MR Imaging Findings of Ovarian Cystadenofibroma: Clues for Making the Differential Diagnosis from Ovarian Malignancy

International Nuclear Information System (INIS)

Byun, Jae Young

2006-01-01

Ovarian cystadenofibromas are uncommon epithelial ovarian tumors in which fibrous stroma is the dominant component of the neoplasm, in addition to the epithelial lining of the cystic tumor. These tumors are classified, according to the epithelial cell types, into the serous, endometrioid, mucinous, clear cell and mixed categories. Outwater et al. have reported that ovarian cystadenofibromas were multilocular cystic masses with a solid component and they had a specific MR signal intensity for the solid portion, which consisted of fibrous tissue that had very low signal intensity on the T2-weighted sequences. Takeuchi et al. reported that small or tiny cystic locules within the solid component are the characteristic findings of cystadenofibroma, corresponding to a black sponge-like appearance on T2-weignted image. Cho et al. found that about half of ovarian cystadenofibromas are purely cystic and the other half are complex cystic masses with one or more solid components on CT or MR imaging. The imaging findings of purely cystic ovarian cystadenofibromas were identical to those of ovarian cystadenomas on CT or MR imaging. Upon reviewing of the pathology of these tumors, they had small foci of fibrous stromas that were detected only on microscopic examination. The cystadenofibromas with a complex cystic nature demonstrated variable amounts of solid components in the cystic tumor on the CT or MR imaging. Familiarity with the above mentioned MR imaging features of ovarian cystadenofibromas may allow a specific diagnosis and help distinguish this benign tumor from malignant tumors, and this can be a big help during surgical planning to avoid inappropriate management or excessive surgical intervention

The non-target bi-ovarian branches occlusion in fibroids embolization on resumption of menses and ovarian function

International Nuclear Information System (INIS)

Guo Wenbo; Yang Jianyong; Chen Wei; Zhuang Wenquan; Yao Shuzhong

2005-01-01

Objective: To evaluate the effect of the non-target bi-ovarian branches occlusion in fibroids embolization on resumption of menses and ovarian function. Methods: The patients with the non-target bi-ovarian branches occlusion in uterine fibroids embolization (UFE) were classified into two groups, one for lipiodol deposited in bi-ovarian areas (Group A) , another for non lipiodol deposited in ovarian areas or in single ovarian area (Group B of non lipiodol deposited in bi-ovarian areas). The statistical difference between the data of group A and group B were assessed with Fisher test. All UFE were performed with the mixture of lipiodol and pingyangmycin. The serum level of Follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) were measured before UFE and 6 months after UFE. The statistical difference between the data of before and after UFE was assessed with t test. Results: Fifteen patients [age ranged 26-46 years, average (39.00 ± 5.62) years] had been followed up for an average (30.5±6.4) months (range 16-47 months). In 12 of 15, regular menses resumed after an average of (3.0 ±0.3) weeks (range 2-6 weeks). In 3 of 15 (20%), regular menses did not resume. The sexual hormone findings of menopause were found in three cases with amenorrhea after UFE. Amenorrhea was found in three cases with lipiodol deposited in bi-ovarian areas (Group A). Non-amenorrhea was found in the group of non-lipiodol deposited in bi-ovarian areas (Group B). There were significant statistical difference between Group A and Group B (P=0.002 19). Non amenorrhea was found in the patients aged over 45 years old. Three patients were found amenorrhea in the patients aged younger than 45 years old. There were no significant statistical difference between the serum level of FSH, LH and E2 before and 6 months after UFE (P>0.05). Conclusion: The incidence of amenorrhea is very high in the patients with lipiodol deposited in bi-ovarian areas when the bi-ovarian branches of

Neovascularisation of the ovary post ligation of ovarian vessels in ...

African Journals Online (AJOL)

Grossly, all harvested ovaries were insignificantly regressed except the ovary of bitch 1 and 4 which showed significant regression and degeneration. Histopathologically, there were diffused necrosis, dense fibrosis of the ovarian cortex and medulla, degeneration of primary and graafian follicles in the ovarian stroma as well ...

Effect of electro-acupuncture on ovarian expression of α (1- and β (2-adrenoceptors, and p75 neurotrophin receptors in rats with steroid-induced polycystic ovaries

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Holmäng Agneta

2005-06-01

Full Text Available Abstract Background Estradiol valerate (EV-induced polycystic ovaries (PCO in rats is associated with an increase in ovarian sympathetic outflow. Low-frequency (2 Hz electro-acupuncture (EA has been shown to modulate sympathetic markers as well as ovarian blood flow as a reflex response via the ovarian sympathetic nerves, in rats with EV-induced PCO. Methods In the present study, we further tested the hypothesis that repeated 2 Hz EA treatments modulate ovarian sympathetic outflow in rats with PCO, induced by a single i.m. injection of EV, by investigating the mRNA expression, the amount and distribution of proteins of α1a-, α1b-, α1d-, and β2-adrenoceptors (ARs, as well as the low-affinity neurotrophin receptor (p75NTR. Results It was found that EV injection results in significantly higher mRNA expression of ovarian α1b- and α1d-AR in PCO rats compared to control rats. The p75NTR and β2-ARs mRNA expression were unchanged in the PCO ovary. Low-frequency EA resulted in a significantly lower expression of β2-ARs mRNA expression in PCO rats. The p75NTR mRNA was unaffected in both PCO and control rats. PCO ovaries displayed significantly higher amount of protein of α1a-, α1b- and α1d-ARs, and of p75NTR, compared to control rats, that were all counteracted by repeated low-frequency EA treatments, except for α1b-AR. Conclusion The present study shows that EA normalizes most of the EV-induced changes in ovarian ARs. Furthermore, EA was able to prevent the EV-induced up regulation of p75NTR, probably by normalizing the sympathetic ovarian response to NGF action. Our data indicate a possible role of EA in the regulation of ovarian responsiveness to sympathetic inputs and depict a possible complementary therapeutic approach to overcoming sympathetic-related anovulation in women with PCOS.

HemoHIM improves ovarian morphology and decreases expression of nerve growth factor in rats with steroid-induced polycystic ovaries.

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Kim, Sung Ho; Lee, Hae June; Kim, Joong Sun; Moon, Changjong; Kim, Jong Choon; Bae, Chun Sik; Park, Hae Ran; Jung, Uhee; Jo, Sung Kee

2009-12-01

Estradiol valerate (EV)-induced polycystic ovaries (PCOs) in rats cause the anovulation and cystic ovarian morphology. We investigated whether treatment with HemoHIM influences the ovarian morphology and the expression of nerve growth factor (NGF) in an EV-induced PCO rat model. PCO was induced by a single intramuscular injection of EV (4 mg, dissolved in sesame oil) in adult cycling rats. HemoHIM was either administered orally (100 mg/kg of body weight/day) for 35 consecutive days or injected intraperitoneally (50 mg/kg of body weight) every other day after EV injection. Ovarian morphology was almost normalized, and NGF was normalized in the PCO + HemoHIM group. HemoHIM lowered the high numbers of antral follicles and increased the number of corpora lutea in PCOs. The results are consistent with a beneficial effect of HemoHIM in the prevention and treatment of PCO syndrome.

Immune cells in the normal ovary and spontaneous ovarian tumors in the laying hen (Gallus domesticus) model of human ovarian cancer.

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Bradaric, Michael J; Penumatsa, Krishna; Barua, Animesh; Edassery, Seby L; Yu, Yi; Abramowicz, Jacques S; Bahr, Janice M; Luborsky, Judith L

2013-01-01

Spontaneous ovarian cancer in chickens resembles human tumors both histologically and biochemically. The goal was to determine if there are differences in lymphocyte content between normal ovaries and ovarian tumors in chickens as a basis for further studies to understand the role of immunity in human ovarian cancer progression. Hens were selected using grey scale and color Doppler ultrasound to determine if they had normal or tumor morphology. Cells were isolated from ovaries (n = 6 hens) and lymphocyte numbers were determined by flow cytometry using antibodies to avian CD4 and CD8 T and B (Bu1a) cells. Ovarian sections from another set of hens (n = 26) were assessed to verify tumor type and stage and to count CD4, CD8 and Bu1a immunostained cells by morphometric analysis. T and B cells were more numerous in ovarian tumors than in normal ovaries by flow cytometry and immunohistochemistry. There were less CD4+ cells than CD8+ and Bu1a+ cells in normal ovaries or ovarian tumors. CD8+ cells were the dominant T cell sub-type in both ovarian stroma and in ovarian follicles compared to CD4+ cells. Bu1a+ cells were consistently found in the stroma of normal ovaries and ovarian tumors but were not associated with follicles. The number of immune cells was highest in late stage serous tumors compared to endometrioid and mucinous tumors. The results suggest that similar to human ovarian cancer there are comparatively more immune cells in chicken ovarian tumors than in normal ovaries, and the highest immune cell content occurs in serous tumors. Thus, this study establishes a foundation for further study of tumor immune responses in a spontaneous model of ovarian cancer which will facilitate studies of the role of immunity in early ovarian cancer progression and use of the hen in pre-clinical vaccine trials.

Polycystic ovarian disease: the adrenal connection.

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Marouliss, George B; Triantafillidis, Ioannis K

2006-01-01

Polycystic ovarian disease (PCOD) is characterized by hyperandrogenemia, ovulatory dysfunction and polycystic ovaries (PCO). The increased androgen production in PCOD comes primarily from the ovaries. However, in about 40% of patients there is excessive adrenal androgen production (DHEA, DHEA-Sulfate, Androstenedione, Testosterone and Dihydrotestosterone). The contribution of the adrenal in the PCOD is suggested by the presence of adrenal androgen excess in PCO, the presence of PCO in women with enzymatic adrenal hyperplasia as well as in women with adrenal tumors. However, the cause of adrenal androgen hypersecretion is not yet fully understood but it may include endogenous hypersecretion of the zona reticularis of unclear cause, hypersecretion of cortical-androgen-stimulating hormone (CASH), stress, hyperprolactinemia, adrenal enzymatic defects etc. This short review covers the aspects of adrenal androgen hypersecretion in PCOD.

The Distribution of Stroma and Antral Follicles Differs between Insulin-Resistance and Hyperandrogenism-Related Polycystic Ovarian Syndrome

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Carlo Alviggi

2017-05-01

Full Text Available IntroductionAlthough insulin resistance plays an important pathogenetic role in polycystic ovary syndrome (PCOS, no correlation between ultrasound PCOS pattern and insulin resistance has yet been reported. The aim of this retrospective observational study was to assess whether the ovarian ultrasonographic parameter differed between PCOS women with insulin resistance and those with a hyperandrogenic profile.Materials and methodsWomen who fulfilled the Rotterdam criteria for PCOS were retrospectively studied. Anthropometric, biochemical, and clinical data were recorded. Women were divided into two groups based on specific transvaginal ultrasound parameters: subjects with more than half of the follicles measuring between 5 and 9 mm in diameter, an ultrasonographic determined stroma/total area (S/A > 0.34 and a “necklace” sign of antral follicles (Group A; and subjects with more than half of the antral follicles measuring between 2 and 4 mm in diameter, an S/A ≤ 0.34; no “necklace” sign but ubiquitously distributed follicles determined by ultrasound (Group B. The association between these ultrasound patterns and the presence of insulin resistance was also evaluated.ResultsSeventy-eight patients were enrolled: 33 with ultrasound sound pattern A and 45 with pattern B. The latter pattern had a sensitivity of 88% and a specificity of 78% in predicting PCOS women with insulin resistance. There were no differences in age, Ferriman–Gallwey score, and serum gonadotropin or androgen levels between the two groups. Body mass index, the waist-to-hip ratio, and homeostasis model assessment were significantly higher in group B than in group A (p < 0.05. Conversely, sex hormone binding globulin levels and ovarian volume were significantly higher in group A (p < 0.05. Insulin resistance was more frequent in group B than in group A (36/41, 87.8% versus 7/32, 21.8%; p < 0.05.ConclusionThese results suggest that insulin resistance

Spectroscopy of Cu(II)-PcoC and the multicopper oxidase function of PcoA, two essential components of Escherichia coli pco copper resistance operon.

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Huffman, David L; Huyett, Jennifer; Outten, F Wayne; Doan, Peter E; Finney, Lydia A; Hoffman, Brian M; O'Halloran, Thomas V

2002-08-06

The plasmid-encoded pco copper resistance operon in Escherichia coli consists of seven genes that are expressed from two pco promoters in response to elevated copper; however, little is known about how they mediate resistance to excess environmental copper. Two of the genes encode the soluble periplasmic proteins PcoA and PcoC. We show here that inactivation of PcoC, and PcoA to a lesser extent, causes cells to become more sensitive to copper than wild-type nonresistant strains, consistent with a tightly coupled detoxification pathway. Periplasmic extracts show copper-inducible oxidase activity, attributed to the multicopper oxidase function of PcoA. PcoC, a much smaller protein than PcoA, binds one Cu(II) and exhibits a weak electronic transition characteristic of a type II copper center. ENDOR and ESEEM spectroscopy of Cu(II)-PcoC and the (15)N- and Met-CD(3)-labeled samples are consistent with a tetragonal ligand environment of three nitrogens and one aqua ligand "in the plane". A weakly associated S-Met and aqua are likely axial ligands. At least one N is a histidine and is likely trans to the in-plane aqua ligand. The copper chemistry of PcoC and the oxidase function of PcoA are consistent with the emerging picture of the chromosomally encoded copper homeostasis apparatus in the E. coli cell envelope [Outten, F. W., Huffman, D. L., Hale, J. A., and O'Halloran, T. V. (2001) J. Biol. Chem. 276, 30670-30677]. We propose a model for the plasmid system in which Cu(I)-PcoC functions in this copper efflux pathway as a periplasmic copper binding protein that docks with the multiple repeats of Met-rich domains in PcoA to effect oxidation of Cu(I) to the less toxic Cu(II) form. The solvent accessibility of the Cu(II) in PcoC may allow for metal transfer to other plasmid and chromosomal factors and thus facilitate removal of Cu(II) from the cell envelope.

Hierarchy of stroma-derived factors in supporting growth of stroma-dependent hemopoietic cells: membrane-bound SCF is sufficient to confer stroma competence to epithelial cells.

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Friel, Jutta; Itoh, Katsuhiko; Bergholz, Ulla; Jücker, Manfred; Stocking, Carol; Harrison, Paul; Ostertag, Wolfram

2002-03-01

Hemopoiesis takes place in a microenvironment where hemopoietic cells are closely associated with stroma by various interactions. Stroma coregulates the proliferation and differentiation of hemopoietic cells. Stroma-hemopoietic-cell contact can be supported by locally produced membrane associated growth factors. The stroma derived growth factor, stem cell factor (SCF) is important in hemopoiesis. We examined the different biological interactions of membrane bound and soluble SCF with human hemopoietic cells expressing the SCF receptor, c-kit. To analyze the function of the SCF isoforms in inducing the proliferation of hemopoietic TF1 or Cord blood (CB) CD34+ cells we used stroma cell lines that differ in their presentation of no SCF, membrane SCF, or soluble SCF. We established a new coculture system using an epithelial cell line that excludes potential interfering effects with other known stroma encoded hemopoietic growth factors. We show that soluble SCF, in absence of membrane-bound SCF, inhibits long term clonal growth of primary or established CD34+ hemopoietic cells, whereas membrane-inserted SCF "dominantly" induces long term proliferation of these cells. We demonstrate a hierarchy of these SCF isoforms in the interaction of stroma with hemopoietic TF1 cells. Membrane-bound SCF is "dominant" over soluble SCF, whereas soluble SCF acts epistatically in interacting with hemopoietic cells compared with other stroma derived factors present in SCF deficient stroma. A hierarchy of stroma cell lines can be arranged according to their presentation of membrane SCF or soluble SCF. In our model system, membrane-bound SCF expression is sufficient to confer stroma properties to an epithelial cell line but soluble SCF does not.

Cytologic diagnosis of hepatobiliary cystadenoma with mesenchymal stroma during intraoperative consultation: a case report.

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Voltaggio, Lysandra; Szeto, Oliver J; Tabbara, Sana O

2010-01-01

Hepatobiliary cystadenoma with mesenchymal stroma (HCMS) is a rare cystic tumor characterized by a layer of mucinous cuboidal to columnar epithelium situated on top of a basement membrane resting on an ovarian-like stroma. Cytologic features of this entity have not been extensively studied. We present a case of HCMS with emphasis on cytologic material obtained at the time of intraoperative consultation (IOC). A 51-year-old woman had partial resection of a liver cyst. Seven months later she sought further medical attention and presented for surgical reevaluation and reexcision of the same lesion. Initial computed tomography revealed a multiloculated liver cyst. Five months after reexcision the lesion recurred and was again excised. During IOC, scrape cytology revealed both biliary epithelial and mesenchymal stromal cells in a cystic background. Permanent sections showed histologic features of HCMS. To the best of our knowledge, this is the first cytologic description of such a neoplasm to include both epithelial and mesenchymal stromal elements. The use of scrape cytology during IOC can be a fast and effective way of identifying both the epithelium and mesenchymal stroma when HCMS is in the differential diagnosis of a cystic liver lesion.

Alfa-fetoprotein secreting ovarian sex cord-stromal tumor

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Kusum D Jashnani

2013-01-01

Full Text Available Ovarian sex cord-stromal tumors are relatively infrequent neoplasms that account for approximately 8% of all primary ovarian tumors. They are a heterogeneous group of neoplasms composed of cells derived from gonadal sex cords (granulosa and Sertoli cells, specialized gonadal stroma (theca and Leydig cells, and fibroblasts. They may show androgenic or estrogenic manifestations. We report such a tumor associated with markedly raised serum alpha-fetoprotein (AFP levels in a young female presenting with a mass and defeminising symptoms. Serum AFP levels returned to normal on removal of tumor.

Metabolic implications of menstrual cycle length in non-hyperandrogenic women with polycystic ovarian morphology.

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Alebić, Miro Šimun; Stojanović, Nataša; Baldani, Dinka Pavičić; Duvnjak, Lea Smirčić

2016-12-01

This cross-sectional study aimed to investigate the association between menstrual cycle lenght and metabolic parameters in non-hyperandrogenic women with polycystic ovarian morphology, n = 250. Metabolic profiles of all participants were evaluated using anthropometric parameters (body mass index, waist circumference), parameters of dyslipidemia (total cholesterol, HDL-cholesterol, triglycerides) and markers of insulin resistance (fasting insulin, homeostasis model assessment for insulin resistance index). The associations between menstrual cycle lenght and cardiometabolic risk factors such as insulin resistance, dyslipidemia, and obesity were investigated. In non-hyperandrogenic women with polycystic ovarian morphology, menstrual cycle lenght was associated with hypertriglyceridemia and insulin resistance independently of body mass index. Moreover, menstrual cycle lenght added value to body mass index in predicting hypertriglyceridemia. The optimal menstrual cycle lenght cut-off value for identifying of non-hyperandrogenic women with polycystic ovarian morphology at metabolic risk was found to be 45 days. Metabolic profile of non-hyperandrogenic women with polycystic ovarian morphology (n = 75) with menstrual cycle lenght >45 days was similar to that of hyperandrogenic women with polycystic ovarian morphology (n = 138) while metabolic profile of non-hyperandrogenic women with polycystic ovarian morphology with menstrual cycle lenght ≤45 days (n = 112) was similar to that of controls (n = 167). Non-hyperandrogenic women with polycystic ovarian morphology with menstrual cycle lenght >45 days had higher prevalence of cardiometabolic risk factors compared to those with menstrual cycle lenght ≤45 days. Non-hyperandrogenic women with polycystic ovarian morphology are not metabolically homogeneous. Menstrual cycle lenght is an easy-to-obtain clinical parameter positively associated with the probability of unfavorable metabolic status in non

Superficial ovarian cortex vascularization is inversely related to the follicle reserve in normal cycling ovaries and is increased in polycystic ovary syndrome.

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Delgado-Rosas, F; Gaytán, M; Morales, C; Gómez, R; Gaytán, F

2009-05-01

The superficial ovarian cortex constitutes the micro-environment where resting and early growing follicles reside. As small follicles do not possess an independent capillary network, both their survival and early growth depend on their proximity to the cortical vessels. Little is known about the possible changes in superficial ovarian cortex vascularization in normal women throughout reproductive life or in pathological conditions such as polycystic ovary syndrome (PCOS) involving abnormal early follicle growth. We studied the vascularization of the superficial and deep cortical stroma (DCS) in normal cycling ovaries from 21 to 50 years of age and in infertile women with PCOS. We used archival ovarian samples and specific CD34 immunostaining to determine blood vessel density and to analyse correlation with age and with the ovarian follicle reserve. Normal cycling ovaries showed an age-related increase in the superficial cortical stroma vascularization that was inversely correlated with the density of small (primordial and primary) follicles. In contrast, blood vessel density in the DCS significantly decreased in women aged >or=40 years. Ovaries from PCOS showed a 2-fold increase in blood vessel density in both superficial cortical stroma and DCS with respect to age-matched controls. The increased vascularization of the superficial cortical stroma in normal ovaries in relation to age and in ovaries from PCOS could have profound effects on cortical metabolic rate, primordial follicle survival/activation and early follicle growth, and may underline changes in follicle dynamics in mid-aged women and in PCOS.

Non-multipotent stroma inhibit the proliferation and differentiation of mesenchymal stromal cells in vitro.

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Rosu-Myles, Michael; Fair, Joel; Pearce, Nelson; Mehic, Jelica

2010-10-01

The ability to expand and maintain bone marrow (BM)-derived mesenchymal stem cells (MSC) in vitro is an important aspect of their therapeutic potential. Despite this, the exact composition of stromal cell types within these cultures and the potential effects of non-stem cells on the maintenance of MSC are poorly understood. C57BL/6J BM stroma was investigated as a model to determine the relationship between MSC and non-multipotent cells in vitro. Whole BM and single-cell derived cultures were characterized using flow cytometry and cell sorting combined with multipotent differentiation. Proliferation of individual stromal populations was evaluated using BrdU. At a single-cell level, MSC were distinguished from committed progenitors, and cells lacking differentiation ability, by the expression of CD105 (CD105+). A 3-fold reduction in the percentage of CD105+ cells was detected after prolonged culture and correlated with loss of MSC. Depletion of CD105+ cells coincided with a 10-20% increase in the frequency of proliferating CD105(-) cells. Removal of CD105(-) stroma caused increased proliferation in CD105+ cells, which could be diminished by conditioned media from parent cultures. Comparison of the multipotent differentiation potential in purified and non-purified CD105+ cells determined that MSC were detectable for at least 3 weeks longer when cultured in the absence of CD105(-) cells. This work identifies a simple model for characterizing the different cellular components present in BM stromal cultures and demonstrates that stromal cells lacking multipotent differentiating capacity greatly reduce the longevity of MSC.

Nedd4L expression is decreased in ovarian epithelial cancer tissues compared to ovarian non-cancer tissue.

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Yang, Qiuyun; Zhao, Jinghe; Cui, Manhua; Gi, Shuting; Wang, Wei; Han, Xiaole

2015-12-01

Recent studies have demonstrated that the neural precursor cell expressed, developmentally downregulated 4-like (Nedd4L) gene plays a role in the progression of various cancers. However, reports describing Nedd4L expression in ovarian cancer tissues are limited. A cohort (n = 117) of archival formalin-fixed, paraffin embedded resected normal ovarian epithelial tissues (n = 10), benign ovarian epithelial tumor tissues (n = 10), serous borderline ovarian epithelial tumor tissues (n = 14), mucous borderline ovarian epithelial tumor tissues (n = 11), and invasive ovarian epithelial cancer tissues (n = 72) were assessed for Nedd4L protein expression using immunohistochemistry. Nedd4L protein expression was significantly decreased in invasive ovarian epithelial cancer tissues compared to non-cancer tissues (P < 0.05). Decreased Nedd4L protein expression correlated with clinical stage, pathological grade, lymph node metastasis and survival (P < 0.05). Nedd4L protein expression may be an independent prognostic marker of ovarian cancer development. © 2015 Japan Society of Obstetrics and Gynecology.

Non-coding RNAs in the Ovarian Follicle

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Rosalia Battaglia

2017-05-01

Full Text Available The mammalian ovarian follicle is the complex reproductive unit comprising germ cell, somatic cells (Cumulus and Granulosa cells, and follicular fluid (FF: paracrine communication among the different cell types through FF ensures the development of a mature oocyte ready for fertilization. This paper is focused on non-coding RNAs in ovarian follicles and their predicted role in the pathways involved in oocyte growth and maturation. We determined the expression profiles of microRNAs in human oocytes and FF by high-throughput analysis and identified 267 microRNAs in FF and 176 in oocytes. Most of these were FF microRNAs, while 9 were oocyte specific. By bioinformatic analysis, independently performed on FF and oocyte microRNAs, we identified the most significant Biological Processes and the pathways regulated by their validated targets. We found many pathways shared between the two compartments and some specific for oocyte microRNAs. Moreover, we found 41 long non-coding RNAs able to interact with oocyte microRNAs and potentially involved in the regulation of folliculogenesis. These data are important in basic reproductive research and could also be useful for clinical applications. In fact, the characterization of non-coding RNAs in ovarian follicles could improve reproductive disease diagnosis, provide biomarkers of oocyte quality in Assisted Reproductive Treatment, and allow the development of therapies for infertility disorders.

Alternative treatment of ovarian cysts with Tribulus terrestris extract: a rat model.

