Plasminogen activator inhibitor-1 is increased in colonic epithelial cells from patients with colitis-associated cancer.

BACKGROUND: Patients with long-term ulcerative colitis are at risk for developing colorectal cancer. METHODS: Archival formalin-fixed paraffin-embedded tissue from ulcerative colitis patients who underwent a colectomy for high-grade dysplasia or carcinoma was examined for changes in expression of plasminogen activator inhibitor-1 (PAI-1) as well as other mediators of inflammation-associated cancer. Epithelia from areas of colons that showed histologic evidence of carcinoma, high-grade dysplasia, and epithelia that were not dysplastic or malignant but did contain evidence of prior inflammation (quiescent colitis) was microdissected using laser capture microscopy. mRNA was extracted from the microdissected tissue and PCR array analysis was performed. To extend our findings, PAI-1 protein levels were determined using immunohistochemistry. RESULTS: The mRNA expression of PAI-1 is increased 6-fold (p=0.02) when comparing the carcinoma group to the quiescent colitis group; increases were also observed in NFKB2, REL, SRC, and VEGFA. The protein levels of PAI-1 are increased by 50% (p<0.001) in high-grade dysplasia and by 60% (p<0.001) in carcinoma when compared to the quiescent colitis group. CONCLUSIONS: The increase in PAI-1 in high-grade dysplasia and carcinoma suggests a functional role for PAI-1 in malignant transformation in colitis-associated cancer. PAI-1 could also prove a useful diagnostic marker to identify patients at risk for neoplasia and it may be a useful therapeutic target to treat colitis-associated cancer.

Truncated neurokinin-1 receptor is increased in colonic epithelial cells from patients with colitis-associated cancer.

Patients with chronic ulcerative colitis (UC) are at high risk for developing colorectal cancer. In this study, archival formalin-fixed paraffin-embedded colonic tissue from patients with UC who developed carcinoma (CA) or high-grade dysplasia (HGD) was examined for changes in expression of the proinflammatory and mitogenic neurokinin-1 receptor (NK-1R). Laser capture microscopy was used to microdissect epithelia from areas of colons that showed histologic evidence of CA, HGD, and epithelia that were not dysplastic or cancerous but did contain evidence of prior inflammation (quiescent colitis). mRNA was extracted from the dissected tissue, and PCR array analysis was performed on extracted mRNA. Two antibodies were necessary to separately estimate the protein levels of the truncated (tr-NK-1R) and full-length (fl-NK-1R) receptors by immunohistochemistry. mRNA expression of tr-NK-1R increased 14-fold (P = 0.02) when comparing the HGD and CA groups. In contrast, the fl-NK-1R transcript showed no significant differences among groups. The protein levels of the total NK-1R increased by 40% (P = 0.02) in HGD and 80% (P = 0.0007) in CA compared with quiescent colitis. There were no significant changes in protein levels of the fl-NK-1R. We conclude that the increase in total NK-1R protein in HGD and CA is attributable to an increase in tr-NK-1R, suggesting there may be a functional role for tr-NK-1R in malignant transformation in colitis-associated cancer. The tr-NK-1R could prove useful as a diagnostic marker to identify patients at risk for neoplasia and may serve as a useful therapeutic target in the treatment of colitis-associated cancer.

HPV vaccine: A comparison of attitudes and behavioral perspectives between Latino and non-Latino women.

OBJECTIVE: Recent scientific advances have lead to the development of a prophylactic, quadrivalent HPV vaccine conferring. We surveyed Latino and non-Latino women directly to examine what motivates them to vaccinate themselves, their daughters, and their sons. METHODS: A written survey was administered to 86 Latinas and 141 non-Latinas, ages 18-55, and attending a general medicine, gynecology, or pediatric unit at an academic center. The instrument included questions on demographics, knowledge and attitudes toward the HPV vaccine, attitudes toward HPV vaccination for the respondents' daughters and/or sons, and the effect of vaccine acceptability on women's attitudes towards their sexual behavior and cervical cancer screening practices. RESULTS: Acceptance for the HPV vaccine was high, with 73% of non-vaccinated, eligible women stating that they would vaccinate themselves. Cervical cancer prevention was the primary motivation for seeking vaccination. Most respondents reported that vaccination should still be accompanied by cervical cancer screening. Seventy-percent of eligible respondent agreed to vaccinate their daughters (97% of Latino and 68.2% of non-Latino mothers, p=0.0078). Eighty-six percent of eligible participants agreed to vaccinate their sons (92.3% of Latino and 76.9% of non-Latino mothers, p=0.0490). Cervical cancer prevention and anal/penile cancer prevention were the primary motivation reported for accepting the vaccine in their daughters and sons, respectively. Fewer than 20% of eligible respondents cited protection of women against developing cervical cancer as the motivation to vaccinate their son(s). CONCLUSIONS: Among vaccine-eligible women, HPV vaccination acceptance for themselves, their daughters, and potentially their sons is high and primarily motivated by cancer prevention for the individual vaccinated.