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Background: Colon cancer with liver metastases (CCLM) characterized by genetic heterogeneity is an evolutionary process leading to variations in response to selective pressure, but the underlying evolutionary models still remains unclear. Methods: Total of 30 samples, including primary tumor and two to four matched liver metastases from 8 treatment-naïve patients with CCLM were collected, and subjected to whole-exome DNA sequencing. PyClone was used to calculate intra and inter-tumor heterogeneity, LICHeE was used to reconstruct the cancer phylogeny trees and investigate the subclonal composition. Results: The genetic differences were observed between primary and metastatic lesions, as well as among multiple metastases in all patients. The natural history models of colorectal cancer in each case were identified, including parallel, linear, and branching evolution. Liver metastases could originate from primary lesions or other metastases. Pathway and process enrichment analysis also showed obvious heterogeneity and enhancement of several molecular functions. Conclusions: Our data reveal the genetic and heterogeneity between primary and metastatic lesions, as well as among multiple metastases and provide genomic evidence for clonal heterogeneity for CCLM. [ABSTRACT FROM AUTHOR]

Purpose: Platelets contain a rich repertoire of RNA species, such as mRNAs and long non-coding RNAs. During the development of tumors, platelets are "educated" by cancer cells, altering their transcriptome and molecular content, thereby, tumor educated platelet (TEP) lncRNA profile has the potential to diagnose lung cancer. The current study was aimed to examine whether TEPs might be a potential biomarker for lung cancer. Methods: Platelet precipitation was obtained by low-speed centrifugation. TEP linc-GTF2H2-1, RP3-466P17.2, and lnc-ST8SIA4-12 were selected by lncRNA microarray and validated by qPCR in a large cohort of lung cancer patients and healthy donors. Besides, we analyzed the association of their expression levels with clinicopathological features. Results: TEP linc-GTF2H2-1 and RP3-466P17.2 were significantly downregulated, while lnc-ST8SIA4-12 was significantly upregulated in patients with lung cancer or with early-stage lung cancer as compared to healthy donors, possessing AUCs of 0.781, 0.788, 0.725 for lung cancer and 0.704, 0.771, 0.768 for early-stage lung cancer, respectively. Notably, their combination demonstrated the markedly elevated AUCs of 0.921 for lung cancer and 0.895 for early-stage lung cancer. Besides, the combination of TEP linc-GTF2H2-1 was capable to facilitate diagnostic efficiencies of CEA, Cyfra21-1, or NSE to distinguish advanced-stage lung cancer patients from early ones, with an AUC of 0.899 based on the integration of these four factors. Conclusion: Our data suggested that lncRNAs sequestered in TEPs enabled blood-based lung cancer diagnosis and progression prediction. [ABSTRACT FROM AUTHOR]

