Molecular characterization, clinical value, and cancer-immune interactions of genes related to disulfidptosis and ferroptosis in colorectal cancer.

BACKGROUND: This research strived to construct a new signature utilizing disulfidptosis-related ferroptosis (SRF) genes to anticipate response to immunotherapy, prognosis, and drug sensitivity in individuals with colorectal cancer (CRC). METHODS: The data for RNA sequencing as well as corresponding clinical information of individuals with CRC, were extracted from The Cancer Genome Atlas (TCGA) dataset. SRF were constructed with the help of the random forest (RF), least absolute shrinkage and selection operator (LASSO), and stepwise regression algorithms. To validate the SRF model, we applied it to an external cohort, GSE38832. Prognosis, immunotherapy response, drug sensitivity, molecular functions of genes, and somatic mutations of genes were compared across the high- and low-risk groups (categories). Following this, all statistical analyses were conducted with the aid of the R (version 4.23) software and various packages of the Cytoscape (version 3.8.0) tool. RESULTS: SRF was developed based on five genes (ATG7, USP7, MMD, PLIN4, and THDC2). Both univariate and multivariate Cox regression analyses established SRF as an independent, prognosis-related risk factor. Individuals from the high-risk category had a more unfavorable prognosis, elevated tumor mutational burden (TMB), and significant immunosuppressive status. Hence, they might have better outcomes post-immunotherapy and might benefit from the administration of pazopanib, lapatinib, and sunitinib. CONCLUSION: In conclusion, SRF can act as a new biomarker for prognosis assessment. Moreover, it is also a good predictor of drug sensitivity and immunotherapy response in CRC but should undergo optimization before implementation in clinical settings.

Chemomechanical Origins of the Dynamic Evolution of Isolated Li Filaments in Inorganic Solid-State Electrolytes.

The penetrating growth of Li into the inorganic solid-state electrolyte (SSE) is one key factor limiting its practical application. Research to understand the underlying mechanism of Li penetration has been ongoing for years and is continuing. Here, we report an in situ scanning electron microscopy methodology to investigate the dynamic behaviors of isolated Li filaments in the garnet SSE under practical cycling conditions. We find that the filaments tend to grow in the SSE, while surprisingly, those filaments can self-dissolve with a decrease in the current density without a reversal of the current direction. We further build a coupled electro-chemo-mechanical model to assess the interplay between electrochemistry and mechanics during the dynamic evolution of filaments. We reveal that filament growth is strongly regulated by the competition between the electrochemical driving force and mechanical resistive force. The numerical results provide rational guidance for the design of solid-state batteries with excellent properties.

Identification of the shared gene signature and biological mechanism between type 2 diabetes and colorectal cancer.

Background: The correlation of type 2 diabetes mellitus (T2DM) with colorectal cancer (CRC) has garnered considerable attention in the scientific community. Despite this, the molecular mechanisms underlying the interaction between these two diseases are yet to be elucidated. Hence, the present investigation aims to explore the shared gene signatures, immune profiles, and drug sensitivity patterns that exist between CRC and T2DM. Methods: RNA sequences and characteristics of patients with CRC and T2DM were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus databases. These were investigated using weighted gene co-expression network analysis (WGCNA) to determine the co-expression networks linked to the conditions. Genes shared between CRC and T2DM were analyzed by univariate regression, followed by risk prognosis assessment using the LASSO regression model. Various parameters were assessed through different software such as the ESTIMATE, CIBERSORT, AND SSGSEA utilized for tumor immune infiltration assessment in the high- and low-risk groups. Additionally, pRRophetic was utilized to assess the sensitivity to chemotherapeutic agents in both groups. This was followed by diagnostic modeling using logistic modeling and clinical prediction modeling using the nomogram. Results: WGCNA recognized four and five modules that displayed a high correlation with T2DM and CRC, respectively. In total, 868 genes were shared between CRC and T2DM, with 14 key shared genes being identified in the follow-up analysis. The overall survival (OS) of patients in the low-risk group was better than that of patients in the high-risk group. In contrast, the high-risk group exhibited higher expression levels of immune checkpoints The Cox regression analyses established that the risk-score model possessed independent prognostic value in predicting OS. To facilitate the prediction of OS and cause-specific survival, the nomogram was established utilizing the Cox regression model. Conclusion: The T2DM + CRC risk-score model enabled independent prediction of OS in individuals with CRC. Moreover, these findings revealed novel genes that hold promise as therapeutic targets or biomarkers in clinical settings.

