The rare circulating tumor microemboli as a biomarker contributes to predicting early colorectal cancer recurrences after medical treatment.

Early prognosis of cancer recurrence remains difficult partially due to insufficient and ineffective screening biomarkers or regimes. This study evaluated the rare circulating tumor microemboli (CTM) from liquid biopsy individually and together with circulating tumor cells (CTCs) and serum CEA/CA19-9 in a panel, on early prediction of colorectal cancer (CRC) recurrence. Stained CTCs/CTM were detected by a microfluidic chip-based automatic rare-cell imaging platform. ROC, AUC, Kaplan-Meier survival, and Cox proportional hazard models regarding 4 selected biomarkers were analyzed. The relative risk, odds ratio, predictive accuracy, and positive/negative predictive value of biomarkers individually and in combination, to predict CRC recurrence were assessed and preliminarily validated. The EpCAM+Hochest+CD45- CTCs/CTM could be found in all cancer stages, where more recurrences were observed in late-stage cases. Significant correlations between CTCs/CTM with metastatic stages and clinical treatment were illustrated. CA19-9 and CTM could be seen as independent risk factors in patient survivals, while stratified patients by grouped biomarkers on the Kaplan-Meier analyses presented more significant differences in predicting CRC recurrences. By monitoring the panel of selected biomarkers, disease progressions of 4 CRC patients during follow-up visits after first treatments within 3 years were predicted successfully. This study unveiled the value of rare CTM on clinical studies and a panel of selected biomarkers on predicting CRC recurrences in patients at the early time after medical treatment, in which the CTM and serum CA19-9 could be applied in clinical surveillance and CRC management to improve the accuracy.

Amplicon size and non-encapsidated DNA fragments define plasma cytomegalovirus DNA loads by automated nucleic acid testing platforms: A marker of viral cytopathology?

Management of cytomegalovirus (CMV) in transplant patients relies on measuring plasma CMV-loads using quantitative nucleic acid testing (QNAT). We prospectively compared the automated Roche-cobas®6800-CMV and Roche-CAP/CTM-CMV with laboratory-developed Basel-CMV-UL54-95bp, and Basel-CMV-UL111a-77bp. Roche-cobas®6800-CMV and Roche-CAP/CTM-CMV were qualitatively concordant in 142/150 cases (95%). In-depth comparison revealed higher CMV-loads of the laboratory-developed assay and correlated with smaller amplicon size. After calibration to the 1.WHO-approved CMV international standard, differences were reduced but remained significant. DNase-I pretreatment significantly reduced CMV-loads for both automated Roche-CAP/CTM-CMV and Roche-cobas®6800-CMV assays, whereby 90% and 95% of samples became undetectable. DNase-I pretreatment also reduced CMV-loads quantified by Basel-CMV-UL54-95bp and Basel-CMV-UL111a-77bp, but remaining detectable in 20% and 35%, respectively. Differences were largest for 110 samples with low-level CMV-DNAemia being detectable but not-quantifiable by Roche-cobas®6800-CMV, whereby the smaller amplicon sizes yielded higher viral loads for concordant positives. We conclude that non-encapsidated fragmented CMV-DNA is the major form of plasma CMV-loads also measured by fully-automated platforms. Amplicons of <150 bp and calibrators are needed for reliable and commutable QNAT-results. We hypothesize that non-encapsidated fragmented CMV-DNA results from lysis of CMV-replicating cells and represent a direct marker of viral cell damage, which contribute to delayed viral load responses despite effective antivirals.

Pediatric Casualties in Terrorist Attacks: A Semi-Quantitative Analysis of Global Events.

