Introduction: Over 74,000 US women are diagnosed annually with endometrial or cervical cancers and experience significant treatment-related difficulties with body image, sexuality, and sexuality. The aims of the research were to examine relationships among body image, sexuality, and sexual functioning, and understand women’s views of these concepts. A novel theoretical framework encompassing these three concepts and contextual variables guided the research. Methods: A non-experimental cross-sectional pilot study was conducted with pre-menopausal women in an academic medical center who had stages I-III cervical or endometrial cancer, were 3-36 months post-treatment, and had no mental health diagnoses. Participants completed the Body Image Scale, Female Sexual Function Index, Female Sexuality Questionnaire, a demographic questionnaire, and open-ended questions and the researchers collected clinical data from the medical record. Results: Twenty women participated, and most reported disruption in body image, sexuality, and sexual functioning. Significant relationships were found between body image and sexuality (p = 0.0244) and sexuality and sexual functioning (p <0.0003). Stages II-III disease were significantly (p= 0.0371) associated with worse body image. Women reported issues with body image, sexuality, sexual functioning, psychosocial areas, reproduction, and communication with healthcare providers and personal caregivers. Discussion: This study is one of the first to examine relationships among body image, sexuality, and sexual functioning simultaneously, highlighting the importance of this approach. Despite design and sample limitations, results demonstrate a need for longitudinal studies using larger samples to further examine relationships among these concepts and selected contextual variables, explore communication issues, and refine the theoretical framework.

Cancer is the second leading cause of death in the USA, following cardiovascular disease. Treating cancer using conventional therapies is associated with low response rates and high toxicity, because these therapies usually lack specific tumor accumulation. Loading anticancer drugs into intelligently designed polymeric nanoparticles (NPs) can serve in delivering these drugs specifically to the tumor site, thus boosting their efficacy and reducing any associated off target toxicity. Targeting NPs to the tumor site can occur through either passive or active means. In passive targeting, NPs of specific size and surface characteristics can exploit the tumor’s erratic vasculature and occluded lymphatic drainage to extravasate the systemic circulation and accumulate preferentially at the tumor site. Active targeting mandates grafting the surface of NPs with a ligand that specifically interacts with a protein expressed at higher levels at the tumor site, in comparison to elsewhere in the body. In the current research, we independently investigated the utilization of passive and active targeting strategies to treat aggressive forms of cancer. Initially, passively targeted poly(lactic-co-glycolic acid) (PLGA) NPs to treat aggressive forms of endometrial cancer (EC) were investigated. A novel combination of soluble paclitaxel (PTX), a first line chemotherapy for EC, and soluble BIBF1120 (BIBF, nintedanib), an antiangiogenic molecular inhibitor, was first tested against three EC cell lines bearing different p53 mutations. The results showed that only EC cells with loss of function (LOF) p53 were sensitive to the combination therapy, indicating the potential of this combination to engender synthetic lethality to PTX. Next, NPs loaded with PTX were investigated with respect to the impact of varying the polymer lactic acid to glycolic acid ratio and the surfactant type on the major physicochemical properties of the prepared nanoparticles, drug loading, cellular uptake, cytotoxicity, and drug release. The optimum formulation was then loaded with BIBF and the combination of independently loaded passively targeted NPs were further evaluated for in vivo activity against a xenograft model of LOF p53 EC. The combination of independently loaded NPs exhibited the highest reduction in tumor volume and prolonged survival when compared to soluble PTX, PTX NPs or untreated control. These data highlight this specific combination of NPs as a novel promising therapy for LOF p53 EC. In a second study, the use of actively targeted NPs to treat liver cancer was explored. In this study, a combination of small interfering RNA (siRNA) against astrocyte elevated gene-1 (AEG-1), and all-trans retinoic acid (ATRA) was investigated as a new therapy for hepatocellular carcinoma (HCC). AEG-1 is a highly expressed oncogene that is directly involved in HCC progression and aggressiveness, in addition to reducing the ability of retinoic acid to induce apoptosis in HCC cells. First, a new conjugate was synthesized that was capable of delivering siRNA selectively to HCC cells, using galactose as a targeting moiety. The conjugate was prepared by linking poly(amidoamine) (PAMAM) dendrimers, polyethylene glycol (PEG) and lactobionic acid (Gal, disaccharide containing galactose) (PAMAM-PEG-Gal). We confirmed the synthesis of the conjugate using 1H-NMR, Mass spectrometry and Matrix-Assisted Laser Desorption/Ionization (MALDI) Mass Spectrometry. Next, nanoplexes of the synthesized conjugate, PAMAM-PEG-Gal, and AEG-1 siRNA were prepared. Nanoplexes were further characterized for their size, surface charge, morphology, and electrophoretic mobility to identify the optimum complexation ratio between PAMAM-PEG-Gal and the siRNA. Then, mice bearing orthotopic luciferase expressing HCC cells were treated with the optimum nanoplex formulation. Results showed that a combination of AEG-1 nanoplexes and ATRA results in a significant reduction in luciferase expression, reduced liver weight, lower AEG-1 mRNA levels and increased apoptosis, when compared to utilizing nanoplexes with silencing control (siCon), siCon+ATRA, or AEG-1 nanoplexes alone. The results indicate that the combination of liver-targeted AEG-1 nanoplexes and ATRA may be a potential treatment for aggressive HCC. These data place targeted NPs as a promising efficient delivery system for cancer treatment.

