Single-Atom Co─O4 Sites Embedded in a Defective-Rich Porous Carbon Layer for Efficient H2O2 Electrosynthesis.

The production of hydrogen peroxide (H2O2) via the two-electron electrochemical oxygen reduction reaction (2e- ORR) is an essential alteration in the current anthraquinone-based method. Herein, a single-atom Co─O4 electrocatalyst is embedded in a defective and porous graphene-like carbon layer (Co─O4@PC). The Co─O4@PC electrocatalyst shows promising potential in H2O2 electrosynthesis via 2e- ORR, providing a high H2O2 selectivity of 98.8% at 0.6 V and a low onset potential of 0.73 V for generating H2O2. In situ surface-sensitive attenuated total reflection Fourier transform infrared spectra and density functional theory calculations reveal that the electronic and geometric modification of Co─O4 induced by defective carbon sites result in decreased d-band center of Co atoms, providing the optimum adsorption energies of OOH* intermediate. The H-cell and flow cell assembled using Co─O4@PC as the cathode present long-term stability and high efficiency for H2O2 production. Particularly, a high H2O2 production rate of 0.25 mol g-1 cat h-1 at 0.6 V can be obtained by the flow cell. The in situ-generated H2O2 can promote the degradation of rhodamine B and sterilize Staphylococcus aureus via the Fenton process. This work can pave the way for the efficient production of H2O2 by using Co─O4 single atom electrocatalyst and unveil the electrocatalytic mechanism.

Impedimetric aptasensor based on porphyrin-based covalent-organic framework for determination of diethylstilbestrol.

An impedimetric sensing strategy was developed for sensitively determining diethylstilbestrol (DES) based on a platform of porphyrin-containing covalent-organic framework (p-COF). The p-COF was synthesized using 5,10,15,20-tetra (4-aminophenyl) porphyrin (TAPP) and 1,3,6,8-tetrakis(4-formylphenyl) pyrene (TFPy) as building blocks via condensation reaction, for which p-COF was named as TAPP-TFPy-COF. Considering the large specific surface area (302.9 m2 g-1), high porosity, rich nitrogen functionality, superior electrochemical activity, and strong bioaffinity toward DNA strands, the TAPP-TFPy-COF-based platform exhibited enhanced, non-label, and amplified electrochemical signal, large number of immobilized DES-targeted aptamer strands, and fast-response toward the analyte. Electrochemical results reveal that the TAPP-TFPy-COF-based aptasensor promoted the sensing performance for the detection of DES, resulting in an extremely low limit of detection of 0.42 fg mL-1 within a DES concentration ranging from 1 fg mL-1 to 0.1 pg mL-1, which was substantially lower than those of most reported DES sensors. Furthermore, the TAPP-TFPy-COF-based aptasensor possessed outperformed stability, high selectivity, ascendant reproducibility, and acceptable applicability in diverse environments. The recovery values for DES detection in milk, tap water, and frozen shrimp were in the range 91.80-118.50% with low relative standard deviation of 0.11-4.26%. This work provides a new sensing electrochemical approach based on COF network for DES detection and shows a deep insight into the construction of COF-based biosensors, which can be extended to be used for other target compounds.

Surface plasmon resonance aptasensor based on niobium carbide MXene quantum dots for nucleocapsid of SARS-CoV-2 detection.

