BackgroundTranslationally controlled tumour protein TCTP is an anti-apoptotic protein frequently overexpressed in cancers, where high levels are often associated with poor patient outcome. TCTP may be involved in protecting cancer cells against the cytotoxic action of anti-cancer drugs. Here we study the early increase of TCTP levels in human colorectal cancer (CRC) and the regulation of TCTP expression in HCT116 colon cancer cells, in response to treatment with the anti-cancer drugs 5-FU and oxaliplatin.MethodsUsing immunohistochemistry, we assessed TCTP levels in surgical samples from adenomas and adenocarcinomas of the colon, compared to normal colon tissue. We also studied the regulation of TCTP in HCT116 colon cancer cells in response to 5-FU and oxaliplatin by western blotting. TCTP mRNA levels were assessed by RT-qPCR. We used mTOR kinase inhibitors to demonstrate mTOR-dependent translational regulation of TCTP under these conditions. Employing the Real-Time Cell Analysis (RTCA) System and the MTS assay, we investigated the effect of TCTP-knockdown on the sensitivity of HCT116 cells to the anti-cancer drugs 5-FU and oxaliplatin.Results1. TCTP levels are significantly increased in colon adenomas and adenocarcinomas, compared to normal colon tissue. 2. TCTP protein levels are about 4-fold upregulated in HCT116 colon cancer cells, in response to 5-FU and oxaliplatin treatment, whereas TCTP mRNA levels are down regulated. 3. mTOR kinase inhibitors prevented the up-regulation of TCTP protein, indicating that TCTP is translationally regulated through the mTOR complex 1 signalling pathway under these conditions. 4. Using two cellular assay systems, we demonstrated that TCTP-knockdown sensitises HCT116 cells to the cytotoxicity caused by 5-FU and oxaliplatin.ConclusionsOur results demonstrate that TCTP levels increase significantly in the early stages of CRC development. In colon cancer cells, expression of this protein is largely upregulated during treatment with the DNA-damaging anti-cancer drugs 5-FU and oxaliplatin, as part of the cellular stress response. TCTP may thus contribute to the development of anti-cancer drug resistance. These findings indicate that TCTP might be suitable as a biomarker and that combinatorial treatment using 5-FU/oxaliplatin, together with mTOR kinase inhibitors, could be a route to preventing the development of resistance to these drugs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12964-017-0164-3) contains supplementary material, which is available to authorized users.

Co-infection with human immunodeficiency virus-1 (HIV) and syphilis is associated with rapid progression to tertiary syphilis. This case report describes the early development of gummatous skin disease and suspected neurosyphilis in a patient with untreated HIV and approaches to treatment.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by extraordinary heterogeneity, due to the complex pathogenesis and diverse manifestations. Stratification of patients for therapy and prognosis represents a major challenge to manage SLE. Conventional biomarkers for disease diagnosis and activity assessment provide very limited insight into immunological pathogenesis and therapeutic response rates. The advancement of “omics” technologies including genomics, transcriptomics, proteomics, and metabolomics has constituted an unprecedented opportunity to characterize the immunopathological landscape in individual patients with SLE. Indeed, genomic studies reveal a subset of SLE patients carrying one or more functional single nucleotide polymorphisms (SNPs) underlying immune dysregulation while transcriptomic studies have revealed subgroups in SLE patients showing distinct signatures for Type I interferon (TI‐IFN) pathway activation or aberrant differentiation of B cells into plasma cells. This review will summarize results from the latest studies using omics technology to understand SLE heterogeneity. In addition, we propose that the application of artificial intelligence, such as by machine learning‐based nonlinear dimensionality reduction method uniform manifold approximation and projection (UMAP) can further strengthen the analysis of omics big data. The combination of new technology and novel analysis pipeline can lead to breakthroughs in stratifying SLE patients for a better monitoring of disease activity and more precise design of treatment regime, not only for conventional immunosuppression but also novel immunotherapies targeting B‐cell activating factor (BAFF), TI‐IFN, and interleukin 2 (IL‐2).

Background Pregnancy-related Atypical Haemolytic Uremic Syndrome (P-aHUS) is a rare condition affecting genetically predisposed women during pregnancy. It is often difficult to diagnose and has a significant impact on maternal and foetal outcomes. It is characterised by microangiopathic haemolytic anaemia and kidney injury from thrombotic microangiopathy. Case presentation A 27-year-old female of Lebanese descent presented at 36 weeks’ gestation with foetal death in-utero (FDIU) with placental abruption on a background of previously normal antenatal visits. She was coagulopathic and anaemic with anuric acute kidney injury, requiring emergency Caesarean section, intubation and dialysis. Her coagulopathy rapidly resolved, however, her anaemia and renal dysfunction persisted. A diagnosis of P-aHUS was made, and she was empirically treated with Eculizumab. Her ADAMTS13 level was normal, effectively excluding thrombotic thrombocytopenic purpura. Within 2 weeks of treatment her haematological parameters improved, and her renal function began to recover and within 2 months she became dialysis independent. Conclusion This case highlights the challenges of a timely diagnosis of P-aHUS from other pregnancy-related diseases. Although our patient is dialysis-independent, her risk of relapse remains high with subsequent pregnancies. Currently we are awaiting her genetic sequencing to complete her assessment for underlying mutations and are determining the safest approach to a future planned pregnancy.