Keratin 36, a specific marker of tongue filiform papillae, is downregulated in squamous cell carcinoma of the mobile tongue.

Human keratin 36 (K36) is a member of the hair keratin family and is a marker of hair cortex differentiation. The human gene is located on the long arm of chromosome 17 and belongs to the cluster of structurally unrelated acidic hair keratins. Recently, it has been reported that mRNA is specifically expressed in normal tongue epithelium and downregulated in squamous cell carcinomas of the mobile tongue.

Oncogenic Viral Protein Interactions with p53 Family Proteins.

Background: Cellular transformation induced by oncogenic viruses is a complex process including viral molecules, host cells and environmental factors. Viruses alone are unable to reproduce and thus they need a host to use their signalling, proteosynthetic and metabolic pathways. One target host molecule is the p53 tumour suppressor.

Role of the Microbiome in the Formation and Development of Colorectal Cancer.

Background: The clinical, histopathological, and molecular characteristics of colorectal cancer vary considerably. Factors associated with the heterogeneity of this disease and with understanding the effects of heterogeneity on disease progression and response to therapy are critical for the better stratification of patients and the development of new therapeutic methods. Although studies have focused mainly on tumor molecular profiling, current molecular predictive and prognostic factors are relevant to specific groups of colorectal cancer patients and are mostly used to predict the applicability of targeted biological agents rather than to predict their benefits.

Tomm34 is commonly expressed in epithelial ovarian cancer and associates with tumour type and high FIGO stage.

Background: Increased activity of the chaperones Hsp70 and Hsp90 is a common feature of solid tumours. Translocase of the outer mitochondrial membrane 34 (Tomm34) is a cochaperone of both Hsp70 and Hsp90 that was found to be overexpressed in colorectal, hepatocellular, lung and breast carcinomas. The expression profile of Tomm34 in ovarian cancer has not been investigated.

Circulating Myeloid-Derived Suppressor Cell Subsets in Patients with Colorectal Cancer - Exploratory Analysis of Their Biomarker Potential.

Background: Myeloid-derived suppressor cells (MDSCs) contribute to tumor escape from host immune surveillance and to tumor progression by producing tumor-promoting factors. We focused on clinical and analytical MDSCs-related issues as potential biomarkers and immune regulators involved in tumor progression.

Patients And Methods: We analyzed 10 patients with advanced colorectal carcinoma (CRC) with (M1 subgroup) or without (M0 subgroup) distant metastases at diagnosis.

Variability in the Solid Cancer Cell Population and Its Consequences for Cancer Diagnostics and Treatment.

Background: Cancer develops as a result of somatic mutations and evolutionary processes with a Darwinian character. Tumors evolve by dynamic clonal expansion and selection to form genetically diverse cell subpopulations adapted to different tumor microenvironmental conditions. Within cancer cells, the genome is shaped by various selective pressures.

[Circulating Myeloid Suppressor Cells and Their Role in Tumour Immunology].

Background: Myeloid-derived suppressor cells (MDSCs) are heterogenic population of multipotent progenitors of myeloid lineage. For their immunosuppressive effect, MDSC are responsible for tumour escape from the host immune surveillance. Furthermore, MDSCs support tumour by promotion of angiogenesis and metastasis.

[Molecular Pathology of Colorectal Cancer, Microsatellite Instability - the Detection, the Relationship to the Pathophysiology and Prognosis].

Background: Colorectal carcinoma (CRC) is third most common cancer worldwide with very heterogenous character. In most cases, it is caused by sporadic events leading to disruption of epithelial cells of the colon. The minority evolves from germline mutations associated with hereditary cancer syndromes.

[Endoplasmic Reticulum Chaperones at the Tumor Cell Surface and in the Extracellular Space].

Background: Endoplasmic reticulum chaperones are stress induced proteins capable of translocation into cytosol, cell membrane or extracellular space. The chaperones are transported from the endoplasmic reticulum particularly under endoplasmic reticulum stress conditions, while their constitutive extracellular expression was found in many cancers. Cell surface or extracellular endoplasmic reticulum chaperones take up distinct functions compared to their endoplasmic reticulum resident variants because they act like multifunctional receptors and thus affect cell signaling and proliferation.

Anterior gradient protein 3 is associated with less aggressive tumors and better outcome of breast cancer patients.

Anterior gradient protein (AGR) 3 is a highly related homologue of pro-oncogenic AGR2 and belongs to the family of protein disulfide isomerases. Although AGR3 was found in breast, ovary, prostate, and liver cancer, it remains of yet poorly defined function in tumorigenesis. This study aimed to determine AGR3 expression in a cohort of 129 primary breast carcinomas and evaluate the clinical and prognostic significance of AGR3 in these tumors.

Mechanisms of anterior gradient-2 regulation and function in cancer.

Proteins targeted to secretory pathway enter the endoplasmic reticulum where they undergo post-translational modification and subsequent quality control executed by exquisite catalysts of protein folding, protein disulphide isomerases (PDIs). These enzymes can often provide strict conformational protein folding solutions to highly cysteine-rich cargo as they facilitate disulphide rearrangement in the endoplasmic reticulum. Under conditions when PDI substrates are not isomerised properly, secreted proteins can accumulate in the endoplasmic reticulum leading to endoplasmic reticulum stress initiation with implications for human disease development.

