Scaffold proteins of cancer signaling networks: The paradigm of FK506 binding protein 51 (FKBP51) supporting tumor intrinsic properties and immune escape

Scaffold proteins are crucial regulators of signaling networks,and their abnormal expression may favor the development of tumors.Among the scaffold proteins,immunophilin covers a unique role as‘protein-philin’(Greek‘philin’=friend)that interacts with proteins to guide their proper assembly.The growing list of human syndromes associated with the immunophilin defect underscores the biological relevance of these proteins that are largely opportunistically exploited by cancer cells to support and enable the tumor’s intrinsic properties.Among the members of the immunophilin family,the FKBP5 gene was the only one identified to have a splicing variant.Cancer cells impose unique demands on the splicing machinery,thus acquiring a particular susceptibility to splicing inhibitors.This review article aims to overview the current knowledge of the FKBP5 gene functions in human cancer,illustrating how cancer cells exploit the scaffolding function of canonical FKBP51 to foster signaling networks that support their intrinsic tumor properties and the spliced FKBP51s to gain the capacity to evade the immune system.

Post-transplantation hepatocellular carcinoma recurrence: Patterns and relation between vascularity and differentiation degree

AIM: To evaluate the relationship between hepatocellular carcinoma(HCC) vascularity and grade; to describe patterns and vascular/histopathological variations of post-transplantation recurrence.METHODS: This retrospective study included 165 patients(143 men, 22 women; median age 56.8 years, range 28-70.4 years) transplanted for HCC who had a follow-up period longer than 2 mo. Pre-transplantation dynamic computed tomography or magnetic resonance examinations were retrospectively reviewed, classifying HCC imaging enhancement pattern into hypervascular and hypovascular based on presence of wash-in during arterial phase. All pathologic reports of the explanted livers were reviewed, collecting data about HCC differentiation degree. The association between imaging vascular pattern and pathological grade was estimated using the Fisher exact test. All follow-up clinical and imaging data were reviewed for evidence of recurrence. Recurrence rate was calculated and imaging features of recurrent tumor were collected, classifying early and late recurrences based on timing(< or ≥ 2 years after transplantation) and intrahepatic, extrahepatic and both intrahepatic and extrahepatic recurrences based onlocation. All intrahepatic recurrences were classified as hypervascular or hypovascular and the differentiation degree was collected where available. The presence of variations in imaging enhancement pattern and pathological grade between the primary tumor and the intrahepatic recurrence was evaluated and the association between imaging and histopatholgical variations was estimated by using the χ2 test. RESULTS: Of the 163 patients with imaging evidence of viable tumor, 156(95.7%) had hypervascular and 7(4.3%) hypovascular HCC. Among the 125 patients with evidence of viable tumor in the explanted liver, 19(15.2%) had grade 1, 56(44.8%) grade 2, 40(32%) grade 3 and 4(3.2%) grade 4 HCC, while the differentiation degree was not assessable for 6 patients(4.8%). A significant association was found between imaging vascularity and pathological grade(P = 0.035). Post-transplantation recurrence rate was 14.55%(24/165). All recurrences occurred in patients who had a hypervascular primary tumor. Three patients(12.5%) experienced late recurrence; the location of the first recurrence was extrahepatic in 14 patients(58.3%), intrahepatic in 7 patients(29.2%) and both intrahepatic and extrahepatic in 3 patients(12.5%). Two patients had a variation in imaging characteristics between the primary HCC(hypervascular) and the intrahepatic recurrent HCC(hypovascular), while 1 patient had a variation of histopathological characteristics(from moderate to poor differentiation), however no association was found between imaging and histopathological variations.CONCLUSION: A correlation was found between HCC grade and vascularity; some degree of variability may exist between the primary and the recurrence imaging/histopathological characteristics, apparently not correlated.

Immunosuppressive treatment and radiotherapy in kidney transplant patients:A systematic review

BACKGROUND Immunosuppression(IS)therapy may contribute to cancer development.Some authors have proposed to reduce immunosuppression drugs dose in case of viral infections,in immunosuppression-related diseases,and in patients undergoing radiotherapy.The present analysis reports the results of a systematic review on kidney transplant recipients undergoing immunosuppression and radiotherapy.AIM To define if it is necessary reduce immunosuppression drugs during radiotherapy.METHODS The literature search was based on three electronic databases(Pubmed,Scopus,and Web of Science)using selected keywords linked through the"AND"and"OR"Boolean operators to build specific strings for each electronic search engine.Two researchers independently screened the citations,and disagreement was resolved by discussion or through the intervention of a third author.The review was conducted and reported according to the PRISMA statement.Extracted data were narratively synthesized,and,where possible,frequencies,percentages,and ranges were calculated.RESULTS The literature search resulted in 147 citations.After abstracts screening,21 records were selected for full-text evaluation.Fifteen of these were excluded,leaving six papers considered suitable for analysis.There is still no clear evidence that withdrawing antimetabolites and/or calcineurin inhibitors and/or mammalian target of rapamycin-inhibitors,as opposed to continuing maintenance IS,improves patient survival in kidney transplant recipients with cancer undergoing radiotherapy.Only few retrospective studies on small cancer patient cohorts are available in this setting,but without comparison of different immunosuppression treatments.Even where immunosuppression therapy was described,patient survival seemed to be correlated only with cancer stage and type.CONCLUSION The results of this systematic review do not support the reduction of immunosuppression dose in patients undergoing radiotherapy.

A rare case of epiploic appendagitis in a patient affected by ulcerative colitis on vedolizumab therapy

Introduction Epiploic appendagitis(EA)is an acute inflammation of the pedunculated mesenteric fat attached to the colonic surface,distinguished into two forms:primary EA,seemingly elicited by local ischaemic factors;and secondary EA(SEA),elicited by the inflammation of the adjacent organs,with diverticulitis being the most common trigger[1].Few case series have described the association between SEA and inflammatory bowel disease(IBD);however,information about clinical,laboratory and imaging findings,outcomes,and the impact of IBD-specific therapy were not reported.We first report the case of a woman affected by ulcerative colitis(UC)who developed a SEA during vedolizumab therapy(Figure 1A).