Targeted Sub-Attomole Cancer Biomarker Detection Based on Phase Singularity 2D Nanomaterial-Enhanced Plasmonic Biosensor

Detection of small cancer biomarkers with low molecular weight and a low concentration range has always been challenging yet urgent in many clinical applications such as diagnosing early-stage cancer,monitoring treatment and detecting relapse.Here,a highly enhanced plasmonic biosensor that can overcome this challenge is developed using atomically thin two-dimensional phase change nanomaterial.By precisely engineering the configuration with atomically thin materials,the phase singularity has been successfully achieved with a significantly enhanced lateral position shift effect.Based on our knowledge,it is the first experimental demonstration of a lateral position signal change>340μm at a sensing interface from all optical techniques.With this enhanced plasmonic effect,the detection limit has been experimentally demonstrated to be 10^(-15) mol L^(−1) for TNF-α cancer marker,which has been found in various human diseases including inflammatory diseases and different kinds of cancer.The as-reported novel integration of atomically thin Ge_(2)Sb_(2)Te_(5) with plasmonic substrate, which results in a phase singularity and thus a giant lateral position shift, enables the detection of cancer markers with low molecular weight at femtomolar level. These results will definitely hold promising potential in biomedical application and clinical diagnostics.

Reporter gene systems for the identification and characterization of cancer stem cells

Cancer stem cells(CSCs)are tumor cells that share functional characteristics with normal and embryonic stem cells.CSCs have increased tumor-initiating capacity and metastatic potential and lower sensitivity to chemo-and radiotherapy,with important roles in tumor progression and the response to therapy.Thus,a current goal of cancer research is to eliminate CSCs,necessitating an adequate phenotypic and functional characterization of CSCs.Strategies have been developed to identify,enrich,and track CSCs,many of which distinguish CSCs by evaluating the expression of surface markers,the initiation of specific signaling pathways,and the activation of master transcription factors that control stemness in normal cells.We review and discuss the use of reporter gene systems for identifying CSCs.Reporters that are under the control of aldehyde dehydrogenase 1A1,CD133,Notch,Nanog homeobox,Sex-determining region Y-box 2,and POU class 5 homeobox can be used to identify CSCs in many tumor types,track cells in real time,and screen for drugs.Thus,reporter gene systems,in combination with in vitro and in vivo functional assays,can assess changes in the CSCs pool.We present relevant examples of these systems in the evaluation of experimental CSCs-targeting therapeutics,demonstrating their value in CSCs research.

2017 Chinese expert consensus on the clinical application ofserum marker for thyroid cancer

In recent years, the clinical incidence of thyroid cancer has been increasing year by year, and its risk assessment and clinical management methods have also been accordingly modified and constantly improved. There are great differences between the clinical diagnostic and therapeutic modes and disease management of thyroid cancer employed by various medical institutions in China, particularly with regard to the clinical application of serum marker of thyroid cancer. To this end, the China Anti-Cancer Association Thyroid Cancer Specialized Committee Chinese Association of Thyroid Oncology organized this compilation of ExpertConsensus on Clinical Application of Serum Marker of Thyroid Cancer to help and impel relevant clinical institutions and professionals to standardize clinical diagnosis, treatment, and long-term management of thyroid cancer, and to properly utilize the serum marker for scientific auxiliary clinical diagnosis and assessment of thyroid cancer before and after operation.

Ardisia gigantifolia ethanolic extract inhibits cell proliferation and targets cancer stem cells in gastric cancer

Objective:To evaluate the effects of ethanol extract from Ardisia gigantifolia leaves on cell proliferation and cancer stem cell(CSC)number in gastric cancer.Methods:The inhibitory effect of Ardisia gigantifolia extract on the proliferation of MKN45 and MKN74 gastric cancer cells was assessed using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay.Non-adherent culture(3D)model was used to evaluate the effect of the extract on tumorsphere size and number.Moreover,the expression of CD44,ALDH,and p21 was determined by immunofluorescence analysis.Flow cytometric analysis was performed to evaluate cell cycle arrest and the expression of gastric CSC markers CD44 and ALDH.Real-time PCR analysis was also carried out to assess the effect of the extract on the expression of cell cycle-regulated genes.Results:Ardisia gigantifolia extract effectively inhibited cell proliferation with an IC_(50)of 55.7μg/m L in MKN45 cells and 123.6μg/m L in MKN74 cells.The extract also arrested cell cycle in the G_(0)/G_(1)phase as well as significantly reduced the size and number of tumorspheres.The markedly increased expression of p21 was observed at both m RNA and protein levels in the extract-treated adherent cells and tumorspheres.In addition,Ardisia gigantifolia extract significantly reduced the number of CD44-and/or ALDH-expressing gastric CSC.Conclusions:The development of gastric CSC can be inhibited by the ethanol extract of Ardisia gigantifolia.

