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1.  ST6Gal-I expression in ovarian cancer cells promotes an invasive phenotype by altering integrin glycosylation and function 
Background
Ovarian adenocarcinoma is not generally discovered in patients until there has been widespread intraperitoneal dissemination, which is why ovarian cancer is the deadliest gynecologic malignancy. Though incompletely understood, the mechanism of peritoneal metastasis relies on primary tumor cells being able to detach themselves from the tumor, escape normal apoptotic pathways while free floating, and adhere to, and eventually invade through, the peritoneal surface. Our laboratory has previously shown that the Golgi glycosyltransferase, ST6Gal-I, mediates the hypersialylation of β1 integrins in colon adenocarcinoma, which leads to a more metastatic tumor cell phenotype. Interestingly, ST6Gal-I mRNA is known to be upregulated in metastatic ovarian cancer, therefore the goal of the present study was to determine whether ST6Gal-I confers a similarly aggressive phenotype to ovarian tumor cells.
Methods
Three ovarian carcinoma cell lines were screened for ST6Gal-I expression, and two of these, PA-1 and SKOV3, were found to produce ST6Gal-I protein. The third cell line, OV4, lacked endogenous ST6Gal-I. In order to understand the effects of ST6Gal-I on cell behavior, OV4 cells were stably-transduced with ST6Gal-I using a lentiviral vector, and integrin-mediated responses were compared in parental and ST6Gal-I-expressing cells.
Results
Forced expression of ST6Gal-I in OV4 cells, resulting in sialylation of β1 integrins, induced greater cell adhesion to, and migration toward, collagen I. Similarly, ST6Gal-I expressing cells were more invasive through Matrigel.
Conclusion
ST6Gal-I mediated sialylation of β1 integrins in ovarian cancer cells may contribute to peritoneal metastasis by altering tumor cell adhesion and migration through extracellular matrix.
doi:10.1186/1757-2215-1-3
PMCID: PMC2584051  PMID: 19014651
2.  A multi-center, randomized, double blind placebo-controlled trial of estrogens to prevent Alzheimer’s disease and loss of memory in women: design and baseline characteristics 
Clinical trials (London, England)  2008;5(5):10.1177/1740774508096313.
Background
Observational studies and small clinical trials suggested that hormone replacement therapy (HRT) decreases risk of cognitive loss and Alzheimer’s disease (AD) in postmenopausal women and may have value in primary prevention.
Purpose
A clinical trial was designed to determine if HRT delays AD or memory loss. This report describes the rationale and original design of the trial and details extensive modifications that were required to respond to unanticipated findings that emerged from other studies during the course of the trial.
Methods
The trial was designed as a multi-center, placebo-controlled primary prevention trial for women 65 years of age or older with a family history of dementia. Recruitment from local sites was supplemented by centralized efforts to use names of Medicare beneficiaries. Inclusion criteria included good general health and intact memory functioning. Participants were randomized to HRT or placebo in a 1:1 ratio. Assignment was stratified by hysterectomy status and site. The primary outcomes were incident AD and memory decline on neuropsychological testing.
Results
Enrollment began in March 1998. In response to the Women’s Health Initiative (WHI) May 2002 report of increased incidence of heart disease, stroke, pulmonary embolism, and breast cancer among women randomized to HRT, participants were re-consented with a revised consent form. Procedural modifications, including discontinuation of study medication and a modification of the planned primary outcome based on a final enrollment below the target enrollment (N = 477), were enacted in response to the subsequent WHI Memory Study report of increased risk of dementia and poorer cognitive function with HRT. The mean length of treatment exposure prior to discontinuation was 2.14 years. Participants’ mean age at baseline was 72.8; mean education was 14.2 years. Minority participation was 19% and 34% had a hysterectomy. The study continues to follow these participants for a total of 5 years blind to the original medication assignment.
Limitations
Results reported from the WHI during the course of this study mandated extensive procedural modifications, including discontinuing recruitment before completion and halting study medication. Alternative strategies for study redesign that were considered are discussed.
doi:10.1177/1740774508096313
PMCID: PMC3884686  PMID: 18827045
3.  Detecting Dementia with the Mini-Mental State Examination (MMSE) in Highly Educated Individuals 
Archives of neurology  2008;65(7):963-967.
Objectives
To evaluate the utility of Mini-Mental State Examination (MMSE) scores in detecting cognitive dysfunction in a sample of highly educated individuals.
Design
Archival data were reviewed on 4248 participants enrolled in the Mayo Clinic Alzheimer's Disease Research Center (ADRC) and Alzheimer's Disease Patient Registry (ADPR).
Patients
1141 primarily Caucasian (93%) individuals with 16 or more years of self-reported education were identified. These included 307 (164 males and 143 females) dementia cases (any type), 176 patients with Mild Cognitive Impairment (106 males and 70 females), and 658 nondemented controls (242 males and 416 females).
Setting
Mayo Clinic ADRC and ADPR cohort.
Main Outcome Measures
Diagnostic accuracy estimates (sensitivity, specificity, positive and negative predictive power) of MMSE cut-scores in detecting cognitive dysfunction.
Results
In this sample of highly educated, largely Caucasian older adults, the standard MMSE cut-score of 24 (23 or below) yielded a sensitivity of .66, specificity of .99 and an overall correct classification rate of 89% in detecting dementia. A cut score to 27 (26 or below) resulted in an optimal balance of sensitivity and specificity (.89 and .91, respectively) with an overall correct classification rate of 90%. In a cognitively impaired group (dementia and MCI), a cut-score of 27 (sensitivity = .69, specificity = .91) or 28 (sensitivity and specificity = .78) might be more appropriate.
Conclusion
Elderly patients with college education who present with complaints of cognitive decline (self- or other-report) and score below 27 on the MMSE are at greater risk of being diagnosed with dementia and should be referred for a comprehensive dementia evaluation, including formal neuropsychological testing.
doi:10.1001/archneur.65.7.963
PMCID: PMC2587038  PMID: 18625866
Alzheimer's disease; dementia; Mini-Mental State Examination; diagnosis
4.  Structural details and composition of Trichomonas vaginalis lipophosphoglycan in relevance to the epithelial immune function 
Glycoconjugate journal  2008;26(1):3-17.
Trichomonas vaginalis causes the most common non-viral sexually transmitted infection linked to increased risk of premature birth, cervical cancer and HIV. This study defines molecular domains of the parasite surface glycol-conjugate lipophosphoglycan (LPG) with distinct functions in the host immunoinflammatory response. The ceramide phospho-inositol glycan core (CPI-GC) released by mild acid had Mr of ~8,700 Da determined by MALDI-TOF MS. Rha, GlcN, Gal and Xyl and small amounts of GalN and Glc were found in CPI-GC. N-acetyllactosamine repeats were identified by endo-β-galactosidase treatment followed by MALDI-MS and MS/MS and capLC/ESI-MS/MS analyses. Mild acid hydrolysis led to products rich in internal deoxyhexose residues. The CPI-GC induced chemokine production, NF-κB and extracellular signal-regulated kinase (ERK)1/2 activation in human cervicovaginal epithelial cells, but neither the released saccharide components nor the lipid-devoid LPG showed these activities. These results suggest a dominant role for CPI-GC in the pathogenic epithelial response to trichomoniasis.
doi:10.1007/s10719-008-9157-1
PMCID: PMC2637367  PMID: 18604640
Trichomonad LPG; Mass spectrometry; Cytokines; NF-κB; ERK; Vaginal mucosal immunity

Results 1-4 (4)