Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency ...of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next‐generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non‐BRCA1/2 gene. Major mutant non‐BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non‐BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER‐2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non‐BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non‐BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.
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The prevalence of mutations in breast cancer predisposition genesare not well investigated in Asia. We assessed germline mutations of 40 cancer susceptibility genes in 937 consecutive selected breast cancer patients from 26 centers of China, and discovered 23.8% of participates carried the pathogenic mutation, including 6.8% with mutations in non‐BRCA1/2 genes, while TP53 and PALB2 had a relatively high mutation rates (1.9% and 1.2%).There was no factors predicted for detrimental mutations in non‐BRCA1/2 genes when treated as a whole.
The simply prepared CuMgAl hydrotalcite (CuMgAl-LDH) has been developed as an efficient catalyst for the aerobic oxidation of ethylbenzene to acetophenone in the presence of N-Hydroxyphthalimide ...(NHPI). Various alkyl arenes could be tolerated under the selected reaction conditions. The kinetic study showed that the oxidation of ethylbenzene is a first-order reaction over CuMgAl-LDH. The mechanism study indicated that CuMgAl-LDH could accelerate not only the conversion of ethylbenzene, but also the transformation of the alcohol intermediate to ketone. The positive effect of surface basicity of the catalyst on the reaction has been observed in the aerobic oxidation of the ethylbenzene.
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•CuMgAl-LDH can efficiently catalyze the aerobic oxidation of ethylbenzene in the presence of NHPI.•Various substrates can be tolerated under the CuMgAl-LDH/NHPI/O2 system.•The kinetic study showed that the oxidation of ethylbenzene is a first-order reaction over CuMgAl-LDH.•The mechanism for the oxidation over CuMgAl-LDH with NHPI was systematically studied.•The positive effect of surface basicity of the catalyst on the reaction has been observed.
The aim of this study was to investigate the frequency distribution of the cytochrome P450 (
) enzymes,
and
, and the form of tamoxifen metab
ion in premenopausal patients with breast cancer in the ...Han and Uygur ethnic groups of Xinjiang to guide rational clinical drug use. A total of 125 Han patients and 121 Uygur patients with premenopausal hormone-receptor-positive breast cancer treated at the Xinjiang Uygur Autonomous Region Cancer Hospital between 1 June 2011 and 1 December 2013 were selected. The common mutation sites in
were analysed using TaqMan® minor groove binder technology. Genetic testing was performed to determine other metabolic types of tamoxifen, and the genotypes and metabolic types were compared using a Chi-squared test. Between the Han and Uygur groups, there were significant differences in the frequencies of the
(*10/*10) and
(*1/*1) genotypes, with
values of 0.002 and 0.015, respectively. Genotypes of
(*1/*1),
(*1/*5),
(*5/*5),
(*5/*10) and
(*3/*3) were expressed in the two patient groups, and the difference was not statistically significant (
> 0.05). In the Han patients, the proportions of extensive, intermediate and poor metabolisers of tamoxifen were 72, 24 and 4%, respectively, whereas those in the Uygur patients were 76.9, 17.4 and 5.7%, respectively, with no significant difference (
> 0.05). In conclusion, There were partial differences in the
and
gene polymorphisms of
between the Han and Uygur patients with premenopausal breast cancer, but there was no significant difference between the
and
phenotypes. Further research is needed to determine the relationship between the enzyme genetic differences of
and the pharmacokinetics and efficacy of tamoxifen. Although there were some differences in genotypes, these did not result in differences in the predicted tamoxifen metabolisation phenotype between the Han and Uygur patients with breast cancer. Therefore, the doses should be adjusted according to the individual genotype data.
Blocking vascular endothelial growth factor pathway can enhance the efficacy of EGFR tyrosine kinase inhibitors in EGFR-mutant NSCLC. ACTIVE is the first phase 3 study conducted in the People’s ...Republic of China evaluating apatinib, a vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor, plus gefitinib as first-line therapy in EGFR-mutant NSCLC.
