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Drug resistance is one of the most formidable obstacles for treatment of glioma. Eukaryotic initiation factor 4E-binding protein ( 4E-BP1), a key component in the rate-limiting step of protein translation initiation, is closely associated with poor prognosis in multiple tumor types. However, it is unclear whether 4E-BP1 is involved in the drug resistance of human glioma. Herein we show that the expression of 4E-BP1 in human SWOZ2- BCNU drug-resistant glioma cells is significantly lower than that of the parent SWOZ2 cell line. Moreover, down-regulation of 4E-BP1 by short interfering RNA significantly impaired the sensitivity of SWOZ2 and U251 cells to carmustine ( BCNU). Furthermore, overexpression of 4E-BP1 with plasmid transfection regained this sensitivity. Clinical studies showed that the expression levels of 4E-BP1 in primary glioma tissues were markedly higher than those of recrudescent glioma tissues. Taken together, our results suggest that 4E-BP1 is a novel protein that contributes to acquired drug resistance and it may be a potential target for reversing drug resistance in human glioma. [ABSTRACT FROM AUTHOR]

Light blue crest (LBC) signs could be seen in the innominate grooves and crypt openings. b The long, linear, LBCs could be seen in tangential view of colonic mucosa (arrowheads). c Dot- or rod-like LBCs could be seen in partial crypt openings. 1 Normal colonic mucosa by magnifying endoscopy and narrow-band imaging. a The colon was partially collapsed and innominate grooves reappeared. [Extracted from the article]

By using the first-principles calculations, structural and electronic properties of Au and Ti adsorbed WS2 monolayers are studied systematically. For Au-adsorbed WS2, metallic interface states are induced in the middle of the band gap across the Fermi level. These interface states origin mainly from the Au-6s states. As to the Ti adsorbed WS2, some delocalized interface states appear and follow the bottom of conduction band. The Fermi level arises into the conduction band and leads to the n-type conducting behavior. The n-type interface states are found mainly come from the Ti-3d and W-5d states due to the strong Ti–S hybridization. The related partial charge densities between Ti and S atoms are much higher and increased by an order of magnitude as compared with that of Au-adsorbed WS2. Therefore, the electron transport across the Ti-adsorbed WS2 system is mainly by the resonant transport, which would further enhances the electronic transparency when monolayer WS2 contacts with metal Ti. These investigations are of significant importance in understanding the electronic properties of metal atom adsorption on monolayer WS2 and offer valuable references for the design and fabrication of 2D nanodevices. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: The aim of this study was to compare the frequency of metabolic syndrome (MetS) in patients with and without interstitial cystitis/bladder pain syndrome (IC/BPS). Methods: This case-control study evaluated the indicators of MetS in 287 females with IC/BPS and in 287 females without IC/BPS in West China Hospital between January 2010 and January 2020. Then, the number of voids per day, frequency of night urination, O'Leary-Sant Interstitial Cystitis Symptom/Problem Index, and visual analog scale were examined in the two groups. Results: Based on both the National Cholesterol Education Program Adult Treatment Panel III recommendations and the International Diabetes Federation criteria, the distribution of MetS was statistically higher in patients with IC/BPS than in the control group, with 34.8% vs 17.8% (P < 0.0001) and 34.2% vs 20.9% (P = 0.0005), respectively. Regarding symptom scores, the IC/BPS group demonstrated significantly higher scores than the control group in all aspects (P < 0.0001). More patients with anxiety (P < 0.0001), insomnia (P < 0.0001), hypertension (P = 0.0001), and diabetes mellitus (P = 0.017) were observed in the IC/BPS group. Moreover, the findings indicated that patients with IC/BPS had a higher BMI (P = 0.0001) and larger waist circumference (P = 0.0001). Blood tests presented a significantly higher level of fasting glycemia, serum cystatin-C, and triglycerides in patients with IC/BPS. Furthermore, higher ORs for the occurrence of MetS among cases were observed, although this was not statistically significant. Conclusions: MetS frequency was relatively high in patients with IC/BPS. Further research is needed to understand the common pathophysiologic mechanism of IC/BPS and MetS. [ABSTRACT FROM AUTHOR]