BACKGROUND: Terrorism remains a major threat and concern in many countries around the world. Pediatric populations represent approximately 30% of the world population, and in the event of a terrorist attack, can either be primary targets, to include the possibility of abduction, or unintended victims. They are unique in their vulnerabilities and, therefore, require special consideration. METHODS: This study is a semi-quantitative, epidemiological analysis of all terrorism-related pediatric fatalities and injuries sustained from 1970-2019. Data collection was performed using a retrospective database search through the Global Terrorism Database (GTD). Summaries of events including search terms associated with pediatric population were individually reviewed and those describing the deaths, injuries, or abductions were tallied. RESULTS: Of the over 200,000 terror events, 2,302 events met inclusion criteria. This represented 1.14% of total events which involved death, injury, or abduction. Of 2,032 events, a total of 2,275 pediatric fatal injuries (FI) were recorded, as well as 2,280 pediatric non-fatal injuries (NFI). The most common weapons used in all attacks involving the pediatric population were explosives (1,539 [66.8%]), firearms (543 [23.5%]), other (169 [7.3%]), and melee (83 [3.6%]). A total of 275 of the 2,032 events were related to abductions, with 71 cases involving the abduction of 10 individuals or more. CONCLUSION: Pediatric casualties in terrorist events represent a small proportion of overall victims. However, it should be understood that the pediatric population has unique vulnerabilities, and when directly impacted by terrorism, can have long-term physical and psychosocial sequelae, as well as a devastating emotional impact on the community.

Clinical and virological features of chronic hepatitis B in the French national surveillance program, 2008-2012: A cross-sectional study.

Background & Aims: Among people living with HBV, only a subset of individuals with chronic hepatitis is in need of treatment, and this proportion varies according to the population, region, and setting. No estimates of the proportion of people who are infected with HBV and meet the treatment eligibility criteria in France are available. Methods: 552 treatment-naïve individuals with chronic HBV infection referred for the first time to a hepatology reference centre between 2008 and 2012 were prospectively included. Demographic, clinical, and laboratory data were analysed. Results: In total, 61.1% of patients were males, with a median age of 37.5 years. Moreover, 64% were born in an intermediate- or high-HBV endemicity country, and 90% were HBeAg-negative. At referral, median HBV DNA and HBsAg levels were 3.3 and 3.6 log IU/ml, respectively; 37.8% of patients had alanine aminotransferase >40 U/L, and 29.0% had moderate or severe fibrosis (≥F2), including 9.4% with cirrhosis. The most prevalent genotypes were D (34.7%), E (27.4%), and A (25.7%). Coinfections were rare: 2.4% were HIV-positive, 4.0% were HCV-positive, and 6.0% were HDV-positive. According to the 2017 EASL Clinical Practice Guidelines, using a single time point analysis, 2.7% of patients were classified as HBeAg-positive chronic infection, 6.1% as HBeAg-positive chronic hepatitis B, 26.5% as HBeAg-negative chronic hepatitis B, and 61.1% as HBeAg-negative chronic infection, whereas 3.6% patients could not be classified. The performance of HBsAg level quantification to identify individuals with HBeAg-negative chronic hepatitis B was poor. A total of 29.1% met the criteria for initiation of antiviral treatment, whereas 66.5% remained under routine clinical surveillance. Most eligible patients initiated recommended first-line therapies, including tenofovir (45.3%), entecavir (36.8%), or pegylated interferon alpha (11.6%). Conclusions: Of all cases, 9.4% had cirrhosis at presentation and 29.1% met the 2017 EASL Clinical Practice Guidelines treatment criteria. HBsAg levels failed to accurately identify individuals with HBeAg-negative chronic infection. Lay summary: Among French adults chronically infected with HBV referred for the first time to hepatology reference centres, about one-third had a significant liver disease. Approximately one-third of individuals met criteria for initiation of antiviral treatment based on entecavir or tenofovir or, occasionally, pegylated interferon alpha.

Nonlinear optical properties and optimization strategies of D-π-A type phenylamine derivatives in the near-infrared region.

Modifying simple molecular structures to significantly improve nonlinear optical (NLO) performance is a primary prerequisite for scientific research. Based on the four phenylamine derivatives reported in previous studies, we designed four organic nonlinear molecules by changing the acceptor group and π-linker. (Time-dependent) density functional theory (DFT/TD-DFT) was performed on molecular geometry optimization, the contribution of π electrons to the bond order, linear and two-photon absorption (TPA) spectra, the intra-molecular charge transfer matrix (CTM), and NLO coefficients. These aspects were considered to analyze in detail how the structural modification of acceptors and π-linkers affects NLO characteristics. The three modification methods were: adding a carbonyl group at the junction of the π-linker and the acceptor group, adding a carbonyl group and a nitrogen atom to the acceptor group, and replacing the quinolinone with a pyrenyl group as the π-linker. The latter two methods can significantly reduce the excitation energy and enhance the intensity of intra-molecular charge transfer during the two-photon transition. The maximum TPA cross-sections and wavelengths of the designed molecules are DPPM (84722.6 GM, 815.7 nm) and DDPM (21600.6 GM, 781.3 nm). These two molecules have large TPA cross-sections in the near-infrared region, which renders them as possible NLO materials with broad application prospects.

