The protein phosphatase 2A regulatory subunit PR70 is a gonosomal melanoma tumor suppressor gene.

Male gender is independently and significantly associated with poor prognosis in melanoma of all clinical stages. The biological underpinnings of this sex difference remain largely unknown, but we hypothesized that gene expression from gonosomes (sex chromosomes) might play an important role. We demonstrate that loss of the inactivated X chromosome in melanomas arising in females is strongly associated with poor distant metastasis-free survival, suggesting a dosage benefit from two X chromosomes.

Identification of six loci associated with pelvic organ prolapse using genome-wide association analysis.

Objective: There is evidence that both environmental and genetic factors contribute to pelvic organ prolapse. We conducted a genome-wide association study to investigate whether common genetic variants modify the risk of pelvic organ prolapse.

Methods: We recruited women who had been evaluated and treated for pelvic organ prolapse at the University of Utah from 1996 to 2008 and their affected female relatives.

GLI2-mediated melanoma invasion and metastasis.

Background: The transforming growth factor-beta (TGF-beta) pathway, which has both tumor suppressor and pro-oncogenic activities, is often constitutively active in melanoma and is a marker of poor prognosis. Recently, we identified GLI2, a mediator of the hedgehog pathway, as a transcriptional target of TGF-beta signaling.

Methods: We used real-time reverse transcription-polymerase chain reaction (RT-PCR) and western blotting to determine GLI2 expression in human melanoma cell lines and subsequently classified them as GLI2high or as GLI2low according to their relative GLI2 mRNA and protein expression levels.

Activated leukocyte cell adhesion molecule expression predicts lymph node metastasis in oral squamous cell carcinoma.

Lymphatic metastasis of oral squamous cell carcinoma (SCC) is important for prognosis and clinical decision making concerning the treatment of the neck but may be difficult to detect. Activated leukocyte cell adhesion molecule (ALCAM), has been shown to correlate with prognosis or tumor grade in different tumor types and may be a predictor of lymphatic metastasis. ALCAM expression at the invasive front in fresh frozen tissue samples of oral SCC's (n=41) was studied immunohistochemically, using a polyclonal antibody directed against ALCAM's extracellular domain.

COL3A1 2209G>A is a predictor of pelvic organ prolapse.

Introduction And Hypothesis: A familial tendency has been demonstrated in the etiology of pelvic organ prolapse (POP), but the specific genetic defects have not been identified. Type III collagen is an important factor in the repair of connective tissue, and gene polymorphisms may impair the tensile strength. We hypothesized that polymorphisms in the alpha I chain of the type III collagen protein-encoding gene (COL3A1) pose women at risk for POP.

Intratumoral rhIL-12 administration in head and neck squamous cell carcinoma patients induces B cell activation.

The objectives of this study were to investigate the effects of intratumorally (i.t.) administered recombinant human interleukin-12 (rhIL-12) on the distribution and function of B cells in the primary tumors, the locoregional lymph nodes and peripheral blood of head and neck squamous cell carcinoma (HNSCC) patients.

Loss of membranous Ep-CAM in budding colorectal carcinoma cells.

Tumor budding is a histological feature that reflects loss of adhesion of tumor cells and is associated with locoregional metastasis of colorectal carcinoma. Although nuclear localization of beta-catenin is associated with tumor budding, the molecular mechanism remains largely elusive. In this study, we hypothesize that the epithelial cell adhesion molecule (Ep-CAM) is involved in tumor budding.

Inflammation, proteases and cancer.

Tumours are complex tissues composed of ever-evolving neoplastic cells, matrix proteins that provide structural support and sequester biologically active molecules, and a cellular stromal component. Reciprocal interactions between neoplastic cells, activated host cells and the dynamic micro-environment in which they live enables tumour growth and dissemination. It has become evident that early and persistent inflammatory responses observed in or around developing neoplasms regulates many aspects of tumour development (matrix remodelling, angiogenesis, malignant potential) by providing diverse mediators implicated in maintaining tissue homeostasis, e.

Tumours can adapt to anti-angiogenic therapy depending on the stromal context: lessons from endothelial cell biology.

It has long been recognized that interference with the blood supply of a tumour is an effective way to halt tumour progression, and even induce tumour regression. This can be accomplished by anti-angiogenic treatment which prevents the formation of a tumour neovasculature, or anti-vascular treatment, which aims at destruction of existent tumour vessels. The latter has received relatively little attention because there is a lack of specific tumour-endothelial markers.

Stromal responses in human primary melanoma of the skin.

Tumour development and progression has long been considered as the consequence of an imbalance between apoptosis and proliferation of transformed cells. However, whereas genetic aberrations leading to the activation of oncogenes and/or loss of tumour suppressor genes are crucial for the transformation towards aberrant cell growth, progression towards a full blown malignancy requires a dynamic interaction between tumour cells and the environment in which they thrive. Over the recent years, it has become evident that the (early) inflammatory and angiogenic response, and remodelling of the extracellular proteins are key factors in creating a microenvironment that sustains tumour growth and metastasis.

Epithelial carcinogenesis: dynamic interplay between neoplastic cells and their microenvironment.

Matrix metalloproteinases (MMPs) have long been thought of as critical factors regulating matrix degradation associated with cell invasion into ectopic tissue compartments during primary tumor growth and metastasis. One member of the MMP family historically linked to these invasive processes is MMP-9/gelatinase B. By studying a transgenic mouse model of de novo epithelial carcinogenesis, new roles for MMP-9 have emerged that broaden the view of its functional contribution to malignant progression.

MMP9 potentiates pulmonary metastasis formation.

Tumor cell dissemination to distant organ sites is a complex process involving multiple cell types, soluble growth factors, adhesion receptors, and tissue remodeling. A new study in this issue of Cancer Cell shows that MMP9-expressing tumor-associated macrophages play a key role in prepping premetastatic sites for eventual malignant cell growth in a manner dependent upon vascular endothelial growth factor receptor-1 (VEGFR-1).