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Immunotherapy, especially immune checkpoint inhibitors (ICIs), has revolutionized the treatment of many types of cancer, particularly advanced-stage cancers. Nevertheless, although a subset of patients experiences dramatic and long-term disease regression in response to ICIs, most patients do not benefit from these treatments. Some may even experience cancer progression. Immune escape by tumor cells may be a key reason for this low response rate. N6-methyladenosine (m6A) is the most common type of RNA methylation and has been recognized as a critical regulator of tumors and the immune system. Therefore, m6A modification and related regulators are promising targets for improving the efficacy of tumor immunotherapy. However, the association between m6A modification and tumor immune escape (TIE) has not been comprehensively summarized. Therefore, this review summarizes the existing knowledge regarding m6A modifications involved in TIE and their potential mechanisms of action. Moreover, we provide an overview of currently available agents targeting m6A regulators that have been tested for their elevated effects on TIE. This review establishes the association between m6A modifications and TIE and provides new insights and strategies for maximizing the efficacy of immunotherapy by specifically targeting m6A modifications involved in TIE.

Background Robotic linac is ideally suited to deliver hypo-fractionated radiotherapy due to its compact head and flexible positioning. The non-coplanar treatment space improves the delivery versatility but the complexity also leads to prolonged optimization and treatment time. Methods In this study, we attempted to use the deep learning (pytorch) framework for the plan optimization of circular cone based robotic radiotherapy. The optimization problem was topologized into a simple feedforward neural network, thus the treatment plan optimization was transformed into network training. With this transformation, the pytorch toolkit with high-efficiency automatic differentiation (AD) for gradient calculation was used as the optimization solver. To improve the treatment efficiency, plans with fewer nodes and beams were sought. The least absolute shrinkage and selection operator (lasso) and the group lasso were employed to address the “sparsity” issue. Results The AD-S (AD sparse) approach was validated on 6 brain and 6 liver cancer cases and the results were compared with the commercial MultiPlan (MLP) system. It was found that the AD-S plans achieved rapid dose fall-off and satisfactory sparing of organs at risk (OARs). Treatment efficiency was improved by the reduction in the number of nodes (28%) and beams (18%), and monitor unit (MU, 24%), respectively. The computational time was shortened to 47.3 s on average. Conclusions In summary, this first attempt of applying deep learning framework to the robotic radiotherapy plan optimization is promising and has the potential to be used clinically.

Background The use of magnetic nanozymes (NZs) with the ability to synchronize gas therapy through photodynamic and chemotherapy in the treatment of breast cancer has received much attention. Results Hence, in this study, we designed a bovine lactoferrin-coated iron sulfide NZs containing doxorubicin (abbreviated as: FeS-Dox@bLf NZs) by wet-chemical synthesis method. Then, the physicochemical characteristics of synthesized NZs were explored by several methods. Also, the level of Fe2+, H2S and Dox releases from FeS-Dox@Lf NZs. Also, the cytotoxic effects of FeS-Dox@Lf NZs were investigated by cellular assays. After intravenous injections of NZs and laser irradiation, significant effects of FeS-Dox@Lf NZs on mice weight and tumor status were observed. Afterwards, not only the distribution of Dox in the body was examined by fluorescent, but also the time of Fe clearance and the amount of Dox and Fe retention in vital tissues were determined. The findings confirm that FeS-Dox@Lf NZs, in addition to targeted drug distribution in tumor tissue, resulted in superior therapeutic performance compared to free Dox due to reduced Dox side effects in vital tissues, and increased level of free radicals in 4T1 cells. Conclusion Overall, FeS-Dox@Lf NZs with the ability to synchronize chemotherapy and gas therapy raised hopes for more effective treatment of breast cancer. Graphic abstract