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Dehghan, A; Esfandiari, A; Bigdeli, S Momeni

2012-02-01

Tribulus terrestris has long been used in traditional medicine to treat impotency and improve sexual functions in man. The aim of this study was to evaluate the efficiency of T. terrestris extract in the treatment of polycystic ovary (PCO) in Wistar rat. Estradiol valerate was injected to 15 mature Wistar rats to induce PCO. Rats were randomly divided into three groups (control, low-dose and high-dose groups) of five each and received 0, 5 and 10 mg of T. terrestris extract, respectively.Treatments began on days 50 and 61 after estradiol injection; at the same time, vaginal smear was prepared. The ovaries were removed on day 62, and histological sections were prepared accordingly. The number and diameter of corpora lutea, thickness of the theca interna layer and the number of all follicles were evaluated in both ovaries. In comparison with the control group, the number of corpora lutea and primary and secondary follicles significantly increased following T. terrestris treatment; however, the number of ovarian cysts significantly decreased. It can be concluded that T. terrestris have a luteinizing effect on ovarian cysts, which may relate to its gonadotropin-like activity; also, a high dose of the extract can efficiently remove ovarian cysts and resume ovarian activity. © 2011 Blackwell Verlag GmbH.

Assessment of Hypoxia in the Stroma of Patient-Derived Pancreatic Tumor Xenografts

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Lohse, Ines; Lourenco, Corey; Ibrahimov, Emin; Pintilie, Melania [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Tsao, Ming-Sound [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Department of Pathology, University Health Network, 200 Elizabeth Street, Toronto, ON M5G2C4 (Canada); Department of Laboratory Medicine and Pathobiology, 27 King’s College Circle, University of Toronto, Toronto, ON M5S1A1 (Canada); Hedley, David W., E-mail: david.hedley@uhn.ca [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Departments of Medical Biophysics University of Toronto, 610 University Ave., Toronto, ON M5G2M9 (Canada); Departments of Medicine, University of Toronto, 610 University Ave., Toronto, ON M5G2M9 (Canada); Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, 610 University Ave., Toronto, ON M5G2M9 (Canada)

2014-02-26

The unusually dense stroma of pancreatic cancers is thought to play an important role in their biological aggression. The presence of hypoxia is also considered an adverse prognostic factor. Although it is usually assumed that this is the result of effects of hypoxia on the epithelial component, it is possible that hypoxia exerts indirect effects via the tumor stroma. We therefore measured hypoxia in the stroma of a series of primary pancreatic cancer xenografts. Nine patient-derived pancreatic xenografts representing a range of oxygenation levels were labeled by immunohistochemistry for EF5 and analyzed using semi-automated pattern recognition software. Hypoxia in the tumor and stroma was correlated with tumor growth and metastatic potential. The extent of hypoxia varied from 1%–39% between the different models. EF5 labeling in the stroma ranged from 0–20% between models, and was correlated with the level of hypoxia in the tumor cell area, but not microvessel density. Tumor hypoxia correlated with spontaneous metastasis formation with the exception of one hypoxic model that showed disproportionately low levels of hypoxia in the stroma and was non-metastatic. Our results demonstrate that hypoxia exists in the stroma of primary pancreatic cancer xenografts and suggest that stromal hypoxia impacts the metastatic potential.

Total renin after gonadotropin stimulation in polycystic ovarian disease.

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Matinlauri, I; Anttila, L; Jaatinen, T A; Koskinen, P; Aalto, M; Irjala, K; Nikkanen, V

1995-02-01

To examine the influence of polycystic ovarian disease (PCOD) on the levels of total renin in plasma and follicular fluid (FF) after stimulation with hMG. Comparative study of the plasma and FF concentrations of total renin in women with and without PCOD after stimulation with hMG. In vitro fertilization-embryo transfer program at the Department of Obstetrics and Gynecology, the University Central Hospital of Turku, Finland. Thirty-six women undergoing IVF-ET for infertility with (n = 10) or without (n = 26) ultrasonographically diagnosed PCOD. Of the latter group, 15 women had tubal infertility, and the rest suffered from an anovulatory infertility and reacted with PCO-like ovarian response to stimulation. The concentrations of total renin in plasma and FF, serum E2, and protein in FF. The concentrations of plasma total renin after the gonadotropin stimulation were significantly higher in the PCOD and PCO-like groups when compared with the tubal group. The concentration of total renin in FF and the ratio of total renin per protein in FF were higher in the PCOD and PCO-like groups than in the tubal group, but the differences did not reach statistical significance. Positive correlations were found between the plasma total renin and serum E2 concentrations in the PCO-like and in the tubal group and between plasma total renin concentrations and the number of mature follicles in all groups. Follicular fluid total renin did not correlate with FF protein in any group. All findings were independent of the total hMG dosage used and the body mass index of the patients. In the present study the concentrations of total renin in plasma were enhanced markedly after gonadotropin stimulation in women with PCOD compared with women having tubal infertility. The pattern of the hormonal secretions revealed a group of infertile patients reacting biochemically like women with PCOD.

Assessment of ovarian stromal blood flow after metformin treatment in women with polycystic ovary syndrome.

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Makled, Ahmed K; El Sherbiny, Mohamed; Elkabarity, Rania

2014-04-01

To authenticate the effect of metformin treatment on ovarian stromal blood flow in women with polycystic ovary syndrome (PCOS) using 3-dimensional (3D) power Doppler. The current case-control study was conducted at Ain Shams University Maternity Hospital. A total of 60 women diagnosed to have PCOS were included as group 1. Another 40 fertile women who were recruited from outpatient clinic for contraception without PCOS with regular menstrual cycles were included as control group (group 2). All women underwent 3D power Doppler evaluations of ovarian stroma. Anthropometric, hormonal and biochemical criteria were also measured. All women in group 1 received metformin hydrochloride 500 mg tablets, which were started in a step-up maneuver every 5 days, from one to three tablets per day. The same parameters were also measured after the 3 months duration of treatment. A total of 100 women were finally analyzed. At the start of the study, there were no statistically significant differences between group 1 and group 2 and regarding age and body mass index, but the waist/hip ratio and Ferriman-Gallwey scoring were statistically different between the 2 groups. The mean ovarian volume and stromal volume were significantly larger in group 1. 3D power Doppler indices [the vascularization index (VI), the flow index (FI) and the (VFI) vascularization-flow index] were much higher in group 1 than in group 2 (1.38 ± 0.76 vs. 4.69 ± 1.37, P treatment significantly reduce VI, FI and VFI (4.69 ± 1.37 vs. 2.95 ± 1.52, P < 0.05, 32.66 ± 4.37 vs. 29.48 ± 4.98, P < 0.05 and 1.54 ± 0.69 vs. 1.21 ± 0.7 P < 0.05, respectively). Using Receiver operator characteristic, there was no cut-off value of VI, FI or VFI to detect ovulation in women of PCOS. Metformin seems to have a beneficial effect in normal weight PCO women via correcting ovarian stromal blood flow and hormonal profiles.

Early Detection of Ovarian Cancer by Molecular Targeted Ultrasound Imaging Together with Serum Markers of Tumor-Associated Nuclear Change and Angiogenesis

Science.gov (United States)

2014-03-01

cells of the tumor also expressed IL-16 ( red arrows). Compared with normal (A), more IL-16+ cells are seen in the stroma of the ovaries with tumor. S...6):538- 50. doi: 10.1111/ aji .12172. Epub 2013 Nov 5. PMID: 24188693. (appended in pages 65-77). Meeting presentations: Abstract published and...S) and surface layer of ovary. B, Section of benign ovarian Tu. C, Section of early-stage ovarian Tu. D, section of late-stage ovarian Tu. Red arrows

Differential responses of calcifying and non-calcifying epibionts of a brown macroalga to present-day and future upwelling pCO2.

Directory of Open Access Journals (Sweden)

Vincent Saderne

Full Text Available Seaweeds are key species of the Baltic Sea benthic ecosystems. They are the substratum of numerous fouling epibionts like bryozoans and tubeworms. Several of these epibionts bear calcified structures and could be impacted by the high pCO2 events of the late summer upwellings in the Baltic nearshores. Those events are expected to increase in strength and duration with global change and ocean acidification. If calcifying epibionts are impacted by transient acidification as driven by upwelling events, their increasing prevalence could cause a shift of the fouling communities toward fleshy species. The aim of the present study was to test the sensitivity of selected seaweed macrofoulers to transient elevation of pCO2 in their natural microenvironment, i.e. the boundary layer covering the thallus surface of brown seaweeds. Fragments of the macroalga Fucus serratus bearing an epibiotic community composed of the calcifiers Spirorbis spirorbis (Annelida and Electra pilosa (Bryozoa and the non-calcifier Alcyonidium hirsutum (Bryozoa were maintained for 30 days under three pCO2 conditions: natural 460 ± 59 µatm, present-day upwelling1193 ± 166 µatm and future upwelling 3150 ± 446 µatm. Only the highest pCO2 caused a significant reduction of growth rates and settlement of S. spirorbis individuals. Additionally, S. spirorbis settled juveniles exhibited enhanced calcification of 40% during daylight hours compared to dark hours, possibly reflecting a day-night alternation of an acidification-modulating effect by algal photosynthesis as opposed to an acidification-enhancing effect of algal respiration. E. pilosa colonies showed significantly increased growth rates at intermediate pCO2 (1193 µatm but no response to higher pCO2. No effect of acidification on A. hirsutum colonies growth rates was observed. The results suggest a remarkable resistance of the algal macro-epibionts to levels of acidification occurring at present day upwellings in the Baltic

Time series pCO2 at a coastal mooring: Internal consistency, seasonal cycles, and interannual variability

Science.gov (United States)

Reimer, Janet J.; Cai, Wei-Jun; Xue, Liang; Vargas, Rodrigo; Noakes, Scott; Hu, Xinping; Signorini, Sergio R.; Mathis, Jeremy T.; Feely, Richard A.; Sutton, Adrienne J.; Sabine, Christopher; Musielewicz, Sylvia; Chen, Baoshan; Wanninkhof, Rik

2017-08-01

Marine carbonate system monitoring programs often consist of multiple observational methods that include underway cruise data, moored autonomous time series, and discrete water bottle samples. Monitored parameters include all, or some of the following: partial pressure of CO2 of the water (pCO2w) and air, dissolved inorganic carbon (DIC), total alkalinity (TA), and pH. Any combination of at least two of the aforementioned parameters can be used to calculate the others. In this study at the Gray's Reef (GR) mooring in the South Atlantic Bight (SAB) we: examine the internal consistency of pCO2w from underway cruise, moored autonomous time series, and calculated from bottle samples (DIC-TA pairing); describe the seasonal to interannual pCO2w time series variability and air-sea flux (FCO2), as well as describe the potential sources of pCO2w variability; and determine the source/sink for atmospheric pCO2. Over the 8.5 years of GR mooring time series, mooring-underway and mooring-bottle calculated-pCO2w strongly correlate with r-values > 0.90. pCO2w and FCO2 time series follow seasonal thermal patterns; however, seasonal non-thermal processes, such as terrestrial export, net biological production, and air-sea exchange also influence variability. The linear slope of time series pCO2w increases by 5.2 ± 1.4 μatm y-1 with FCO2 increasing 51-70 mmol m-2 y-1. The net FCO2 sign can switch interannually with the magnitude varying greatly. Non-thermal pCO2w is also increasing over the time series, likely indicating that terrestrial export and net biological processes drive the long term pCO2w increase.

Reprogramming of the Ovarian Tumor Stroma by Activation of a Biomechanical ECM Switch

Science.gov (United States)

2016-09-01

cells into natural killer (NK)-like cells called ITNK cells that express high levels of perforin, granzyme B, and INF-gamma, which collectively...ovarian tumors and benign granulomas for expression of the HU177 cryptic collagen epitope. Serial sections from frozen tissues were stained by

Locus coeruleus lesions and PCOS: role of the central and peripheral sympathetic nervous system in the ovarian function of rat

Directory of Open Access Journals (Sweden)

Farideh Zafari Zangeneh

2012-01-01

Full Text Available Polycystic ovary syndrome (PCOS is a complex endocrine and metabolic disorder associated with ovulatory dysfunction”. “Autonomic and central nervous systems play important roles in the regulation of ovarian physiology”. The noradrenergic nucleus locus coeruleus (LC plays a central role in the regulation of the sympathetic nervous system and synaptically connected to the preganglionic cell bodies of the ovarian sympathetic pathway and its activation is essential to trigger spontaneous or induced LH surges. This study evaluates sympathetic outflow in central and peripheral pathways in PCO rats. Objective: Our objectives in this study were (1 to estimate LC activity in rats with estradiol valerate (EV-induced PCO; (2 to antagonized alpha2a adrenoceptor in systemic conditions with yohimbine. Materials and Methods: Forty two rats were divided into two groups: 1 LC and yohimbine and 2 control. Every group subdivided in two groups: eighteen rats were treated with estradiol valerate for induction of follicular cysts and the remainders were sesame oil groups. Results: Estradiol concentration was significantly augmented by the LC lesion in PCO rats (p<0.001, while LC lesion could not alter serum concentrations of LH and FSH, like yohimbine. The morphological observations of ovaries of LC lesion rats showed follicles with hyperthecosis, but yohimbine reduced the number of cysts, increased corpus lutea and developed follicles. Conclusion: Rats with EV-induced PCO increased sympathetic activity. LC lesion and yohimbine decreased the number of cysts and yohimbine increased corpus lutea and developed follicles in PCO rats.

Regulation of corneal stroma extracellular matrix assembly.

Science.gov (United States)

Chen, Shoujun; Mienaltowski, Michael J; Birk, David E

2015-04-01

The transparent cornea is the major refractive element of the eye. A finely controlled assembly of the stromal extracellular matrix is critical to corneal function, as well as in establishing the appropriate mechanical stability required to maintain corneal shape and curvature. In the stroma, homogeneous, small diameter collagen fibrils, regularly packed with a highly ordered hierarchical organization, are essential for function. This review focuses on corneal stroma assembly and the regulation of collagen fibrillogenesis. Corneal collagen fibrillogenesis involves multiple molecules interacting in sequential steps, as well as interactions between keratocytes and stroma matrix components. The stroma has the highest collagen V:I ratio in the body. Collagen V regulates the nucleation of protofibril assembly, thus controlling the number of fibrils and assembly of smaller diameter fibrils in the stroma. The corneal stroma is also enriched in small leucine-rich proteoglycans (SLRPs) that cooperate in a temporal and spatial manner to regulate linear and lateral collagen fibril growth. In addition, the fibril-associated collagens (FACITs) such as collagen XII and collagen XIV have roles in the regulation of fibril packing and inter-lamellar interactions. A communicating keratocyte network contributes to the overall and long-range regulation of stromal extracellular matrix assembly, by creating micro-domains where the sequential steps in stromal matrix assembly are controlled. Keratocytes control the synthesis of extracellular matrix components, which interact with the keratocytes dynamically to coordinate the regulatory steps into a cohesive process. Mutations or deficiencies in stromal regulatory molecules result in altered interactions and deficiencies in both transparency and refraction, leading to corneal stroma pathobiology such as stromal dystrophies, cornea plana and keratoconus. Copyright © 2014 Elsevier Ltd. All rights reserved.

Multimodality imaging findings of massive ovarian edema in children

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Dahmoush, Hisham [Stanford University Medical Center, Department of Radiology, Neuroradiology Division, Stanford, CA (United States); Anupindi, Sudha A.; Chauvin, Nancy A. [University of Pennsylvania, The Children' s Hospital of Philadelphia, Department of Radiology, Perelman School of Medicine, Philadelphia, PA (United States); Pawel, Bruce R. [University of Pennsylvania, The Children' s Hospital of Philadelphia, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, Philadelphia, PA (United States)

2017-05-15

Massive ovarian edema is a rare benign condition that predominantly affects childbearing women as well as preadolescent girls. It is thought to result from intermittent or partial torsion of the ovary compromising the venous and lymphatic drainage but with preserved arterial supply. The clinical features of massive ovarian edema are nonspecific and can simulate tumors, leading to unnecessary oophorectomy. To demonstrate imaging features that should alert radiologists to consider the diagnosis of massive ovarian edema preoperatively so that fertility-sparing surgery may be considered. We identified five girls diagnosed with massive ovarian edema at pathology. Presenting symptoms, sidedness, imaging appearance, preoperative diagnosis, and operative and histopathological findings were reviewed. Age range was 9.6-14.3 years (mean age: 12.5 years). Common imaging findings included ovarian enlargement with edema of the stroma, peripherally placed follicles, isointense signal on T1-W MRI and markedly hyperintense signal on T2-W MRI, preservation of color Doppler flow by US, and CT Hounsfield units below 40. The uterus was deviated to the affected side in all patients. Two of the five patients had small to moderate amounts of free pelvic fluid. Mean ovarian volume on imaging was 560 mL (range: 108-1,361 mL). While the clinical presentation of massive ovarian edema is nonspecific, an enlarged ovary with stromal edema, peripherally placed follicles and preservation of blood flow may be suggestive and wedge biopsy should be considered intraoperatively to avoid unnecessary removal of the ovary. (orig.)

Multimodality imaging findings of massive ovarian edema in children

International Nuclear Information System (INIS)

Dahmoush, Hisham; Anupindi, Sudha A.; Chauvin, Nancy A.; Pawel, Bruce R.

2017-01-01

Massive ovarian edema is a rare benign condition that predominantly affects childbearing women as well as preadolescent girls. It is thought to result from intermittent or partial torsion of the ovary compromising the venous and lymphatic drainage but with preserved arterial supply. The clinical features of massive ovarian edema are nonspecific and can simulate tumors, leading to unnecessary oophorectomy. To demonstrate imaging features that should alert radiologists to consider the diagnosis of massive ovarian edema preoperatively so that fertility-sparing surgery may be considered. We identified five girls diagnosed with massive ovarian edema at pathology. Presenting symptoms, sidedness, imaging appearance, preoperative diagnosis, and operative and histopathological findings were reviewed. Age range was 9.6-14.3 years (mean age: 12.5 years). Common imaging findings included ovarian enlargement with edema of the stroma, peripherally placed follicles, isointense signal on T1-W MRI and markedly hyperintense signal on T2-W MRI, preservation of color Doppler flow by US, and CT Hounsfield units below 40. The uterus was deviated to the affected side in all patients. Two of the five patients had small to moderate amounts of free pelvic fluid. Mean ovarian volume on imaging was 560 mL (range: 108-1,361 mL). While the clinical presentation of massive ovarian edema is nonspecific, an enlarged ovary with stromal edema, peripherally placed follicles and preservation of blood flow may be suggestive and wedge biopsy should be considered intraoperatively to avoid unnecessary removal of the ovary. (orig.)

Furan induced ovarian damage in non-diabetic and diabetic rats and cellular protective role of lycopene.

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Uçar, Semra; Pandir, Dilek

2017-11-01

In our work, furan, lycopene, and furan + lycopene treatments were applied to non-diabetic and diabetic female rats via gavage. Ovarian tissue alterations with histopathology, immunohistochemistry, malondialdehyde levels, oxidative stress parameters such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and harmful effect on ovarian tissue DNA were evaluated in all groups for 28 days. Furan caused the changes histological, ovarian cell's DNA structure, malondialdehyde levels, antioxidant enzymes activities as in a statistically significant manner in each group. Useful effect of lycopene was determined both in non-diabetic and diabetic treatment groups against furan according to the used experimental parameters. Although some histopathological alterations were seen in diabetic and non-diabetic/diabetic plus furan-treated group's ovarians, lycopene restored these variations near to normal levels in furan + lycopene treated groups for in 28 days. Additionally, the results of our immunohistochemical analysis and alterations of the oxidative stress parameters results also supported these findings. Our result confirms that lycopene has protective effect and significantly altered diabetes and furan-induced toxicity in the rat ovarian tissue.

Rate of Appendiceal Metastasis with Non-Serous Epithelial Ovarian Cancer in Manitoba.

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Altman, Alon D; Lefas, Georgia; Power, Laura; Lambert, Pascal; Lotocki, Robert; Dean, Erin; Nachtigal, Mark W

2018-02-01

This study sought to evaluate the rate of appendiceal involvement in non-serous mucinous and endometrioid-associated epithelial ovarian cancers. The Manitoba Cancer Registry and CancerCare database were used to find all women with non-serous epithelial ovarian, fallopian tube, or primary peritoneal cancer between 1995 and 2011. All patients with an appendectomy were then identified, and their final pathology findings were reviewed. Women who did not receive treatment or lacked follow-up were excluded. We identified 338 patients from 1995-2011 with no prior appendectomy. Of these, 16.6% received an appendectomy, and 22.8% were clinically evaluated. Most cases within this cohort were mucinous (62%) and stage 1 (63%). Four appendiceal metastases were identified (7.2%), and one half appeared clinically normal at the time of surgery (3.6%). Within the mucinous histologic type, 32.7% of patients received an appendectomy, with a metastatic rate of 5.7%. Of the 127 endometrioid cases, only 10 patients received an appendectomy, and 2 were found to have metastases. No metastases were found in the 85 patients in the clear cell cohort, only 5 of whom received an appendectomy. Routine appendectomy or clinical assessment of the appendix is valuable for all non-serous ovarian cancers. The rate of involvement for endometriosis-associated ovarian cancers may be significantly higher than expected, and further studies need to be conducted. Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

Influence of aspirin and non-aspirin NSAID use on ovarian and endometrial cancer

DEFF Research Database (Denmark)

Verdoodt, F.; Kjaer, S. K.; Friis, S.

2017-01-01

Increasing evidence supports a role for aspirin use in reducing the incidence and mortality of several cancer types. This has spurred a new wave of interest in this widely used drug. In this review, we present and evaluate the epidemiologic evidence of the association between the use of aspirin....... Overall, observational studies indicate modest reductions in risk of ovarian and endometrial cancer with aspirin use, whereas the results for non-aspirin NSAID use are equivocal. The strongest inverse associations have been reported for long-term consistent aspirin use, notably among subgroups of users (e.......g., those with high body mass index). Few studies have evaluated the influence of NSAID use on the mortality of ovarian or endometrial cancer, and substantial heterogeneity of study characteristics and results preclude any conclusions. Additional studies of aspirin and non-aspirin NSAID use and ovarian...

A novel combinational pH-PCO2 microelectrode.

Science.gov (United States)

Rao, X; Ma, Y

1993-07-01

A novel combinational pH-PCO2 microelectrode based on a neutral carrier hydrogen ion exchanger is described. It is easy to fabricate and allows pH and PCO2 to be measured simultaneously. The microelectrode has a 5-microns tip. The PCO2 microelectrode exhibits a linear response in the range 1.75 x 10(-5)-10(-2) mol/liter with a Nernstian slope of 57.0 mV/decade at 25 degrees C. The detection limit is 10(-5) mol/liter. The pH microelectrode exhibits a linear response in the range pH 4-12 with a Nernstian slope of 60.0 mV/decade at 25 degrees C. The 95% steady-state response time of the PCO2 microelectrode is about 2 min, while it is about 10 s for pH microelectrode. The electromotive force drift is 4.3 mV/h (PCO2) and 2.6 mV/h (pH), respectively. The lifetime is 3 to 4 days. The microelectrode can measure pH and PCO2 in body fluids simultaneously with satisfactory results. It is also a good basic electrode for enzyme microelectrolysis.

[Insulin resistance in the pathogenesis of polycystic ovarian disease (PCOD)].

Science.gov (United States)

Jakowicki, J

1994-10-01

In polycystic ovarian disease there is a strong association between hyperinsulinemia and hyperandrogenism but not with obesity alone. The magnitude of peripheral insulin resistance is similar to that seen in non-insulin-dependent diabetes mellitus. Mild hyperinsulinemia in PCOD patients is not impair the carbohydrate metabolism. The elimination of the cause of hyperandrogenism by bilateral oophorectomy, long-acting Gn-RH agonist or antiandrogen cyproterone acetate did not improve the associated insulin resistance. In opposition to insulin resistance in the tissues responsible for metabolism of carbohydrate, the ovary remains sensitive to the effects of pancreatic hormone. Presumably this mechanism involved the interaction with IGF-I receptors to stimulate thecal and stromal androgen production. Insulin may sensitize the stroma to the stimulatory effect of LH. In the mechanism of follicular arrest take part increased level of binding proteins for IGF-I, mainly IGFBP 2, -4 and 5 inhibit FSH and IGF-I action.

Patterns of ovarian morphology in polycystic ovary syndrome: a study utilising magnetic resonance imaging

International Nuclear Information System (INIS)

Barber, Thomas M.; Smith, Rachel; Marland, Anne; Wass, John A.H.; Alvey, Christopher; Greenslade, Tessa; Gooding, Mark; Barber, Debbie; Child, Tim; McCarthy, Mark I.; Franks, Stephen; Golding, Stephen J.

2010-01-01

To evaluate and compare MRI-based ovarian morphology in groups of women with polycystic ovary syndrome (PCOS) and controls. All PCOS cases (n = 44) had oligo-amenorrhoea and hyperandrogenism irrespective of ovarian morphology, and fulfilled NIH/Rotterdam diagnostic criteria for PCOS. All control women (n = 40) had normal menses and normoandrogenaemia. All subjects were of white British/Irish origin and pre-menopausal. Group comparisons were based on independent-sample t tests. Polycystic ovarian morphology was defined by at least 12 follicles 2-9 mm in diameter and/or an ovarian volume greater than 10 cm 3 . Ovarian morphology differed significantly in PCOS cases and controls (follicle number geometric mean [SD range] 18.6 [9.9, 35.0] vs 6.6 [3.1, 14.2], unadjusted P = 1.3 x 10 -16 ; calculated ovarian volume 8.8 cm 3 [5.0, 15.5] vs 5.1 cm 3 [2.5, 10.3], unadjusted P = 3.0 x 10 -7 ; peripheral follicle location in 55% vs 18% of ovaries, P = 7.9 x 10 -6 ; visible central ovarian stroma in 61% vs 24% of ovaries, P = 2.3 x 10 -5 ). Follicle number and calculated ovarian volume were not concordant with clinical/biochemical assignment of PCOS/control status in 36 (23%) and 52 (34%) of ovaries, respectively. Ovarian morphology overlaps in PCOS cases and controls, emphasising the importance of considering clinical/biochemical presentation together with imaging ovarian morphology in the diagnosis of PCOS. (orig.)

