Recent advances in living cell nucleic acid probes based on nanomaterials for early cancer diagnosis

The early diagnosis of cancer is vital for effective treatment and improved prognosis. Tumor biomarkers, which can be used for the early diagnosis, treatment, and prognostic evaluation of cancer, have emerged as a topic of intense research interest in recent years. Nucleic acid, as a type of tumor biomarker, contains vital genetic information, which is of great significance for the occurrence and development of cancer. Currently, living cell nucleic acid probes, which enable the in situ imaging and dynamic monitoring of nucleic acids, have become a rapidly developing field. This review focuses on living cell nucleic acid probes that can be used for the early diagnosis of tumors. We describe the fundamental design of the probe in terms of three units and focus on the roles of different nanomaterials in probe delivery.

Controversies in the diagnosis and management of early gastric cancer

Early diagnosis and treatment is the key to improving the prognosis of gastric cancer. The past decades have wimessed the rapid advances in the diagnosis and management of early gastric cancer （EGC）： endoscopy has played an increasingly important role, whereas laparoscopic techniques have also been introduced for EGC treatment. In China, the proportion of EGC is gradually increasing, and this condition will soon become a hot research topic. In this article, we will elucidate some major controversies in the diagnosis and management of EGC.

Upgrading the definition of early gastric cancer: better staging means more appropriate treatment

Since Murakami defined early gastric cancer(EGC) as a "carcinoma limited to the gastric mucosa and/or submucosa regardless of the lymph node status", several authors have focused on the most influential histopathological parameters for predicting the development of lymph node metastases by considering the lymph node status as an important prognostic factor. A few authors have also considered the depth of invasion as one of the keys to explaining the existence of subgroups of patients affected by EGC with poor prognoses. In any case, EGC is still considered an initial phase of tumor progression with good prognosis. The introduction of modern endoscopic devices has allowed a precise diagnosis of early lesions, which can lead to improved definitions of tumors that can be radically treated with endoscopic mucosal resection or endoscopic submucosal dissection(ESD). Given the widespread use of these techniques, the Japanese Gastric Cancer Association( JGCA) identified in 2011 the standard criteria that should exclude the presence of lymph node metastases. At that time, EGCs with nodal involvement should have been asserted as no longer fitting the definition of an early tumor. Some authors have also demonstrated that the morphological growth pattern of a tumor, according to Kodama's classification, is one of the most important prognostic factors, thereby suggesting the need to report it in histopathological drafts. Notwithstanding the acquired knowledge regarding the clinical behavior of EGC, Murakami's definition is still being used. This definition needs to be upgraded according to the modern staging of the disease so that the appropriate treatment would be selected.

Determination of breath isoprene in 109 suspected lung cancer patients using cavity ringdown spectroscopy

Background:Lung cancer is one of the most common malignant tumors worldwide.Currently,effective screening methods for early lung cancer are still scarce.Breath analysis provides a promising method for the pre-screening or early screening of lung cancer.Isoprene is a potential and important breath biomarker of lung cancer.Material and Methods:To investigate the clinical value of isoprene for diagnosing lung cancer patients,a cavity ringdown spectroscopy(CRDS)based near-real time,sensitive analysis method of breath isoprene is developed in our lab.In this paper,92 breath samples from lung cancer patients,17 breath samples from patients with benign lesions,and 107 breath samples from healthy people were collected.Results:Research indicates that breath isoprene concentration is significantly higher in healthy individuals(221:3±122:2 ppbv)than in patients with lung cancer(112:0±36:6 ppbv)and benign lung lesions(127:9±41:2 ppbv).The result of Receiver Operating Characteristic(ROC)curve suggests that the concentration of isoprene is meaningful for the diagnosis of lung cancer(AUC=0:822,sensitivity=63:6%,specificity=90:2%,P<0:01).Conclusion:This study demonstrates that the CRDS breath isoprene analysis system can effectively analyze a large sample of human breath isoprene,and preliminarily confirms the use of breath isoprene as a biomarker for lung diseases.

