Biomarkers and Genomic Medicine最新文献

Retroperitoneal malignant melanomas, either primary or metastatic, are rare. We present our clinical experience concerning one case with ileus secondary to a huge retroperitoneal malignant melanoma. A 77-year-old woman was admitted to the hospital due to progressive abdominal fullness and decreased appetite for 4 months. Plain films showed soft-tissue density in the left lower quadrant of the abdomen, as well as rightward displacement of the intestine. Laboratory data excluded any metabolic or septic causes of ileus. Abdominal computed tomography scan identified a huge retroperitoneal tumor with invasion of the left lower peritoneal space. The mass measured approximately 18.2 × 21.5 cm in the largest section. Immunohistochemical analysis of the tumor biopsies at minilaparotomy showed positive staining of tumor cells for S-100 protein, human melanoma black-45, and vimentin. Thus, a diagnosis of malignant melanoma with peritoneal metastases was established. This case highlights the possibility of a retroperitoneal malignant melanoma exerting a mass effect on the surrounding organs. The authors suggest that malignant melanoma should be taken into consideration as a possible differential diagnosis of retroperitoneal neoplasms.

Research has shown drug resistance as the major cause of failure of cancer chemotherapy. In this study, doxorubicin-sensitive human uterine cancer cell (hUCC) MES/SA, as well as doxorubicin-resistant hUCC MES/SA-DxR 2μM and MES/SA-DxR 8μM were used. Subsequently, asparagine synthetase (ASNS), a protein that had previously been proposed to be a putative cancer drug target in our laboratory, was silenced by siRNA knockdown to study the mechanism of doxorubicin-induced resistance further. After potent knockdown of ASNS, cell viability in two doxorubicin-resistant cell lines MES/SA-DxR 2μM and MES/SA-DxR 8μM was decreased, as indicated by an MTT cell proliferation assay. By coupling two-dimensional differential gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry, proteins that play a vital role in ASNS signaling network and development of doxorubicin-induced resistance were identified. Among all the proteins that we have identified, GRP78 and AKR1C1 appear to be involved in drug resistance, replication factor C appears to participate in DNA repairing, and PP6C is proposed to play a role in cell cycle arrest.

Colorectal cancer (CRC) has a high metastasis rate. MicroRNA (miRNA) is an epigenetic factor required to regulate cell proliferation, tumor cell growth, cancer formation, and metastasis by regulating tumor-suppressor genes or oncogenes. The objective of this study is to identify miRNAs and their target genes related to CRC migration and metastasis. Previously, we used miRNA microarray to reveal that miR-338-5p was significantly upregulated in patients with recurrent CRC. The expression level of miR-338-5p in tumor tissues of metastatic patients is higher than that in nonmetastatic patients. In this study, we report that miR-338-5p expression level was positively correlated with high migration activity of CRC cells. Overexpression of miR-338-5p induced the migration of CRC HCT-116 cells. Furthermore, overexpression of miR-338-5p inhibited its target gene phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) messenger RNA (mRNA) and protein expression in HCT-116 cells. Downregulation of miR-338-5p increased PIK3C3 mRNA and protein expression in CRC SW480 cells. Furthermore, our study results show that miR-338-5p blocked autophagy, as demonstrated by decreased LC3 type II expression. Autophagy inhibited the migration of colon cancer cell HCT-116 after rapamycin treatment. It can thus be concluded that miR-338-5p induces CRC cell migration by suppressing PIK3C3 expression and autophagy.

A weighted enzymatic chip array (WEnCA) can detect the gene expression of circulating tumor cells (CTCs) in the peripheral blood of patients with colorectal cancer (CRC). In this study, we used a reagent kit, the GeneCling CRC Enzymatic Gene Chip Detection Kit, which was specifically developed for the WEnCA operation platform to analyze the expression of 31 CRC-related genes of CTCs in the peripheral blood of 30 CRC patients. We moreover evaluated the expression of the genes by simultaneously using real-time quantitative polymerase chain reaction (RT-QPCR). The results showed the overexpression rate of nine genes—DVL1, ELAVL4, CHRNB1, UBE2C, PSAT1, CEA, PTTG1, KRT19, and hTERT—was greater than 90% in the CRC patients. This is concordant with the results of the original WEnCA operation procedure. Linear regression analysis demonstrated a high correlation (r = 0.901; p < 0.0001) between the experimental data of the detection kit and RT-QPCR. The GeneCling CRC Enzymatic Gene Chip Detection Kit is easy, fast, and convenient to operate for detecting gene expression of CTCs from peripheral blood. However, the correlation between the differential expression and the clinicopathological features of the 31 CRC-related genes needs further investigation to verify the clinical value.

Drug resistance is a key contributor for treatment failure in hematologic and other malignancies. Nilotinib has been observed with significant activity in patients with chronic phase chronic myeloid leukemia (CML) who have failed or are intolerant of imatinib therapy. Recent reports have suggested that microRNA (miRNA) expression changes are involved in the drug response of human cancer. Several miRNAs have been previously found to be consistently deregulated in imatinib resistance; however, very limited information is available for nilotinib-treated patients who have failed imatinib therapy. Many reports have discovered circulating miRNAs as noninvasive biomarkers of disease and therapy response. The aim of this study was to explore miRNA regulation and find candidate miRNA markers for CML that can be used for drug response prediction. Here we demonstrate the circulating miRNA profile in the culture supernatant of imatinib-resistant K562 CML cells (K562-R) by microarray chip analysis. We have identified specific miRNAs that are associated with nilotinib sensitivity by comparison of miRNA expression patterns from the culture supernatant of nilotinib-treated K562-R cells with the culture supernatant of untreated K562-R cells. The information obtained from this study may have the potential to become a novel biomarker to predict drug response in the future and can also be applied to developing novel therapeutic treatment for CML.