Comparison of two methods for calculating the mean vascularization index of ovarian stroma on the basis of spatio-temporal image correlation high-definition flow technology.

Science.gov (United States)

Kudla, Marek J; Kandzia, Tomasz; Alcázar, Juan Luis

2013-11-01

The aim of our study was to determine the agreement between two different methods for calculating the mean vascularization index (VI) of ovarian stroma using spatio-temporal image correlation-high definition flow (STIC-HDF) technology. Stored 4-D STIC-HDF volume data for ovaries of 34 premenopausal women were assessed retrospectively. We calculated the mean VI from the VI values derived for each 3-D volume within the STIC sequence. Then, the examiner subjectively selected the two volumes with the highest and lowest color signals, respectively. We averaged these two values. Agreement between VI measurements was estimated by calculating intra-class correlation coefficients. The intra-class correlation coefficient for the VI was 0.999 (95% confidence interval: 0.999-1.000). The mean time needed to calculate the mean VI using the entire 4-D STIC sequence was significantly longer than the mean time needed to calculate the average value from the volumes with the highest and lowest color signals determined by the operator (p < 0001). We conclude that there is significant agreement between the two methods. Calculating the average VI from the highest and lowest values is less time consuming than calculating the mean VI from the complete STIC sequence. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Role of the Microenvironment in Ovarian Cancer Stem Cell Maintenance

Directory of Open Access Journals (Sweden)

Jennifer Pasquier

2013-01-01

Full Text Available Despite recent progresses in cancer therapy and increased knowledge in cancer biology, ovarian cancer remains a challenging condition. Among the latest concepts developed in cancer biology, cancer stem cells and the role of microenvironment in tumor progression seem to be related. Indeed, cancer stem cells have been described in several solid tumors including ovarian cancers. These particular cells have the ability to self-renew and reconstitute a heterogeneous tumor. They are characterized by specific surface markers and display resistance to therapeutic regimens. During development, specific molecular cues from the tumor microenvironment can play a role in maintaining and expanding stemness of cancer cells. The tumor stroma contains several compartments: cellular component, cytokine network, and extracellular matrix. These different compartments interact to form a permissive niche for the cancer stem cells. Understanding the molecular cues underlying this crosstalk will allow the design of new therapeutic regimens targeting the niche. In this paper, we will discuss the mechanisms implicated in the interaction between ovarian cancer stem cells and their microenvironment.

Pyruvate Dehydrogenase and Pyruvate Dehydrogenase Kinase Expression in Non Small Cell Lung Cancer and Tumor-Associated Stroma

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Michael I. Koukourakis

2005-01-01

Full Text Available Pyruvate dehydrogenase (PDH catalyzes the conversion of pyruvate to acetyl-coenzyme A, which enters into the Krebs cycle, providing adenosine triphosphate (ATP to the cell. PDH activity is under the control of pyruvate dehydrogenase kinases (PDKs. Under hypoxic conditions, conversion of pyruvate to lactate occurs, a reaction catalyzed by lactate dehydrogenase 5 (LDH5. In cancer cells, however, pyruvate is transformed to lactate occurs, regardless of the presence of oxygen (aerobic glycolysis/Warburg effect. Although hypoxic intratumoral conditions account for HIFia stabilization and induction of anaerobic metabolism, recent data suggest that high pyruvate concentrations also result in HIFia stabilization independently of hypoxia. In the present immunohistochemical study, we provide evidence that the PDH/PDK pathway is repressed in 73% of non small cell lung carcinomas, which may be a key reason for HIFia stabilization and “aerobic glycolysis.” However, about half of PDHdeficient carcinomas are not able to switch on the HIF pathway, and patients harboring these tumors have an excellent postoperative outcome. A small subgroup of clinically aggressive tumors maintains a coherent PDH and HIF/LDH5 expression. In contrast to cancer cells, fibroblasts in the tumor-supporting stroma exhibit an intense PDH but reduced PDK1 expression favoring maximum PDH activity. This means that stroma may use lactic acid produced by tumor cells, preventing the creation of an intolerable intratumoral acidic environment at the same time.

Decoding critical long non-coding RNA in ovarian cancer epithelial-to-mesenchymal transition.

Science.gov (United States)

Mitra, Ramkrishna; Chen, Xi; Greenawalt, Evan J; Maulik, Ujjwal; Jiang, Wei; Zhao, Zhongming; Eischen, Christine M

2017-11-17

Long non-coding RNA (lncRNA) are emerging as contributors to malignancies. Little is understood about the contribution of lncRNA to epithelial-to-mesenchymal transition (EMT), which correlates with metastasis. Ovarian cancer is usually diagnosed after metastasis. Here we report an integrated analysis of >700 ovarian cancer molecular profiles, including genomic data sets, from four patient cohorts identifying lncRNA DNM3OS, MEG3, and MIAT overexpression and their reproducible gene regulation in ovarian cancer EMT. Genome-wide mapping shows 73% of MEG3-regulated EMT-linked pathway genes contain MEG3 binding sites. DNM3OS overexpression, but not MEG3 or MIAT, significantly correlates to worse overall patient survival. DNM3OS knockdown results in altered EMT-linked genes/pathways, mesenchymal-to-epithelial transition, and reduced cell migration and invasion. Proteotranscriptomic characterization further supports the DNM3OS and ovarian cancer EMT connection. TWIST1 overexpression and DNM3OS amplification provides an explanation for increased DNM3OS levels. Therefore, our results elucidate lncRNA that regulate EMT and demonstrate DNM3OS specifically contributes to EMT in ovarian cancer.

Patterns of ovarian morphology in polycystic ovary syndrome: a study utilising magnetic resonance imaging

Energy Technology Data Exchange (ETDEWEB)

Barber, Thomas M.; Smith, Rachel; Marland, Anne; Wass, John A.H. [Churchill Hospital, Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford (United Kingdom); Alvey, Christopher [John Radcliffe Hospital, Oxford MRI Centre, Oxford (United Kingdom); Greenslade, Tessa [John Radcliffe Hospital, Department of Medicine, Oxford (United Kingdom); Gooding, Mark [University of Oxford, Department of Engineering, Oxford (United Kingdom); Barber, Debbie; Child, Tim [John Radcliffe Hospital, Department of Obstetrics and Gynaecology, Oxford (United Kingdom); McCarthy, Mark I. [Churchill Hospital, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford (United Kingdom); Franks, Stephen [Imperial College (Hammersmith Campus), Institute of Reproductive and Developmental Biology, London (United Kingdom); Golding, Stephen J. [John Radcliffe Hospital, Oxford MRI Centre, Oxford (United Kingdom); University of Oxford, Department of Engineering, Oxford (United Kingdom)

2010-05-15

To evaluate and compare MRI-based ovarian morphology in groups of women with polycystic ovary syndrome (PCOS) and controls. All PCOS cases (n = 44) had oligo-amenorrhoea and hyperandrogenism irrespective of ovarian morphology, and fulfilled NIH/Rotterdam diagnostic criteria for PCOS. All control women (n = 40) had normal menses and normoandrogenaemia. All subjects were of white British/Irish origin and pre-menopausal. Group comparisons were based on independent-sample t tests. Polycystic ovarian morphology was defined by at least 12 follicles 2-9 mm in diameter and/or an ovarian volume greater than 10 cm{sup 3}. Ovarian morphology differed significantly in PCOS cases and controls (follicle number geometric mean [SD range] 18.6 [9.9, 35.0] vs 6.6 [3.1, 14.2], unadjusted P = 1.3 x 10{sup -16}; calculated ovarian volume 8.8 cm{sup 3} [5.0, 15.5] vs 5.1 cm{sup 3} [2.5, 10.3], unadjusted P = 3.0 x 10{sup -7}; peripheral follicle location in 55% vs 18% of ovaries, P = 7.9 x 10{sup -6}; visible central ovarian stroma in 61% vs 24% of ovaries, P = 2.3 x 10{sup -5}). Follicle number and calculated ovarian volume were not concordant with clinical/biochemical assignment of PCOS/control status in 36 (23%) and 52 (34%) of ovaries, respectively. Ovarian morphology overlaps in PCOS cases and controls, emphasising the importance of considering clinical/biochemical presentation together with imaging ovarian morphology in the diagnosis of PCOS. (orig.)

Endometriosis-Associated Ovarian Cancer: A Review of Pathogenesis

Directory of Open Access Journals (Sweden)

Shu-Wing Ng

2013-03-01

Full Text Available Endometriosis is classically defined as the presence of endometrial glands and stroma outside of the endometrial lining and uterine musculature. With an estimated frequency of 5%–10% among women of reproductive age, endometriosis is a common gynecologic disorder. While in itself a benign lesion, endometriosis shares several characteristics with invasive cancer, has been shown to undergo malignant transformation, and has been associated with an increased risk of epithelial ovarian carcinoma (EOC. Numerous epidemiologic studies have shown an increased risk of EOC among women with endometriosis. This is particularly true for women with endometrioid and clear cell ovarian carcinoma. However, the carcinogenic pathways by which endometriosis associated ovarian carcinoma (EAOC develops remain poorly understood. Current molecular studies have sought to link endometriosis with EAOC through pathways related to oxidative stress, inflammation and hyperestrogenism. In addition, numerous studies have sought to identify an intermediary lesion between endometriosis and EAOC that may allow for the identification of endometriosis at greatest risk for malignant transformation or for the prevention of malignant transformation of this common gynecologic disorder. The objective of the current article is to review the current data regarding the molecular events associated with EAOC development from endometriosis, with a primary focus on malignancies of the endometrioid and clear cell histologic sub-types.

Atmospheric pCO2 Reconstructed across the Early Eocene Hyperthermals

Science.gov (United States)

Cui, Y.; Schubert, B.

2015-12-01

Negative carbon isotope excursions (CIEs) are commonly associated with extreme global warming. The Early Eocene is punctuated by five such CIEs, the Paleocene-Eocene thermal maximum (PETM, ca. 55.8 Ma), H1 (ca. 53.6 Ma), H2 (ca. 53.5 Ma), I1 (ca. 53.3 Ma), and I2 (ca. 53.2 Ma), each characterized by global warming. The negative CIEs are recognized in both marine and terrestrial substrates, but the terrestrial substrates exhibit a larger absolute magnitude CIE than the marine substrates. Here we reconcile the difference in CIE magnitude between the terrestrial and marine substrates for each of these events by accounting for the additional carbon isotope fractionation by C3 land plants in response to increased atmospheric pCO2. Our analysis yields background and peak pCO2 values for each of the events. Assuming a common mechanism for each event, we calculate that background pCO2 was not static across the Early Eocene, with the highest background pCO2 immediately prior to I2, the last of the five CIEs. Background pCO2 is dependent on the source used in our analysis with values ranging from 300 to 720 ppmv provided an injection of 13C-depleted carbon with δ13C value of -60‰ (e.g. biogenic methane). The peak pCO2 during each event scales according to the magnitude of CIE, and is therefore greatest during the PETM and smallest during H2. Both background and peak pCO2 are higher if we assume a mechanism of permafrost thawing (δ13C = -25‰). Our reconstruction of pCO2 across these events is consistent with trends in the δ18O value of deep-sea benthic foraminifera, suggesting a strong link between pCO2 and temperature during the Early Eocene.

Hereditary association between testicular cancer and familial ovarian cancer: A Familial Ovarian Cancer Registry study.

Science.gov (United States)

Etter, John Lewis; Eng, Kevin; Cannioto, Rikki; Kaur, Jasmine; Almohanna, Hani; Alqassim, Emad; Szender, J Brian; Joseph, Janine M; Lele, Shashikant; Odunsi, Kunle; Moysich, Kirsten B

2018-04-01

Although family history of testicular cancer is well-established as a risk factor for testicular cancer, it is unknown whether family history of ovarian cancer is associated with risk of testicular cancer. Using data from the Familial Ovarian Cancer Registry on 2636 families with multiple cases of ovarian cancer, we systematically compared relative frequencies of ovarian cancer among relatives of men with testicular and non-testicular cancers. Thirty-one families with cases of both ovarian and testicular cancer were identified. We observed that, among men with cancer, those with testicular cancer were more likely to have a mother with ovarian cancer than those with non-testicular cancers (OR = 3.32, p = 0.004). Zero paternal grandmothers of men with testicular cancer had ovarian cancer. These observations provide compelling preliminary evidence for a familial association between ovarian and testicular cancers Future studies should be designed to further investigate this association and evaluate X-linkage. Copyright © 2018 Elsevier Ltd. All rights reserved.

Towards prevention of ovarian cancer.

Science.gov (United States)

Ali, Aus Tariq

2018-01-01

Ovarian cancer is the leading cause of death of all gynaecological cancers. To date, there is no reliable, specific screening procedure for detecting ovarian cancer. The risk factors of ovarian cancer include modifiable and non-modifiable factors. The main goal of the ovarian cancer prevention program is to significantly reduce the risk of development of ovarian cancer and other cancers such as breast and/or peritoneal cancer. The application of non-surgical preventive approaches such as oral contraceptives, parity and breastfeeding has been shown to be highly protective against ovarian cancer development. Targeting inflammation has been also reported to be associated with a protective trend against ovarian cancer and can be achieved through either non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin or lifestyle modifications or both. Lifestyle modification that includes regular exercise, healthy diet supplemented with anti-oxidants and anti-inflammatory elements reduces the risk of the disease even further. Surgical protective approaches include; tubal ligation, hysterectomy and prophylactic bilateral salpingo-oophorectomy and the former is the most effective approach to protect against ovarian cancer. A better understanding of the risk factors of ovarian cancer and the current approaches to prevent it may increase the awareness and help to decrease the incidence of ovarian cancer, increase the five-year survival rate and decrease the mortality rate significantly in the general population especially among those at high risk for ovarian cancer. This review is an attempt to outline a potential program of ovarian cancer prevention and the potential challenges. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Distribution of Stroma and Antral Follicles Differs between Insulin-Resistance and Hyperandrogenism-Related Polycystic Ovarian Syndrome

DEFF Research Database (Denmark)

Alviggi, Carlo; Conforti, Alessandro; De Rosa, Pasquale

2017-01-01

groups based on specific transvaginal ultrasound parameters: subjects with more than half of the follicles measuring between 5 and 9 mm in diameter, an ultrasonographic determined stroma/total area (S/A) > 0.34 and a "necklace" sign of antral follicles (Group A); and subjects with more than half...... of the antral follicles measuring between 2 and 4 mm in diameter, an S/A ≤ 0.34; no "necklace" sign but ubiquitously distributed follicles determined by ultrasound (Group B). The association between these ultrasound patterns and the presence of insulin resistance was also evaluated. RESULTS: Seventy...

Warming and pCO2 effects on Florida stone crab larvae

Science.gov (United States)

Gravinese, Philip M.; Enochs, Ian C.; Manzello, Derek P.; van Woesik, Robert

2018-05-01

Greenhouse gas emissions are increasing ocean temperatures and the partial pressure of CO2 (pCO2), resulting in more acidic waters. It is presently unknown how elevated temperature and pCO2 will influence the early life history stages of the majority of marine coastal species. We investigated the combined effect of elevated temperature (30 °C control and 32 °C treatment) and elevated pCO2 (450 μatm control and 1100 μatm treatment) on the (i) growth, (ii) survival, (iii) condition, and (iv) morphology of larvae of the commercially important Florida stone crab, Menippe mercenaria. At elevated temperature, larvae exhibited a significantly shorter molt stage, and elevated pCO2 caused stage-V larvae to delay metamorphosis to post-larvae. On average, elevated pCO2 resulted in a 37% decrease in survivorship relative to the control; however the effect of elevated temperature reduced larval survivorship by 71%. Exposure to both elevated temperature and pCO2 reduced larval survivorship by 80% relative to the control. Despite this, no significant differences were detected in the condition or morphology of stone crab larvae when subjected to elevated temperature and pCO2 treatments. Although elevated pCO2 could result in a reduction in larval supply, future increases in seawater temperatures are even more likely to threaten the future sustainability of the stone-crab fishery.

Long non-coding RNA TUG1 regulates ovarian cancer proliferation and metastasis via affecting epithelial-mesenchymal transition.

Science.gov (United States)

Kuang, Defeng; Zhang, Xiaoping; Hua, Shaofang; Dong, Wei; Li, Zhiguo

2016-10-01

Ovarian cancer is the fifth leading cause of cancer-related death in women worldwide, and recent studies have highlighted the role of long non-coding RNAs (lncRNAs) in cancer development. However, the role of lncRNAs in ovarian cancer is largely unclear. In this study, we focused on the taurine up-regulated gene 1 (TUG1) and examined its molecular mechanism in ovarian cancer. Here, we reported that TUG1 was up-regulated in ovarian cancer tissues and ovarian cancer cells, and TUG1 expression was positively correlated with tumor grade and FIGO stage. In vitro functional assays (CCK-8 assay, colony formation assay, and cell invasion assay) revealed that knock-down of TUG1 by small RNA inference significantly inhibited cell proliferation, colony formation and cell invasion in ovarian cancer cells. Further experiment showed that knock-down of TUG1 induced cell apoptosis and altered the protein expression levels of apoptosis-related mediators in ovarian cancer cells. More importantly, knock-down of TUG1 also reversed epithelial-mesenchymal transition in ovarian cancer. In summary, our results suggest that knock-down of TUG1 may represent a novel therapeutic strategy for the treatment of ovarian cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantifying pCO2 in biological ocean acidification experiments: A comparison of four methods.

Science.gov (United States)

Watson, Sue-Ann; Fabricius, Katharina E; Munday, Philip L

2017-01-01

Quantifying the amount of carbon dioxide (CO2) in seawater is an essential component of ocean acidification research; however, equipment for measuring CO2 directly can be costly and involve complex, bulky apparatus. Consequently, other parameters of the carbonate system, such as pH and total alkalinity (AT), are often measured and used to calculate the partial pressure of CO2 (pCO2) in seawater, especially in biological CO2-manipulation studies, including large ecological experiments and those conducted at field sites. Here we compare four methods of pCO2 determination that have been used in biological ocean acidification experiments: 1) Versatile INstrument for the Determination of Total inorganic carbon and titration Alkalinity (VINDTA) measurement of dissolved inorganic carbon (CT) and AT, 2) spectrophotometric measurement of pHT and AT, 3) electrode measurement of pHNBS and AT, and 4) the direct measurement of CO2 using a portable CO2 equilibrator with a non-dispersive infrared (NDIR) gas analyser. In this study, we found these four methods can produce very similar pCO2 estimates, and the three methods often suited to field-based application (spectrophotometric pHT, electrode pHNBS and CO2 equilibrator) produced estimated measurement uncertainties of 3.5-4.6% for pCO2. Importantly, we are not advocating the replacement of established methods to measure seawater carbonate chemistry, particularly for high-accuracy quantification of carbonate parameters in seawater such as open ocean chemistry, for real-time measures of ocean change, nor for the measurement of small changes in seawater pCO2. However, for biological CO2-manipulation experiments measuring differences of over 100 μatm pCO2 among treatments, we find the four methods described here can produce similar results with careful use.

Updates of the role of oxidative stress in the pathogenesis of ovarian cancer.

Science.gov (United States)

Saed, Ghassan M; Diamond, Michael P; Fletcher, Nicole M

2017-06-01

Clinical and epidemiological investigations have provided evidence supporting the role of reactive oxygen species (ROS) and reactive nitrogen species (RNS), collectively known as oxidative stress, in the etiology of cancer. Exogenous factors such as chronic inflammation, infection and hypoxia are major sources of cellular oxidative stress. Specifically, oxidative stress plays an important role in the pathogenesis, neoangiogenesis, and dissemination of local or distant ovarian cancer, as it is known to induce phenotypic modifications of tumor cells by cross talk between tumor cells and the surrounding stroma. Subsequently, the biological significance of the relationship between oxidative stress markers and various stages of epithelial ovarian cancer highlights potential therapeutic interventions as well as provides urgently needed early detection biomarkers. In the light of our scientific research and the most recent experimental and clinical observations, this review provides the reader with up to date most relevant findings on the role of oxidative stress in the pathogenesis of ovarian cancer and the possible therapeutic implications. Copyright © 2017 Elsevier Inc. All rights reserved.

pCO2 And pH regulation of cerebral blood flow

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SeongHun eYoon

2012-09-01

Full Text Available CO2 Serves as one of the fundamental regulators of cerebral blood flow. It is widely considered that this regulation occurs through pCO2-driven changes in pH of the cerebral spinal fluid, with elevated and lowered pH causing direct relaxation and contraction of the smooth muscle, respectively. However, some findings also suggest that pCO2 acts independently of and/or in conjunction with altered pH. This action may be due to a direct effect of cerebral spinal fluid pCO2 on the smooth muscle as well as on the endothelium, nerves, and astrocytes. Findings may also point to an action of arterial pCO2 on the endothelium to regulate smooth muscle contractility. Thus, the effects of pH and pCO2 may be influenced by the absence/presence of different cell types in the various experimental preparations. Results may also be influenced by experimental parameters including myogenic tone as well as solutions containing significantly altered HCO3- concentrations, i.e., solutions routinely employed to differentiate the effects of pH from pCO2. In sum, it appears that pCO2, independently and in conjunction with pH, may regulate cerebral blood flow.

A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF: a multicenter randomized non-inferiority trial.

Science.gov (United States)

Youssef, M A; van Wely, M; Al-Inany, H; Madani, T; Jahangiri, N; Khodabakhshi, S; Alhalabi, M; Akhondi, M; Ansaripour, S; Tokhmechy, R; Zarandi, L; Rizk, A; El-Mohamedy, M; Shaeer, E; Khattab, M; Mochtar, M H; van der Veen, F

2017-01-01

In subfertile women with poor ovarian reserve undergoing IVF does a mild ovarian stimulation strategy lead to comparable ongoing pregnancy rates in comparison to a conventional ovarian stimulation strategy? A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF leads to similar ongoing pregnancy rates as a conventional ovarian stimulation strategy. Women diagnosed with poor ovarian reserve are treated with a conventional ovarian stimulation strategy consisting of high-dose gonadotropins and pituitary downregulation with a long mid-luteal start GnRH-agonist protocol. Previous studies comparing a conventional strategy with a mild ovarian stimulation strategy consisting of low-dose gonadotropins and pituitary downregulation with a GnRH-antagonist have been under powered and their effectiveness is inconclusive. This open label multicenter randomized trial was designed to compare one cycle of a mild ovarian stimulation strategy consisting of low-dose gonadotropins (150 IU FSH) and pituitary downregulation with a GnRH-antagonist to one cycle of a conventional ovarian stimulation strategy consisting of high-dose gonadotropins (450 IU HMG) and pituitary downregulation with a long mid-luteal GnRH-agonist in women of advanced maternal age and/or women with poor ovarian reserve undergoing IVF between May 2011 and April 2014. Couples seeking infertility treatment were eligible if they fulfilled the following inclusion criteria: female age ≥35 years, a raised basal FSH level >10 IU/ml irrespective of age, a low antral follicular count of ≤5 follicles or poor ovarian response or cycle cancellation during a previous IVF cycle irrespective of age. The primary outcome was ongoing pregnancy rate per woman randomized. Analyses were on an intention-to-treat basis. We randomly assigned 195 women to the mild ovarian stimulation strategy and 199 women to the conventional ovarian stimulation strategy. Ongoing pregnancy rate was 12.8% (25/195) for mild

Transcriptome Analysis of Individual Stromal Cell Populations Identifies Stroma-Tumor Crosstalk in Mouse Lung Cancer Model

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Hyejin Choi

2015-02-01

Full Text Available Emerging studies have begun to demonstrate that reprogrammed stromal cells play pivotal roles in tumor growth, metastasis, and resistance to therapy. However, the contribution of stromal cells to non-small-cell lung cancer (NSCLC has remained underexplored. We used an orthotopic model of Kras-driven NSCLC to systematically dissect the contribution of specific hematopoietic stromal cells in lung cancer. RNA deep-sequencing analysis of individually sorted myeloid lineage and tumor epithelial cells revealed cell-type-specific differentially regulated genes, indicative of activated stroma. We developed a computational model for crosstalk signaling discovery based on ligand-receptor interactions and downstream signaling networks and identified known and novel tumor-stroma paracrine and tumor autocrine crosstalk-signaling pathways in NSCLC. We provide cellular and molecular insights into components of the lung cancer microenvironment that contribute to carcinogenesis. This study has the potential for development of therapeutic strategies that target tumor-stroma interactions and may complement conventional anti-cancer treatments.

