Does the LHPP gene share a common biological function in pancancer progression?

Although emerging evidence has revealed that LHPP, a histidine phosphatase protein, suppresses the progression of different cancers, a pan-cancer analysis still remains unavailable. Therefore, we first utilized different bioinformatics tools to explore the tumor inhibitory role of LHPP protein across 33 tumor types based on the TCGA project. Additionally, HGC-27 gastric cancer cells were used to evaluate the biological functions of LHPP after stable transfection with lentiviruses. Consequently, LHPP mRNA and protein expression were down-regulated in the most cancer tissues corresponding to normal tissues. The data showed that patients with higher LHPP performance had a better prognosis of overall survival (OS) and disease-free survival (DFS) in brain glioma and renal carcinoma. In addition, we found that enhancement of LHPP expression attenuated the proliferation, migration and invasion of gastric cancer cells. The expression levels of cell-cycle-related and EMT-related molecules, such as CDK4, CyclinD1, Vimentin and Snail, were clearly reduced. Moreover, a genetic alteration analysis showed that the most frequent mutation types in LHPP protein was amplification. The patients without LHPP mutation showed a better tendency of prognosis in UCEC, STAD and COAD. Cancer-associated fibroblast infiltration was also observed in head and neck squamous cell carcinoma, stomach adenocarcinoma and testicular germ cell tumors. In summary, our pancancer analysis among various tumor types could provide a comprehensive understanding of LHPP biological function in the progression of malignant diseases and promote the development of novel therapeutic targets.

Circ_0001944 Contributes to Glycolysis and Tumor Growth by Upregulating NFAT5 Through Acting as a Decoy for miR-142-5p in Non-Small Cell Lung Cancer.

BACKGROUND: Circular RNAs (circRNAs) participate in the tumorigenesis of various cancers. CircRNA hsa_circ_0001944 (circ_0001944), derived from the TCONS_l2_00030860 gene, has been uncovered to be upregulated in NSCLC (non-small cell lung cancer). Nevertheless, the influence of circ_0001944 on glycolysis and tumor growth in NSCLC is unclear. METHODS: Expression trend of circ_0001944 in NSCLC tissues and cells were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Loss-of-function experiments were performed to assess the influence of circ_0001944 knockdown on proliferation, migration, invasion, and glycolysis of NSCLC cells. Protein levels were assessed by Western blotting. The regulatory mechanism of circ_0001944 was analyzed by bioinformatics analysis, dual-luciferase reporter assay, and/or RNA pull-down assay. The tumorigenicity of circ_0001944 was confirmed by xenograft assay. RESULTS: Circ_0001944 was highly expressed in NSCLC, and NSCLC patients with high expression of circ_0001944 had a worse prognosis. Circ_0001944 silencing decreased xenograft tumor growth in vivo and repressed proliferation, migration, invasion, and glycolysis of NSCLC cells in vitro. Circ_0001944 was verified as a decoy for microRNA (miR)-142-5p, which targeted NFAT5 (nuclear factor of activated T cells 5). MiR-142-5p was downregulated while NFAT5 was upregulated in NSCLC. Both miR-142-5p inhibition and NFAT5 overexpression offset the suppressive impact of circ_0001944 silencing on proliferation, migration, invasion, and glycolysis of NSCLC cells. Circ_0001944 adsorbed miR-142-5p to elevate NFAT5 expression in NSCLC cells. CONCLUSION: Circ_0001944 promotes proliferation, migration, invasion, and glycolysis of NSCLC cells by upregulating NFAT5 through adsorbing miR-142-5p, offering a novel mechanism for understanding the advancement of NSCLC.

An intergenic region ALK fusion identified by DNA sequencing and validated by IHC in an early-stage lung adenocarcinoma.

Anaplastic Lymphoma Kinase (ALK) fusion is an important driver mutation and therapeutic target. At present, more than 20 fusion partners for ALK in NSCLC have been reported. However, ALK intergenic-breakpoint fusions confound fusion detection and target treatment. Here, we reported a 53-year-old early-stage lung adenocarcinoma patient with an MIR548AD-ALK intergenic fusion and was verified by immunohistochemical staining (IHC). In early-stage NSCLC, compared with other clinically relevant driver mutations, ALK fusions were associated with a trend toward poor disease outcomes. Our Next-generation sequencing (NGS) and IHC results may indicate the prognosis of the patient and provide an alternative treatment option for postoperative recurrence.

