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INTRODUCTION: Basal like-breast cancer expresses none of the three breast cancer markers (ER, PR and Her2) and is associated with a poorer prognosis since it is treated with conventional and moderately successful chemotherapies. miRNAs are small, regulatory molecules approximately 21-24 nucleotides in length. They function at the post-transcriptional level by controlling the expression of more than 50% of human protein-coding genes and play an essential role in cell signaling pathways. AIM OF STUDY: The objective of the present study was to explore the expression profile of oncomiRs and tumor-suppressor miRs, and to define their possible correlations in triple-negative (ER, PR and Her2/neu) primary breast cancers. MATERIALS AND METHODS: Forty-nine primary triple-negative breast cancer cases, along with 34 matched tumor-associated normal samples were investigated for the expression of 9 miRNAs using qPCR. Relationships among the expression of miR-10b, miR-21, miR-122a, miR-145, miR-205, miR-210, miR-221, miR-222 and miR-296 and the pathologic features of the tumors were examined, as were as the influences of miR expression on patient overall and cancer-specific survival. RESULTS: miR-21, miR-210 and miR-221 were significantly over-expressed (fold expression±SD of miR-21, 2.55±1.88, p

INTRODUCTION: microRNAs (miRNAs) are a class of ~22 nt non-coding RNAs that regulate gene expression post-transcriptionally. The oncogenic miRNAs (oncomiRs) display anti-apoptotic activity and are over-expressed in cancer cells, whereas, miRNAs with anti-proliferative and pro-apoptotic activity function as tumor-suppressor genes and are under-expressed in cancer cells. AIM OF STUDY: Our goal was to investigate the expression profile of a various oncomiRs and tumor-suppressor miRs in urinary bladder cancer (BC). MATERIALS AND METHODS: Seventy-seven urinary BC cases, along with 77 matched tumor-associated normal samples were investigated for the expression of 11 miRNAs using qPCR. The relationship among the expression of miR-10b, miR-19a, miR-19b, miR-21, miR-126, miR-145, miR-205, miR-210, miR-221, miR-296-5p and miR-378-1, as well as with the pathologic features of the tumors, was further examined. The influence of miR expression on the overall and cancer-specific survival of the patients, as well as putative target genes of the up- and down-regulated miRNAs were also predicted. RESULTS: As expected, the majority of the microRNAs studied (miR-10b, miR-19a, miR-19b, miR-126_1, miR-145, miR-221, miR-296-5p and miR-378-1) exhibited significant down-regulation in BC vs. the normal tissue. A great range in the x-fold expression values of all microRNAs was noticed. High expression of miR-21 correlated with worse overall survival (p=0.0099). Univariate analysis showed that miR-21 and miR-210 can be used as independent prognostic factors for overall survival (p=0.015 and p=0.049, respectively). Moreover, univariate analysis revealed that miR-21 can be used as independent prognostic factor for metastasis (p=0.049). Multivariate analysis revealed that miR-21, miR-210 and miR-378 can be used as independent prognostic factors for overall survival (p=0.005, p=0.033 and p=0.012, respectively); miR-21 and miR-378 can be used as independent prognostic factors for recurrence (p=0.030 and p=0.031, respectively); and miR-21 can be used as independent prognostic factors for metastasis (p=0.049). DISCUSSION: The data reported here demonstrate that several microRNAs are deregulated in BC through down-regulation. miR-21 can be used as independent prognostic factor both for patient survival and metastasis. miR-210 can be used as an independent prognostic factor for overall survival.

We evaluated mast cell density (MCD) in myeloma bone marrow biopsies and correlated it with stage of disease and markers of angiogenesis. Fifty-three untreated myeloma patients and 28 of them responded to therapy were studied. Mast cells were highlighted using immunohistochemical stain for tryptase. Angiogenesis was evaluated measuring microvascular density and serum levels of basic-fibroblast growth factor and tumor necrosis factor-alpha. MCD was higher in untreated patients, compared to healthy population and responders. Significant association was found between MCD with angiogenesis and clinical stage of disease, suggesting that mast cells could be used as target for myeloma treatment. (C) 2013 Elsevier Ltd. All rights reserved.

