Protective effect of miR-18a in resected liver metastases of colorectal cancer and FOLFOX treatment.

BACKGROUND: Colorectal cancer ranks second in terms of cancer associated deaths worldwide, whereas miRNA play a pivotal role in the etiology of cancer and its metastases. AIMS: Studying the expression and cellular function of miR-18a in metastatic colorectal cancer and association to progression-free survival. METHODS AND RESULTS: Colorectal liver metastases (N = 123) and primary colorectal cancer (N = 27) where analyzed by RT-PCR and correlated with clinical follow up data. Invasion and migration assays were performed with the liver metastatic cell line LIM2099 after miR-18a knockdown. Cell viability under FOLFOX treatment and knockdown was measured. We found that the expression of miR-18a was increased 4.38-fold in liver metastases and 3.86-fold in colorectal tumor tissue compared to healthy liver tissue and colorectal mucosa, respectively (p ≤ .001). Patients with a high miR-18a expression in liver metastases had a progression-free survival (PFS) of 13.6 months versus 8.9 months in patients with low expression (N = 123; p = .024). In vitro migration of LIM2099 cells was reduced after miR-18a knockdown and cell viability was significantly increased after miR-18a knockdown and treatment with folinic acid or oxaliplatin. Subgroup analysis of PFS revealed significant benefits for patients with high miR-18a expression receiving 5-FU, folinic acid or oxaliplatin. CONCLUSIONS: High expression of miR-18a in colorectal liver metastases might have a protective effect after resection of metastases and FOLFOX treatment regarding PFS.

Cancer-Associated Fibroblast Heterogeneity and Its Influence on the Extracellular Matrix and the Tumor Microenvironment.

The tumor microenvironment comprises multiple cell types, like cancer cells, endothelial cells, fibroblasts, and immune cells. In recent years, there have been massive research efforts focusing not only on cancer cells, but also on other cell types of the tumor microenvironment, thereby aiming to expand and determine novel treatment options. Fibroblasts represent a heterogenous cell family consisting of numerous subtypes, which can alter immune cell fractions, facilitate or inhibit tumor growth, build pre-metastatic niches, or stabilize vessels. These effects can be achieved through cell-cell interactions, which form the extracellular matrix, or via the secretion of cytokines or chemokines. The pro- or antitumorigenic fibroblast phenotypes show variability not only among different cancer entities, but also among intraindividual sites, including primary tumors or metastatic lesions. Commonly prescribed for arterial hypertension, the inhibitors of the renin-angiotensin system have recently been described as having an inhibitory effect on fibroblasts. This inhibition leads to modified immune cell fractions and increased tissue stiffness, thereby contributing to overcoming therapy resistance and ultimately inhibiting tumor growth. However, it is important to note that the inhibition of fibroblasts can also have the opposite effect, potentially resulting in increased tumor growth. We aim to summarize the latest state of research regarding fibroblast heterogeneity and its intricate impact on the tumor microenvironment and extracellular matrix. Specifically, we focus on highlighting recent advancements in the comprehension of intraindividual heterogeneity and therapy options within this context.

Hexanematic crossover in epithelial monolayers depends on cell adhesion and cell density.

Changes in tissue geometry during developmental processes are associated with collective migration of cells. Recent experimental and numerical results suggest that these changes could leverage on the coexistence of nematic and hexatic orientational order at different length scales. How this multiscale organization is affected by the material properties of the cells and their substrate is presently unknown. In this study, we address these questions in monolayers of Madin-Darby canine kidney cells having various cell densities and molecular repertoires. At small length scales, confluent monolayers are characterized by a prominent hexatic order, independent of the presence of E-cadherin, monolayer density, and underlying substrate stiffness. However, all three properties affect the meso-scale tissue organization. The length scale at which hexatic order transits to nematic order, the "hexanematic" crossover scale, strongly depends on cell-cell adhesions and correlates with monolayer density. Our study demonstrates how epithelial organization is affected by mechanical properties, and provides a robust description of tissue organization during developmental processes.

Type 2 T cell responses against distinct epitopes of the desmoglein 3 ectodomain in pemphigus vulgaris.