A novel label-free surface plasmon resonance (SPR) aptasensor has been constructed for the detection of N-gene of SARS-CoV-2 by using thiol-modified niobium carbide MXene quantum dots (Nb2C-SH QDs) as the bioplatform for anchoring N-gene-targeted aptamer. In the presence of SARS-CoV-2 N-gene, the immobilized aptamer strands changed their conformation to specifically bind with N-gene. It thus increased the contact area or enlarged the distance between aptamer and the SPR chip, resulting in a change of the SPR signal irradiated by the laser (He-Ne) with the wavelength (λ) of 633 nm. Nb2C QDs were derived from Nb2C MXene nanosheets via a solvothermal method, followed by functionalization with octadecanethiol through a self-assembling method. Subsequently, the gold chip for SPR measurements was modified with Nb2C-SH QDs via covalent binding of the Au-S bond also by self-assembling interaction. Nb2C-SH QDs not only resulted in high bioaffinity toward aptamer but also enhanced the SPR response. Thus, the Nb2C-SH QD-based SPR aptasensor had low limit of detection (LOD) of 4.9 pg mL-1 toward N-gene within the concentration range 0.05 to 100 ng mL-1. The sensor also showed excellent selectivity in the presence of various respiratory viruses and proteins in human serum and high stability. Moreover, the Nb2C-SH QD-based SPR aptasensor displayed a vast practical application for the qualitative analysis of N-gene from different samples, including seawater, seafood, and human serum. Thus, this work can provide a deep insight into the construction of the aptasensor for detecting SARS-CoV-2 in complex environments. A novel label-free surface plasmon resonance aptasensor has been constructed to detect sensitively and selectively the N-gene of SARS-CoV-2 by using thiol-modified niobium carbide MXene quantum dots as the scaffold to anchor the N-gene-targeted aptamer.

Cancer pain and neuropathic pain are associated with A ß sensory neuronal plasticity in dorsal root ganglia and abnormal sprouting in lumbar spinal cord.

Evidence suggests that there are both nociceptive and neuropathic components of cancer-induced pain. We have observed that changes in intrinsic membrane properties and excitability of normally non-nociceptive Aß sensory neurons are consistent in rat models of peripheral neuropathic pain and cancer-induced pain. This has prompted a comparative investigation of the intracellular electrophysiological characteristics of sensory neurons and of the ultrastructural morphology of the dorsal horn in rat models of neuropathic pain and cancer-induced pain. Neuropathic pain model rats were induced with a polyethylene cuff implanted around a sciatic nerve. Cancer-induced pain model rats were induced with mammary rat metastasis tumour-1 rat breast cancer or MATLyLu rat prostate cancer cells implanted into the distal epiphysis of a femur. Behavioural evidence of nociception was detected using von Frey tactile assessment. Aß-fibre low threshold mechanoreceptor neurons in both cancer-induced pain and neuropathic pain models exhibited slower dynamics of action potential genesis, including a wider action potential duration and lower action potential amplitude compared to those in control animals. Enhanced excitability of Aß-fibre low threshold mechanoreceptor neurons was also observed in cancer-induced pain and neuropathic pain models. Furthermore, both cancer-induced pain and neuropathic pain models showed abundant abnormal axonal sprouting in bundles of myelinated axons in the ipsilateral spinal laminae IV and V. The patterns of changes show consistency between rat models of cancer-induced pain and neuropathic pain. These findings add to the body of evidence that animal models of cancer-induced pain and neuropathic pain share features that may contribute to the peripheral and central sensitization and tactile hypersensitivity in both pain states.

Multiple active cobalt species embedded in microporous nitrogen-doped carbon network for the selective production of hydrogen peroxide.

To obtain excellent electrocatalysts for improving H2O2 yield and selectivity, we formulated a novel method for embedding cobalt catalytic active sites in porous two-dimensional nitrogen-doped carbon network (CNy) network and employed them as excellent two-electron oxygen reduction reaction (2e--ORR) electrocatalysts. The polymeric cobalt-based metal-organic framework (polyCo-MOF) and melamine-cyanuric acid-complex (MCA) hybrid (denoted as polyCo-MOF@MCA) was used as a precursor for preparing a series of electrocatalysts comprising multiple active sites such as metallic Co, CoOx, or Co-N, which are homogeneously embedded in the porous two-dimensional CNy network through pyrolysis at high temperatures (600 °C, 700 °C, and 800 °C) under N2 atmosphere. The obtained CoOx/Co@CNy,700 hybrid by pyrolyzing polyCo-MOF@MCA at 700 °C displayed remarkably high H2O2 production and large selectivity in an alkaline solution. The possible catalytic mechanism of CoOx/Co@CNy,700 toward 2e--ORR was identified by determining the catalytic kinetics and control experiments. The cathode assembled with the CoOx/Co@CNy,700 hybrid showed the maximum H2O2 production of 405 mmol L-1gcat.-1h-1 with a high Faradaic efficiency of 88.9 % at 0.65 V. The present work demonstrated a novel strategy for identifying excellent electrocatalysts with homogeneously dispersed multiple active sites and high production and selectivity for H2O2 synthesis, extending the applications of porous organic frameworks to the field of clean energy.

