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Abstract Background The aim of our study was to analyze the effect of taxane-based chemotherapy on tumor angiogenesis in patients with advanced epithelial ovarian cancer. Methods Within a prospective phase II trial, 32 patients with stage IIIC and IV ovarian cancer were treated with either two or three cycles of neoadjuvant chemotherapy prior to cytoreductive surgery. Carboplatin (AUC5) and docetaxel (75 mg/m2) were administered intravenously in a 3-weekly schedule. Changes in intratumor microvessel density (MVD) were assessed with immunohistochemistry by staining pre- and posttreatment surgical tumor specimens with panendothelial, neovascular and lymphatic vessel markers. Results Mean values of MVD defined by CD31, CD34, CD105 and D2-40 antibodies showed 12.3, 21.0, 2.7 and 3.1 vessels per high power field (HPF) before chemotherapy and increased after treatment to 15.3, 21.8, 4.8 and 3.6 per HPF, respectively. These changes were significant for CD31 (p = 0.04) and for CD105 (p = 0.02). Conclusion Taxane-based chemotherapy appears to promote tumor vascularization when administered every 3 weeks. A possible explanation is the secondary recovery of MVD in response to immediate cytotoxic and antiangiogenic effects of the chemotherapy. If confirmed prospectively, these findings favor shorter treatment intervals of taxane-based chemotherapy to counteract proangiogenic recovery.

Therapeutic oligonucleotides including siRNA and immunostimulatory ligands of Toll-like receptors (TLR) or RIG-I like helicases (RLH) are a promising novel class of drugs. They are in clinical development for a broad spectrum of applications, e.g. as adjuvants in vaccines and for the immunotherapy of cancer. Species-specific immune activation leading to cytokine release is characteristic for therapeutic oligonucleotides either as an unwanted side effect or intended pharmacology. Reliable in vitro tests designed for therapeutic oligonucleotides are therefore urgently needed in order to predict clinical efficacy and to prevent unexpected harmful effects in clinical development. To serve this purpose, we here established a human whole blood assay (WBA) that is fast and easy to perform. Its response to synthetic TLR ligands (R848: TLR7/8, LPS: TLR4) was on a comparable threshold to the more time consuming peripheral blood mononuclear cell (PBMC) based assay. By contrast, the type I IFN profile provoked by intravenous CpG-DNA (TLR9 ligand) in humans in vivo was more precisely replicated in the WBA than in stimulated PBMC. Since Heparin and EDTA, but not Hirudin, displaced oligonucleotides from their delivery agent, only Hirudin qualified as the anticoagulant to be used in the WBA. The Hirudin WBA exhibited a similar capacity as the PBMC assay to distinguish between TLR7-activating and modified non-stimulatory siRNA sequences. RNA-based immunoactivating TLR7/8- and RIG-I-ligands induced substantial amounts of IFN-α in the Hirudin-WBA dependent on delivery agent used. In conclusion, we present a human Hirudin WBA to determine therapeutic oligonucleotide-induced cytokine release during preclinical development that can readily be performed and offers a close reflection of human cytokine response in vivo. [ABSTRACT FROM AUTHOR]

Optical coherence tomography (OCT) is a new imaging method with promising results for several dermatological indications, including preoperative skin tumour characterization. While high-frequency ultrasound (HFUS) is frequently used for this purpose, overestimation of tumour thickness is a problem, due to subtumoral inflammatory infiltration that cannot be differentiated from tumour tissue. The aim of this single-centre study was to describe OCT features of basal cell carcinoma (BCC) and to determine vertical tumour thickness accurately, including a comparison with HFUS and histopathology. Tumour thickness values of 10 BCCs measured by OCT did not differ significantly from those measured by histopathology (median difference 0.12 mm). By contrast, the difference between HFUS and histopathology was greater (median difference 0.3 mm). A Pearson's correlation coefficient of 0.83 showed a stronger correlation of OCT in measuring tumour thickness compared with HFUS (0.59). Bland-Altman plots revealed a better agreement of OCT and histopathology concerning tumour thickness measurements. On the basis of this explorative study cohort, OCT was more exact than HFUS in preoperative tumour thickness estimation of BCCs compared with histopathological measurements. [ABSTRACT FROM AUTHOR]

Summary: Recently, the functional role of Jun activation domain binding protein 1 (Jab1) as a putative novel oncogene in hepatocellular carcinoma (HCC) has been postulated. We show that expression of p27Kip1, a negative cell cycle regulator, correlates inversely with Jab1 expression in HCC (P = .014). We observed nuclear Jab1 expression in 57% (55/97) and p27Kip1 expression in 32% (31/97) of HCCs. Neither Jab1 nor p27Kip1 nor inverse Jab1 and p27Kip1 expression correlated with clinicopathological parameters. However, HCCs lacking p27Kip1 with increased proliferative activity were frequently found to express Jab1 (P = .048). Normal liver tissue, cirrhosis, and tumor-like lesions (focal nodular hyperplasia, dysplastic nodules in cirrhotic liver) showed no significant Jab1 expression. In transfection studies in the hepatoma cell line Huh 7, Jab1 overexpression resulted in reduced p27Kip1 protein levels. We conclude that Jab1 expression may lead to down-regulation of the negative cell cycle regulator p27Kip1, pointing to a possible mechanism that promotes hepatocarcinogenesis. [Copyright &y& Elsevier]

