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

Radiation protection of the gastrointestinal tract and growth inhibition of prostate cancer xenografts by a single compound.

Normal tissue toxicity markedly reduces the therapeutic index of genotoxic anticancer agents, including ionizing radiation. Countermeasures against tissue damage caused by radiation are limited by their potential to also protect malignant cells and tissues. Here, we tested a panel of signal transduction modifiers for selective radioprotection of normal but not tumor tissues. These included three inhibitors of GSK3 (LiCl, SB216763, and SB415286) and two inhibitors of NF-κB (ethyl pyruvate and RTA 408). Among these, the thiol-reactive triterpenoid RTA 408 emerged as a robust and effective protector of multiple organ systems (gastrointestinal, skin, and hemopoietic) against lethal doses of radiation. RTA 408 preserved survival and proliferation of intestinal crypt cells in lethally irradiated mice while reducing apoptosis incidence in crypts and villi. In contrast, RTA 408 uniformly inhibited growth of established CWR22Rv1, LNCaP/C4-2B, PC3, and DU145 xenografts either alone or combined with radiation. Antitumor effects in vivo were associated with reduced proliferation and intratumoral apoptosis and with inhibition of NF-κB-dependent transcription in PC3 cells. Selective protection of normal tissue compartments by RTA 408 critically depended on tissue context and could not be replicated in vitro. Collectively, these data highlight the potential of RTA 408 as a cytoprotective agent that may be safely used in chemoradiation approaches

EpCAM (CD326) finding its role in cancer

Although epithelial cell adhesion/activating molecule (EpCAM/CD326) is one of the first tumour-associated antigens identified, it has never received the same level of attention as other target proteins for therapy of cancer. It is also striking that ever since its discovery in the late 1970s the actual contribution of EpCAM to carcinogenesis remained unexplored until very recently. With a First International Symposium on EpCAM Biology and Clinical Application this is now changing. Key topics discussed at the meeting were the frequency and level of EpCAM expression on various cancers and its prognostic potential, the role of EpCAM as an oncogenic signalling molecule for cancer cells, recent progress on EpCAM-directed immunotherapeutic approaches in clinical development and the interaction of EpCAM with other proteins, which may provide a basis for a therapeutic window and repression of its growth-promoting signalling in carcinoma. Future research on EpCAM may benefit from a unified nomenclature and more frequent exchange among those who have been working on this cancer target during the past 30 years and will do so in the future

Ep-CAM expression in squamous cell carcinoma of the esophagus: a potential therapeutic target and prognostic marker

BACKGROUND: To evaluate the expression and test the clinical significance of the epithelial cellular adhesion molecule (Ep-CAM) in esophageal squamous cell carcinoma (SCC) to check the suitability of esophageal SCC patients for Ep-CAM directed targeted therapies. METHODS: The Ep-CAM expression was immunohistochemically investigated in 70 primary esophageal SCCs using the monoclonal antibody Ber-EP4. For the interpretation of the staining results, we used a standardized scoring system ranging from 0 to 3+. The survival analysis was calculated from 53 patients without distant metastasis, with R0 resection and at least 2 months of clinical follow-up. RESULTS: Ep-CAM neo-expression was observed in 79% of the tumors with three expression levels, 1+ (26%), 2+ (11%) and 3+ (41%). Heterogeneous expression was observed at all expression levels. Interestingly, tumors with 3+ Ep-CAM expression conferred a significantly decreased median relapse-free survival period (log rank, p = 0.0001) and median overall survival (log rank, p = 0.0003). Multivariate survival analysis disclosed Ep-CAM 3+ expression as independent prognostic factor. CONCLUSION: Our results suggest Ep-CAM as an attractive molecule for targeted therapy in esophageal SCC. Considering the discontenting results of the current adjuvant concepts for esophageal SCC patients, Ep-CAM might provide a promising target for an adjuvant immunotherapeutic intervention

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

Transcription factors and molecular epigenetic marks underlying EpCAM overexpression in ovarian cancer

BACKGROUND: The epithelial cell adhesion molecule (EpCAM) is overexpressed on carcinomas, and its downregulation inhibits the oncogenic potential of multiple tumour types. Here, we investigated underlying mechanisms of epcam overexpression in ovarian carcinoma. METHODS: Expression of EpCAM and DNA methylation (bisulphite sequencing) was determined for ovarian cancer cell lines. The association of histone modifications and 16 transcription factors with the epcam promoter was analysed by chromatin immunoprecipitation. Treatment with 5-Aza-2'-deoxycytidine (5-AZAC) was used to induce EpCAM expression. RESULTS: Expression of EpCAM was correlated with DNA methylation and histone modifications. Treatment with 5-AZAC induced EpCAM expression in negative cells. Ten transcription factors were associated with the epcam gene in EpCAM expressing cells, but not in EpCAM-negative cells. Methylation of an Sp1 probe inhibited the binding of nuclear extract proteins in electromobility shift assays; such DNA methylation sensitivity was not observed for an NF-kappa B probe. CONCLUSION: This study provides insights in transcriptional regulation of epcam in ovarian cancer. Epigenetic parameters associated with EpCAM overexpression are potentially reversible, allowing novel strategies for sustained silencing of EpCAM expression. British Journal of Cancer (2011) 105, 312-319. doi: 10.1038/bjc.2011.231 www.bjcancer.com Published online 21 June 2011 (C) 2011 Cancer Research U

Characterization of the human TESTIN gene localized in the FRA7G region at 7q31.2

Cancer-associated chromosomal aberrations often involve regions containing fragile sites. FRA7G is a common aphidicolin-inducible fragile site at 7q31.2, showing loss of heterozygosity in human malignancies. To investigate the structure of FRA7G, we constructed a bacterial artificial chromosome contig spanning the region between marker D7S486 and Met H. Analysis of the FRA7G sequence allowed us to identify a gene encoding a 421-amino-acid protein with three LIM domains and 89% identity to murine Testin. We determined the genomic structure of the human TESTIN locus and characterized three alternative transcripts. Although TESTIN mRNA is expressed in all normal human tissues examined, we observed lack of expression in 22% of cancer cell lines and 44% of the cell lines derived from hematological malignancies. We further determined that in most of these cases the inactivation of TESTIN expression is due to methylation of a CpG island. Analysis of the TESTIN coding region in 26 tumor cell lines revealed three missense mutations. Our findings suggest that TESTIN may represent a candidate tumor suppressor gene at 7q31.2. (C) 2000 Academic Press