Clinicopathological characteristics and value of HER2-low expression evolution in breast cancer receiving neoadjuvant chemotherapy.

OBJECTIVE: The present study aimed to evaluate the clinicopathological characteristics and value of HER2-low expression evolution in breast cancer receiving neoadjuvant chemotherapy (NAC). METHODS: Patients with HER2 negative breast cancer receiving NAC from January 2017 to December 2020 were enrolled in this study. The clinicopathological characteristics, response to NAC, evolution of HER2 and prognostic value were retrospectively analyzed. RESULTS: 410 patients were included. The proportion of HR positive disease in HER2-low cases was higher than in HER2-zero population (75.8 % vs. 65.8 %, P = 0.040). No statistical significant difference in pCR rate was observed between HER2-low and HER2-zero patients (33.8 % vs. 39.3 %, P = 0.290) when pCR was defined as ypTis/0ypN0. Exploratory analysis revealed that the pCR rate of HER2-low cases was significantly lower than HER2-zero patients in the entire population (19.8 % vs. 33.3 %, P = 0.004) and HR positive population (12.6 % vs. 29.9 %, P = 0.001) when pCR was defined as ypT0ypN0. The evolution rate of HER2 expression after NAC was 31.0 % in HER2-zero patients and 24.7 % in HER2-low patients. Compared with patients with HR positive disease, patients with TNBC had higher evolution rate of HER2 expression after NAC (37.7 % vs. 23.6 %). Significant association was observed between HER2 evolution with histology type and Ki-67 index in HER2-zero patients and with lymph node involvement, HR status and Ki-67 index in HER2-low patients. Prognostic impact of HER2 evolution was not observed. CONCLUSIONS: HR positive and HR negative HER2-low breast cancer exhibit different clinicopathological features, response to NAC and HER2 evolution after treatment.

Two-dimensional MN4 materials as effective multifunctional electrocatalysts for the hydrogen-evolution, oxygen-evolution, and oxygen-reduction reactions.

Two-dimensional (2D) materials confining single atoms (SAs) for catalysis, such as graphene confining metal single atoms (M-N-C), integrate both aspects of 2D materials and single-atom catalysts (SACs). Significant advantages have been established in this new category of catalysts, which have seen rapid development in recent years. Recent studies have suggested a new class of novel 2D materials with a chemical formula of MN4 naturally holding a uniformly distributed M-N4 moiety. We investigated MN4 monolayers as multifunctional catalysts for the hydrogen-evolution reaction (HER), oxygen-evolution reaction (OER), and oxygen-reduction reaction (ORR). Among them, the IrN4 monolayer demonstrated high catalytic activity towards these three reactions. The CoN4 monolayer was predicted to be an excellent bifunctional catalyst for the OER and ORR. A uniformly distributed and short-distanced M-N4 moiety on the MN4 monolayer made reactions between the intermediates during the OER and ORR possible, facilitating the release of O2 and H2O, respectively. In addition, the M atom of the MN4 monolayer having electronic states located at the Fermi level was active for catalyzing the HER. More importantly, changes in the Gibbs free energy of the two key intermediates of adsorption (ΔGOH* and ΔGOOH*) correlated closely with the Bader charge on the M atom (BM).

Extension of the TraPPE Force Field for Battery Electrolyte Solvents.

Optimizing electrolyte formulations is key to improving performance of Li-/Na-ion batteries, where transport properties (diffusion coefficient, viscosity) and permittivity need to be predicted as functions of temperature, salt concentration and solvent composition. More efficient and reliable simulation models are urgently needed, owing to the high cost of experimental methods and the lack of united-atom molecular dynamics force fields validated for electrolyte solvents. Here the computationally efficient TraPPE united-atom force field is extended to be compatible with carbonate solvents, optimizing the charges and dihedral potential. Computing the properties of electrolyte solvents, ethylene carbonate (EC), propylene carbonate (PC), dimethyl carbonate (DMC), diethyl carbonate (DEC), and dimethoxyethane (DME), we observe that the average absolute errors in the density, self-diffusion coefficient, permittivity, viscosity, and surface tension are approximately 15% of the corresponding experimental values. Results compare favorably to all-atom CHARMM and OPLS-AA force fields, offering computational performance improvement of at least 80%. We further use TraPPE to predict the structure and properties of LiPF6 salt in these solvents and their mixtures. EC and PC form complete solvation shells around Li+ ions, while the salt in DMC forms chain-like structures. In the poorest solvent, DME, LiPF6 forms globular clusters despite DME's higher permittivity than DMC.

