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Background The advanced lung cancer inflammation index (ALI) was first introduced for prognosis prediction in lung cancer patients and since then evaluated in several other malignancies. However, in pancreatic cancer (PC) the ALI and its prognostic utility were only investigated in a comparably small and specific cohort of locally advanced PC patients treated with chemoradiotherapy. Methods In our single‐center cohort study, we included 429 patients with histologically verified PC who were treated between 2003 and 2015 at our academic institution. The ALI was defined as body mass index (BMI; kg/m2) × serum albumin levels (g/dL)/neutrophil‐lymphocyte ratio (NLR) and we defined the optimal cutoff for biomarker dichotomization by ROC‐analysis. Kaplan‐Meier method as well as uni‐ and multivariate Cox regression Hazard proportional models were implemented to assess the prognostic potential of ALI in PC patients. We considered cancer‐specific survival (CSS) as the primary endpoint of the study. Results The ALI showed a significant negative correlation with CA19‐9 levels and C‐reactive protein levels whereas we found an association with localized tumor stage and better performance status (P, The advanced lung cancer inflammation index (ALI) was originally established as a prognostic tool in lung cancer patients and consequently validated in various other types of cancer. To date, however, in pancreatic cancer (PC) patients, the prognostic value of the ALI has only been investigated in a relatively small cohort of chemoradiotherapy‐treated patients with locally advanced PC. Converse to previous results, in this large cohort of PC patients, the ALI does not add additional prognostic value to the established clinicopathological prognostic factors.

Streptavidin is a homotetrameric protein binding the vitamin biotin and peptide analogues with an extremely high affinity, which leads to a large variety of applications. The biotin-auxotrophic yeast Pichia pastoris has recently been identified as a suitable host for the expression of the streptavidin gene, allowing both high product concentrations and productivities. However, so far only methanol-based expression systems have been applied, bringing about increased oxygen demand, strong heat evolution and high requirements for process safety, causing increased cost. Moreover, common methanol-based processes lead to large proportions of biotin-blocked binding sites of streptavidin due to biotin-supplemented media. Targeting these problems, this paper provides strategies for the methanol-free production of highly bioactive core streptavidin by P. pastoris under control of the constitutive GAP promoter. Complex were superior to synthetic production media regarding the proportion of biotin-blocked streptavidin. The optimized, easily scalable fed-batch process led to a tetrameric product concentration of up to 4.16 +/- 0.11 mu M of biotin-free streptavidin and a productivity of 57.8 nM h(-1) based on constant glucose feeding and a successive shift of temperature and pH throughout the cultivation, surpassing the concentration in un-optimized conditions by a factor of 3.4. Parameter estimation indicates that the optimized conditions caused a strongly increased accumulation of product at diminishing specific growth rates ( approximate to D

The protein streptavidin (SAV) is applied in a large variety of molecular methods due to an extraordinarily strong binding to the vitamin biotin (BIO). The protein structure is homotetrameric, characterized by one binding site for BIO per subunit. Therefore, one of the major criteria to determine the quality of SAV isolates is the proportion of BIO-blocked binding sites per tetramer. A rapid analysis of BIO-free binding sites is achieved by fluorescence quenching of biotin-4-fluorescein (B4F). However, BIO-blocked binding sites can only be determined by costly and laborious procedures such as ELISA-based methods or radioactive labeling. This study describes the systematic, model-supported development of a method for the quick and simple detection of BIO-blocked binding sites, based on a short-term heat incubation of the sample in the presence of B4F. Kinetic modeling and parameter estimation yielded dissociation constants of 1.22 +/- 0.27 x 10(-11) M for the complex SAV-BIO and 5.16 +/- 0.70 x 10(-13) M for SAV-B4F at 70 degrees C, allowing a displacement of SAV-bound BIO by B4F. This method allows the rapid monitoring of BIO-blocked binding sites in fermentation processes, independent from the chain length of SAV and the concentration of contaminating proteins, e.g. when optimizing the BIO concentration in cultivation media.