Lack of clinical utility of serum macrophage migration inhibitory factor (MIF) for monitoring therapy response and estimating prognosis in advanced lung cancer.

BACKGROUND: Lung cancer is a major burden to global health and is still among the most frequent and most lethal malignant diseases. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in a variety of processes including tumorigenesis, formation of a tumor microenvironment and metastasis. It is therefore a potential prognostic biomarker in malignant diseases. OBJECTIVE: In this study, we investigated the applicability of MIF in serum samples as a biomarker in lung cancer. METHODS: In a retrospective approach, we analyzed the sera of 79 patients with non-small-cell lung cancer (NSCLC) and 14 patients with small-cell lung cancer (SCLC) before the start of chemotherapy, as well as before the second and third chemotherapy cycle, respectively. Serum MIF levels were measured using a sandwich immunoassay with a sulfo-tag-labelled detection antibody, while pro-gastrin releasing peptide (proGRP) levels were determined with an enzyme-linked immunosorbent assay. RESULTS: No difference in serum MIF levels between responders and non-responders to chemotherapy was observed at all time points, while proGRP levels were significantly lower in responders before the second chemotherapy cycle (p = 0.012). No differences in biomarker levels depending on the histopathological classification of NSCLC patients was found. Moreover, in ROC curve analyses MIF was not able to distinguish between responders and non-responders to therapy. proGRP could differentiate between responders and non-responders before the second chemotherapy cycle (p = 0.015) with sensitivities of 43% at 90% and 95% specificity, respectively. Likewise, proGRP yielded significantly longer survival times of patients with low proGRP concentrations before the second chemotherapy cycle (p = 0.015) in Kaplan-Meier analyses, yet MIF showed no significant differences in survival times at all time points. Comparison with the biomarkers CEA and CYFRA 21-1 in the same cohort showed that these established biomarkers clearly performed superior to MIF and proGRP. CONCLUSIONS: From the present results, there is no indication that serum MIF may serve as a biomarker in prognosis and monitoring of response to therapy in lung cancer. Limitations of this study include its retrospective design, the inclusion of a larger NSCLC and a smaller SCLC subgroup, the classical chemotherapeutic treatment, the use of a non-diagnostic immunoassay (RUO-test) for MIF measurement and the lack of a validation cohort. Strengths of the study are its highly standardized procedures concerning sample collection, preanalytic treatment, measurements and quality control of the laboratory assays.

Digital Smoking Cessation With a Comprehensive Guideline-Based App-Results of a Nationwide, Multicentric, Parallel, Randomized Controlled Trial in Germany.

BACKGROUND: Smoking tobacco implies significant health hazards. Digital cessation support can get more smokers in contact with guideline-based cessation. The objective was to test the efficacy of a guideline-based smoking cessation app (NichtraucherHelden®). The hypothesis was a significantly higher cessation rate in the intervention group. METHODS: The study was a nationwide, multicentric, prospective, parallel, randomized controlled trial in Germany from November 2021 to March 2023. Recruitment took place in medical practices and by telephone via study centers. Eligible participants were adult tobacco-dependent smokers according to ICD-10 (F17.2). Randomization (1:1) was operated by a computer-generated stratified 1:1 block procedure. Intervention (IG; n = 336) and control group (CG; n = 325) were briefly advised with regard to stop smoking, IG was additionally treated with the cessation app. The primary endpoint was the self-reported 7-day-point abstinence after 6 months with an intention to treat analysis. Secondary endpoints comprised prolonged abstinence and biochemically verified abstinence. The study was registered at the German Registry of Clinical Trials (DRKS00025933, UTN U1111-1268-2181) and was approved by the competent ethics committees (leading ethic committee Berlin #Eth-52/20). RESULTS: Three hundred thirty six participants (IG) and 325 (CG) were analyzed. Seven-day point prevalence was significantly higher in the app group (IG) (20% vs. 10%, OR 2.2 (1.4-3.4)). Additionally, the prolonged abstinence and the objective abstinence rates were significantly higher in the app group. CONCLUSIONS: The NichtraucherHelden app doubles the abstinence rate. Apps can bridge the gap between the small number of therapeutic offers and the need for modern evidence-based cessation support. IMPLICATIONS: The study is the first to provide evidence for the feasibility and efficacy of guideline-based digital smoking cessation provided by a smartphone app for the German statutory health insurance (SHI) system. Smoking cessation support by smartphone apps could be broadly distributed and thus bring more smokers in contact with guideline-based cessation support than to date and increase the number of successful quitters substantially.

