Renal cell carcinoma (RCC) represents the 9th most common malignancy in the world, having an incidence peak in the range of 60 to 70 years of age. Most of these malignancies are detected in an advanced stage. Thus, there is an urgent need for developing new tools composed of biomarkers.

It was discovered that the somatic mutation in JAK2 exon 14 (JAK2V617F) totally modified the understanding and diagnosis of Philadelphia-Negative myeloproliferative neoplasm (Ph-MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Real-time quantitative PCR is the most widely used method for JAK2V617F detection in clinical laboratory. In this study, we aimed to evaluate the clinical significance of JAK2V617F allele burden in Ph-MPNs detected by real-time quantitative PCR.

In lung cancer, miR-29b can act as a tumor suppressor, influencing epigenetic regulation, cell proliferation, differentiation, apoptosis, metastasis, and chemosensitivity. However, its expression and biological function in Xuanwei lung cancer (XWLC) remains unknown.

Although many epidemiological studies have investigated the CYP1A1 exon7 polymorphism and -GSTM1 interaction with esophageal cancer (EC), definite conclusions cannot be drawn. This study was conducted to explore this association in the Chinese population using meta-analysis.

Promoter methylation of tumor suppressor genes is an important epigenetic alteration that occurs in the primary stages of human tumors, including breast cancer. Identification of methylated genes and their relationship to clinical features can contribute to the prognosis and early detection of tumors. In this study, we explored the methylation status of APC and BRCA1 genes and their relationship to clinical factors in breast cancer patients.

Differentiated thyroid carcinomas (DTC) account for most of the thyroid cancers. The emergence of DTC may be affected by various predisposing genetic alterations and environmental factors The aim of this study was to investigate the role of VEGF C936T and IL-8 A251T gene polymorphisms in the pathogenesis and metastasis of differentiated thyroid cancer.

FLT3-internal tandem duplication mutations (ITDs) are found in approximately 30% of patients with acute myeloid leukemia (AML) and are markers of poor prognosis. However, the characteristics of FLT3/ ITDs in Chinese AML patients have rarely been reported. The aim of this study was to analyze the frequency and characteristics of FLT3/ITDs in Chinese AML patients.

Chromosomal aberrations in exfoliated urothelial cells have been associated with the development of urothelial carcinoma. This study aimed to evaluate the efficacy of two kinds of fluorescence in situ hybridization (FISH) kit probes in diagnosing urothelial carcinoma (UC).

Internal tandem duplication (ITD) of FMS-related tyrosine kinase 3 (FLT3) gene, which occurs in exons 14 and 15, is one of the most prevalent somatic mutations in adult acute myeloid leukemia (AML) and has biological, prognostic, and therapeutic implications. The prognostic importance of codon 835 tyrosine kinase domain (TKD) mutation (exon 20), which occurs relatively frequently in adult AML, is often debated. We aimed to study the FLT3 gene mutation profile and prognosis in 139 adult Iranian patients with newly diagnosed AML.

Although progress in clinical and basic research has significantly increased our understanding of breast cancer, little is known about the molecular mechanism underlying breast cancer metastasis. Identification of effective therapeutic targets to prevent breast cancer metastasis is urgently needed. The function of miR-503-3p has been investigated in other cancers, but its role in breast cancer remains undefined. Here, we found that miR-503-3p was overexpressed in breast cancer tissue and plasma compared with adjacent normal breast tissue and with plasma from healthy individuals. Moreover, we identified miR-503-3p to be an oncogene of breast cancer cell proliferation, migration and invasion. Upregulation of miR-503-3p in breast cancer cells inhibited expression of epithelial-mesenchymal transition (EMT)-related protein SMAD2 and the epithelial marker protein E-cadherin by directly binding to their mRNA 3' untranslated region, whereas increased expression of mesenchymal marker proteins, including vimentin and N-cadherin. Taken together, our findings support a critical role for miR-503-3p in induction of breast cancer EMT and suggest that plasma miR-503-3p may be a useful diagnostic biomarker for breast cancer.

Gestational (GC) (derived from the placenta) and non-gestational (NGC) choriocarcinomas are trophoblastic diseases originated from abnormal proliferation of trophoblastic cells. These rare tumors share similar morphology and pathological features and differ on chemotherapy response, genetic origin and prognosis. In this study, the genomic profile of choriocarcinomas was performed according to their origin (GC or NGC) aiming to better understand these poorly characterized diseases.

Despite the benefits from different options of therapy for breast cancer, resistance of the disease to these therapies is rising and a novel agent is needed. Erythro-austrobailignan-6 (EA6) exhibits anti-cancer activity. However, the detailed anti-tumor mechanisms by which EA6 inhibits 4T-1 and MCF-7 cell growth have not been well studied.

Genetic diseases associated with defects in primary cilia are classified as ciliopathies. Pancreatic lesions and ductal cysts are found in patients with ciliopathic polycystic kidney diseases suggesting a close connection between pancreatic defects and primary cilia. Here we investigate the role of two genes whose deletion is known to cause primary cilium defects, namely Hnf6 and Lkb1, in pancreatic ductal homeostasis. We find that mice with postnatal duct-specific deletion of Hnf6 or Lkb1 show duct dilations. Cells lining dilated ducts present shorter cilia with swollen tips, suggesting defective intraciliary transport. This is associated with signs of chronic pancreatitis, namely acinar-to-ductal metaplasia, acinar proliferation and apoptosis, presence of inflammatory infiltrates, fibrosis and lipomatosis. Our data reveal a tight association between ductal ciliary defects and pancreatitis with perturbed acinar homeostasis and differentiation. Such injuries can account for the increased risk to develop pancreatic cancer in Peutz-Jeghers patients who carry LKB1 loss-of-function mutations.

