This study aimed to assess the predictive value of tumor growth rate estimates based on serial cancer antigen-125 (CA-125) levels on therapy response and survival of patients with recurrent high-grade serous ovarian cancer (HGSOC). In total, 301 consecutive patients with advanced HGSOC (exploratory cohort n = 155, treated at the Medical University of Vienna; external validation cohort n = 146, from the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) consortium) were enrolled. Tumor growth estimates were obtained using a validated two-phase equation model involving serial CA-125 levels, and their predictive value with respect to treatment response to the next chemotherapy and the prognostic value with respect to disease-specific survival and overall survival were assessed. Tumor growth estimates were an independent predictor for response to second-line chemotherapy and an independent prognostic factor for second-line chemotherapy use in both univariate and multivariable analyses, outperforming both the predictive (second line p = 0.003, HR 5.19 [1.73-15.58] vs.  https://www.selleckchem.com/products/Sunitinib-Malate-(Sutent).html  p = 0.453, HR 1.95 [0.34-11.17]) and prognostic values (second line p = 0.042, HR 1.53 [1.02-2.31] vs. p = 0.331, HR 1.39 [0.71-2.27]) of a therapy-free interval (TFI) less then 6 months. Tumor growth estimates were a predictive factor for response to third- and fourth-line chemotherapy and a prognostic factor for third- and fourth-line chemotherapy use in the univariate analysis. The CA-125-derived tumor growth rate estimate may be a quantifiable and easily assessable surrogate to TFI in treatment decision making for patients with recurrent HGSOC.Bacterial keratitis (BK) is a critical ocular infection that can lead to serious visual disability. Ciprofloxacin (CIP), moxifloxacin (MOX), and levofloxacin (LFX) have been accepted as monotherapies by the US Food and Drug Administration for BK treatment. CIP is available commercially at 0.3% w/v concentration as an ophthalmic solution and as an ointment for ocular delivery. Because of solubility issues at physiological pH, CIP precipitation can occur at the corneal surface post instillation of the solution dosage form. Consequently, the ocular bioavailability of CIP is reduced. The ointment dosage form is associated with side effects such as blurred vision, itching, redness, eye discomfort, and eye dryness. This study aimed to design a CIP loaded nanoemulsion (NE; CIP-NE) to facilitate drug penetration into the corneal layers for improved therapeutic outcomes as well as to overcome the drawbacks of the current commercial ophthalmic formulations. CIP-NE formulations were prepared by hot homogenization and ultrasonication, using oleic acid (CIP-O-NE) and Labrafac® Lipophile WL 1349 (CIP-L-NE) as the oily phase, and Tween® 80 and Poloxamer 188 as surfactants. Optimized CIP-NE was further evaluated with respect to in vitro release, ex vivo transcorneal permeation, and moist heat sterilization process, using commercial CIP ophthalmic solution as a control. Optimized CIP-O-NE formulation showed a globule size, polydispersity index, and zeta potential of 121.6 ± 1.5 nm, 0.13 ± 0.01, and -35.1 ± 2.1 mV, respectively, with 100.1 ± 2.0% drug content and was spherical in shape. In vitro release and ex vivo transcorneal permeation studies exhibited sustained release and a 2.1-fold permeation enhancement, respectively, compared with commercial CIP ophthalmic solution. Autoclaved CIP-O-NE formulation was found to be stable for one month (last time-point tested) at refrigerated and room temperature. Therefore, CIP-NE formulation could serve as an effective delivery system for CIP and could improve treatment outcomes in BK.Heterologous protein production is a highly demanded biotechnological process. Secretion of the product to the culture broth is advantageous because it drastically reduces downstream processing costs. We exploit unconventional secretion for heterologous protein expression in the fungal model microorganism Ustilago maydis. Proteins of interest are fused to carrier chitinase Cts1 for export via the fragmentation zone of dividing yeast cells in a lock-type mechanism. The kinase Don3 is essential for functional assembly of the fragmentation zone and hence, for release of Cts1-fusion proteins. Here, we are first to develop regulatory systems for unconventional protein secretion using Don3 as a gatekeeper to control when export occurs. This enables uncoupling the accumulation of biomass and protein synthesis of a product of choice from its export. Regulation was successfully established at two different levels using transcriptional and post-translational induction strategies. As a proof-of-principle, we applied autoinduction based on transcriptional don3 regulation for the production and secretion of functional anti-Gfp nanobodies. The presented developments comprise tailored solutions for differentially prized products and thus constitute another important step towards a competitive protein production platform.Canine gastric disorders are common in veterinary clinical practice and among these neoplasms require rapid identification and characterization. Standard ultrasound (US) is the imaging modality of choice for gastric wall assessment. The aim of this prospective study is to describe the specific B-mode and contrast enhanced US (CEUS) features of normal, inflammatory, and neoplastic gastric wall in dogs. B-mode US and CEUS of the stomach were performed in anesthetized dogs with or without gastric disorders. Gastric wall qualitative and quantitative parameters were evaluated on B-mode US and CEUS examination. A total of 41 dogs were included 6 healthy (HEA) as the control group; 9 gastritis (INF); 8 adenocarcinoma (AC); 8 alimentary lymphoma (AL); 4 leiomyosarcoma (LEIS); 2 gastrointestinal stromal tumor (GIST); 2 leiomyoma; 1 undifferentiated sarcoma; 1 metastatic gastric hemangiosarcoma. Gastric tumors appear as a marked wall thickness with absent layers definition and possible regional lymphadenopathy (AC and AL) and steatitis (AC) while gastritis generally shows no/mild thickening and no other alterations on B-mode US. On CEUS, neoplasm shows a higher and faster wash in if compared to that of gastritis. B-mode and CEUS assessment may be useful in the evaluation of canine gastric disorders in the distinction between gastritis and gastric neoplasms, even if there are no specific features able to discriminate between the different tumor histotypes.