HER2-low expression does not affect the clinical outcomes of metastatic breast cancer treated with CDK4/6 inhibitor: A real-world study.

Background: There is accumulating evidence support human epidermal growth factor receptor 2 (HER2)-low as a biologically distinct subtype of breast cancer. The present study was conducted to explore whether HER2-low expression will affect the clinical efficacy of cyclin-dependent kinase (CDK) 4/6 inhibitor for patients with hormone receptor (HR)-positive, HER-2 negative metastatic breast cancer. Methods: Patients with HR+/HER2- metastatic breast cancer who were treated with palbociclib from January 2019 to June 2021 were retrospectively analyzed based on real-world clinical practice. HER2-zero was defined as immunohistochemistry (IHC) 0, and HER2-low was defined as IHC 1+ or IHC 2+/fluorescence in situ hybridization (FISH) negative. The primary end point was progression free survival (PFS), and the secondary end points were objective response rate (ORR), disease control rate (DCR), overall survival(OS) and safety. Results: 45 patients received palbociclib plus aromatase inhibitor (AI) or fulvestrant therapy, including 24 HER-2-zero and 21 HER-2-low patients. There were no statistically significant differences in clinicopathological characteristics between the two groups. No significant differences were observed in ORR (41.7% vs. 28.6%, P=0.360) and DCR (79.2% vs. 76.2%, P=0.811) between HER-2-zero and HER-2-low patients. And simultaneously, HER2-zero and HER2-low patients obtained similar median PFS (16.2m vs. 14.1m, P=0.263). The median OS was not reached. Neutropenia and leukopenia were the most common adverse events. Grade 3-4 adverse events(AEs) occurred in 58.3% and 57.1% of patients, respectively. Conclusions: HER2-low expression does not affect the clinical efficacy of palbociclib and our present study did not support incorporating HER2-low into systemic therapy decisions for patients with HR+/HER2- metastatic breast cancer treated with CDK4/6 inhibitor.

A real-world study of anlotinib as third-line or above therapy in patients with her-2 negative metastatic breast cancer.

Background: Antiangiogenic agents provides an optional treatment strategy for patients with metastatic breast cancer. The present study was conducted to evaluate the efficacy and safety of anlotinib as third-line or above therapy for patients with HER-2 negative metastatic breast cancer. Methods: Patients with HER-2 negative metastatic breast cancer who have failed from prior therapy and treated with anlotinib monotherapy or combined with chemotherapy or immunotherapy from June 2018 to December 2020 were retrospectively analyzed based on real-world clinical practice. The primary end point was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results: 47 patients with HER-2 negative metastatic breast cancer received anlotinib monotherapy or combination therapy as third-line or above therapy. In the general population, 10 patients achieved PR, 25 patients had SD and 12 patients had PD. The overall ORR and DCR were 21.3% and 74.5%, respectively. Subgroup analysis suggested that there were no statistically significant differences in ORR and DCR with respect to HR status (positive vs. negative), treatment programs (monotherapy vs. combination) and treatment type in combination group (chemotherapy vs. immunotherapy). The patients who did not received previously anti-angiogenesis therapy had superior DCR (84.8% vs. 50.0%, P=0.012). Median PFS and OS were 5.0 months (95% CI=4.3-5.7) and 21.0 (95% CI=14.9-27.1) months, respectively. The PFS (6.5m vs. 3.5m, P=0.042)and OS (28.2m vs. 12.6m, P=0.040) were better in HR positive patients than HR negative patients. And simultaneously, patients who received anlotinib combination therapy obtained better PFS (5.5m vs. 3.0m, P=0.045). The incidence of Grade 3-4 adverse events(AEs) was 31.9%. Conclusions: Anlotinib monotherapy or combination therapy provide a viable third-line or above therapeutic strategy in patients with HER-2 negative metastatic breast cancer, a median PFS of 5.0 months was obtained with well tolerated toxicity.

Clinical, Pathological Complete Response, and Prognosis Characteristics of HER2-Low Breast Cancer in the Neoadjuvant Chemotherapy Setting: A Retrospective Analysis.