[Implementation of smoking cessation in the workflow of a lung cancer screening program in Germany - A Position Paper of the German Respiratory Society (DGP)]. / Implementierung der Tabakentwöhnung in den Workflow des Lungenkrebsscreenings in Deutschland.

Both tobacco cessation and low-dose CT screening in at-risk individuals reduce lung cancer-specific and all-cause mortality. As part of a national screening program for the early detection of lung cancer, smoking cessation must be a mandatory part of the counseling given to participants. This increases the cost-benefit effectiveness of the screening program. As part of the initial consultation evidence-based measures for smoking cessation must be offered to smoking participants of the screening program in form of a minimal intervention. If participants do not want to participate in a quit smoking measure they must actively refuse (opt-out rule). The costs of quitting smoking, including the costs of withdrawal-inhibiting medication, have to be fully covered by statutory health insurance for participants in the lung cancer screening program.

[Medical societies in Germany call for a ban on flavors in e-cigarettes - A Position Paper of the German Respiratory Society (DGP) in cooperation with other professional associations and organizations]. / Medizinische Fachgesellschaften fordern ein Verbot von Aromen in E-Zigaretten.

E-cigarettes are primarily used by teenagers and young adults. Flavors in e-cigarettes increase their attractiveness and encourage young people and adults to start using them. This exposes young people in particular to the risk of nicotine addiction and various toxic substances from the aerosol of e-cigarettes. There are indications that various flavors in e-cigarettes are harmful to health, although toxicological studies are still lacking for the majority of flavors. There is a need for independent scientific investigations in this area. The scientific societies involved are calling for a ban on flavors in e-cigarettes, a ban on disposable e-cigarettes, effective regulation of the sale of e-cigarettes and effective control and implementation of the provisions for the protection of minors.

[Smoking cessation in hospitalised patients - Initiate among inpatients, continue when outpatients - A Position Paper by the German Respiratory Society (DGP) Taskforce for Smoking Cessation]. / Tabakentwöhnung bei hospitalisierten Patienten:innen ­ Stationär einleiten, ambulant fortführen.

Tobacco smoking is the greatest preventable health risk. The effects are serious, both individually and societal. Nevertheless, the current prevalence of tobacco smokers in Germany is still high at around 35 %. A recent strong increase in actively smoking adolescents (14- to 17-year-olds, current prevalence approx. 16 %) and young adults (18- to 24-year-olds, current prevalence approx. 41 %) is also a cause for concern. About a third of all inpatients continue smoking while being treated. The hospitalization of active smokers in acute and rehabilitation hospitals serves as a "teachable moment" for initiation of cessation offers. An intervention that begins in hospital and continues for at least a month after discharge results in about 40 % additional smokefree patients. It is scientifically well-researched, effective and cost-efficient. After initiation in hospital these measures can be continued via ambulatory cessation programs, rehabilitation facilities, an Internet or telephone service. In Germany, there are structured and quality-assured cessation offers, both for the inpatient and for the outpatient area. The biggest obstacle to broad establishment of such offers is the lack of reimbursement. Two feasible ways to change this would be the remuneration of the existing OPS 9-501 "Multimodal inpatient treatment for smoking cessation" and the establishment of quality contracts according to §â€Š110a SGB V. An expansion of tobacco cessation measures in healthcare facilities would reduce smoking prevalence, associated burden of disease and consecutive costs.

[Tobacco Cessation - The Underused Potential in Clinical Routine]. / Tabakentwöhnung ­ die bisher wenig genutzte Chance im ärztlichen Alltag.

