. Furthermore, we found a positive correlation between stromal PD-L2 expression and the infiltration of CD68+ macrophages and CD4+Foxp3+ Treg cells in NPC stromal tissues (Pearson correlation=0.181 and 0.098, respectively). Conclusions: Our results suggest that different PD-L2 expression patterns have distinct predictive values. PD-L2 expressed on stromal cells might play a role in the regulation of NPC progression, and involve in immune activation in the tissue microenvironment and have an independent good prognosis for NPC patients.

Effects of He-D Interaction on Irradiation-Induced Swelling in Fe9Cr Alloys.

The atomic-scale defects such as (deuterium, helium)-vacancy clusters in nuclear energy materials are one of the causes for the deterioration of the macroscopic properties of materials. Unfortunately, they cannot be observed by transmission electron microscopy (TEM) before they grow to the nanometer scale. Positron annihilation spectroscopy (PAS) has been proven to be sensitive to open-volume defects, and could characterize the evolution of the size and concentration of the vacancy-like nanoclusters. We have investigated the effects of He-D interaction on the formation of nanoscale cavities in Fe9Cr alloys by PAS and TEM. The results show that small-sized bubbles are formed in the specimen irradiated with 5 × 1016 He+/cm2, and the subsequent implanted D-ions contribute to the growth of these helium bubbles. The most likely reason is that helium bubbles previously formed in the sample captured deuterium injected later, causing bubbles to grow. In the lower dose He-irradiated samples, a large number of small dislocations and vacancies are generated and form helium-vacancy clusters with the helium atoms.

[Summary on WEI Li-fu's experience in clinical treatment of spasmodic torticollis].

The thinking and experience of professor WEI Li-fu in the treatment of spasmodic torticollis under the guidance of ZHU Lian's academic thoughts are introduced. In pathogenesis, spasmodic torticollis is related to the obstruction of yang qi circulation and malnutrition of tendons and vessels. "Promoting yang and benefiting qi" is considered as the main treating principle. In the affected local area, the acupoints are selected from yangming meridians, shaoyang meridians and taiyang meridians of hand and foot. The acupoints of the governor vessel, the he-sea points of the involved yang meridians on the four limbs as well as "four-gate" points are selected as the distal acupoints. During treatment, the "restricting" needling technique invited by ZHU Lian is combined, deqi (qi arrival) is emphasized particularly. Besides, the ironing moxibustion technique is commonly adopted in combination in the affected area.

[Effects of moxibustion on the expression of cell cycle protein P 16 and retinoblastoma and c-fos in the cerebral cortex of senile mice].

OBJECTIVE: To observe the influence of moxibustion on the cyclin and cellular proliferin of the cerebral cortex in senile mice so as to explore its underlying mechanism in delaying aging. METHODS: Sixty male mice were randomly and equally divided into control, model, moxibustion of "Zusanli" (ST 36) and "Xuanzhong" (GB 39, M-ST 36-GB 39), moxibustion of "Baihui" (GV 20) and "Guanyuan" (CV 4,M-GV 20-COV 4) ,and medication groups. The aging model was established by subcutaneous injection of D-galactose for 42 days. Moxibustion was applied to ST 36, GB 39, GV 20 and CV 4 separately for 3 moxa-cones, once every other day for one month. The expression of cell cycle protein P 16 and retinoblastoma (pRb), and c-fos protein in the cerebral cortex tissue of the senile mice were detected by immunohistochemistry. RESULTS: Compared with control group, the number of P16 immunoreaction (IR) positive neurons in the cerebral cortex increased significantly in the model group (P < 0.01), and those of cortical pRb and c-fos IR-positive neurons decreased considerably in model group (P < 0.01). In comparison with the model group, the number of cortical P 16 IR-positive neurons reduced significantly in M-ST 36-GB 39, M-GV 20-CV 4 and medication groups (P < 0.01), and those of cortical pRb and c-fos IR-positive neurons increased remarkably in M-ST 36-GB 39, M-GV 20-CV 4 and medication groups (P < 0.01, P < 0.05). No significant differences were found in the aforementioned 3 indexes among M-ST 36-GB 39, M-GV 20-CV 4 and medication groups (P > 0.05). CONCLUSION: Moxibustion of ST 36-GB 39 and GV 20-CV 4 can down-regulate the P 16 expression,and up-regulate pRb and c-fos protein expression in the cerebral cortex of senile mice, which possibly contributes to its effect in delaying aging.