Long-term surface pCO2 trends from observations and models

International Nuclear Information System (INIS)

Tjiputra, Jerry F.; Olsen, Are; Heinze, Christoph; Bopp, Laurent; Roy, Tilla

2014-01-01

We estimate regional long-term surface ocean pCO 2 growth rates using all available underway and bottled biogeochemistry data collected over the past four decades. These observed regional trends are compared with those simulated by five state-of-the-art Earth system models over the historical period. Oceanic pCO 2 growth rates faster than the atmospheric growth rates indicate decreasing atmospheric CO 2 uptake, while ocean pCO 2 growth rates slower than the atmospheric growth rates indicate increasing atmospheric CO 2 uptake. Aside from the western sub-polar North Pacific and the subtropical North Atlantic, our analysis indicates that the current observation-based basin-scale trends may be underestimated, indicating that more observations are needed to determine the trends in these regions. Encouragingly, good agreement between the simulated and observed pCO 2 trends is found when the simulated fields are sub sampled with the observational coverage. In agreement with observations, we see that the simulated pCO 2 trends are primarily associated with the increase in surface dissolved inorganic carbon (DIC) associated with atmospheric carbon uptake, and in part by warming of the sea surface. Under the RCP8.5 future scenario, DIC continues to be the dominant driver of pCO 2 trends, with little change in the relative contribution of SST. However, the changes in the hydrological cycle play an increasingly important role. For the contemporary (1970-2011) period, the simulated regional pCO 2 trends are lower than the atmospheric growth rate over 90% of the ocean. However, by year 2100 more than 40% of the surface ocean area has a higher oceanic pCO 2 trend than the atmosphere, implying a reduction in the atmospheric CO 2 uptake rate. The fastest pCO 2 growth rates are projected for the sub-polar North Atlantic, while the high-latitude Southern Ocean and eastern equatorial Pacific have the weakest growth rates, remaining below the atmospheric pCO 2 growth rate. Our work

Long-term surface pCO2 trends from observations and models

Directory of Open Access Journals (Sweden)

Jerry F. Tjiputra

2014-05-01

Full Text Available We estimate regional long-term surface ocean pCO2 growth rates using all available underway and bottled biogeochemistry data collected over the past four decades. These observed regional trends are compared with those simulated by five state-of-the-art Earth system models over the historical period. Oceanic pCO2 growth rates faster than the atmospheric growth rates indicate decreasing atmospheric CO2 uptake, while ocean pCO2 growth rates slower than the atmospheric growth rates indicate increasing atmospheric CO2 uptake. Aside from the western subpolar North Pacific and the subtropical North Atlantic, our analysis indicates that the current observation-based basin-scale trends may be underestimated, indicating that more observations are needed to determine the trends in these regions. Encouragingly, good agreement between the simulated and observed pCO2 trends is found when the simulated fields are subsampled with the observational coverage. In agreement with observations, we see that the simulated pCO2 trends are primarily associated with the increase in surface dissolved inorganic carbon (DIC associated with atmospheric carbon uptake, and in part by warming of the sea surface. Under the RCP8.5 future scenario, DIC continues to be the dominant driver of pCO2 trends, with little change in the relative contribution of SST. However, the changes in the hydrological cycle play an increasingly important role. For the contemporary (1970–2011 period, the simulated regional pCO2 trends are lower than the atmospheric growth rate over 90% of the ocean. However, by year 2100 more than 40% of the surface ocean area has a higher oceanic pCO2 trend than the atmosphere, implying a reduction in the atmospheric CO2 uptake rate. The fastest pCO2 growth rates are projected for the subpolar North Atlantic, while the high-latitude Southern Ocean and eastern equatorial Pacific have the weakest growth rates, remaining below the atmospheric pCO2 growth rate. Our work

Spatio-temporal Variability in Surface Ocean pCO2 Inferred from Observations

OpenAIRE

Jones, Steve

2012-01-01

The variability of surface ocean pCO2 is examined on multiple spatial and temporal scales. Temporal autocorrelation analysis is used to examine pCO2 variability over multiple years. Spatial autocorrelation analysis describes pCO2 variability over multiple spatial scales. Spatial autocorrelation lengths range between

Left-right differences in ovarian volume and antral follicle count in 1423 women of reproductive age

DEFF Research Database (Denmark)

Korsholm, Anne-Sofie; Hvidman, Helene Westring; Bentzen, Janne Gasseholm

2017-01-01

The aim of this cross-sectional study was to investigate side differences in antral follicle count (AFC) and ovarian volume in left versus right ovaries in relation to chronological and "biological" age, the latter estimated by anti-Müllerian hormone (AMH) levels. The cohort comprised 1423 women...... ≤ 0.003). AFC was significantly higher in the right compared to the left ovary in the three upper AMH quartiles (p ≤ 0.005). The findings were similar when stratified in age quartiles. More than half (54.8%) had polycystic ovarian (PCO) morphology in at least one ovary. Of these women, 46.3% (n = 361......: 1014 fertile and 409 infertile. All were examined by transvaginal sonography and serum AMH. Overall the right ovary contained 8.1% more antral follicles (p = 0.002) and had 10.7% larger volume compared with the left (p right ovarian volume was larger than the left (p...

Expression and Functional Pathway Analysis of Nuclear Receptor NR2F2 in Ovarian Cancer

Science.gov (United States)

Hawkins, Shannon M.; Loomans, Holli A.; Wan, Ying-Wooi; Ghosh-Choudhury, Triparna; Coffey, Donna; Xiao, Weimin; Liu, Zhandong; Sangi-Haghpeykar, Haleh

2013-01-01

Context: Recent evidence implicates the orphan nuclear receptor, nuclear receptor subfamily 2, group F, member 2 (NR2F2; chicken ovalbumin upstream promoter-transcription factor II) as both a master regulator of angiogenesis and an oncogene in prostate and other human cancers. Objective: The objective of the study was to determine whether NR2F2 plays a role in ovarian cancer and dissect its potential mechanisms of action. Design, Setting, and Patients: We examined NR2F2 expression in healthy ovary and ovarian cancers using quantitative PCR and immunohistochemistry. NR2F2 expression was targeted in established ovarian cancer cell lines to assess the impact of dysregulated NR2F2 expression in the epithelial compartment of ovarian cancers. Results: Our results indicate that NR2F2 is robustly expressed in the stroma of healthy ovary with little or no expression in epithelia lining the ovarian surface, clefts, or crypts. This pattern of NR2F2 expression was markedly disrupted in ovarian cancers, in which decreased levels of stromal expression and ectopic epithelial expression were frequently observed. Ovarian cancers with the most disrupted patterns of NR2F2 were associated with significantly shorter disease-free interval by Kaplan-Meier analysis. Targeting NR2F2 expression in established ovarian cancer cell lines enhanced apoptosis and increased proliferation. In addition, we found that NR2F2 regulates the expression of NEK2, RAI14, and multiple other genes involved in the cell cycle, suggesting potential pathways by which dysregulated expression of NR2F2 impacts ovarian cancer. Conclusions: These results uncover novel roles for NR2F2 in ovarian cancer and point to a unique scenario in which a single nuclear receptor plays potentially distinct roles in the stromal and epithelial compartments of the same tissue. PMID:23690307

Ultrastructure Organization of Collagen Fibrils and Proteoglycans of Stingray and Shark Corneal Stroma

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Saud A. Alanazi

2015-01-01

Full Text Available We report here the ultrastructural organization of collagen fibrils (CF and proteoglycans (PGs of the corneal stroma of both the stingray and the shark. Three corneas from three stingrays and three corneas from three sharks were processed for electron microscopy. Tissues were embedded in TAAB 031 resin. The corneal stroma of both the stingray and shark consisted of parallel running lamellae of CFs which were decorated with PGs. In the stingray, the mean area of PGs in the posterior stroma was significantly larger than the PGs of the anterior and middle stroma, whereas, in the shark, the mean area of PGs was similar throughout the stroma. The mean area of PGs of the stingray was significantly larger compared to the PGs, mean area of the shark corneal stroma. The CF diameter of the stingray was significantly smaller compared to the CF diameter in the shark. The ultrastructural features of the corneal stroma of both the stingray and the shark were similar to each other except for the CFs and PGs. The PGs in the stingray and shark might be composed of chondroitin sulfate (CS/dermatan sulfate (DS PGs and these PGs with sutures might contribute to the nonswelling properties of the cornea of the stingray and shark.

pCO2 and enzymatic activity in a river floodplain system of the Danube under different hydrological settings.

Science.gov (United States)

Sieczko, Anna; Demeter, Katalin; Mayr, Magdalena; Meisterl, Karin; Peduzzi, Peter

2014-05-01

Surface waters may serve as either sinks or sources of CO2. In contrast to rivers, which are typically sources of CO2 to the atmosphere, the role of fringing floodplains in CO2 flux is largely understudied. This study was conducted in a river-floodplain system near Vienna (Austria). The sampling focused on changing hydrological situations, particularly on two distinct flood events: a typical 1-year flood in 2012 and an extraordinary 100-year flood in 2013. One objective was to determine partial pressure of CO2 (pCO2) in floodplain lakes with different degree of connectivity to the main channel, and compare the impact of these two types of floods. Another aim was to decipher which fraction of the dissolved organic matter (DOM) pool contributed to pCO2 by linking pCO2 with optical properties of DOM and extracellular enzymatic activity (EEA) of microbes. The EEA is a valuable tool, especially for assessing the non-chromophoric but rapidly utilized DOM-fraction during floods. In 2012 and 2013, the floodplain lakes were dominated by supersaturated pCO2 conditions, which indicates that they served as CO2 sources. Surprisingly, there were no significant differences in pCO2 between the two types of flood. Our findings imply that the extent of the flood had minor impact on pCO2, but the general occurrence of a flood appears to be important. During the flood in 2013 significantly more dissolved organic carbon (DOC) (pcarbohydrates.

Buckyball Nucleation of HiPco Tubes

Science.gov (United States)

Smalley, Richard E.

2012-01-01

The purpose of this innovation is to enhance nucleation of single-wall nanotubes (SWNTs) in the HiPco process, selectively producing 10,10 tubes, something which until now has not been thought possible. This is accomplished by injecting C60, or a derivative of C60, solubilized in supercritical CO2 together with a transition metal carboneal cocatalyst into the HiPco reactor. This is a variant on the supercritical disclosure. C60 has never been used to nucleate carbon nanotubes in the gas phase. C60 itself may not have adequate solubility in supercritical CO2. However, fluorinated C60, e.g., C60F36, is easy to make cheaply and should have much enhanced solubility.

Atmospheric pCO2 reconstructed across five early Eocene global warming events

Science.gov (United States)

Cui, Ying; Schubert, Brian A.

2017-11-01

Multiple short-lived global warming events, known as hyperthermals, occurred during the early Eocene (56-52 Ma). Five of these events - the Paleocene-Eocene Thermal Maximum (PETM or ETM1), H1 (or ETM2), H2, I1, and I2 - are marked by a carbon isotope excursion (CIE) within both marine and terrestrial sediments. The magnitude of CIE, which is a function of the amount and isotopic composition of carbon added to the ocean-atmosphere system, varies significantly between marine versus terrestrial substrates. Here we use the increase in carbon isotope fractionation by C3 land plants in response to increased pCO2 to reconcile this difference and reconstruct a range of background pCO2 and peak pCO2 for each CIE, provided two potential carbon sources: methane hydrate destabilization and permafrost-thawing/organic matter oxidation. Although the uncertainty on each pCO2 estimate using this approach is low (e.g., median uncertainty = + 23% / - 18%), this work highlights the potential for significant systematic bias in the pCO2 estimate resulting from sampling resolution, substrate type, diagenesis, and environmental change. Careful consideration of each of these factors is required especially when applying this approach to a single marine-terrestrial CIE pair. Given these limitations, we provide an upper estimate for background early Eocene pCO2 of 463 +248/-131 ppmv (methane hydrate scenario) to 806 +127/-104 ppmv (permafrost-thawing/organic matter oxidation scenario). These results, which represent the first pCO2 proxy estimates directly tied to the Eocene hyperthermals, demonstrate that early Eocene warmth was supported by background pCO2 less than ∼3.5× preindustrial levels and that pCO2 > 1000 ppmv may have occurred only briefly, during hyperthermal events.

Influences of tumor stroma on the malignant phenotype

DEFF Research Database (Denmark)

Nielsen, Jørgen Dau; Moeslund, Mette; Wandall, Hans H

2008-01-01

and laminin 5 was investigated. RESULTS: We found that expression of glycosylated oncofetal fibronectin was increased in the invasive phenotype of oral carcinoma cell lines. Furthermore we demonstrated that certain concentrations of collagen in the connective tissue equivalent, appears to stimulate......, fibronectin and laminin 5 are all characteristics of the tumor stroma. Less is, however, known of the significance of the biophysical properties of the tumor stroma. The purpose of the present study was to investigate how cellular and mechanical properties of the three-dimensional collagen matrix may...

Ovarian ultrasound and ovarian and adrenal hormones before and after treatment for hyperthyroidism.

Science.gov (United States)

Skjöldebrand Sparre, L; Kollind, M; Carlström, K

2002-01-01

To relate thyroid, steroid and pituitary hormones to ovarian ultrasonographic findings in hyperthyroid patients before and during treatment. Ultrasonography of the ovaries and serum hormone determination by immunoassay were performed before and during thiamazole therapy in 18 women of fertile age treated for hyperthyroidism at the Danderyd Hospital from 1996 to 1998. When hyperthyreotic, the patients had elevated serum levels of sex hormone-binding globulin (SHBG) and subnormal values of cortisol, free testosterone (fT) and dehydroepiandrosterone (DHEA). In the euthyreotic state following treatment, endocrine variables were normalized. Patients with a short duration of the disease had higher pretreatment levels of free thyroxine (fT4), SHBG and testosterone and lower corticosteroid binding globulin (CBG) and cortisol levels compared to patients with a long duration of the disease. The pretreatment ultrasonographic picture was abnormal in 16 of 18 patients. Of the 8 patients who were examined by ultrasonography after 3 months of treatment, all but 1 showed a normal picture. Samples from patients showing an abnormal ultrasonographic picture had significantly higher fT4 and lower free testosterone (fT) values than samples from patients with a normal ultrasonographic picture. Ultrasonographic findings showing a multicystic/multifollicular picture, resembling polycystic ovaries (PCO), in hyperthyroidism may be related to direct effects of thyroid hormones on the ovaries and/or altered intraovarian androgen environment due to elevated SHBG levels. It is highly recommended to assess the thyroid status in patients with multicystic/multifollicular ovaries/PCO. Copyright 2002 S. Karger AG, Basel

Lead, selenium and nickel concentrations in epithelial ovarian cancer, borderline ovarian tumor and healthy ovarian tissues.

Science.gov (United States)

Canaz, Emel; Kilinc, Metin; Sayar, Hamide; Kiran, Gurkan; Ozyurek, Eser

2017-09-01

Wide variation exists in ovarian cancer incidence rates suggesting the importance of environmental factors. Due to increasing environmental pollution, trace elements and heavy metals have drawn attention in studies defining the etiology of cancer, but scant data is available for ovarian cancer. Our aim was to compare the tissue concentrations of lead, selenium and nickel in epithelial ovarian cancer, borderline tumor and healthy ovarian tissues. The levels of lead, selenium and nickel were estimated using atomic absorption spectrophotometry in formalin-fixed paraffin-embedded tissue samples. Tests were carried out in 20 malignant epithelial ovarian cancer, 15 epithelial borderline tumor and 20 non-neoplastic healthy ovaries. Two samples were collected for borderline tumors, one from papillary projection and one from the smooth surface of cyst wall. Pb and Ni concentrations were found to be higher both in malignant and borderline tissues than those in healthy ovaries. Concentrations of Pb and Ni in malignant tissues, borderline papillary projections and capsular tissue samples were not different. Comparison of Se concentrations of malignant, borderline and healthy ovarian tissues did not reveal statistical difference. Studied metal levels were not found to be different in either papillary projection or in cyst wall of the borderline tumors. This study revealed the accumulation of lead and nickel in ovarian tissue is associated with borderline and malignant proliferation of the surface epithelium. Accumulation of these metals in epithelial ovarian cancer and borderline ovarian tumor has not been demonstrated before. Copyright © 2017 Elsevier GmbH. All rights reserved.

Involvement of host stroma cells and tissue fibrosis in pancreatic tumor development in transgenic mice.

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Itai Spector

Full Text Available INTRODUCTION: Stroma cells and extracellular matrix (ECM components provide the pivotal microenvironment for tumor development. The study aimed to evaluate the importance of the pancreatic stroma for tumor development. METHODS: Pancreatic tumor cells were implanted subcutaneously into green fluorescent protein transgenic mice, and stroma cells invading the tumors were identified through immunohistochemistry. Inhibition of tumor invasion by stroma cells was achieved with halofuginone, an inhibitor of TGFβ/Smad3 signaling, alone or in combination with chemotherapy. The origin of tumor ECM was evaluated with species-specific collagen I antibodies and in situ hybridization of collagen α1(I gene. Pancreatic fibrosis was induced by cerulean injection and tumors by spleen injection of pancreatic tumor cells. RESULTS: Inhibition of stroma cell infiltration and reduction of tumor ECM levels by halofuginone inhibited development of tumors derived from mouse and human pancreatic cancer cells. Halofuginone reduced the number only of stroma myofibroblasts expressing both contractile and collagen biosynthesis markers. Both stroma myofibroblasts and tumor cells generated ECM that contributes to tumor growth. Combination of treatments that inhibit stroma cell infiltration, cause apoptosis of myofibroblasts and inhibit Smad3 phosphorylation, with chemotherapy that increases tumor-cell apoptosis without affecting Smad3 phosphorylation was more efficacious than either treatment alone. More tumors developed in fibrotic than in normal pancreas, and prevention of tissue fibrosis greatly reduced tumor development. CONCLUSIONS: The utmost importance of tissue fibrosis and of stroma cells for tumor development presents potential new therapy targets, suggesting combination therapy against stroma and neoplastic cells as a treatment of choice.

Oysters and eelgrass: potential partners in a high pCO2 ocean.

Science.gov (United States)

Groner, Maya L; Burge, Colleen A; Cox, Ruth; Rivlin, Natalie; Turner, Mo; Van Alstyne, Kathryn L; Wyllie-Echeverria, Sandy; Bucci, John; Staudigel, Philip; Friedman, Carolyn S

2018-05-25

Climate change is affecting the health and physiology of marine organisms and altering species interactions. Ocean acidification (OA) threatens calcifying organisms such as the Pacific oyster, Crassostrea gigas. In contrast, seagrasses, such as the eelgrass Zostera marina, can benefit from the increase in available carbon for photosynthesis found at a lower seawater pH. Seagrasses can remove dissolved inorganic carbon from OA environments, creating local daytime pH refugia. Pacific oysters may improve the health of eelgrass by filtering out pathogens such as Labyrinthula zosterae (LZ), which causes eelgrass wasting disease (EWD). We examined how co-culture of eelgrass ramets and juvenile oysters affected the health and growth of eelgrass and the mass of oysters under different pCO 2 exposures. In Phase I, each species was cultured alone or in co-culture at 12°C across ambient, medium, and high pCO 2 conditions, (656, 1158 and1606 μatm pCO 2 , respectively). Under high pCO 2 , eelgrass grew faster and had less severe EWD (contracted in the field prior to the experiment). Co-culture with oysters also reduced the severity of EWD. While the presence of eelgrass decreased daytime pCO 2 , this reduction was not substantial enough to ameliorate the negative impact of high pCO 2 on oyster mass. In Phase II, eelgrass alone or oysters and eelgrass in co-culture were held at 15°C under ambient and high pCO 2 conditions, (488 and 2013 μatm pCO 2 , respectively). Half of the replicates were challenged with cultured LZ. Concentrations of defensive compounds in eelgrass (total phenolics and tannins), were altered by LZ exposure and pCO 2 treatments. Greater pathogen loads and increased EWD severity were detected in LZ exposed eelgrass ramets; EWD severity was reduced at high relative to low pCO 2 . Oyster presence did not influence pathogen load or EWD severity; high LZ concentrations in experimental treatments may have masked the effect of this treatment. Collectively, these

Remodeling of Tumor Stroma and Response to Therapy

Energy Technology Data Exchange (ETDEWEB)

Johansson, Anna; Ganss, Ruth, E-mail: ganss@waimr.uwa.edu.au [Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, Perth 6000 (Australia)

2012-03-27

Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy.

Remodeling of Tumor Stroma and Response to Therapy

International Nuclear Information System (INIS)

Johansson, Anna; Ganss, Ruth

2012-01-01

Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy

Prevalence of ovarian adrenal rest tumours and polycystic ovaries in females with congenital adrenal hyperplasia: results of ultrasonography and MR imaging

Energy Technology Data Exchange (ETDEWEB)

Stikkelbroeck, Nike M.M.L.; Schouten, Diana; Otten, Barto J. [University Medical Centre Nijmegen, Department of Paediatric Endocrinology, P.O. Box 9101, Nijmegen (Netherlands); Hermus, Ad R.M.M. [University Medical Centre Nijmegen, Department of Endocrinology, P.O. Box 9101, Nijmegen (Netherlands); Suliman, Harold M.; Jager, Gerrit J. [University Medical Centre Nijmegen, Department of Radiology, P.O. Box 9101, Nijmegen (Netherlands); Braat, Didi D.M. [University Medical Centre Nijmegen, Department of Obstetrics and Gynaecology, P.O. Box 9101, Nijmegen (Netherlands)

2004-10-01

The aim of the investigation was to assess the prevalence of ovarian adrenal rest tumours and polycystic ovaries in female patients with congenital adrenal hyperplasia (CAH). Thirteen female CAH patients (median age 19.8 years, range 14.8-23.5 years) underwent transvaginal (n=6) or transabdominal (n=7) ultrasonography by a gynaecologist and MR imaging (n=13) of the ovaries (pre and post contrast-enhanced T1- and T2-weighted images). Ovarian adrenal rest tumours were defined as small hypoechoic and multifocal nodules on ultrasound and isointense lesions on T1- and hypointense on T2-weighted MR images (derived from characteristics of testicular adrenal rest tumours). Polycystic ovaries were defined as the presence of {>=}10 follicles arranged peripherally around or scattered throughout increased stroma. No ovarian adrenal rest tumours were found either on ultrasound, or by MR imaging. Polycystic ovaries were found in 2 of the 13 patients (15.4%), both with ultrasound and MR. No ovarian adrenal rest tumours were detected in these female CAH patients, which suggests that ovarian adrenal rest tumours in CAH females are rare. The prevalence of polycystic ovaries corresponded to that in the general population. From these results, we would suggest that routine ovarian imaging in CAH females is not indicated. However, when ovarian dysfunction is present, ovarian imaging is advised, first by ultrasonography, to detect ovarian adrenal rest tumours or polycystic ovaries. (orig.)

Prevalence of ovarian adrenal rest tumours and polycystic ovaries in females with congenital adrenal hyperplasia: results of ultrasonography and MR imaging

International Nuclear Information System (INIS)

Stikkelbroeck, Nike M.M.L.; Schouten, Diana; Otten, Barto J.; Hermus, Ad R.M.M.; Suliman, Harold M.; Jager, Gerrit J.; Braat, Didi D.M.

2004-01-01

The aim of the investigation was to assess the prevalence of ovarian adrenal rest tumours and polycystic ovaries in female patients with congenital adrenal hyperplasia (CAH). Thirteen female CAH patients (median age 19.8 years, range 14.8-23.5 years) underwent transvaginal (n=6) or transabdominal (n=7) ultrasonography by a gynaecologist and MR imaging (n=13) of the ovaries (pre and post contrast-enhanced T1- and T2-weighted images). Ovarian adrenal rest tumours were defined as small hypoechoic and multifocal nodules on ultrasound and isointense lesions on T1- and hypointense on T2-weighted MR images (derived from characteristics of testicular adrenal rest tumours). Polycystic ovaries were defined as the presence of ≥10 follicles arranged peripherally around or scattered throughout increased stroma. No ovarian adrenal rest tumours were found either on ultrasound, or by MR imaging. Polycystic ovaries were found in 2 of the 13 patients (15.4%), both with ultrasound and MR. No ovarian adrenal rest tumours were detected in these female CAH patients, which suggests that ovarian adrenal rest tumours in CAH females are rare. The prevalence of polycystic ovaries corresponded to that in the general population. From these results, we would suggest that routine ovarian imaging in CAH females is not indicated. However, when ovarian dysfunction is present, ovarian imaging is advised, first by ultrasonography, to detect ovarian adrenal rest tumours or polycystic ovaries. (orig.)

Influence of aspirin and non-aspirin NSAID use on ovarian and endometrial cancer: Summary of epidemiologic evidence of cancer risk and prognosis.

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Verdoodt, F; Kjaer, S K; Friis, S

2017-06-01

Increasing evidence supports a role for aspirin use in reducing the incidence and mortality of several cancer types. This has spurred a new wave of interest in this widely used drug. In this review, we present and evaluate the epidemiologic evidence of the association between the use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) and the incidence and prognosis of ovarian and endometrial cancer. The evidence of a preventive effect of NSAID use on risk of ovarian or endometrial cancer is based primarily on results from observational studies and, consequently, is only suggestive. Overall, observational studies indicate modest reductions in risk of ovarian and endometrial cancer with aspirin use, whereas the results for non-aspirin NSAID use are equivocal. The strongest inverse associations have been reported for long-term consistent aspirin use, notably among subgroups of users (e.g., those with high body mass index). Few studies have evaluated the influence of NSAID use on the mortality of ovarian or endometrial cancer, and substantial heterogeneity of study characteristics and results preclude any conclusions. Additional studies of aspirin and non-aspirin NSAID use and ovarian or endometrial cancer risk and prognosis are warranted. In the present review, we discuss the importance of comprehensive exposure definitions (i.e., duration, timing, consistency and intensity/dose) and evaluation of potential effect modification according to user characteristics, with the aim of identifying women who may experience the largest benefit of aspirin or non-aspirin NSAID use on risk or prognosis of ovarian and endometrial cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Bioactive self-assembled peptide nanofibers for corneal stroma regeneration.

