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Displaying publications 21 - 29 of 29 in total

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Hypoxia-inducible factor-1 alpha Correlates with Tumor-Associated Macrophages Infiltration, Influences Survival of Gastric Cancer Patients

Zhang WJ, Chen C, Zhou ZH, Gao ST, Tee TJ, Yang LQ, et al.

J Cancer, 2017;8(10):1818-1825.
PMID: 28819379 DOI: 10.7150/jca.19057

Background: Hypoxia was a common feature for accelerating tumor metastasis by both inducting epithelial-mesenchymal transition (EMT) of tumor cells and polarization of tumor-associated macrophages (TAMs). The association and roles between hypoxia, EMT and TAMs in the biological behavior of gastric cancer (GC) for the time being recurrence is unclear. Material and methods: hypoixa by expression of hypoxia-inducible factor-1 alpha (HIF-1α), polarized functional status of infiltrated TAMs by immunohistochemical staining of CD68 and CD163, and the expression of E-cadherin as EMT property had been evaluated in 236 patients consecutive with histologically confirmed GC. Clinical significance was assessed for all these patients. Results: High expression of HIF-1α was found in patients with aggressive features, especially for recurrent patients. High infiltration of TAMs and abnormal expression of EMT-marker were also related to aggressive characteristics and predicted poor prognosis in GC. Meanwwhile, there existed a significant correlation among expression of HIF-1α, infiltration of TAMs and EMT marker in GC tissues. Multivariate Cox analysis revealed that high expression of HIF-1α combined TAMs infiltration were independent prognostic factors for disease-specific survival rate. Conclusion: HIF-1α is an unfavorable indicator for prognosis, may promote tumor progression through the induction of EMT and establishment of a pro-tumor immunosuppressive microenvironment. Further investigation into the therapeutic effects of blocking hypoxia is possible a potential strategy for GC treatment.
Fulltext Microbiota organization is a distinct feature of proximal colorectal cancers

Dejea CM, Wick EC, Hechenbleikner EM, White JR, Mark Welch JL, Rossetti BJ, et al.

Proc Natl Acad Sci U S A, 2014 Dec 23;111(51):18321-6.
PMID: 25489084 DOI: 10.1073/pnas.1406199111

Environmental factors clearly affect colorectal cancer (CRC) incidence, but the mechanisms through which these factors function are unknown. One prime candidate is an altered colonic microbiota. Here we show that the mucosal microbiota organization is a critical factor associated with a subset of CRC. We identified invasive polymicrobial bacterial biofilms (bacterial aggregates), structures previously associated with nonmalignant intestinal pathology, nearly universally (89%) on right-sided tumors (13 of 15 CRCs, 4 of 4 adenomas) but on only 12% of left-sided tumors (2 of 15 CRCs, 0 of 2 adenomas). Surprisingly, patients with biofilm-positive tumors, whether cancers or adenomas, all had biofilms on their tumor-free mucosa far distant from their tumors. Bacterial biofilms were associated with diminished colonic epithelial cell E-cadherin and enhanced epithelial cell IL-6 and Stat3 activation, as well as increased crypt epithelial cell proliferation in normal colon mucosa. High-throughput sequencing revealed no consistent bacterial genus associated with tumors, regardless of biofilm status. However, principal coordinates analysis revealed that biofilm communities on paired normal mucosa, distant from the tumor itself, cluster with tumor microbiomes as opposed to biofilm-negative normal mucosa bacterial communities also from the tumor host. Colon mucosal biofilm detection may predict increased risk for development of sporadic CRC.
Sofosbuvir-velpatasvir for treatment of chronic hepatitis C virus infection in Asia: a single-arm, open-label, phase 3 trial

Wei L, Lim SG, Xie Q, Văn KN, Piratvisuth T, Huang Y, et al.

Lancet Gastroenterol Hepatol, 2019 02;4(2):127-134.
PMID: 30555048 DOI: 10.1016/S2468-1253(18)30343-1

BACKGROUND: Treatment with combined sofosbuvir and velpatasvir has resulted in high sustained virological response rates in patients chronically infected with hepatitis C virus (HCV) with genotypes 1-6 in clinical trials and real-world settings, but its efficacy and safety has not been assessed in Asia, a region with diverse HCV genotypes.
METHODS: In this single-arm, open-label, phase 3 trial, we recruited patients from 38 sites across China, Thailand, Vietnam, Singapore, and Malaysia, who were chronically infected with HCV genotypes 1-6, and were HCV treatment-naive or treatment-experienced, either without cirrhosis or with compensated cirrhosis. Patients self-administered a combined sofosbuvir (400 mg) and velpatasvir (100 mg) tablet once daily for 12 weeks. The primary efficacy endpoint was sustained virological response, defined as HCV RNA less than 15 IU/mL at 12 weeks after completion of treatment (SVR12), assessed in all patients who received at least one dose of study drug. The primary safety endpoint was the proportion of adverse events leading to premature discontinuation of study drug. This trial is registered with ClinicalTrials.gov, number NCT02671500, and is completed.
FINDINGS: Between April 14, 2016, and June 30, 2017, 375 patients were enrolled in the study, of whom 374 completed the full treatment course and one discontinued treatment. Overall, 362 (97% [95% CI 94-98]) of 375 patients achieved SVR12. Among 42 patients with HCV genotype 3b, all of whom had baseline resistance-associated substitutions in NS5A, 25 (89% [95% CI 72-98]) of 28 patients without cirrhosis and seven (50% [23-77]) of 14 patients with cirrhosis achieved SVR12. The most common adverse events were upper respiratory tract infection (36 [10%] patients) and headache (18 [5%] patients). There were no discontinuations due to adverse events. Serious adverse events were reported in three (1%) patients, none of which was judged to be related to sofosbuvir-velpatasvir treatment.
INTERPRETATION: Consistent with data from other phase 3 studies, single-tablet sofosbuvir-velpatasvir for 12 weeks is an efficacious and safe treatment for Asian patients with chronic HCV infection, but might have lower efficacy in those infected with HCV genotype 3b and with cirrhosis.
FUNDING: Gilead Sciences.
Fulltext Was Wuhan the early epicenter of the COVID-19 pandemic?-A critique