Deoxyribonucleic acid methylation driven aberrations in pancreatic cancer-related pathways

Pancreatic cancer(PanCa)presents a catastrophic disease with poor overall survival at advanced stages,with immediate requirement of new and effective treatment options.Besides genetic mutations,epigenetic dysregulation of signaling pathway-associated enriched genes are considered as novel therapeutic target.Mechanisms beneath the deoxyribonucleic acid methylation and its utility in developing of epi-drugs in PanCa are under trails.Combinations of epigenetic medicines with conventional cytotoxic treatments or targeted therapy are promising options to improving the dismal response and survival rate of PanCa patients.Recent studies have identified potentially valid pathways that support the prediction that future PanCa clinical trials will include vigorous testing of epigenomic therapies.Epigenetics thus promises to generate a significant amount of new knowledge of biological and medical importance.Our review could identify various components of epigenetic mechanisms known to be involved in the initiation and development of pancreatic ductal adenocarcinoma and related precancerous lesions,and novel pharmacological strategies that target these components could potentially lead to breakthroughs.We aim to highlight the possibilities that exist and the potential therapeutic interventions.

Biliary tract cancer stem cells-translational options and challenges

Management of biliary tract cancer remains challenging. Tumors show high recurrence rates and therapeutic resistance, leading to dismal prognosis and short survival. The cancer stem cell model states that a tumor is a heterogeneous conglomerate of cells, in which a certain subpopulation of cells-the cancer stem cells-possesses stem cell properties. Cancer stem cells have high clinical relevance due to their potential contributions to development, progression and aggressiveness as well as recurrence and metastasis of malignant tumors. Consequently, reliable identification of as well as pharmacological intervention with cancer stem cells is an intensively investigated and promising research field. The involvement of cancer stem cells in biliary tract cancer is likely as a number of studies demonstrated their existence and the obvious clinical relevance of several established cancer stem cell markers in biliary tract cancer models and tissues. In the present article, we review and discuss the currently available literature addressing the role of putative cancer stem cells in biliary tract cancer as well as the connection between known contributors of biliary tract tumorigenesis such as oncogenic signaling pathways, micro-RNAs and the tumor microenvironment with cancer stem cells.

Tissue-specific cancer stem/progenitor cells:Therapeutic implications

Surgical resection,chemotherapy,and radiation are the standard therapeutic modalities for treating cancer.These approaches are intended to target the more mature and rapidly dividing cancer cells.However,they spare the relatively quiescent and intrinsically resistant cancer stem cells(CSCs)subpopulation residing within the tumor tissue.Thus,a temporary eradication is achieved and the tumor bulk tends to revert supported by CSCs'resistant features.Based on their unique expression profile,the identification,isolation,and selective targeting of CSCs hold great promise for challenging treatment failure and reducing the risk of cancer recurrence.Yet,targeting CSCs is limited mainly by the irrelevance of the utilized cancer models.A new era of targeted and personalized anti-cancer therapies has been developed with cancer patient-derived organoids(PDOs)as a tool for establishing pre-clinical tumor models.Herein,we discuss the updated and presently available tissue-specific CSC markers in five highly occurring solid tumors.Additionally,we highlight the advantage and relevance of the threedimensional PDOs culture model as a platform for modeling cancer,evaluating the efficacy of CSC-based therapeutics,and predicting drug response in cancer patients.