Tobacco control, psychosocial and medical assistance regarding tobacco cessation is still a hidden potential within the German health care system. So far doctors rarely talk to their patients about their smoking status and physical and psychological benefits of quitting.This paper focusses on recommended current diagnostic and treatment standards, as well as evidence-based methods to address the topic on how to stop smoking and its association with certain diseases such as COPD, lung cancer and COVID-19 infection. The role of e-cigarettes as a cessation tool and its health related risks are critically examined. Consequences and advice how to implement smoking cessation procedures into daily practice are presented.

Bi-allelic Mutations in LSS, Encoding Lanosterol Synthase, Cause Autosomal-Recessive Hypotrichosis Simplex.

Hypotrichosis simplex (HS) is a rare form of hereditary alopecia characterized by childhood onset of diffuse and progressive scalp and body hair loss. Although research has identified a number of causal genes, genetic etiology in about 50% of HS cases remains unknown. The present report describes the identification via whole-exome sequencing of five different mutations in the gene LSS in three unrelated families with unexplained, potentially autosomal-recessive HS. Affected individuals showed sparse to absent lanugo-like scalp hair, sparse and brittle eyebrows, and sparse eyelashes and body hair. LSS encodes lanosterol synthase (LSS), which is a key enzyme in the cholesterol biosynthetic pathway. This pathway plays an important role in hair follicle biology. After localizing LSS protein expression in the hair shaft and bulb of the hair follicle, the impact of the mutations on keratinocytes was analyzed using immunoblotting and immunofluorescence. Interestingly, wild-type LSS was localized in the endoplasmic reticulum (ER), whereas mutant LSS proteins were localized in part outside of the ER. A plausible hypothesis is that this mislocalization has potential deleterious implications for hair follicle cells. Immunoblotting revealed no differences in the overall level of wild-type and mutant protein. Analyses of blood cholesterol levels revealed no decrease in cholesterol or cholesterol intermediates, thus supporting the previously proposed hypothesis of an alternative cholesterol pathway. The identification of LSS as causal gene for autosomal-recessive HS highlights the importance of the cholesterol pathway in hair follicle biology and may facilitate novel therapeutic approaches for hair loss disorders in general.

[COVID-19 and Smoking - A Position Paper by the DGP Taskforce for Smoking Cessation]. / COVID-19 und Rauchen.

Tobacco smoking is associated with severe health risks. In 2020, the WHO estimated that 8 million people have died due to smoking. Furthermore, smoking tobacco is a well-known risk factor for various infectious pulmonary diseases. The question raised, whether smoking is facilitating SARS-CoV-2-infections and increases adverse outcomes of COVID-19. To answer these questions a narrative review was conducted, finally including 7 systematic reviews with meta-analyses published in January and February 2021. Tobacco smoking was associated with an increased COVID-19 disease severity (odds ratio range of active vs. never smokers 1.55-2.19 and former vs. never smokers 1.20-2.48) and an increased COVID-19 in-hospital mortality (odds ratio range of active vs. never smokers 1.35-1.51 and former vs. never smokers 1.26-2.58). Beside immediate pulmonary toxic effects through active smoking, the cumulative livelong tobacco exposition and subsequent tobacco-associated diseases seem to predominantly predict adverse outcomes in patients with COVID-19. Data regarding an increased risk of infection among smokers is conflicting. However, a large observational study from England with 2.4 million persons reported an association between tobacco smoking and typical symptoms of COVID-19. For e-cigarettes and vaping less data exist, but experimental and first clinical investigations also suggest an increased risk for adverse outcomes for their use and SARS-CoV-2 infections. Especially during the current SARS-CoV-2 pandemic with limited therapeutic options it is particularly important to advise smokers of their increased risks for unfavourable COVID-19 outcomes. Evidence based support for smoking cessation should be offered. In Germany, the existing and well-established methods to support tobacco cessation need to be reimbursed by statutory health insurances.

[Smoking Cessation and Prescription of Ambulatory Exercise Training as Part of Pulmonary Rehabilitation in Germany]. / Tabakentwöhnung und Verordnung von ambulantem Lungensport im Rahmen der pneumologischen Rehabilitation in Deutschland.