Tinospora cordifolia and arabinogalactan exert chemopreventive action during benzo(a)pyrene-induced pulmonary carcinogenesis: studies on ultrastructural, molecular, and biochemical alterations.

The aim of the present study was to unveil the chemopreventive potentials of aqueous Tinospora cordifolia stem extract and its active component viz. Arabinogalactan against Benzo(a)pyrene-induced pulmonary carcinogenesis. Animals were divided into six groups: (I) Control, (II) aqueous Tinospora cordifolia (200 mg/kg b.wt, p.o.), (III) arabinogalactan (7.5 mg/kg b.wt, p.o.), (IV) benzo(a)pyrene (50 mg/kg b.wt, i.p.) at second and fourth week of study, (V) benzo(a)pyrene + aqueous Tinospora cordifolia, and (VI) benzo(a)pyrene + arabinogalactan. The benzo(a)pyrene treatment resulted in severe alterations in the cellular arrangement and morphology of the alveolar tissue in benzo(a)pyrene group. However, benzo(a)pyrene + aqueous Tinospora cordifolia and benzo(a)pyrene + arabinogalactan groups revealed classical features of apoptosis including chromatin condensation and formation of apoptotic bodies. Furthermore, Fourier transform Infrared spectroscopy analysis showed disturbed phospholipid saturation and protein secondary structures in benzo(a)pyrene treated animals. Depletion in relative glycogen and enhancement in total nucleic acid content was observed in benzo(a)pyrene treated animals, and the same was found to be restored upon arabinogalactan and aqueous Tinospora cordifolia supplementation. Benzo(a)pyrene insult also upregulated the phase I carcinogen metabolizing enzymes and differentially modulated the phase II metabolizing enzymes during pulmonary carcinogenesis. Also, depleted (reduced glutathione) and increased lipid peroxidation levels were observed in benzo(a)pyrene treated animals, which was found to be normalized upon aqueous Tinospora cordifolia and arabinogalactan administration. Clastogenic damage inflicted by benzo(a)pyrene was also reversed in benzo(a)pyrene + aqueous Tinospora cordifolia and benzo(a)pyrene + arabinogalactan group. Thus, the present study infers that aqueous Tinospora cordifolia and arabinogalactan showed promising anticancer activity against lung tumorigenesis in terms of ultrastructural, biochemical, and biomolecular aspects.

Autologous ilium graft combination with Y-shaped titanium plate fixation for chest wall reconstruction after resection of primary sternal tumors-a clinical study from three institutions.

BACKGROUND: The technique for anterior chest wall reconstruction after resection of primary sternal tumors (PST) still continue to evolve. METHODS: A total of 12 PST patients from three hospitals who underwent en-bloc resection were included in our study. After finishing sternum resection, autologous iliac bone combined with Y-shaped titanium plate were applied to rebuild the anterior chest wall. Postoperative outcomes were analyzed. RESULTS: There were 10 different types of tumors located in manubrium (6 cases), sternum body (4 cases) and Louis's angle (2 cases) in our research. For these patients, the median resected tumor size and the area of defect after sternal resection were 279.0 cm3 and 215.0 cm2, respectively. The mean operative time was 299.2±65.2 min and intra-operative blood loss was 431.2±213.0 mL. Mean duration of drainage was 9.9±2.6 days. In their perioperative period, significant circulatory and respiratory complications occurred in 8 patients. Postoperative chest X-ray and tridimensional CT images showed autogenous reconstruction of the sternum and titanium in good position. No side effects were observed 6-12 months post reconstructive surgery, but one patient suffered from anchor loss and prosthesis migration. Y-shaped titanium plates from two patients were separately removed at 24 and 26 months when the reconstructive sternum integrated with skeleton anterior chest wall well. CONCLUSIONS: Our study demonstrates the safety and feasibility of this new technique for anterior chest wall reconstruction after sternectomies.

Long non­coding RNA00887 reduces the invasion and metastasis of non­small cell lung cancer by causing the degradation of miRNAs.

Long non­coding RNAs (lncRNAs) can act as carcinogenic or cancer suppressive factors during the pathogenesis, invasion and metastasis of non­small cell lung cancer (NSCLC). The current study explored the role of long intergenic non­protein coding RNA 00887 (LINC00887) and competing endogenous RNAs (ceRNAs). It was revealed that LINC00887 interacts with several microRNAs (miRs), which regulates downstream genes such as fibronectin 1, MET proto­oncogene, receptor tyrosine kinase and mothers against decapentaplegic homolog 4, which are associated with the spread of lung cancer. The experimental results also suggested that LINC00887 can stimulate miR­613, miR­206 and miR­1­2 to become competing endogenous RNAs, which may regulate the epithelial­mesenchymal transition of NSCLC cells through the transforming growth factor­â signal transduction pathway, and therefore promote the migration of cells and the acquisition of stem cell characteristics. Therefore, it can be concluded that high levels of LINC00887 can accelerate the malignant transformation ability of NSCLC cells.