Management of esophagogastric fistula caused by adjustable gastric band erosion: A case report and literature review.

Laparoscopic adjustable gastric banding (LAGB) is commonly used in the treatment of morbid obesity. However, with clinical application and long-term follow-up, the shortcomings of this procedure were also exposed, bringing about surgery-related complications include dysphagia, intragastric band migration, slippage, and gastric band erosion. Lower esophageal and gastric fistula is a rare but dangerous complication after LAGB. We describe a case of esophagogastric fistula occurring twelve years after a laparoscopic band procedure and its successful management in a multidisciplinary and staged manner, followed by a short review of the literature.

The risk factors of postoperative nausea and vomiting in patients undergoing laparoscopic sleeve gastrectomy and laparoscopic distal gastrectomy: a propensity score matching analysis.

Postoperative nausea and vomiting (PONV) is a common side effect after laparoscopic surgery. The aim of the study is to investigate the variables that could predict PONV in patients who underwent laparoscopic gastrectomy. We divided patients who underwent laparoscopic gastrectomy into PONV and No-PONV groups. Propensity score matching (PSM) was applied to adjust confounding factors for further validation, and ordinal logistic regression analysis was used to identify predictors for PONV. In the ordinal logistic regression analysis, the preoperative neutrophil-to-lymphocyte ratio (NLR) (odds ratio [OR]: 3.19, 95% confidence interval [CI]: 1.38-7.38; p < 0.01) was identified as an independent risk factor for the presence of PONV and a predictor of the severity of PONV (OR: 3.44, 95% CI: 1.67-5.20; p < 0.01) in 94 PSM patients. Besides, NLR was positively correlated with the PONV score (r = 0.534, p < 0.001). In the receiver-operating characteristic (ROC) curve analysis, an NLR with an optimal cutoff value of 1.59 predicted severe PONV with a sensitivity of 72% and specificity of 81%. The NLR was an independent risk factor for the presence of PONV, and a high NLR tends to be positively associated with the severity of PONV after laparoscopic gastrectomy.

Realizing Holistic Charging-Discharging for Dendrite-Free Lithium Metal Anodes via Constructing Three-Dimensional Li+ Conductive Networks.

Lithium (Li) metal is a promising candidate for next-generation anode materials with high energy densities. However, Li dissolution/deposition processes are limited at the upper surface in contact with the electrolyte, which brings a locally high current density and then results in dendritic Li growth. This restraint of the local surface reaction during cycling has not been solved by commonly used modification strategies. In this study, a three-dimensional (3D) Li+ conductive skeleton is activated from atomic layer deposition (ALD) coating Li3PO4 (LPO) on the surface of the Ni foam (LPNF). Then, the skeleton is efficiently constructed in the Li metal anode by the lower-temperature Li infusion. Ionic conductor LPO layers and electronic conductor Ni fibers supply charge transport channels between the electrolyte and the internal Li. The mixed conductive network realizes holistic charge transfer, which is proved by in situ scanning electron microscopy experiments. In virtue of dispersive dissolution/deposition and optimized electrochemical kinetics brought by a Li+ conductive network, the composited Li electrode presents an excellent symmetric battery cycling stability (over 1200 h) and enhanced rate performances (stable cycling even at 10.0 mA cm-2). When matching with a LiCoO2 (LCO) cathode, LCO||Li@LPNF full batteries exhibit a capacity retention of 80.8% over 250 cycles. During cycling, there was no evidence of dendrite growth and the remaining Li in the composited anode showed a smooth, compact, and well-combined condition with LPNF. Through constructing a 3D Li+ conductive network, the composited Li metal anode breaks through the limit of the local surface reaction; this work proposes a novel insight of realizing holistic charging/discharging for the dendrite-free Li metal anode.