Science.gov (United States)

Uzunalli, G; Soran, Z; Erkal, T S; Dagdas, Y S; Dinc, E; Hondur, A M; Bilgihan, K; Aydin, B; Guler, M O; Tekinay, A B

2014-03-01

Defects in the corneal stroma caused by trauma or diseases such as macular corneal dystrophy and keratoconus can be detrimental for vision. Development of therapeutic methods to enhance corneal regeneration is essential for treatment of these defects. This paper describes a bioactive peptide nanofiber scaffold system for corneal tissue regeneration. These nanofibers are formed by self-assembling peptide amphiphile molecules containing laminin and fibronectin inspired sequences. Human corneal keratocyte cells cultured on laminin-mimetic peptide nanofibers retained their characteristic morphology, and their proliferation was enhanced compared with cells cultured on fibronectin-mimetic nanofibers. When these nanofibers were used for damaged rabbit corneas, laminin-mimetic peptide nanofibers increased keratocyte migration and supported stroma regeneration. These results suggest that laminin-mimetic peptide nanofibers provide a promising injectable, synthetic scaffold system for cornea stroma regeneration. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Validation of multi-detector computed tomography as a non-invasive method for measuring ovarian volume in macaques (Macaca fascicularis).

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Jones, Jeryl C; Appt, Susan E; Werre, Stephen R; Tan, Joshua C; Kaplan, Jay R

2010-06-01

The purpose of this study was to validate low radiation dose, contrast-enhanced, multi-detector computed tomography (MDCT) as a non-invasive method for measuring ovarian volume in macaques. Computed tomography scans of four known-volume phantoms and nine mature female cynomolgus macaques were acquired using a previously described, low radiation dose scanning protocol, intravenous contrast enhancement, and a 32-slice MDCT scanner. Immediately following MDCT, ovaries were surgically removed and the ovarian weights were measured. The ovarian volumes were determined using water displacement. A veterinary radiologist who was unaware of actual volumes measured ovarian CT volumes three times, using a laptop computer, pen display tablet, hand-traced regions of interest, and free image analysis software. A statistician selected and performed all tests comparing the actual and CT data. Ovaries were successfully located in all MDCT scans. The iliac arteries and veins, uterus, fallopian tubes, cervix, ureters, urinary bladder, rectum, and colon were also consistently visualized. Large antral follicles were detected in six ovaries. Phantom mean CT volume was 0.702+/-SD 0.504 cc and the mean actual volume was 0.743+/-SD 0.526 cc. Ovary mean CT volume was 0.258+/-SD 0.159 cc and mean water displacement volume was 0.257+/-SD 0.145 cc. For phantoms, the mean coefficient of variation for CT volumes was 2.5%. For ovaries, the least squares mean coefficient of variation for CT volumes was 5.4%. The ovarian CT volume was significantly associated with actual ovarian volume (ICC coefficient 0.79, regression coefficient 0.5, P=0.0006) and the actual ovarian weight (ICC coefficient 0.62, regression coefficient 0.6, P=0.015). There was no association between the CT volume accuracy and mean ovarian CT density (degree of intravenous contrast enhancement), and there was no proportional or fixed bias in the CT volume measurements. Findings from this study indicate that MDCT is a valid non

Preservation of human ovarian follicles within tissue frozen by vitrification in a xeno-free closed system using only ethylene glycol as a permeating cryoprotectant.

Science.gov (United States)

Sheikhi, Mona; Hultenby, Kjell; Niklasson, Boel; Lundqvist, Monalill; Hovatta, Outi

2013-07-01

To study the preservation of follicles within ovarian tissue vitrified using only one or a combination of three permeating cryoprotectants. Experimental study. University hospital. Ovarian tissue was donated by consenting women undergoing elective cesarean section. Ovarian tissue was vitrified in closed sealed vials using either a combination of dimethyl sulfoxide, 1,2-propanediol, and ethylene glycol (EG), or only EG as permeating cryoprotectants. Ovarian tissue was vitrified with the use of two vitrification methods. Tissue from the same donor was used for comparison of two different solutions. The morphology of the follicles was evaluated after vitrification, warming, and culture by light microscopy and transmission electron microscopy. Apoptosis was assessed by immunohistochemistry for active caspase-3 in fresh and vitrified tissue. Light and electron microscopic analysis showed equally well preserved morphology of oocytes, granulosa cells, and ovarian stroma when either of the vitrification solutions was used. No apoptosis was observed in primordial and primary follicles. Using only EG as a permeating cryoprotectant in a closed tube gives as good ultrastructural preservation of ovarian follicles as a more complicated system using several cryoprotectants. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

In Vitro Maturation in Women with vs. without Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis

Science.gov (United States)

Siristatidis, Charalampos; Sergentanis, Theodoros N.; Vogiatzi, Paraskevi; Kanavidis, Prodromos; Chrelias, Charalampos; Papantoniou, Nikolaos; Psaltopoulou, Theodora

2015-01-01

Objective To evaluate in vitro maturation (IVM) in sub-fertile women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilisation (IVF), by comparing outcomes with a control group of non-PCOS. Study design A search strategy was developed for PubMed and studies reporting rates of the following outcomes (live birth; clinical pregnancy; implantation; cycle cancellation; oocyte maturation; oocyte fertilization; miscarriage) between patients with PCOS, PCO and controls undergoing IVM were deemed eligible. The review was conducted in accordance to the PRISMA guidelines and included studies quality was assessed through the Newcastle-Ottawa Quality scale. ORs with their corresponding 95% CIs were calculated for the main analysis and subgroup analyses were performed for PCOS cases vs. controls and PCOS vs. PCO cases. Alternative analyses were performed for live birth and clinical pregnancy, based on cycles and on women. Subgroup analyses for FSH stimulation, hCG priming and type of procedure (IVF/ICSI) were undertaken for all meta-analyses encompassing at least four study arms. Random effects models were used to calculate pooled effect estimates. Results Eleven studies were identified. A total of 268 PCOS patients (328 cycles), 100 PCO patients (110 cycles) and 440 controls (480 cycles) were included in the meta-analysis. A borderline trend towards higher birth rates among PCOS patients emerged (pooled OR = 1.74, 95%CI: 0.99–3.04) mainly reflected at the subgroup analysis vs. controls. Clinical pregnancy (pooled OR = 2.37, 95%CI: 1.53–3.68) and implantation rates (pooled OR = 1.73, 95%CI: 1.06–2.81) were higher, while cancellation rates lower (pooled OR = 0.18, 95%CI: 0.06-0.47) among PCOS vs. non-PCOS subjects; maturation and miscarriage rates did not differ between groups, while a borderline trend towards lower fertilization rates among PCOS patients was observed. Conclusion The present meta-analysis provides preliminary evidence on the effectiveness of

Early postradiation recovery of precursor cells of hemopoietic stroma

International Nuclear Information System (INIS)

Todriya, T.V.

1984-01-01

Ability of stroma precursor cells to early postradiation recovery was studied in male mices using the method of fraction irradiation of bone marrow. Donor mices of bone marrow were irradiated in vivo once by the total dose (nonfraction irradiation) and fractionally with 6 h interval between two irradiation doses. The cumulative irradiation doses equal to 10, 12, 14, 16 Gr were investigated. Irradiation was carried out using gamma facility. Bone marrow of the femur was implanted immediately after irradiation under kidney capsule of nonirradiated syngeneic recipient. The ability of stroma precursor cells to intracellular repair (repair index) was evaluated according to the ratio of the number of hemopoietic cells formed in heterotropic transplants in groups with fraction irradiation to the same one in groups with nonfraction irradiation. The obtained results testify to the fact that slowly regenerated highly radioresistant population of precursor cells of hemopoietic stroma is capable to early postradiation recovery

Response of Nodularia spumigena to pCO2 – Part 1: Growth, production and nitrogen cycling

Directory of Open Access Journals (Sweden)

M. Nausch

2012-08-01

Full Text Available Heterocystous cyanobacteria of the genus Nodularia form extensive blooms in the Baltic Sea and contribute substantially to the total annual primary production. Moreover, they dispense a large fraction of new nitrogen to the ecosystem when inorganic nitrogen concentration in summer is low. Thus, it is of ecological importance to know how Nodularia will react to future environmental changes, in particular to increasing carbon dioxide (CO2 concentrations and what consequences there might arise for cycling of organic matter in the Baltic Sea. Here, we determined carbon (C and dinitrogen (N2 fixation rates, growth, elemental stoichiometry of particulate organic matter and nitrogen turnover in batch cultures of the heterocystous cyanobacterium Nodularia spumigena under low (median 315 μatm, mid (median 353 μatm, and high (median 548 μatm CO2 concentrations. Our results demonstrate an overall stimulating effect of rising pCO2 on C and N2 fixation, as well as on cell growth. An increase in pCO2 during incubation days 0 to 9 resulted in an elevation in growth rate by 84 ± 38% (low vs. high pCO2 and 40 ± 25% (mid vs. high pCO2, as well as in N2 fixation by 93 ± 35% and 38 ± 1%, respectively. C uptake rates showed high standard deviations within treatments and in between sampling days. Nevertheless, C fixation in the high pCO2 treatment was elevated compared to the other two treatments by 97% (high vs. low and 44% (high vs. mid at day 0 and day 3, but this effect diminished afterwards. Additionally, elevation in carbon to nitrogen and nitrogen to phosphorus ratios of the particulate biomass formed (POC : POP and PON : POP was observed at high pCO2. Our findings suggest that rising pCO2 stimulates the growth of heterocystous diazotrophic cyanobacteria, in a similar way as reported for the non-heterocystous diazotroph Trichodesmium. Implications for biogeochemical cycling and food web dynamics, as well as ecological and socio-economical aspects in the

Recurrence of ICA-PCoA aneurysms after neck clipping.

Science.gov (United States)

Sakaki, T; Takeshima, T; Tominaga, M; Hashimoto, H; Kawaguchi, S

1994-01-01

Between 1975 and 1992, 2211 patients underwent aneurysmal neck clipping at the Nara Medical University clinic and associated hospitals. The aneurysm in 931 of these patients was situated at the junction of the internal carotid artery (ICA) and posterior communicating artery (PCoA). Seven patients were readmitted 4 to 17 years after the first surgery because of regrowth and rupture of an ICA-PCoA aneurysmal sac that had arisen from the residual neck. On angiograms obtained following aneurysmal neck clipping, a large primitive type of PCoA was demonstrated in six patients and a small PCoA in one. A small residual aneurysm was confirmed in only two patients and angiographically complete neck clipping in five. Recurrent ICA-PCoA aneurysms were separated into two types based on the position of the old clip in relation to the new growth. Type 1 aneurysms regrow from the entire neck and balloon eccentrically. In this type, it is possible to apply the clip at the neck as in conventional clipping for a ruptured aneurysm. Type 2 includes aneurysms in which the proximal portion of a previous clip is situated at the corner of the ICA and aneurysmal neck and the distal portion on the enlarged dome of the aneurysm, because the sac is regrowing from a portion of the residual neck. In this type of aneurysm, a Sugita fenestrated clip can occlude the residual neck, overriding the old clip. Classifying these aneurysms into two groups is very useful from a surgical point of view because it is possible to apply a new clip without removing the old clip, which was found to be adherent to surrounding tissue.

Evaluation of a Prototype pCO2 Optical Sensor

Science.gov (United States)

Sanborn-Marsh, C.; Sutton, A.; Sabine, C. L.; Lawrence-Salvas, N.; Dietrich, C.

2016-12-01

Anthropogenic greenhouse gas emissions continue to rise, driving climate change and altering the ocean carbonate systems. Carbonate chemistry can be characterized by any two of the four parameters: pH, total alkalinity, dissolved inorganic carbon, and partial pressure of dissolved carbon dioxide gas (pCO2). To fully monitor these dynamic systems, researchers must deploy a more temporally and spatially comprehensive sensor network. Logistical challenges, such as the energy consumption, size, lifetime, depth range, and cost of pCO2 sensors have limited the network's reach so far. NOAA's Pacific Marine Environmental Laboratory has conducted assessment tests of a pCO2 optical sensor (optode), recently developed by Atamanchuk et al (2014). We hope to deploy this optode in the summer of 2017 on high-resolution moored profiler, along with temperature, salinity, and oxygen sensors. While most pCO2 optodes have energy consumptions of 3-10 W, this 36mm-diameter by 86mm-long instrument consumes a mere 7-80 mW. Initial testing showed that its accuracy varied within an absolute range of 2-75 μatm, depending on environmental conditions, including temperature, salinity, response time, and initial calibration. Further research independently examining the effects of each variable on the accuracy of the data will also be presented.

Chemokine receptor expression in tumour islets and stroma in non-small cell lung cancer

International Nuclear Information System (INIS)

Ohri, Chandra M; Shikotra, Aarti; Green, Ruth H; Waller, David A; Bradding, Peter

2010-01-01

We have previously demonstrated that tumour islet infiltration by macrophages is associated with extended survival (ES) in NSCLC. We therefore hypothesised that patients with improved survival would have high tumour islet expression of chemokine receptors known to be associated with favourable prognosis in cancer. This study investigated chemokine receptor expression in the tumour islets and stroma in NSCLC. We used immunohistochemistry to identify cells expressing CXCR1, CXCR2, CXCR3, CXCR4, CXCR5 and CCR1 in the tumour islets and stroma in 20 patients with surgically resected NSCLC. Correlations were made with macrophage and mast cell expression. There was increased expression of CXCR2, CXCR3, and CCR1 in the tumour islets of ES compared with poor survival (PS) patients (p = 0.007, 0.01, and 0.002, respectively). There was an association between 5 year survival and tumour islet CXCR2, CXCR3 and CCR1 density (p = 0.02, 0.003 and <0.001, respectively) as well as stromal CXCR3 density (p = 0.003). There was a positive correlation between macrophage density and CXCR3 expression (r s = 0.520, p = 0.02) and between mast cell density and CXCR3 expression (r s = 0.499, p = 0.03) in the tumour islets. Above median expression of CXCR2, CXCR3 and CCR1 in the tumour islets is associated with increased survival in NSCLC, and expression of CXCR3 correlates with increased macrophage and mast cell infiltration in the tumour islets

Inhibition of Hedgehog signaling antagonizes serous ovarian cancer growth in a primary xenograft model.

Directory of Open Access Journals (Sweden)

Christopher K McCann

Full Text Available Recent evidence links aberrant activation of Hedgehog (Hh signaling with the pathogenesis of several cancers including medulloblastoma, basal cell, small cell lung, pancreatic, prostate and ovarian. This investigation was designed to determine if inhibition of this pathway could inhibit serous ovarian cancer growth.We utilized an in vivo pre-clinical model of serous ovarian cancer to characterize the anti-tumor activity of Hh pathway inhibitors cyclopamine and a clinically applicable derivative, IPI-926. Primary human serous ovarian tumor tissue was used to generate tumor xenografts in mice that were subsequently treated with cyclopamine or IPI-926.Both compounds demonstrated significant anti-tumor activity as single agents. When IPI-926 was used in combination with paclitaxel and carboplatinum (T/C, no synergistic effect was observed, though sustained treatment with IPI-926 after cessation of T/C continued to suppress tumor growth. Hh pathway activity was analyzed by RT-PCR to assess changes in Gli1 transcript levels. A single dose of IPI-926 inhibited mouse stromal Gli1 transcript levels at 24 hours with unchanged human intra-tumor Gli1 levels. Chronic IPI-926 therapy for 21 days, however, inhibited Hh signaling in both mouse stromal and human tumor cells. Expression data from the micro-dissected stroma in human serous ovarian tumors confirmed the presence of Gli1 transcript and a significant association between elevated Gli1 transcript levels and worsened survival.IPI-926 treatment inhibits serous tumor growth suggesting the Hh signaling pathway contributes to the pathogenesis of ovarian cancer and may hold promise as a novel therapeutic target, especially in the maintenance setting.

Effect of 241-americium on bone marrow stroma

International Nuclear Information System (INIS)

Heuvel, R. van den

1990-01-01

The regulation of haemopoiesis occurs via complex interactions between the stroma and the haemopoietic cells. An attempt to further clarifying the mechanisms and the exact role of the stroma in the regulation was made in a study. Results revealed that the murine bone marrow stromal cells are highly radiosensitive after injection with 241-americium and can thus be considered as a target population after internal contamination. In addition, observations are made which may be important for risk estimation for the developing animal and during pregnancy. Contamination in utero and by lactation shows persistent damage up to 1 year after contamination at an average annual dose of 5 cGy. (author)

Ratio of ovarian stroma and total ovarian area by ultrasound in prediction of hyperandrogenemia in reproductive-aged Thai women with polycystic ovary syndrome: a diagnostic test.

Science.gov (United States)

Leerasiri, Pichai; Wongwananuruk, Thanyarat; Rattanachaiyanont, Manee; Indhavivadhana, Suchada; Techatraisak, Kitirat; Angsuwathana, Surasak

2015-02-01

To evaluate the performance of ovarian stromal area to total ovarian area (S/A) ratio for the prediction of biochemical hyperandrogenism in Thai women with polycystic ovary syndrome (PCOS). A cross-sectional study was performed in 222 reproductive-aged Thai women with PCOS attending the Gynecologic Endocrinology Unit (GEU), Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital from May 2007 to January 2009. The patients were interviewed for medical history and examined for anthropometry and clinical hyperandrogenism. Venous blood samples were obtained for androgen profiles. An ovarian ultrasonogram was obtained via transvaginal or transrectal ultrasonography. The prevalences of clinical and biochemical hyperandrogenism were 48.6% and 81.1%, respectively. The S/A ratio at a cut-off point of 0.33 had modest predictability for hyperandrogenism, namely, 0.537 area under the receiver-operator curve, 36.6% sensitivity, 72.1% specificity, 83.8% positive predictive value (PPV) and 20.9% negative predictive value (NPV). The combination of clinical hyperandrogenism and S/A ratio improved the predictability for biochemical hyperandrogenism, with sensitivity, specificity, PPV and NPV of 72.1%, 58.1%, 87.8% and 33.3%, respectively. The S/A ratio alone is not a good predictor for biochemical hyperandrogenism in Thai PCOS women attending GEU for menstrual dysfunction. The combination of S/A ratio and clinical hyperandrogenism has better performance than the S/A ratio alone to predict biochemical hyperandrogenism. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Prognostic markers for colorectal cancer: estimating ploidy and stroma.

Science.gov (United States)

Danielsen, H E; Hveem, T S; Domingo, E; Pradhan, M; Kleppe, A; Syvertsen, R A; Kostolomov, I; Nesheim, J A; Askautrud, H A; Nesbakken, A; Lothe, R A; Svindland, A; Shepherd, N; Novelli, M; Johnstone, E; Tomlinson, I; Kerr, R; Kerr, D J

2018-03-01

We report here the prognostic value of ploidy and digital tumour-stromal morphometric analyses using material from 2624 patients with early stage colorectal cancer (CRC). DNA content (ploidy) and stroma-tumour fraction were estimated using automated digital imaging systems and DNA was extracted from sections of formalin-fixed paraffin-embedded (FFPE) tissue for analysis of microsatellite instability. Samples were available from 1092 patients recruited to the QUASAR 2 trial and two large observational series (Gloucester, n = 954; Oslo University Hospital, n = 578). Resultant biomarkers were analysed for prognostic impact using 5-year cancer-specific survival (CSS) as the clinical end point. Ploidy and stroma-tumour fraction were significantly prognostic in a multivariate model adjusted for age, adjuvant treatment, and pathological T-stage in stage II patients, and the combination of ploidy and stroma-tumour fraction was found to stratify these patients into three clinically useful groups; 5-year CSS 90% versus 83% versus 73% [hazard ratio (HR) = 1.77 (95% confidence interval (95% CI): 1.13-2.77) and HR = 2.95 (95% CI: 1.73-5.03), P < 0.001]. A novel biomarker, combining estimates of ploidy and stroma-tumour fraction, sampled from FFPE tissue, identifies stage II CRC patients with low, intermediate or high risk of CRC disease specific death, and can reliably stratify clinically relevant patient sub-populations with differential risks of tumour recurrence and may support choice of adjuvant therapy for these individuals.

Peritoneal inflammation – A microenvironment for Epithelial Ovarian Cancer (EOC

Directory of Open Access Journals (Sweden)

Liu Jinsong

2004-06-01

Full Text Available Abstract Epithelial ovarian cancer (EOC is a significant cause of cancer related morbidity and mortality in women. Preferential involvement of peritoneal structures contributes to the overall poor outcome in EOC patients. Advances in biotechnology, such as cDNA microarray, are a product of the Human Genome Project and are beginning to provide fresh opportunities to understand the biology of EOC. In particular, it is now possible to examine in depth, at the molecular level, the complex relationship between the tumor itself and its surrounding microenvironment. This review focuses on the anatomy, physiology, and current immunobiologic research of peritoneal structures, and addresses certain potentially useful animal models. Changes in both the inflammatory and non-inflammatory cell compartments, as well as alterations to the extracellular matrix, appear to be signal events that contribute to the remodeling effects of the peritoneal stroma and surface epithelial cells on tumor growth and spread. These alterations may involve a number of proteins, including cytokines, chemokines, growth factors, either membrane or non-membrane bound, and integrins. Interactions between these molecules and molecular structures within the extracellular matrix, such as collagens and the proteoglycans, may contribute to a peritoneal mesothelial surface and stromal environment that is conducive to tumor cell proliferation and invasion. These alterations need to be examined and defined as possible prosnosticators and as therapeutic or diagnostic targets.

Dominant lethal and ovarian effects of plutonium-239 in female mice

International Nuclear Information System (INIS)

Searle, A.G.; Beechey, C.V.; Green, D.; Howells, G.R.

1982-01-01

(C3H x 101)F 1 female mice were injected intravenously with 239 Pu in trisodium citrate, then mated in pairs to strain CBA males, to test for dominant lethality. In the first experiment 10μCi kg -1 and in the second 20μCi kg -1 body mass was injected. Matings were after 6 days in the first experiment (estimated ovarian absorbed dose of 0.1 Gy) and after 3,6 or 12 weeks in the second (estimated ovarian doses of 1.11, 2.45 and 5.91 Gy respectively). No evidence of dominant lethal induction was found in the first experiment, but in the second there was a significant increase over controls in pre-implantation loss in all three series. Post-implantation lethality increased significantly (by 12%) only after 12 weeks' exposure. With the 6- and 12-week exposures (especially the latter) luteal counts fell, fewer females becoming pregnant than in controls. This is attributed to oocyte killing by the α-particles. Histological and autoradiographic investigations showed a marked reduction in ovarian size and follicular numbers with fission-tracks clustered mainly over the medullary stroma. The preimplantation loss may stem from lowered fertilization of oocytes because of their damage, so that the best measure of dominant lethality is that based on post-implantation death. (author)

Tumor stroma with senescence-associated secretory phenotype in steatohepatitic hepatocellular carcinoma.

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Jee San Lee

Full Text Available Senescence secretome was recently reported to promote liver cancer in an obese mouse model. Steatohepatitic hepatocellular carcinoma (SH-HCC, a new variant of HCC, has been found in metabolic syndrome patients, and pericellular fibrosis, a characteristic feature of SH-HCC, suggests that alteration of the tumor stroma might play an important role in SH-HCC development. Clinicopathological characteristics and tumor stroma showing senescence and senescence-associated secretory phenotype (SASP were investigated in 21 SH-HCCs and 34 conventional HCCs (C-HCCs. The expression of α-smooth muscle actin (α-SMA, p21Waf1/Cif1, γ-H2AX, and IL-6 was investigated by immunohistochemistry or immunofluorescence. SH-HCCs were associated with older age, higher body mass index, and a higher incidence of metabolic syndrome, compared to C-HCC (P <0.05, all. The numbers of α-SMA-positive cancer-associated fibroblasts (CAFs (P = 0.049 and α-SMA-positive CAFs co-expressing p21Waf1/Cif1 (P = 0.038, γ-H2AX (P = 0.065, and IL-6 (P = 0.048 were greater for SH-HCCs than C-HCCs. Additionally, non-tumoral liver from SH-HCCs showed a higher incidence of non-alcoholic fatty liver disease and a higher number of α-SMA-positive stellate cells expressing γ-H2AX and p21Waf1/Cif1 than that from C-HCCs (P <0.05, all. In conclusion, SH-HCCs are considered to occur more frequently in metabolic syndrome patients. Therein, senescent and damaged CAFs, as well as non-tumoral stellate cells, expressing SASP including IL-6 may contribute to the development of SH-HCC.

Effect of high ovarian response on the expression of endocrine gland-derived vascular endothelial growth factor (EG-VEGF) in peri-implantation endometrium in IVF women.

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Xu, Li-Zhen; Gao, Min-Zhi; Yao, Li-Hua; Liang, A-Juan; Zhao, Xiao-Ming; Sun, Zhao-Gui

2015-01-01

To investigate the effect of ovarian stimulation on the expression of EG-VEGF mRNA and protein in peri-implantation endometrium in women undergoing IVF and its relation with endometrial receptivity (ER). Prospective laboratory study. University hospital. Eighteen women in stimulated cycles (SC) as study subjects and 18 women in natural cycles (NC) as controls. Women in SC group were classified with two subgroups, high ovarian response (SC1, n=9) with peak serum E2>5,000 pg/mL and moderate ovarian response (SC2, n=9) with peak serum E2 1,000-5,000 pg/mL. Endometrial biopsies were collected 6 days after ovulation in NC or after oocyte retrieval in SC. Endometrium histological dating was observed with HE staining. EG-VEGF mRNA expression levels determined by real-time polymerase chain reaction analysis, and protein levels by immunohistochemistry. All endometrial samples were in the secretory phase. The endometrial development in SC1 was 1 to 2 days advanced to NC, and with dyssynchrony between glandular and stromal tissue. Immunohistochemistry analysis showed that EG-VEGF protein was predominantly expressed in the glandular epithelial cells and endothelial cells of vessels, and also presented in the stroma. The image analysis confirmed that both the gland and stroma of endometrium in SC1 had a significantly lower EG-VEGF protein expression than that in SC2 and NC endometrium. Moreover, EG-VEGF mRNA levels were significantly lower in SC1 than in NC. Both EG-VEGF protein and mRNA levels had no significant difference between SC2 and NC. Decreased expression of EG-VEGF in the peri-implantation is associated with high ovarian response, which may account for the impaired ER and lower implantation rate in IVF cycles.

