Risikofaktoren für die Entstehung von Zweitkarzinomen im Bereich des oberen Aerodigestivtraktes

Diese Arbeit widmet sich möglichen Risikofaktoren für die Entstehung von Zweitkarzinomen im Bereich des oberen Aerodigestivtraktes. Es wurden 177 Pat.(HNO-Abt. BWK Ulm) gemäß den Einschlusskriterien ausgewählt und die klinischen Daten erhoben. Von März-Oktober 2006 wurden die personenbezogenen Daten mittels Fragebogen(6 Abschnitte,53 Fragen) erhoben. 106 Pat. wurden eingeschlossen (12 Pat. verstorben,59 Pat. Ausschlusskriterien). Durchschnittliches Alter der Patientengruppen A:55,9Jahre, B:53,3Jahre. Verhältnis Männer zu Frauen=8:1. Signifikante Ergebnisse bei Familienstand (Gr.A -Pat.ohne Zweitumor-7%,Gr.B -Pat.mit Zweittumor-26% allein lebend,p<0,05), Zahnprothesenträger (Gr.A6%,Gr.B26%,p<0,05), regelm. Medikamenteneinnahme (Gr.A55%,Gr.B83%,p<0,05). Tendenziell höhere Komorbidität in Gr.B (87%,Gr.A71%,p=0,168), Tabak- (Gr.A19%,Gr.B35%,p=0,154) und Alkoholkonsum (Gr.A48%,Gr.B52%,p=0,809), nicht abgeschlossene Schul- (Gr.A6%,Gr.B13%,p=0,36) und Berufsausbildung (Gr.A16%,Gr.B22%,p=0,535), keine regelm. Zahnarztbesuche (Gr.A17%,Gr.B26%,p=0,375). Ausgeprägte Unterschiede bei subjektive Wahrnehmung der regelm.Nachsorgetermine (je 97%) und validierte Termine (Gr.A26%,Gr.B13%,p=0,541). Keinen Einfluss zeigten Ernährung, fam.Prädisposition, histolog.Kriterien des Ersttumors. Regelm. Alkohol-und Tabakkonsum nach Therapie des Ersttumors scheint das Risiko für die Entstehung von Zweitkarzinomen tendenziell zu erhöhen, ebenso wie eine vorhandene Komorbidität und einer hier signifikant höheren Medikamenteneinnahme. Soziodemographische Faktoren, eine nicht abgeschlossene Schul-und Berufsausbildung scheinen eine Rolle zu spielen. Keinen nachweisbaren Einfluss zeigten Ernährung, fam.Prädisposition und histolog.Kriterien des Ersttumors. Eine bessere Nachsorgecompliance der Zweittumorpatienten hätte eventuell einige Zweittumore bereits als Vorstufen erfassen können, um die begrenzten Therapiemöglichkeiten bestmöglich nutzen zu können(Bedeutende Führungsrolle des behand. Arztes)

Combined [18F]-Fluoroethylcholine PET/CT and 99mTc-Macroaggregated Albumin SPECT/CT Predict Survival in Patients With Intermediate-Stage Hepatocellular Carcinoma

