Combined blockade of HER2 and VEGF exerts greater growth inhibition of HER2-overexpressing gastric cancer xenografts than individual blockade

Gastric cancer overexpressing the human epidermal growth factor 2 (HER2) protein has a poor outcome, although a combination of chemotherapy and the anti-HER2 antibody trastuzumab has been approved for the treatment of advanced gastric cancer. Vascular endothelial growth factor (VEGF) expression in gastric cancer is correlated with recurrence and poor prognosis; however, the anti-VEGF antibody bevacizumab has shown limited efficacy against gastric cancer in clinical trials. In this study, we evaluated the antitumor effects of trastuzumab; VEGF-Trap binding to VEGF-A, VEGF-B and placental growth factor (PlGF); and a combination of trastuzumab and VEGF-Trap in a gastric cancer xenograft model. Although trastuzumab and VEGF-Trap each moderately inhibited tumor growth, the combination of these agents exerted greater inhibition compared with either agent alone. Immunohistochemical analyses indicated that the reduction in tumor growth was associated with decreased proliferation and increased apoptosis of tumor cells and decreased tumor vascular density. The combined treatment resulted in fewer proliferating tumor cells, more apoptotic cells and reduced tumor vascular density compared with treatment with trastuzumab or VEGF-Trap alone, indicating that trastuzumab and VEGF-Trap had additive inhibitory effects on the tumor growth and angiogenesis of the gastric cancer xenografts. These data suggest that trastuzumab in combination with VEGF-Trap may represent an effective approach to treating HER2-overexpressing gastric cancer.     

Metal-organic framework derived Co3O4/PPy bifunctional electrocatalysts for efficient overall water splitting

In this work, we report Co₃O₄@PPy hybrid structured electrode materials for overall water splitting. The as-synthesized Co₃O₄/PPy-120 samples present excellent electrocatalytic performances for OER and HER and long durability. It only requires an operating potential of 1.67 V to deliver a current density of 10 mA/cm² with a remarkable durability for 28 h. The superior electrocatalytic performances mainly can be attributed to the unique heterostructures and the synergistic effects between PPy and Co₃O₄ electrode materials.     

Embedding Amorphous Molybdenum Sulfide within a Porous Poly(3,4‐ethylenedioxythiophene) Matrix to Enhance its H2‐evolving Catalytic Activity and Robustness

Amorphous molybdenum sulfide (MoS_x) is a promising alternative to Pt catalyst for the H₂ evolution in water. However, it is suffered of an electrochemical corrosion. In this report, we present a strategy to tack this issue by embedding the MoS_x catalyst within a porous poly(3,4‐ethylenedioxythiophene) (PEDOT) matrix. The PEDOT host is firstly grown onto a fluorine‐doped tin oxide (FTO) electrode by electrochemical polymerization of EDOT monomer in an acetonitrile solution to perform a porous structure. The MoS_x catalyst is subsequently deposited onto the PEDOT by an electrochemical oxidation of [MoS₄]^2? monomer. In a 0.5 M H₂SO₄ electrolyte solution, the MoS_x/PEDOT shows higher H₂‐evolving catalytic activities (current density of 34.2 mA/cm² at ?0.4 V vs RHE) in comparison to a pristine MoS_x grown on a planar FTO electrode having similar catalyst loading (24.2 mA/cm²). The PEDOT matrix contributes to enhance the stability of MoS_x catalyst by a significant manner. As such, the MoS_x/PEDOT retains 81 % of its best catalytic activity after 1000 potential scans from 0 to ?0.4 V vs. RHE, whereas a planar MoS_x catalyst is completely degraded after about 240 potential scans, due to its complete corrosion.     