PURPOSE: This survey was conducted on behalf of the German Respiratory Society (DGP) section 12. The aim was to assess the means of achieving tobacco cessation and prescription of exercise training on an outpatient basis after discharge from pulmonary rehabilitation clinic as part of aftercare of pulmonary rehabilitation programs in Germany. METHODS: We contacted all pulmonary rehabilitation clinics in Germany. Of the 67 clinics we identified, 62 fulfilled the inclusion criteria; 39 clinics (62.9 %) agreed to participate and returned the completed questionnaires. RESULTS: Each clinic rated ambulatory exercise training sessions as effective aftercare. In each case, slightly above 50 % of the sample informed their patients via standardized talks or information brochures. In 38.5 % of the clinics, ambulatory exercise in groups was provided as aftercare. The number of patients who received prescription for aftercare at the end of the rehabilitation program ranged between 0 % and 100 %. Only a quarter of the clinics had ever been asked by the funding organizations regarding the success rate of the exercise program. All clinics assessed the smoking status of their patients and explained the importance of tobacco abstinence to them. The percentage of smokers was estimated to be 33 %; 69.7 % of the clinics stated that the rehabilitation program included standardized talks regarding tobacco cessation and 61.5 % reported having therapeutic group meetings on a regular basis. Further treatment options included psychological counselling (89.7 %), nicotine replacement therapy (61.5 %), or varenicline (15.4 %). Aftercare was offered only in 10.3 % of the clinics. On average, the percentage of smokers who achieved tobacco abstinence during the rehabilitation program was 32 %. Only one clinic (2.6 %) had ever been asked by the funding organization regarding the success rate of the tobacco cessation program. CONCLUSION: This survey emphasizes that most of the pulmonary rehabilitation clinics in Germany have already achieved a good standard regarding tobacco cessation and exercise training programs for their inpatients; however, there are still areas of improvement as far as providing care after discharge from a rehabilitation clinic is concerned with regard to smoking cessation and prescription of ambulatory exercise training.

Ionic Liquids with Weakly Coordinating [M(III)(OR(F))4](-) Anions.

Ionic liquids (ILs) are defined as salts with melting points below 100 °C. They attracted much attention in the last two decades due to their unique set of properties, including high conductivities, low viscosities, negligible vapor pressure, and high electrochemical resistance. ILs are seen as tunable systems, of which (also in mixtures) up to 10(19) combinations may exist. These properties make ILs interesting candidates for a variety of fundamental to industrial applications. Our addition to this field was weakly coordinating, little interacting anions, the highly fluorinated aluminates [Al(OR(F))4](-) (R(F) = C(CF3)3, C(CH3), (CF3)2, and CH(CF3)2 and later also CH2(CF3)). We have used these anions in a broad spectrum of applications, including the stabilization of reactive cations, (polymerization) catalysis, and conducting salts for cyclic voltammetry or in electrochemical cells. Especially the [Al(Ohfip)4](-) (hfip = CH(CF3)2) anions in combination with asymmetric organic cations turned out to be very well suited for the synthesis of ILs with very low melting points, some even far below 0 °C. Also the analogous borates, [B(OR(F))4](-), were shown to yield ILs, and currently a plethora of such aluminate and borate ILs have been synthesized and thoroughly investigated. In many aspects, at least the [Al(Ohfip)4](-) ILs present almost ideally noninteracting prototype ILs with (nearly) isotropic but weak and flat Coulomb potential. Consequently, their overall interionic interactions are significantly reduced compared with other classes of ILs, resulting in an extraordinarily low degree, or (for short cation chain lengths below six) even complete absence of ion pairing. From thorough analysis of the principles governing the physical properties of this highly fluorinated IL class with minimized interactions, we were able to learn basic principles that could be extended, for example, to the prediction of the principal properties of a wide variety of typical ILs. In this Account, we give a comprehensive review of their syntheses, thermal and toxicological behavior, physical as well as dynamic properties, and use in electrochemical applications. We delineate advantages and limitations of the [M(III)(OR(F))4](-) ILs developed in our lab and give an outlook on those fields, in which there is still a lack of knowledge.

Tunable Aryl Alkyl Ionic Liquids with Weakly Coordinating Tetrakis((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)borate [B(hfip)4 ] Anions.