Pemphigus vulgaris (PV) is an autoimmune blistering disorder of the skin and/or mucous membranes caused by IgG autoantibodies which predominantly target two transmembrane desmosomal cadherins, desmoglein (Dsg)1 and Dsg3. Dsg-specific T cells play a central role in PV pathogenesis as they provide help to autoreactive B cells for autoantibody production. We here characterized Dsg3-specific peripheral T cells in a cohort of 52 PV patients and 41 healthy controls (HC) with regard to cytokine profile and epitope specificity. By ELISpot analysis, type 2 T cells reactive with the Dsg3 ectodomain were significantly increased in PV patients compared to HC. By dextramer analysis, CD4+ T cells specific for an epitope within the extracellular domain of Dsg3, Dsg3(206-220), were found at significantly higher frequencies in PV patients than in HLA-matched HC. T cell recognition of two distinct Dsg3 epitopes, i.e. Dsg3(206-220) and Dsg3(378-392), correlated significantly suggesting a synergistic effect in B cell help. Immunization of HLA-DRB1*04:02-transgenic PV mice with the same set of Dsg3 peptides induced pathogenic Dsg3-specific IgG antibodies which induced loss of keratinocyte adhesion in vitro. Thus, Dsg3 peptide-specific T cells are of particular interest as surrogate marker of disease activity and potential therapeutic targets in PV.

Computational exploration of the global microbiome for antibiotic discovery.

Novel antibiotics are urgently needed to combat the antibiotic-resistance crisis. We present a machine learning-based approach to predict prokaryotic antimicrobial peptides (AMPs) by leveraging a vast dataset of 63,410 metagenomes and 87,920 microbial genomes. This led to the creation of AMPSphere, a comprehensive catalog comprising 863,498 non-redundant peptides, the majority of which were previously unknown. We observed that AMP production varies by habitat, with animal-associated samples displaying the highest proportion of AMPs compared to other habitats. Furthermore, within different human-associated microbiota, strain-level differences were evident. To validate our predictions, we synthesized and experimentally tested 50 AMPs, demonstrating their efficacy against clinically relevant drug-resistant pathogens both in vitro and in vivo. These AMPs exhibited antibacterial activity by targeting the bacterial membrane. Additionally, AMPSphere provides valuable insights into the evolutionary origins of peptides. In conclusion, our approach identified AMP sequences within prokaryotic microbiomes, opening up new avenues for the discovery of antibiotics.

Evaluation of In2Care mosquito stations for suppression of the Australian backyard mosquito, Aedes notoscriptus (Diptera: Culicidae).

Aedes notoscriptus (Skuse) is a container-inhabiting mosquito endemic to Australia that vectors arboviruses and is suspected to transmit Mycobacterium ulcerans, the cause of Buruli ulcer. We evaluated the effectiveness of the In2Care station, which suppresses mosquito populations via the entomopathogenic fungus, Beauveria bassiana, and the insect growth regulator pyriproxyfen, the latter of which is autodisseminated among larval habitats by contaminated mosquitoes. A field trial was conducted using 110 In2Care stations in a 50,000 m2 area and results were compared to 4 control areas that did not receive the treatment. Efficacy was evaluated by comparing egg counts and measuring larvicidal impact in surrounding breeding sites. Laboratory experiments validated the effect of B. bassiana on adult survival. Results of this field trial indicate that, 6 wk after the In2Care stations were deployed, treatment site ovitraps contained 43% fewer eggs than control site ovitraps, and 33% fewer eggs after 10 wk, suggesting that the In2Care station was able to reduce the egg density of Ae. notoscriptus. Population reduction remained evident for up to 3 wk after In2Care stations were removed. Treatment site ovitraps had significantly fewer Ae. notoscriptus eclosing than control site ovitraps, confirming the pyriproxyfen autodissemination feature of the stations. An average reduction of 50% in adult eclosion was achieved. Exposure to B. bassiana resulted in four-times higher mortality among adult mosquitoes. Additionally, using fresh In2Care nettings led to an 88% decrease in average survival compared to 4-wk-old nettings. The use of In2Care stations has potential for suppressing Ae. notoscriptus egg density.

Chemical Constituents from Ficus sagittifolia Stem Bark and Their Antimicrobial Activities.