Gold nanoparticles synthesized from Curcuma wenyujin inhibits HER-2/neu transcription in breast cancer cells (MDA-MB-231/HER2)

Breast cancer is the second leading cancer diagnosed globally and every year about two million new incidences were accounted. Curcuma wenyujin, a rhizome grown abundantly in china and used in various traditional Chinese medicines. Recent times the research on anticancer property of Curcuma wenyujin is extensively on progress and it is proved by many researchers. The major drawback of herbal drugs are their limited bio-availability, to overcome this we formulated a herbal gold nanodrug with Curcuma wenyujin (CW-AuNPs) and examined its anticancer potential against breast cancer cells. The cytotoxic effect of synthesized CW-AuNPs against MDA-MB231/HER2 cell line was inspected by MTT assay and the dosage for further analysis was calculated. The apoptosis triggered by CW-AuNPs was investigated by intracellular ROS and caspases levels in CW-AuNPs treated MDA-MB231/HER2 cell line. Over expression of HER2/neu, oncogene leads to meager prognosis in most of the breast cancer patients. Therefore in the current exploration, we investigated the inhibitory potential of CW-AuNPs against the expression of HER2/neu in breast cancer cell line by immunocytochemical and immunoblotting analysis. Our results of UV-Spec, FTIR, TEM and Atomic force investigation confirms, the synthesized nanodrug CW-AuNPs satisfies the characteristic features of a nanodrug. The results authentically proves that CW-AuNPs possessed the potent anticancer activity, increases ROS in breast cancer cells which in turn inhibits the HER2/neu, key oncogene expression and inhibited the cancer cell proliferation.     

Highly Efficient CO2 Utilization via Aqueous Zinc– or Aluminum–CO2 Systems for Hydrogen Gas Evolution and Electricity Production

Atmospheric carbon dioxide (CO₂) has increased from 278 to 408 parts per million (ppm) over the industrial period and has critically impacted climate change. In response to this crisis, carbon capture, utilization, and storage/sequestration technologies have been studied. So far, however, the economic feasibility of the existing conversion technologies is still inadequate owing to sluggish CO₂ conversion. Herein, we report an aqueous zinc– and aluminum–CO₂ system that utilizes acidity from spontaneous dissolution of CO₂ in aqueous solution to generate electrical energy and hydrogen (H₂). The system has a positively shifted onset potential of hydrogen evolution reaction (HER) by 0.4 V compared to a typical HER under alkaline conditions and facile HER kinetics with low Tafel slope of 34 mV dec^?1. The Al–CO₂ system has a maximum power density of 125 mW cm^?2 which is the highest value among CO₂ utilization electrochemical system.     

Atomic Arrangement in Metal‐Doped NiS2 Boosts the Hydrogen Evolution Reaction in Alkaline Media

We report a novel modulation strategy by introducing transition metals into NiS₂ nanosheets (NSs) to flexibly optimize the electronic configurations and atomic arrangement. The Co‐NiS₂ NSs exhibit excellent hydrogen evolution reaction (HER) performance with an overpotential of 80 mV at j=10 mA cm^?2 and long‐term stability of 90 h in alkaline media. The turnover frequencies (TOFs) of 0.55 and 4.1 s^?1 at an overpotential of 100 and 200 mV also confirm their remarkable performance. DFT calculations reveal that the surface dopants abnormally sensitize surface Ni‐3d bands in the long‐range order towards higher electron‐transfer activity, acting as the electron‐depletion center. Meanwhile, the high lying surface S‐sites possess substantially high selectivity for splitting the adsorbing H₂O that guarantee the high HER performance within alkaline conditions. This work opens opportunities for enhancing water splitting by atomic‐arrangement‐assisted electronic modulation via a facile doping strategy.     

Design,synthesis, crystal structures and biological evaluation of some 1,3-thiazolidin-4-ones as dual CDK2/EGFR potent inhibitors with potential apoptotic antiproliferative effects

