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1.
Molecules ; 25(3)2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32012911

RESUMO

Naringenin, a flavonoid compound which exists abundantly in Citrus fruits, is proven to possess excellent antitussive and expectorant effects. However, the clinical applications of naringenin are restricted by its poor solubility and low local concentration by oral administration. The aim of the present study is to prepare a naringenin-hydroxypropyl-ß-cyclodextrin (naringenin-HPßCD) inclusion as an inhalation solution for pulmonary delivery. The naringenin-HPßCD inclusion was characterized by phase solubility study, XRD, differential scanning calorimetry (DSC), proton nuclear magnetic resonance (1HNMR), and two-dimensional rotating frame Overhauser effect spectroscopy (2D ROESY). The in vitro permeability of the inclusion was evaluated on Calu-3 cells and the pharmacokinetic profile of pulmonary delivery was investigated in Sprague-Dawley (SD) rats. Based on the linear model of phase solubility study, the relationship between naringenin and HPßCD was identified as AL type with a 1:1 stoichiometry. XRD, DSC, and NMR studies indicated that the entire naringenin molecule is encapsulated into the cavity of HPßCD. HPßCD could increase the concentration of naringenin in the epithelium-lining fluid (ELF) of Calu-3 cells and act as a sustained release system for naringenin. The pharmacokinetic profile of naringenin-HPßCD inclusion showed rapid response and higher local concentration by pulmonary delivery. In conclusion, pulmonary delivery of naringenin-HPßCD inclusion is a promising formulation strategy, which could provide a new possibility for the clinical application of naringenin.

2.
Nutrients ; 12(1)2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952251

RESUMO

Ganpu tea is an emerging tea drink produced from Pu-erh tea and the pericarp of Citrus reticulate Chachi (GCP). Recently, it has been increasingly favored by consumers due to the potential health effects and special taste. However, information concerning its chemical profile and biological activities is scarce. In this work, a total of 92 constituents were identified in hot-water extracts of Ganpu tea with ultra-high performance liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS). Moreover, the antioxidative and gut microbiota modulatory properties of Ganpu tea were investigated in rats after long-term dietary consumption. Ganpu tea and GCP could significantly enhance the activities of superoxide dismutase (SOD) by 13.4% (p < 0.05) and 15.1% (p < 0.01), as well as the activities of glutathione peroxidase (GSH-Px) by 16.3% (p < 0.01) and 20.5% (p < 0.01), respectively. Both showed better antioxidant capacities than Pu-erh tea. Ganpu tea increased the abundance of Bifidobacterium, Lactobacillus, and Lactococcus, suggesting the potential of Ganpu tea in modulating the gut microbiota to benefit human health. The obtained results provide essential information for further investigation of Ganpu tea.

3.
Interdiscip Sci ; 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31983041

RESUMO

BACKGROUND: Although microsatellite instability (MSI) is most commonly detected in colorectal cancer (CRC), improvement in MSI analysis method can always help us better assessing MSI phenotypes and gaining useful information in challenging cases. The purpose of current study is to explore whether the ProDx® MSI analysis System (ProDx® MSI) can improve MSI classification in CRC. METHODS: We compared the MSI profiles of 97 FFPE samples from CRC patients by ProDx® MSI with Promega MSI analysis System 1.2 and NCI panel. The result is then confirmed by IHC test, which evaluate MMR protein expression. Furthermore, next generation sequencing was performed to double confirm the specimens with discordant results. RESULTS: Among the total 97 CRC cases, 35 were scored as MSI-High by ProDx® MSI, Promega MSI analysis System 1.2, and NCI panel simultaneously. Three extra MSI-High cases were identified by ProDx® MSI. These three cases were classified as MSI-Low by NCI panel, while two of these as MSI-Low, and 1 as MSS by Promega MSI analysis System 1.2. ProDx® MSI had higher concordance with IHC detection compared with Promega MSI Analysis System 1.2 and NCI panel at 99.0%, 96.9%, and 95.9%, respectively. The ProDx® MSI distinguished MSI status with 100% sensitivity and 98.4% specificity. Our data showed that MSI-High phenotype occurred most frequently in tumor development stage I and stage II. CONCLUSIONS: The colorectal cancer can be classified according to MSI status accurately by ProDx® MSI. More cases with MSI-High feature may be revealed by ProDx® MSI than by previous test systems in colorectal cancer.