BACKGROUND: The present study was conducted to evaluate the clinical, pathological response, and prognosis characteristics of human epidermal growth factor receptor 2 (HER2)-low breast cancer in the neoadjuvant chemotherapy setting. METHODS: Patients with HER2-negative breast cancer who received neoadjuvant chemotherapy from January 2017 to December 2019 were retrospectively analyzed. HER2-negative breast cancer was divided into two groups: HER2-zero (defined as immunohistochemistry [IHC] 0) and HER2-low (defined as IHC 1+, or IHC 2+ and fluorescence in-situ hybridization-negative. RESULTS: Overall, 314 patients with HER2-negative breast cancer were analyzed. The proportion of HER2-low patients with hormone receptor (HR)-positive disease was higher than in triple-negative breast cancer (TNBC; 75.3% vs. 63.2%, p = 0.032). In HR-positive breast cancer, HER2-low tumors presented less nodal involvement (p = 0.023) and earlier clinical stage (p = 0.015) compared with HER2-zero tumors; however, in TNBC, HER2-low patients had a later clinical stage (p = 0.028). With the pathological complete response (pCR) defined as ypTis/0ypN0, there was no difference in pCR rates among the entire cohort, HR-positive disease, and TNBC. However, with the pCR defined as ypT0ypN0, the pCR rate in HER2-low breast cancer was significantly lower than HER2-zero breast cancer in the entire cohort (24.3% vs. 36.4%, p = 0.032) and the HR-positive subgroup (18.7% vs. 32.1%, p = 0.035), but not for TNBC. Multivariate analysis demonstrated that HER2 status (low vs. zero) was an independent predictive factor for pCR (p = 0.013) in HR-positive breast cancer. There were no statistically significant differences in 3-year disease-free survival and overall survival between HER2-low and HER2-zero breast cancer among the entire cohort, HR-positive disease, and TNBC. CONCLUSIONS: HER2-low breast cancer exhibits specific clinical features and different response to treatment associated with HR status in the neoadjuvant chemotherapy setting.

Electronic and Magnetic Properties of Defected Monolayer WSe2 with Vacancies.

By adopting the first-principle methods based on the density functional theory, we studied the structural, electronic, and magnetic properties of defected monolayer WSe2 with vacancies and the influences of external strain on the defected configurations. Our calculations show that the two W atom vacancies (VW2) and one W atom and its nearby three pairs of Se atom vacancies (VWSe6) both induce magnetism into monolayer WSe2 with magnetic moments of 2 and 6 µB, respectively. The magnetic moments are mainly contributed by the atoms around the vacancies. Particularly, monolayer WSe2 with VW2 is half-metallic. Additionally, one Se and one W atom vacancies (VSe, VW), two Se atom vacancies (VSe-Se), and one W atom and the nearby three Se atoms on the same layer vacancy (VWSe3)-doped monolayer WSe2 remain as non-magnetic semiconducting. But the impure electronic states attributed from the W d and Se p orbitals around the vacancies locate around the Fermi level and narrow down the energy gaps. Meanwhile, our calculations indicate that the tensile strain of 0~7% not only manipulates the electronic properties of defected monolayer WSe2 with vacancies by narrowing down their energy gaps, but also controls the magnetic moments of VW-, VW2-, and VWSe6-doped monolayer WSe2.

Pmma-XO (X = C, Si, Ge) monolayer as promising anchoring materials for lithium-sulfur battery: a first-principles study.

Lithium-sulfur (Li-S) batteries hold great promise for the next-generation lithium-ion energy storage devices. A key issue in the Li-S batteries is, however, the dissolving and migrating of the soluble polysulfides during the charge and discharge processes and introducing anchoring materials (AM) in the batteries effectively prevent the problem and improve the cycling stability of the Li-S batteries. Herein, Pmma-XO (X = C, Si, Ge, Sn) monolayers are introduced as AM to confine the lithium polysulfides and their anchoring properties are studied with the density functional theory methods. Particularly, Pmma-SiO and GeO monolayers are studied for the first time, and our calculations show that these two materials are stable semiconductive monolayers with direct-band-gaps and moderate binding with lithium polysulfides Li2S n (n = 8, 6, 4, 2 and 1). The Pmma-SiO and GeO trap Li2S n species on their surfaces and keep them intact during the charge and discharge, and the adsorption of Li2S n species leads to the enhanced conductivity of Pmma-SiO and GeO monolayers. Our study suggests that the Pmma-SiO and GeO monolayers are the promising AM for highly efficient Li-S batteries.

3-Fold-Periodic Size-Dependence in Electronic Properties of Monolayer-TMDC Nanotriangles.