Clinical Observation of MRI Image in Floating Needle Therapy for Cervical Spondylosis of Cervical Type.

In order to solve the problem of cervical spondylosis in the early stage of various cervical spondylosis, effective treatment can prevent the deterioration of the disease. This paper presents the results of a clinical trial examining magnetic resonance imaging in the treatment of cervical spondylosis with flotation therapy and selected 68 patients with cervical spondylosis. According to research commodity, using a rigorous randomized controlled trial, 34 cases were divided into a control group (acupuncture group). The needles were kept for 30 minutes once a day. The treatment group (acupuncture combined with floating acupuncture group) was treated with acupuncture on the 1st, 3rd, and 5th days and floating acupuncture on the 2nd, 4th, and 6th days, respectively. Both groups were treated for 6 consecutive days and rested for 1 day. After 2 weeks of treatment, the simplified McGill Pain Scale (MPQ), visual analogue scale (VAS), and neck pain scale (NPQ) were observed and recorded to compare the curative effects. Finally, Excel software is used to manage the data, and SPSS21.0 is used for statistical analysis. Measurements of gender, age, disease, VAS, simple MPQ, and NPQ of the two groups were compared in the two groups, P > 0.05, which was not significant and comparable. After treatment, VAS, simple MPQ, and NPQ of the two groups were compared in and between groups, the total P < 0.05, with the mean data. Topics. Acupuncture combined with float needle and acupuncture therapy can improve the pain and breathing of cervical spondylosis and improve the quality of life of patients, but acupuncture combined with needle float is more pronounced than acupuncture groups.

Ultralong Lifespan for High-Voltage LiCoO2 Enabled by In Situ Reconstruction of an Atomic Layer Deposition Coating Layer.

Although the rapid development of electrical energy storage devices has slowed down environmental pollution, their large-scale application has posed huge challenges to battery-related mineral resources; thus, extending the lifespan of high-voltage lithium cobalt oxide (LCO) is of great importance. Surface oxide coating is considered as the most common low-cost modification method for addressing unstable cycling performance. However, studies have shown that the oxide layer would further react with an electrolyte, while the investigation on the corresponding component evolution is lacking. Herein, a typical example utilizing the above reaction to realize surface reconstruction is presented. Applying atomic layer deposition (ALD), originally, an ultrathin Al2O3 layer is coated on the LCO surface; however, this coating layer has undergone reconstruction after reacting with electrolyte decomposition products during the cycling. Compared with simple coating, the in situ formed Li3AlF6 layer has a tighter binding to the LCO surface while possessing good Li+ conductivity and electrochemical stability. In addition, the unique properties of the ALD technology allow us to achieve ultrathin (1 nm) and conformal coating, which is beneficial for electronic conductivity and cycling stability. Furthermore, the surface phase transition layer stripping failure mechanism has first been revealed to explain the loss of Co and O, while the reconstructed Li3AlF6 effectively suppresses the surface stripping. Thus, excellent high-voltage performance has been realized (an 89% capacity retention after 1000 cycles at 4.5 V and an 88% capacity retention after 200 cycles at 4.6 V). This work casts a new understanding on the surface reconstruction of the oxide coating layer, which is also significant for other electrode materials' modification.

Peripheral blood neutrophil-to-lymphocyte ratio in inflammatory bowel disease and disease activity: A meta-analysis.

