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Discovery of prognostic factors for diagnosis and treatment of epithelial-derived ovarian cancer from laying hens.

ABSTRACT: Ovarian cancer is a lethal gynecological cancer causing cancer-related deaths in women worldwide. It is difficult to diagnosis at an early stage when more than 90% patients can be cured because of lack of specific symptoms and early detection markers. Most of malignant ovarian tumors are originated from the germinal epithelium of the ovary. For investigation with animal models of epithelial-derived ovarian cancer (EOC), laying hens are the most relevant animal models because they spontaneously develop EOC as occurs in women through ovulating almost every day. As in women, EOC in the hen is age-related and grossly and histologically similar to that in women. However, domesticated animals are inappropriate for research human EOC due to multiple pregnancies and lactating or seasonally anestrous. In addition, the non-spontaneous nature of rodents EOC limits clinical relevance with human EOC. Recent studies have shown that ovarian cancer could arise from epithelium from the oviduct as oviduct-related genes are up-regulated in EOC of hens. Therefore, we showed in the review: 1) characterization and classification of EOC; 2) chicken models for EOC; 3) relationship estrogen with EOC; 4) candidate prognostic factors for EOC including serpin peptidase inhibior, clade B (ovalbumin), member 3 (SERPINB3), SERPINB11, gallicin 11 (GAL11), secreted phosphoprotein 1 (SPP1) and alpha 2 macroglobulin (A2M) in normal and cancerous ovaries of laying hens; 5) biological roles of microRNAs in development of EOC. Collectively, the present reviews indicate that expression of SERPINB3, SERPINB11, GAL11, SPP1 and A2M is clearly associated with the development of ovarian carcinogenesis. These results provide new insights into the prognostic biomarkers for EOC to diagnose and to evaluate responses to therapies for treating EOC of humans.

SUBMITTER: Lim W

PROVIDER: S-EPMC4189469 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Discovery of prognostic factors for diagnosis and treatment of epithelial-derived ovarian cancer from laying hens.

Lim Whasun W Song Gwonhwa G

Journal of cancer prevention 20130901 3

Ovarian cancer is a lethal gynecological cancer causing cancer-related deaths in women worldwide. It is difficult to diagnosis at an early stage when more than 90% patients can be cured because of lack of specific symptoms and early detection markers. Most of malignant ovarian tumors are originated from the germinal epithelium of the ovary. For investigation with animal models of epithelial-derived ovarian cancer (EOC), laying hens are the most relevant animal models because they spontaneously d ...[more]

PMID: 25337548

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Project description:Keel bone fractures (KBF) in commercial poultry production systems are a major welfare problem with possible economic consequences for the poultry industry. Recent investigations suggest that the overall situation may be worsening. Depending on the housing system, fracture prevalences exceeding 80% have been reported from different countries. No specific causes have yet been identified and this has consequently hampered risk factor identification. The objective of the current study was to investigate the prevalence of KBF in Danish layer hens and to identify risk factors in relation to KBF in all major productions systems, including parent stock production. For risk factor identification, production data from the included flocks was used. In total, 4794 birds from 40 flocks were investigated at end-of-lay. All birds were euthanized on farm and underwent inspection and palpation followed by necropsy. All observations were recorded and subsequently analysed using the SAS statistical software package. In flocks from non-caged systems, fracture prevalence in the range 53%-100%, was observed whereas the prevalence in flocks from enriched cages ranged between 50-98%. Furthermore, often multiple fractures (≥4) were observed in individual birds (range 5-81% of the birds with fractures) depending on the flock. The localization of the fractures at the distal end of the keel bone is highly consistent in all flocks (>96%). Macroscopically the fractures varied morphologically from an appearance with an almost total absence of callus, most frequently observed in caged birds, to large callus formations in and around the fracture lines, which was a typical finding in non-caged birds. Despite being housed under cage-free conditions, parent birds had significantly fewer fractures (all flocks were 60 weeks old) per bird, than other birds from cage-free systems. The body weight at end-of-lay had an effect on the risk of having fractures, heavy hens have significantly fewer fractures at end-of-lay. The older the hens were at onset of lay, the lower was the flock prevalence at end-of-lay. Additionally, the daily egg size at onset of lay was of importance for the risk of developing fractures, the production of heavier eggs initially, resulted in higher fracture prevalence at depopulation. The odds ratio of body weight, (+100 g) was 0.97, age at onset of lay (+1 week) was 0.87 and daily egg weight at onset (+1 gram) was 1.03. In conclusion, the study demonstrated a very high prevalence of KBF in hens from all production systems and identified hen size, age at onset of lay and daily egg weight at onset of lay to be major risk factors for development of KBF in the modern laying hen. Further research regarding this is warranted to strengthen the longevity and enhance the welfare of laying hens.

Project description:BackgroundNutrition intake during growth strongly influences ovarian follicle development and egg laying in chicken hens, yet the underlying endocrine regulatory mechanism is still poorly understood. The relevant research progress is hindered by difficulties in detection of leptin gene and its expression in the chicken. However, a functional leptin receptor (LEPR) is present in the chicken which has been implicated to play a regulatory role in ovarian follicle development and egg laying. The present study targeted LEPR by immunizing against its extracellular domain (ECD), and examined the resultant ovarian follicle development and egg-laying rate in chicken hens.MethodsHens that have been immunized four times with chicken LEPR ECD were assessed for their egg laying rate and feed intake, numbers of ovarian follicles, gene expression profiles, serum lipid parameters, as well as STAT3 signaling pathway.ResultsAdministrations of cLEPR ECD antigen resulted in marked reductions in laying rate that over time eventually recovered to the levels exhibited by the Control hens. Together with the decrease in egg laying rate, cLEPR-immunized hens also exhibited significant reductions in feed intake, plasma concentrations of glucose, triglyceride, high-density lipoprotein, and low-density lipoprotein. Parallelled by reductions in feed intake, mRNA gene expression levels of AgRP, orexin, and NPY were down regulated, but of POMC, MC4R and lepR up-regulated in Immunized hen hypothalamus. cLEPR-immunization also promoted expressions of apoptotic genes such as caspase3 in theca and fas in granulosa layer, but severely depressed IGF-I expression in both theca and granulosa layers.ConclusionsImmunization against cLEPR ECD in egg-laying hens generated antibodies that mimic leptin bioactivity by enhancing leptin receptor transduction. This up-regulated apoptotic gene expression in ovarian follicles, negatively regulated the expression of genes that promote follicular development and hormone secretion, leading to follicle atresia and interruption of egg laying. The inhibition of progesterone secretion due to failure of follicle development also lowered feed intake. These results also demonstrate that immunization against cLEPR ECD may be utilized as a tool for studying bio-functions of cLEPR.

Dataset Information

Discovery of prognostic factors for diagnosis and treatment of epithelial-derived ovarian cancer from laying hens.

Publications

Discovery of prognostic factors for diagnosis and treatment of epithelial-derived ovarian cancer from laying hens.

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