Treatment-naive patients with stage IIIB or IV nonsquamous NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, and EGFR exon 19 deletion or exon 21 L858R mutation were randomized 1:1 to receive oral gefitinib (250 mg/d), plus apatinib (500 mg/d; apatinib A + gefitinib G group), or placebo (placebo P + gefitinib G group). Stratification factors were mutation type, sex, and performance status. The primary end point was progression-free survival (PFS) by blinded independent radiology review committee (IRRC). Secondary end points were investigator-assessed PFS, overall survival, quality of life (QoL), safety, etc. Next-generation sequencing was used to explore efficacy predictors and acquired resistance.
A total of 313 patients were assigned to the A + G (n = 157) or P + G group (n = 156). Median IRRC PFS in the A + G group was 13.7 months versus 10.2 months in the P + G group (hazard ratio 0.71, p = 0.0189). Investigator- and IRRC-assessed PFS were similar. Overall survival was immature. The most common treatment-emergent adverse events greater than or equal to grade 3 were hypertension (46.5%) and proteinuria (17.8%) in the A + G group and increased alanine aminotransferase (10.4%) and aspartate aminotransferase (3.2%) in the P + G group. QoL in the two groups had no statistical differences. Post hoc analysis revealed PFS benefits tended to favor the A + G group in patients with TP53 exon 8 mutation.
Apatinib + gefitinib as first-line therapy had superior PFS in advanced EGFR-mutant NSCLC versus placebo + gefitinib. Combination therapy brought more adverse events but did not interfere QoL.
NCT02824458.
Many tissues and organ systems have intrinsic regeneration capabilities that are largely driven and maintained by tissue-resident stem cell populations. In recent years, growing evidence has ...demonstrated that cellular metabolic homeostasis plays a central role in mediating stem cell fate, tissue regeneration, and homeostasis. Thus, a thorough understanding of the mechanisms that regulate metabolic homeostasis in stem cells may contribute to our knowledge on how tissue homeostasis is maintained and provide novel insights for disease management. In this review, we summarize the known relationship between the regulation of metabolic homeostasis and molecular pathways in stem cells. We also discuss potential targets of metabolic homeostasis in disease therapy and describe the current limitations and future directions in the development of these novel therapeutic targets.
Research on incorporation of both growth factors and silver (Ag) into hydroxyapatite (HA) coatings on metallic implant surfaces for enhancing osteoinductivity and antibacterial properties is a ...challenging work. Generally, Ag nanoparticles are easy to agglomerate and lead to a large increase in local Ag concentration, which could potentially affect cell activity. On the other hand, growth factors immobilization requires mild processing conditions so as to maintain their activities. In this study, bone morphology protein-2 (BMP-2) and Ag nanoparticle contained HA coatings were prepared on Ti surfaces by combining electrochemical deposition (ED) of Ag and electrostatic immobilization of BMP-2. During the ED process, chitosan (CS) was selected as the stabilizing agent to chelate Ag ions and generate Ag nanoparticles that are uniformly distributed in the coatings. CS also reduces Ag toxicity while retaining its antibacterial activity. Afterwards, a BMP/heparin solution was absorbed on the CS/Ag/HA coatings. Consequently, BMP-2 was immobilized on the coatings by the electrostatic attraction between CS, heparin, and BMP-2. Sustained release of BMP-2 and Ag ions from HA coatings was successfully demonstrated for a long period. Results of antibacterial tests indicate that the CS/Ag/HA coatings have high antibacterial properties against both Staphylococcus epidermidis and Escherichia coli. Osteoblasts (OB) culture reveals that the CS/Ag/HA coatings exhibit good biocompatibility. Bone marrow stromal cells (BMSCs) culture indicates that the BMP/CS/Ag/HA coatings have good osteoinductivity and promote the differentiation of BMSCs. Ti bars with BMP/CS/Ag/HA coatings were implanted into the femur of rabbits to evaluate the osteoinductivity of the coatings. Results indicate that BMP/CS/Ag/HA coatings favor bone formation in vivo. In summary, this study presents a convenient and effective method for the incorporation of growth factors and antibacterial agents into HA coatings. This method can be utilized to modify a variety of metallic implant surfaces.