Stable nanotriangles of monolayer transitional metal dichalcogenides (referred herein as MS2 mNTs) grown via ordinary deposition conditions, where M = Mo or W, exhibit a peculiar 3-fold periodic size-dependence in electronic and chemical properties. For " k" being the number of M atoms per edge, mNTs are (a) intrinsic-semiconducting when k = 3 i + 1, such as k = 7, 10, 13, 16; (b) metallic-like with no bandgap when k = 3 i; (c) n+ semiconducting when k = 3 i - 1. Besides changes in electronic properties, the catalytic properties for hydrogen evolution reaction also switch from active for k = 3 i and 3 i - 1 to inactive for k = 3 i + 1. The peculiar periodic size-dependence roots from the chemistry of edge-reconstruction and the consequential evolution of band structure. Further, such chemistry and thereby the size-dependence can be manipulated by adding or depleting the atomic concentration of sulfur atoms along the mNT edges.

Expression and significance of DDX43 in lung adenocarcinoma.

This paper aims to determine the expression and clinical significance of DDX43 in lung adenocarcinoma. Expression of DDX43 gene and protein of lung adenocarcinoma tissue and para-carcinoma tissues was observed in 27 cases by RT-PCR and immunohistochemistry. These patients were diagnosed as lung adenocarcinoma in the Huaihe Hospital of Henan University from February 2015 to December 2015. The relative ratio of DDX43 mRNA expression in lung adenocarcinoma and para-carcinoma tissues was 0.87±0.62 versus 0.21±0.77 and the difference between the two groups was statistically significant (P<0.01). The expression of DDX43 in normal lung tissues and lung adenocarcinoma tissues was different. The positive rate of DDX43 expression in lung adenocarcinoma tissues was significantly higher than that in normal lung tissues, and the difference was statistically significant (P<0.05). The analysis of clinical pathological characteristics showed that the increase of protein expression was related to the stage and metastasis of lung adenocarcinoma. DDX43 is highly expressed in lung adenocarcinoma, and the expression level is related to the stage and metastasis of lung adenocarcinoma, suggesting that DDX43 is closely related to the occurrence and development of lung adenocarcinoma, and may be a molecular marker for early diagnosis of lung adenocarcinoma.

First-Principles Study on the Stability and STM Image of Borophene.

Very recently, borophene (atomic-thin two-dimensional boron sheet) has been successfully synthesized on the Ag(111) surface by deposition. Two kinds of structures were found. However, the identification of the monolayer boron sheets grown on the metal substrate, as well as the stability of different 2D boron sheets, is controversial. By performing the first-principles calculations, present study investigates the atomic structure, stability, and electronic properties of the most possible boron sheets grown on metal surface, namely, buckled triangular, ß12, and χ3 types of crystal lattice. Our result shows that all the three freestanding sheets are thermodynamically unstable and all are metallic. On the other hand, our result indicates the Ag(111) substrate stabilize these sheets. Additionally, our simulated STM images of these monoatomic-thin boron sheets on Ag(111) surface reproduce the experiment observations well and clearly identify the as-grown boron sheets.

MicroRNA-146a affects the chemotherapeutic sensitivity and prognosis of advanced gastric cancer through the regulation of LIN52.

The present study aimed to evaluate the correlation between the expression of microRNA-146a (miR-146a) and its target gene, LIN52, in advanced gastric cancer, and determine their potential effects on chemotherapeutic sensitivity and prognosis. Total RNA was extracted from 93 tissue samples of advanced gastric cancer and corresponding adjacent non-tumor tissues to quantify the relative expression levels of miR-146a using reverse transcription-quantitative polymerase chain reaction analysis. The expression of LIN52 was detected in tumors and normal tissues using immunohistochemical analysis. Correlation analysis was performed to assess the correlation between the expression of miR-146a and LIN52 and clinicopathological parameters of gastric cancer, including clinical diagnostic specificity, clinical tumor-necrosis-metastasis staging, lymph node metastasis, differentiation grade, chemotherapeutic sensitivity and prognosis. The expression of miR-146a in advanced gastric cancer tissues was lower, compared with that in the adjacent non-tumor tissues, and was negatively correlated with lymph node metastasis (P<0.05). Gastric cancer tissues with a low expression level of miR146a exhibited an increased expression level of LIN52 (P<0.05). Receiver operating characteristic curve regression analysis showed that miR-146a had 98% sensitivity in distinguishing gastric cancer tissues and adjacent non-tumor tissues. A high expression of miR-146a in gastric cancer was associated with improved treatment efficacy in patients. The chemotherapeutic sensitivity of patients with tumors expressing high levels of miR-146a was significantly higher, compared with that of patients with tumors expressing low levels of miR-146a (P<0.05). The expression of miR-146a was low in advanced gastric cancer tissues. As a tumor suppressor gene in advanced gastric cancer, miR-146a had a significant negative correlation with LIN52. High expression levels of miR-146a in advanced gastric cancer tissue may be associated with improved treatment efficacy of chemotherapy, suggesting that miR-146a may be a molecular marker for the diagnosis, prediction of treatment efficacy and prognosis of advanced gastric cancer.