Hierarchical CoCoPBA@PCN-221 nanostructure for the highly sensitive detection of deoxynivalenol in foodstuffs.

An electrochemical impedimetric immunosensor was constructed based on a hierarchical nanostructured CoCo Prussian blue analogue entrapped by a Zr-based porphyrin MOF (denoted by CoCoPBA@PCN-221) for the sensitive detection of deoxynivalenol (DON). Given that CoCoPBA@PCN-221 demonstrated a hierarchical nanostructure, large specific surface area, and the synergistic effect between mixed metal valence states (Co2+/Co3+) and Zr clusters, it thus displayed a high binding interaction with the DON-targeted antibody. Compared with CoCoPBA and PCN-221, CoCoPBA@PCN-221 showed a superior stabilization ability toward the antibody-antigen complex in aqueous solution. Under optimum conditions, the CoCoPBA@PCN-221-based impedimetric immunosensor exhibited a good linear range from 1 fg mL-1 to 1 ng mL-1, and an ultralow detection limit of 0.14 fg mL-1, accompanied by high selectivity, reproducibility, stability, and applicability in foodstuffs. This method allows the integration of MOFs with cascading properties for applications in the biosensing and food safety fields.

Heregulin-ß1-induced GPR30 upregulation promotes the migration and invasion potential of SkBr3 breast cancer cells via ErbB2/ErbB3-MAPK/ERK pathway.

Estrogen receptor (ER)-negative breast cancer cells are probably more aggressive with larger metastatic potential than ER-positive cells. Loss of ER in recurrent breast cancer is associated with poor response to endocrine therapy. G protein-coupled receptor 30 (GPR30) is expressed in half of ER-negative breast cancers. Tumor cell-derived heregulin-ß1 (HRG-ß1) is also found mainly in ER-negative cancer. In SkBr3 breast cancer cells that lack ER but express GPR30, HRG-ß1 upregulates mRNA and protein levels of GPR30 by promoting ErbB2-ErbB3 heterodimerization and activating the downstream MAPK-ERK signaling pathway. Moreover, GPR30 boosts HRG-ß1-induced migration and invasion of SkBr3 cells after combinative treatment with E2, 4-hydroxy-tamoxifen or the specific GPR30 agonist G-1, which are blocked by the specific GPR30 antagonist G-15 or the transfection with the small interfering RNA for GPR30. The ErbB2 inhibitor AG825 and the MEK1/2 inhibitor U0126 also partly inhibit the enhanced migration and invasion. Therefore, HRG-ß1-induced migration and invasion partly depend on the upregulation of GPR30 expression through activation of the ErbB2-ERK pathway in SkBr3 cells. The results of this study indicate that the crosstalk between GPR30 and HRGs signaling is important for endocrine therapy resistance and may provide a new therapeutic way to treat breast cancer.

Pathological significance of epidermal growth factor receptor expression and amplification in human gliomas.