Uptake and outcomes of small intestinal and urinary tract cancer surveillance in Lynch syndrome

BACKGROUND Lynch syndrome(LS)is a hereditary cancer predisposition syndrome associated with increased risk of multiple cancers.While colorectal cancer surveillance decreases mortality in LS and is recommended by guidelines,there is lack of evidence for the efficacy of surveillance for extra-colonic cancers associated with LS,including small intestinal cancer(SIC)and urinary tract cancer(UTC).Given the limited evidence,guidelines do not consistently recommend surveillance for SIC and UTC,and it remains unclear how often individuals will choose to undergo and follow through with extra-colonic surveillance recommendations.AIM To study factors associated with SIC and UTC surveillance uptake and outcomes in LS.METHODS This is an IRB-approved retrospective analysis of individuals with LS seen at a tertiary care referral center.Included individuals had a pathogenic or likely pathogenic variant in MLH1,MSH2,MSH6,PMS2,or EPCAM,or were a confirmed obligate carrier,and had at least one documented visit to our center.Information regarding SIC and UTC surveillance was captured for each individual,and detailed personal and family history was obtained for individuals who had an initial LS management visit in our center’s dedicated high-risk LS clinic between January 1,2017 and October 29,2020.During these initial management visits,all patients had in-depth discussions of SIC and UTC surveillance with 1 of 3 providers experienced in LS management to promote informed decision-making about whether to pursue SIC and/or UTC surveillance.Statistical analysis using Pearson’s chi-squared test and Wilcoxon rank-sum test was completed to understand the factors associated with pursuit and completion of SIC and UTC surveillance,and a P value below 0.05 was deemed statistically significant.RESULTS Of 317 individuals with LS,86(27%)underwent a total of 105 SIC surveillance examinations,with 5 leading to additional work-up and no SICs diagnosed.Additionally,99(31%)patients underwent a total of 303 UTC surveillance examinations,with 19 requiring further evaluation and 1 UTC identified.Of 155 individuals who had an initial LS management visit between January 1,2017 and October 29,2020,63(41%)chose to undergo SIC surveillance and 58(37%)chose to undergo UTC surveillance.However,only 26(41%)and 32(55%)of those who initially chose to undergo SIC or UTC surveillance,respectively,successfully completed their surveillance examinations.Individuals with a pathogenic variant in MSH2 or EPCAM were more likely to initially choose to undergo SIC surveillance(P=0.034),and older individuals were more likely to complete SIC surveillance(P=0.007).Choosing to pursue UTC surveillance was more frequent among older individuals(P=0.018),and females more frequently completed UTC surveillance(P=0.002).Personal history of cancer and family history of SIC or UTC were not significantly associated with electing nor completing surveillance.Lastly,the provider discussing SIC/UTC surveillance was significantly associated with subsequent surveillance choices.CONCLUSION Pursuing and completing SIC/UTC surveillance in LS is influenced by several factors,however broad incorporation in LS management is likely unhelpful due to low yield and frequent false positive results.

An Approach to the Simultaneous Detection of Multiple Biomarkers for the Early Diagnosis of Liver Cancer Using Quantum Dot Nanoprobes

Biomarker-based early diagnosis of liver cancer is of high clinical value for reducing the mortality rate.However,it has been challenging to establish early detection methods with a single biomarker such as alpha-fetoprotein(AFP)because of limited diagnostic sensitivity and specificity.Therefore,developing multiplexed biomarker detection assays is crucially important for early diagnosis.Yet,simultaneous detection methods involving three or more biomarkers have been scarce.Here we suggest employing the serological biomarker panel of glypican-3(GPC3),dickkopf-1(DKK1),and AFP for liver cancer detection.We present a rapid simultaneous detection approach for the biomarker panel labeled with three fluorescent quantum dot nanoprobes(emission wavelengths at 565 nm,605 nm,and 655 nm).As a proof-of-concept,simultaneous fluorescence detection of the biomarker panel was demonstrated using mixed reference samples containing human recombinant GPC3,DKK1,and AFP antigens.Our simultaneous detection approach conferred a linear range of 0.625–2.5 ng·mL^(-1)for the entire biomarker panel,which merits further clinical validation for the simultaneous and accurate determination of the biomarker panel in human serum samples.

Era of Barrett’s surveillance: Does equipment matter?