OBJECTIVE: The peripheral blood neutrophil-to-lymphocyte ratio (NLR) is a valuable predictor of clinical disease activity in inflammatory bowel disease (IBD). Therefore, we conducted a meta-analysis to evaluate the clinical significance of peripheral blood NLR in IBD patients. METHODS: A comprehensive literature search was conducted by searching PubMed, Embase, Web of Science, Cochrane Library, and Chinese databases from inception to May 10, 2021. We used the standard mean difference (SMD) with a 95% confidence interval (CI) to estimate the pooled effect and subgroup analysis to investigate heterogeneity. RESULTS: Sixteen studies including 2185 IBD patients and 993 healthy controls (HCs) were enrolled in this study. The peripheral blood NLR values were significantly higher in 1,092 IBD patients than in 933 HCs (SMD = 1.54, 95% CI = 1.05-2.02, P < 0.001) and in 1,269 patients with active IBD than in 1,056 patients with remissive IBD (SMD = 1.55, 95% CI = 1.06-2.05, P < 0.001). Subgroup analysis of the major subtypes of IBD revealed significantly elevated peripheral blood NLR values in patients with active ulcerative colitis (UC) compared to HCs (SMD = 2.04), remissive UC than HCs (SMD = 0.63), and active UC than in those with remissive UC (SMD = 1.32) (P < 0.05). Both Crohn's disease (CD) patients and active CD patients had significantly elevated peripheral blood NLR values than HCs with the SMD of 0.52 and 3.53 (P < 0.001). CONCLUSIONS: Peripheral blood NLR could serve as a valuable biomarker for predicting disease severity in IBD patients.

Effect of multi-platform extended care on postoperative self-efficacy and quality of life in patients with osteoporotic vertebral compressive fracture.

OBJECTIVES: This study analyzed the effect of multi-platform extended care on postoperative self-efficacy and quality of life in patients with osteoporotic vertebral compressive fracture (OVCF). METHODS: 162 OVCF patients who underwent percutaneous vertebroplasty (PVP) or percutanous kyphoplasty (PKP) surgery in our hospital from January 2018 to June 2019 were classified into a control group (n=78) and an observation group (n=84) based on the admission time. The control group was given conventional health guidance and follow-up by telephone, and the observation group got multi-platform extended care. The postoperative incidence of re-fracture, Oswestry dysfunction index (ODI) before and after intervention, self-efficacy and quality of life were compared between the two groups. RESULTS: Incidence of re-fracture in the observation group was higher than that of the control group (P<0.05). The ODI scores of the two groups 3, 6, and 12 months after operation were lower than those on discharge (P<0.05), and the observation group had lower OD scores than the control group 6 and 12 months after operation (P<0.05). The self-efficacy scores of the two groups 6 months after discharge were higher than that on discharge (P<0.05), and the index in the observation group was higher than that of the control group (P<0.05). In addition, the scores of all dimensions of quality of life in two groups 6 months of discharge were higher than those on discharge (P<0.05), and the scores in the observation group were higher than those of the control group (P<0.05). CONCLUSION: Multi-platform extended care can effectively reduce the risk of postoperative re-fracture in OVCF patients, facilitate the improvement of patients' lumbar function, self-efficacy, and quality of life, and improve the prognosis of patients, which is worthy of clinical promotion.

Meta-analysis of the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in Henoch-Schonlein purpura and its complications.

OBJECTIVE: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with the severity of Henoch-Schonlein purpura (HSP). Therefore, we conducted a meta-analysis to evaluate the clinical significance of NLR and PLR in HSP and its complications. METHODS: A comprehensive literature search was conducted by searching the PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang, VIP, and SinoMed databases from their inception to September 31, 2020. We used the standard mean difference (SMD) with a 95% confidence interval (CI) to estimate the pooled effect and used subgroup analysis to investigate heterogeneity. RESULTS: A total of 1,691 HSP patients and 563 healthy controls (HCs) from 15 studies were included in the analysis. The NLR value was significantly higher in 431 HSP patients with gastrointestinal complications (HSP-GCs) than that in 833 HSP patients without GCs (SMD = 1.09, 95% CI: 0.62-1.57, P < 0.001); in 83 HSP adult patients with renal involvement (HSP-RI) than that in 131 adult HSP patients without RI (SMD = 0.33, 95% CI: 0.05-0.60, P = 0.021); and in 831 HSP patients than that in 563 HCs (SMD = 0.70, 95% CI: 0.51-0.89, P < 0.001). The PLR was significantly higher in 417 HSP patients than that in 264 HCs (SMD = 0.39, 95% CI: 0.06-0.71, P = 0.02). CONCLUSIONS: NLR could serve as a useful biomarker to predict GCs and RI in patients with HSP. However, further well-designed and large cohort studies are warranted to confirm these findings.

