Magic™ Anti-S100P polyclonal antibody [Biotin]

Intrahepatic cholangiocarcinomas are histologically heterogenous. Using a cohort of 184 clinically defined, resected intrahepatic cholangiocarcinomas, we retrospectively classified the histology into 4 subtypes: large duct (LD), small duct (SD) (predominantly tubular [SD1] or predominantly anastomosing/cholangiolar, [SD2]), or indeterminate. Then, we tested the 4 subtypes for associations with risk factors, patient outcomes, histology, and immunophenotypic characteristics. SD was the most common (84%; 24% SD1 and 60% SD2) with lower proportions of LD (8%), and indeterminate (8%). Primary sclerosing cholangitis was rare (2%), but correlated with LD (P = 0.005). Chronic hepatitis, frequent alcohol use, smoking, and steatosis had no histologic association. LD was associated with mucin production (P < 0.001), perineural invasion (P = 0.002), CA19-9 staining (P < 0.001), CK7(+), CK19(+), CD56(-) immunophenotype (P = 0.005), and negative albumin RNA in situ hybridization (P < 0.001). SD was histologically nodular (P = 0.019), sclerotic (P < 0.001), hepatoid (P = 0.042), and infiltrative at the interface with hepatocytes (P < 0.001). Albumin was positive in 71% of SD and 18% of LD (P = 0.0021). Most albumin positive tumors (85%) lacked extracellular mucin (P < 0.001). S100P expression did not associate with subtype (P > 0.05). There was no difference in disease-specific or recurrence-free survival among the subtypes. Periductal infiltration and American Joint Committee on Cancer eighth edition pT stage predicted survival by multivariable analysis accounting for gross configuration, pT stage, and histologic type. pT2 had worse outcome relative to other pT stages. Significant differences in histology and albumin expression distinguish LD from SD, but there is insufficient evidence to support further subclassification of SD.

Cytokine interleukin-11 (IL-11) is a multifunctional protein with diverse roles in the normal cell signaling and in various pathologies. The structure of IL-11 is characterized by a four-helix bundle motif comprising two pairs of antiparallel alpha-helices arranged in an up-up-down-down configuration. Evaluation of the intrinsic disorder predisposition of human IL-11 by several computational tools clearly shows that this protein is predicted to have functional disordered regions potentially involved in interaction with natural binding partners. Signaling by IL-11 proceeds via an interaction of the protein with its membrane-specific receptor IL-11R alpha and a subsequent interaction of the complex with the transmembrane signal-transducing receptor GP130. Cytoplasmic domain of IL-11R alpha is predicted to be very disordered, and noticeable amount of disorder is present even in the large extracellular domain of the protein. GP130 is also predicted to have long disordered region that is located at the C-terminal of the protein and is expected to have several disorder-based binding sites. It shows that intrinsic disorder might play an important role in functioning of this signaling machine. A specific subset of the calcium sensor proteins (calmodulin, S100P, S100B, NCS-1, GCAP-1/2) exhibits metal-dependent binding of IL-11 with dissociation constants in a range of 1-19 mu M, and the structural features of their hinge regions likely ensure selectivity and calcium sensitivity of IL-11 binding to the EF-hand proteins studied. IL-11 exhibits multiple effects on hematopoietic and non-hematopoietic systems. It plays a major role in orchestrating complex processes of tumor development and progression.