Aim The aim of this study was to retrospectively analyze the prognostic value of combined Tc-99m-macroaggregated albumin (MAA) SPECT/CT and [F-18]-fluoroethylcholine (FEC) PET/CT before radioembolization for survival of patients with intermediate-stage hepatocellular carcinoma. Methods Twenty-four patients with known hepatocellular carcinoma Barcelona Clinic Liver Cancer stage B were eligible for this analysis. All patients were scheduled for radioembolization and received a pretherapeutic [F-18]FEC PET/CT scan as well as Tc-99m-MAA SPECT/CT for hepatopulmonary shunting. Laboratory and semiquantitative PET parameters and morphologic and metabolic (intersection) volumes of MAA and FEC were evaluated. Spearman correlation with overall survival, receiver operating curve analyses, univariate and multivariate Cox regression, and Kaplan-Meier-analysis was applied. Results All patients (5 female/19 male) are deceased within the observational period. Median survival was 395 days (51 days;range, 23-1122 days). The percentage of hypervascularized metabolically active tumor volume (vascularized tumor ratio;defined as high MAA and FEC uptake) correlated significantly with survival. Vascularized tumor ratio was a significant predictor in univariate and multivariate analyses (P = 0.026;hazard ratio, 11.65;95% confidence interval, 1.62-83.73;P = 0.015). Statistical significance was not reached by all other variables in multivariate analysis. Receiver operating curve analysis for 1-year survival revealed an area under the curve of 0.77 (P = 0.024) for vascularized tumor ratio. At a cutoff value of 9%, sensitivity, specificity, and positive and negative prediction were 83%, 67%, and 71% and 80% (P = 0.036). Patients with a higher tumor vascularization had a median survival of 274 +/- 80 versus 585 +/- 284 days (P = 0.015). Conclusion: s Hepatocellular carcinoma with high vascularization in metabolic active areas as assessed by combined FEC PET/CT and Tc-MAA SPECT/CT represents an unfavorable subgroup with reduced overall survival after radioembolization

European Journal of Nuclear Medicine and Molecular Imaging / [18F]DOPA PET/ceCT in diagnosis and staging of primary medullary thyroid carcinoma prior to surgery

Purpose Medullary thyroid carcinoma (MTC) is characterized by a high rate of metastasis. In this study we evaluated the ability of [18F]DOPA PET/ceCT to stage MTC in patients with suspicious thyroid nodules and pathologically elevated serum calcitonin (Ctn) levels prior to total thyroidectomy and lymph node (LN) dissection. Methods A group of 32 patients with sonographically suspicious thyroid nodules and pathologically elevated basal Ctn (bCtn) and stimulated Ctn (sCtn) levels underwent DOPA PET/ceCT prior to surgery. Postoperative histology served as the standard of reference for ultrasonography and DOPA PET/ceCT region-based LN staging. Univariate and multivariate regression analyses as well as receiver operating characteristic analysis were used to evaluate the correlations between preoperative and histological parameters and postoperative tumour persistence or relapse. Results Primary MTC was histologically verified in all patients. Of the 32 patients, 28 showed increased DOPA decarboxylase activity in the primary tumour (sensitivity 88%, mean SUVmax 10.5). Undetected tumours were exclusively staged pT1a. The sensitivities of DOPA PET in the detection of central and lateral metastatic neck LN were 53% and 73%, in contrast to 20% and 39%, respectively, for neck ultrasonography. Preoperative bCtn and carcinoembryonic antigen levels as well as cN1b status and the number of involved neck regions on DOPA PET/ceCT were predictive of postoperative tumour persistence/relapse in the univariate regression analysis (P < 0.05). Only DOPA PET/ceCT cN1b status remained significant in the multivariate analysis (P = 0.016, relative risk 4.02). Conclusion This study revealed that DOPA PET/ceCT has high sensitivity in the detection of primary MTC and superior sensitivity in the detection of LN metastases compared to ultrasonography. DOPA PET/ceCT identification of N1b status predicts postoperative tumour persistence. Thus, implementation of a DOPA-guided LN dissection might improve surgical success.(VLID)360071

Dual-Tracer PET-MRI-Derived Imaging Biomarkers for Prediction of Clinically Significant Prostate Cancer

