Applying science in practice: the optimization of biological therapy in rheumatoid arthritis

Most authorities recommend starting biological agents upon failure of at least one disease-modifying agent in patients with rheumatoid arthritis. However, owing to the absence of head-to-head studies, there is little guidance about which biological to select. Still, the practicing clinician has to decide. This review explores the application of published evidence to practice, discussing the goals of treatment, the (in) ability to predict individual responses to therapy, and the potential value of indirect comparisons. We suggest that cycling of biological agents, until remission is achieved or until the most effective agent for that individual patient is determined, deserves consideration in the current stage of knowledge

Tumorigenesis and peritoneal colonization from fallopian tube epithelium.

Ovarian cancer is the most lethal gynecological malignancy, primarily because its origin and initiation factors are unknown. A secretory murine oviductal epithelial (MOE) model was generated to address the hypothesis that the fallopian tube is an origin for high-grade serous cancer. MOE cells were stably altered to express mutation in p53, silence PTEN, activate AKT, and amplify KRAS alone and in combination, to define if this cell type gives rise to tumors and what genetic alterations are required to drive malignancy. Cell lines were characterized in vitro and allografted into mice. Silencing PTEN formed high-grade carcinoma with wide spread tumor explants including metastasis into the ovary. Addition of p53 mutation to PTEN silencing did not enhance this phenotype, whereas addition of KRAS mutation reduced survival. Interestingly, PTEN silencing and KRAS mutation originating from ovarian surface epithelium generated endometrioid carcinoma, suggesting that different cellular origins with identical genetic manipulations can give rise to distinct cancer histotypes. Defining the roles of specific signaling modifications in tumorigenesis from the fallopian tube/oviduct is essential for early detection and development of targeted therapeutics. Further, syngeneic MOE allografts provide an ideal model for pre-clinical testing in an in vivo environment with an intact immune system

Comparison of 18F-FDG PET/CT methods of analysis for predicting response to neoadjuvant chemoradiation therapy in patients with locally advanced low rectal cancer

Purpose: The aim of this study was to prospectively investigate the predictive value of 18F-FDG PET/CT semiquantitative parameters for locally advanced low rectal cancer (LARC) treated by neoadjuvant chemoradiation therapy (nCRT). Methods: 68 patients with LARC had 18F-FDG PET/CT scans twice (baseline and 5–6 weeks post-nCRT). All patients underwent surgery with preservation of the sphincter 8 weeks later. 18F-FDG PET/CT analysis was performed by visual response assessment (VRA) and semiquantitative parameters: SUVmaxbaseline, SUVmeanbaseline, MTVbaseline, TLGbaseline, SUVmaxpost-nCRT, SUVmeanpost-nCRT, MTVpost-nCRT, TLGpost-nCRT; ΔSUVmax and mean and Response indexes (RImax% and RImean%). Assessment of nCRT tumor response was performed according to the Mandard’s Tumor Regression Grade (TRG) and (y)pTNM staging on the surgical specimens. Concordances of VRA with TRG, and with (y)pTNM criteria were evaluated by Cohen’s K. Results were compared by t student test for unpaired groups. ROC curve analysis was performed. Results: VRA analysis of post-nCRT 18F-FDG PET/CT scan for the (y)pTNM outcome showed sensitivity, specificity, accuracy, PPV, and NPV of 87.5%, 66.7%, 83.8%, 92.5%, and 53.3%, respectively. Concordances of VRA with TRG and with (y)pTNM were moderate. For the outcome variable TRG, the statistical difference between responders and non-responders was significant for SUVmaxpost-nCRT and RImean%; for the outcome variable (y)pTNM, there was a significant difference for MTVbaseline, SUVmaxpost-nCRT, SUVmeanpost-nCRT, MTVpost-nCRT, RImax%, and RImean%. ROC analysis showed better AUCs: for the outcome variable TRG for SUVmaxpost-nCRT, SUVmeanpost-nCRT, and RImean%; for the outcome variable (y)pTNM for MTVbaseline, SUVmaxpost-nCRT, SUVmeanpost-nCRT, MTVpost-nCRT, RImax%, and RImean%. No significant differences among parameters were found. Conclusions: Qualitative and semiquantitative evaluations for 18F-FDG PET/CT are the optimal approach; a valid parameter for response prediction has still to be established. © 2014, Springer Science+Business Media New York