Tetraspanins: Novel Molecular Regulators of Gastric Cancer

Gastric cancer is the fourth and fifth most common cancer worldwide in men and women, respectively. However, patients with an advanced stage of gastric cancer still have a poor prognosis and low overall survival rate. The tetraspanins belong to a protein superfamily with four hydrophobic transmembrane domains and 33 mammalian tetraspanins are ubiquitously distributed in various cells and tissues. They interact with other membrane proteins to form tetraspanin-enriched microdomains and serve a variety of functions including cell adhesion, invasion, motility, cell fusion, virus infection, and signal transduction. In this review, we summarize multiple utilities of tetraspanins in the progression of gastric cancer and the underlying molecular mechanisms. In general, the expression of TSPAN8, CD151, TSPAN1, and TSPAN4 is increased in gastric cancer tissues and enhance the proliferation and invasion of gastric cancer cells, while CD81, CD82, TSPAN5, TSPAN9, and TSPAN21 are downregulated and suppress gastric cancer cell growth. In terms of cell motility regulation, CD9, CD63 and CD82 are metastasis suppressors and the expression level is inversely associated with lymph node metastasis. We also review the clinicopathological significance of tetraspanins in gastric cancer including therapeutic targets, the development of drug resistance and prognosis prediction. Finally, we discuss the potential clinical value and current limitations of tetraspanins in gastric cancer treatments, and provide some guidance for future research

Sunshine duration reconstruction in the southeastern Tibetan Plateau based on tree-ring width and its relationship to volcanic eruptions

Sunshine is as essential as temperature and precipitation for tree growth, but sunshine duration reconstructions based on tree rings have not yet been conducted in China. In this study, we presented a 497-year sunshine duration reconstruction for the southeastern Tibetan Plateau using a width chronology of Abies forrestii from the central Hengduan Mountains. The reconstruction accounted for 53.5% of the variance in the observed sunshine during the period of 1961-2013 based on a stable and reliable linear regression. This reconstructed sunshine duration contained six sunny periods (1630-1656, 1665-1697, 1731-1781, 1793-1836, 1862-1895 and 1910-1992) and seven cloudy periods (1522-1629, 1657-1664, 1698-1730, 1782-1792, 1837-1861, 1896-1909 and 1993-2008) at a low-frequency scale. There was an increasing trend from the 16th century to the late 18th and early 19th centuries and a decreasing trend from the mid-19th to the early 21st centuries. Sunshine displayed inverse patterns to the local Palmer drought severity index on a multidecadal scale, indicating that this region likely experienced droughts under more sunshine conditions. The decrease in sunshine particularly in recent decades was mainly due to increasing atmospheric anthropogenic aerosols. In terms of the interannual variations in sunshine, weak sunshine years matched well with years of major volcanic eruptions. The significant cycles of the 2- to 7-year, 20.0-year and 35.2-year durations as well as the 60.2-year and 78.7-year durations related to the El-Nino Southern Oscillation, the Pacific Decadal Oscillation and the Atlantic Multidecadal Oscillation suggested that the variation in sunshine duration in the southeastern Tibetan Plateau was possibly affected by large-scale ocean-atmosphere circulations. (C) 2018 Elsevier B.V. All rights reserved

Effects of lidocaine and ropivacaine on gastric cancer cells through down-regulation of ERK1/2 phosphorylation in vitro

Background: Lidocaine and ropivacaine have been widely used in gastric cancer surgery. In recent years, lidocaine and ropivacaine have attracted increasing attention in cancer research, whilst effects of lidocaine and ropivacaine on gastric cancer cells have not been investigated before. This study explored the effect of lidocaine and ropivacaine on AGS and HGC-27 gastric cancer cells. Materials and Methods: AGS and HGC-27 cells were incubated with lidocaine or ropivacaine at concentrations of 10, 100 and 1 mM. At 24, 48 and 72 h after treatment, proliferation and invasion were evaluated by crystal violet assay and transwell invasion assay. Electric cell-substrate impedance sensing was applied to measure the migration of cancer cells. Phosphorylation status of extracellular-regulated protein kinases (ERK1/2) was evaluated by western blot analysis. Results: Lidocaine (1 mM) and ropivacaine (1 mM) significantly inhibited the proliferation of AGS and HG-27 cells, but had no significant effects on invasion. Lidocaine (1 mM) and ropivacaine (1 mM) also inhibited the migration of AGS and HGC-27cells. After treatment with lidocaine (1 mM) or ropivacaine (1 mM) for 24 h, the phosphorylation of ERK1/2 in AGS and HGC-27 cells was reduced. Conclusion: Lidocaine at a clinically relevant concentration (10 μM), and ropivacaine at 1 mM inhibited the proliferation of gastric cancer cell lines by down-regulation of p-ERK1/2. The migration of HGC-27 cells, rather than AGS cells was more obviously inhibited by lidocaine (1 mM) and ropivacaine (1 mM). This research is easy to implement, and lays a foundation for the future research of local anaesthetics in cancer

