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.

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.

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.