Nontypeable (NTHi) is an important pathogen in individuals of all ages. The lipooligosaccharide (LOS) of NTHi has evolved a complex structure that can be attributed to a multiplicity of glycosyltransferases, the random switching of glycosyltransferase gene expression via phase variation, and the complex structure of its core region with multiple glycoform branch points. This article adds to that complexity by describing a multifunctional enzyme (LsgB) which optimally functions when the species is grown on a solid surface and which can add either a ketodeoxyoctanoate (KDO) or an -acetylneuramic acid (Neu5Ac) moiety to a terminal acetyllactosamine structure of LOS.
View Article and Find Full Text PDFPseudotyping lentivirus-based vectors is a strategy used to study conferred vector tropism and mechanisms of envelope glycoprotein function. Lentiviruses and filoviruses both assemble at the plasma membrane and have homotrimeric structural envelope glycoproteins that mediate both receptor binding and fusion. Such similarities help foster efficient pseudotyping.
View Article and Find Full Text PDFHaemophilus haemolyticus and nontypeable Haemophilus influenzae (NTHi) are closely related upper airway commensal bacteria that are difficult to distinguish phenotypically. NTHi causes upper and lower airway tract infections in individuals with compromised airways, while H. haemolyticus rarely causes such infections.
View Article and Find Full Text PDFPlatinum compounds display clinical activity against a wide variety of solid tumors; however, resistance to these agents is a major limitation in cancer therapy. Reduced platinum uptake and increased platinum export are examples of resistance mechanisms that limit the extent of DNA damage. Here, we report the discovery and characterization of the role of ATP11B, a P-type ATPase membrane protein, in cisplatin resistance.
View Article and Find Full Text PDFMaspin, a tumour suppressor gene, is differentially expressed in the human placenta. Decreased expression of maspin in the first trimester corresponds with the period of maximum trophoblast invasion, suggesting a role in cell invasion and motility. Although methylation of CpG islands regulates maspin expression in cancer cells, the mechanism of maspin regulation in the human placenta is unknown.
View Article and Find Full Text PDFIntroduction: Malignant cells are capable of an unlimited number of cell divisions, either through production of telomerase, or through the alternate lengthening of telomere (ALT) mechanism. Yeast cells with genomic instability have been shown to survive in the absence of telomerase by increased recombination events. We hypothesized that ovarian cancers with high microsatellite instability (MSI-H) are more likely to lack telomerase activation.
View Article and Find Full Text PDFFocal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is activated by integrin clustering. There are limited data regarding the functional role of FAK in ovarian cancer migration and invasion. In the current study, FAK expression was evaluated in ovarian cell lines (nontransformed and cancer), 12 benign ovarian samples, and in 79 invasive epithelial ovarian cancers.
View Article and Find Full Text PDFObjective: We previously demonstrated that aggressive ovarian cancer cells are able to display in vitro vasculogenic mimicry, which is reflected by their ability to form vasculogenic-like networks in 3-dimensional cultures and to express vascular cell-associated markers. The goal of this study was to examine the functional role of specific matrix metalloproteinases in the formation of vasculogenic-like networks and extracellular matrix remodeling in vitro. We also investigated the clinical relevance of matrix metalloproteinase-2 and -9 and membrane type 1-matrix metalloproteinase in human ovarian cancers with evidence of tumor cell-lined vasculature.
View Article and Find Full Text PDFPurpose: Stress has long been believed to influence carcinogenesis, but little is known about physiological mechanisms that may underlie these effects. We have recently observed lower levels of vascular endothelial growth factor (VEGF) in ovarian cancer patients with greater social support, whereas higher VEGF was found in patients with greater distress. The goal of this study was to examine possible mechanisms underlying these relationships.
View Article and Find Full Text PDFVasculogenic mimicry reflects the plasticity of aggressive tumor cells that express vascular cell markers and line tumor vasculature; such has been demonstrated in aggressive ovarian carcinoma. This study measured the clinical significance of tumor cell-lined vasculature in ovarian carcinomas (n=77), which was detected in 23 (29.8%) tumors.
View Article and Find Full Text PDFTelomerase activation and p53 dysfunction are important events in the development and progression of most cancers including ovarian cancer. However, many cancer cell lines and human tumors have been shown to lack telomerase, and maintain telomerase through the ALT (alternative lengthening of telomeres). It is not known whether specific types of p53 mutations are correlated with telomerase activity in human tumors.
View Article and Find Full Text PDFPurpose: To assess the clinical relevance of serum vascular endothelial growth factor (VEGF) levels in distinguishing patients with ovarian cancer from those with benign adnexal masses.
Experimental Design: Preoperative serum VEGF levels were assessed in 101 women with invasive epithelial ovarian cancer, 16 with low malignant potential (LMP) ovarian tumors, and 34 women with benign ovarian tumors. VEGF levels were determined using an ELISA (R&D Systems, Minneapolis, MN).
Maspin is a noninhibitory member of the serpin family that is down-regulated in breast carcinoma but overexpressed in pancreatic carcinoma. There are no published data regarding the role of maspin in ovarian carcinoma, which is the focus of the present study. Ovarian cell lines (normal and cancer) and tumors (80 invasive, 14 benign, and 10 low malignant potential) were evaluated for maspin expression and localization.
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