Adolescent and Juvenile Idiopathic Scoliosis: Which Patients Obtain Good Results with 12 Hours of Cheneau-Toulouse-Munster Nighttime Bracing?

BACKGROUND: The results of 12 h nighttime Cheneau-Toulouse-Munster (CTM) brace wear on adolescent idiopathic scoliosis are poorly described. OBJECTIVE: The main objective was to analyze the efficiency of 12 h nighttime CTM brace wear on adolescent idiopathic scoliosis. The secondary objective was to identify the factors influencing good results. METHODS: One hundred and fifty consecutive patients treated between 2006 and 2017 were retrospectively analyzed with subgroup analysis for the main curve pattern (main thoracic or main lumbar). The inclusion criteria were evolutive scoliosis, 12 h nighttime CTM brace wear, Risser stages 0-1-2 at the time of the prescription, and Cobb angle below 45 degrees. Success was defined as no surgery, and the main curve Cobb angle (CA) progression ≤5°. The overcurve was defined as the proximal thoracic curve above the main thoracic and mid-thoracic above the main lumbar curves. A logistic regression model was built to assess the predictors of success. RESULTS: Overall success was 70%: 60% for main thoracic (MT) and 84% for main lumbar scoliosis (ML) (p = 0.003). Efficacy was 62% at Risser stage 0 and 78% at Risser stage 1-2 (p = 0.054). For MT, failure was associated with high in-brace sagittal C7 tilt (Odds Ratio = 0.72, p = 0.014) and low initial overcurve CA (Odds Ratio = 0.42, p = 0.044). For ML, a high standing height was associated with success (OR = 1.42, p = 0.035), and frontal unbalanced C7 tilt was associated with failure (OR = 0.43, p = 0.02). CONCLUSION: Twelve-hour nighttime CTM brace wear provided good results for main lumbar curves with balanced frontal C7 tilt. For MT, this treatment is indicated if the in-brace sagittal C7 tilt is well balanced from Risser stage 2.

Prognostic value of circulating tumor cells and analysis of clinicopathological factors in liver cancer.

Objective and Aims: The number of circulating tumor cells (CTCs) and the presence of circulating tumor microemboli (CTM) were determined in the peripheral blood of patients with liver cancer (LC). The relationship between CTCs, CTM, clinicopathologic features, and prognosis of LC was analyzed. The objective of this study was to determine the diagnostic and prognostic value of CTCs/CTM in LC. Subjects and Methods: Patients with LC were enrolled between May 2013 and August 2017, and 67 patients were included in the study. Overall survival curves were built using the Kaplan-Meier method and the log-rank test to identify risk factors. The results were analyzed using a Cox proportional hazards model and expressed as hazard ratio and 95% confidence interval (95% CI). Results: CTCs and either CTCs or CTM were detected in 27 patients (40.3%) and 29 patients (43.3%). CTM were found in four patients. One-year, 3-year, and 5-year survival rates were 42%, 20%, and 15%, respectively. Univariate Cox regression analysis showed that alpha-fetoprotein (AFP), number of CTCs, presence of CTM, and positive CTC/CTM were associated with survival time. Multivariate Cox regression analysis showed that alpha fetoprotein (AFP), number of CTCs, and presence of CTM were independent risk factors for survival in patients with LC. Conclusion: There was no significant correlation between the number of CTCs, the presence of CTM, and clinicopathologic factors. AFP, number of CTCs, and presence of CTM were independent risk factors for survival in patients with LC.

Potential Values of Circulating microRNA-21 to Predict Early Recurrence in Patients with Colorectal Cancer after Treatments.

