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1.
Ann Med ; 54(1): 1303-1312, 2022 12.
Article in English | MEDLINE | ID: mdl-35535687

ABSTRACT

Breast cancer (BC) is a group of markedly heterogeneous tumours. There are many subtypes with different biological behaviours and clinicopathological characteristics, leading to significantly different prognosis. Despite significant advances in the treatment of BC, early metastatic is a critical factor for poor prognosis in BC patients. Tumour budding (TB) is considered as the first step process of tumour metastasis and is related to the epithelial-mesenchymal transition (EMT). TB has been observed in a variety of cancers, such as colorectal and gastric cancer, and had been considered as a distinct clinicopathological characteristics for early metastasis. However, TB evaluation standards and clinical application are not uniform in BC, as well as its molecular mechanism is not fully understood. Here, we reviewed the interpretation criteria, mechanism, clinicopathological characteristics and clinical application prospects of TB in BC. Key messagesCurrently, tumour budding is a poor prognosis for various solid tumours, also in breast cancer.Tumour budding is based on epithelial-mesenchymal transition and tumour microenvironment factors and is presumed to be an early step in the metastatic process.Breast cancer tumour budding still needs multi-centre experiments. We summarize the current research on breast cancer tumour budding, analyse the method of discriminating breast cancer tumour budding and explore the prognostic role and mechanism in breast cancer.


Subject(s)
Breast Neoplasms , Biomarkers, Tumor , Breast Neoplasms/diagnosis , Epithelial-Mesenchymal Transition , Female , Humans , Prognosis , Tumor Microenvironment
2.
Eur J Pharmacol ; 877: 173093, 2020 Jun 15.
Article in English | MEDLINE | ID: mdl-32234525

ABSTRACT

The important physiological function of microtubules makes them an indispensable and clinically effective target of anti-tumor agents. Herein, we sought to design, synthesize, and evaluate a novel 4-anilinoquinazoline derivative and identify its anti-tumor activity in vitro and in vivo. The novel compound, N-(4-methoxyphenyl)-N-methyl-2-(methyl-d3)quinazolin-4-amine (AQ-4), was identified as a representative scaffold and potent microtubule-targeting agent. As a promising antimitotic agent, AQ-4 displayed remarkable anti-tumor activity with an average IC50 value of 19 nM across a panel of 14 human cancer cell lines. AQ-4 also exhibited nearly identical potent activities against drug-resistant cells, with no evidence of toxicity towards normal cells. A further target verification study revealed that AQ-4 targets the tubulin-microtubule system by significantly inhibiting tubulin polymerization and disrupting the intracellular microtubule spindle dynamics. According to the results of mechanism study, AQ-4 induced cell cycle arrest in the G2/M phase, promoting evident apoptosis and a collapses of mitochondrial membrane potential. The superior anti-tumor effect of AQ-4 in vivo suggests that it should be further investigated to validate its use for cancer therapy.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Deuterium/chemistry , Microtubules/drug effects , Microtubules/metabolism , A549 Cells , Apoptosis/drug effects , Drug Discovery , Drug Resistance, Neoplasm/drug effects , G2 Phase Cell Cycle Checkpoints/drug effects , Humans , M Phase Cell Cycle Checkpoints/drug effects , Microtubules/pathology
3.
J Phys Condens Matter ; 31(7): 075803, 2019 Feb 20.
Article in English | MEDLINE | ID: mdl-30523803

ABSTRACT

Interface effects in magnetic nanostructures play a critical role in the magnetic properties. By using first-principles density functional theory calculations, we investigate the electronic and magnetic properties of Fe/SrTiO3 interfaces, in which both the nonpolar surface SrTiO3(0 0 1) and the polar surface SrTiO3(1 1 0) are considered. A particular emphasis is placed on the magnetic anisotropy energy (MAE). Comparing MAE of the Fe/SrTiO3 interfaces and the corresponding Fe monolayers, we find the Fe/SrTiO3(0 0 1) interface decreases MAE, while the Fe/SrTiO3(1 1 0) interface increases MAE. The interface orbital hybridization and orbital magnetic moments are analyzed in detail to understand the different interface magnetic anisotropy. Our investigation indicates that interface engineering can be an effective way to modulate the magnetic properties.

4.
Nanoscale ; 9(45): 17957-17962, 2017 Nov 23.
Article in English | MEDLINE | ID: mdl-29125168

ABSTRACT

GeTe is a prototypical compound of a new class of multifunctional materials, i.e., ferroelectric Rashba semiconductors (FRS). In the present work, by combining the first-principles calculations and Rashba model analysis, we reexamine Rashba spin-orbit coupling (SOC) in a GeTe(111) crystal and clarify its linear Rashba SOC strength. We further investigate Rashba SOC at the interface of a GeTe(111)/InP(111) superlattice and demonstrate the ferroelectric manipulation of Rashba SOC in detail. A large modulation of Rashba SOC is obtained, and surprisingly, we find that Rashba SOC does not monotonically increase with the increase of ferroelectric displacement, due to the parabola opening reversal of Rashba splitting bands. In addition, a reversal of the spin texture is realized by tuning the ferroelectric polarization. Our investigation provides a deep insight into the ferroelectric control of Rashba SOC, which is of great importance in FRS spin field effect transistors.

