BRCAness is considered a predictive biomarker to platinum and poly(ADP‐ribose) polymerase (PARP) inhibitors. However, recent trials showed that its predictive value was limited in triple‐negative ...breast cancer (TNBC) treated with platinum. Moreover, tumors with mutations of DNA damage response (DDR) genes, such as homologous recombination (HR) genes, could be sensitive to platinum and PARP inhibitors. Thus, we aim to explore the relationship between mutation status of DDR genes and BRCAness in TNBC. We sequenced 56 DDR genes in 120 TNBC and identified BRCAness by array comparative genomic hybridization. The sequencing results showed that 13, 14, and 14 patients had BRCA, non‐BRCA HR, and non‐HR DDR gene mutations, respectively. Array comparative genomic hybridization revealed that BRCA‐mutated and HR gene‐mutated TNBC shared similar BRCAness features, both having higher numbers and longer length of large‐scale structural aberration (LSA, >10 Mb) and similar altered chromosomal regions of LSA. These suggested non‐BRCA HR gene‐mutated TNBC shared similar characteristics with BRCA‐mutated TNBC, indicating non‐BRCA HR gene‐mutated TNBC sensitive to platinum and PARP inhibitors. Among tumors with mutation of non‐HR DDR genes, 3 PTEN and 1 MSH6 mutation also contained significant LSAs (BRCAness); however, they had different regions of genomic alteration to BRCA and HR gene‐mutated tumors, might explain prior findings that PTEN‐ and MSH6‐mutated cancer cells not sensitive to PARP inhibitors. Therefore, we hypothesize that the heterogeneous genomic background of BRCAness indicates different responsiveness to platinum and PARP inhibitors. Direct sequencing DDR genes in TNBC should be applied to predict their sensitivity toward platinum and PARP inhibitors.
High‐grade genomic instability (BRCAness) can be present in triple‐negative breast cancer with BRCA, non‐BRCA HR gene, PTEN and MSH6 mutation. We hypothesize that the heterogeneous genomic background of BRCAness indicates different responsiveness to platinum and PARP inhibitors.
In this study, we used a high quality epitaxial TiN thin film grown on MgO (001) substrate for the investigation of the TiN/MgO interface structure which was characterized with scanning transmission ...electron microscopy (STEM) at atomic resolution. Analyses of high angle annular dark-field and annular bright-field STEM image contrast with X-ray energy dispersive spectroscopy maps show that a 2~4nm diffuse interlayer of mixed compositions exists coherently between TiN and MgO with the same structure and across the interface the ionic bonding sequences are maintained without any interruption.
•A diffuse interlayer exists between titanium nitride(TiN) and magnesium oxide(MgO).•The interlayer has the rocksalt structure with in-plane lattice matched with TiN and MgO.•Across the interlayer the ionic bonding sequences of cations with anions
Patients with stage II to III breast cancer have a high recurrence rate. The early detection of recurrent breast cancer remains a major unmet need. Circulating tumor DNA (ctDNA) has been proven to be ...a marker of disease progression in metastatic breast cancer. We aimed to evaluate the prognostic value of ctDNA in the setting of neoadjuvant therapy (NAT).
Plasma was sampled at the initial diagnosis (defined as before NAT) and after breast surgery and neoadjuvant therapy(defined as after NAT). We extracted ctDNA from the plasma and performed deep sequencing of a target gene panel. ctDNA positivity was marked by the detection of alterations, such as mutations and copy number variations.
A total of 95 patients were enrolled in this study; 60 patients exhibited ctDNA positivity before NAT, and 31 patients exhibited ctDNA positivity after NAT. A pathologic complete response (pCR) was observed in 13 patients, including one ER(+)Her2(-) patient, six Her2(+) patients and six triple-negative breast cancer (TNBC) patients. Among the entire cohort, multivariate analysis showed that N3 classification and ctDNA positivity after NAT were independent risk factors that predicted recurrence (N3, hazard ratio (HR) 3.34, 95% confidence interval (CI) 1.26 - 8.87, p = 0.016; ctDNA, HR 4.29, 95% CI 2.06 - 8.92, p < 0.0001). The presence of ctDNA before NAT did not affect the rate of recurrence-free survival. For patients with Her2(+) or TNBC, patients who did not achieve pCR were associated with a trend of higher recurrence (p = 0.105). Advanced nodal status and ctDNA positivity after NAT were significant risk factors for recurrence (N2 - 3, HR 3.753, 95% CI 1.146 - 12.297, p = 0.029; ctDNA, HR 3.123, 95% CI 1.139 - 8.564, p = 0.027). Two patients who achieved pCR had ctDNA positivity after NAT; one TNBC patient had hepatic metastases six months after surgery, and one Her2(+) breast cancer patient had brain metastasis 13 months after surgery.
This study suggested that the presence of ctDNA after NAT is a robust marker for predicting relapse in stage II to III breast cancer patients.