Targeting replication stress response is currently emerging as new therapeutic strategy for cancer treatment, based on monotherapy and combination approaches. As a key sensor in response to DNA damage, ataxia telangiectasia and rad3-related (ATR) kinase has become a potential therapeutic target as tumor cells are to rely heavily on ATR for survival. The tumor suppressor phosphatase and tensin homolog (PTEN) plays a crucial role in maintaining chromosome integrity. Although ATR inhibition was recently confirmed to show a synergistic inhibitory effect in PTEN-deficient triple-negative breast cancer cells, the molecular mechanism needs to be further elucidated. Additionally, whether the PTEN-deficient breast cancer cells are more preferentially sensitized than PTEN-wild type breast cancer cells to cisplatin plus ATR inhibitor remains unanswered. We demonstrate PTEN dysfunction promotes the killing effect of ATR blockade through the use of RNA interference for PTEN and a highly selective ATR inhibitor VE-821, and certify that VE-821 (1.0 μmol/L) aggravates cytotoxicity of cisplatin on breast cancer cells, especially PTEN-null MDA-MB-468 cells which show more chemoresistance than PTEN-expressing MDA-MB-231 cells. The co-treatment with VE-821 and cisplatin significantly reduced cell viability and proliferative capacity compared with cisplatin mono-treatment (P < 0.05). The increased cytotoxic activity is tied to the enhanced poly (ADP-ribose) polymerase (PARP) cleavage and consequently cell death due to the decrease in phosphorylation levels of checkpoint kinases 1 and 2 (CHK1/2), the reduction of radiation sensitive 51 (RAD51) foci and the increase in phosphorylation of the histone variant H2AX (γ-H2AX) foci (P < 0.05) as well. Together, these findings suggest combination therapy of ATR inhibitor and cisplatin may offer a potential therapeutic strategy for breast tumors. • ATR inhibition significantly enhances cytotoxicity effect of cisplatin on PTEN-deficient breast cancer cells. • ATR inhibition reinforces the accumulation of cisplatin-induced DNA damage. • ATR inhibition potentiates cisplatin-induced genotoxic stress by disturbing HR-mediated DNA repair. [ABSTRACT FROM AUTHOR]

Expression of monocyte chemoattractant protein-1 (MCP-1) and CC chemokine receptor 2 (CCR2) and its significance has been demonstrated in some cancer cells in recent clinical studies. However, the role of tumor MCP-1 and CCR2 expression in non-small cell lung cancer (NSCLC) remains unknown. The aim of the present study was to investigate the prognostic significance of MCP-1 and CCR2 expression in NSCLC cells. The relationship between MCP-1 and CCR2 expression in NSCLC cancer cells was examined by immunohistochemical staining of surgical specimens from 134 patients. Sixty-five of these patients had follow-up records. Kaplan-Meier analysis and Cox regression model were used to assess overall survival according to the presence or absence of MCP-1 and CCR2 expression in tumor cells. MCP-1 was detected in cancer cells of 107 NSCLC (79.9 %) and CCR2 was detected in cancer cells of 39 NSCLC (29.1 %). MCP-1 expression was correlated with sex, smoking habits, histology, and tumor size. Presence of MCP-1 in tumor cells was associated with better overall survival ( P = 0.018). By multivariate analysis, MCP-1 expression in cancer cells showed an independent prognostic factor for overall survival ( P = 0.002, hazard ratio [HR] = 0.256, 95 % confidence interval [CI] = 0.106-0.616). There was no significant relationship between CCR2 expression in tumor cells and clinical and pathological characteristics. Also, no significant positive correlation between MCP-1 and CCR2 expression was revealed by Spearman correlation analysis. Our data indicate that MCP-1 is overexpressed in NSCLC cells. Its expression in cancer cells is associated with better survival in NSCLC patients. [ABSTRACT FROM AUTHOR]