Decorated Au NPs on agar modified Fe3O4 NPs: Investigation of its catalytic performance in the degradation of methylene orange, and anti-human breast carcinoma properties.

This work describes an eco-friendly approach for in situ immobilization of Au nanoparticles on the surface of Fe3O4 nanoparticles, with help of Agar and ultrasound irradiations, without using any toxic reducing and capping agents. The structure, morphology, and physicochemical properties were characterized by various analytical techniques such as Fourier transformed infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), inductively coupled plasma (ICP) and vibrating sample magnetometer (VSM). The desired catalyst showed great efficiency in the reductive degradation of methylene orange (MO) dye over NaBH4 at room temperature. The MO was fully reduced in only 70 s and achieved rate constant of 9.6 × 10-2 s-1. The catalyst was reused for 10 runs without significant loss in catalytic activity. Cell viability of Fe3O4/agar/Au NPs was very low against breast adenocarcinoma (MCF7), breast carcinoma (Hs 578Bst), infiltrating ductal cell carcinoma (Hs 319.T), and metastatic carcinoma (MDA-MB-453) cell lines without any cytotoxicity on the normal cell line. According to the above findings, the Fe3O4/agar/Au NPs may be administrated for the treatment of several types of human breast carcinoma in humans.

FAM83D promotes epithelial-mesenchymal transition, invasion and cisplatin resistance through regulating the AKT/mTOR pathway in non-small-cell lung cancer.

PURPOSE: FAM83D has been proposed to act as an oncoprotein in several types of human cancer. Its role and mode of action in human non-small cell lung cancer (NSCLC) metastasis and its impact on chemotherapy are as yet, however, poorly understood. METHODS: FAM83D expression was measured in NSCLC cells and normal lung epithelial cells, as well as in primary NSCLC tissues and corresponding adjacent non-cancerous tissues, using qRT-PCR, Western blotting and immunohistochemistry. FAM83D was stably overexpressed in BEAS2B cells or silenced in A549 and H1299 cells using retroviral or lentiviral vectors. The growth capacity of NSCLC cells was evaluated using MTT and colony formation assays. Epithelial-mesenchymal transition (EMT) was assessed using Western blotting and immunofluorescence. NSCLC cell invasive capacities were assessed using scratch wound healing and Boyden chamber assays. NSCLC cell viability in response to cisplatin treatment was assessed using MTT assays in vitro and a xenograft model in vivo. RESULTS: We found that FAM83D expression levels were significantly elevated in NSCLC cells and tissues, and positively correlated with tumor progression and a poor prognosis. Exogenous FAM83D overexpression promoted, while FAM83D silencing inhibited NSCLC cell proliferation, EMT and invasion. FAM83D silencing also reduced cisplatin resistance. Concordantly, we found that NSCLC patients with a low FAM83D expression benefited most from chemotherapy. Mechanistically, we found that FAM83D activated the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Pharmacological treatment with either AKT or mTOR inhibitors reverted FAM83D-induced tumorigenic phenotypes. CONCLUSIONS: Our results suggest a role of FAM83D in NSCLC development. In addition, our results indicate that NSCLC patients exhibiting FAM83D overexpression are likely to benefit from AKT and/or mTOR inhibitor treatment.

Fabrication and characterization of solid lipid nano-formulation of astraxanthin against DMBA-induced breast cancer via Nrf-2-Keap1 and NF-kB and mTOR/Maf-1/PTEN pathway.