4.
Biomaterials ; 234: 119772, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31945618

RESUMO

Photodynamic therapy (PDT) is a promising treatment modality for tumor suppression. However, the hypoxic state of most solid tumors might largely hinder the efficacy of PDT. Here, a functional covalent organic framework (COF) is fabricated to enhance PDT efficacy by remodeling the tumor extracellular matrix (ECM). Anti-fibrotic drug pirfenidone (PFD) is loaded in an imine-based COF (COFTTA-DHTA) and followed by the decoration of poly(lactic-co-glycolic-acid)-poly(ethylene glycol) (PLGA-PEG) to fabricate PFD@COFTTA-DHTA@PLGA-PEG, or PCPP. After injected intravenously, PCPP can accumulate and release PFD in tumor sites, leading to down-regulation of ECM compenents such as hyaluronic acid (HA) and collagen I. Such depletion of tumor ECM reduces the intratumoral solid stress, a compressive force exerted by the ECM and cells, decompresses tumor blood vessels, and increases the density of effective vascular areas, resulting in significantly improved oxygen supply in tumor. Furthermore, PCPP-mediated tumor ECM depletion also enhances the tumor uptake of subsequently injected Protoporphyrinl IX (PPIX)-conjugated peptide formed nanomicelles (NM-PPIX) due to the improved enhanced permeability and retention (EPR) effect. Both the alleviated tumor hypoxia and improved tumor homing of photosensitizer (PS) molecules after PCPP treatment significantly increase the reactive oxygen species (ROS) generation in tumor and therefore realize greatly enhanced PDT effect of tumor in vivo.

5.
Chem Commun (Camb) ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31989129

RESUMO

A novel electron donor, namely, TMDBP is designed by angularly fusing two acridine moieties. The DMAC subunits in TMDBP exhibit a dominant quasi-equatorial conformation due to steric H-H repulsion. The new TADF emitters render excellent OLED performances with EQE up to 24.2% and small efficiency roll-off.

6.
J Control Release ; 320: 159-167, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31978443

RESUMO

Glucose-responsive insulin delivery system mimicking the function of pancreatic ß-cells to maintain blood glucose homeostasis would effectively alleviate diabetes. Here, a new glucose-responsive delivery (ZIF@Ins&GOx) for self-regulated insulin release was constructed by encapsulating insulin and glucose oxidase (GOx) into pH-sensitive zeolitic imidazole framework-8 (ZIF-8) nanocrystals. After entering the cavities of ZIF-8, glucose can be oxidized into gluconic acid by GOx, causing a decrease in local pH. Then, ZIF-8 nanocrystals would be degraded under the acidic microenvironment that in turn triggers the release of insulin in a glucose responsive fashion. In vitro studies indicated that the biological activity of insulin could be protected by the rigid structure of ZIF-8 and the release of insulin could be modulated in response to glucose concentrations. In vivo experiments demonstrated that a single subcutaneous injection of the ZIF@Ins&GOx would facilitate the stabilization of blood glucose level of normoglycemic state for up to 72 h in type 1 diabetes (T1D). The multifunctional insulin delivery system shows a new proof-of-concept for T1D treatment by using ZIF-8 nanocrystals loaded with insulin and enzyme.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31821965

RESUMO

Naringin has been documented to possess multiple pharmacological activities. Reported pharmacokinetic studies revealed that oral bioavailability of naringin was low, in contrast to its significant pharmacological effects. The in vivo distribution of naringin and derived metabolites might partly explain this discrepancy. In this study, an ultra-fast liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry system (UFLC-Q-TOF-MS/MS) was used for profiling the distribution of naringin and its metabolites in rat plasma and fourteen tissues after oral administration. Naringin was widely distributed and its concentrations in certain tissues were much higher than that in plasma, especially in trachea and lung. Moreover, a total of 23 flavonoid metabolites and 15 phenolic catabolites were screened. Naringenin glucuronides were principal metabolites in plasma, while free naringenin and naringenin-7-O-sulfate were the major molecular forms in most tissues. Meanwhile, phenolic catabolites derived from naringin were found to be abundant in liver and kidney. These pharmacokinetic results would be useful to explain the pharmacodynamics of naringin.