Background Long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) plays a positive role in the progression of human malignant tumors. However, the molecular mechanism of SNHG1 remains elusive in breast cancer. Results LncRNA SNHG1 was upregulated and had a positive relationship with poor prognosis according to bioinformatics analysis in pan-cancer including breast cancer. Silencing SNHG1 inhibited tumorigenesis in breast cancer both in vitro and in vivo. Mechanistically, SNHG1 functioned as a competing endogenous RNA (ceRNA) to promote TERT expression by sponging miR-18b-5p in breast cancer. miR-18b-5p acted as a tumor repressor in breast cancer. Moreover, the combination of SNHG1 knockdown and TERT inhibitor administration showed a synergistic inhibitory effect on breast cancer growth in vivo. Finally, E2F1 as a transcription factor, binding to SNHG1 promoter and enhanced SNHG1 transcription in breast cancer. Conclusions Our results provide a comprehensive understanding of the oncogenic mechanism of lncRNA SNHG1 in breast cancer. Importantly, we identified a novel E2F1–SNHG1–miR-18b-5p–TERT axis, which may be a potential therapeutic target for breast cancer. Our results also provided a potential treatment for breast cancer when knockdown SNHG1 and TERT inhibitor administration simultaneously.

The motion of three-phase contact line of a droplet is always halted by the contact angle hysteresis on a common solid surface. In this work, the Ag/Cu surface and Cu(OH)2/Cu surface with water contact angle of 25.0° were fabricated and found favorable for two-component droplet moving. The droplet, water with propylene glycol in irregular shape could restore to a circle (top view) on these prepared surfaces. Inspired by the shape restoration, the directed motion of two-component droplet without back-end pinning was achieved on both the wedge-shaped Ag/Cu and Cu(OH)2/Cu composite surfaces. The two-component droplet moves in a way of the front-end spreading with the subsequent back-end shrinking. The needle-like Cu(OH)2 microstructure is more conducive to the front-end spreading, while the spheroidal Ag particles on Cu substrate is in favor of the back-end shrinking. In addition, the segmented Ag@Cu(OH)2/Cu wedge-shaped composite surfaces with Ag film on the narrow end of the track and Cu(OH)2 on the wide end could enhance the droplet moving. Finally, a micro-chemical reactor was designed capable of driving two dispersed droplets to move in a specific direction, converge, and then react with each other.

A superhydrophobic film with good durability was fabricated by simple spraying a mixed solution of a POSS-based fluorinated acrylate polymer and ethyl-α-cyanoacrylate on a glass slide. The polymer was firstly synthesized via a typical free radical solution polymerization and could self-assemble into spherical micelle, thus leading to the formation of a rough film with hierarchical nano-microstructure through spray coating. The adding of ethyl-α-cyanoacrylate can improve the mechanical durability of the film. The film shows robust superhydrophobicity with a high water angle contact of 158° and an ultralow water sliding angle of 1.9°. More importantly, the film not only can withstand 25 abrasion cycles under a load of 200 g and approximately 5.5 m high static water pressure without losing superhydrophobicity, but also exhibits favorable resistance to acidic and basic solutions over a wide range of pH values from 2 to 14. Besides, the transmittance of the coated glass slide is above 75% in the visible light range of 400–800 nm, reflecting high transparency of the film. This film may be a promising candidate in practical applications, including coating of optical devices, solar cell panel and outdoor instruments, because this method to fabricate supehydrophobic surfaces is facile, effective and scalable, and the superhydrophobic coating has good water resistance, high transparency and enough durability.