Insufficient prognosis of local recurrence contributes to the poor progression-free survival rate and death in colorectal cancer (CRC) patients. Various biomarkers have been explored in predicting CRC recurrence. This study investigated the expressions of plasma/exosomal microRNA-21 (miR-21) in 113 CRC patients by qPCR, their values of predicting CRC recurrence, and the possibility to improve the prognostic efficacy in early CRC recurrence in stratified patients by combined biomarkers including circulating miR-21s, circulating tumour cells/microemboli (CTCs/CTM), and serum carcinoembryonic antigen (CEA)/carbohydrate antigen 19-9 (CA19-9). Expressions of plasma and exosomal miR-21s were significantly correlated (p < 0.0001) in all and late-stage patients, presenting similar correlations with other biomarkers. However, stage IV patients stratified by a high level of exosomal miR-21 and stage I to III patients stratified by a high level of plasma miR-21 displayed significantly worse survival outcomes in predicting CRC recurrence, suggesting their different values to predict CRC recurrence in stratified patients. Comparable and even better performances in predicting CRC recurrence in late-stage patients were found by CTCs/CTM from our blood samples as sensitive biomarkers. Improved prognosing efficacy in CRC recurrence and better outcomes to significantly differentiate recurrence in stratified patients could be obtained by analysing combined biomarkers.

Identification of Atypical Circulating Tumor Cells with Prognostic Value in Metastatic Breast Cancer Patients.

Circulating tumor cells have a strong potential as a quasi-non-invasive tool for setting up a precision medicine strategy for cancer patients. Using a second-generation "filtration-based" technology to isolate CTCs, the Screencell™ technology (Sarcelles, France), we performed a large and simultaneous analysis of all atypical circulating tumor cells (aCTCs) isolated from the blood of metastatic breast cancer (mBC) patients. We correlated their presence with clinicopathological and survival data. We included 91 mBC patients from the PERMED-01 study. The median number of aCTCs was 8.3 per mL of blood. Three subsets of aCTCs, absent from controls, were observed in patients: single (s-aCTCs), circulating tumor micro-emboli (CTM), and giant-aCTCs (g-aCTCs). The presence of g-aCTCs was associated with shorter progression free survival and overall survival. This study highlights the heterogeneity of aCTCs in mBC patients both at the cytomorphological and molecular levels. In addition, it suggests the usefulness of the g-aCTC subset as a prognostic factor and a potential stratification tool to treat late-stage mBC patients and improve their chances of benefiting from early clinical trials.

Gasdermin D in pyroptosis.

Pyroptosis is the process of inflammatory cell death. The primary function of pyroptosis is to induce strong inflammatory responses that defend the host against microbe infection. Excessive pyroptosis, however, leads to several inflammatory diseases, including sepsis and autoimmune disorders. Pyroptosis can be canonical or noncanonical. Upon microbe infection, the canonical pathway responds to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), while the noncanonical pathway responds to intracellular lipopolysaccharides (LPS) of Gram-negative bacteria. The last step of pyroptosis requires the cleavage of gasdermin D (GsdmD) at D275 (numbering after human GSDMD) into N- and C-termini by caspase 1 in the canonical pathway and caspase 4/5/11 (caspase 4/5 in humans, caspase 11 in mice) in the noncanonical pathway. Upon cleavage, the N-terminus of GsdmD (GsdmD-N) forms a transmembrane pore that releases cytokines such as IL-1ß and IL-18 and disturbs the regulation of ions and water, eventually resulting in strong inflammation and cell death. Since GsdmD is the effector of pyroptosis, promising inhibitors of GsdmD have been developed for inflammatory diseases. This review will focus on the roles of GsdmD during pyroptosis and in diseases.

Profiling heterogenous sizes of circulating tumor microemboli to track therapeutic resistance and prognosis in advanced gastric cancer.

Circulating tumor microemboli (CTM) aggregated by ≥ 2 circulating tumor cells (CTCs) are more migratory than single CTCs. Aside from the plasticity in their molecular characteristics, which have been considered tumor migration, CTM also possesses high size heterogeneity. This study, therefore, systematically investigated the heterogeneous sizes of CTM and their involvement in therapeutic resistance in 114 patients with advanced gastric cancer (GC) using a pre-established surface molecule-independent subtraction enrichment (SE)-iFISH strategy. CTM, which was pre-therapeutically detected in 33.3% of GC patients, can further form in another 34.78% of patients following chemo-/targeted therapies. The presence of CTM is relevant to liver metastasis as well as higher CTC levels (≥ 5/6 mL). Further size-based profiling of GC-CTM revealed that CTM with 2 CTCs (CTM2) was the dominant subtype, accounting for 50.0% of all detected GC-CTMs. However, CTM with 3-4 CTCs (CTM3-4) specifically associates with chemo-/targeted therapeutic resistance and inferior prognosis. Patients with ≥ 1 CTM3-4/6 mL have shorter median progression-free survival and median overall survival. Unlike CTM2 and CTM3-4, which are detectable in pre-therapy and post-therapy, larger aggregated CTM≥5 (CTM with ≥ 5 CTCs) was only intra-therapeutically detected in four HER2+ GC patients, of which three experienced liver metastases. Obtained results suggested that the cluster size of GC-CTM should be dynamically profiled beyond pre-therapeutic whole CTM enumeration in terms of chemo-/targeted resistance or metastasis monitoring. GC-CTM3-4 could be a potential indicator of therapeutic resistance, while the dynamic presence of GC-CTM≥5 implies liver metastasis in HER2+ GC patients.