Does elevated pCO2 affect reef octocorals?

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Gabay, Yasmin; Benayahu, Yehuda; Fine, Maoz

2013-03-01

Increasing anthropogenic pCO2 alters seawater chemistry, with potentially severe consequences for coral reef growth and health. Octocorals are the second most important faunistic component in many reefs, often occupying 50% or more of the available substrate. Three species of octocorals from two families were studied in Eilat (Gulf of Aqaba), comprising the zooxanthellate Ovabunda macrospiculata and Heteroxenia fuscescens (family Xeniidae), and Sarcophyton sp. (family Alcyoniidae). They were maintained under normal (8.2) and reduced (7.6 and 7.3) pH conditions for up to 5 months. Their biolological features, including protein concentration, polyp weight, density of zooxanthellae, and their chlorophyll concentration per cell, as well as polyp pulsation rate, were examined under conditions more acidic than normal, in order to test the hypothesis that rising pCO2 would affect octocorals. The results indicate no statistically significant difference between the octocorals exposed to reduced pH values compared to the control. It is therefore suggested that the octocorals' tissue may act as a protective barrier against adverse pH conditions, thus maintaining them unharmed at high levels of pCO2.

Combined Effects of Elevated pCO2 and Warming Facilitate Cyanophage Infections

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Kai Cheng

2017-06-01

Full Text Available Elevated pCO2 and warming are generally expected to influence cyanobacterial growth, and may promote the formation of blooms. Yet, both climate change factors may also influence cyanobacterial mortality by favoring pathogens, such as viruses, which will depend on the ability of the host to adapt. To test this hypothesis, we grew Plectonema boryanum IU597 under two temperature (25 and 29°C and two pCO2 (400 and 800 μatm conditions for 1 year, after which all treatments were re-exposed to control conditions for a period of 3 weeks. At several time points during the 1 year period, and upon re-exposure, we measured various infection characteristics of it associated cyanophage PP, including the burst size, latent period, lytic cycle and the efficiency of plaquing (EOP. As expected, elevated pCO2 promoted growth of P. boryanum equally over the 1 year period, but warming did not. Burst size increased in the warm treatment, but decreased in both the elevated pCO2 and combined treatment. The latent period and lytic cycle both became shorter in the elevated pCO2 and higher temperature treatment, and were further reduced by the combined effect of both factors. Efficiency of plaquing (EOP decreased in the elevated pCO2 treatment, increased in the warm treatment, and increased even stronger in the combined treatment. These findings indicate that elevated pCO2 enhanced the effect of warming, thereby further promoting the virus infection rate. The re-exposure experiments demonstrate adaptation of the host leading to higher biomass build-up with elevated pCO2 over the experimental period, and lower performance upon re-exposure to control conditions. Similarly, virus burst size and EOP increased when given warm adapted host, but were lower as compared to the control when the host was re-exposed to control conditions. Our results demonstrate that adaptation but particularly physiological acclimation to climate change conditions favored viral infections, while

Screening of the residual normal ovarian tissue adjacent to orthotopic epithelial ovarian carcinomas in nude mice.

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Zhu, G H; Wang, S T; Yao, M Z; Cai, J H; Chen, C Y; Yang, Z X; Hong, L; Yang, S Y

2014-04-16

The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P tissue (P tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

Gene expression during ovarian differentiation in parasitic and non-parasitic lampreys: implications for fecundity and life history types.

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Spice, Erin K; Whyard, Steven; Docker, Margaret F

2014-11-01

Lampreys diverged from the jawed vertebrate lineage approximately 500million years ago. Lampreys undergo sex differentiation much later than most other vertebrates, and ovarian differentiation occurs several years before testicular differentiation. The genetic basis of lamprey sex differentiation is of particular interest both because of the phylogenetic importance of lampreys and because of their unusual pattern of sex differentiation. As well, differences between parasitic and non-parasitic lampreys may first become evident at ovarian differentiation. However, nothing is known about the genetic basis of ovarian differentiation in lampreys. This study examined potential differences in gene expression before, during, and after ovarian differentiation in parasitic chestnut lamprey Ichthyomyzon castaneus and non-parasitic northern brook lamprey Ichthyomyzonfossor. Eight target genes (17β-hydroxysteroid dehydrogenase, germ cell-less, estrogen receptor β, insulin-like growth factor 1 receptor, daz-associated protein 1, cytochrome c oxidase subunit III, Wilms' tumour suppressor protein 1, and dehydrocholesterol reductase 7) were examined. Northern brook lamprey displayed higher expression of cytochrome c oxidase subunit III, whereas chestnut lamprey displayed higher expression of insulin-like growth factor 1 receptor; these genes may be involved in apoptosis and oocyte growth, respectively. Presumptive male larvae had higher expression of Wilms' tumour suppressor protein 1, which may be involved in the undifferentiated gonad and/or later testicular development. Differentiated females had higher expression of 17β hydroxysteroid dehydrogenase and daz-associated protein 1, which may be involved in female development. This study is the first to identify genes that may be involved in ovarian differentiation and fecundity in lampreys. Copyright © 2014 Elsevier Inc. All rights reserved.

Stroma cell priming in enteric lymphoid organ morphogenesis

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Manuela eFerreira

2012-07-01

Full Text Available The lymphoid system is equipped with a network of specialized platforms located at strategic sites, which grant strict immune-surveillance and efficient immune responses. The development of these peripheral secondary lymphoid organs occurs mainly in utero, while tertiary lymphoid structures can form in adulthood generally in response to persistent infection and inflammation. Regardless of the lymphoid tissue and intrinsic cellular and molecular differences, it is now well established that the recruitment of fully functional Lymphoid Tissue inducer (LTi cells to presumptive lymphoid organ sites, and their consequent close and reciprocal interaction with resident stroma cells, are central to secondary lymphoid organ formation. In contrast, the nature of events that initially prime resident sessile stroma cells to recruit and retain LTi cells remains poorly understood.

Management of ovarian cysts

DEFF Research Database (Denmark)

Knudsen, Ulla Breth; Tabor, Ann; Mosgaard, Berit Jul

2004-01-01

BACKGROUND: The treatment of an ovarian cyst relies on its nature, and accurate preoperative discrimination of benign and malignant cysts is therefore of crucial importance. This study was undertaken to review the literature concerning the preoperative diagnosis and treatment of ovarian cysts....... METHODS: Articles concerning ovarian cysts from a medline literature search during the period 1985-2003 were included in addition to articles found as references in the initial publications. RESULTS: Different methods for discriminating between benign and malignant ovarian cysts are discussed....... The diagnosis and the treatment are assessed in relation to age, menopausal status, pregnancy, and whether the cyst is presumed to be benign or malignant. In general, expectant management is the choice in premenopausal and pregnant women with non-suspicious cysts and normal levels of CA-125. In postmenopausal...

Intramucosal–arterial PCO 2 gap fails to reflect intestinal dysoxia in hypoxic hypoxia

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Dubin, Arnaldo; Murias, Gastón; Estenssoro, Elisa; Canales, Héctor; Badie, Julio; Pozo, Mario; Sottile, Juan P; Barán, Marcelo; Pálizas, Fernando; Laporte, Mercedes

2002-01-01

Introduction An elevation in intramucosal–arterial PCO 2 gradient (ΔPCO 2) could be determined either by tissue hypoxia or by reduced blood flow. Our hypothesis was that in hypoxic hypoxia with preserved blood flow, ΔPCO 2 should not be altered. Methods In 17 anesthetized and mechanically ventilated sheep, oxygen delivery was reduced by decreasing flow (ischemic hypoxia, IH) or arterial oxygen saturation (hypoxic hypoxia, HH), or no intervention was made (sham). In the IH group (n = 6), blood...

Impact of laparoscopic ovarian drilling on serum anti-mullerian hormone levels in patients with anovulatory Polycystic Ovarian syndrome.

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Paramu, Sobhana

2016-12-01

Anti-mullerian hormone (AMH) is a marker of the activity of recruitable ovarian follicles. It is useful in the prediction of ovarian reserve. Women with polycystic ovarian syndrome (PCOS) have elevated circulating and intrafollicular AMH levels. Laparoscopic ovarian drilling (LOD) in patients with PCOS destroys ovarian androgen-producing tissue and reduces their peripheral conversion to estrogens. Identifying factors that determine the response of patients with PCOS to LOD will help in selecting the patients who would likely benefit from this treatment. AMH is one such marker that can predict the response to LOD. To evaluate the effect of LOD on serum AMH levels among PCOS responders and non-responders and the usefulness of AMH as a tool in predicting the response to LOD, and to whether there was loss of ovarian function after LOD. This is a prospective cohort study including 30 clomiphene-resistant women with anovulatory PCOS undergoing LOD. Statistical analysis was performed to evaluate the effect of LOD on serum levels of AMH on these women. A significant fall in the levels of AMH was observed after LOD in both responders and non-responders (p8.3 ng/mL showed a significantly lower ovulation rate (33.3%). LOD was not associated with a risk of diminished ovarian reserve. LOD is an effective first-line treatment for women with PCOS who are clomiphene resistant. LOD has no negative effect on ovarian reserve. AMH is a useful marker in predicting the outcome of LOD.

Androgen receptor-mediated non-genomic effects of vinclozolin on porcine ovarian follicles and isolated granulosa cells: Vinclozolin and non-genomic effects in porcine ovarian follicles.

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Wartalski, Kamil; Knet-Seweryn, Malgorzata; Hoja-Lukowicz, Dorota; Tabarowski, Zbigniew; Duda, Malgorzata

2016-05-01

The present study investigated the influence of the androgen receptor (AR) agonists testosterone (T) and dihydrotestosterone (DHT), and vinclozolin (Vnz), a fungicide with antiandrogenic activity, on non-genomic signal transduction within ovarian follicles. Porcine granulosa cells (GCs) isolated from mature follicles were cultured for 48h. For the last 24h of culture, they were exposed to T (10(-7)M), DHT (10(-7)M), Vnz (1.4×10(-5)M), T and Vnz (T+Vnz), or DHT and Vnz (DHT+Vnz) at the same concentrations. To better imitate in vivo conditions, whole follicles (4-6mm in diameter) were incubated (24h) in an organ culture system with the same factors. Expression of AR mRNA and protein was determined by real-time PCR and western blot analyses. To demonstrate AR localization in cultured GCs and whole follicles, immunocytochemistry and immunohistochemistry were performed, respectively. To elucidate the possible non-genomic action of Vnz in GCs, protein expression and the activity of ERK1/2 and Akt kinases were determined by western blot and ELISA analyses. The immunocytochemistry and immunohistochemistry results showed that exposure of GCs and follicles to Vnz resulted in cytoplasmic and perinuclear AR localization. Real-time PCR and western blot analysis showed that AR mRNA and protein expression increased (P≤0.001) in GC cultures after combined treatment with an androgen and Vnz. In whole follicles, such treatment also increased AR mRNA with a decrease in the respective protein expression (P≤0.001). Moreover, addition of T or DHT with Vnz increased the activity of ERK1/2 and Akt kinases in cultured GCs (P≤0.001). The results suggest a novel mechanism for Vnz action in porcine ovarian follicles on both AR mRNA and protein levels. Thus, this environmental antiandrogen activates non-genomic signaling pathways, as indicated by the increased activity of both investigated kinases observed within minutes of Vnz addition. Given the widespread presence of Vnz in the

Crystal structure and dimerization equilibria of PcoC, a methionine-rich copper resistance protein from Escherichia coli

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Wernimont, A.K.; Huffman, D.L.; Finney, L.A.; Demeler, B.; O' Halloran, T.V.; Rosenzweig, A.C.

2010-03-08

PcoC is a soluble periplasmic protein encoded by the plasmid-born pco copper resistance operon of Escherichia coli. Like PcoA, a multicopper oxidase encoded in the same locus and its chromosomal homolog CueO, PcoC contains unusual methionine rich sequences. Although essential for copper resistance, the functions of PcoC, PcoA, and their conserved methionine-rich sequences are not known. Similar methionine motifs observed in eukaryotic copper transporters have been proposed to bind copper, but there are no precedents for such metal binding sites in structurally characterized proteins. The high-resolution structures of apo PcoC, determined for both the native and selenomethionine-containing proteins, reveal a seven-stranded barrel with the methionines unexpectedly housed on a solvent-exposed loop. Several potential metal-binding sites can be discerned by comparing the structures to spectroscopic data reported for copper-loaded PcoC. In the native structure, the methionine loop interacts with the same loop on a second molecule in the asymmetric unit. In the selenomethionine structure, the methionine loops are more exposed, forming hydrophobic patches on the protein surface. These two arrangements suggest that the methionine motifs might function in protein-protein interactions between PcoC molecules or with other methionine-rich proteins such as PcoA. Analytical ultracentrifugation data indicate that a weak monomer-dimer equilibrium exists in solution for the apo protein. Dimerization is significantly enhanced upon binding Cu(I) with a measured {Delta}({Delta}G{sup o}) {le} -8.0 kJ/mole, suggesting that copper might bind at the dimer interface.

Impact of laparoscopic ovarian drilling on serum anti-mullerian hormone levels in patients with anovulatory Polycystic Ovarian syndrome

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Sobhana Paramu

2016-12-01

Full Text Available Objectives: Anti-mullerian hormone (AMH is a marker of the activity of recruitable ovarian follicles. It is useful in the prediction of ovarian reserve. Women with polycystic ovarian syndrome (PCOS have elevated circulating and intrafollicular AMH levels. Laparoscopic ovarian drilling (LOD in patients with PCOS destroys ovarian androgen-producing tissue and reduces their peripheral conversion to estrogens. Identifying factors that determine the response of patients with PCOS to LOD will help in selecting the patients who would likely benefit from this treatment. AMH is one such marker that can predict the response to LOD. To evaluate the effect of LOD on serum AMH levels among PCOS responders and non-responders and the usefulness of AMH as a tool in predicting the response to LOD, and to whether there was loss of ovarian function after LOD. Materials and Methods: This is a prospective cohort study including 30 clomiphene-resistant women with anovulatory PCOS undergoing LOD. Statistical analysis was performed to evaluate the effect of LOD on serum levels of AMH on these women. Results: A significant fall in the levels of AMH was observed after LOD in both responders and non-responders (p8.3 ng/mL showed a significantly lower ovulation rate (33.3%. LOD was not associated with a risk of diminished ovarian reserve. Conclusion: LOD is an effective first-line treatment for women with PCOS who are clomiphene resistant. LOD has no negative effect on ovarian reserve. AMH is a useful marker in predicting the outcome of LOD.

High-resolution Atmospheric pCO2 Reconstruction across the Paleogene Using Marine and Terrestrial δ13C records

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Cui, Y.; Schubert, B.

2016-02-01

The early Paleogene (63 to 47 Ma) is considered to have a greenhouse climate1 with proxies suggesting atmospheric CO2 levels (pCO2) approximately 2× pre-industrial levels. However, the proxy based pCO2 reconstructions are limited and do not allow for assessment of changes in pCO2 at million to sub-million year time scales. It has recently been recognized that changes in C3 land plant carbon isotope fractionation can be used as a proxy for pCO2 with quantifiable uncertainty2. Here, we present a high-resolution pCO2 reconstruction (n = 597) across the early Paleogene using published carbon isotope data from both terrestrial organic matter and marine carbonates. The minimum and maximum pCO2 values reconstructed using this method are broad (i.e., 170 +60/-40 ppmv to 2000 +4480/-1060 ppmv) and reflective of the wide range of environments sampled. However, the large number of measurements allows for a robust estimate of average pCO2 during this time interval ( 400 +260/-120 ppmv), and indicates brief (sub-million-year) excursions to very high pCO2 during hyperthermal events (e.g., the PETM). By binning our high-resolution pCO2 data at 1 million year intervals, we can compare our dataset to the other available pCO2 proxies. Our result is broadly consistent with pCO2 levels reconstructed using other proxies, with the exception of paleosol-based pCO2 estimates spanning 53 to 50 Ma. At this timescale, no proxy suggests pCO2 higher than 2000 ppmv, whereas the global surface ocean temperature is considered to be >10 oC warmer than today. Recent climate modeling suggests that low atmospheric pressure during this time period could help reconcile the apparent disconnect between pCO2 and temperature and contribute to the greenhouse climate3. References1. Huber, M., Caballero, R., 2011. Climate of the Past 7, 603-633. 2. Schubert, B.A., Jahren, A.H., 2015. Geology 43, 435-438. 3. Poulsen, C.J., Tabor, C., White, J.D., 2015. Science 348, 1238-1241.

Columnar cell lesions and pseudoangiomatous hyperplasia like stroma: is there an epithelial-stromal interaction?

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Recavarren, Rosemary A; Chivukula, Mamatha; Carter, Gloria; Dabbs, David J

2009-10-10

The significance of association between cancer and its microenvironment has been increasingly recognized. It has been shown in animal models that interaction between neoplastic epithelial cells and adjacent stroma can modulate tumor behavior. Carcinoma associated stromal cells can transform normal epithelial cells into neoplastic cells. In breast, columnar cell lesions are non-obligate precursors of low grade ductal carcinoma in situ. Columnar cell lesions can be seen intimately associated with PASH-like-stroma, a lesion we termed as CCPLS. Our aim is to investigate epithelial-stromal interactions in CCPLS and compare them to PASH without columnar cell lesions in breast core needle biopsies. Normal terminal duct lobular unit (TDLU) epithelium was seen in association with columnar cell lesions as well as PASH. Eight (8) cases of each category were examined by a panel of immunostains: CD117 (C-kit), CD34, CD105, bFGF, AR, ER-beta, MIB-1. We observed a markedly decreased expression of c-kit in columnar cell lesions compared to TDLU-epithelium. CD105 showed a quantitative increase in activated vessels in CCPLS compared to PASH. A subset of CCPLS and PASH were androgen receptor positive. A strong nuclear positivity for ER-beta is observed in the epithelium and stroma of all CCPLS cases. We conclude that (1) activated blood vessels predominate in CCPLS; (2) A molecular alteration is signified by c-kit loss in columnar cell lesions; (3) ER-beta and androgen receptor positivity indicate CCPLS are hormonally responsive lesions. Our study suggests an intimate vascular and hormone dependent epithelial-stromal interaction exists in CCPLS lesions.

In vitro extracellular matrix model to evaluate stroma cell response to transvaginal mesh.

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Wu, Ming-Ping; Huang, Kuan-Hui; Long, Cheng-Yu; Yang, Chau-Chen; Tong, Yat-Ching

2014-04-01

The use of surgical mesh for female pelvic floor reconstruction has increased in recent years. However, there is paucity of information about the biological responses of host stroma cells to different meshes. This study was aimed to establish an in vitro experimental model to study the micro-environment of extracellular matrix (ECM) with embedded mesh and the stroma cell behaviors to different synthetic meshes. Matrigel multi-cellular co-culture system with embedded mesh was used to evaluate the interaction of stroma cells and synthetic mesh in a simulated ECM environment. Human umbilical vein endothelial cells (HUVEC) and NIH3T3 fibroblasts were inoculated in the system. The established multi-cellular Matrigel co-culture system was used to detect stroma cell recruitment and tube formation ability for different synthetic meshes. HUVEC and NIH3T3 cells were recruited into the mesh interstices and organized into tube-like structures in type I mesh material from Perigee, Marlex and Prolift 24 hr after cell inoculation. On the contrary, there was little recruitment of HUVEC and NIH3T3 cells into the type III mesh of intra-vaginal sling (IVS). The Matrigel multi-cellular co-culture system with embedded mesh offers a useful in vitro model to study the biological behaviors of stroma cells in response to different types of synthetic meshes. The system can help to select ideal mesh candidates before actual implantation into the human body. © 2013 Wiley Periodicals, Inc.

Elastic microfibril distribution in the cornea: Differences between normal and keratoconic stroma.

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White, Tomas L; Lewis, Philip N; Young, Robert D; Kitazawa, Koji; Inatomi, Tsutomu; Kinoshita, Shigeru; Meek, Keith M

2017-06-01

The optical and biomechanical properties of the cornea are largely governed by the collagen-rich stroma, a layer that represents approximately 90% of the total thickness. Within the stroma, the specific arrangement of superimposed lamellae provides the tissue with tensile strength, whilst the spatial arrangement of individual collagen fibrils within the lamellae confers transparency. In keratoconus, this precise stromal arrangement is lost, resulting in ectasia and visual impairment. In the normal cornea, we previously characterised the three-dimensional arrangement of an elastic fiber network spanning the posterior stroma from limbus-to-limbus. In the peripheral cornea/limbus there are elastin-containing sheets or broad fibers, most of which become microfibril bundles (MBs) with little or no elastin component when reaching the central cornea. The purpose of the current study was to compare this network with the elastic fiber distribution in post-surgical keratoconic corneal buttons, using serial block face scanning electron microscopy and transmission electron microscopy. We have demonstrated that the MB distribution is very different in keratoconus. MBs are absent from a region of stroma anterior to Descemet's membrane, an area that is densely populated in normal cornea, whilst being concentrated below the epithelium, an area in which they are absent in normal cornea. We contend that these latter microfibrils are produced as a biomechanical response to provide additional strength to the anterior stroma in order to prevent tissue rupture at the apex of the cone. A lack of MBs anterior to Descemet's membrane in keratoconus would alter the biomechanical properties of the tissue, potentially contributing to the pathogenesis of the disease. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Bilateral ovarian Burkitt's lymphoma. A case presentation].

Science.gov (United States)

Briseño-Hernández, Andrés Alejandro; Quezada-López, Deissy Roxana; Castañeda-Chávez, Agar; Dassaejv Macías-Amezcua, Michel; Pintor-Belmontes, Julio Cesar

2014-01-01

Burkitt lymphoma, is described as an aggressive form of non-Hodgkin lymphoma of B cells which occurs most often in children and young adults, ovarian lymphoma can appear as a primary lesion or more commonly referred to as a metastasis. Primary ovarian lesions are rare manifestations corresponding to 0.5% of non-Hodgkin lymphoma and 1.5% of ovarian tumors. Clinic case: 31 years old female with general weakness, march incapacity, dyspnea, hyporexia, fever, diaphoresis, weight loss of 20 kg, flat abs with abdominal pain; Ca125 610 U/ml. Abdominal computed tomography shows a solid aspect tumor which affects the right pelvic cavity. Bilateral ovarian tumors were removed. Microscopically, both lesions show a "starry sky" pattern composed by a monotonous infiltration of lymphocytes mixed with large and clear macrophages, several atypical mitoses, and necrosis and hemorrhage areas. Immunohistochemistry was positive for CD10, CD20, and negative for CD3 and high Ki67 proliferation index. Bilateral ovarian Burkitt's lymphoma was diagnosed. Bilateral ovarian Burkitt's lymphoma is a rare entity, with a variability of presentations, the abdominal pain and abdominal tumors are the most frequent. The patient's prognosis at short term is poor, therefore it's necessary to know this entity and make an early diagnosis.

Follicular fluid placental growth factor is increased in polycystic ovarian syndrome: correlation with ovarian stimulation.

Science.gov (United States)

Tal, Reshef; Seifer, David B; Grazi, Richard V; Malter, Henry E

2014-08-20

Polycystic ovarian syndrome (PCOS) is characterized by increased ovarian angiogenesis and vascularity. Accumulating evidence indicates that vascular endothelial growth factor (VEGF) is increased in PCOS and may play an important role in these vascular changes and the pathogenesis of this disease. Placental growth factor (PlGF), a VEGF family member, has not been previously characterized in PCOS women. We investigated levels and temporal expression patterns of PlGF and its soluble receptor sFlt-1 (soluble Fms-like tyrosine kinase) in serum and follicular fluid (FF) of women with PCOS during controlled ovarian stimulation. This was a prospective cohort study of 14 PCOS women (Rotterdam criteria) and 14 matched controls undergoing controlled ovarian stimulation. Serum was collected on day 3, day of hCG and day of oocyte retrieval. FF was collected on retrieval day. PlGF, sFlt-1 and anti-mullerian hormone (AMH) protein concentrations were measured using ELISA. Since sFlt-1 binds free PlGF, preventing its signal transduction, we calculated PlGF bioavailability as PlGF/sFlt-1 ratio. Serum PlGF and sFlt-1 levels were constant throughout controlled ovarian stimulation, and no significant differences were observed in either factor in PCOS women compared with non-PCOS controls at all three measured time points. However, FF PlGF levels were increased 1.5-fold in PCOS women compared with controls (p ovarian reserve marker anti-mullerian hormone (AMH) and negatively with age. In addition, FF sFlt-1 levels were decreased 1.4-fold in PCOS women compared to controls (p = 0.04). PlGF bioavailability in FF was significantly greater (2-fold) in PCOS women compared with non-PCOS controls (p ovarian stimulation and that its bioavailability is increased in women with PCOS undergoing controlled ovarian stimulation. This suggests that PlGF may play a role in PCOS pathogenesis and its angiogenic dysregulation.