Background: During the development of tumors, tumors "educate" platelets causing changes in their mRNAs expression profiles and phenotypes, thereby, tumor-educated platelet (TEP) mRNA profile has the potential to diagnose lung cancer. The current study aimed to examine whether TEPs might be a potential biomarker for lung cancer diagnostics. Methods: Platelet precipitation was obtained by low-speed centrifugation and subjected to Trizol for total RNA extraction. Platelet MAX, MTURN, and HLA-B mRNA were selected by microarray, validated by qPCR, and analyzed combined with related clinical factors. Results: Our results showed that a three-platelet mRNA set: MAX, MTURN, and HLA-B was significantly up-regulated in lung cancer patients as well as in early-stage lung cancer patients compared with those from healthy donors, the area under the curve (AUC) was 0.734, 0.787, respectively, among which platelet MTURN mRNA processed a dramatically high diagnostic efficiency in female patients with lung cancer, its AUC for female was 0.825. More importantly, the three-platelet mRNA set: MAX, MTURN, and HLA-B was associated with chemotherapeutic effect, low mRNA expression of this three-platelet set was correlated with "favorable" first chemotherapy response. Conclusions: A three-platelet mRNA set: MAX, MTURN and HLA-B enables blood-based lung cancer diagnosis and chemotherapy response prediction. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to determine the optimal time to perform sentinel lymph node biopsy (SLNB) for patients with clinically node-negative (cN0) disease following neoadjuvant chemotherapy (NAC). Method: From April 2008 to April 2018, 592 patients with breast cancer underwent after NAC were included in this study. Patients with cN0 before and ycN0 disease after NAC received SLNB and axillary lymph node dissection (ALND) in case of positive sentinel lymph nodes (SLNs). For patients with clinically node-positive (cN+) disease, the axillary surgery is based on the doctor's decision. Result: In general, 17.6% (104/592) of patients achieved total pathologic complete response (pCR), which was 6.9%, 33.3%, 32.3% and 15.3%, respectively, among patients with hormone receptor (HR) positive/ human epidermal growth factor receptor-2 (HER-2) negative (HR+/HER2−) subtype, triple-negative (TN) subtype, HER-2 positive (HER2+) subtype with and without targeted therapy (p < 0.001). Among the 525 cN+ patients, the axillary nodal pCR (apCR) rate was 34.5%, and the apCR rate was significantly higher in patients with HER2+ (58.6% with and 28.2% without targeted therapy respectively) and TN subtype (53.2%) than that in patients with HR+/HER2−subtype (21.2%, p < 0.001). Among the 67 cN0 patients, the positive rate of SLNs was 19.4% (13/67), which was 28.1% (9/32), 13.3% (2/15) and 10.0% (2/20), respectively, among patients with HR+/HER2−, TN and HER2 + subtypes. Conclusion: The pCR rates were significantly related to molecular subtype. Combining the apCR rates in different molecular subtypes of cN+ patients and the excellent locoregional control of AOSOG Z0011 and AMAROS trials in cN0 patients, it would be preferable to perform SLNB prior to NAC for cN0 patients with HR+/HER2− subtype, and SLNB after NAC for those cN0 patients with TN and HER2+ subtype to increase the chance of avoiding ALND. Among cN0 patients, TN and HER2 + subtypes would benefit more from axillary de-escalating surgery after NAC than HR+/HER2− subtype. [ABSTRACT FROM AUTHOR]

The authors describe a new kind of enzymatic glucose assay. The strategy involves three processes: (a) Generation of HO via glucose oxidase catalyzed oxidation of glucose; (b) production of 2,3-diaminophenazine (DAP) from HO and o-phenylenediamine (OPD) via peroxidase-catalyzed oxidation; and (c) a reduction of the blue fluorescence of SiNPs with emission maxima at 445 nm via an inner filter effect that is caused by DAP which is yellow and has an absorption peak at 450 nm. Fluorescence drops with increasing glucose concentrations in the 0.01 to 7 mM concentration range, and the detection limit is 3.5 μM. The assay was successfully applied to the analysis of glucose in human serum. [ABSTRACT FROM AUTHOR]

Background: Mutant Phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit alpha ( PIK3CA) has been shown to be associated with the occurrence, development and prognosis in colorectal cancer (CRC). However, its detection has been limited because of complicated procedures and the low sensitivity of the present approaches. Methods: We established an ultra-sensitive peptide nucleic acid-mediated polymerase chain reaction (PNA-PCR) assay to detect PIK3CA gene mutation in exon 9 and exon 20 with cell-free DNA (cfDNA). Using this technology, we detected the mutation status of PIK3CA in 128 colorectal cancer patients. 6 CRC patients receiving targeted therapy were chosen at random to undergo continuous PIK3CA mutation detection. Results: The results showed that the sensitivity of PNA-PCR clamping method was 0.1% for the exon 9 and 0.2% for the exon 20 variant alleles. When the PIK3CA mutation status was determined by PNA-PCR plus sequencing, 38.3% (49/128) of CRC carried at least one mutation, either E545Kor H1047R. The clinic-pathological parameters of age ( p = 0.358), gender ( p = 0.622), disease stage ( p = 0.353) and disease location ( p = 0.307) were not associated with the PIK3CA mutation. In the continuous monitoring study, we found that the gene status was associated with the effect of treatment. Furthermore, when the PIK3CA variant was determined by only the PNA-PCR method, there was a good linear relationship between ΔCp values and the proportion of variant DNA. The accuracy of PNA-PCR was 93.75 and 92.27% respectively when the cut-off values of ΔCp at 9.0 and 8.0 were set for determining the E545K and H1047R mutations. Conclusions: A simple, noninvasive, ultra-sensitive PNA-PCR technology was developed and was especially suitable for the dynamic detection of PIK3CA variants using cfDNA. [ABSTRACT FROM AUTHOR]