The Protective Role of β-Carotene and Hesperidin on Some Hematological and Myocardial Measurements against Imidacloprid Toxicity in Albino Rats

Neonicotinoids including IM （Imidacloprid） are widely used as plant systemic insecticides. Several studies have indicated that pesticide toxicity may be associated with the enhanced production of ROS （reactive oxygen species）. Both β-carotene （I3C） and hesperidin （H） have an antioxidant property and quench free radicals. This study aimed to clarify the protective role of β-carotene and hesperidin as natural antioxidants on IM induced toxicity in hematological parameters and markers of cardiac muscle activity in male albino rats. The treatment of rats with IM showed a significant decrease in hemoglobin （Hb %）, MCH （mean corpuscular hemoglobin）, MCHC （mean corpuscular hemoglobin concentration）, HCT （hematocrit） values and RBCs count comparing with control group. On the other hand, MCV （mean corpuscular volume）, WBCs （white blood cells） and Pits （platelets） count pronounced a significant increase in IM group comparing to control. Also, αFP （plasma alpha fetoprotein）, CEA （carcinoembryonic antigen）, CK （creatine kinase）, CK-MB （creatine phosphokinase myocardial band） and LDH （lactate dehydrogenase） clarify a significant increase in IM group comparing to control. Both β-carotene and hesperidin mitigate the deleterious effects of IM on previous parameters. β-Carotene and hesperidin may protect hematopoietic system and heart muscle against toxicity of IM. These improvements of the results clarify the protective effect of the used antioxidants. Conclusion： β-carotene and hesperidin, natural antioxidants, have a protective effect against IM evoked hematological and biochemical changes.

Structure regulation for ultra-high luminescence quantum yield lanthanide complex and simultaneous detection of cancer marker and ferrous ion

The exploitation of a highly selective and sensitive probe to detect both cancer marker and metal ion is of great importance.In this work,the "one stone two bird" agent of 1,10-phenanthroline(phen) is designed to disrupt the polymeric lanthanide MOFs(LnMOFs,[Ln(CHO_(2))_(3)]n,Ln=Tb,la;Eu,1 b,CHO_(2)=formic acid) {[Ln(CHO_(2))_(4)·(C_(2) H_(8) N)]n,Ln=Y,2 a;Gd,2 b;Dy,2 c,C_(2)H_(8) N=dimethylamine}) into a soluble mononuclear species [Ln(phen)_(2)(NO_(3))_(3),Ln=Tb,3 a;Eu,3 b] as well as to provide an antenna for efficient photons absorption,resulting in an ultra-high luminescence quantum yield(QY,90%) europium complex.The luminescence QY is among the highest record of monomeric(zero-dimensional) lanthanide complexes.Furthermore,mononuclear Tb3+complex(3 a) functions as a multiplex sensor towards both Fe^(2+)and cancer marker of 5-hydroxyindole-3-acetic acid(5-HIAA).Importantly,the limit of detection(LOD)for sensing 5-HIAA is an ultra-sensitive value of 1 × 10 s mol/L,which is even lower than that necessary for the early diagnosis of carcinoid tumors.More interestingly,sensing results in simulated urine reveals that 3 a has potential application for early diagnosis in the clinic.

Molecular insights into colorectal cancer stem cell regulation by environmental factors

Colorectal cancer remains a signifi cant cause of cancer-related mortality worldwide,mainly because of tumor relapse and metastases.Cancer stem cells(CSCs)are considered to be the main cause of resistance to chemotherapeutic agents,as well as being responsible for distant metastases.Although CSCs themselves possess innate abilities for self-renewal and differentiation,the environment surrounding CSCs provides oxygen,nutrients and secreted factors,and also supports angiogenesis,thus it's responsible for maintaining their CSC properties.Furthermore,extensive investigations have revealed that obesity,accompanied by excess visceral adipose tissue,induces chronic infl ammation,and is linked to the risk and progression of several gastrointestinal cancers,through modulating the capacities of the CSCs.This review presents the evidence linking colorectal CSCs and their environment and summarizes our current understanding of the molecular mechanisms underlying this relationship.