Cao Y, Chen L, Chen H, Cun Y, Dai X, Du H, et al.

Natl Sci Rev, 2023 Apr;10(4):nwac287.
PMID: 37089192 DOI: 10.1093/nsr/nwac287
First Evidence for cos2β>0 and Resolution of the Cabibbo-Kobayashi-Maskawa Quark-Mixing Unitarity Triangle Ambiguity

Adachi I, Adye T, Ahmed H, Ahn JK, Aihara H, Akar S, et al.

Phys Rev Lett, 2018 Dec 28;121(26):261801.
PMID: 30636113 DOI: 10.1103/PhysRevLett.121.261801

We present first evidence that the cosine of the CP-violating weak phase 2β is positive, and hence exclude trigonometric multifold solutions of the Cabibbo-Kobayashi-Maskawa (CKM) Unitarity Triangle using a time-dependent Dalitz plot analysis of B^{0}→D^{(*)}h^{0} with D→K_{S}^{0}π^{+}π^{-} decays, where h^{0}∈{π^{0},η,ω} denotes a light unflavored and neutral hadron. The measurement is performed combining the final data sets of the BABAR and Belle experiments collected at the ϒ(4S) resonance at the asymmetric-energy B factories PEP-II at SLAC and KEKB at KEK, respectively. The data samples contain (471±3)×10^{6}BB[over ¯] pairs recorded by the BABAR detector and (772±11)×10^{6}BB[over ¯] pairs recorded by the Belle detector. The results of the measurement are sin2β=0.80±0.14(stat)±0.06(syst)±0.03(model) and cos2β=0.91±0.22(stat)±0.09(syst)±0.07(model). The result for the direct measurement of the angle β of the CKM Unitarity Triangle is β=[22.5±4.4(stat)±1.2(syst)±0.6(model)]°. The measurement assumes no direct CP violation in B^{0}→D^{(*)}h^{0} decays. The quoted model uncertainties are due to the composition of the D^{0}→K_{S}^{0}π^{+}π^{-} decay amplitude model, which is newly established by performing a Dalitz plot amplitude analysis using a high-statistics e^{+}e^{-}→cc[over ¯] data sample. CP violation is observed in B^{0}→D^{(*)}h^{0} decays at the level of 5.1 standard deviations. The significance for cos2β>0 is 3.7 standard deviations. The trigonometric multifold solution π/2-β=(68.1±0.7)° is excluded at the level of 7.3 standard deviations. The measurement resolves an ambiguity in the determination of the apex of the CKM Unitarity Triangle.
Evidence for the Higgs Boson Decay to a Z Boson and a Photon at the LHC

Aad G, Abbott B, Abeling K, Abicht NJ, Abidi SH, Aboulhorma A, et al.

Phys Rev Lett, 2024 Jan 12;132(2):021803.
PMID: 38277607 DOI: 10.1103/PhysRevLett.132.021803

The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018. These correspond to integrated luminosities of around 140 fb^{-1} for each experiment, at a center-of-mass energy of 13 TeV. The measured signal yield is 2.2±0.7 times the standard model prediction, and agrees with the theoretical expectation within 1.9 standard deviations.
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.

Autophagy, 2016;12(1):1-222.
PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
Combination of Measurements of the Top Quark Mass from Data Collected by the ATLAS and CMS Experiments at sqrt[s]=7 and 8 TeV

Hayrapetyan A, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, et al.

Phys Rev Lett, 2024 Jun 28;132(26):261902.
PMID: 38996325 DOI: 10.1103/PhysRevLett.132.261902

A combination of fifteen top quark mass measurements performed by the ATLAS and CMS experiments at the LHC is presented. The datasets used correspond to an integrated luminosity of up to 5 and 20 fb^{-1} of proton-proton collisions at center-of-mass energies of 7 and 8 TeV, respectively. The combination includes measurements in top quark pair events that exploit both the semileptonic and hadronic decays of the top quark, and a measurement using events enriched in single top quark production via the electroweak t channel. The combination accounts for the correlations between measurements and achieves an improvement in the total uncertainty of 31% relative to the most precise input measurement. The result is m_{t}=172.52±0.14(stat)±0.30(syst) GeV, with a total uncertainty of 0.33 GeV.
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1

Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.

Autophagy, 2021 Jan;17(1):1-382.
PMID: 33634751 DOI: 10.1080/15548627.2020.1797280

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.