Barrett’s esophagus is a consequence of long standing gastro-esophageal reflux disease and predisposes to the development of esophageal adenocarcinoma. Regular surveillance endoscopies can detect curable early neoplasia in asymptomatic patients, which in turn could improve the prognosis compared to symptomatic cancer. Early neoplastic lesions, which are amenable for local therapy, could be treated endoscopically, avoiding a major surgery. However, in the absence of obvious mucosal lesions, random four quadrant biopsies are done, which is associated with significant sampling error. Newer imaging modalities, such as autofluorescence endoscopy, are helpful in detecting subtle lesions that could be examined in detail with narrow band imaging to characterize and target biopsies. This has the potential benefit of reducing the number of random biopsies with a better yield of dysplasia. Confocal endomicroscopy provides "optical biopsies" and is a valuable tool in targeting biopsies to improve dysplasia detection; however, this is technically challenging. Fuji intelligent chromoendoscopy and I-Scan are recent additions to the imaging armamentarium that have produced notable early results. While all these additional new imaging techniques are promising, a thorough examination by high resolution white light endoscopy after clearing the mucosa with mucolytics should be the minimum standard to improve dysplasia detection during Barrett’s surveillance.

Early Diagnostic Value of Circulating MiRNA-21 in Lung Cancer: A Meta-Analysis

To evaluate the early diagnostic value of circulating miRNA-21 in diagnosis of lung cancer, databases such as Wan Fang, VIP, PubMed, and Elsevier were systematically searched from 2005 to 2013 to collect relevant references in which the diagnostic value had been evaluated. The statistics were consolidated and the qualities of the studies were classified. The data were analyzed using Meta Disc1.4 software. The diagnostic value of circulating miRNA-21 in lung cancer was assessed by pooling sensitivity, specificity, the likelihood ratio, and the Summary Receiver Operating Characteristic（SROC） curve. Publication biases of the studies involved were analyzed using Stata 11.0 software. A total of 143 papers were collected of which 8 were included, which contained 600 cases and440 controls. A heterogeneity test proved the existence of homogeneity in this study. Upon analysis using random effects models, the weighted sensitivity was 0.68, the specificity 0.77, the positive likelihood ratio 2.84, the negative likelihood ratio 0.40, and the SROC Area Under the Curve（AUC） was 0.8133. Further analysis by subgroup showed that the 5 indicators mentioned above were 0.72, 0.84, 4.50, 0.27, and 0.8987, respectively, for the serum group and 0.63, 0.70, 1.95, 0.53, and 0.7318, respectively, for the plasma group. We conclude that circulating miRNA-21can be regarded a valuable reference in diagnosis of lung cancer. This research showed that in lung cancer the early diagnostic value of miRNA-21 in serum was better than that in plasma.

Application of serum surface-enhanced laser desorption/ionization proteomic patterns in distinguishing lung cancer patients from healthy people

Screening and early diagnosis of lung cancer relies mainly on chest X-ray, low-dose computed tomography, bronchoscopy, sputum cytology, and measurement of tumor markers such as carcinoembryonic antigen (CEA), cytokeratin-19 fragments (Cyfra21-1), and neuron-specific enolase (NSE). However, all these methods lack adequate sensitivity and/or specificity. 1-3 Better methods are therefore urgently needed in screening and early diagnosis of lung cancer, and proteomic fingerprinting represents a promising approach. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS), an innovative proteomic technology, has overcome many of the limitations of two-dimensional electrophoresis (2D) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). 4,5 Recently, this technology has been successfully used to distinguish pancreatic, ovarian and prostate cancer patients from healthy control subjects. 5-7 The aim of the current study was to investigate the application of serum SELDI protein profiling in distinguishing lung cancer patients from healthy persons.

Two-photon microscopy in pre-clinical and clinical cancer research

The applications of two-photon microscopy （TPM） on pre-clinical and clinical study of human cancer and diseases are reviewed in this paper. First, the principle of two-photon excitation （TPE） is introduced. The resulting advantages of TPM for imaging studies of animal models and human samples are then elaborated. Subsequently, the applications of TPM on various aspects of tumor studies, including tumor angiogenesis, invasion and metastasis, tumor microenvironment and metabolism are introduced. Furthermore, studies of TPM on clinical human skin biopsy and the development of two-photon microendoscopy are reviewed. Finally, potential future directions are discussed.