Maternal contributions from the uterine endometrial luminal (LE) and glandular (GE) epithelia are unequivocally required to support ruminant conceptus growth and development, elongation and implantation. Therefore, studies were conducted to examine expression of endometrial genes hypothesized to regulate conceptus development. The first study investigated two genes specifically expressed in the LE and superficial GE of the ovine uterus. Insulin-like growth factor binding protein (IGFBP1) and (IGFBP3) expression was coordinate with ovine conceptus elongation. Treatment with P4 induced and IFNT stimulated IGFBP1, but not IGFBP3; however, IFNT only moderately stimulated IGFBP1, indicating that another conceptus-derived factor stimulates endometrial IGFBP1 expression. IGFBP1 did not affect proliferation of ovine trophectoderm (oTr) cells in vitro, but stimulated their migration and attachment. Results indicated that IGFBP1, but not IGFBP3 is a marker of conceptus elongation in ruminants and stimulates cell migration and attachment. The second study evaluated the effects of pregnancy, P4 and IFNT on expression of hydroxysteroid (11-beta) dehydrogenases (HSD11B1 and HSD11B2), nuclear receptor subfamily 3, group C, member 1 (NR3C1), and prostaglandin-endoperoxide synthase 2 (PTGS2) in the ovine uterus. Expression of HSD11B1 mRNA and PTGS2 protein in endometrial LE and sGE were coordinate with conceptus elongation, while HSD11B2 mRNA was expressed primarily in the conceptus. Further, P4 induced, but IFNT only moderately stimulated HSD11B1. Thus, HSD11B1 expression may be regulated by prostaglandins (PGs) during early pregnancy. The presence of NR3C1 in the ovine uterus implicates cortisol, the main product of HSD11B1, in peri-implantation period events that include elongation of the ovine conceptus. The third study determined in vivo effects of PGs on ovine conceptus elongation and endometrial gene expression. Compared to control ewes, intrauterine infusions of a PTGS2 inhibitor, meloxicam, retarded elongation and decreased expression of elongation-related genes including IGFBP1, IGFBP3, HSD11B1, galectin 15 (LGALS15), solute carrier family 2, member 1 (SLC2A1), gastrin-releasing peptide (GRP), cystatin C (CST3), radical S-adenosyl methionine domain containing 2 (RSAD2), and ISG15 ubiquitin-like modifer (ISG15). Collectively, these studies assessed the effects of pregnancy, P4, IFNT, and PGs on endometrial genes implicated in conceptus growth. These results indicate that IGFBP1 is a marker of conceptus elongation in ruminants and provide novel roles for both cortisol and PGs in endometrial gene expression and conceptus elongation.