The phytochemical investigation of the ethylacetate fraction of an ethanolic extract obtained from the stem bark of Ficus sagittifolia (Moraceae) led to the isolation of four flavonoids: (2R)-eriodictyol (1), 2'- hydroxygenistein (2), erycibenin A (3), and genistein (4); a dihydrobenzofuran: moracin P (5); a coumarin: peucedanol (6); and an apocarotenoid terpenoid: dihydrophaseic acid (7). These were identified via 1D and 2D nuclear magnetic resonance spectroscopy (NMR) and ultra-high-resolution liquid chromatography-quadrupole time-of-flight mass spectroscopy (UHPLC-QTOF MS). Moracin P (5) is being reported for the first time in the genus Ficus, while the others are known compounds (1-4 and 6-7) isolated previously from the genus but being reported for the first time from the species F. sagittifolia. Their antimicrobial activity against various pathogens (five bacteria: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Salmonella typhi; two fungi: Aspergillus niger and Candida albicans) was tested. The mixture of genistein and moracin P (4+5) exhibited strong activity against K. pneumoniae (MIC < 0.0039 mg/mL), whereas dihydrophaseic acid (7) was the most active against P. aeruginosa and A. niger (MIC = 0.0078 and <0.0039 mg/mL, respectively). These compounds might be considered potential antimicrobial agents with the potential to be starting points for the development of antimicrobial drugs.

Analysis of training pathway to reach expert performance levels based on proficiency-based progression in robotic-assisted minimally invasive esophagectomy (RAMIE).

BACKGROUND: Robotic-assisted minimally invasive esophagectomy (RAMIE) was first introduced in 2003 and has since then shown to significantly improve the postoperative course. Previous studies have shown that a structured training pathway based on proficiency-based progression using individual skill levels as measures of reach of competence can enhance surgical performance. The aim of this study was to evaluate and help understand our pathway to reach surgical expert levels using a proficiency-based approach introducing RAMIE at our German high-volume center. METHODS: All patients undergoing RAMIE performed by two experienced surgeons for esophageal cancer since the introduction of the robotic technique in 2017 was included in this analysis. Intraoperative outcomes and postoperative outcomes were included in the analysis. The cumulative sum method was used to analyze how many cases are needed to reach expert levels for different performance characteristics and skill sets during robotic-assisted minimally invasive esophagectomy. RESULTS: From 06/2017 to 03/2022, a total of 154 patients underwent RAMIE at our facility and were included in the analysis. An advancement in performance level was observed for total operating time after 70 cases and for thoracic operative time after 79 cases. Lymph node yield showed an increase up until case 60 in the CUSUM analysis. Length of hospital stay stabilized after case 55. The CCI score inflection point was at case 55 in both CUSUM and regression analyses. Anastomotic leak rate stabilized at case 38 and showed another inflection point after case 83. CONCLUSION: Our data and analysis showed the progression from proficient to expert performance levels during the implementation of RAMIE at a European high-volume center. Further analysis of surgeons, especially with a different training status has yet to reveal if the caseloads found in this study are universally applicable. However, skill acquisition and respective measures of such are diverse and as a great range of number of cases was observed, we believe that the learning curve and ascent in performance levels cannot be defined by one parameter alone.

Prehabilitation in older patients prior to elective cardiac procedures (PRECOVERY): study protocol of a multicenter randomized controlled trial.

BACKGROUND: Previous studies have demonstrated the efficacy of rehabilitation after a cardiovascular procedure. Especially older and multimorbid patients benefit from rehabilitation after a cardiac procedure. Prehabilitation prior to cardiac procedures may also have positive effects on patients' pre- and postoperative outcomes. Results of a current meta-analysis show that prehabilitation prior to cardiac procedures can improve perioperative outcomes and alleviate adverse effects. Germany currently lacks a structured cardiac prehabilitation program for older patients, which is coordinated across healthcare sectors. METHODS: In a randomized, controlled, two-arm parallel group, assessor-blinded multicenter intervention trial (PRECOVERY), we will randomize 422 patients aged 75 years or older scheduled for an elective cardiac procedure (e.g., coronary artery bypass graft surgery or transcatheter aortic valve replacement). In PRECOVERY, patients randomized to the intervention group participate in a 2-week multimodal prehabilitation intervention conducted in selected cardiac-specific rehabilitation facilities. The multimodal prehabilitation includes seven modules: exercise therapy, occupational therapy, cognitive training, psychosocial intervention, disease-specific education, education with relatives, and nutritional intervention. Participants in the control group receive standard medical care. The co-primary outcomes are quality of life (QoL) and mortality after 12 months. QoL will be measured by the EuroQol 5-dimensional questionnaire (EQ-5D-5L). A health economic evaluation using health insurance data will measure cost-effectiveness. A mixed-methods process evaluation will accompany the randomized, controlled trial to evaluate dose, reach, fidelity and adaptions of the intervention. DISCUSSION: In this study, we investigate whether a tailored prehabilitation program can improve long-term survival, QoL and functional capacity. Additionally, we will analyze whether the intervention is cost-effective. This is the largest cardiac prehabilitation trial targeting the wide implementation of a new form of care for geriatric cardiac patients. TRIAL REGISTRATION: German Clinical Trials Register (DRKS; http://www.drks.de ; DRKS00030526). Registered on 30 January 2023.