Weakly coordinating borate or aluminate anions have recently been shown to yield interesting properties of the resulting ionic liquids (ILs). The same is true for large phenyl-substituted imidazolium cations, which can be tuned by the choice, position, or number of substituents on the aromatic ring. We were therefore interested to combine these aryl alkyl imidazolium cations with the weakly coordinating tetrakis((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)borate [B(hfip)4 ](-) anions to study the physical properties and viscosities of these ionic liquids. Despite the large size and high molecular weight of these readily available ILs, they are liquid at room temperature and show remarkably low glass transition points and relatively high decomposition temperatures.

A liposomal formulation of the synthetic curcumin analog EF24 (Lipo-EF24) inhibits pancreatic cancer progression: towards future combination therapies.

BACKGROUND: Pancreatic cancer is one of the most lethal of human malignancies known to date and shows relative insensitivity towards most of the clinically available therapy regimens. 3,5-bis(2-fluorobenzylidene)-4-piperidone (EF24), a novel synthetic curcumin analog, has shown promising in vitro therapeutic efficacy in various human cancer cells, but insufficient water solubility and systemic bioavailability limit its clinical application. Here, we describe nano-encapsulation of EF24 into pegylated liposomes (Lipo-EF24) and evaluation of these particles in preclinical in vitro and in vivo model systems of pancreatic cancer. RESULTS: Transmission electron microscopy and size distribution studies by dynamic light scattering confirmed intact spherical morphology of the formed liposomes with an average diameter of less than 150 nm. In vitro, treatment with Lipo-EF24 induced growth inhibition and apoptosis in MIAPaCa and Pa03C pancreatic cancer cells as assessed by using cell viability and proliferation assays, replating and soft agar clonogenicity assays as well as western blot analyses. Lipo-EF24 potently suppressed NF-kappaB nuclear translocation by inhibiting phosphorylation and subsequent degradation of its inhibitor I-kappa-B-alpha. In vivo, synergistic tumor growth inhibition was observed in MIAPaCa xenografts when Lipo-EF24 was given in combination with the standard-of-care cytotoxic agent gemcitabine. In line with in vitro observations, western blot analysis revealed decreased phosphorylation of I-kappa-B-alpha in excised Lipo-EF24-treated xenograft tumor tissues. CONCLUSION: Due to its promising therapeutic efficacy and favorable toxicity profile Lipo-EF24 might be a promising starting point for development of future combinatorial therapeutic regimens against pancreatic cancer.

Effect of Dimethyl Carbonate on the Dynamic Properties and Ionicities of Ionic Liquids with [M(III) (hfip)4 ](-) (M=B, Al) Anions.

Several ionic liquids (ILs) comprising [B(hfip)4 ](-) [hfip=OCH(CF3 )2 ] or [Al(hfip)4 ](-) anions and imidazolium or ammonium cations were prepared and mixed with up to 270 mol % of dimethyl carbonate (DMC). The viscosities, conductivities, and self-diffusion constants of these mixtures and, where possible, of the neat ILs were measured and compared with common [NTf2 ](-) based ILs and their mixtures with DMC. A tremendous decrease of the viscosities and a likewise increase of the conductivities and diffusion constants can be achieved for all classes of ILs. However, the order of the conductivities is partially reversed in the diffusion data. This is probably due to the low dielectric constant of DMC and the, thus, favored ion pairing, as evidenced, for example, by the calculated ionicities. Altogether, our data show that the chemically robust, but high-melting and more viscous [B(hfip)4 ](-) ILs might be candidates for electrolytes when mixed with suitable molecular solvents.

Size matters! On the way to ionic liquid systems without ion pairing.