Expression changes in the stroma of prostate cancer predict subsequent relapse.

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Zhenyu Jia

Full Text Available Biomarkers are needed to address overtreatment that occurs for the majority of prostate cancer patients that would not die of the disease but receive radical treatment. A possible barrier to biomarker discovery may be the polyclonal/multifocal nature of prostate tumors as well as cell-type heterogeneity between patient samples. Tumor-adjacent stroma (tumor microenvironment is less affected by genetic alteration and might therefore yield more consistent biomarkers in response to tumor aggressiveness. To this end we compared Affymetrix gene expression profiles in stroma near tumor and identified a set of 115 probe sets for which the expression levels were significantly correlated with time-to-relapse. We also compared patients that chemically relapsed shortly after prostatectomy (<1 year, and patients that did not relapse in the first four years after prostatectomy. We identified 131 differentially expressed microarray probe sets between these two categories. 19 probe sets (15 genes overlapped between the two gene lists with p<0.0001. We developed a PAM-based classifier by training on samples containing stroma near tumor: 9 rapid relapse patient samples and 9 indolent patient samples. We then tested the classifier on 47 different samples, containing 90% or more stroma. The classifier predicted the risk status of patients with an average accuracy of 87%. This is the first general tumor microenvironment-based prognostic classifier. These results indicate that the prostate cancer microenvironment exhibits reproducible changes useful for predicting outcomes for patients.

Non-steroidal anti-inflammatory drugs decrease E2F1 expression and inhibit cell growth in ovarian cancer cells.

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Blanca L Valle

Full Text Available Epidemiological studies have shown that the regular use of non-steroidal anti-inflammatory (NSAIDs drugs is associated with a reduced risk of various cancers. In addition, in vitro and experiments in mouse models have demonstrated that NSAIDs decrease tumor initiation and/or progression of several cancers. However, there are limited preclinical studies investigating the effects of NSAIDs in ovarian cancer. Here, we have studied the effects of two NSAIDs, diclofenac and indomethacin, in ovarian cancer cell lines and in a xenograft mouse model. Diclofenac and indomethacin treatment decreased cell growth by inducing cell cycle arrest and apoptosis. In addition, diclofenac and indomethacin reduced tumor volume in a xenograft model of ovarian cancer. To identify possible molecular pathways mediating the effects of NSAID treatment in ovarian cancer, we performed microarray analysis of ovarian cancer cells treated with indomethacin or diclofenac. Interestingly, several of the genes found downregulated following diclofenac or indomethacin treatment are transcriptional target genes of E2F1. E2F1 was downregulated at the mRNA and protein level upon treatment with diclofenac and indomethacin, and overexpression of E2F1 rescued cells from the growth inhibitory effects of diclofenac and indomethacin. In conclusion, NSAIDs diclofenac and indomethacin exert an anti-proliferative effect in ovarian cancer in vitro and in vivo and the effects of NSAIDs may be mediated, in part, by downregulation of E2F1.

Genetic profiles distinguish different types of hereditary ovarian cancer

DEFF Research Database (Denmark)

Domanska, Katarina; Malander, Susanne; Staaf, Johan

2010-01-01

(HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide array comparative genomic hybridization was applied to 12 HBOC associated tumors with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene mutations with 24 sporadic ovarian cancers......Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian cancer...... that HBOC and HNPCC associated ovarian cancer develop along distinct genetic pathways and genetic profiles can thus be applied to distinguish between different types of hereditary ovarian cancer....

Ocean acidification effects on calcification in pCO2 acclimated Caribbean scleractinian coral

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Ocean acidification (OA) is projected to increase the acidity of coral reef habitats 2-3 times that of present day pCO2 levels. Many studies have shown the adverse effects on scleractinian calcification when exposed to elevated pCO2 levels, however, in these studies, corals have ...

Features of ovarian cancer in Lynch syndrome (Review).

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Nakamura, Kanako; Banno, Kouji; Yanokura, Megumi; Iida, Miho; Adachi, Masataka; Masuda, Kenta; Ueki, Arisa; Kobayashi, Yusuke; Nomura, Hiroyuki; Hirasawa, Akira; Tominaga, Eiichiro; Aoki, Daisuke

2014-11-01

Lynch syndrome is a hereditary ovarian cancer with a prevalence of 0.9-2.7%. Lynch syndrome accounts for 10-15% of hereditary ovarian cancers, while hereditary breast and ovarian cancer syndrome accounts for 65-75% of these cancers. The lifetime risk for ovarian cancer in families with Lynch syndrome is ~8%, which is lower than colorectal and endometrial cancers, and ovarian cancer is not listed in the Amsterdam Criteria II. More than half of sporadic ovarian cancers are diagnosed in stage III or IV, but ≥80% of ovarian cancers in Lynch syndrome are diagnosed in stage I or II. Ovarian cancers in Lynch syndrome mostly have non-serous histology and different properties from those of sporadic ovarian cancers. A screening method for ovarian cancers in Lynch syndrome has yet to be established and clinical studies of prophylactic administration of oral contraceptives are not available. However, molecular profiles at the genetic level indicate that ovarian cancer in Lynch syndrome has a more favorable prognosis than sporadic ovarian cancer. Inhibitors of the phosphatidylinositol 3-kinase/mammalian target of the rapamycin pathway and anti-epidermal growth factor antibodies may have efficacy for the disease. To the best of our knowledge, this is the first review focusing on ovarian cancer in Lynch syndrome.

Global high-resolution monthly pCO2 climatology for the coastal ocean derived from neural network interpolation

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G. G. Laruelle

2017-10-01

Full Text Available In spite of the recent strong increase in the number of measurements of the partial pressure of CO2 in the surface ocean (pCO2, the air–sea CO2 balance of the continental shelf seas remains poorly quantified. This is a consequence of these regions remaining strongly under-sampled in both time and space and of surface pCO2 exhibiting much higher temporal and spatial variability in these regions compared to the open ocean. Here, we use a modified version of a two-step artificial neural network method (SOM-FFN; Landschützer et al., 2013 to interpolate the pCO2 data along the continental margins with a spatial resolution of 0.25° and with monthly resolution from 1998 to 2015. The most important modifications compared to the original SOM-FFN method are (i the much higher spatial resolution and (ii the inclusion of sea ice and wind speed as predictors of pCO2. The SOM-FFN is first trained with pCO2 measurements extracted from the SOCATv4 database. Then, the validity of our interpolation, in both space and time, is assessed by comparing the generated pCO2 field with independent data extracted from the LDVEO2015 database. The new coastal pCO2 product confirms a previously suggested general meridional trend of the annual mean pCO2 in all the continental shelves with high values in the tropics and dropping to values beneath those of the atmosphere at higher latitudes. The monthly resolution of our data product permits us to reveal significant differences in the seasonality of pCO2 across the ocean basins. The shelves of the western and northern Pacific, as well as the shelves in the temperate northern Atlantic, display particularly pronounced seasonal variations in pCO2,  while the shelves in the southeastern Atlantic and in the southern Pacific reveal a much smaller seasonality. The calculation of temperature normalized pCO2 for several latitudes in different oceanic basins confirms that the seasonality in shelf pCO2 cannot solely be explained by

Epigenetically Aberrant Stroma in MDS Propagates Disease via Wnt/β-Catenin Activation.

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Bhagat, Tushar D; Chen, Si; Bartenstein, Matthias; Barlowe, A Trevor; Von Ahrens, Dagny; Choudhary, Gaurav S; Tivnan, Patrick; Amin, Elianna; Marcondes, A Mario; Sanders, Mathijs A; Hoogenboezem, Remco M; Kambhampati, Suman; Ramachandra, Nandini; Mantzaris, Iaonnis; Sukrithan, Vineeth; Laurence, Remi; Lopez, Robert; Bhagat, Prafullla; Giricz, Orsi; Sohal, Davendra; Wickrema, Amittha; Yeung, Cecilia; Gritsman, Kira; Aplan, Peter; Hochedlinger, Konrad; Yu, Yiting; Pradhan, Kith; Zhang, Jinghang; Greally, John M; Mukherjee, Siddhartha; Pellagatti, Andrea; Boultwood, Jacqueline; Will, Britta; Steidl, Ulrich; Raaijmakers, Marc H G P; Deeg, H Joachim; Kharas, Michael G; Verma, Amit

2017-09-15

The bone marrow microenvironment influences malignant hematopoiesis, but how it promotes leukemogenesis has not been elucidated. In addition, the role of the bone marrow stroma in regulating clinical responses to DNA methyltransferase inhibitors (DNMTi) is also poorly understood. In this study, we conducted a DNA methylome analysis of bone marrow-derived stromal cells from myelodysplastic syndrome (MDS) patients and observed widespread aberrant cytosine hypermethylation occurring preferentially outside CpG islands. Stroma derived from 5-azacytidine-treated patients lacked aberrant methylation and DNMTi treatment of primary MDS stroma enhanced its ability to support erythroid differentiation. An integrative expression analysis revealed that the WNT pathway antagonist FRZB was aberrantly hypermethylated and underexpressed in MDS stroma. This result was confirmed in an independent set of sorted, primary MDS-derived mesenchymal cells. We documented a WNT/β-catenin activation signature in CD34 + cells from advanced cases of MDS, where it associated with adverse prognosis. Constitutive activation of β-catenin in hematopoietic cells yielded lethal myeloid disease in a NUP98-HOXD13 mouse model of MDS, confirming its role in disease progression. Our results define novel epigenetic changes in the bone marrow microenvironment, which lead to β-catenin activation and disease progression of MDS. Cancer Res; 77(18); 4846-57. ©2017 AACR . ©2017 American Association for Cancer Research.

The Functional Role of Reactive Stroma in Benign Prostatic Hyperplasia

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Schauer, Isaiah G.; Rowley, David R.

2011-01-01

The human prostate gland is one of the only internal organs that continue to enlarge throughout adulthood. The specific mechanisms that regulate this growth, as well as the pathological changes leading to the phenotype observed in the disease benign prostatic hyperplasia (BPH), are essentially unknown. Recent studies and their associated findings have made clear that many complex alterations occur, involving persistent and chronic inflammation, circulating hormonal level deregulation, and aberrant wound repair processes. BPH has been etiologically characterized as a progressive, albeit discontinuous, hyperplasia of both the glandular epithelial and stromal cell compartments coordinately yielding an expansion of the prostate gland and clinical symptoms. Interestingly, the inflammatory and repair responses observed in BPH are also key components of general wound repair in post-natal tissues. These responses include altered expression of chemokines, cytokines, matrix remodeling factors, chronic inflammatory processes, altered immune surveillance and recognition, as well as the formation of a prototypical ‘reactive’ stroma which is similar to that observed across various fibroplasias and malignancies of a variety of tissue sites. Stromal tissue, both embryonic mesenchyme, and adult reactive stroma myofibroblasts, has been shown to exert potent and functional regulatory control over epithelial proliferation and differentiation as well as immunoresponsive modulation. Thus, the functional biology of a reactive stroma, within the context of an adult disease typified by epithelial and stromal aberrant hyperplasia, is critical to understand within the context of prostate disease and beyond. The mechanisms that regulate reactive stroma biology in BPH represent targets of opportunity for new therapeutic approaches that may extend to other tissue contexts. Accordingly, this review seeks to address the dissection of important factors, signaling pathways, genes, and other

21 CFR 862.1120 - Blood gases (PCO2, PO2) and blood pH test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Blood gases (PCO2, PO2) and blood pH test system... Test Systems § 862.1120 Blood gases (PCO2, PO2) and blood pH test system. (a) Identification. A blood gases (PCO2, PO2) and blood pH test system is a device intended to measure certain gases in blood, serum...

The Complex Interaction of Matrix Metalloproteinases in the Migration of Cancer Cells through Breast Tissue Stroma

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Kerry J. Davies

2014-01-01

Full Text Available Breast cancer mortality is directly linked to metastatic spread. The metastatic cell must exhibit a complex phenotype that includes the capacity to escape from the primary tumour mass, invade the surrounding normal tissue, and penetrate into the circulation before proliferating in the parenchyma of distant organs to produce a metastasis. In the normal breast, cellular structures change cyclically in response to ovarian hormones leading to regulated cell proliferation and apoptosis. Matrix metalloproteinases (MMPs are a family of zinc dependent endopeptidases. Their primary function is degradation of proteins in the extracellular matrix to allow ductal progression through the basement membrane. A complex balance between matrix metalloproteinases and their inhibitors regulate these changes. These proteinases interact with cytokines, growth factors, and tumour necrosis factors to stimulate branching morphologies in normal breast tissues. In breast cancer this process is disrupted facilitating tumour progression and metastasis and inhibiting apoptosis increasing the life of the metastatic cells. This paper highlights the role of matrix metalloproteinases in cell progression through the breast stroma and reviews the complex relationships between the different proteinases and their inhibitors in relation to breast cancer cells as they metastasise.

Appendectomy in the surgical staging of ovarian carcinoma.

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Beşe, T; Kösebay, D; Kaleli, S; Oz, A U; Demirkiran, F; Gezer, A

1996-06-01

Extensive debulking is accepted as the primary method of operative management for carcinoma of the ovary. However, there is no consensus regarding the role of appendectomy in primary surgical treatment. The aim of this study was to assess the role of appendectomy in the surgical staging and cytoreduction of ovarian carcinoma. The study was a retrospective review of 90 primary malignant ovarian carcinoma patients who had an appendectomy in addition to primary cytoreductive surgery. Out of 90 patients, 10 (11.1%) had metastasis to the appendix. The rate of metastasis to the appendix was 11.5% (9/78) in malignant epithelial ovarian carcinomas and 8.3% (1/12) in non-epithelial ovarian tumors. Of the patients with metastasis in the appendix, malignant epithelial ovarian tumors were identified in 90% (serous: 70%; clear cell: 20%), and non-epithelial malignant ovarian tumor were disclosed in 10% (granulosa cell carcinoma). There were no metastases to the appendix in the other histological types. Although metastasis to the appendix was not observed in early stage ovarian carcinomas, it was detected in 21.4% (9/42) of stage III and 50% (1/2) of stage IV. Macroscopic tumor metastasis in the abdomen was noted in all patients with metastasis to the appendix. Appendectomy for stage I and II patients was not beneficial and did not affect final staging. As a result, for the proper staging of ovarian carcinoma there is no advantage to the addition of routine appendectomy to primary cytoreductive surgery in early stage (stage I and II) malignant epithelial ovarian tumors. Appendectomy would contribute to the cytoreduction of advanced stage disease if it is macroscopically involved.

Skeletal mineralogy of coral recruits under high temperature and pCO2

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Foster, T.; Clode, P. L.

2016-03-01

Aragonite, which is the polymorph of CaCO3 precipitated by modern corals during skeletal formation, has a higher solubility than the more stable polymorph calcite. This higher solubility may leave animals that produce aragonitic skeletons more vulnerable to anthropogenic ocean acidification. It is therefore important to determine whether scleractinian corals have the plasticity to adapt and produce calcite in their skeletons in response to changing environmental conditions. Both high pCO2 and lower Mg / Ca ratios in seawater are thought to have driven changes in the skeletal mineralogy of major marine calcifiers in the past ˜ 540 Ma. Experimentally reduced Mg / Ca ratios in ambient seawater have been shown to induce some calcite precipitation in both adult and newly settled modern corals; however, the impact of high pCO2 on the mineralogy of recruits is unknown. Here we determined the skeletal mineralogy of 1-month-old Acropora spicifera coral recruits grown under high temperature (+3 °C) and pCO2 (˜ 900 µatm) conditions, using X-ray diffraction and Raman spectroscopy. We found that newly settled coral recruits produced entirely aragonitic skeletons regardless of the treatment. Our results show that elevated pCO2 alone is unlikely to drive changes in the skeletal mineralogy of young corals. Not having an ability to switch from aragonite to calcite precipitation may leave corals and ultimately coral reef ecosystems more susceptible to predicted ocean acidification. An important area for prospective research would be the investigation of the combined impact of high pCO2 and reduced Mg / Ca ratio on coral skeletal mineralogy.

RKIP Suppresses Breast Cancer Metastasis to the Bone by Regulating Stroma-Associated Genes

International Nuclear Information System (INIS)

Bevilacqua, E.; Frankenberger, C.A.; Rosner, M.R.

2012-01-01

In the past decade cancer research has recognized the importance of tumor stroma interactions for the progression of primary tumors to an aggressive and invasive phenotype and for colonization of new organs in the context of metastasis. The dialogue between tumor cells and the surrounding stroma is a complex and dynamic phenomenon, as many cell types and soluble factors are involved. While the function of many of the players involved in this cross talk have been studied, the regulatory mechanisms and signaling pathways that control their expression have not been investigated in depth. By using a novel, interdisciplinary approach applied to the mechanism of action of the metastasis suppressor, Raf kinase inhibitory protein (RKIP), we identified a signaling pathway that suppresses invasion and metastasis through regulation of stroma-associated genes. Conceptually, the approach we developed uses a master regulator and expression arrays from breast cancer patients to formulate hypotheses based on clinical data. Experimental validation is followed by further bioinformatics analysis to establish the clinical significance of discoveries. Using RKIP as an example we show here that this multi-step approach can be used to identify gene regulatory mechanisms that affect tumor-stroma interactions that in turn influence metastasis to the bone or other organs

Combinatorial effect of non-steroidal anti-inflammatory drugs and NF-κB inhibitors in ovarian cancer therapy.

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Luiz F Zerbini

Full Text Available Several epidemiological studies have correlated the use of non-steroidal anti-inflammatory drugs (NSAID with reduced risk of ovarian cancer, the most lethal gynecological cancer, diagnosed usually in late stages of the disease. We have previously established that the pro-apoptotic cytokine melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24 is a crucial mediator of NSAID-induced apoptosis in prostate, breast, renal and stomach cancer cells. In this report we evaluated various structurally different NSAIDs for their efficacies to induce apoptosis and mda-7/IL-24 expression in ovarian cancer cells. While several NSAIDs induced apoptosis, Sulindac Sulfide and Diclofenac most potently induced apoptosis and reduced tumor growth. A combination of these agents results in a synergistic effect. Furthermore, mda-7/IL-24 induction by NSAIDs is essential for programmed cell death, since inhibition of mda-7/IL-24 by small interfering RNA abrogates apoptosis. mda-7/IL-24 activation leads to upregulation of growth arrest and DNA damage inducible (GADD 45 α and γ and JNK activation. The NF-κB family of transcription factors has been implicated in ovarian cancer development. We previously established NF-κB/IκB signaling as an essential step for cell survival in cancer cells and hypothesized that targeting NF-κB could potentiate NSAID-mediated apoptosis induction in ovarian cancer cells. Indeed, combining NSAID treatment with NF-κB inhibitors led to enhanced apoptosis induction. Our results indicate that inhibition of NF-κB in combination with activation of mda-7/IL-24 expression may lead to a new combinatorial therapy for ovarian cancer.

ATF4-Induced Metabolic Reprograming Is a Synthetic Vulnerability of the p62-Deficient Tumor Stroma.

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Linares, Juan F; Cordes, Thekla; Duran, Angeles; Reina-Campos, Miguel; Valencia, Tania; Ahn, Christopher S; Castilla, Elias A; Moscat, Jorge; Metallo, Christian M; Diaz-Meco, Maria T

2017-12-05

Tumors undergo nutrient stress and need to reprogram their metabolism to survive. The stroma may play a critical role in this process by providing nutrients to support the epithelial compartment of the tumor. Here we show that p62 deficiency in stromal fibroblasts promotes resistance to glutamine deprivation by the direct control of ATF4 stability through its p62-mediated polyubiquitination. ATF4 upregulation by p62 deficiency in the stroma activates glucose carbon flux through a pyruvate carboxylase-asparagine synthase cascade that results in asparagine generation as a source of nitrogen for stroma and tumor epithelial proliferation. Thus, p62 directly targets nuclear transcription factors to control metabolic reprogramming in the microenvironment and repress tumorigenesis, and identifies ATF4 as a synthetic vulnerability in p62-deficient tumor stroma. Copyright © 2017 Elsevier Inc. All rights reserved.

Mismatch repair and treatment resistance in ovarian cancer

International Nuclear Information System (INIS)

Helleman, Jozien; Staveren, Iris L van; Dinjens, Winand NM; Kuijk, Patricia F van; Ritstier, Kirsten; Ewing, Patricia C; Burg, Maria EL van der; Stoter, Gerrit; Berns, Els MJJ

2006-01-01

The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR) inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. We determined, microsatellite instability (MSI) as a marker for MMR inactivation (analysis of BAT25 and BAT26), MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA) and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR) in 75 ovarian carcinomas and eight ovarian cancer cell lines MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation), SKOV3 (no MLH1 mRNA expression) and 2774 (no altered expression of MMR genes). Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response). The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation

Mismatch repair and treatment resistance in ovarian cancer

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Helleman, Jozien; Staveren, Iris L van [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Dinjens, Winand NM [Department of Pathology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Kuijk, Patricia F van; Ritstier, Kirsten [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Ewing, Patricia C [Department of Pathology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Burg, Maria EL van der; Stoter, Gerrit [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Berns, Els MJJ [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Erasmus MC, Department of Medical Oncology, Josephine Nefkens Institute, Room Be424, P.O. Box 1738, 3000 DR (Netherlands)

2006-07-31

The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR) inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. We determined, microsatellite instability (MSI) as a marker for MMR inactivation (analysis of BAT25 and BAT26), MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA) and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR) in 75 ovarian carcinomas and eight ovarian cancer cell lines MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation), SKOV3 (no MLH1 mRNA expression) and 2774 (no altered expression of MMR genes). Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response). The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation.

Mismatch repair and treatment resistance in ovarian cancer

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van der Burg Maria EL

2006-07-01

Full Text Available Abstract Background The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. Methods We determined, microsatellite instability (MSI as a marker for MMR inactivation (analysis of BAT25 and BAT26, MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR in 75 ovarian carcinomas and eight ovarian cancer cell lines Results MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation, SKOV3 (no MLH1 mRNA expression and 2774 (no altered expression of MMR genes. Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response. The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. Conclusion No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation.

Effect of increased pCO2 level on early shell development in great scallop (Pecten maximus Lamarck larvae

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S. Andersen

2013-10-01

Full Text Available As a result of high anthropogenic CO2 emissions, the concentration of CO2 in the oceans has increased, causing a decrease in pH, known as ocean acidification (OA. Numerous studies have shown negative effects on marine invertebrates, and also that the early life stages are the most sensitive to OA. We studied the effects of OA on embryos and unfed larvae of the great scallop (Pecten maximus Lamarck, at pCO2 levels of 469 (ambient, 807, 1164, and 1599 μatm until seven days after fertilization. To our knowledge, this is the first study on OA effects on larvae of this species. A drop in pCO2 level the first 12 h was observed in the elevated pCO2 groups due to a discontinuation in water flow to avoid escape of embryos. When the flow was restarted, pCO2 level stabilized and was significantly different between all groups. OA affected both survival and shell growth negatively after seven days. Survival was reduced from 45% in the ambient group to 12% in the highest pCO2 group. Shell length and height were reduced by 8 and 15%, respectively, when pCO2 increased from ambient to 1599 μatm. Development of normal hinges was negatively affected by elevated pCO2 levels in both trochophore larvae after two days and veliger larvae after seven days. After seven days, deformities in the shell hinge were more connected to elevated pCO2 levels than deformities in the shell edge. Embryos stained with calcein showed fluorescence in the newly formed shell area, indicating calcification of the shell at the early trochophore stage between one and two days after fertilization. Our results show that P. maximus embryos and early larvae may be negatively affected by elevated pCO2 levels within the range of what is projected towards year 2250, although the initial drop in pCO2 level may have overestimated the effect of the highest pCO2 levels. Future work should focus on long-term effects on this species from hatching, throughout the larval stages, and further into the

Skeletal mineralogy of coral recruits under high temperature and pCO2

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T. Foster

2016-03-01

Our results show that elevated pCO2 alone is unlikely to drive changes in the skeletal mineralogy of young corals. Not having an ability to switch from aragonite to calcite precipitation may leave corals and ultimately coral reef ecosystems more susceptible to predicted ocean acidification. An important area for prospective research would be the investigation of the combined impact of high pCO2 and reduced Mg ∕ Ca ratio on coral skeletal mineralogy.

A Stratification Boomerang: Nonlinear Dependence of Deep Southern Ocean Ventilation on PCO2

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Galbraith, E. D.; Merlis, T. M.

2014-12-01

Strong correlations between atmospheric CO2, Antarctic temperatures, and marine proxy records have hinted that ventilation of the deep Southern Ocean may have played a central role in the variations of CO2 over glacial-interglacial cycles. One proposition is that, in general, the Southern Ocean ventilates the deep more strongly under higher CO2, due to a change in winds and/or the dominance of thermal stratification in a warm ocean, which weakens ocean biological carbon storage. Here, we explore this idea with a suite of multi-millennial simulations using the GFDL CM2Mc global coupled model. The results are, indeed, consistent with increasing ventilation of the Southern Ocean as pCO2 increases above modern. However, they reveal a surprising twist under low pCO2: increased salinity of the Southern Ocean, due in part to weakening atmospheric moisture transport, actually increases ventilation rate of the deep ocean under low pCO2 as well. This implies that a nadir of Southern Ocean ventilation occurs at intermediate pCO2, which the model estimates as being close to that of the present-day. This is at odds with the interpretation that weak ventilation of the deep Southern Ocean was the unifying coupled mechanism for the glacial pCO2 cycles. Rather, it suggests that factors other than the ventilation rate of the deep Southern Ocean, such as iron fertilization, ecosystem changes, water mass distributions, and sea ice cover, were key players in the glacial-interglacial CO2 changes.