Purpose To evaluate the prognostic significance of cytokeratin-19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in peripheral blood of women with early-stage breast cancer after the completion of adjuvant chemotherapy. Patients and Methods Blood was obtained from 437 patients with early breast cancer before the start and after the completion of adjuvant chemotherapy, and the presence of CK-19 mRNA-positive CTCs was assessed by real-time reverse transcriptase polymerase chain reaction. Interaction with known prognostic factors and association of CTCs with clinical outcome were investigated. Results CK-19 mRNA-positive CTCs were detected before chemotherapy in 179 patients (41.0%). After adjuvant chemotherapy, a significant change in CK-19 status was observed, as status for 51% of patients with initially CK-19 mRNA-positive disease turned negative, and status for 22% of patients with initially CK-19 mRNA-negative disease became positive (McNemar test P = .004). The detection of CK-19 mRNA-positive CTCs postchemotherapy was associated with involvement of more than three axillary lymph nodes (P = .026). Clinical relapses and disease-related deaths were significantly increased in patients with detectable postchemotherapy CK-19 mRNA-positive CTCs (both P < .001, respectively). Disease-free and overall survival were significantly reduced in patients with detectable CK-19 mRNA-positive CTCs postchemotherapy (P < .001 and P = .001, respectively). In multivariate analysis, the detection of CK-19 mRNA-positive CTCs before and after adjuvant chemotherapy was an independent factor associated with reduced disease-free survival (P < .001) and overall survival (P = .003). Conclusion The detection of CK-19 mRNA-positive CTCs in the blood after adjuvant chemotherapy is an independent risk factor indicating the presence of chemotherapy-resistant residual disease.

Angiogenesis is a prerequisite for solid tumor growth, but there is relatively limited data regarding Hodgkin lymphoma. The purpose of this study was to examine the immunohistochemical expression of angiogenic and proliferation markers in Hodgkin biopsies in relation to clinical parameters. Immunostaining was performed on 65 Hodgkin biopsies with vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 alpha (HIF-1 alpha), platelet-derived growth factor receptor alpha (PDGFR alpha), Ki-67, and p53. Microvessel density (MVD) was determined by CD31 staining. In all cases, neoplastic cells and reactive background cells were evaluated. The neoplastic population expressed VEGF in 48% of the cases, HIF-1 alpha in 54% of the cases, and PDGFR alpha in 95% of the cases. Both Ki-67 and p53 were positive in neoplastic cells in over 60% of the cases. The MVD had a median of 2.6/0.0625 mm(2) which was not different from normal lymph nodes. VEGF in the non-neoplastic compartment showed increased staining in Ann Arbor stage I-II versus III-IV. In conclusion, VEGF, HIF-1 alpha, and predominantly PDGFRa are expressed in neoplastic cells in the majority of Hodgkin lymphomas. As microvessel formation is not increased in Hodgkin, additional functions of these angiogenic molecules should be investigated. (C) 2008 Elsevier GmbH. All rights reserved.

Background: Interleukin-17 (IL-17) is a CD4 T-cell-derived mediator of angiogenesis that stimulates vascular endothelial cell migration and regulates the production of a variety of proangiogenic factors, such as tumor necrosis factor-alpha (TNF-alpha) and vascular endothelial cell growth factor (VEGF). Angiogenesis is implicated in the progression of multiple myeloma (MM). Methods: We measured serum levels of IL-17, TNF-alpha, and VEGF, as well as microvessel density (MVD) in 40 untreated MM patients. Results: Levels of IL-17 in the sera of patients with MM were higher than those in matched controls; however, the difference did not reach statistical significance. Serum levels of both TNF-alpha and VEGF in MM patients were significantly higher than those in controls (P