Purpose: To investigate if imaging biomarkers derived from 3-Tesla dual-tracer [(18)F]fluoromethylcholine (FMC) and [68Ga]Ga-PSMAHBED-CC conjugate 11 (PSMA)-positron emission tomography can adequately predict clinically significant prostate cancer (csPC). Methods: We assessed 77 biopsy-proven PC patients who underwent 3T dual-tracer PET/mpMRI followed by radical prostatectomy (RP) between 2014 and 2017. We performed a retrospective lesion-based analysis of all cancer foci and compared it to whole-mount histopathology of the RP specimen. The primary aim was to investigate the pretherapeutic role of the imaging biomarkers FMC- and PSMA-maximum standardized uptake values (SUVmax) for the prediction of csPC and to compare it to the mpMRI-methods and PI-RADS score. Results: Overall, we identified 104 cancer foci, 69 were clinically significant (66.3%) and 35 were clinically insignificant (33.7%). We found that the combined FMC+PSMA SUVmax were the only significant parameters (p p = 0.049) for the prediction of csPC. ROC analysis showed an AUC for the prediction of csPC of 0.695 for PI-RADS scoring (95% CI 0.591 to 0.786), 0.792 for FMC SUVmax (95% CI 0.696 to 0.869), 0.852 for FMC+PSMA SUVmax (95% CI 0.764 to 0.917), and 0.852 for the multivariable CHAID model (95% CI 0.763 to 0.916). Comparing the AUCs, we found that FMC+PSMA SUVmax and the multivariable model were significantly more accurate for the prediction of csPC compared to PI-RADS scoring (p = 0.0123, p = 0.0253, respectively). Conclusions: Combined FMC+PSMA SUVmax seems to be a reliable parameter for the prediction of csPC and might overcome the limitations of PI-RADS scoring. Further prospective studies are necessary to confirm these promising preliminary results

Thyroid and androgen receptor signaling are antagonized by μ-Crystallin in prostate cancer.

Androgen deprivation therapy (ADT) remains a key approach in the treatment of prostate cancer (PCa). However, PCa inevitably relapses and becomes ADT resistant. Besides androgens, there is evidence that thyroid hormone thyroxine (T4) and its active form 3,5,3'-triiodo-L-thyronine (T3) are involved in the progression of PCa. Epidemiologic evidences show a higher incidence of PCa in men with elevated thyroid hormone levels. The thyroid hormone binding protein μ-Crystallin (CRYM) mediates intracellular thyroid hormone action by sequestering T3 and blocks its binding to cognate receptors (TRα/TRβ) in target tissues. We show in our study that low CRYM expression levels in PCa patients are associated with early biochemical recurrence and poor prognosis. Moreover, we found a disease stage-specific expression of CRYM in PCa. CRYM counteracted thyroid and androgen signaling and blocked intracellular choline uptake. CRYM inversely correlated with [18F]fluoromethylcholine (FMC) levels in positron emission tomography/magnetic resonance imaging of PCa patients. Our data suggest CRYM as a novel antagonist of T3- and androgen-mediated signaling in PCa. The role of CRYM could therefore be an essential control mechanism for the prevention of aggressive PCa growth

Engaging the public effectively in recycling activities: a systematic approach

Although frequently used as protein production host, there is only a limited set of promoters available to drive the expression of recombinant proteins in Pichia pastoris. Fine-tuning of gene expression is often needed to maximize product yield and quality. However, for efficient knowledge-based engineering, a better understanding of promoter function is indispensable. Consequently, we created a promoter library by deletion and duplication of putative transcription factor-binding sites within the AOX1 promoter (PAOX1) sequence. This first library initially spanned an activity range between ∼6% and \u3e160% of the wild-type promoter activity. After characterization of the promoter library employing a green fluorescent protein (GFP) variant, the new regulatory toolbox was successfully utilized in a ‘real case’, i.e. the expression of industrial enzymes. Characterization of the library under repressing, derepressing and inducing conditions displayed at least 12 cis-acting elements involved in PAOX1-driven high-level expression. Based on this deletion analysis, novel short artificial promoter variants were constructed by combining cis-acting elements with basal promoter. In addition to improving yields and quality of heterologous protein production, the new PAOX1 synthetic promoter library constitutes a basic toolbox to fine-tune gene expression in metabolic engineering and sequential induction of protein expression in synthetic biology