A theory of visibility measures in the dissociation paradigm.

Research on perception without awareness primarily relies on the dissociation paradigm, which compares a measure of awareness of a critical stimulus (direct measure) with a measure indicating that the stimulus has been processed at all (indirect measure). We argue that dissociations between direct and indirect measures can only be demonstrated with respect to the critical stimulus feature that generates the indirect effect, and the observer's awareness of that feature, the critical cue. We expand Kahneman's (Psychological Bulletin, 70, 404-425, 1968) concept of criterion content to comprise the set of all cues that an observer actually uses to perform the direct task. Different direct measures can then be compared by studying the overlap of their criterion contents and their containment of the critical cue. Because objective and subjective measures may integrate different sets of cues, one measure generally cannot replace the other without sacrificing important information. Using a simple mathematical formalization, we redefine and clarify the concepts of validity, exclusiveness, and exhaustiveness in the dissociation paradigm, show how dissociations among different awareness measures falsify both single-valued measures and monocausal theories of "consciousness," and formulate the demand that theories of visual awareness should be sufficiently specific to explain dissociations among different facets of awareness.

A Nature-Inspired Antioxidant Strategy based on Porphyrin for Aromatic Hydrocarbon Containing Fuel Cell Membranes.

The use of hydrocarbon-based proton conducting membranes in fuel cells is currently hampered by the insufficient durability of the material in the device. Membrane aging is triggered by the presence of reactive intermediates, such as HO⋅, which attack the polymer and eventually lead to chain breakdown and membrane failure. An adequate antioxidant strategy tailored towards hydrocarbon-based ionomers is therefore imperative to improve membrane lifetime. In this work, we perform studies on reaction kinetics using pulse radiolysis and γ-radiolysis as well as fuel cell experiments to demonstrate the feasibility of increasing the stability of hydrocarbon-based membranes against oxidative attack by implementing a Nature-inspired antioxidant strategy. We found that metalated-porphyrins are suitable for damage transfer and can be used in the fuel cell membrane to reduce membrane aging with a low impact on fuel cell performance.

[Surgical treatment of pseudomyxoma peritonei-Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy]. / Chirurgische Therapie des Pseudomyxoma-peritonei-Syndroms ­ zytoreduktive Chirurgie und hypertherme intraperitoneale Chemotherapie.

BACKGROUND: Pseudomyxoma peritonei syndrome (PMP) is an orphan disease. Surgery is the fundament of treatment. METHOD: Short review summarizing the state of the art treatment. RESULTS: Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) form the foundations of treatment for PMP. The peritoneal cancer index should be preoperatively determined based on imaging and/or laparoscopy, intraoperatively validated and both should be documented. An extraperitoneal surgical preparation technique leads to effective en bloc resection of the peritoneum and the affected abdominal area. The HIPEC technique should be performed with mitomycin C for 60-90 min. Complete CRS (CC = 0, CC = 1) and the histological subtype are relevant for the prognosis. Structured educational programs and mentoring can optimize the learning curve. The aftercare should be performed at the surgical center. After follow-up imaging at 3 months after CRS, in the first 2 years a control should be carried out every 6 months. Thereafter, the intervals can be extended to 1 year. CONCLUSION: Standardized surgical treatment and HIPEC, optimized specific surgical training and structured follow-up at the center lead to an excellent long-term prognosis for patients with PMP.

An X-ray free-electron laser with a highly configurable undulator and integrated chicanes for tailored pulse properties.