Tree-ring stable carbon isotope-based April-June relative humidity reconstruction since AD 1648 in Mt. Tianmu, China

Based on accurate dating, we have determined the stable carbon isotope ratios (delta C-13) of five Cryptomeria fortunei specimens from Mt. Tianmu, a subtropical area in southern China. The five delta C-13 time series records are combined into a single representative delta C-13 time series using a "numerical mix method." These are normalized to remove temporal variations of delta(13) C in atmospheric CO2 to obtain a carbon isotopic discrimination (Delta C-13) time series, in which we observe a distinct correlation between Delta C-13 and local April to June mean relative humidity (RH (AMJ) ) (n = 64, r = 0.858, p < 0.0001). We use this relationship to reconstruct RH (AMJ) variations from ad 1648 to 2014 at Mt. Tianmu. The reconstructed sequence show that over the past 367 years, Mt. Tianmu area was relatively wet, but in the latter part of the twentieth century, under the influence of increasing global warming, it has experienced a sharp reduction in relative humidity. Spatial correlation analysis reveals a significant negative correlation between RH (AMJ) at Mt. Tianmu and Sea Surface Temperature (SSTs) in the western equatorial Pacific and Indian Ocean. In other words, there is a positive correlation between tree-ring delta C-13 in Mt. Tianmu and SSTs. Both observed and reconstructed RH (AMJ) show significant positive correlations with East Asian and South Asian monsoons from 1951 to 2014, which indicate that RH (AMJ) from Mt. Tianmu reflects the variability of the Asian summer monsoon intensity to a great extent. The summer monsoon has weakened since 1960. However, an increase in relative humidity since 2003 implies a recent enhancement in the summer monsoon

Full-length transcriptome sequencing reveals the molecular mechanism of monoterpene and sesquiterpene biosynthesis in Cinnamomum burmannii

Essential oil of Cinnamomum burmannii is rich in monoterpenes and sesquiterpenes and is widely used in cosmetics and medicines. Knowledge about the enzymes that catalyze the formation of monoterpenes and sesquiterpenes in C. burmannii is insufficient. Therefore, anatomy observation of C. burmannii at the four developmental stages (7 days, CBS1; 14 days, CBS2; 21 days, CBS3, and 28 days, CBS4) were conducted to elucidate the origins of essential oil production. Twelve full-length transcriptomes of C. burmannii leaves at the four stages were generated using Oxford Nanopore Technologies. GC-MS analysis revealed 15 monoterpene and sesquiterpenes dramatically increased from CBS1 to CBS4. A weighted correlation network analysis (WGCNA) in association and differentially expressed genes across four developmental stages were performed. A total of 44 differentially expressed genes (DEGs) were involved in terpenoid syntheses during leaf development. Among them, the DEGs of the mevalonate acid (MVA) pathway were predominantly expressed at CBS1, while those of the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway showed increased expression from CBS2 to CBS4. Besides, fourteen genes were associated with monoterpene synthesis and nine with sesquiterpene synthesis. Functions of these DEGs were further predicted with regard to gene expression profile and phylogenetic relationship with those characterized in previous studies. In addition, 922 long noncoding RNAs (lncRNAs) were detected, of which twelve were predicted to regulate monoterpene and sesquiterpene biosynthesis. The present study provided new insights the molecular mechanisms of monoterpenoid and sesquiterpenoid syntheses of C. burmannii