Several, partly new, ionic liquids (ILs) containing imidazolium and ammonium cations as well as the medium-sized [NTf2 ](-) (0.230 nm(3) ; Tf=CF3 SO3 (-) ) and the large [Al(hfip)4 ](-) (0.581 nm(3) ; hfip=OC(H)(CF3 )2 ) anions were synthesized and characterized. Their temperature-dependent viscosities and conductivities between 25 and 80 °C showed typical Vogel-Fulcher-Tammann (VFT) behavior. Ion-specific self-diffusion constants were measured at room temperature by pulsed-gradient stimulated-echo (PGSTE) NMR experiments. In general, self-diffusion constants of both cations and anions in [Al(hfip)4 ](-) -based ILs were higher than in [NTf2 ](-) -based ILs. Ionicities were calculated from self-diffusion constants and measured bulk conductivities, and showed that [Al(hfip)4 ](-) -based ILs yield higher ionicities than their [NTf2 ](-) analogues, the former of which reach values of virtually 100 % in some cases.From these observations it was concluded that [Al(hfip)4 ](-) -based ILs come close to systems without any interactions, and this hypothesis is underlined with a Hirshfeld analysis. Additionally, a robust, modified Marcus theory quantitatively accounted for the differences between the two anions and yielded a minimum of the activation energy for ion movement at an anion diameter of slightly greater than 1 nm, which fits almost perfectly the size of [Al(hfip)4 ](-) . Shallow Coulomb potential wells are responsible for the high mobility of ILs with such anions.

New water-stable ionic liquids based on tetrakis-(2,2,2-trifluoroethoxy)borate.

Several new ionic liquids (ILs) were prepared from Na[B(tfe)4] (tfe=OCH2 CF3 ) via metathesis, including one room temperature IL (RTIL). Prior to synthesis, suitable cations were chosen via predictive quantum-chemical calculations. Nuclear magnetic resonance monitoring over almost a month showed a total stability of the anion in the presence of water. The temperature-dependent viscosities and melting points of all the new ILs were determined. The data indicate that [B(tfe)4 ](-) ILs may be too viscous for electrochemical applications, but are interesting candidates for lubricant research.

[Tobacco cessation - the underused potential in clinical routine]. / Tabakentwöhnung ­ die bisher wenig genutzte Chance im ärztlichen Alltag.

Tobacco control, psychosocial and medical assistance regarding tobacco cessation is still a hidden potential within the German health care system. So far doctors rarely talk to their patients about their smoking status and physical and psychological benefits of quitting.This paper focusses on recommended current diagnostic and treatment standards, as well as evidence-based methods to address the topic on how to stop smoking and its association with certain diseases such as COPD, lung cancer and COVID-19 infection. The role of e-cigarettes as a cessation tool and its health related risks are critically examined. Consequences and advice how to implement smoking cessation procedures into daily practice are presented.

[Guideline-based digital smoking cessation with computer, tablet or smartphone]. / Leitlinienbasierte digitale Tabakentwöhnung mit PC, Tablet oder Smartphone.

INTRODUCTION: Tobacco smoking is related with a substantial morbidity and mortality as well as with tremendous socioeconomic burden. Therefore, an early successful smoking cessation bears an enormous medical and socioeconomic importance. The gold standard of smoking cessation, a combination of behavioral und pharmacologic therapy reaches only few smokers every year and so, guideline-based, low-threshold and broadly available digital cessation support could considerably increase the annual cessation rate. With the digital cessation program "Nichtraucherhelden" such a guideline-based program is available in Germany since December 2016. METHODS: The program consists of 2 preparation days and 10 program days und contains the major features of common smoking cessation courses. The present study examined the participants from December 2016 to November 2019 (n = 2491) regarding acceptance, adherence and effectivity. 69 % were female and the average age was 46 years. RESULTS: On average cessation was attained after 19 days. One year after the program a cessation rate of 15 % was achieved. Surprisingly, the cessation rate was higher in more addictive compared to less addictive participants. CONCLUSION: The study shows that a digital guideline-based cessation program is feasible and effectual. For confirmation a control and randomized study is required.

Immunogenic Biomarkers HMGB1 and sRAGE Are Potential Diagnostic Tools for Ovarian Malignancies.

