Rote Liste der Schwebfliegen (Diptera: Syrphidae) Baden-Württembergs / [Autoren Dieter Doczkal, Klaus Rennwald & Ulrich Schmid]. Fachdienst Naturschutz ... Hrsg. von der Landesanstalt für Umweltschutz Baden-Württemberg

Schwebfliegen kommen in großer Zahl in fast allen terrestrischen Lebensräumen vor. Dennoch spielen sie bisher in der praktischen Naturschutzarbeit eine untergeordnete Rolle. Verglichen mit anderen Tiergruppen, wie den Tagfaltern, Laufkäfern oder Wildbienen, werden sie nur selten im Rahmen raumrelevanter Planungen berücksichtigt. Dabei decken sie wie keine andere der häufiger untersuchten Gruppen ein breites Spektrum unterschiedlicher Lebensweisen ab. Während die Imagines der meisten Arten eifrige Blütenbesucher sind und eine wichtige Funktion als Bestäuber ausüben, zeichnen sich die Larven durch eine hohe Diversität von Lebensstrategien aus. Die phytophagen Arten minieren in Stängeln, Wurzeln oder Blättern, befallen unterirdische Speicherorgane von Pflanzen oder zapfen das Kambium von Nadelbäumen an. Manche Arten leben in den Fruchtkörpern von Pilzen. Saprophage Arten nutzen abgestorbene feuchte Pflanzen, an organischem Material reiche Gewässer (Pfützen, Teiche, wassergefüllte Baumhöhlen, etc.), leben in Schleimflüssen von Bäumen, in sich zersetzendem Holz, in Säugerkot oder ernähren sich vom Abfall in Wespen- und Hummelnestern. Die zoophagen Vertreter fressen Blattläuse, Raupen, Wespen- oder Ameisenbrut. Schwebfliegen findet man in praktisch allen terrestrischen Lebensräumen, im Wald ebenso wie auf Äckern und im Grünland, auf Sandrasen wie im Hochmoor. In Mitteleuropa sind die meisten Arten eher in frischen bis feuchten Lebensräumen zu finden, Wälder und andere gehölzreiche Lebensräume sind artenreicher als ganz offene Biotope. Einen für interessierte Laien geschriebenen Überblick über die Lebensweise der Schwebfliegen hat SCHMID (1996) veröffentlicht

Tadalafil Enhances Immune Signatures in Response to Neoadjuvant Nivolumab in Resectable Head and Neck Squamous Cell Carcinoma

Purpose: We hypothesize that the addition of the phosphodiesterase-5 inhibitor tadalafil to the PD-1 inhibitor nivolumab, is safe and will augment immune-mediated antitumor responses in previously untreated squamous cell carcinoma of the head and neck (HNSCC). Patients and methods: We conducted a two-arm multi-institutional neoadjuvant randomized trial in any-stage resectable HNSCC (NCT03238365). Patients were stratified at randomization by human papillomavirus (HPV) status. Patients in both arms received nivolumab 240 mg intravenously on days 1 and 15 followed by surgery on day 28. Those in the combination therapy arm also received tadalafil 10 mg orally once daily for 4 weeks. Imaging, blood, and tumor were obtained pretreatment and posttreatment for correlative analysis. Results: Neoadjuvant therapy was well-tolerated with no grade 3 to 5 adverse events and no surgical delays. Twenty-five of 46 (54%) evaluable patients had a pathologic treatment response of ≥20%, including three (7%) patients with a complete pathologic response. Regardless of HPV status, tumor proliferation rate was a negative predictor of response. A strong pretreatment T-cell signature in the HPV-negative cohort was a predictor of response. Tadalafil altered the immune microenvironment, as evidenced by transcriptome data identifying enriched B- and natural killer cell gene sets in the tumor and augmented effector T cells in the periphery. Conclusions: Preoperative nivolumab ± tadalafil is safe in HNSCC and results in more than 50% of the patients having a pathologic treatment response of at least 20% after 4 weeks of treatment. Pretreatment specimens identified HPV status-dependent signatures that predicted response to immunotherapy while posttreatment specimens showed augmentation of the immune microenvironment with the addition of tadalafil

Prognostic and therapeutic impact of Argininosuccinate Synthetase 1 control in bladder cancer as monitored longitudinally by PET imaging

[[abstract]]Targeted therapies have yet to have significant impact on the survival of patients with bladder cancer. In this study, we focused on the urea cycle enzyme argininosuccinate synthetase 1 (ASS1) as a therapeutic target in bladder cancer, based on our discovery of the prognostic and functional import of ASS1 in this setting. ASS1 expression status in bladder tumors from 183 Caucasian and 295 Asian patients was analyzed, along with its hypothesized prognostic impact and association with clinicopathologic features, including tumor size and invasion. Furthermore, the genetics, biology, and therapeutic implications of ASS1 loss were investigated in urothelial cancer cells. We detected ASS1 negativity in 40% of bladder cancers, in which multivariate analysis indicated worse disease-specific and metastasis-free survival. ASS1 loss secondary to epigenetic silencing was accompanied by increased tumor cell proliferation and invasion, consistent with a tumor-suppressor role for ASS1. In developing a treatment approach, we identified a novel targeted antimetabolite strategy to exploit arginine deprivation with pegylated arginine deiminase (ADI-PEG20) as a therapeutic. ADI-PEG20 was synthetically lethal in ASS1-methylated bladder cells and its exposure was associated with a marked reduction in intracellular levels of thymidine, due to suppression of both uptake and de novo synthesis. We found that thymidine uptake correlated with thymidine kinase-1 protein levels, and that thymidine levels were imageable with [18F]-fluoro-L-thymidine (FLT)-positron emission tomography (PET). In contrast, inhibition of de novo synthesis was linked to decreased expression of thymidylate synthase and dihydrofolate reductase. Notably, inhibition of de novo synthesis was associated with potentiation of ADI-PEG20 activity by the antifolate drug pemetrexed. Taken together, our findings argue that arginine deprivation combined with antifolates warrants clinical investigation in ASS1-negative urothelial and related cancers, using FLT-PET as an early surrogate marker of response