Uveitis comprises a group of rare diseases characterised by intraocular inflammation which may cause vision impairment and blindness and mostly affects people of working age. Non-infectious uveitis involving the posterior pole or the entire eye is often treated with different immunomodulating or disease-modifying anti-rheumatic drugs (DMARDs). However, the evidence on long-term management strategies and reduction/termination of treatment is limited. To help develop treatment exit strategies for patients with quiescent uveitis on long-term DMARD treatment, the Treatment Exit Options for Non-infectious Uveitis registry was initiated by the German ophthalmological society. A key aspect of the registry is active participation of patients (patient-reported outcomes, PROs). In a pilot study involving members of patient organizations, a combination of questionnaires covering vision- and general health-related quality of life, adherence to treatment, productivity and effects of treatment were evaluated. As the pilot study showed coverage of relevant patient-related aspects of the disease and its effect on daily life, the evaluated questionnaires were implemented in the registry's patient module. The registry including the patient module uses the electronic data capture (EDC) software REDCap (Version 9, Vanderbilt University, USA). By involving patients in both conceptualization and ongoing data collection, the TOFU registry emphasizes the patients' perspectives, and the inclusion of patient-relevant evidence for such as the development of guidelines and treatment recommendations is ensured., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Assessing whether an association exists between drainage to multiple basins and lymphatic metastasis in patients with truncal melanoma (TM)., Methods: The study included 260 patients with primary TM (163 men; median age 56.5 y/o) with a cN0 M0, who underwent a sentinel lymph node scintigraphy and biopsy. The median tumor thickness (TT) was 1.51 mm., Results: One hundred and three patients showed more than one basin; of these, 95 patients had 2 basins, 6 had 3 basins, and 2 had 4 basins of drainage. Nodal histology was positive for metastatic disease in 65 patients, of whom, 40 had 1 basin, 24 had 2 basins and 1 had 3 basins of drainage. Of the 195 node-negative patients, 116 had 1 basin, 70 had 2 basins, 5 had 3 basins, and 2 had 4 basins of drainage (P=0.89). In a median follow-up of 36 months, 26 patients showed progressive disease, of whom 15 had 1 basin and 11 had 2 basins (P=0.76). Twenty patients died, of whom 11 had 1 basin and 9 had 2 basins (P=0.8)., Conclusions: There is no significant association between the number of drainage basins and sentinel node positivity or further progress of the disease in patients with TM.

Background: To determine serum levels of circulating cell-free DNA (cfDNA) throughout the stages of endometrial proliferation and apoptosis during the menstrual cycle., Materials and Methods: cfDNA was measured in 176 blood samples from 17 healthy volunteers taken at three different time points (menstruation, follicular and secretory phase). Additionally, blood samples from 20 newly diagnosed breast cancer patients were analysed. Quantitative real-time PCR was performed in order to quantify cfDNA fragments of 106 bp., Results: In healthy individuals, levels of cfDNA did not differ significantly during the menstrual cycle. In breast cancer patients, the median cfDNA level was significantly higher compared to healthy individuals, irrespective of the cycle phase (p<0.001)., Conclusion: The female cycle does not influence cfDNA serum level measurements. Considering the diagnostic or prognostic value of cfDNA in cancer patients, different time points of blood sampling in premenopausal women seem to be negligible.

Background: Breast cancer is one of the most frequent tumors worldwide. Currently applied diagnostic approaches are frequently not able to recognize early stages in tumor development therefore impairing outcomes. The focus of this study is the creation of a non-invasive predictive diagnostic approach by pathology-specific blood proteome analysis., Patients and Methods: Circulating leukocytes were isolated from fresh blood samples of breast cancer patients, benign breast pathologies and healthy controls. In patients with all kinds of breast pathologies, blood samples were taken before core needle biopsy of the lump. Comparative protein mapping was performed by 2D-PAGE followed by MALDI-TOF analysis and Western-blot quantification of differentially expressed protein spots., Results: By protein mapping, 64 protein spots were identified. Pathology-specific differential expression patterns comprised microfilamental network-associated proteins: Calgranulin A (S100), LyGDI (Rho GDIbeta), RhoA and profilin 1. RhoA and profilin values discriminated between healthy controls and patients with all breast pathologies., Conclusion: Microfilamental network-associated proteins are involved in the regulation of a variety of central cellular processes functionally linked with each other and known to be highly relevant for all stages of tumorigenesis including precancerous lesions and metastases. Pathology-related molecular patterns are currently considered for the creation of a novel highly sensitive minimally-invasive approach for predictive diagnosis of breast cancer.