Diagnostic and Prognostic Value of CEA and CA19-9 in Colorectal Cancer

Colorectal cancer (CRC) is the third most common cancer worldwide. A diagnosis at early stages with enhanced screening methods is vital as metastases and recurrences increase mortality. The aim of this study was to analyze the tumor markers CEA and CA19-9 combined in correlation with diagnostics and prognosis. Therefore, 1487 patients with CRC who were diagnosed and treated between 2000 and 2015 at the University Hospital Ulm, Germany, were retrospectively evaluated. Overall and recurrence-free survival was analyzed in association with preoperative CEA and CA19-9 separately and combined and a multivariate analysis was performed. The 5-year overall survival was significantly shorter in patients with a CEA or CA19-9 level ≥200 compared to patients with an increased, but <200, or normal level (CEA: 69%/44%/7%; CA19-9: 66%/38%/8%). Patients with both tumor markers increased also showed a remarkably shorter 5-year survival rate (CEA+/CA19-9+: 23%). The multivariate analysis emphasizes these results (p-value < 0.0001). Patients with both tumor markers elevated had the shortest 5-year recurrence-free survival rate, followed by patients with either CEA or CA19-9 elevated (CEA-/CA19-9-: 79%; CEA+/CA19-9; CEA-/CA19-9+: 65%; CEA+/CA19-9+: 44%). In conclusion, measuring CEA and CA19-9 preoperatively in CRC patients is reasonable and could be useful as a prognostic factor

Friend or Foe: S100 Proteins in Cancer

S100 proteins are widely expressed small molecular EF-hand calcium-binding proteins of vertebrates, which are involved in numerous cellular processes, such as Ca(2+)homeostasis, proliferation, apoptosis, differentiation, and inflammation. Although the complex network of S100 signalling is by far not fully deciphered, several S100 family members could be linked to a variety of diseases, such as inflammatory disorders, neurological diseases, and also cancer. The research of the past decades revealed that S100 proteins play a crucial role in the development and progression of many cancer types, such as breast cancer, lung cancer, and melanoma. Hence, S100 family members have also been shown to be promising diagnostic markers and possible novel targets for therapy. However, the current knowledge of S100 proteins is limited and more attention to this unique group of proteins is needed. Therefore, this review article summarises S100 proteins and their relation in different cancer types, while also providing an overview of novel therapeutic strategies for targeting S100 proteins for cancer treatment

The role of the casein kinase 1 (CK1) family in different signaling pathways linked to cancer development

The members of the casein kinase 1 (CK1) family are highly conserved and are expressed in many eukaryotes ranging from yeast to humans. Mammalian CK1 isoforms (alpha, beta, gamma, delta, epsilon) and their splice variants are involved in diverse cellular processes including membrane trafficking, circadian rhythm, cell cycle progression, chromosome segregation, apoptosis and cellular differentiation. Mutations and deregulation of CK1 expression and activity has been linked to various diseases including neurodegenerative disorders such as Alzheimer's and Parkinson's disease, sleeping disorders and proliferative diseases such as cancer. In this review, we summarize the functions of CK1 and outline the participation of CK1 in signal transduction pathways linked to cancer development

Analysis of the CDK4/6 Cell Cycle Pathway in Leiomyosarcomas as a Potential Target for Inhibition by Palbociclib

Leiomyosarcoma (LMS) is characterized by high genomic complexity, and to date, no specific targeted therapy is available. In a genome-wide approach, we profiled genomic aberrations in a small cohort of eight primary tumours, two relapses, and eight metastases across nine different patients. We identified CDK4 amplification as a recurrent alteration in 5 out of 18 samples (27.8%). It has been previously shown that the LMS cell line SK-LMS-1 has a defect in the p16 pathway and that this cell line can be inhibited by the CDK4 and CDK6 inhibitor palbociclib. For SK-LMS-1 we confirm and for SK-UT-1 we show that both LMS cell lines express CDK4 and that, in addition, strong CDK6 expression is seen in SK-LMS-1, whereas Rb was expressed in SK-LMS-1 but not in SK-UT-1. We confirm that inhibition of SK-LMS-1 with palbociclib led to a strong decrease in protein levels of Phospho-Rb (Ser780), a decreased cell proliferation, and G0/G1-phase arrest with decreased S/G2 fractions. SK-UT-1 did not respond to palbociclib inhibition. To compare these in vitro findings with patient tissue samples, a p16, CDK4, CDK6, and p-Rb immunohistochemical staining assay of a large LMS cohort (n=99 patients with 159 samples) was performed assigning a potential responder phenotype to each patient, which we identified in 29 out of 99 (29.3%) patients. Taken together, these data show that CDK4/6 inhibitors may offer a new option for targeted therapy in a subset of LMS patients