AIMS: To investigate epidermal growth factor receptor (EGFR) expression and amplification in gliomas and to assess their association with survival. METHODS AND RESULTS: Immunohistochemistry and fluorescence in-situ hybridization were performed to analyse EGFR status in 158 cases of primary glioma. Kaplan-Meier survival and Cox regression analyses were performed to analyse the prognosis of patients. Overexpression of EGFR and expression of EGFR variant III (EGFRvIII) were found in 102 cases (64.6%) and 47 cases (29.7%), respectively. Overexpression of EGFR was significantly correlated with World Health Organization (WHO) grade and Karnofsky performance score (KPS) (both P < 0.05). Expression of EGFRvIII was significantly correlated with WHO grade, gender, age, and KPS (all P < 0.05). EGFR amplification was found in 46 cases (29.1%), and was significantly correlated with WHO grade, age, KPS and EGFR overexpression (all P < 0.05). Cox multifactor analysis showed that EGFR amplification was an independent unfavourable prognostic factor for human gliomas at all ages, and EGFRvIII was an independent prognostic factor in patients older than 60 years. CONCLUSION: EGFR amplification and EGFRvIII expression were associated with an unfavourable prognosis for patients of all ages, and for those older than 60 years, respectively. The differing significance of EGFR status in young and old glioma patients and its impact on prognosis needs further study.

Construction of bifunctional electrochemical biosensors for the sensitive detection of the SARS-CoV-2 N-gene based on porphyrin porous organic polymers.

In this study, a novel porphyrin-based porous organic polymer (POP) was constructed using 5,10,15,20-tetramine (4-aminophenyl) porphyrin (TAPP) and 5,5'-diformyl-2,2'-bipyridine (DPDD) as organic ligands via a solvothermal method (represented as TAPP-DPDD-POP). Then, it was utilized as a bifunctional scaffold for constructing a sensitive sensing strategy toward the nucleocapsid phosphoprotein (N-gene) of SARS-CoV-2. The obtained TAPP-DPDD-POP is composed of nanospheres with a size of 100-300 nm and possesses a highly conjugated and π-π stacking network. The coexistence of the porphyrin and bipyridine moieties of TAPP-DPDD-POP afforded considerable electrochemical activity and a strong binding interaction toward the SARS-CoV-2 N-gene-targeted antibody and targeted the aptamer strands of the N-gene. The TAPP-DPDD-POP-based aptasensor and immunosensor were manufactured for the sensitive analysis of SARS-CoV-2 N-gene, and exhibited the limit of detection (LOD) of 0.59 fg mL-1 and 0.17 fg mL-1, respectively, within the range of 0.1 fg mL-1 to 1 ng mL-1 of N-gene. The sensing performances of both the TAPP-DPDD-POP-based aptasensor and immunosensor were better than those of existing electrochemical biosensors for analyzing the N-gene, accompanied with excellent stability, high selectivity and reproducibility. The TAPP-DPDD-POP-based aptasensor and immunosensor were then employed to detect the N-gene from various environments, including human serum, river water, and seafoods. This work provides a new method of using an electrochemically active POP to sensitively and selectively analyze SARS-CoV-2 in diverse environments.

Porphyrin-based covalent organic framework as bioplatfrom for detection of vascular endothelial growth factor 165 through fluorescence resonance energy transfer.

A fluorescent aptasensor based on porphyrin-based covalent organic framework (p-COF) and carbon dots (CDs) was constructed for detecting vascular endothelial growth factor 165 (VEGF165) and for imaging of the breast cancer cell line Michigan cancer foundation-7 (MCF-7). CDs synthesized with strong photoluminescence at λ∼380 nm were used as donors to label the VEGF165-targeted aptamers (AptVEGF/CDs). Additionally, the p-COF nanostructure comprised rich functional groups of CN on the surface and π-stacking planar nanostructure, resulting in the CDs adsorption via weakly π-π stacking, hydrogen bond and the Van der Waals force. Thereby, the fluorescence resonance energy transfer (FRET) occurred due to the close distance between the p-COF network and CDs, leading to the quenching of the fluorescence feature of CDs and p-COF. In the presence of VEGF165, the G-quadruplex was formed via the specific binding between VEGF165 and aptamer. It impelled that the release of partial VEGF165-AptVEGF/CDs complex, affording the fluorescence recovery of the sensing system to some extent. Consequently, the proposed AptVEGF/CDs/p-COF fluorescence biosensor offered excellent analytical performances for the VEGF165 detection, displaying a detection limit of 20.9 fg mL-1 within a wide linear range of the VEGF165 concentration of 1.0 pg mL-1-100 ng mL-1. The developed fluorescence biosensor was also used to determine VEGF165-overexpressed in MCF-7 cancer cells. Thereby, the present work can greatly widen the application of COFs in the development of aptasensors and cancer diagnosis.

