Detection of circulating tumor cells in colorectal and gastric cancer using a multiplex PCR assay.

AIM: The aim of this study was the development of a multiplex-PCR assay for the detection of circulating tumor cells in patients with colorectal and gastric cancer. PATIENTS AND METHODS: Peripheral blood samples were collected from 81 patients with colorectal cancer, 16 with gastric cancer and 38 healthy blood donors, as controls. The samples were processed for RNA extraction and cDNA synthesis and were subsequently analyzed for the expression of cytokeratin 19 (CK19), cytokeratin 20(CK20) and epidermal growth factor receptor (EGFR) with multiplex PCR. RESULTS: Statistical analysis revealed that the combination of CK19 and CK20 could be useful in the exclusion of colorectal cancer, as well as the diagnosis and exclusion of gastric cancer. Furthermore, the expression of EGFR was correlated with the presence of systemic disease in patients with colorectal cancer. CONCLUSION: Multiplex-PCR-based detection of circulating tumor cells could serve as a useful tool for the diagnosis, and monitoring of patients with colorectal and gastric cancer.

Survivin beyond physiology: orchestration of multistep carcinogenesis and therapeutic potentials.

Survivin, a member of the inhibitor of apoptosis protein family, has been associated with protection from cell apoptosis and regulation of mitosis. Survivin exhibits low to undetectable expression in most finally differentiated adult tissues but is abundantly over-expressed in almost all cancers. The aberrant high expression of survivin in cancers is associated with advanced disease, increased rate of tumor recurrence, abbreviated overall survival and resistance to chemo- and radio- therapy. Survivin touches nearly every aspect of cancer and is involved in the initiation, maintenance and development of tumor. Therefore, its significance in cancer dictates the pursuit for anti-survivin cancer therapies.

Epigenetic modifications in colorectal cancer: molecular insights and therapeutic challenges.

Colorectal cancer, a leading cause of mortality worldwide, is a multistep disorder that results from the alteration of genetic and epigenetic mechanisms under contextual influence. Epigenetic aberrations, including DNA methylation, histone modifications, chromatin remodeling and non-coding RNAs, affect every aspect of tumor development from initiation to metastasis. Cancer stem cell promotion is also included in the wide spectrum of epigenetic dysregulations. Elucidation of this complex crosstalk network may offer new insights in the molecular interactions involved in the pathogenesis of colorectal carcinogenesis. In the era of translational medicine new horizons are opened for the pursuit of personalized therapeutic approaches and the development of novel and accurate diagnostic, prognostic and therapy-assessment markers. This review discusses the implications of epigenetic mechanisms in tumor biology and their applications "from bench to bedside".

NF-κB in colorectal cancer.

Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide, responsible for more than half a million deaths annually. CRC is a multistep process that entails the accumulation of genetic/epigenetic aberrations, which lead to the simultaneous failure of protective mechanisms and the activation of tumorigenic pathways. In most cases of CRC a deregulation of the Wnt-signaling pathway is required. The transcription factor nuclear factor κB (NF-κB) has been recognized as a key player in the initiation and propagation of CRC. Under physiological conditions, NF-κB orchestrates the inflammatory process and participates in the modulation of various steps of cell cycle and survival. It is normally kept in an inactive state in the cytoplasm by binding to a group of inhibitory proteins. Upon receipt of a signal, its inhibitor is phosphorylated and proteolytically degraded and NF-κB is actively translocated to the nucleus, where it facilitates target-gene transcription. Recent experimental data reveal the important role of NF-κB in tumor cells as well as in the surrounding "cancerous" and reactive microenvironment. Various tumor cell-derived and contextual cues feed constantly this vicious circuitry sustaining inflammation and promoting proliferation, angiogenesis, invasion and eventually metastasis. Therefore NF-κB along with its upstream and downstream network presents a rational target for therapeutic interventions. Numerous small molecules, inhibitory peptides, antisense RNAs, natural compounds, as well as gene therapy strategies interfere with multiple steps of the NF-κΒ signaling cascade. The design of NF-κΒ-targeted treatment may aid the efforts towards the pursuit of more efficient therapeutic measures devoid of severe systemic side-effects.

Targeting transcription factor corepressors in tumor cells.

By being the "integration" center of transcriptional control as they move and target transcription factors, corepressors fine-tune the epigenetic status of the nucleus. Many of them utilize enzymatic activities to modulate chromatin through histone modification or chromatin remodeling. The clinical and etiological relevance of the corepressors to neoplastic growth is increasingly being recognized. Aberrant expression or function (both loss and gain of) of corepressors has been associated with malignancy and contribute to the generation of transcriptional "inflexibility" manifested as distorted signaling along certain axes. Understanding and predicting the consequences of corepressor alterations in tumor cells has diagnostic and prognostic value, and also have the capacity to be targeted through selective epigenetic regimens. Here, we evaluate corepressors with the most promising therapeutic potential based on their physiological roles and involvement in malignant development, and also highlight areas that can be exploited for molecular targeting of a large proportion of clinical cancers and their complications.