Highly Correlated Recurrence Prognosis in Patients with Metastatic Colorectal Cancer by Synergistic Consideration of Circulating Tumor Cells/Microemboli and Tumor Markers CEA/CA19-9.

Circulation tumor cells (CTCs) play an important role in metastasis and highly correlate with cancer progression; thus, CTCs could be considered as a powerful diagnosis tool. Our previous studies showed that the number of CTCs could be utilized for recurrence prediction in colorectal cancer (CRC); however, the odds ratio was still lower than five. To improve prognosis in CRC patients, we analyzed CTC clusters/microemboli, CTC numbers, and carcinoembryonic antigen (CEA)/carbohydrate antigen 19-9 (CA19-9) levels using a self-assembled cell array (SACA) chip system for recurrence prediction. In CRC patients, the presence of CTC clusters/microemboli may have higher correlation in metastasis when compared to the high number of CTCs. Additionally, when both the number of CTCs and serum CEA levels are high, very high odds ratios of 24.4 and 17.1 are observed in patients at all stages and stage III of CRC, respectively. The high number of CTCs and CTC clusters/microemboli simultaneously suggests the high chance of relapse (odds ratio 8.4). Overall, the characteristic of CTC clusters/microemboli, CEA level, and CTC number have a clinical potential to enhance CRC prognosis.

Clinical significance of circulating tumour cells and Ki-67 in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is a common malignant tumour of the genitourinary system. We aimed to analyse the potential value of metastasis-related biomarkers, circulating tumour cells (CTCs) and the proliferative marker Ki-67 in the diagnosis of RCC. METHODS: Data from 24 laparoscopic radical nephrectomies (RNs) and 17 laparoscopic partial nephrectomies (PNs) were collected in 2018. The numbers and positive rates of CTCs and circulating tumour microemboli (CTM) in the peripheral blood were obtained at three different time points: just before surgery, immediately after surgery and 1 week after surgery. Ki-67 protein expression was evaluated in the RCC tissue by immunohistochemistry. RESULTS: Except for the statistically significant association between the preoperative CTC counts and tumour size, no association between the number and positive rate of perioperative CTCs and clinicopathological features was found. The CTC counts gradually decreased during the perioperative period, and at 1 week after surgery, they were significantly lower than those before surgery. High Ki-67 expression was significantly positively correlated with preoperative CTC counts. In addition, Ki-67 expression was higher in the high CTC group (≥ 5 CTCs). CONCLUSION: Our results suggest that surgical nephrectomy is associated with a decrease in CTC counts in RCC patients. CTCs can act as a potential biomarker for the diagnosis and prognosis of RCC. A careful and sufficient long-term follow-up is needed for patients with high preoperative CTC counts.

Effect of tunable π bridge on two-photon absorption property and intramolecular charge transfer process of polycyclic aromatic hydrocarbons.

The influences of the conjugation effect on the charge transfer and nonlinear optical (NLO) properties of polycyclic aromatic hydrocarbons (PAHs) are comprehensively investigated at the microscopic molecular level. We found that the conjugation effect of π bridge is negatively correlated with molecular planarity, excitation energy, two-photon absorption (TPA) cross-section, and the second hyperpolarizability. For the first time, the charge transfer matrix (CTM) is applied to the molecular two-photon transition process. Combining the charge difference density (CDD) diagram with CTM heat map to visually quantitative investigate the characteristics of excited states, the charge transfer path and transfer amount between atoms. During the two-photon transition of all molecules, the electronic excited state is locally excited. Compared with the first process, the range of intramolecular charge transfer in the second process of the two-photon transition is expanded. Comprehensive results prove that the π bridge with large conjugation effect distorts the molecular structure, which is not conducive to the intramolecular charge transfer. Therefore, the molecule DBP-1 with a carbon-carbon double bond as the π bridge has the largest transition dipole moments, TPA cross-section, and second static hyperpolarizability. Our research method can provide effective guidance for the design and optimization of nonlinear organic conjugated molecular materials.