We report on the synthesis of flower-like 3D titanium dioxide (fl-TiO) using a hydrothermal method. This material possesses a large specific surface and displays an electrochemiluminescence (ECL) intensity that is much stronger than the one of TiO nanoparticles having smooth surfaces. It was used to label the secondary antibody in a sandwich immunoassay. A thin layer of metallic gold (Au) and palladium (Pd) was deposited on an indium tin oxide (ITO) electrode by code-position at a potential of 0.2 V in the respective chloride solutions. The Au/Pd-modified ITO electrode showed good conductivity. An ECL based immunoassay for the prostate specific antigen (PSA) was then worked out by immobilizing the first antibody on the Au/Pd layer on the ITO electrode, then exposing the electrode to a sample containing PSA, then forming the sandwich with the fl-TiO labeled secondary antibody, and finally measuring the intensity of ECL at a potential of −1.5 V. This ECL sensor has a response range that extends from 0.001 to 600 ng∙mL, a lower detection limit of 0.32 pg∙mL, good specificity, acceptable stability and good reproducibility. It gave satisfactory results when used for the determination of PSA in (spiked) diluted solutions of human serum. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

We have prepared carbon dots (C-dots) by pyrolysis of citric acid. The one-pot synthetic strategy is time-saving and simple and the resulting C-dots display blue luminescence with high quantum yield at an anodic potential of +0.6 V. An electrochemiluminescence (ECL) immunoassay was designed for the sensitive determination of cancer antigen 125 (CA125) by using amino-functionalized mesoporous silica nanoparticles (NH-MSNs) capped with C-dots. These act as amplification labels on a novel kind of paper working electrode modified with silver nanoparticles (Ag-PWE). This electrode was fabricated by a seed-mediated growth approach and served as a support for the attachment of the antibody. The NH-MSNs possess higher volume-to-surface ratio than the solid nanoparticles that can carry more C-dots which improves the sensitivity of the immunoassay. The ECL immunoassay was operated by using triethanolamine as a coreactant that is less toxic and more soluble than other popular coreactants. The assay has a linear response over a wide range of 0.01-50 U mL, and the detection limit is 4.3 mU mL. This makes the method one of the most sensitive assays for CA125. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

An easy-to-operate sandwich-type electrochemiluminescence (ECL) immunosensor was constructed on a glassy carbon electrode in this work. In order to fabricate a high-performance sensor, Au-Pt nanoparticles were electrodeposited onto the electrode surface, where they acted as the immunosensing platform, greatly improving the electronic transmission rate and increasing the amount of PSA primary antibody (PSA-Ab) present. To increase the sensitivity of the sensor even further, stable CdTe/ZnO nanoparticles were synthesized, characterized by scanning electron microscopy, and then employed to label PSA secondary antibody (PSA-Ab). When the appropriate antigen was recognized by this antibody, PSA-Ab, PSA, and PSA-Ab formed a sandwich-type immunocomplex that produced ECL in the presence of SO coreactant. Under optimal conditions, the ECL immunosensor showed a good linear range (0.0025-100.0 ng cm) and a low detection limit (1.0 pg cm). It was therefore demonstrated that the proposed strategy is a repeatable, stable, and potent method that can be expanded to detect other proteins. Graphical Abstract: [Figure not available: see fulltext.]. [ABSTRACT FROM AUTHOR]