In the current experimental study, we scrutinized the chemoprotective effect of astraxanthin against the 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer via Nrf-2-Keap1 and NF-kB and mTOR/Maf-1/PTEN pathway. The double emulsion solvent displacement method was used for the preparation of astraxanthin solid lipid nanoparticles (SLN). SLNs were appraised for entrapment, potential, size, drug-release performance, and gastric stability. DMBA (8 mg/kg) was used for the induction of breast cancer. Tumor weight, body weight, and tumor incidence were estimated at a regular interval. Different biochemical parameters such as Na+/K+, Ca2+, and Mg2+ activity, antioxidant, lipid, glycoprotein, phase I and II biotransformation enzymes, mitochondrial TCA cycle, and carbohydrate metabolizing enzymes were estimated. Keap1-Nrf-2, associated HO-1, and NF-kB expressions were estimated. Moreover, it estimated the mRNA expression of LXR (α,ß), HMG-CoAR, PTEN, Maf1, PI3K, mTOR, Akt, FASN, and ACC1. AX-SLN reduced the tumor incidence, tumor weight, and increased the body weight. AX-SLN exhibited the protective effect against the LPO, enzymic (SOD, CuZnSOD, MnSOD, GPx, and CAT), and nonenzymic (GSH) in the serum, mammary gland, renal, and hepatic tissues. AX-SLN reduced the p-AKT which is accountable for the reduction in the NF-kB expression and also reduced the expression of Keap1 and NF-kB along with increasing the expression of HO-1 and Nrf-2. Further, AX-SLN significantly altered the mRNA of LXR (α,ß), HMG-CoAR, PTEN, Maf1, PI3K, mTOR, Akt, FASN, and ACC1. On the basis of the results, we can conclude that AX-SLN inhibits the mammary gland carcinogenesis via Nrf-2-Keap1, NF-kB, and mTOR/Maf-1/PTEN pathway.

Emotional labor strategies and job burnout in preschool teachers: Psychological capital as a mediator and moderator.

BACKGROUND: Preschool teachers can easily become exhausted and worn out, otherwise known as job burnout. Studies have explored the effects of emotional labor strategies and psychological capital on job burnout; however, few have examined their trilateral relationship, especially the role of psychological capital with respect to emotional labor strategies and job burnout. OBJECTIVE: This study explored the mediating and moderating effects of psychological capital in the relationship between three kinds of emotional labor strategies and job burnout in preschool teachers. METHODS: A cross-sectional study was conducted among preschool teachers in China. A total of 355 preschool teachers completed a self-report questionnaire, including three scales that measured emotional labor strategies, psychological capital, and job burnout. Resultant data were analyzed based on correlations, multiple regressions, and structural equation modeling. RESULTS: Results showed that for preschool teachers, two emotional labor strategies (deep acting and expression of natural emotion) were found to be negatively correlated with psychological capital and positively correlated with job burnout. However, surface acting was positively correlated with psychological capital and negatively correlated with job burnout. Psychological capital partially mediated the effects of the three emotional labor strategies on job burnout. Additionally, psychological capital significantly moderated the effects of surface acting and deep acting on job burnout. CONCLUSIONS: Psychological capital can significantly mediate and moderate the effects of emotional labor strategies on job burnout.

Unveiling the thickness-dependent mechanical properties of graphene papers by in situ SEM tension.

With more and more applications, the mechanical strength of graphene paper (GP) has attracted significant attention in recent years. In this report, GPs were prepared by flow-induced filtration of electrochemical exfoliated graphene sheets. By adjusting the concentration of solution, we found graphene sheets fabricated in 0.1 M K2SO4 have the thinnest average thickness. And by uniaxial in-plane tensile tests operated on a self-developed in situ scanning electron microscopy (SEM) tensile stage, the corresponding GP has the best fracture strength of 192 MPa. This is due to that the thickness decrease of exfoliated graphene will increase the quantity of interlayer crosslinks, thus improving the mechanical properties of GPs. This research may open a new way to obtain high-strength GPs for applications.

Scandium doping brings speed improvement in Sb2Te alloy for phase change random access memory application.