Response to pregabalin and progesterone differs in male and female rat models of neuropathic and cancer pain.

Background: Cancer pain involves nervous system damage and pathological neurogenesis. Neuropathic pain arises from damage to the nervous system and is driven by ectopic signaling. Both progesterone and pregabalin are neuroprotective in animal models, and there is evidence that both drugs bind to and inhibit voltage-gated calcium channels. Aims: This study was designed to characterize the effects of progesterone and pregabalin in preclinical models of cancer and neuropathic pain in both sexes. Methods: We measured peripheral sensory signaling by intracellular in vivo electrophysiology and behavioral indicators of pain in rat models of cancer-induced bone pain and neuropathic pain. Results: Female but not male models of cancer pain showed a behavioral response to treatment and pregabalin reduced excitability in C and A high-threshold but not low-threshold sensory neurons of both sexes. Male models of neuropathic pain treated with pregabalin demonstrated higher signaling thresholds only in A high-threshold neurons, and behavioral data indicated a clear recovery to baseline mechanical withdrawal thresholds in all treatment groups. Female rat treatment groups did not show excitability changes in sensory neurons, but all demonstrated higher mechanical withdrawal thresholds than vehicle-treated females, although not to baseline levels. Athymic female rat models of neuropathic pain showed no behavioral or electrophysiological responses to treatment. Conclusions: Both pregabalin and progesterone showed evidence of efficacy in male models of neuropathic pain. These results add to the evidence demonstrating differential effects of treatments for pain in male and female animals and widely differing responses in models of cancer and neuropathic pain.

Contexte: La douleur cancéreuse implique des lésions du système nerveux et une neurogenèse pathologique. La douleur neuropathique résulte d'une lésion du système nerveux et est provoquée par une signalisation ectopique. La progestérone et la prégabaline sont toutes deux neuroprotectrices dans les modèles animaux et il est prouvé que ces deux médicaments se lient aux canaux calciques à tension contrôlée et les inhibent.Objectifs: Cette étude visait à caractériser les effets de la progestérone et de la prégabaline dans des modèles précliniques de cancer et de douleur neuropathique chez les deux sexes.Méthodes: Nous avons mesuré la signalisation sensorielle périphérique par électrophysiologie intracellulaire in vivo, ainsi que les indicateurs comportementaux de la douleur dans des modèles de rats atteints de douleurs osseuses et de douleurs neuropathiques induites par le cancer.Résultats: Contrairement aux modèles masculins, les modèles féminins atteints de douleur cancéreuse ont montré une réponse comportementale au traitement, tandis que la prégabaline a réduit l'excitabilité des neurones sensoriels C et A à seuil élevé mais non à seuil bas chez les deux sexes. Les modèles masculins atteints de douleur neuropathique traités à la prégabaline ont montré des seuils de signalisation plus élevés uniquement dans les neurones A à seuil élevé, tandis que les données comportementales ont indiqué un net retour aux seuils de retrait mécanique de départ dans tous les groupes de traitement. Les groupes de rats femelles traités n'ont pas montré de changements d'excitabilité dans les neurones sensoriels, mais tous ont montré des seuils de retrait mécanique plus élevés que les femelles traitées avec le vecteur, sans toutefois atteindre les niveaux de départ. Les modèles atteints de douleur neuropathique parmi les rats femelles athymiques n'ont montré aucune réponse comportementale ou électrophysiologique au traitement.Conclusions: La prégabaline et la progestérone ont toutes deux démontré leur efficacité dans les modèles masculins atteints de douleur neuropathique. Ces résultats s'ajoutent aux données probantes démontrant les effets différentiels des traitements de la douleur chez les animaux mâles et femelles, et les réponses très différentes dans les modèles atteints de cancer et de douleur neuropathique.