A series of novel thiazolidine-4-one derivatives was synthesized by reacting 1,4-disubstituted hydrazine carbothioamides with diethyl azodicarboxylate. The structures were confirmed by spectroscopic data as well as single-crystal X-ray analyses. The antiproliferative activity of the synthesized compounds was investigated against four human cancer cell lines using an MTT assay. Compounds 5d, 5e, and 5f revealed the most potent antiproliferative activity with GI₅₀ values ranging from 0.70 µM to 1.20 µM, compared to doxorubicin GI₅₀ value = 1.10 µM. Compounds 5d, 5e, and 5f were further investigated for their inhibitory activities against CDK2 and EGFR as potential targets for their molecular mechanism. Compounds 5e and 5f have showed potent inhibitory activity to CDK2 enzyme with IC₅₀ values of 18 and 14 nM, which is more potent than the reference dinaciclib (IC₅₀ = 20 nM). Moreover, compounds 5e and 5f were the most potent EGFR inhibitors, with IC₅₀ values of 93 and 87 nM, respectively, compared to the reference erlotinib (IC₅₀ = 70 nM). In addition, the most potent derivatives were tested for their apoptotic activity against caspases 3, 8, and 9, and the results showed that compounds 5d, 5e, and 5f revealed a greater increase in active caspases 3,8 and 9 than doxorubicin. Also, compounds 5d, 5e, and 5f elevated cytochrome C levels in the MCF-7 human breast cancer cell line by about 15.5, 15.8, and 16.5 times, respectively. Finally, a molecular docking study was performed to investigate the binding sites of these compounds within the active sites of CDK2 and EGFR targets, and the results confirmed that the most potent CDK2 and EGFR inhibitor 5h also have showed the highest docking score.     

[89Zr]-Pertuzumab PET Imaging Reveals Paclitaxel Treatment Efficacy Is Positively Correlated with HER2 Expression in Human Breast Cancer Xenograft Mouse Models

Paclitaxel (PTX) treatment efficacy varies in breast cancer, yet the underlying mechanism for variable response remains unclear. This study evaluates whether human epidermal growth factor receptor 2 (HER2) expression level utilizing advanced molecular positron emission tomography (PET) imaging is correlated with PTX treatment efficacy in preclinical mouse models of HER2+ breast cancer. HER2 positive (BT474, MDA-MB-361), or HER2 negative (MDA-MB-231) breast cancer cells were subcutaneously injected into athymic nude mice and PTX (15 mg/kg) was administrated. In vivo HER2 expression was quantified through [⁸⁹Zr]-pertuzumab PET/CT imaging. PTX treatment response was quantified by [¹⁸F]-fluorodeoxyglucose ([¹⁸F]-FDG) PET/CT imaging. Spearman’s correlation, Kendall’s tau, Kolmogorov–Smirnov test, and ANOVA were used for statistical analysis. [⁸⁹Zr]-pertuzumab mean standard uptake values (SUV_mean) of BT474 tumors were 4.9 ± 1.5, MDA-MB-361 tumors were 1.4 ± 0.2, and MDA-MB-231 (HER2−) tumors were 1.1 ± 0.4. [¹⁸F]-FDG SUV_mean changes were negatively correlated with [⁸⁹Zr]-pertuzumab SUV_mean (r = −0.5887, p = 0.0030). The baseline [¹⁸F]-FDG SUV_mean was negatively correlated with initial [⁸⁹Zr]-pertuzumab SUV_mean (r = −0.6852, p = 0.0002). This study shows PTX treatment efficacy is positively correlated with HER2 expression level in human breast cancer mouse models. Molecular imaging provides a non-invasive approach to quantify biological interactions, which will help in identifying chemotherapy responders and potentially enhance clinical decision-making.     

Structure–reactivity relationships in Chevrel phase electrocatalysts for small-molecule reduction reactions

Chevrel phases, M_xMo₆X₈ (M = metal intercalant, X = chalcogen), constitute a family of materials with composition-dependent physicochemical properties that have shown promising electrocatalytic activity for various small-molecule reduction reactions. The wide range of possible compositions among the Chevrel phase family offers the opportunity to tune the local and electronic structure of discrete Mo₆X₈ cluster units within the extended M_xMo₆X₈ framework. Thus, making them an ideal platform for studying structure–function relationships and generating design principles for improved electrocatalytic reactivity. This review summarizes the state of the art in experimental and computational evaluations of Chevrel phases as electrocatalysts for hydrogen evolution, CO₂ reduction, and nitrogen reduction reactions. We aim to elucidate the uncharted small-molecule electrochemical reactivity of Chevrel phases as a function of composition and consequently guide the design of promising multinary chalcogenides for energy conversion reactions.