Search

Cervical cancer is a major global public health care concern and the second most commonly diagnosed malignancy among females worldwide. B7-H4 is an immunoregulatory protein that has been shown to be overexpressed in several types of cancer and is often associated with more advanced disease and poor prognosis. We investigated whether B7-H4 is a prognostic maker for cervical cancer by detecting its expression in cervical cancer specimens. Formalin-fixed, paraffin-embedded tissue blocks from cervical cancer were evaluated for B7-H4 expression by immunohistochemistry with free R software analysis. The intensity of B7-H4 immunoexpression was evaluated according to age, histological type, International Federation of Gynecology and Obstetrics (FIGO) stage, lymphovascular space invasion (LVSI) and lymph node status. We investigated the distribution and expression of B7-H4 in 102 cervical cancer specimens and determined the association between its expression and clinicopathological characteristics, including patient outcomes. Of the 102 specimens, 31 were found to be negative for B7-H4 immunoexpression, whereas 71 were B7-H4-positive. When classified by negative vs. positive expression, B7-H4 was not found to be associated with any of the clinicopathological parameters investigated. A positive B7-H4 expression significantly predicted poor overall survival (OS) when compared to negative expression (P<0.05). In the multivariate analysis, positive B7-H4 expression was identified as an independent prognostic factor for OS (P<0.05). Our data suggested that positive B7-H4 expression may be a useful biomarker in patients with cervical cancer likely to have an unfavorable clinical outcome. [ABSTRACT FROM AUTHOR]

A three-dimensional (3D) cell culture system has been fabricated using a magnetic force based cell patterning method, demonstrating a facile approach for the analysis of invasive capacity of BALB/3T3/v-srcusing an magnetic force and magnetite nanoparticles. The 3D cell patterning was performed using an external magnetic force and a pin holder, which enables the assembly of the magnetically labeled cells on the collagen gel-coated surface as array-like cell patterns, resulting in the development of a 3D in vitroculture model. The cells embedded in type I collagen showed a compacted, spheroid like configuration at each spot, and distinct, accelerated cell growth was observed in cancer model cells compared with the control cells. The developed 3D cell culture array was applied to the susceptibility assay of the GM6001 matrix metalloproteinase (MMP) inhibitor, a collagenase inhibitor; a distinct suppression of cell proliferation was observed, while little change was observed in 2D. The developed 3D cell culture array system is useful to assess the effects of pharmacologic and/or microenvironmental influences on tumor cell invasion. [ABSTRACT FROM AUTHOR]

Ovarian cancer is a highly invasive and metastatic disease with a poor prognosis if diagnosed at an advanced stage, which is often the case. Recent studies argue that ovarian cancer cells that have undergone epithelial-to-mesenchymal transition (EMT) acquire aggressive malignant properties, but the relevant molecular mechanisms in this setting are not well-understood. Here, we report findings from an siRNA screen that identified the homeobox transcription factor ALX1 as a novel regulator of EMT. RNA interference--mediated attenuation of ALX1 expression restored E-cadherin expression and cell--cell junction formation in ovarian cancer cells, suppressing cell invasion, anchorage-independent growth, and tumor formation. Conversely, enforced expression of ALX1 in ovarian cancer cells or nontumorigenic epithelial cells induced EMT. We found that ALX1 upregulated expression of the key EMT regulator Snail (SNAI1) and that it mediated EMT activation and cell invasion by ALX1. Our results define the ALX1/Snail axis as a novel EMT pathway that mediates cancer invasion. [ABSTRACT FROM AUTHOR]