An evaluation of the anti-hyperalgesic effects of cannabidiolic acid-methyl ester in a preclinical model of peripheral neuropathic pain.

BACKGROUND AND PURPOSE: Chronic neuropathic pain (NEP) is associated with growing therapeutic cannabis use. To promote quality of life without psychotropic effects, cannabinoids other than Δ9-tetrahydrocannabidiol, including cannabidiol and its precursor cannabidiolic acid (CBDA), are being evaluated. Due to its instability, CBDA has been understudied, particularly as an anti-nociceptive agent. Adding a methyl ester group (CBDA-ME) significantly enhances its stability, facilitating analyses of its analgesic effects in vivo. This study examines early treatment efficacy of CBDA-ME in a rat model of peripherally induced NEP and evaluates sex as a biological variable. EXPERIMENTAL APPROACH: After 14 consecutive days of intraperitoneal CBDA-ME administration at 0.01, 0.1 and 1 µg·kg-1 , commencing 1 day after surgically implanting a sciatic nerve-constricting cuff to induce NEP, the anti-nociceptive efficacy of this cannabinoid was assessed in male and female Sprague-Dawley rats relative to vehicle-treated counterparts. In females, 2 and 4 µg·kg-1 daily doses of CBDA-ME were also evaluated. Behavioural tests were performed for hind paw mechanical and thermal withdrawal thresholds once a week for 8 weeks. At endpoint, in vivo electrophysiological recordings were obtained to characterize soma threshold changes in primary sensory neurons. KEY RESULTS: In males, CBDA-ME elicited a significant concentration-dependent chronic anti-hyperalgesic effect, also influencing both nociceptive and non-nociceptive mechanoreceptors, which were not observed in females at any of the concentrations tested. CONCLUSION AND IMPLICATIONS: Initiating treatment of a peripheral nerve injury with CBDA-ME at an early stage post-surgery provides anti-nociception in males, warranting further investigation into potential sexual dimorphisms underlying this response.

Antibiotic Prophylaxis in the Management of Open Fractures: A Systematic Survey of Current Practice and Recommendations.

BACKGROUND: Evidence with regard to antibiotic prophylaxis for patients with open fractures of the extremities is limited. We therefore conducted a systematic survey addressing current practice and recommendations. METHODS: We included publications from January 2007 to June 2017. We searched Embase, MEDLINE, CINAHL, the Cochrane Central Registry of Controlled Trials (CENTRAL), and the Cochrane Database of Systematic Reviews for clinical studies and surveys of surgeons; WorldCat for textbooks; and web sites for guidelines and institutional protocols. RESULTS: We identified 223 eligible publications that reported 100 clinical practice patterns and 276 recommendations with regard to systemic antibiotic administration, and 3 recommendations regarding local antibiotic administration alone. Most publications of clinical practice patterns used regimens with both gram-positive and gram-negative coverage and continued the administration for 2 to 3 days. Most publications recommended prophylactic systemic antibiotics. Most recommendations suggested gram-positive coverage for less severe injuries and administration duration of 3 days or less. For more severe injuries, most recommendations suggested broad antimicrobial coverage continued for 2 to 3 days. Most publications reported intravenous administration of antibiotics immediately. CONCLUSIONS: Current practice and recommendations strongly support early systemic antibiotic prophylaxis for patients with open fractures of the extremities. Differences in antibiotic regimens, doses, and durations of administration remain in both practice and recommendations. Consensus with regard to optimal practice will likely require well-designed randomized controlled trials. CLINICAL RELEVANCE: The current survey of literature systematically provides surgeons' practice and the available expert recommendations from 2007 to 2017 on the use of prophylactic antibiotics in the management of open fractures of extremities.