Endometrial glands are required for adult uterine function and develop post-natally in mammalian species. Therefore, studies were conducted using neonatal ewes as a model to determine: 1) the roles of estradiol-17-alpha and estrogen receptor-alpha (ER-beta) in endometrial gland development; 2) the role of ovaries in endometrial gland development; 3) the role of prolactin in endometrial gland development; and 4) factors regulating prolactin receptor expression in endometrial glands. Study one determined the effects of neonatal exposure of ewes to estradiol-17-alpha valerate (EV); EM-800, an ER-beta antagonist; or CGS-20267, an aromatase inhibitor on endometrial gland development. Results indicate E2-17-alpha does not regulate endometrial gland differentiation or development. Additionally, ER-beta does not regulate primary differentiation of glandular epithelium, but does influence coiling and branching morphogenesis of endometrial glands. Study two determined the effects of ovariectomy on endometrial gland morphogenesis. Results suggest that the ovary and, thus, an ovarian-derived factor(s) regulate, in part, the coiling and branching of endometrial glands. Expression of subunits of activin, follistatin, and inhibin in the neonatal ovine ovary in addition to modulation of the components of the activin/follistatin system in the uterus of ovariectomized ewes supports the hypothesis that the ovarian factors that influence endometrial adenogenesis in the neonatal ewe may be activin, follistatin, and/or inhibin. Studies three and four determined the role of prolactin in endometrial adenogenesis in the neonatal ewe. Studies in which either hypoprolactinemia or hyperprolactinemia were induced indicate that prolactin regulates ovine endometrial adenogenesis in the neonatal ewe. The aim of study five was to determine transcription factors that regulate the glandular epithelium specific expression of prolactin receptor. Prolactin receptor exon 2 was cloned and sequenced, but no identifiable exon 1 or promoter was found. Additionally, many bovine contigs containing portions of the prolactin receptor gene were identified suggesting the bovine genome will be a useful tool as it becomes more complete. These results indicate ER-beta, prolactin and prolactin receptor, along with an unidentified ovarian factor(s), influence endometrial gland development in the neonatal ewe; however, exposure of the neonatal ewe to exogenous estradiol-17-alpha prevents differentiation and development of endometrial glands.

Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Göteborg : Univ. , 2009. / Härtill 4 uppsatser.

Thesis (M.S.)--West Virginia University, 2000. / Title from document title page. Document formatted into pages; contains vii, 79 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 68-79).

Thesis (M.S.)--University of Florida, 2005. / Title from title page of source document. Document formatted into pages; contains 80 pages. Includes vita. Includes bibliographical references.

Individuals who identify themselves as transgender have gender identities that do not match their anatomical sex. Females who identify as male, also known as female-to-male transgender (FTM), may opt to undergo hormonal and surgical treatment in order to transition to the male phenotype, including high-dose testosterone treatment to develop male secondary sexual characteristics and surgical procedures. Currently, the recommendation is for the patient to have a hysterectomy within five years of initiating testosterone therapy to decrease the risk of developing endometrial cancer. However, long-term testosterone treatment has not been proven to cause an increased risk of endometrial cancer. With the use of gene expression and immunohistochemical studies, this study aimed to show no upregulation of genes associated with proliferation (Ki-67) and endometrial cancer (ZIC2) in endometrial tissue from FTM individuals treated with long-term testosterone compared to endometrial tissue from postmenopausal women, premenopausal women with benign endometrium, and women with endometrial cancer. Our findings showed that Ki-67 and ZIC2 expression in the FTM samples was significantly lower than in the endometrial cancer samples. Our findings call into question the concept that long-term testosterone treatment causes neoplastic changes in endometrial tissue and the need for routine hysterectomy in these patients. / 2018-07-11T00:00:00Z

Chlamydia trachomatis (Ct), the most common sexually transmitted bacterium, has been associated with adverse pregnancy outcomes including controversial data on miscarriage, intrauterine growth restriction and low birth weight, however the causative mechanisms are unknown. A successful pregnancy requires normal endometrial stromal cell (ESC) decidualisation and trophoblast invasion, processes that involve chemokine action and lead to successful implantation. My objectives were to determine whether Ct infection impacts upon ESC decidualisation and chemokine secretion on human primary ESC invitro, to investigate the role of Ct infection in pregnancy in-vivo using a murine model of pregnancy and to investigate the role of Ct in miscarriage in a statistically powered case control study. A novel finding is that Ct can infect and proliferate in ESC, resulting in suboptimal decidualisation as measured by decidualisation marker prolactin’s reduced mRNA and protein levels in infected ESC. Furthermore, the altered secreted chemokine profile of decidualised ESC suggests an attenuated innate immune response from infected ESC. Focusing on chemokines C-X-C motif chemokine 12 (CXCL12) and CXCL16, important for trophoblast invasion, decreased mRNA and protein concentrations were detected in infected decidualised cells. From the in-vivo mouse model of past Ct infection in pregnancy, it was demonstrated that Ct infection did neither affect the fertility of the mice, pregnancy or resorption numbers in C3H mice nor alter embryonic and placental weight on e12 embryos. However, Ct infection caused reduction of embryo and placenta weight on e14 embryos. Finally, preliminary data from the case control study indicate that past Ct infection is not associated with miscarriage. Our in house PGP3 ELISA that detects past Ct infection was more sensitive than a commercially available MOMP ELISA. My data suggests that Ct infection affects pregnancy during the implantation stage by impairing decidualisation and altering chemokine secretion predisposing for adverse pregnancy outcomes that include growth restriction during later gestation.