The effects of surface pre-treatments and the role of an AlN buffer layer for 2H-SiC growth on
c
-plane sapphire substrates by thermal CVD are investigated. While the crystallinity of SiC directly ...grown on sapphire substrate always degrades with a hydrogen pre-treatment but improves by optimizing carbonization, the crystallinity of SiC grown on sapphire substrate using an AlN buffer grown by MOCVD improves with sufficient time of exposure to the H pre-treatment but always deteriorates with carbonization. Detailed microstructural analysis by phi-scan x-ray diffraction reveals that SiC film grown on sapphire substrate consists of crystalline domains with two different crystallographic orientations which are rotated relative to each other along the 111 axis by 60°. A highly oriented hexagonal 2H-SiC film is obtained on low-cost c-plane sapphire substrate by using an AlN buffer. 2H-SiC is unambiguously determined not only by phi-scan x-ray diffraction but also by high-resolution transmission electron microscopy. The growth relationship between 2HSiC and 2H-AlN are coherent due to the favorable bonding of C and Al between SiC and AlN.
An unconventional non-polar (123¯0)ZnO epitaxial film is grown on (118)LaAlO3(LAO) substrate by pulsed laser deposition. X-ray diffraction pole figures and transmission electron microscopy show that ...the crystal orientation relationships between non-polar (123̄0)ZnO and (118)LAO substrate are (0001)ZnO//(1̄10)LAO and (112̄0)ZnO//(001)LAO. The Raman spectrum with a significant E2 peaked at 439cm−1 clearly indicates the formation of non-polar ZnO film. Photoluminescence measurement of the non-polar ZnO film shows a strong near-band-edge emission located at 3.3eV with negligible green-yellow emission.
•The growth of non-polar (123¯0)ZnO film is demonstrated on (118)LaAlO3.•The non-polar (123¯0)ZnO film forms single crystallized epitaxial film on (118)LaAlO3.•The crystal orientation relationships between (123¯0)ZnO and (118)LaAlO3 are (0001)ZnO//(1¯10)LAO and (112¯0)ZnO//(001)LAO.
We investigate the effect of chemical composition and residual stress on the mechanical properties of high-quality epitaxial TiNxOy films deposited on MgO(001) substrates by using nanoindentation. ...The lattice parameters and residual strain/stress of TiNxOy films decrease as oxygen concentration increases. Hardness and Young's modulus determined by nanoindentation are about 17–26GPa and 355–430GPa, respectively, which vary with chemical composition and residual stress.
•The lattice parameters and residual strain/stress of TiNxOy films decrease as oxygen concentration increases.•The hardness (H) and Young's modulus (E) of TiNxOy films are about 17–26GPa and 355–430GPa, respectively.•H and E of TiNxOy films decrease with increasing oxygen content and increase with increasing nitrogen content.•H and E of TiNxOy films decrease with decreasing residual compressive stress.
High-quality epitaxial TiNxOy films with different oxygen content were deposited on MgO(001) substrates by pulsed laser deposition method. The chemical composition of the deposited films was ...determined by X-ray photoelectron spectroscopy. X-ray diffraction results showed that the TiNxOy films are heteroepitaxially grown on MgO with good crystallinity and their lattice parameters decrease with increased oxygen concentration. Transmission electron microscopy analyses showed that TiNO films contain a low density of dislocations. Atomic force microscopy revealed very smooth surfaces of TiNxOy films with roughness of 0.26–0.29nm. The resistivity of TiNxOy films determined by Hall measurement was about 28–33μΩcm. Nanoindentation measurements showed the film hardness and Young's modulus of about 23–26GPa and 400–430GPa, respectively.
► High-quality epitaxial TiNxOy films with different oxygen content are successfully grown on MgO(001) substrates. ► The TiNxOy films contain a low density of defects. ► The lattice parameters of TiNxOy decrease with increased oxygen concentration. ► The TiNxOy films are very electrically conducting with resistivity of 28–33μΩcm. ► The TiNxOy films show the hardness and Young's modulus of about 23–26GPa and 400–430GPa, respectively.
Growth of nonpolar (101¯0) and semipolar (112¯2¯) ZnO on (112) LaAlO3 (LAO) substrates can be obtained by annealing the substrate surface in vacuum and oxygen ambient conditions prior to ZnO ...deposition, respectively. We investigated the origin of the two different growth relationships by inspecting their interface in atomic scale using high angle annular dark field scanning transmission electron microscopy. (101¯0) ZnO was grown on flat (112)LAO surface due to the similar atomic configurations and small lattice mismatch between them at the interface, and (112¯2¯) ZnO was grown on a faceted surface with (001)LAO and (110)LAO facets on which accommodation growth of both (112¯0) ZnO and (0001¯) ZnO are consistent with 11¯00ZnO//11¯0LAO.
•Growth control of (101¯0) and (112¯2¯) ZnO on (112) LaAlO3 was shown by annealing.•The surface structure of (112) LAO can be modified by annealing.•(101¯0) ZnO was grown on flat (112)LAO plane due to similar atomic configuration.•(112¯2¯) ZnO was grown on the surface with atomic (001)LAO and (110)LAO facets.
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