Nanopolygons of Monolayer MS2: Best Morphology and Size for HER Catalysis.

With first-principles calculations, we find a new strategy for developing high-performance catalysts for hydrogen evolution reaction (HER) via controlling the morphology and size of nanopolygons of monolayer transition-metal dichalcogenides (npm-MS2, with M = Mo, W, or V). Particularly, through devising a quantitative method to measure HER-active sites per unit mass and using such HER site density to comparatively gauge npm-MS2 performance, we identify three keys in making npm-MS2 with optimal HER performance: (a) npm-MS2 should be triangular with each edge being M-terminated and each edge-M atom passivated by one S atom; (b) each edge of npm-MoS2 and WS2 should have 5-6 metal atoms as HER site density drops below/above these sizes optimal both for HER and practical npm growth; and (c) npm-VS2 is immune to this overly fastidious size dependence. Known experimental data on npm-MoS2 indeed support the plausibility of practicing these design rules. We expect that raising the nucleation density and controlling the growth time to favor the production of our proposed ultrasmall npm-MS2 are critical but practical. Research on npm-VS2 would bear the highest impact because of its size-forgiving HER performance and relatively high abundance and low cost.

Clinical significance of HOTAIR expression in colon cancer.

AIM: To detect the expression of the long noncoding RNA HOTAIR in colon cancer and analyze its relationship with clinicopathological parameters of colon cancer. METHODS: Total RNA was extracted from 80 colon cancer tissues and matched tumor-adjacent normal colon tissues and reverse transcribed. Quantitative polymerase chain reaction was used to detect the expression of HOTAIR. The relationship between the expression of HOTAIR and clinicopathological parameters of colon cancer was analyzed. RESULTS: The expression of HOTAIR was significantly higher in colon cancer tissues than in matched tumor-adjacent normal colon tissues (P < 0.05). HOTAIR expression was significantly higher in cases with lymph node metastasis than in those without metastasis; in lowly differentiated and undifferentiated cases than in highly and moderately differentiated cases; and in stages III + IV cases than in stages I + II cases (P < 0.05). CONCLUSION: HOTAIR expression is upregulated in colon cancer, suggesting that HOTAIR plays an important role in the tumorigenesis, development and metastasis of colon cancer. HOTAIR may act as an oncogene and represents a new molecular target for the treatment of colon cancer.

[Effects of hydroxycamptothecin and teniposide on proliferation and apoptosis of gastric cancer cell line BGC-823].

BACKGROUND & OBJECTIVE: Some studies have showed that topoisomerase (Topo)I and II inhibitors have synergistic effects in tumor therapy, but the combinations have seldom been used in gastric cancer. This study was to investigate the effects of Topo I inhibitor hydroxycamptothecin (HCPT) and Topo II inhibitor teniposide (VM-26) on the proliferation and apoptosis of gastric cancer cell line BGC-823. METHODS: MTT assay was used to examine the inhibitory effects of VM-26 and HCPT, used alone or in combination, on the proliferation of BGC-823 cells. Cell apoptosis was examined by flow cytometry (FCM). RESULTS: The inhibition rates of BGC-823 cell proliferation were 15.99%-80.83% when treated with 1.963-31.413 micromol/L VM-26; the apoptosis rates were 3.90%, 4.42%, 7.36%, 17.07% when exposed to 1.963 micromol/L VM-26 for 0, 12, 24, 48 h, respectively. The inhibition rates of BGC-823 cell proliferation were 7.89%-70.32% when treated with 8.577-137.227 micromol/L HCPT; the apoptosis rates were 2.80%, 8.50%, 10.50%, 13.30% when exposed to 8.577 micromol/L HCPT for 0, 12, 24, 48 h, respectively. When treated with 1.963 micromol/L VM-26 and 3.125 microg/ml HCPT for 0, 12, 24, 48 h, the inhibition rates of BGC-823 cell proliferation were 21.32%-87.74%, and the apoptosis rates were 2.80%, 15.50%, 15.70%, 20.20%, respectively. The combination index (CI) was 1.293. CONCLUSION: HCPT and VM-26 used alone could inhibit the proliferation and induce the apoptosis of BGC-823 cells, and they have antagonistic effect on gastric cancer BGC-823 cells.