Novel Genetically Modified Mouse Model to Assess Soman-Induced Toxicity and Medical Countermeasure Efficacy: Human Acetylcholinesterase Knock-in Serum Carboxylesterase Knockout Mice.

The identification of improved medical countermeasures against exposure to chemical warfare nerve agents (CWNAs), a class of organophosphorus compounds, is dependent on the choice of animal model used in preclinical studies. CWNAs bind to acetylcholinesterase and prevent the catalysis of acetylcholine, causing a plethora of peripheral and central physiologic manifestations, including seizure. Rodents are widely used to elucidate the effects of CWNA-induced seizure, albeit with a caveat: they express carboxylesterase activity in plasma. Carboxylesterase, an enzyme involved in the detoxification of some organophosphorus compounds, plays a scavenging role and decreases CWNA availability, thus exerting a protective effect. Furthermore, species-specific amino acid differences in acetylcholinesterase confound studies that use oximes or other compounds to restore its function after inhibition by CWNA. The creation of a human acetylcholinesterase knock-in/serum carboxylesterase knockout (C57BL/6-Ces1ctm1.1LocAChEtm1.1Loc/J; a.k.a KIKO) mouse may facilitate better modeling of CWNA toxicity in a small rodent species. The current studies characterize the effects of exposure to soman, a highly toxic CWNA, and evaluate the efficacy of anti-seizure drugs in this newly developed KIKO mouse model. Data demonstrate that a combination of midazolam and ketamine reduces seizure duration and severity, eliminates the development of spontaneous recurrent seizures, and protects certain brain regions from neuronal damage in a genetically modified model with human relevance to organophosphorus compound toxicity. This new animal model and the results of this study and future studies using it will enhance medical countermeasures development for both defense and homeland security purposes.

Multicenter Evaluation of the Cepheid Xpert® HBV Viral Load Test.

Accurate measurement of the hepatitis B virus (HBV) DNA is important for the management of patients with chronic HBV infection. Here, the performance of the Xpert® HBV Viral Load test (Xpert HBV Viral Load) versus the Roche COBAS® Ampliprep/COBAS® TaqMan® system (CAP/CTM HBV) HBV test v2.0 was evaluated. From September 2017 to December 2017, a total of 876 prospectively collected or archived serum or EDTA plasma specimens from subjects chronically infected with HBV were tested using the Xpert HBV Viral Load and the CAP/CTM HBV v2.0 assays. Of the 876 specimens tested, 560 were within the quantitative range of both assays. The agreement between the two methods was 90.0%. No difference in plasma or serum samples was observed. Deming regression analysis showed a good correlation of the Xpert HBV Viral Load assay with the CAP/CTM HBV v2.0 assay. The Bland-Altman analysis showed a good agreement between the results of the Xpert HBV Viral Load assay and the CAP/CTM HBV assay, with a mean difference (±1.96 standard deviation) of 0.0091 ± 0.3852 Log IU/mL. Comparing the two assays, only nineteen specimens (2.1%) had a difference greater than 1.96 times the standard deviation. The Xpert® HBV Viral Load test is suitable for monitoring patients with HBV infection and is useful in diagnostic settings.

Specific study of biological tumor cytology: a narrative review.

