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Abstract : MiR-708-5p as a Predictive Marker of Colorectal Cancer Prognosis
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Abstract: Background: MicroRNAs (miRNA) are short non-coding RNA that act as negative regulators of gene expression. Altered levels of miR-708-5p have recently been described in many tumors, although its contribution in colorectal cancer (CRC) pathophysiology remains unclear. Methods/Patients: Quantitative real-time polymerase chain reaction was employed to evaluate the expression of miR-708-5p in 50 CRC and 20 paired adjacent noncancerous tissues. The relationship between miRNA levels and clinicopathological features was estimated using the Mann-Whitney test, and survival curves calculated by the Kaplan-Meier method. Additionally, in vitro assays were performed to investigate the possible role of miR-708-5p on CRC cell survival. Results: The expression level of miR-708-5p was significantly decreased in CRC tissues (3.79 fold-change, p=0.0112) when compared with non-neoplastic colon samples. Paired analysis in 20 CRC samples with their corresponding adjacent non-neoplastic tissue showed miR-708 downregulation in 60% of them. The same pattern was seen in DLD1 and HT-29 cell lines (~50-fold decrease). Interestingly, higher expression is observed in patients with poor prognosis such as stage III/IV, relapse/metastasis and death, and shorter 5-year event free survival. Exogenous expression of miR-708 exerted a significant influence on clonogenicity in vitro. Conclusion: These results suggest that reduced miR-708-5p expression may contribute to the first stages of colorectal carcinogenesis. A shift in the regulation of miR-708-5p might operate in more severe stages of the disease. It seems that lower levels of miR-708 expression might connote less advanced disease and better prognosis. Further studies are needed to corroborate our results and better elucidate the role of miR-708 in CRC. Keywords: microRNA, colorectal tumor, DLD1, HT-29, cell lines.Download Full Article |
Abstract : Mutations by Next Generation Sequencing in Stool DNA from Colorectal Carcinoma Patients – A Literature Review and our Experience with this Methodology
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Abstract: It is well-known that colorectal carcinoma is a disease involving multistep carcinogenesis (hyperplasia-adenoma-carcinoma-metastasizing carcinoma). It is also a disease where therapeutically important driver mutations (especially in the EGFR signaling pathway) have been identified. Since genetic mutations can serve as good diagnostic and predictive markers, their reliable detection in the early stages of the disease and also in the follow-up of treatment efficacy is crucial. There is a fundamental problem encountered with the commonly used formalin-fixed paraffin-embedded (FFPE) specimens from biopsied tumor tissue i.e. it is unlikely that the material for the mutation analysis will be available in either the early stage of the disease or during the treatment period. Therefore recently attempts have been made to identify reliable markers from plasma/serum or from stool specimens. In particular, non-invasive stool specimens have been speculated to represent the situation of ongoing tumorigenesis and thus they can be used to assess treatment efficacy in the follow-upof the patient. The key aims of this paper are firstly, to review the key methodological points when studying genomic alterations in DNA extracted from cells in stool specimens, and secondly, to review results related to biomarker screening and their therapeutic importance. A further aim is to present our new findings by focusing on the issues inherent in Next Generation Sequencing of stool specimens from patients with gastrointestinal tumors. Even though the focus of our paper is human genomic alterations in stool specimens, in our “future aspects” chapter, we also deal with the bacterial spectrum and its possible interaction with the genomic mutations. Keywords: Mutation, DNA, Stool specimen, Colorectal carcinoma, Next generation sequencing.Download Full Article |
Abstract : Mutagenesis Associated with DNA-Damage-Stress Response
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Abstract: In this manuscript we aim to take on the controversies in oncology, such as those related to costs and screening guidelines. Are we recently at new turning point with our existing methodology? During the past 30 years of evolution methods of awareness and screening have lead to an emphasis on early diagnoses of cancer and not only cancer. Recent trends and clinical trials show that these goals have not been met. International data demonstrate significant increase in early stage disease, without a proportional decrease in later-stage disease. We need to more differentiate in methodology because cancers are heterogenous with multiple paths, not all of which progress to metastases and death. This broader definition of disease named cancer must include also indolent disease that causes no harm during patients lifetime. Overdiagnosis and overtreatment result in billions of USD of wasted money. Our methodology must be completed with methods which take proper account of the real-life environment. Keywords: The stress-induced mutagenesis, the epigenetic diversity, stress response, awareness and screening, overdiagnosis, overtreatment.Download Full Article |
Abstract : A Case of Sigmoid Colon Cancer in which Somatic Pain was Rapidly Alleviated after Panitumumab Administration Despite Tumor Progression
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Abstract: We present a 72-year-old woman with sigmoid colon cancer in whom the somatic pain was alleviated rapidly after the administration of anti-epidermal growth factor antibodies. Our patient had received 4 cycles of FOLFIRI therapy (irinotecan, 5-fluorouracil, and leucovorin) in combination with panitumumab (Pmab) for the treatment of unresectable primary cancer accompanied with multiple liver metastases and peritonitis carcinomatosa. As grade 3 paronychia eventually occurred, chemotherapy was stopped. After recovery of the grade 3 paronychia, Pmab was re-introduced and administered every alternate cycle to reduce the extent of adverse events. The patient had complained of somatic pain in the lower right abdomen just before re-initiating Pmab administration. The pain intensity decreased immediately after the administration of Pmab. On the next day her pain had remarkably alleviated and she was free from pain for a week. This phenomenon was repeatedly observed. After the re-introduction of Pmab, tumor response was evaluated on computed tomography, which showed progressive disease. We demonstrated that Pmab was effective in the alleviation of somatic pain, although the size of the tumors gradually increased. Download Full Article |