Clonality: A New Marker for Gastric Cancer Survival

Continuous efforts have been made to identify molecular markers for the prognosis of gastric cancer, the second leading cause of cancer death accounting for 10% of cancer mortality worldwide （Ferlay et al., 2010; Chen et al., 2013）. Studies using candidate gene approach, GWAS （genome-wide asso- ciation study）, and expression profiling have reported markers significantly associated with gastric cancer survival （Luo et al., 2011; Kang et al., 2014; Song et al., 2014）, and these markers have contributed to the clinical prediction of patients＇ outcome. However, gastric cancer is a highly heterogeneous disease etiologically, clinically, and pathologically. In this sense, it is plausible that single markers like DNA sequence variation, or gene/microRNA expression cannot fully reflect the heterogeneous survival of gastric cancer.

PROSPECTIVE STUDY OF MULTIPLE GENETIC TUMOR MARKER ASSAY BY QUANTITATIVE REAL-TIME PCR TO PREDICT RECURRENCE IN COLORECTAL CANCER PATIENTS

Objective To describe correlation between multiple genetic tumor markers,carcinoembryonic antigen (CEA),cytokeratin 20 (CK20),and Survivin,and clinicopathological features of colorectal cancer (CRC) and to assess prognostic diagnosis value in cancer recurrence and metastasis.Methods A total of 92 patients with CRC,68 patients with precancerous lesions,and 29 control volunteers were collected for the detection of CEA,CK20,and Survivin expressions by using quantitative Real-Time PCR technology.Associations among these measurements and clinicopathological features of CRC,and cancer recurrence and metastasis rates in 4-year follow-up were analyzed.Results No mRNA expressions of CEA,CK20,or Survivin were detected in the control group.Expressions of CEA,CK20,and Survivin were 41.3%,47.8%,and 72.8% in CRC patients,respectively.The expressions of genetic tumor markers were related to the clinical stage and lymph node metastasis.In patients with Survivin high expression,4-year survival rate was significantly lower than that in Survivin low expression.The multiple tumor markers assay for CRC patients showed higher specificity and positive detection rate than single marker assay.Patients with CEA,CK20,and Survivin simultaneous expressions had significantly higher 4-year recurrence rate and death rate than those with only one or two markers expression.ConclusionMultiple tumor markers assay including CEA,CK20,and Survivin in peripheral blood by quantitative Real-Time PCR can be an ideal method for the surveillance of the recurrence and prognosis for CRC patients.

Highly sensitive luminescent lanthanide metal-organic framework sensor for L-kynurenine

L-kynurenine(L-kyn)is a marker of prostate cancer.At present,the expensive instruments are usually applied to detect L-kyn clinically,which limits its wide application for cancer diagnosis.Herein,three lanthanide metal-organic frameworks([Ln(CHO_(2))_(3)]_(n),Ln=Eu,Gd,and Tb)were designed and obtained,and detailly characterized by single crystal X-ray diffraction(SCXRD),powder X-ray diffraction(PXRD),Fourier transform infrared spectroscopy(FT-IR),thermogravimetric analysis(TGA),and luminescence spectroscopy.Further study reveals that[Tb(CHO_(2))_(3)]_(n)is a highly selective,ultra-sensitive,of strong anti-interference,highly stable,and non-expensive sensor for prostate cancer marker L-kyn.The limit of detection(LOD)for L-kyn sensing is a highly sensitive value of 1.0×10^(−9)mol/L.Furthermore,the sensing mechanism is discussed in detail.

Toehold-mediated strand displacement reaction-propelled cascade DNAzyme amplifier for microRNA let-7a detection

DNAzyme amplifiers have been extensively explored as a useful sensing platform,but single DNAzyme amplifier is limited in biosensing applications by its low sensitivity.Herein,a cascade DNAzyme amplifier was designed by exploiting concurrent amplification cycle principles of toehold-mediated strand displacement reaction(TSDR)and Zn^(2+)-assisted DNAzyme cycle with lower cost and simpler procedures.Compared with single DNAzyme amplifier,the proposed TSDR-propelled cascade DNAzyme amplifier exhibited higher sensitivity by releasing more DNAzyme through TSDR to cleave substrate strand during the DNAzyme cycle.Base on this,let-7a could be sensitively detected in the range of 5-50 nmol/L with a detection limit of 64 pmol/L.Furthermore,the dual signal amplification strategy of the cascade DNAzyme amplifier exhibited excellent selectivity to distinguish single-base mismatched DNA strands,which has been successfully applied to the determination of let-7a in blood serum,showing high promise in early cancer diagnosis.