8.
Biomater Sci ; 8(2): 702-711, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31777864

RESUMO

Although chemotherapy is the most common method in clinical therapeutics with a straightforward mechanism, conventional anti-tumor drugs are still almost incapable of preventing the occurrence of tumor metastasis. In this study, we developed a multi-functional drug delivery system EINP@DOX consisting of a tea-derived polyphenol EGCG, iron ions and DOX. The system integrated the functions of tumor inhibition, diagnosis and metastasis prevention to achieve a systematic tumor treatment. The nanoscale size of EINP@DOX facilitated its accumulation in tumor tissues by means of the enhanced permeability and retention (EPR) effect, and it was then transferred to endosomes. The weakly acidic microenvironment in the endosomes of the tumor cells could destroy the coordination structure of EINP@DOX to realize the release of DOX for tumor therapy. Furthermore, the dissociative EGCG played the role of an adjuvant to restrain EMT and down-regulate the MMP levels, which could prevent the occurrence of tumor metastasis. Meanwhile, iron ions as superior magnetic resonance imaging (MRI) contrast agents provided visual evidence for the accurate location of EINP@DOX. In vitro and in vivo studies demonstrated that EINP@DOX showed a remarkable performance in tumor diagnosis and excellent therapeutic efficacy, inhibiting the metastasis of tumor cells effectively at the same time.

9.
J Agric Food Chem ; 68(1): 409-417, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31833363

RESUMO

Naringin has been documented to possess various bioactivities. Due to thorny endogenous interferences, the metabolism pathways of naringin and exact amounts of derived phenolic catabolites have not been definitely assigned. In this work, stable isotope-labeling-based liquid chromatography-mass spectrometry methods were developed to eliminate the endogenous interferences. [2',3',5',6'-D4]-naringin was orally administrated to rats. Urine and feces samples were collected and then analyzed with ultrahigh-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS). A total of 21 flavonoid metabolites and 11 phenolic catabolites were screened. The metabolism and catabolism pathways were proposed. Furthermore, deuterated naringin and its main metabolites were determined with rapid resolution liquid chromatography tandem triple quadrupole mass spectrometry (RRLC-QqQ-MS/MS). The overall recovery of ingested deuterated naringin was calculated as 56.9% without endogenous interferences. The obtained results provide essential information for further pharmacological studies of naringin.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Fezes/química , Flavanonas/química , Flavanonas/metabolismo , Marcação por Isótopo/métodos , Espectrometria de Massas/métodos , Animais , Medicamentos de Ervas Chinesas/metabolismo , Feminino , Flavanonas/urina , Masculino , Ratos , Ratos Sprague-Dawley
10.
World J Surg ; 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31863139

RESUMO

BACKGROUND: Cervical lymph node metastasis is a prognostic factor of papillary thyroid carcinoma (PTC). Skip metastasis (central lymph node negative and lateral lymph node positive) of PTC is not uncommon. This study aimed to retrospectively investigate the risk factors for skip metastasis in PTC and develop a prediction model for skip metastasis. METHODS: A total of 745 PTC patients underwent total thyroidectomy and central plus lateral lymph node dissection at the First Affiliated Hospital of Chongqing Medical University from January 2012 to December 2017. Clinicopathological characteristics were collected and analyzed. Univariate and multivariate analyses were performed to detect the risk factors for skip metastasis. A prediction model was established based on the results of multivariate analyses. RESULTS: The skip metastasis rate was 9.7% (72/745). Age > 55 years (OR 2.63, 95% CI 1.34-5.04, p = 0.004), tumor located in the upper portion (OR 4.15, 95% CI 2.30-7.63, p = 0.001), and unilaterality (OR 2.76, 95% CI 1.14-8.23, p = 0.040) were independent risk factors for skip metastasis. Clinically lymph node-negative (cN0) patients with tumor in the upper portion (24.6%, 43/175) had higher possibility of skip metastasis than those of clinically lateral lymph node-positive (cN1b) patients (5.9%, 10/169) (p = 0.001). The area under the receiver operating characteristic curve of prediction model was 0.734 and 0.740 in derivation group and validation group, respectively. However, skip metastasis was not associated with tumor-free survival rate of PTC patients (p = 0.274). CONCLUSION: Age > 55 years, tumor located in the upper portion, and unilaterality may increase the risk of skip metastasis. We developed the first prediction model for skip metastasis based on clinicopathological parameters in PTC patients.