Palmitate, the enzymatic product of FASN, and palmitate-derived lipids support cell metabolism, membrane architecture, protein localization, and intracellular signaling. Tubulins are among many proteins that are modified post-translationally by acylation with palmitate. We show that FASN inhibition with TVB-3166 or TVB-3664 significantly reduces tubulin palmitoylation and mRNA expression. Disrupted microtubule organization in tumor cells is an additional consequence of FASN inhibition. FASN inhibition combined with taxane treatment enhances inhibition of in vitro tumor cell growth compared to treatment with either agent alone. In lung, ovarian, prostate, and pancreatic tumor xenograft studies, FASN inhibition and paclitaxel or docetaxel combine to inhibit xenograft tumor growth with significantly enhanced anti-tumor activity. Tumor regression was observed in 3 of 6 tumor xenograft models. FASN inhibition does not affect cellular taxane concentration in vitro. Our data suggest a mechanism of enhanced anti-tumor activity of the FASN and taxane drug combination that includes inhibition of tubulin palmitoylation and disruption of microtubule organization in tumor cells, as well as a sensitization of tumor cells to FASN inhibition-mediated effects that include gene expression changes and inhibition of β-catenin. Together, the results strongly support investigation of combined FASN inhibition and taxane treatment as a therapy for a variety of human cancers.

Canine mammary tumours are frequent neoplasms mostly affecting intact female dogs, for which no 100% efficient therapy is available. Platelet derived growth factor β receptor (PDGFβR) is a tyrosine kinase receptor (TKR) with a potential role in human breast cancer and a series of canine tumours. In this study we demonstrated, for the first time, expression of PDGFβR and its downstream transduction molecules, mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) and extracellular signal-regulated kinase (ERK), as well as their activated forms in canine mammary tumours by both biochemical analysis and immunohistochemistry. PDGFβR was expressed and hyperphosphorylated in the majority of tumour samples and tumour derived cell lines. Additionally, both MEK and ERK were expressed and activated in cell lines as well as biopsies. TKR inhibitors (TKRi) are currently under investigation as possible therapy in human breast and several canine tumours, thus our in vivo and in vitro findings pave the way for future studies aimed at establishing a potential therapeutic employment of TKRi for the treatment of canine mammary cancer.

MicroRNAs are the largest group of short regulatory RNAs. They regulate genes participating in many physiological and pathological processes. The role of micro RNAs in cancer development is also considerable. Therefore, the aim of this study was to evaluate the relationship between DROSHA (rs6877842) and DGCR8 (rs417309, rs1640299) gene polymorphisms with risk of occurrence of laryngeal cancer. The study included 100 patients and 100 healthy subjects. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissues. Analysis of the gene polymorphisms was performed using TaqMan SNP Genotyping Assay. The rs417309 AA genotype was found to be correlated with increased risk of larynx cancer. The rs1640299 TG and rs6877842 CG heterozygotes were significantly inversely associated with the presence of larynx cancer. Additionally, rs417309 AA genotype increased the risk of larynx cancer in the T1 stage, and the rs1640299 TG heterozygote occurred more frequently in the control group than those in the T3 and T4 stage. The rs417309 and rs1640299 polymorphisms of the DGCR8 gene as well as rs6877842 of the DROSHA gene might be associated with a risk of laryngeal cancer occurrence in the Polish population.

The first signs of oral cancer may resemble developing infections in the mucous membranes, with throat cancer symptoms being similar to those of upper respiratory tract infections. This greatly hinders rapid diagnosis and treatment. Better knowledge of the changes occurring in the metabolism of folic acid can help in understanding the carcinogenesis affecting DNA methylation and genome stability. Polymorphisms in genes encoding enzymes involved in this pathway may influence enzyme activity and thereby interfere with the concentrations of homocysteine and S-adenosylmethionine, which are important for DNA synthesis and cellular methylation reactions. The aim of the study was to determine the risk of oral cancer associated with the TC2 C776G polymorphism, as determined in 119 patients. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The test genotype was found to correspond to the Hardy-Weinberg (HW) equilibrium (p > 0.05). In our population G/G homozygosity of C776G TC2 gene polymorphism increases the risk of oral cancer; OR (odds ratio): 4.3875; 95% CI (confidence interval): 2.0518-9.319; p = 0.001. Regarding C/G genotype of the C776G TC2 gene, polymorphism also increases the risk of developing this cancer; OR 2.4146 95% CI: 1.2803-4.5541; p = 0.01.

High-throughput technology could generate thousands to millions biomarker measurements in one experiment. However, results from high throughput analysis are often barely reproducible due to small sample size. Different statistical methods have been proposed to tackle this "small n and large p" scenario, for example different datasets could be pooled or integrated together to provide an effective way to improve reproducibility. However, the raw data is either unavailable or hard to integrate due to different experimental conditions, thus there is an emerging need to develop a method for "knowledge integration" in high-throughput data analysis.

Aberrant epigenetic modifications, including DNA methylation, are key regulators of gene activity in tumorigenesis. Breast cancer is a heterogeneous disease, and large-scale analyses indicate that tumor from normal and benign tissues, as well as molecular subtypes of breast cancer, can be distinguished based on their distinct genomic, transcriptomic, and epigenomic profiles. In this study, we used affinity-based methylation sequencing data in 30 breast cancer cell lines representing functionally distinct cancer subtypes to investigate methylation and mutation patterns at the whole genome level.