A superhydrophobic and superoleophilic polymer-infiltrated nanoparticle film-coated stainless-steel mesh (PINF-SSM) was prepared with a novel and facile nature-inspired approach. The approach involves the use of low-cost raw materials and simple spray coating of hydrophobic silica nanoparticles onto stainless-steel mesh (SSM) surface. With acrylic resin pre-coating layer on both surfaces, it is conveniently transformed into an integrated polymer-infiltrated nanoparticle film on SSM after annealing above the resin’s glass transition temperature. The obtained PINF-SSM shows robust superhydrophobicity after multiple cycles rubbing with sandpaper, long-term UV irradiation, long-term storage, and exposure to strong acidic, alkaline, and saline solutions. The as-prepared PINF-SSM was successfully used to separate various oil/water mixtures with high-efficiency for at least 50 cycles and collect oil slick on water surface efficiently. Sequential coating thermoplastic acrylic resin and hydrophobic silica nanoparticles on the surface of SSM allow for extended storage time of the coating materials, easy resin processing with high silica content, quick repairing, and easy recovery of the superhydrophobic surface, making it suitable in various oil/water separation practices.

Superhydrophobic–superoleophilic meshes with hierarchical structures were fabricated by spraying a POSS hybrid acrylic polymer on stainless steel mesh for oil–water separation in this paper. Fourier transform infrared spectroscopy, nuclear magnetic resonance (1H NMR), and thermogravimetric analyses were used to verify the chemical composition and thermostability of the POSS hybrid acrylic polymer, which was synthesized via a free radical solution polymerization. The obtained mesh was characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, and optical contact angle meter to confirm the morphology, composition, and wettability of the film surface. The coated mesh, with a static water contact angle of 153° and a sliding angle of 4.5°, was applied to separate a series of oil–water mixtures, such as n-hexane, isooctane, petroleum ether, kerosene, and vegetable oil, with separation efficiency nearly 99%. In addition, the coated mesh still kept separation efficiency approximately 99% even after 25 separation cycles for n-hexane/water mixture. After 20 abrasion cycles, the water contact angle of the mesh remained 145°, and separation efficiency for n-hexane/water mixture is approximately 99%, indicating the coated mesh possessed good mechanical stability. The as-prepared mesh will be a promising material in oil–water separation, due to the simple, low-cost, and easily scalable fabrication method and the excellent separation performance in radical oil–water separation.

Background An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play essential roles in tumor initiation and progression. LncRNAs act as tumor promoters or suppressors by targeting specific genes via epigenetic modifications and competing endogenous RNA (ceRNA) mechanisms. In this study, we explored the function and detailed mechanisms of long intergenic nonprotein coding RNA 673 (LINC00673) in breast cancer progression. Methods Quantitative real-time PCR (qRT-PCR) was used to examine the expression of LINC00673 in breast cancer tissues and in adjacent normal tissues. Gain-of-function and loss-of function experiments were conducted to investigate the biological functions of LINC00673 in vitro and in vivo. We also explored the potential role of LINC00673 as a therapeutic target using antisense oligonucleotide (ASO) in vivo. RNA sequencing (RNA-seq), dual-luciferase reporter assays, chromatin immunoprecipitation (ChIP) assay, and rescue experiments were performed to uncover the detailed mechanism of LINC00673 in promoting breast cancer progression. Results In the present study, LINC00673 displayed a trend of remarkably increased expression in breast cancer tissues and was associated with poor prognosis in breast cancer patients. Importantly, LINC00673 depletion inhibited breast cancer cell proliferation by inhibiting the cell cycle and increasing apoptosis. Furthermore, ASO therapy targeting LINC00673 substantially suppressed breast cancer cell proliferation in vivo. Mechanistically, LINC00673 was found to act as a ceRNA by sponging miR-515-5p to regulate MARK4 expression, thus inhibiting the Hippo signaling pathway. Finally, ChIP assay showed that the transcription factor Yin Yang 1 (YY1) could bind to the LINC00673 promoter and increase its transcription in cis. Conclusions YY1-activated LINC00673 may exert an oncogenic function by acting as a sponge for miR-515-5p to upregulate the MARK4 and then inhibit Hippo signaling pathway, and may serve as a potential therapeutic target.