In this work, an easy approach was reported to synthesize novel poly(acrylic acid) coated FeO magnetic nanoparticles which showed high water solubility and biocompatibility. Primary antibodies were immobilized onto the surface of the prepared nanoparticles using cysteine as a coupling agent. A large number of negatively charged CdTe quantum dots were coated on the poly(diallyldimethylammonium chloride) coated carbon nanotubes via self-assembly electrostatic reactions, and used as carriers of secondary antibodies, which could significantly amplify the electroluminescence signal. Coupled with a microfluidic strategy, the electroluminescence immunosensors could be easily separated and assembled on the surface of indium tin oxide glass with external magnetic forces. With a sandwich-type immunoassay format, the electroluminescence intensity increased linearly with the logarithm of the human chorionic gonadotrophin concentration in the range of 0.005-50 ng cm and the detection limit was 2.8 pg cm. In particular, this approach has the advantages of high sensitivity, specificity, and stability and could become of great promise for clinical application. Graphical Abstract: [Figure not available: see fulltext.]. [ABSTRACT FROM AUTHOR]

We describe here the preparation of carbon-coated Fe 3O 4 magnetic nanoparticles that were further fabricated into multifunctional core/shell nanoparticles (Fe 3O 4@C@CNCs) through a layer-by-layer self-assembly process of carbon nanocrystals (CNCs). The nanoparticles were applied in a photoluminescence (PL) immunosensor to detect the carcinoembryonic antigen (CEA), and CEA primary antibody was immobilized onto the surface of the nanoparticles. In addition, CEA secondary antibody and glucose oxidase were covalently bonded to silica nanoparticles. After stepwise immunoreactions, the immunoreagent was injected into the PL cell using a flow-injection PL system. When glucose was injected, hydrogen peroxide was obtained because of glucose oxidase catalysis and quenched the PL of the Fe 3O 4@C@CNC nanoparticles. The here proposed PL immunosensor allowed us to determine CEA concentrations in the 0.005–50 ng · mL -1 concentration range, with a detection limit of 1.8 pg · mL -1. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

We report on an ultrasensitive fluorescence immunoassay for human chorionic gonadotrophin antigen (hCG). It is based on the use of silica nanoparticles coated with a copolymer (prepared from a fluorene, a phenylenediamine, and divinylbenzene; PF@SiO 2) that acts as a fluorescent label for the secondary monoclonal antibody to β-hCG antigen. In parallel, Fe 3O 4 nanoparticles were coated with polyaniline, and these magnetic particles (Fe 3O 4@PANI) served as a solid support for the primary monoclonal antibody to β-hCG antigen. The PF@SiO 2 exhibited strong fluorescence and good dispersibility in water. A fluorescence sandwich immunoassay was developed that enables hCG concentrations to be determined in the 0.01–100 ng·mL −1 concentration range, with a detection limit of 3 pg·mL −1. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Purpose: To find new signaling pathways that may be involved in the cellular response to ionizing radiation. Methods: Two radioresistant subclones (A549/R and SPCA1/R) derived from lung adenocarcinoma cell lines A549 and SPCA1 were established after eight rounds of sublethal irradiation. The new subclones were tested for radioresistant features using clonogenic assay and apoptosis analysis. The genes expressed differentially were screened with cDNA microarray analysis consisting of 48,000 transcript probes and confirmed by quantitative real-time PCR. Results: Stable and significant radioresistance was observed in the screened subclones. The microarray analysis showed 65 genes were up-regulated and 141 genes down-regulated in SPCA1/R cells. The up-regulated and down-regulated genes were 708 and 230 in A549/R cells, respectively. Twenty-seven altered genes were consistent in both subclones. Interestingly, members the of human solute carrier (SLC) gene superfamily were among in 27 genes. Conclusions: The differentially expressed genes in both cell lines may contribute to their radioresistant phenotype. This extensive list of genes identified in the experiment provides a large body of potentially valuable information for studying the molecular mechanism(s) of radiosensitivity and identification of candidate molecular markers of radiation sensitivity. Thus, to our knowledge, the SLC gene superfamily is the first being reported to involve in acquired radioresistance. [ABSTRACT FROM AUTHOR]