11.
Chem Commun (Camb) ; 55(100): 15125-15128, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31782442

RESUMO

Fused twin-acridine scaffolds of TMQAC and MeTMQAC were designed as novel donors to construct new organic emitters. TMQAC-based emitters were TADF active, while the TADF character was turned off in MeTMQAC-based emitters by the extra methyl group. The TMQAC-based emitters exhibited high OLED performances, with external quantum efficiencies (EQEs) of up to 20.7%.

12.
Theranostics ; 9(26): 8026-8047, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31754379

RESUMO

Abnormal cell metabolism with vigorous nutrition consumption is one of the major physiological characteristics of cancers. As such, the strategy of cancer starvation therapy through blocking the blood supply, depleting glucose/oxygen and other critical nutrients of tumors has been widely studied to be an attractive way for cancer treatment. However, several undesirable properties of these agents, such as low targeting efficacy, undesired systemic side effects, elevated tumor hypoxia, induced drug resistance, and increased tumor metastasis risk, limit their future applications. The recent development of starving-nanotherapeutics combined with other therapeutic methods displayed the promising potential for overcoming the above drawbacks. This review highlights the recent advances of nanotherapeutic-based cancer starvation therapy and discusses the challenges and future prospects of these anticancer strategies.

13.
Front Pharmacol ; 10: 1128, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632272

RESUMO

Naoxintong capsule (NXT), a Chinese medicine, has performed excellent effects on the prevention and treatment against cardiovascular diseases. NXT is a fine powder mixture without any herb extraction, and there must be lots of ingredients hard to be absorbed. However, little is known about the correlation between the NXT's cardioprotective effects and gut microbiota. Herein, we report the effect of NXT on the development of cardiovascular diseases and clarify the correlation between NXT's cardioprotective effects and gut microbiota. In the current study, minipigs were selected and fed with high-fat diet and NXT daily for successive 8 months. During the process, up to 18 biomedical parameters were monthly determined to observe the dynamic changes after NXT treatment. At the end of experimental process, pathological examinations of heart, coronary artery, carotid artery, thoracic aorta, and abdominal aorta were conducted by HE staining and 16SrDNA sequencing, and analyzing of gut microbiota were conducted. Our results showed that NXT's effects against cardiovascular diseases were through regulating blood lipid profiles, inhibiting vascular inflammation, enhancing antioxidant capacity, and alleviating myocardial injury, without damages on liver and kidney particularly. Concurrently, we also found that long-term administration of NXT increased the diversity of gut microbiota, influenced the microbiome structure and composition stably, and revered the increase of the ratio of the Firmicutes to Bacteroidetes (F/B ratio) in relative abundance. Specifically, our results revealed some key bacterium of Caproiciproducens (enhanced), Sutterella (enhanced), Erysipelotrichaceae (enhanced), and Romboutsia (decreased) that were closely involved in NXT's effects. Taken together, our study demonstrates that NXT can inhibit the development of cardiovascular diseases by ameliorating high-fat diet-induced metabolic disorders and partly through improving gut microbiota.

14.
Angew Chem Int Ed Engl ; 58(49): 17651-17655, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31588647

RESUMO

Aggregation-induced emission (AIE), thermally activated delayed fluorescence (TADF), room-temperature phosphorescence (RTP), and mechanoluminescence (ML) have attracted widespread interest. However, a multifunctional organic emitter exhibiting simultaneous AIE, TADF, RTP, and ML has not been reported. Now, two multifunctional blue emitters with very simple structures, mono-DMACDPS and Me-DMACDPS, exhibit typical AIE, TADF, and RTP properties but different behavior in mechanoluminescence. Crystal structure analysis reveals that large dipole moment and multiple intermolecular interactions with tight packing mode endow mono-DMACDPS with strong ML. Combined with the data of crystal analysis and theoretical calculation, the separated monomer and dimer in the crystal lead to the typical TADF and RTP properties, respectively. Simple-structure mono-DMACDPS is the first example realizing TADF, RTP, AIE, and ML simultaneously.