Anthropogenic Aerosols Cause Recent Pronounced Weakening of Asian Summer Monsoon Relative to Last Four Centuries

The Asian Summer Monsoon (ASM) affects ecosystems, biodiversity, and food security of billions of people. In recent decades, ASM strength (as represented by precipitation) has been decreasing, but instrumental measurements span only a short period of time. The initiation and the dynamics of the recent trend are unclear. Here for the first time, we use an ensemble of 10 tree ring-width chronologies from the west-central margin of ASM to reconstruct detail of ASM variability back to 1566 CE. The reconstruction captures weak/strong ASM events and also reflects major locust plagues. Notably, we found an unprecedented 80-year trend of decreasing ASM strength within the context of the 448-year reconstruction, which is contrary to what is expected from greenhouse warming. Our coupled climate model shows that increasing anthropogenic sulfate aerosol emissions over the Northern Hemisphere could be the dominant factor contributing to the ASM decrease. Plan Language Summary Monsoonal rainfall has a certain influence on agriculture and industry in the regions of Asian Summer Monsoon (ASM). An understanding of the spatial-temporal variability of the ASM and the associated dynamics is vital for terrestrial ecosystems, water resources, forests, and landscapes. We have developed a 448-year ASM reconstruction back to 1566 CE using 10 tree ring chronologies from the margin region of ASM. We find that historical severe droughts and locust plague disasters during weak ASM events. The recent decreasing ASM trend persisting for over 80 years is unprecedented over the past 448 years. Coupled climate models show that increasing anthropogenic aerosol emissions are the dominant underlying factor. Our aim is that the time series will find a wide range of utility for understanding past climate variability and for predicting future climate change.National Natural Science Foundation of China [41630531]; National Research Program for Key Issues in Air Pollution Control [DQGG0104]; Chinese Academy of Sciences [QYZDJ-SSW-DQC021, XDPB05, GJHZ1777]; Institute of Earth Environment, Chinese Academy of Sciences; State Key Laboratory of Loess and Quaternary Geology6 month embargo; first published: 09 April 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

A Phase Ib Study of the Simmitecan Single Agent and in Combination With 5-Fluorouracil/Leucovorin or Thalidomide in Patients With Advanced Solid Tumor

Background: Simmitecan is a potent inhibitor of topoisomerase I with anti-tumor activity. This phase Ib trial was conducted to investigate the safety and anti-tumor effect of simmitecan alone or in combination with other drugs.Methods: Eligible patients with advanced solid tumor had no further standard treatment options. Patients were allocated to receive simmitecan alone, simmitecan in combination with 5-fluorouracil (5-FU)/leucovorin (LV), or simmitecan in combination with thalidomide, 14 days a cycle, until disease progression or unacceptable toxicity occurred.Results: A total of 41 patients were enrolled, with a median age of 55 (range 29–69) years. Among them, 13 patients received simmitecan monotherapy, 10 received simmitecan + 5-FU/LV, and 18 received simmitecan + thalidomide. No dose-limiting toxicity occurred. Overall, the most common grade 3/4 adverse event (AE) was neutropenia (46.2, 70.0, and 88.9%, respectively, in simmitecan, simmitecan + 5-FU/LV, and simmitecan + thalidomide cohorts), and treatment-related severe AEs included anemia and febrile neutropenia (7.7% each in simmitecan cohort), diarrhea (10% in simmitecan +5-FU/LV cohort), and febrile neutropenia (5.6% in simmitecan + thalidomide cohort). The majority of patients (24/41, 58.3%) had progressed on prior irinotecan; nevertheless, partial response was achieved in one colorectal cancer patients treated with simmitecan + thalidomide. The disease control rates of simmitecan, simmitecan + 5-FU/LV, and simmitecan + thalidomide cohorts were 46.2, 80.0, and 61.1%, respectively.Conclusion: This study demonstrated a manageable safety profile of simmitecan as a single agent or as part of a combination therapy. There have not been any safety concerns with simmitecan in combination when compared to simmitecan alone. Simmitecan + 5-FU/LV regimen seemed to have a better efficacy. Nonetheless, the efficacy of this regimen needs to be further explored in the subsequent study