Effects of insulin therapy on inflammatory mediators in infants undergoing cardiac surgery with cardiopulmonary bypass.

To determine whether insulin administration modulates the systemic inflammatory response in infants undergoing cardiac surgery with cardiopulmonary bypass, 60 infants undergoing cardiopulmonary bypass were randomly assigned into a routine therapy group or to an intensive insulin therapy group with 30 infants in each group. Plasma IL-1beta, IL-6, IL-10, and TNF-alpha levels were determined before anesthesia, at the initiation of cardiopulmonary bypass, and at 0, 6, 12, 24, and 48 h after cardiopulmonary bypass. Nuclear factor-kappaBp65 expression and IkappaB expression in peripheral blood mononuclear cells were also measured by Western blot analysis. TNF-alpha, IL-1beta, IL-6, and IL-10 levels were all elevated after the initiation of cardiopulmonary bypass. However, TNF-alpha, IL-1beta, and IL-6 levels were significantly attenuated in the intensive insulin therapy group compared to those in the routine therapy group after initiation of cardiopulmonary bypass (p<0.05 or <0.01). Meanwhile, plasma IL-10 levels were significantly higher in the intensive insulin therapy group than in the routine therapy group after initiation of cardiopulmonary bypass (p<0.05 or <0.01). Accordingly, Nuclear factor-kappaBp65 expression and IkappaB expression were significantly increased after initiation of cardiopulmonary bypass in both groups (p<0.05 or <0.01). The expression of Nuclear factor-kappaBp65, which induces the transcription of pro-inflammatory cytokines was significantly attenuated in the intensive insulin therapy group (p<0.05 or <0.01). Meanwhile, the expression of IkappaB, an inhibitor of NF-kappaB, was significantly higher in the intensive insulin therapy group (p<0.05 or <0.01). These results suggested that intensive insulin therapy may attenuate the systemic inflammatory response in infants undergoing cardiopulmonary bypass.

[Effects of intensive insulin therapy on plasma nitric oxide and endothelin-1 levels in patients undergoing cardiac surgery under cardiopulmonary bypass].

OBJECTIVE: To investigate the effects of intensive insulin therapy on plasma nitric oxide (NO) and endothelin-1 (ET-1) levels in patients undergoing cardiac valve replacement under cardiopulmonary bypass (CPB). METHODS: A total of 36 patients were randomly assigned to routine therapy (RT) group and intensive insulin therapy (IT) group, with 18 patients in each group. The blood glucose levels during surgery were maintained at 3.9 to 10.0 mmol/L and those after surgery at 3.9 to 6.1 mmol/L in IT group, whereas patients in RT group didn't undergo the treatment of controlling glucose levels during operation and maintained below 13.9 mmoVL after operation. Levels of plasma NO and ET-1 in both groups were respectively measured before surgical anesthesia, at the initiation of CPB, and 0 h, 4 h, 12 h, 24 h and 48 h after the termination of CPB. RESULTS: In RT group, plasma NO concentration was decreased since the initiation of CPB [from (68.2 +/- 16.3) micromol/L to (67.8 +/- 8.4) micromol/L] and reached the trough at the termination of CPB [ (60.0 +/- 10.2) micromol/L, P < 0.05 compared with that before anesthesia]. Then it began to increase and neared to the preoperational level 48 h after the termination of CPB. In contrast, plasma ET-1 concentration was increased since the initiation of CPB [from (62.2 +/- 10.2) ng/L to (68.3 +/- 10.8) ng/L] and reached the peak at the termination of CPB [ (112.5 +/- 18.6) ng/L, P < 0.01 compared with that before anesthesia]. Then it began to decrease and reached the preoperational level 24 h after the termination of CPB. In IT group, however, the changes of NO and ET-1 levels at different time points during CPB and thereafter didn't reach the significance as compared with those before anesthesia. CONCLUSIONS: Intensive insulin therapy may relieve the changes of CPB-induced NO and ET-1 levels during cardiovascular surgery, which suggests its protective effects on cardiovascular function.