X-ray free-electron lasers (FELs) are state-of-the-art scientific tools capable to study matter on the scale of atomic processes. Since the initial operation of X-ray FELs more than a decade ago, several facilities with upgraded performance have been put in operation. Here we present the first lasing results of Athos, the soft X-ray FEL beamline of SwissFEL at the Paul Scherrer Institute in Switzerland. Athos features an undulator layout based on short APPLE-X modules providing full polarisation control, interleaved with small magnetic chicanes. This versatile configuration allows for many operational modes, giving control over many FEL properties. We show, for example, a 35% reduction of the required undulator length to achieve FEL saturation with respect to standard undulator configurations. We also demonstrate the generation of more powerful pulses than the ones obtained in typical undulators. Athos represents a fundamental step forward in the design of FEL facilities, creating opportunities in FEL-based sciences.

Consistency across multi-omics layers in a drug-perturbed gut microbial community.

Multi-omics analyses are used in microbiome studies to understand molecular changes in microbial communities exposed to different conditions. However, it is not always clear how much each omics data type contributes to our understanding and whether they are concordant with each other. Here, we map the molecular response of a synthetic community of 32 human gut bacteria to three non-antibiotic drugs by using five omics layers (16S rRNA gene profiling, metagenomics, metatranscriptomics, metaproteomics and metabolomics). We find that all the omics methods with species resolution are highly consistent in estimating relative species abundances. Furthermore, different omics methods complement each other for capturing functional changes. For example, while nearly all the omics data types captured that the antipsychotic drug chlorpromazine selectively inhibits Bacteroidota representatives in the community, the metatranscriptome and metaproteome suggested that the drug induces stress responses related to protein quality control. Metabolomics revealed a decrease in oligosaccharide uptake, likely caused by Bacteroidota depletion. Our study highlights how multi-omics datasets can be utilized to reveal complex molecular responses to external perturbations in microbial communities.

Surface charge dynamics on air-exposed ferroelectric Pb(Zr,Ti)O3(001) thin films.

Probing of the free surface ferroelectric properties of thin polar films can be achieved either by estimating the band bending variance under the top-most layer or by studying the extent of the extrinsic charge accumulated outside the surface. Photoemitted or incoming low-energy electrons can be used to characterize locally both properties in a spectromicroscopic approach. Thin ferroelectric lead zirco-titanate (PZT) is investigated by combining low energy/mirror electron microscopy (LEEM/MEM) with photoemission electron microscopy (PEEM) and high-resolution photoelectron spectroscopy (XPS). Significant extrinsic negative compensation charge is proven to accumulate on the surface of the outward polarized thin film, indicated by high MEM-LEEM transition values, up to 15.3 eV, and is correlated with the surface electrostatic potential, which can be partially screened either by electrons interacting with the sample or by soft X-rays through the ejection of secondary electrons and generation of positive charge under the surface. A radiation-induced surface charge compensation effect is observed. The study indicates that air-exposed high quality ferroelectric thin films show large negative surface potentials, determined locally on the surface, which are nevertheless sensitive to beam damage and molecular desorption. These values represent a confirmation of previously estimated surface potential energy values determined from the LEED data on clean surfaces.

Scuba diving after a heart transplant: excessive daring or calculable risk?

Over the past 50 years, outcomes after heart transplantation (HTX) have continuously and significantly improved. In the meantime, many heart transplant recipients live almost normal lives with only a few limitations. In some cases, even activities that actually seemed unreasonable for these patients turn out to be feasible. This article describes the encouraging example of a patient returning to recreational scuba diving after HTX. So far, there were no scientific experiences documented in this area. We worked out the special hemodynamic features and the corresponding risks of this sport for heart transplant recipients in an interdisciplinary manner and evaluated them using the patient as an example. The results show that today, with the appropriate physical condition and compliance with safety measures, a wide range of activities, including scuba diving, are possible again after HTX. They illustrate again the significant development and the enormous potential of this therapy option, which is unfortunately only available to a limited extent.NEW & NOTEWORTHY Example for shared decision-making process for tricky questions: First scientific publication about heart transplantation (HTX)-recipient restarting scuba diving. As exercise physiology after HTX combined with specific diving medicine aspects is challenging, we formed a multidisciplinary team to identify, evaluate, and mitigate the risks involved. The results show that today, with the appropriate physical condition and compliance with safety measures, a wide range of activities are possible again after HTX.