Attitudes toward the Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain: A qualitative study.

BACKGROUND: Chronic noncancer pain (CNCP) refers to all pain disorders, not due to cancer, that persist for ≥3 months. The point prevalence of CNCP in the general population of Western countries is between 19 and 33 percent. Opioids are commonly prescribed for CNCP and are associated with both benefits and harms. The Canadian Guideline for Safe and Effective Use of Opioids for CNCP was published in 2010 to provide guidance for optimal opioid prescribing in patients with CNCP. OBJECTIVES: To investigate the attitudes toward, and use of, the Canadian Opioids Guideline among pain physicians. DESIGN: A qualitative study using one-on-one, semistructured interviews with 12 pain physicians in Ontario, Canada, and thematic analysis of verbatim transcripts. RESULTS: Major themes that emerged from interviews included: (1) generally positive attitudes toward the 2010 Canadian Opioids Guideline, but limited use-half (six of 12) reported they did not use the guideline in practice; (2) strongly contrasting views regarding the 200 mg/d morphine equivalent watchful dose; (3) recognition of gaps in the guideline, especially recommendations for urine drug screening and pain severity-specific therapy; (4) the guideline is excessively long and the format suboptimal; and (5) improved dissemination and education are needed to enhance guideline uptake. CONCLUSIONS: Despite its merits, the Canadian Opioids Guideline suffers from information gaps and from limited uptake, at least in part due to suboptimal format and suboptimal dissemination.

Correlation of epidermal growth factor receptor overexpression with increased epidermal growth factor receptor gene copy number in esophageal squamous cell carcinomas.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignancies in China and epidermal growth factor receptor (EGFR) is widely distributed in human epithelial cell membrane. The aim of this study was to investigate the protein overexpression and gene copy number of EGFR in ESCC, and help to identify patients who may benefit from EGFR targeted therapies. METHODS: Immunohistochemistry (IHC) was performed to analyze the expression of EGFR in 105 cases of ESCC, 16 cases of squamous epithelial atypical hyperplasia, and 11 cases of normal esophageal tissue. Fluorescence in situ hybridization (FISH) was performed to analyze the gene copy number in 80 cases of ESCC, eight cases of squamous epithelial atypical hyperplasia, and eight samples of normal esophageal tissue. RESULTS: The IHC-positive rates of EGFR in 105 cases of ESCC, 16 cases of squamous epithelial atypical hyperplasia, and 11 normal esophageal tissues were 97% (102/105), 44% (7/16), and 18% (2/11) respectively. The difference in the expression of EGFR among different esophageal tissue groups had statistically significance (P < 0.05). Among the 105 cases of ESCC, overexpression of EGFR was found in 90 cases (86%), of which 55 cases scored 3+ for EGFR staining and 35 cases scored 2+. In ESCC, the expression of EGFR was significantly correlated with depth of invasion and TNM stage (P < 0.05), but not with other parameters. The FISH-positive rates of EGFR in 80 cases of ESCC, the eight cases of squamous epithelial atypical hyperplasia, and eight samples of normal esophageal tissue were 31.3% (25/80), 0 (0/8) and 0 (0/8) respectively. In ESCC, EGFR gene amplification was found in 17 (21%) cases, high polysomy in 8 (10%) cases, disomy in 34 cases, low trisomy in 17 cases, and high trisomy in four cases. EGFR FISH-positive was significantly correlated with depth of invasion and lymph node metastasis (P < 0.05). EGFR FISH-positive was significantly associated with overexpression of EGFR. CONCLUSION: Protein overexpression and/or increased gene copy number of EGFR is common in ESCC, and EGFR targeted therapy may be appropriate for ESCC patients.