Discovery of a novel ligand that modulates the protein-protein interactions of the AAA+ superfamily oncoprotein reptin.

Developing approaches to discover protein-protein interactions (PPIs) remains a fundamental challenge. A chemical biology platform is applied here to identify novel PPIs for the AAA+ superfamily oncoprotein reptin. An screen coupled with chemical optimization provided Liddean, a nucleotide-mimetic which modulates reptin's oligomerization status, protein-binding activity and global conformation.

Novel arylazopyrazole inhibitors of cyclin-dependent kinases.

Here, we describe new 4-arylazo-3,5-diamino-1H-pyrazole derivatives developed from CAN508, one of the first inhibitors to show preference for transcriptional regulator cyclin-dependent kinase 9. By substituting nitrogen in the pyrazole ring and employing a heteroatom in the 4-aryl ring, we obtained more potent derivatives differing in their CDK-selectivity profiles. The antiproliferative and anti-CDK kinase activities of the novel arylazopyrazoles were examined.

The role of AGR2 and AGR3 in cancer: similar but not identical.

In the past decades, highly related members of the protein disulphide isomerase family, anterior gradient protein AGR2 and AGR3, attracted researchers' attention due to their putative involvement in developmental processes and carcinogenesis. While AGR2 has been widely demonstrated as a metastasis-related protein whose elevated expression predicts worse patient outcome, little is known about AGR3's role in tumour biology. Thus, we aim to confront the issue of AGR3 function in physiology and pathology in the following review by comparing this protein with the better-described homologue AGR2.

[In situ proximity ligation assay for detection of proteins, their interactions and modifications].

To understand cellular processes and events responsible for their perturbations, proteomic analyses are needed in bio-medical research and clinical diagnostics. Several techniques based on specifically binding reagents (antibodies) or recombinant proteins (GFP fusion protein, methods of fluorescence/ bio-luminescence resonance energy transfer) are generally used to study protein location and activity resulting from secondary modifications and interactions. The in situ proximity ligation assay represents a novel technique of in situ protein imaging using DNA as a reporter molecule and DNA amplification processes.

Differential expression of anterior gradient protein 3 in intrahepatic cholangiocarcinoma and hepatocellular carcinoma.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer next to hepatocellular carcinoma (HCC). Despite the significant difference of the therapeutic strategy for both diseases, their histological appearance may be very similar. Thus the correct diagnosis is crucial for treatment choice but is often difficult to achieve.

Anterior gradient 2 and mucin 4 expression mirrors tumor cell differentiation in pancreatic adenocarcinomas, but aberrant anterior gradient 2 expression predicts worse patient outcome in poorly differentiated tumors.

Objectives: This study aimed to determine anterior gradient 2 (AGR2) expression in biopsies from pancreatic ductal adenocarcinomas (PDACs) and to evaluate AGR2 as a potential independent prognostic factor.

Methods: Tissue sample sections from a cohort of 135 consecutive surgically resectable PDACs were subjected to semiquantitative immunohistochemical analysis of AGR2 and mucin 4 (MUC4) expression.

Results: Anterior gradient 2 was over-expressed in PDAC compared with normal ductal cells.

AGR2 predicts tamoxifen resistance in postmenopausal breast cancer patients.

Endocrine resistance is a significant problem in breast cancer treatment. Thus identification and validation of novel resistance determinants is important to improve treatment efficacy and patient outcome. In our work, AGR2 expression was determined by qRT-PCR in Tru-Cut needle biopsies from tamoxifen-treated postmenopausal breast cancer patients.

Identification of an AKT-dependent signalling pathway that mediates tamoxifen-dependent induction of the pro-metastatic protein anterior gradient-2.

The pro-metastatic protein anterior gradient-2 (AGR2) was previously demonstrated as a predictive factor of poor response to tamoxifen treatment. In this study we aimed to delineate the key signalling pathway that may contribute to regulation of AGR2 protein induction in order to identify novel targets to overcome tamoxifen resistance in tumour cells. Together, our data identify PDPK1-AKT as a pro-oncogenic signalling pathway that triggers AGR2 protein induction in response to tamoxifen and suggest that AKT inhibitors could be used as part of a therapeutic strategy to treat tamoxifen resistant, AGR2 over-expressing cancers.

Anterior gradient 2: a novel player in tumor cell biology.

AGR2 has evolutionarily conserved roles in development and tissue regeneration and is linked with several human cancers. The exact functions and regulation of AGR2 are poorly understood, but current data identify AGR2 as a clinically relevant factor that modulates the behavior and response of hormone-dependent cancers (breast, prostate) and hormone-independent cancers (colorectal, pancreatic, esophageal and other common cancers). AGR2 protein expression induces metastasis, acts as a p53 tumor suppressor inhibitor and survival factor, participates directly in neoplastic transformation and is involved in drug resistance.

Erythrocytes of uranium miners: the activity of the pentose phosphate pathway.

287-290. The functioning of erythrocytes was studied by determination of the activity of the pentose phosphate pathway in 431 individuals - 221 uranium miners, 42 employees of a uranium ore trimming station (30 of whom were exposed), 36 former uranium miners, 32 coal miners, and 100 persons not working in mines and with no previous exposure. In the groups exposed to long-term occupational radiation, the activity of the pentose phosphate cycle was found to be enhanced.