Tumor metastasis is a very complex invasion. The concept of circulating tumor cells (CTCs), which describes the tumor cells diffusing into the blood, is being increasingly recognized for its role in cancer metastasis as well as it is considered the key step of tumor blood metastasis. Epithelial-mesenchymal transition (EMT) is the reverse transition from mesenchymal phenotypes to an epithelial one. Tumor cells undergoing this process have stronger metastatic potential. Though the biological characteristics of CTCs after EMT can help explain the unknown phenomena in tumor metastasis, the biomarkers of CTCs after EMT are not accurate. Also the correlation between CTCs after EMT and the prognosis of patients and the dynamic transformation of cell groups during treatment are not clear. Tumor metastasis initiating cells (MIC), which eventually lead to metastasis in CTCs, are types of cancer stem cells, or at least tumor cells with many stem cell characteristics. Further investigation of the maintenance of tumor stem cell characteristics of CTCs is required. The circulating tumor microemboli (CTM) can prevent CTCs from losing their nests, and the presence of host cells facilitates special metastasis and helps tumor cells escape immune surveillance. In this paper, we reviewed research on the biological cytological characteristics of CTCs in recent years, and provided relevant supporting evidence for monitoring tumor recurrence, assessing patient prognosis, evaluating the sensitivity of anti-tumor biological drugs, and selecting an individualized treatment plan.

Minimal Residual Disease in Melanoma:molecular characterization of in transit cutaneous metastases and Circulating Melanoma Cells recognizes an expression panel potentially related to disease progression.

Isolating circulating melanoma cells (CMCs) represents a powerful method to monitor minimal residual disease. We documented that MCAM/MUC18/CD146 expression is strongly associated with disease progression. ABCB5 is melanoma-stem antigen with self-renewal, proliferation, differentiation, tumorigenicity capabilities. These findings supported us to improve CMC detection, investigating MCAM/MUC18/CD146 and ABCB5 as enrichment targets in MM progression. Moreover, we decided to compare possible molecular diversity of these CMC fractions with metastatic tissue expression, collecting concomitantly cutaneous in transit metastases (CTM). We enriched CMCs from eight melanoma patients staged ≥pT1b AJCC, who developed CTMs at baseline or during follow up. We assessed a gene expression panel comprising ABCB5, the differentiation markers (Tyrosinase, MART1), angiogenic factors (VEGF, bFGF), the cell-cell adhesion molecules (MCAM/MUC18/CD146 5'-portion, Long, and Short isoforms, E-Cadherin, N-Cadherin, VE-Cadherin) and matrix-metallo-proteinases (MMP2 and MMP9) via high-sensitive RT-PCR. Preliminary findings defined three distinct sub-populations: "endothelial" CD45-CD146+CMCs, "stem" CD45-ABCB5+CMCs and a "hybrid- stem-endothelial"- CD45-MCAM+ABCB5+CMCs. The expression panel documented that - almost high expression found in CTMs - like in 73.5% of CMCs resulted positive for at least one transcript at baseline, showing gene-expression variability. Longitudinal monitoring documented shut-down of all gene-expressions in "endothelial"- and "hybrid stem-endothelial"-subsets, whilst persistency or acquisition of MCAM/MUC18/CD146, VE-CADH and MMPs was documented in disease-progression status.Conversely, a drastic expression shut-down was documented when patients achieved clinical remission. The "stem"- CMCs fraction" showed quite lower gene expression frequencies. MCAM/MUC18/CD146 and ABCB5 as melanoma-specific-targets are effective in the selection of highly primitive CMCs and highlights those putative genes associated with disease spreading progression.

Co-Clinical Imaging Resource Program (CIRP): Bridging the Translational Divide to Advance Precision Medicine.

The National Institutes of Health's (National Cancer Institute) precision medicine initiative emphasizes the biological and molecular bases for cancer prevention and treatment. Importantly, it addresses the need for consistency in preclinical and clinical research. To overcome the translational gap in cancer treatment and prevention, the cancer research community has been transitioning toward using animal models that more fatefully recapitulate human tumor biology. There is a growing need to develop best practices in translational research, including imaging research, to better inform therapeutic choices and decision-making. Therefore, the National Cancer Institute has recently launched the Co-Clinical Imaging Research Resource Program (CIRP). Its overarching mission is to advance the practice of precision medicine by establishing consensus-based best practices for co-clinical imaging research by developing optimized state-of-the-art translational quantitative imaging methodologies to enable disease detection, risk stratification, and assessment/prediction of response to therapy. In this communication, we discuss our involvement in the CIRP, detailing key considerations including animal model selection, co-clinical study design, need for standardization of co-clinical instruments, and harmonization of preclinical and clinical quantitative imaging pipelines. An underlying emphasis in the program is to develop best practices toward reproducible, repeatable, and precise quantitative imaging biomarkers for use in translational cancer imaging and therapy. We will conclude with our thoughts on informatics needs to enable collaborative and open science research to advance precision medicine.