15.
Adv Mater ; 31(43): e1904495, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31497903

RESUMO

Natural killer (NK) cells can not only recognize and eliminate abnormal cells but also recruit and re-educate immune cells to protect the host. However, the functions of NK cells are often limited in the immunosuppressive tumor microenvironment (TME). Here, artificial NK cells (designated as aNK) with minor limitations of TME for specific tumor killing and renegade macrophage re-education are created. The red blood cell membrane (RBCM) cloaks perfluorohexane (PFC) and glucose oxidase (GOX) to construct the aNK. The aNK can directly kill tumor cells by exhausting glucose and generating hydrogen peroxide (H2 O2 ). The generated H2 O2 is also similar to cytokines and chemokines for recruiting immune cells and re-educating survived macrophages to attack tumor cells. In addition, the oxygen-carried PFC can strengthen the catalytic reaction of GOX and normalize the hypoxic TME. In vitro and in vivo experiments display that aNK with slight TME limitations exhibit efficient tumor inhibition and immune activation. The aNK will provide a new sight to treat tumor as the supplement of aggressive NK cells.

16.
Thorac Cancer ; 10(10): 1936-1944, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31407509

RESUMO

BACKGROUND: Following drug resistance in patients with lung cancer treated by EGFR TKIs, a biopsy is required to obtain sufficient cancer tissue for T790M detection in order to select potential beneficiaries suitable for third-generation EGFR TKIs, such as osimertinib. The purpose of this study was to explore the feasibility of using a new in situ analysis technique based on RNA target sequences to detect EGFR T790M in lung cancer. METHODS: A total of 28 formalin-fixed paraffin-embedded (FFPE) samples from 24 lung adenocarcinoma patients archived in Peking Union Medical College Hospital from 2015 to 2016 were collected. The BaseScope T790M detection technique by in situ hybridization on FFPE slides was used to analyze the mutation of EGFR T790M, and then the results were compared with the data acquired by Scorpions ARMS assay, which is the so-called gold standard for EGFR gene mutation testing. The sensitivity and specificity of the BaseScope T790M detection technique were preliminarily evaluated. RESULTS: Of the 28 FFPE specimens, the average proportion of T790M-positive cells was 35.78% ± 17.68% in 18 samples with EGFR T790M, confirmed by Scorpions ARMS assay, Compared with real-time PCR assay, the sensitivity and specificity of BaseScope T790M were all 100% in our cohort. CONCLUSION: BaseScope T790M assay could be completed on only one FFPE slide and the visualized molecular result overplayed with histomorphological information perfectly, so it may be the alternative method for EGFR T790M evaluation. BaseScope assay has potential clinical utility, and it will be necessary to carry out validation with a large number of cases.

17.
J Pharm Biomed Anal ; 176: 112806, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31421286

RESUMO

Naoxintong Capsule (NXTC) is a well-known Traditional Chinese Medicine (TCM) medication that has been widely employed in the treatment of cardiovascular and cerebrovascular diseases. Although its chemical constituents had been characterized, the in vivo biotransformation of those components remain obscured. In this study, by applying the ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS), we have investigated the in vivo metabolism of NXTC in beagle dog urine and feces. After a single dose of oral administration, a total of 36 prototype compounds and 52 metabolites of NXTC were identified or tentatively characterized in beagle dog urine and feces. We have also proposed the in vivo transformation pathways of such metabolites including phase I (reduction, oxidation, hydroxylation, demethylation) and phase II reactions (glucuronidation, sulfation, methylation). For the first time, our results have unsealed the in vivo metabolic profiles of chemical components of NXTC in beagle dogs and added novel knowledge into the understanding of efficacy contributing compounds of NXTC that deserves further investigation.

18.
BMC Geriatr ; 19(1): 214, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31390985

RESUMO

BACKGROUND: Hearing loss is one of the most common modifiable factors associated with cognitive and functional decline in geriatric populations. An accurate, easy-to-apply, and inexpensive hearing screening method is needed to detect hearing loss in community-dwelling elderly people, intervene early and reduce the negative consequences and burden of untreated hearing loss on individuals, families and society. However, available hearing screening tools do not adequately meet the need for large-scale geriatric hearing detection due to several barriers, including time, personnel training and equipment costs. This study aimed to propose an efficient method that could potentially satisfy this need. METHODS: In total, 1793 participants (≥60 years) were recruited to undertake a standard audiometric air conduction pure tone test at 4 frequencies (0.5-4 kHz). Audiometric data from one community were used to train the decision tree model and generate a pure tone screening rule to classify people with or without moderate or more serious hearing impairment. Audiometric data from another community were used to validate the tree model. RESULTS: In the decision tree analysis, 2 kHz and 0.5 kHz were found to be the most important frequencies for hearing severity classification. The tree model suggested a simple two-step screening procedure in which a 42 dB HL tone at 2 kHz is presented first, followed by a 47 dB HL tone at 0.5 kHz, depending on the individual's response to the first tone. This approach achieved an accuracy of 91.20% (91.92%), a sensitivity of 95.35% (93.50%) and a specificity of 86.85% (90.56%) in the training dataset (testing dataset). CONCLUSIONS: A simple two-step screening procedure using the two tones (2 kHz and 0.5 kHz) selected by the decision tree analysis can be applied to screen moderate-to-profound hearing loss in a community-based geriatric population in Shanghai. The decision tree analysis is useful in determining the optimal hearing screening criteria for local elderly populations. Implanting the pair of tones into a well-calibrated sound generator may create a simple, practical and time-efficient screening tool with high accuracy that is readily available at healthcare centers of all levels, thereby facilitating the initiation of extensive nationwide hearing screening in older adults.

