Search PubMed⌕ Search

Biomedical subjects

R R Riley

Publications and source records attributed to R R Riley.

8 recordsLinked to original sources
PubMed2000

Sensitivity of the cervical transformation zone to estrogen-induced squamous carcinogenesis.

Regions where one type of epithelium replaces another (metaplasia) have a predilection for cancer formation. Environmental factors are closely linked to metaplastic carcinogenesis. In particular, cervical cancers associated with human papillomavirus (HPV) infection develop primarily at the transformation zone, a region where metaplastic squamous cells are detected in otherwise columnar epithelial-lined endocervical glands. Previously, we reported estrogen-induced multistage vaginal and cervical carcinogenesis in transgenic mice expressing HPV16 oncogenes in basal squamous epithelial cells. In the present study to investigate the threshold neoplastic response to exogenous estrogen, we treated groups of transgenic mice with lower hormone doses. A 5-fold reduction in estrogen dose induced squamous carcinogenesis solely at the cervical transformation zone compared with other reproductive tract sites. Further study delineated stages of transformation zone carcinogenesis, including formation of hyperplastic lower uterine glands and emergence of multiple foci of squamous metaplasia from individual stem-like glandular reserve cells, followed by neoplastic progression of metaplasia to dysplasia and squamous cancer. We propose that a combination of low-dose estrogen and low-level HPV oncogene expression biases transformation zone glandular reserve cells toward squamous rather than columnar epithelial fate decisions. Synergistic activation of proliferation by viral oncoprotein cell cycle dysregulation and estrogen receptor signaling, together with altered paracrine stromal-epithelial interactions, may conspire to support and promote neoplastic progression and cancer formation.

Animals↗
PubMed1999

Difluoromethylornithine chemoprevention of epidermal carcinogenesis in K14-HPV16 transgenic mice.

To be informative for chemoprevention, animal models must both closely emulate human disease and possess surrogate endpoint biomarkers that facilitate rapid drug screening. This study elucidated site-specific histopathological and biochemical surrogate endpoint biomarkers of spontaneous epidermal carcinogenesis in K14-HPV16 transgenic mice and demonstrated that the incidence and severity of these markers were decreased by the ornithine decarboxylase (ODC) inhibitor difluoromethylornithine (DFMO). The cumulative incidence of visible epidermal cancers in 127 untreated transgenic mice was 42% by 52 weeks of age, most frequently affecting the chest as flat lesions in association with chronic ulcers, or in the ear as protuberant masses. Microscopic malignancies were detected in 39% of 32-week-old transgenic mice and were found to emerge from precursor lesions that were of two distinct types: dysplastic sessile ear papillomas and hyperproliferative follicular/interfollicular chest dysplasias. ODC activity and tissue polyamine contents were differentially elevated in ear and chest skin during carcinogenesis, such that there was a marked elevation of both parameters of polyamine metabolism as early as 4 weeks of age in the ear, whereas in the chest, polyamine metabolism was increased significantly only in the late stages of neoplastic progression and in epidermal cancers. Administration of 1.0% DFMO in the drinking water from 4 to 32 weeks of age prevented both visible and microscopic malignancies and significantly decreased the incidence of chest and ear precursor lesions. ODC activity and tissue putrescine content were markedly diminished by DFMO chemoprevention in ear skin, whereas there was a more modest decline of these parameters in chest skin. DFMO treatment of transgenic mice from 28 to 32 weeks of age was associated with an absence of ear cancer and a marked regression of dysplastic papillomas. In contrast, the results in chest skin were complex in that the severity of chest precursors diminished, but their incidence was unchanged, and microscopic cancers were still detectable within these lesions. Collectively, this study highlights the utility of multistage epidermal carcinogenesis in K14-HPV16 transgenic mice both for the study of the biology of, and as a screening tool for, novel drugs and chemopreventive regimens.

Administration, Oral↗
PubMed1984

Follow-up assessment of St. Jude Medical prosthetic valve in the tricuspid position: clinical and hemodynamic results.

Seven patients underwent postoperative right heart catheterization implantation of the St. Jude Medical prosthetic valve in the tricuspid position. Six patients were in atrial fibrillation at catheterization, and 1 was in normal sinus rhythm. At postoperative catheterization, the mean right atrial pressure ranged between 4 and 16 mm Hg (mean, 9.7 mm Hg); right ventricular systolic pressure was normal in 1 patient, mildly elevated (less than 50 mm Hg) in 4 patients, and moderately elevated (65 and 70 mm Hg) in 2. The cardiac output ranged between 3.0 and 7.0 L/min (mean, 4.2 L/min). There was no end-diastolic gradient across the St. Jude Medical prosthesis in 6 patients. The other patient had a gradient of 2 mm Hg across the valve when cardiac output was 7.0 L/min. On fluoroscopy, both discs demonstrated full excursion in all patients. These data demonstrate that a normally functioning St. Jude Medical valve in the tricuspid position does not create obstruction to forward flow, and they support use of this prosthesis in patients with tricuspid valve disease.

Adult↗