Phase change random access memory (PCRAM) has gained much attention as a candidate for nonvolatile memory application. To develop PCRAM materials with better properties, especially to draw closer to dynamic random access memory (DRAM), the key challenge is to research new high-speed phase change materials. Here, Scandium (Sc) has been found it is helpful to get high-speed and good stability after doping in Sb2Te alloy. Sc0.1Sb2Te based PCRAM cell can achieve reversible switching by applying even 6 ns voltage pulse experimentally. And, Sc doping not only promotes amorphous stability but also improves the endurance ability comparing with pure Sb2Te alloy. Moreover, according to DFT calculations, strong Sc-Te bonds lead to the rigidity of Sc centered octahedrons, which may act as crystallization precursors in recrystallization process to boost the set speed.

Driving better and safer HER2-specific CARs for cancer therapy.

Given the clinical efficacy of chimeric antigen receptor (CAR)-based therapy in hematological malignancies, CAR T-cell therapy for a number of solid tumors has been actively investigated. Human epidermal growth factor receptor 2 (HER2) is a well-established therapeutic target in breast, as well as other types of cancer. However, HER2 CAR T cells pose a risk of lethal toxicity including cytokine release syndrome from "on-target, off-tumor" recognition of HER2. In this review, we summarize the development of conventional HER2 CAR technology, the alternative selection of CAR hosts, the novel HER2 CAR designs, clinical studies and toxicity. Furthermore, we also discuss the main strategies for improving the safety of HER2 CAR-based cancer therapies.

Potential therapeutic strategy for gastric cancer peritoneal metastasis by NKG2D ligands-specific T cells.

PURPOSE: Despite advancements in its treatment, gastric cancer continues to be one of the leading causes of cancer deaths worldwide. Adoptive transfer of chimeric antigen receptor-modified T cells is a promising antitumor therapy for many cancers. The purpose of this study was to construct a chimeric receptor linking the extracellular domain of NKG2D to the CD28 and CD3zeta chain intracellular domains to target gastric cancers that expressed NKG2D ligands. METHODS: Expression of NKG2D ligands including MICA, MICB, and ULBP1-3 in a gastric cancer cell line and primary gastric cancer cells from ascites samples were analyzed using flow cytometry. Co-culture experiments were performed by incubating chNKG2D T cells with gastric cancer cell lines and with primary human gastric cancer cells isolated from ascites and by measuring cytokine and chemokine release and cytotoxicity. RESULTS: Gastric cancer cell lines and ascites-derived primary human gastric cancer cells expressed high levels of MICA, MICB, and ULBP2. ChNKG2D T cells secreted proinflammatory cytokines and chemokines when cultured with these cancer cells. In addition, chNKG2D T cells lysed gastric cancer cell lines and the ascites-derived primary human gastric cancer cells. CONCLUSION: These data indicate that treatment with chNKG2D-expressing T cells is a potential immunotherapy for gastric cancer with peritoneal metastasis.

Evaluation of biomarker changes after administration of various neoadjuvant chemotherapies in breast cancer.

To assess the changes in estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 expression in breast cancer patients after various neoadjuvant chemotherapies. Data from 138 locally advanced breast cancer patients with histological diagnoses were reviewed. Seventy patients (group 1) were given 4 cycles of 500 mg/m(2) cyclophosphamide and 50 mg/m(2) pirarubicin every 21 days. Sixty-eight patients (group 2) were given 4 cycles of 500 mg/m(2) cyclophosphamide and 75 mg/m(2) docetaxel every 21 days. The biomarker changes of the operated tumor tissues were compared with the initial core biopsies. ER, PR, HER2 and Ki-67 expression changed by 28.6%, 22.9%, 17.1% and 54.3%, respectively, after neoadjuvant chemotherapy in group 1 and 16.2%, 22.1%, 13.2% and 70.6%, respectively, after neoadjuvant chemotherapy in group 2. There were significant differences between the groups regarding ER and Ki-67 status changes, and these changes can be used to inform treatment strategies.