19.
Breast Cancer Res Treat ; 178(2): 275-281, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31388934

RESUMO

PURPOSE: Human epidermal growth factor receptor 2 (HER2) status is both an independent prognostic factor and a predictive factor for the efficacy of targeted therapy for breast cancer, so it is critical to accurately detect HER2 protein expression and/or gene amplification. According to the recommendations of the 2013 American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) guidelines for HER2 breast cancer testing, an additional test should be pursued on a different block from the same tumor as one of the options for patients with immunohistochemistry (IHC) 2+ and a HER2/CEP17 ratio of < 2.0 with an average HER2 signals per tumor cell of ≥ 4.0 and < 6.0 by reflex test using dual-probe fluorescence in situ hybridization (FISH) (double-equivocal HER2). Our aim in this study is to explore the consistency of HER2 status between the two blocks. METHODS: We retrospectively analyzed 5685 primary invasive breast cancers between April 2015 and January 2019 from Peking Union Medical College Hospital. For cases with double-equivocal HER2 revealed in initial blocks, HER2 gene status was evaluated by FISH in a different block from the same tumor. The FISH score was interpreted according to the 2013 ASCO/CAP guidelines for HER2 testing. RESULTS: In our cohort of 5685 specimens, the overall HER2 IHC3+, 2+, 1+ and 0 cases were 20.5%, 31.8%, 28.3%, and 19.5%, respectively. Then, 13.7%, 66.3%, and 20.0% of HER2 amplification, non-amplification, and equivocation rates were found, respectively, in IHC2+ patients (n = 1777) by reflex FISH assay. For specimens with double-equivocal HER2 (n = 333), HER2 status was assessed in another block from the same tumor by FISH and then the frequency of HER2 positive, negative, and equivocation was estimated at 5.7%, 22.5%, and 71.8%, respectively. Because double-equivocal HER2 cases are classified in the HER2 negative category by the 2018 ASCO/CAP HER2 testing guidelines, only 1.3% (19/1511) of HER2 positive patients were determined through additional HER2 testing in another block from the HER2 negative population. CONCLUSIONS: HER2 status in different blocks from the same tumor in primary invasive breast cancer was highly concordant. Our data supported the recommendation of the 2018 ASCO/CAP HER2 testing guidelines in breast cancer to remove the suggestion for additional HER2 testing using another block contained in the previous version.

20.
Nanotechnology ; 30(37): 375203, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31170702

RESUMO

Recently, molybdenum disulfide (MoS2), an emerging 2D material, has become an alternative candidate for ultra-sensitive biosensors due to its semiconducting behavior and the unique layer-by-layer atomic structure. Here, we report on highly stable and repeatable real-time pH sensing with few-layer MoS2 field-effect transistor (FET) biosensors, fabricated with both HfO2 and Al2O3/HfO2 gate dielectrics on top of MoS2 flakes exfoliated from natural crystals onto SiO2/Si samples. Both types of sensors demonstrate a highly linear, stable and repeatable response over a wide pH range with near-ideal pH sensitivity close to the theoretical limit of 59.6 mV pH-1. Ascribing from a different device operation regime in the pH sensing test-subthreshold regime for a sensor with an Al2O3/HfO2 dielectric and linear regime for a sensor with HfO2-a sensor with Al2O3/HfO2 shows significantly higher current sensitivity (∼105-fold) and relatively better linearity than a sensor with HfO2, while the latter shows relatively higher stability and higher repeatability. An Al2O3/HfO2-coated MoS2 FET reveals a high sensitivity or low detection limit of 0.01 pH.

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