Overexpression of caveolin-1 in cancer-associated fibroblasts predicts good outcome in breast cancer.

BACKGROUND: The aim of this study was to investigate the expression of caveolin-1 (Cav-1) in cancer-associated fibroblasts (CAFs) and to explore its correlation with clinicopathologic parameters and prognosis. MATERIALS AND METHODS: Cav-1 expression was detected in the stroma of 143 patients with breast cancer, 10 patients with ductal carcinoma in situ (DCIS), and 10 normal breast tissue samples. RESULTS: Overexpression of stromal Cav-1 in breast cancer was associated with histological type, low histological grade, estrogen receptor (ER) negativity, and molecular subtypes. The expression rate of stromal Cav-1 in breast cancer (65.7%, 94/143) was significantly higher than that of DCIS (0%, 0/10) and normal breast tissue (0%, 0/10) (p = 0.000). A positive correlation was found between stromal Cav-1 and ER (p = 0.046, rs = 0.218). Stromal Cav-1 expression in luminal B was significantly higher than in basal-like type (p = 0.048). Furthermore, stromal expression of Cav-1 was significantly correlated with the 5-year survival rate (p = 0.029), and it was an independent prognostic factor (p = 0.009). CONCLUSION: Cav-1 expression in CAFs was correlated with histological type, histological grade, ER status, and molecular subtypes in breast cancer. Stromal Cav-1 expression was an independent prognostic factor, and the absence or reduction of Cav-1 expression in stromal CAFs of invasive breast cancer predicts poor prognostic outcome.

Correlation of epidermal growth factor receptor overexpression with increased epidermal growth factor receptor gene copy number in esophageal squamous cell carcinomas / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignancies in China and epidermal growth factor receptor (EGFR) is widely distributed in human epithelial cell membrane. The aim of this study was to investigate the protein overexpression and gene copy number of EGFR in ESCC, and help to identify patients who may benefit from EGFR targeted therapies.</p><p><b>METHODS</b>Immunohistochemistry (IHC) was performed to analyze the expression of EGFR in 105 cases of ESCC, 16 cases of squamous epithelial atypical hyperplasia, and 11 cases of normal esophageal tissue. Fluorescence in situ hybridization (FISH) was performed to analyze the gene copy number in 80 cases of ESCC, eight cases of squamous epithelial atypical hyperplasia, and eight samples of normal esophageal tissue.</p><p><b>RESULTS</b>The IHC-positive rates of EGFR in 105 cases of ESCC, 16 cases of squamous epithelial atypical hyperplasia, and 11 normal esophageal tissues were 97% (102/105), 44% (7/16), and 18% (2/11) respectively. The difference in the expression of EGFR among different esophageal tissue groups had statistically significance (P < 0.05). Among the 105 cases of ESCC, overexpression of EGFR was found in 90 cases (86%), of which 55 cases scored 3+ for EGFR staining and 35 cases scored 2+. In ESCC, the expression of EGFR was significantly correlated with depth of invasion and TNM stage (P < 0.05), but not with other parameters. The FISH-positive rates of EGFR in 80 cases of ESCC, the eight cases of squamous epithelial atypical hyperplasia, and eight samples of normal esophageal tissue were 31.3% (25/80), 0 (0/8) and 0 (0/8) respectively. In ESCC, EGFR gene amplification was found in 17 (21%) cases, high polysomy in 8 (10%) cases, disomy in 34 cases, low trisomy in 17 cases, and high trisomy in four cases. EGFR FISH-positive was significantly correlated with depth of invasion and lymph node metastasis (P < 0.05). EGFR FISH-positive was significantly associated with overexpression of EGFR.</p><p><b>CONCLUSION</b>Protein overexpression and/or increased gene copy number of EGFR is common in ESCC, and EGFR targeted therapy may be appropriate for ESCC patients.</p>