BACKGROUND: High mobility group box 1 (HMGB1), soluble receptor of advanced glycation end products (sRAGE) and programmed cell death markers PD-1 and PD-L1 are immunogenic serum biomarkers that may serve as novel diagnostic tools for cancer diagnosis. METHODS: We investigated the four markers in sera of 231 women, among them 76 with ovarian cancer, 87 with benign diseases and 68 healthy controls, using enzyme immunoassays. Discrimination between groups was calculated using receiver operating characteristic (ROC) curves and sensitivities at fixed 90% and 95% specificities. RESULTS: HMGB1 levels were significantly elevated and sRAGE levels were decreased in cancer patients as compared to benign and healthy controls. In consequence, the ratio of HMGB1 and sRAGE discriminated best between diagnostic groups. The areas under the curve (AUCs) of the ROC curves for differentiation of cancer vs. healthy were 0.77 for HMGB1, 0.65 for sRAGE and 0.78 for the HMGB1/sRAGE ratio, and slightly lower for the differentiation of cancer vs. benigns with 0.72 for HMGB1, 0.61 for sRAGE and 0.74 for the ratio of both. The highest sensitivities for cancer detection at 90% specificity versus benign diseases were achieved using HMGB1 with 41.3% and the HMGB1/sRAGE ratio with 39.2%, followed by sRAGE with 18.9%. PD-1 showed only minor and PD-L1 no power for discrimination between ovarian cancer and benign diseases. CONCLUSION: HMGB1 and sRAGE have differential diagnostic potential for ovarian cancer detection and warrant inclusion in further validation studies.

Clinical Applicability of Tissue Polypeptide Antigen and CA-125 in Gynecological Malignancies.

BACKGROUND: Nowadays there still is no sufficient screening tool for ovarian and uterine cancer. OBJECTIVE: The current study aimed to investigate whether cancer antigen 125 (CA-125), tissue polypeptide antigen (TPA) or the combination of both markers are able to act as screening tools for ovarian or uterine cancer. METHODS: A total of 275 blood samples from different cohorts (ovarian cancer, uterine cancer, benign control group) were prospectively drawn and analyzed. RESULTS: Established biomarkers TPA and CA-125 showed elevated serum concentrations in patients with malignant tumors as compared to healthy women and women with benign diseases. In ROC curve analyses, both biomarkers were well able to discriminate between malignant and healthy, benign or overall non-malignant cases in the whole sample, with AUCs of 0.842 and above. While TPA was the best diagnostic marker in patients with uterine cancer, CA 125 was the best in patients with ovarian cancer. CONCLUSIONS: TPA and CA-125 both showed promising results for the detection of gynecologic malignancies. The combination of CA-125 and TPA did not improve sensitivity in comparison to single markers.

Serum biomarker panel diagnostics in pancreatic ductal adenocarcinoma: the clinical utility of soluble interleukins, IFN-γ, TNF-α and PD-1/PD-L1 in comparison to established serum tumor markers.

PURPOSE: Novel biomarkers to better predict outcome and select the best therapeutic strategy for the individual patient are necessary for pancreatic ductal adenocarcinoma (PDAC). METHODS: Using a panel assay, multiple biomarkers (IFN-γ, IL-10, IL-6, IL-8, TNF-α, CEA, CA 19-9, CYFRA 21-1, HE4, PD-1 and PD-L1 levels) were measured in serum samples of 162 patients with resected, locally advanced and metastatic PDAC in this retrospective single-center study. Optimal cut-off values to differentiate prognostic subgroups with significantly different overall survival (OS) were determined by receiver operator characteristics and Youden Index analysis. Marker levels were assessed before the start of chemotherapy and correlated with OS by univariate and multivariate Cox analysis. RESULTS: Median OS for resected patients was 28.2 months, for locally advanced patients 17.9 months and for patients with metastatic disease 8.6 months. CYFRA 21-1 and IL-8 discriminated metastatic from locally advanced patients best (AUC 0.85 and AUC 0.81, respectively). In univariate analyses, multiple markers showed prognostic relevance in the various subgroups. However, multivariate Cox models comprised only CYFRA 21-1 in the resected group (HR 1.37, p = 0.015), IL-10 in locally advanced PDAC (HR 10.01, p = 0.014), as well as CYFRA 21-1 and CA 19-9 in metastatic PDAC (p = 0.008 and p = 0.010) as an independent prognostic marker for overall survival. CONCLUSION: IL-10 levels may have independent prognostic value in locally advanced PDAC, whereas CYFRA 21-1 levels are prognostic after PDAC surgery. CYFRA 21-1 and IL-8 have been identified to best discriminate metastatic from locally advanced patients.