Background The landscape and biological functions of tumor suppressor long noncoding RNAs in breast cancer are still unknown. Methods Data from whole transcriptome sequencing of 33 breast specimens in the Harbin Medical University Cancer Center cohort and The Cancer Genome Atlas was applied to identify and validate the landscape of tumor suppressor long noncoding RNAs, which was further validated by The Cancer Genome Atlas pancancer data including 33 cancer types and 12,839 patients. Next, the expression model, prognostic roles, potential biological functions and epigenetic regulation of tumor suppressor long noncoding RNAs were investigated and validated in the breast cancer and pancancer cohorts. Finally, EPB41L4A-AS2 was selected to validate our novel finding, and the tumor suppressive roles of EPB41L4A-AS2 in breast cancer were examined. Results We identified and validated the landscape of tumor suppressor long noncoding RNAs in breast cancer. The expression of the identified long noncoding RNAs was downregulated in cancer tissue samples compared with normal tissue samples, and these long noncoding RNAs correlated with a favorable prognosis in breast cancer patients and the patients in the pancancer cohort. Multiple carcinogenesis-associated biological functions were predicted to be regulated negatively by these long noncoding RNAs. Moreover, these long noncoding RNAs were transcriptionally regulated by epigenetic modification, including DNA methylation and histone methylation modification. Finally, EPB41L4A-AS2 inhibited breast cancer cell proliferation, migration and invasion and induced cell apoptosis in vitro. Mechanistically, EPB41L4A-AS2, acting at least in part as a tumor suppressor, upregulated tumor suppressor gene expression. Moreover, ZNF217 recruited EZH2 to the EPB41L4A-AS2 locus and suppressed the expression of EPB41L4A-AS2 by epigenetically increasing H3K27me3 enrichment. Conclusions This work enlarges the functional landscape of known long noncoding RNAs in human cancer and provides novel insights into the suppressive roles of these long noncoding RNAs. Electronic supplementary material The online version of this article (10.1186/s13046-019-1096-0) contains supplementary material, which is available to authorized users.

An ambient-temperature self-crosslinkable acrylic resin was synthesized by solution polymerization, with ethanol as solvent; butyl acrylate (BA), methyl methacrylate (MMA), acrylic acid (AA), hydroxypropyl acrylate (HPA), and diacetone acrylamide (DAAM) as monomers; and adipic acid dihydrazide (ADH) as crosslinker. The resin could be diluted by water. The resin was used for PE film ink, and its curing behavior and film properties were studied. FTIR and DSC results indicated that the reaction between ketone carbonyl and hydrazine groups could occur during film curing at ambient temperature and improved glass transition temperature (T g) of the film by 12.67°C. Crosslinking density of film increased with DAAM content and m(ADH)/m(DAAM) ratio. Adhesion on PE film increased with DAAM content, while it first increased then decreased with m(ADH)/m(DAAM) ratio. Water absorption of film decreased with DAAM content, while it first decreased then increased with m(ADH)/m(DAAM) ratio. The optimal m(ADH)/m(DAAM) ratio and DAAM content in this experiment are 0.8:1 and 2%, respectively. Compared with ambient-temperature self-crosslinkable emulsion, this water-soluble resin shows film not only with the same adhesion, but also without any shrinkage void, indicating better film-forming ability on PE film. The ambient-temperature self-crosslinkable water-soluble acrylic resin shows excellent potential application in water-based ink for PE film because of good film-forming ability and adhesion and low water absorption.