Impact of the Surgical Approach for Neoadjuvantly Treated Gastro-Esophageal Junction type II Tumors- a Multi-National, High-Volume Center Retrospective Cohort Analysis.

OBJECTIVE: To explore oncologic outcomes of transhiatal gastrectomy (THG) or transthoracic esophagectomy (TTE) for neoadjuvantly treated gastroesophageal junction (GEJ) Siewert type II adenocarcinomas, a multi-national, high-volume center cohort analysis was undertaken. BACKGROUND: Neoadjuvant radiochemotherapy (RCTx) or perioperative chemotherapy (CTx) followed by surgery is the standard therapy for locally advanced GEJ. However, the optimal surgical approach for type II GEJ tumors remains unclear, as the decision is mainly based on individual experience and assessment of operative risk. METHODS: A retrospective analysis of five prospectively maintained databases was conducted. Between 2012-2021, 800 patients fulfilled inclusion criteria for type II GEJ tumors and neoadjuvant RCTx or CTx. The primary endpoint was median overall survival (mOS). Propensity score matching (PSM) was performed to minimize selection bias. RESULTS: Patients undergoing THG (n=163, 20.4%) had higher ASA classification and cT-stage (P<0.001) than patients undergoing TTE (n=637, 79.6%). Neoadjuvant therapy was different as the THG-group were mainly undergoing CTx (87.1%, P<0.001). The TTE-group showed higher tumor regression (P=0.009), lower ypT-/ypM-categories (both P<0.001), higher nodal yield (P=0.009) and higher R0-resection rate (P=0.001). The mOS after TTE was longer (78.0 versus 40.0 months (P=0.013). After PSM a higher R0-resection rate (P=0.004) and mOS benefit after TTE remained (P=0.04). Subgroup analyses of patients without distant metastasis (P=0.037) and patients only after neoadjuvant chemotherapy (P=0.021) confirmed the survival benefit of TTE. TTE was an independent predictor of longer survival. CONCLUSIONS: Awaiting results of the randomized CARDIA-trial, TTE should in high-volume centers be considered the preferred approach due to favorable oncologic outcomes.

Effect of Exercise Training on Peak Aerobic Power Post Heart Transplant: A Brief Review.

Heart transplantation (HTP) is a life-saving therapy for select individuals with end-stage refractory heart failure. Despite improvements in quality of life and survival, HTP recipients' peak aerobic power (peak VO2) remains up to 50% lower than age-matched healthy controls secondary to abnormal cardiovascular and skeletal muscle function. Currently, little is known regarding the effect of exercise training (ET) to improve peak VO2 post HTP. This brief review aims to summarise existing evidence regarding the role of ET on peak VO2 and its determinants, highlights the upper limits of endurance performance in highly trained HTP athletes, and identifies areas for future HTP exercise rehabilitation research.

High NANOG expression correlates with worse patients' survival in esophageal adenocarcinoma.

BACKGROUND: Patients diagnosed with esophageal cancer demonstrate a low overall survival even despite the established multimodal therapy as the current standard of care. Therefore, further biomarkers for patients with high-risk and additional therapy options are needed. NANOG is a transcription factor, which can be found in stem cells and is known to support tumorigenesis. METHODS: Six hundred sixty patients with esophageal adenocarcinoma, who were operated at the University of Cologne with a curative intent, were included. Immunohistochemical stainings for NANOG were performed. The study population was divided into NANOG-positive and -negative subgroups. RESULTS: Positive NANOG expression correlates significantly with worse overall survival (p = 0.002) and could be confirmed as an independent risk factor for worse patient survival in multivariate analysis (HR = 1.40, 95%CI = 1.09-1.80, p = 0.006). This effect could be detected in the subgroup of primarily operated patients, but not in patients after neoadjuvant therapy. CONCLUSIONS: We describe a NANOG-positive subgroup of patients with esophageal cancer, who exhibit worse overall survival in a large patient cohort. This discovery suggests the potential use of NANOG as a biomarker for both intensified therapy and stricter follow-up regimes. Additionally, NANOG-positive stem cell-like cancer cells could be used as a new antitumoral treatment target if validated in mechanistic and clinical studies.