The design of a coordination complex that involves a ligand combining both a tetrathiafulvalene core and a helicene fragment was achieved thanks to the reaction between the new ...2-{1-2-methyl6helicene-4,5-4,5-bis(propylthio)tetrathiafulvalenyl-1H-benzimidazol-2-yl}pyridine ligand (L) and the Dy(hfac)3·2H2O metalloprecursor. Magnetic investigations showed field-induced single-molecule-magnet (SMM) behavior under an applied magnetic field of 1000 Oe for Dy(hfac)3(L)·0.5CH2Cl2, while experimentally oriented single-crystal magnetic measurements allowed for determination of the magnetic anisotropy orientation. The magnetic behavior was rationalized through ab initio CASSCF/SI-SO calculations. This redox-active chiral-field-induced SMM paves the way for the design of switchable-multiproperty SMMs.
Gastric cancer and liver cancer are among the most common malignancies and the leading causes of death worldwide,due to late detection and high recurrence rates.Today,these cancers have a heavy ...socioeconomic burden,for which a full understanding of their pathophysiological features is warranted to search for promising biomarkers and therapeutic targets.Osteopontin （OPN） is overexpressed in most patients with gastric and liver cancers.Over the past decade,emerging evidence has revealed a correlation of OPN level and clinicopathological features and prognosis in gastric and liver cancers,indicating its potential as an independent prognostic indicator in such patients.Functional studies have verified the potential of OPN knockdown as a therapeutic approach in vitro and in vivo .Furthermore,OPN mediates multifaceted roles in the interaction between cancer cells and the tumor microenvironment,in which many details need further exploration.OPN signaling results in various functions,including prevention of apoptosis,modulation of angiogenesis,malfunction of tumor-associated macrophages,degradation of extracellular matrix,activation of phosphoinositide 3-kinase-Akt and nuclear factor-κB pathways,which lead to tumor formation and progression,particularly in gastric and liver cancers.This editorial aims to review recent findings on alteration in OPN expression and its clinicopathological associations with tumor progression,its potential as a therapeutic target,and putative mechanisms in gastric and liver cancers.Better understanding of the implications of OPN in tumorigenesis might facilitate development of therapeutic regimens to benefit patients with these deadly malignancies.
Superhydrophobic coatings on iron surface have a wide application potential in medical instruments, chemical industrial equipment, and house construction. In this work, we developed a ...multi-functional superhydrophobic coating on iron surface with a high air/water contact angle of 162.3° and a low sliding angle of 2.4°. The construction of superhydrophobic coating involves physical friction processing to fabricate micropatterns and structures, followed by annealing treatment and surface chemical modification with 1H,1H,2H,2H-tridecafluoro-n-octyltrimethoxysilane. The obtained organic-inorganic composite material exhibited considerable optimization potential to anti-condensation performance. The low surface energy of the superhydrophobic coating also leads to poor adhesion of water, dust, and blood platelets, which is beneficial for applications in medical devices. The electrochemical and impedance test results demonstrated that the superhydrophobic surface provided effective corrosion protection for the iron substrate, with an 84.63% increase in corrosion protection efficiency. The experimental results showed that the anti-bacterial ratios reached 90% for
and 85% for
, while the anti-bacterial ratios of ordinary iron were only 8% for
and 15% for
, respectively.
Pulmonary large cell neuroendocrine carcinoma (LCNEC), which accounts for approximately 1% of all lung cancers, is a rare and highly aggressive malignancy with a poor prognosis. Therefore, it is ...important to devise an effective treatment strategy. In the treatment of locally advanced complex LCNEC, it is unique to first administer radiotherapy combined with albumin-bound paclitaxel plus carboplatin, followed by durvalumab for immune maintenance treatment after concurrent radiotherapy and chemotherapy to achieve complete remission. We report a 54-year-old man who smoked and who felt chest tightness for 2 weeks and was diagnosed as having combined pulmonary LCNEC. For patients with locally advanced pulmonary LCNEC, chemoradiotherapy increases overall survival. After surgical resection and chemoradiotherapy, our patient achieved complete remission. Durvalumab was then started to consolidate the treatment. After six courses of immune maintenance therapy, the patient developed grade 2 immune-related pneumonitis and took prednisone orally until the symptoms resolved, and then reached complete remission again. The patient achieved complete remission, which was a challenge with this rare carcinoma, through albumin-bound paclitaxel plus platinum-based chemotherapy combined with radiotherapy and durvalumab for immune maintenance therapy. This approach may provide a treatment option for locally advanced combined pulmonary LCNEC.
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