Eosinophil granule ontogeny transcript (EGOT) is a long noncoding RNA involved in the regulation of eosinophil granule protein transcript expression. However, little is known about the role of EGOT in malignant disease. This study aimed to assess the potential role of EGOT in the pathogenesis of breast cancer. Quantitative real-time polymerase chain reaction was performed to detect the expression levels of EGOT in 250 breast cancerous tissues and 50 adjacent noncancerous tissues. The correlation of EGOT expression with clinicopathological features and prognosis was also analyzed. EGOT expression was lower in breast cancer compared with the adjacent noncancerous tissues (P

A series of cationic poly(hydroxyethyl methacrylate)-g-poly(carboxybetaine methacrylate ester) (PHEMA-g-PCBMAE) hydrogels (HCGs) were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. The HCGs were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and swelling behaviors. It was found that the HCG hydrogels showed enhanced mechanical strengths compared with PCBMAE hydrogel. In addition, it was observed that the cationic HCGs exhibited excellent antibacterial properties. We found that the equilibrium swelling ratios, mechanical properties, and drug release behaviors were related to the feed ratios of the gels. The tetracycline hydrochloride (TCHC) release results indicated that the drug released from HCGs could be prolonged by increasing the content of hydroxyethyl methacrylate (HEMA) in the gel networks.

Background Few long noncoding RNAs (lncRNAs) that act as oncogenic genes in breast cancer have been identified. Methods Oncogenic lncRNAs associated with tumourigenesis and worse survival outcomes were examined and validated in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), respectively. Then, the potential biological functions and expression regulation of these lncRNAs were studied via bioinformatics and genome data analysis. Moreover, progressive breast cancer subtype-specific lncRNAs were investigated via high-throughput sequencing in our cohort and TCGA validation. To elucidate the mechanisms of the regulation of these lncRNAs, genomic alterations from the TCGA, Broad, Sanger and BCCRC data, as well as epigenetic modifications from GEO data, were then applied and examined to meet this objective. Finally, cell proliferation assays, flow cytometry analyses and TUNEL assays were applied to validate the oncogenic roles of these lncRNAs in vitro. Results A cluster of oncogenic lncRNAs that was upregulated in breast cancer tissue and was associated with worse survival outcomes was identified. These oncogenic lncRNAs are involved in regulating immune system activation and the TGF-beta and Jak-STAT signalling pathways. Moreover, TINCR, LINC00511, and PPP1R26-AS1 were identified as subtype-specific lncRNAs associated with HER-2, triple-negative and luminal B subtypes of breast cancer, respectively. The up-regulation of these oncogenic lncRNAs is mainly caused by gene amplification in the genome in breast cancer and other solid tumours. Finally, the knockdown of TINCR, DSCAM-AS1 or HOTAIR inhibited breast cancer cell proliferation, increased apoptosis and inhibited cell cycle progression in vitro. Conclusions These findings enhance the landscape of known oncogenic lncRNAs in breast cancer and provide insights into their roles. This understanding may potentially aid in the comprehensive management of breast cancer. Electronic supplementary material The online version of this article (doi:10.1186/s12943-017-0696-6) contains supplementary material, which is available to authorized users.

Recent studies have revealed that many, perhaps most women with hormone-responsive breast cancer have low adherence to tamoxifen adjuvant hormonal therapy. However, limited data are available on tamoxifen adherence in male breast cancer (MBC) patients. The goal of this study was to assess tamoxifen adherence and its relationship to mortality in MBC patients. A cohort of 116 men who were diagnosed with receptor-positive breast cancer between June 1987 and July 2012 was recruited for the study using the cancer prevention and treatment system database of Heilongjiang Province. From the 116 patients who received a five-year tamoxifen prescription, only 64.6 % were still taking their medication 1 year later, and this percentage decreased to 46.4 and 28.7 % after 2 and 3 years, respectively, to 25.8 % after 4 years, and to 17.7 % in the last year. After multivariate adjustment, factors that significantly decreased tamoxifen adherence were low social support [Hazard ratio (HR) = 2.45, 95 % CI 1.32-4.55], age (HR = 1.10, 95 % CI 1.01-1.21), and adverse effects (HR = 2.19, 95 % CI 1.57-3.04). The primary endpoints in the adherence or low-adherence groups from this study were overall survival (OS) and disease-free survival (DFS) of the MBC patients. The five- and ten-year OS of the patients was 97.9 and 79.6 %, respectively, in the adherence group, and 84.7 and 50.4 %, respectively, in the low-adherence group (p = 0.008). The five- and ten-year DFS of the patients was 95.4 and 72.8 %, respectively, in the adherence group, and 72.6 and 42.3 %, respectively, in the low-adherence group (p = 0.007). The consequences of low treatment adherence in men, who have a potentially long life expectancy, may be significant. In light of these findings, there is an urgent need to acknowledge and tackle the issue of tamoxifen adherence in this patient group.