5.
Oncotarget ; 8(8): 12784-12791, 2017 Feb 21.
Article in English | MEDLINE | ID: mdl-28061463

ABSTRACT

The 2014-2015 Ebola epidemic was considered to be the largest and most complex outbreak, which caused 11,310 reported deaths. The epidemic disease can cause a mental health crisis, however, there is only a small amount of scientific literature available related to this health issue so far. We evaluated the psychological symptoms of 161 participants including Ebola survivors and healthcare workers in Sierra Leone, analyzed the impact of job classification, education level on psychological status. We found that the order of total general severity index (GSI) scores from high to low was EVD survivors, SL medical staff, SL logistic staff, SL medical students, and Chinese medical staff. There were 5 dimensions (obsession-compulsion, anxiety, hostility, phobic anxiety, and paranoid ideation) extremely high in EVD survivors. GSI were associated with university education negatively. We believed our information is necessary to develop the comprehensive emergency response plan for emerging infectious disease outbreak.


Subject(s)
Health Personnel/psychology , Hemorrhagic Fever, Ebola/psychology , Mental Disorders/epidemiology , Mental Disorders/etiology , Survivors/psychology , Adolescent , Adult , Child , Cross-Sectional Studies , Disease Outbreaks , Female , Hemorrhagic Fever, Ebola/epidemiology , Humans , Male , Middle Aged , Neuropsychological Tests , Prevalence , Sierra Leone , Young Adult
6.
Infect Dis Poverty ; 5(1): 101, 2016 Nov 03.
Article in English | MEDLINE | ID: mdl-27806732

ABSTRACT

BACKGROUND: Clinical and laboratory data were collected and analysed from patients with Ebola virus disease (EVD) in Jui Government Hospital in Freetown, Sierra Leone, where patients with EVD were received and/or treated from October 1, 2014 to March 21, 2015 during the West Africa EVD outbreak. METHODS: The study admitted 285 patients with confirmed EVD and followed them up till the endpoint (recovery or death). EVD was confirmed by quantitative RT-PCR assays detecting blood Ebola virus (EBOV). RESULTS: Among the 285 lab-confirmed EVD cases in Jui Government Hospital, 146 recovered and 139 died, with an overall survival rate of 51.23 %. Patients under the age of 6 years had a lower survival rate (37.50 %). Most non-survivors (79.86 %) died within 7 days after admission and the mean hospitalization time for non-survivors was 5.56 ± 6.11 days. More than half survivors (63.69 %) turned blood EBOV negative within 3 weeks after admission and the mean hospitalization time for survivors was 20.38 ± 7.58 days. High blood viral load (≥106 copies/ml) was found to be predictive of the non-survival outcome as indicated by the Receiver Operating Characteristic (ROC) curve analysis. The probability of patients' survival was less than 15 % when blood viral load was greater than 106 copies/ml. Multivariate analyses showed that blood viral load (P = 0.005), confusion (P = 0.010), abdominal pain (P = 0.003), conjunctivitis (P = 0.035), and vomiting (P = 0.004) were factors independently associated with the outcomes of EVD patients. CONCLUSIONS: Most death occurred within 1 week after admission, and patients at the age of 6 or younger had a lower survival rate. Most surviving patients turned blood EBOV negative within 1-4 weeks after admission. Factors such as high blood viral load, confusion, abdominal pain, vomiting and conjunctivitis were associated with poor prognosis for EVD patients.


Subject(s)
Ebolavirus/physiology , Hemorrhagic Fever, Ebola/diagnosis , Hemorrhagic Fever, Ebola/mortality , Hospitalization , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Hemorrhagic Fever, Ebola/physiopathology , Hemorrhagic Fever, Ebola/prevention & control , Hospitalization/statistics & numerical data , Humans , Infant , Infant, Newborn , Male , Middle Aged , Prognosis , Retrospective Studies , Sierra Leone , Viral Load , Young Adult
7.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 29(11): 979-81, 2009 Nov.
Article in Chinese | MEDLINE | ID: mdl-20329605

ABSTRACT

OBJECTIVE: To investigate the clinical efficacy of modified Sanmiao Powder (SMP) in treating chronic uric acid nephropathy (CUAN). METHODS: Ninety-four patients with CUAN were equally randomized to the treated group and the control group. Conventional treatment was given to all patients and the treated group was administered with SMP additionally for 12 weeks. Changes of symptoms were observed, and laboratory indexes, as urinary protein quantity (UPro), urinary RBC count (URBC), urinary beta2 microglobulin (beta2-M), urinary beta-N-acetylglucosaminidase (NAG), blood urea nitrogen (BUN), serum creatine (SCr) and serum uric acid (SUA), were detected before and after treatment. RESULTS: The total effective rate in the treated group was 87.2% (41/47), and in the control group was 61.7% (21/47), showing significant difference between groups (P < 0.01); significant improvement of UPro, URBC, beta2-M, NAG, BUN, SCr and SUA were shown in the treated group (P < 0.05, P < 0.01); but in the control group, only URBC count was significantly decreased (P < 0.05), no statistically significant change of other indexes was found (P > 0.05). SUA decreased in both groups (P < 0.01), which was markedly lower in the treated group than in the control group (P < 0.05); SCr and BUN were also decreased in the treated group (P < 0.01). CONCLUSIONS: Combined therapy of SMP and conventional Western medicine shows a favorable effect in treating CUAN. It could not only reduce SUA, but also alleviate the albuminuria and hematuria, lower the urinary levels of beta2-M and NAG to improve renal function.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Kidney Diseases/drug therapy , Phytotherapy , Adult , Aged , Female , Humans , Kidney Diseases/etiology , Male , Medicine, Chinese Traditional/methods , Middle Aged , Uric Acid
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