Polyester-PEG dendrimers are attractive for in vivo delivery of anti-cancer drug because of their biodegradability and low cytotoxicity. In this drug delivery system, G5-PEG polyester dendrimer is composed of hydrophobic polyester dendritic blocks and hydrophilic poly (ethylene glycol) (PEG), in which DOX molecules are efficiently encapsulated in the core of microspheres due to their affinity with G5 dendritic blocks. A dissipative particle dynamics (DPD) computational method was used to investigate the loading/release mechanism of anti-cancer drug doxorubicin (DOX) in G5-PEG polyester dendrimer. Four sequential transient stages were found during the drug encapsulation process: (1) all components distribute randomly in the cubic box at the initial stage, (2) DOX molecules dispersion in the G5-PEG dendritic microsphere, (3) amalgamation of the small core–shell dendritic microspheres into bigger ones, and (4) the stabilization stage. The loaded DOX content was calculated to be 16.7 % with a loading efficiency of 100 %, which is close to the experiment results (15.2 % DOX content with the loading efficiency of 99 %). The simulation also successfully revealed the drug release dynamics at pH 7.4 and pH 5 (37 °C). At pH 7.4, no DOX molecule was released from G5-PEG/DOX when only considered the influence of temperature on drug release. It demonstrates that the increase of system temperature (from 25 to 37 °C) is not the major factor for drug release at pH 7.4. When considered protonation of DOX at pH 5, it is benefit to generate some pores on the surface of G5-PEG/DOX microspheres, and the aperture of the pores increased with the simulation steps increased, which leads to the increasingly exposure of DOX molecules to water. However, the drug could not release toward the aqueous solution. It demonstrated that the protonation of DOX is not the major factor for the drug’s rapid release at pH 5 though it may facilitate the drug release process. Such results are in qualitatively consistent with the experimental observations and could provide valuable guidance in later design and optimization of this drug delivery system. The same tool could also be used to evaluate and design other similar drug/gene delivery systems.

Background The purpose of the present study was to investigate the feasibility of using volumetric modulated arc therapy with SmartArc (VMAT-S) to achieve radiation delivery efficiency higher than that of intensity-modulated radiotherapy (IMRT) and helical tomotherapy (HT) when treating endometrial cancer, while maintaining plan quality. Methods Nine patients with endometrial cancer were retrospectively studied. Three plans per patient were generated for VMAT-S, IMRT and HT. The dose distributions for the planning target volume (PTV), organs at risk (OARs) and normal tissue were compared. The monitor units (MUs) and treatment delivery time were also evaluated. Results The average homogeneity index was 1.06, 1.10 and 1.07 for the VMAT-S, IMRT and HT plans, respectively. The V40 for the rectum, bladder and pelvis bone decreased by 9.0%, 3.0% and 3.0%, respectively, in the VMAT-S plan relative to the IMRT plan. The target coverage and sparing of OARs were comparable between the VMAT-S and HT plans. The average MU was 823, 1105 and 8403 for VMAT-S, IMRT and HT, respectively; the average delivery time was 2.6, 8.6 and 9.5 minutes, respectively. Conclusions For endometrial cancer, the VMAT-S plan provided comparable quality with significantly shorter delivery time and fewer MUs than with the IMRT and HT plans. In addition, more homogeneous PTV coverage and superior sparing of OARs in the medium to high dose region were observed in the VMAT-S relative to the IMRT plan.