Effects of carbon dioxide level (PCO2) on the fibrinolytic activity (FA) of pulmonary artery endothelial cells (PAEC)

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Langleben, D.; Moroz, L.A.; Danes, D.

1990-01-01

Recovery from pulmonary thromboembolism depends on the rapidity and completeness of clot lysis. This involves endogenous fibrinolytic mechanisms, particularly the balance between plasminogen activators and inhibitors produced by endothelial cells. Hypocapnia is common in pulmonary embolism, however it is not known if endothelial fibrinolytic function is affected by PCO 2 . The authors therefore measured the FA in medium (MCDB-131, 0.5% albumin) conditioned for 20 hours in-vitro by exposure to confluent cultures of bovine proximal PAEC. During conditioning, cells were exposed to 5% CO 2 in air (PCO 2 - 36-40mm Hg, CONTROL), or various PCO 2 levels (30-55 mmHg, in air). FA of conditioned medium was determined by 125 I-fibrin solid phase assay, with addition of plasminogen (10 ug/ml). With PCO 2 levels ≤ 35 mmHg, FA in the conditioned medium was 5 to 18% higher than CONTROL FA. When PCO 2 was ≥ 45 mmHg, FA decreased 5 to 60% as compared to CONTROL FA. There was a significant negative linear relationship between PCO 2 and FA. Thus, PCO 2 level can affect PAEC mediated plasminogen activation. This finding may be relevant to in-vivo clearance of clots from pulmonary arteries

Sensory Qualities of Oysters Unaltered by a Short Exposure to Combined Elevated pCO2 and Temperature

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Anaëlle J. Lemasson

2017-11-01

Full Text Available Reliance on the marine environment for the provision of food is ever-increasing, but future climate change threatens production. Despite this concern, the impact on seafood quality and success of the seafood industry is unknown. Using a short-term study, we test these concerns using a major aquaculture species—Crassostrea gigas—exposing them to three acidification and warming scenarios: (1 ambient pCO2 (~400 ppm & control temperature (15°C, (2 ambient pCO2 (~400 ppm & elevated temperature (20°C, (3 elevated pCO2 (~1,000 ppm & elevated temperature (20°C. Oyster quality was assessed by scoring appearance, aroma, taste, and overall acceptability. A panel of five experts was asked to score nine oysters—three from each treatment—according to agreed criteria. Results indicate that these levels of acidification and warming did not significantly alter the sensory properties of C. gigas, and notably the overall acceptability remained unchanged. Non-statistically supported trends suggest that several sensory attributes—opacity, mouthfeel, aspect of meat, shininess, meat resistance, meat texture, and creaminess—may improve under acidification and warming scenarios. These findings can be considered positive for the future of the aquaculture and food sectors. Crassostrea gigas therefore is expected to remain a key species for food security that is resilient to climate change, whilst retaining its valuable attributes.

Ovarian size and response to laparoscopic ovarian electro-cauterization in polycystic ovarian disease.

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Alborzi, S; Khodaee, R; Parsanejad, M E

2001-09-01

To evaluate endocrine and ovulatory changes in polycystic ovarian disease (PCOD) in relation to patients' ovarian size. Three hundred and seventy-one women with clomiphene citrate-resistant PCOD underwent laparoscopic ovarian cauterization [type I or typical with ovarian volume >8 cm(3) or cross-sectional area >10 cm(2) (n=211), type II with normal size ovary (n=160)]. Serum levels of LH, FSH, DHEAS, PRL, and T before and 10 days after ovarian cautery, spontaneous and induced ovulation and pregnancy rates were compared. Both groups responded to therapy in a similar manner, with a marked decrease in LH, FSH, DHEAS and T levels, with ovulation rates in type I 90.99%, type II 88.75% and pregnancy rates, 73.45% and 71.25%, respectively, with no statistical differences. Hormonal changes, ovulation and pregnancy rates were similar in the two types of PCOD, therefore it can be concluded that ovarian size is not a prognostic factor for response of PCOD patients to laparoscopic ovarian electro-cauterization.

Evolutionary Dynamics of Tumor-Stroma Interactions in Multiple Myeloma.

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Javad Salimi Sartakhti

Full Text Available Cancer cells and stromal cells cooperate by exchanging diffusible factors that sustain tumor growth, a form of frequency-dependent selection that can be studied in the framework of evolutionary game theory. In the case of multiple myeloma, three types of cells (malignant plasma cells, osteoblasts and osteoclasts exchange growth factors with different effects, and tumor-stroma interactions have been analysed using a model of cooperation with pairwise interactions. Here we show that a model in which growth factors have autocrine and paracrine effects on multiple cells, a more realistic assumption for tumor-stroma interactions, leads to different results, with implications for disease progression and treatment. In particular, the model reveals that reducing the number of malignant plasma cells below a critical threshold can lead to their extinction and thus to restore a healthy balance between osteoclast and osteoblast, a result in line with current therapies against multiple myeloma.

Distribution of the partial pressure of CO2 in surface water (pCO2w) between Japan and the Hawaiian Islands: pCO2w-SST relationship in the winter and summer

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Inoue, Hisayuki Y.; Ishii, Masao; Matsueda, Hidekazu; Kawano, Takeshi; Murata, Akihiko; Takasugi, Yoshio

2003-01-01

On the basis of measurements of the partial pressure of carbon dioxide in surface seawater (pCO 2 w) between Japan and the Hawaiian Islands in winter and summer, we examined the relationship between pCO 2 w and the sea surface temperature (SST) in the North Pacific Subtropical Gyre (NPSG). In winter, pCO 2 w correlated well with the SST (0.14-0.24%/deg C), suggesting a monotonous change in the carbonate system. However, in summer, five different pCO 2 w-SST relationships were found in the NPSG (including the Kuroshio Extension) due to changes in the relative contribution of ocean dynamics (upwelling, vertical mixing and advection), biological activity in the absence (very low level) of macro-nutrients and thermodynamics. The increase in pCO 2 w corresponding to a unit increase in the SST from January to July was low (<2.5%/deg C) west (leeward side) of the Hawaiian Islands (19-22 deg N, 158-168 deg W) and in the Kuroshio Extension (33-35 deg N, 140-165deg E), and high (3%/deg C) south of the Kuroshio Extension (25-30 deg N, 180-165 deg W) and the Hawaiian Islands (15-19 deg N, 157-162 deg W). This suggested that the drawdown of dissolved inorganic carbon was affected by the enhanced biological activity due to upwelling events associated with eddies and/or the transport of dissolved nutrients from gyre edges to the interior

Development of an innovative 3D cell culture system to study tumour--stroma interactions in non-small cell lung cancer cells.

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Arno Amann

Full Text Available INTRODUCTION: We describe a novel 3D co-culture model using non-small cell lung cancer (NSCLC cell lines in combination with lung fibroblasts. This model allows the investigation of tumour-stroma interactions and addresses the importance of having a more in vivo like cell culture model. METHODS: Automation-compatible multi-well hanging drop microtiter plates were used for the production of 3D mono- and co-cultures. In these hanging drops the two NSCLC cell lines A549 and Colo699 were cultivated either alone or co-cultured with lung fibroblasts. The viability of tumour spheroids was confirmed after five and ten days by using Annexin V/Propidium Iodide staining for flow-cytometry. Tumour fibroblast spheroid formation was characterized by scanning electron microscope (SEM, semi-thin sections, fluorescence microscope and immunohistochemistry (IHC. In addition to conventional histology, protein expression of E-Cadherin, vimentin, Ki67, fibronectin, cytokeratin 7 and α-smooth muscle actin (α-SMA was investigated by IHC. RESULTS: Lower viability was observed in A549 monocultures compared to co-cultures, whereas Colo699 monocultures showed better viability compared to co-cultures. Ki67 expression varied significantly between mono- and co-cultures in both tumour cell lines. An increase of vimentin and decreased E-Cadherin expression could be detected during the course of the cultivation suggesting a transition to a more mesenchymal phenotype. Furthermore, the fibroblast cell line showed an expression of α-SMA only in co-culture with the cancer cell line A549, thereby indicating a mesenchymal to mesenchymal shift to an even more myofibroblast phenotype. CONCLUSION: We demonstrate that our method is a promising tool for the generation of tumour spheroid co-cultures. Furthermore, these spheroids allow the investigation of tumour-stroma interactions and a better reflection of in vivo conditions of cancer cells in their microenvironment. Our method holds

The effect of resveratrol on oxidative stress in the liver and serum of a rat model of polycystic ovary syndrome: An experimental study

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Mahnaz Ghowsi

2018-03-01

Full Text Available Background: Studies of oxidative status in polycystic ovarian syndrome (PCOS patients are limited with inconsistent results. The effects of resveratrol as a natural antioxidant on oxidative status in PCOS aren’t clear. Objective: This study evaluated effects of resveratrol on oxidative stress in the liver and serum of the PCOS rats. Materials and Methods: Fifteen female Wistar rats (3 wk old were divided into 3 groups (n=5/each e: Control group, PCO-Control group, and PCO-Resveratrol group. For induction of polycystic ovary phenotype, testosterone enanthate 10 mg/kg was injected for 35 days subcutaneously. Then, resveratrol 10 mg/kg was injected intraperitoneally for 28 days to rats of the PCO-Resveratrol group. Ovarian sections were stained with hematoxylin/eosin. The serum glucose and insulin and the levels of malondialdehyde (MDA and total antioxidant capacity (TAC in serum and liver were measured. Results: Control animals showed normal ovarian morphology and PCO-Control animals exhibited cystic follicles. There were no significant differences in liver TAC between groups. The serum MDA (p=0.034, and homeostatic model assessment insulin resistance (HOMA-IR (p=0.014 levels in PCO-Control rats were higher than the controls. The liver MDA in PCO-Control rats was more than that of controls (p=0.001. The HOMA-IR (p=0.008 and serum MDA (p=0.006 levels in PCO-Control rats were more than those of PCO-Resveratrol rats (p=0.008. In PCO-Resveratrol group, serum TAC was higher than that of PCO-Control group (p=0.022 and liver MDA was more than controls (p=0.01. Conclusion: Results indicated that the induction of PCOS in rats increased lipid peroxidation and insulin resistance and resveratrol improved these complications.

Ovarian Stem Cell Nests in Reproduction and Ovarian Aging.

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Ye, Haifeng; Zheng, Tuochen; Li, Wei; Li, Xiaoyan; Fu, Xinxin; Huang, Yaoqi; Hu, Chuan; Li, Jia; Huang, Jian; Liu, Zhengyv; Zheng, Liping; Zheng, Yuehui

2017-01-01

The fixed primordial follicles pool theory, which monopolized reproductive medicine for more than one hundred years, has been broken by the discovery, successful isolation and establishment of ovarian stem cells. It has brought more hope than ever of increasing the size of primordial follicle pool, improving ovarian function and delaying ovarian consenescence. Traditional view holds that stem cell aging contributes to the senility of body and organs. However, in the process of ovarian aging, the main factor leading to the decline of the reproductive function is the aging and degradation of ovarian stem cell nests, rather than the senescence of ovarian germ cells themselves. Recent studies have found that the immune system and circulatory system are involved in the formation of ovarian germline stem cell niches, as well as regulating the proliferation and differentiation of ovarian germline stem cells through cellular and hormonal signals. Therefore, we can improve ovarian function and delay ovarian aging by improving the immune system and circulatory system, which will provide an updated program for the treatment of premature ovarian failure (POF) and infertility. © 2017 The Author(s). Published by S. Karger AG, Basel.

Coupling of heterotrophic bacteria to phytoplankton bloom development at different pCO2 levels: a mesocosm study

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R. Thyrhaug

2008-07-01

Full Text Available The predicted rise in anthropogenic CO2 emissions will increase CO2 concentrations and decrease seawater pH in the upper ocean. Recent studies have revealed effects of pCO2 induced changes in seawater chemistry on a variety of marine life forms, in particular calcifying organisms. To test whether the predicted increase in pCO2 will directly or indirectly (via changes in phytoplankton dynamics affect abundance, activities, and community composition of heterotrophic bacteria during phytoplankton bloom development, we have aerated mesocosms with CO2 to obtain triplicates with three different partial pressures of CO2 (pCO2: 350 μatm (1×CO2, 700 μatm (2×CO2 and 1050 μatm (3×CO2. The development of a phytoplankton bloom was initiated by the addition of nitrate and phosphate. In accordance to an elevated carbon to nitrogen drawdown at increasing pCO2, bacterial production (BPP of free-living and attached bacteria as well as cell-specific BPP (csBPP of attached bacteria were related to the C:N ratio of suspended matter. These relationships significantly differed among treatments. However, bacterial abundance and activities were not statistically different among treatments. Solely community structure of free-living bacteria changed with pCO2 whereas that of attached bacteria seemed to be independent of pCO2 but tightly coupled to phytoplankton bloom development. Our findings imply that changes in pCO2, although reflected by changes in community structure of free-living bacteria, do not directly affect bacterial activity. Furthermore, bacterial activity and dynamics of heterotrophic bacteria, especially of attached bacteria, were tightly correlated to phytoplankton development and, hence, may also potentially depend on changes in pCO2.

Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.

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Tothill, Richard W; Tinker, Anna V; George, Joshy; Brown, Robert; Fox, Stephen B; Lade, Stephen; Johnson, Daryl S; Trivett, Melanie K; Etemadmoghadam, Dariush; Locandro, Bianca; Traficante, Nadia; Fereday, Sian; Hung, Jillian A; Chiew, Yoke-Eng; Haviv, Izhak; Gertig, Dorota; DeFazio, Anna; Bowtell, David D L

2008-08-15

The study aim to identify novel molecular subtypes of ovarian cancer by gene expression profiling with linkage to clinical and pathologic features. Microarray gene expression profiling was done on 285 serous and endometrioid tumors of the ovary, peritoneum, and fallopian tube. K-means clustering was applied to identify robust molecular subtypes. Statistical analysis identified differentially expressed genes, pathways, and gene ontologies. Laser capture microdissection, pathology review, and immunohistochemistry validated the array-based findings. Patient survival within k-means groups was evaluated using Cox proportional hazards models. Class prediction validated k-means groups in an independent dataset. A semisupervised survival analysis of the array data was used to compare against unsupervised clustering results. Optimal clustering of array data identified six molecular subtypes. Two subtypes represented predominantly serous low malignant potential and low-grade endometrioid subtypes, respectively. The remaining four subtypes represented higher grade and advanced stage cancers of serous and endometrioid morphology. A novel subtype of high-grade serous cancers reflected a mesenchymal cell type, characterized by overexpression of N-cadherin and P-cadherin and low expression of differentiation markers, including CA125 and MUC1. A poor prognosis subtype was defined by a reactive stroma gene expression signature, correlating with extensive desmoplasia in such samples. A similar poor prognosis signature could be found using a semisupervised analysis. Each subtype displayed distinct levels and patterns of immune cell infiltration. Class prediction identified similar subtypes in an independent ovarian dataset with similar prognostic trends. Gene expression profiling identified molecular subtypes of ovarian cancer of biological and clinical importance.

Structural alterations of the mucosa stroma in the Barrett's esophagus metaplasia-dysplasia-adenocarcinoma sequence.

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Bobryshev, Yuri V; Killingsworth, Murray C; Lord, Reginald V N

2012-09-01

Accumulating evidence suggests that the extracellular matrix play important roles in intercellular communications and contribute to the development of a number of diseases, including diseases of the gastrointestinal tract. The present study examined the structural characteristics and alterations of the extracellular matrix of the mucosa stroma in the Barrett's esophagus metaplasia-dysplasia-adenocarcinoma sequence. A total of 41 esophageal tissue specimens (15 esophageal adenocarcinoma, 10 Barrett's esophagus intestinal metaplasia, seven dysplasia and nine normal esophagus) were studied. The present study used transmission electron microscopy and computerized quantitative electron-microscopic analysis in order to investigate the characteristics of the extracellular matrix of the mucosa. The study revealed that marked structural alterations of the mucosa stroma, relating to changes in the distribution and appearance of collagen fibers as well as to changes in numbers of matrix microvesicles, occur in Barrett's esophagus and esophageal adenocarcinoma. It was found that there were 3.1 times more microvesicles in the stroma in Barrett's esophagus than in the stroma of the normal esophagus (P<0.0001) and that there were 5.8 times more microvesicles in esophageal adenocarcinoma than in the normal esophagus (P<0.0001). There were 1.9 times more microvesicles in esophageal adenocarcinoma than in Barrett's esophagus (P=0.0043). The study demonstrates distinctive alterations of the mucosa stroma extracellular matrix in the metaplasia-dysplasia-adenocarcinoma sequence. The findings suggest that the redistribution of collagen fibers and increases in numbers of matrix microvesicles may play roles in the formation of specialized intestinal metaplasia and the development of adenocarcinoma. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

An autonomous drifting buoy system for long term pCO2 observation

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Nakano, Y.; Fujiki, T.; Wakita, M.; Azetsu-Scott, K.; Watanabe, S.

2009-04-01

Many studies have been carried out around the world to understand what happens to carbon dioxide (CO2) once it is emitted into the atmosphere, and how it relates to long-term climate change. However, the sea surface pCO2 observations on volunteer observation ships and research vessels concentrated in the North Atlantic and North Pacific. To assess the spatial and temporal variations of surface pCO2 in the global ocean, new automated pCO2 sensor which can be used in platform systems such as buoys or moorings is strongly desired. We have been developing the small drifting buoy system (diameter 250-340 mm, length 470 mm, weight 15 kg) for pCO2 measurement, with the support of the Japan EOS Promotion Program (JEPP), the Ministry of Education, Culture, Sports, Science and Technology (MEXT). The objective is to provide simplified, automated measurements of pCO2 over all the world's oceans, an essential factor in understanding how the ocean responds to climate change. The measurement principle for the pCO2 sensor is based on spectrophotometry (e.g. Lefèvre et al., 1993; Degrandpre et al., 1995). The CO2 in the surrounding seawater equilibrates with the indicator solution across the gas permeable membranes. The equilibration process causes a change of pH in the indicator solution, which results in the change of optical absorbance. The pCO2 is calculated from the optical absorbance of the pH indicator solution equilibrated with CO2 in seawater through a gas permeable membrane. In our analytical system, we used an amorphous fluoropolymer tubing form of AF-2400 by DuPontTM for the gas permeable membrane due to its high gas permeability coefficients. The measurement system of the sensor consisted mainly of a LED light source, optical fibers, a CCD detector, and a downsized PC. The measured data were transmitted to the laboratory by satellite communication (Argos system). In the laboratory experiment, we obtained a high response time (less than 2 minutes) and a precision

Acute respiratory failure following ovarian hyperstimulation syndrome

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Antonello Nicolini

2013-03-01

Full Text Available Ovarian hyperstimulation syndrome is a serious and potentially life-threatening physiological complication that may be encountered in patients who undergo controlled ovarian hyperstimulation cycles. The syndrome is typically associated with regimes of exogenous gonadotropins, but it can be seen, albeit rarely, when clomiphene is administered during the induction phase. Although this syndrome is widely described in scientific literature and is well known by obstetricians, the knowledge of this pathological and potentially life-threatening condition is generally less than satisfactory among physicians. The dramatic increase in therapeutic strategies to treat infertility has pushed this condition into the realm of acute care therapy. The potential complications of this syndrome, including pulmonary involvement, should be considered and identified so as to allow a more appropriate diagnosis and management. We describe a case of a woman with an extremely severe (Stage 6 ovarian hyperstimulation syndrome who presented ascites, bilateral pleural effusion and severe respiratory failure treated with non-invasive ventilation. The patient was admitted to the intensive care unit because of severe respiratory failure, ascites, and bilateral pleural effusion due to ovarian hyperstimulation syndrome. Treatment included non-invasive ventilation and three thoracentesis procedures, plus the administration of albumin, colloid solutions and high-dose furosemid. Severe form of ovarian hyperstimulation syndrome is observed in 0.5-5% of the women treated, and intensive care may be required for management of thromboembolic complications, renal failure and severe respiratory failure. Pulmonary intensive care may involve thoracentesis, oxygen supplementation and, in more severe cases, assisted ventilation. To our knowledge, there have been only two studies in English language medical literature that describe severe respiratory failure treated with non

Polymorphism in the GALNT1 gene and epithelial ovarian cancer in non-Hispanic white women: the Ovarian Cancer Association Consortium

DEFF Research Database (Denmark)

Phelan, Catherine M; Tsai, Ya-Yu; Goode, Ellen L

2010-01-01

Aberrant glycosylation is a well-described hallmark of cancer. In a previous ovarian cancer case control study that examined polymorphisms in 26 glycosylation-associated genes, we found strong statistical evidence (P = 0.00017) that women who inherited two copies of a single-nucleotide polymorphism...... in the UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase, GALNT1, had decreased ovarian cancer risk. The current study attempted to replicate this observation. The GALNT1 single-nucleotide polymorphism rs17647532 was genotyped in 6,965 cases and 8,377 controls from 14 studies forming...... the Ovarian Cancer Association Consortium. The fixed effects estimate per rs17647532 allele was null (odds ratio, 0.99; 95% confidence interval, 0.92-1.07). When a recessive model was fit, the results were unchanged. Test for heterogeneity of the odds ratios revealed consistency across the 14 replication...

CD117 expression in fibroblasts-like stromal cells indicates unfavorable clinical outcomes in ovarian carcinoma patients.

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Ruixia Huang

Full Text Available The stem cell factor (SCF receptor CD117 (c-kit, is widely used for identification of hematopoietic stem cells and cancer stem cells. Moreover, CD117 expression in carcinoma cells indicates a poor prognosis in a variety of cancers. However the potential expression in tumor microenvironment and the biological and clinical impact are currently not reported. The expression of CD117 was immunohistochemically evaluated in a serial of 242 epithelial ovarian cancer (EOC cases. Thirty-eight out of 242 cases were CD117 positive in fibroblast-like stromal cells and 22 cases were positive in EOC cells. Four cases were both positive in fibroblast-like stromal cells and EOC cells for CD117. CD117 expression in fibroblast-like stromal cells in ovarian carcinoma was closely linked to advanced FIGO stage, poor differentiation grade and histological subtype (p<0.05, and it was significantly associated with poor overall survival (OS and progression free survival (PFS (Kaplan-Meier analysis; p<0.05, log-rank test. CD117 expression in ovarian carcinoma cells was not associated with these clinicopathological variables. The CD117 positive fibroblast-like stromal cells were all positive for mesenchymal stem/stromal cell (MSC marker CD73 but negative for fibroblast markers fibroblast activation protein (FAP and α smooth muscle actin (α-SMA, indicating that the CD117+/CD73+ fibroblast-like stromal cells are a subtype of mesenchymal stem cells in tumor stroma, although further characterization of these cells are needed. It is concluded herewith that the presence of CD117+/CD73+ fibroblast-like stromal cells in ovarian carcinoma is an unfavorable clinical outcome indication.

Apparent diffusion coefficient correlation with oesophageal tumour stroma and angiogenesis

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Aoyagi, Tomoyoshi; Shuto, Kiyohiko; Okazumi, Shinichi; Hayano, Kohichi; Satoh, Asami; Saitoh, Hiroshige; Shimada, Hideaki; Nabeya, Yoshihiro; Matsubara, Hisahiro [Chiba University, Department of Frontier Surgery, Graduate School of Medicine, Chiba (Japan); Kazama, Toshiki [Chiba University, Department of Radiology, Graduate School of Medicine, Chiba (Japan)

2012-06-15

Because diffusion-weighted imaging (DWI) can predict the prognosis of patients with oesophageal squamous cell carcinoma (ESCC), we hypothesised that apparent diffusion coefficient (ADC) values might be correlated with the collagen content and tumour angiogenesis. The purpose of this study was to determine the correlation between ADC values of ESCC before treatment and oesophageal tumour stroma and angiogenesis. Seventeen patients with ESCC were enrolled. The ADC values were calculated from the DWI score. Seventeen patients who had undergone oesophagectomy were analysed for tumour stroma, vascular endothelial growth factor (VEGF) and CD34. Tissue collagen was stained with azocarmine and aniline blue to quantitatively analyse the extracellular matrix in cancer stroma. Tissues were stained with VEGF and CD34 to analyse the angiogenesis. The ADC values decreased with stromal collagen growth. We found a negative correlation between the tumour ADC and the amount of stromal collagen (r = -0.729, P = 0.001), i.e. the ADC values decreased with growth of VEGF. We also found a negative correlation between the ADC of the tumours and the amount of VEGF (r = 0.538, P = 0.026). Our results indicated that the ADC value may be a novel prognostic factor and contribute to the treatment of oesophageal cancer. circle Magnetic resonance apparent diffusion coefficient values inversely indicate tumour stromal collagen circle There is also negative correlation between ADCs and vascular endothelial growth factor circle ADC values may contribute to the treatment of oesophageal cancer. (orig.)

Apparent diffusion coefficient correlation with oesophageal tumour stroma and angiogenesis

International Nuclear Information System (INIS)

Aoyagi, Tomoyoshi; Shuto, Kiyohiko; Okazumi, Shinichi; Hayano, Kohichi; Satoh, Asami; Saitoh, Hiroshige; Shimada, Hideaki; Nabeya, Yoshihiro; Matsubara, Hisahiro; Kazama, Toshiki

2012-01-01

Because diffusion-weighted imaging (DWI) can predict the prognosis of patients with oesophageal squamous cell carcinoma (ESCC), we hypothesised that apparent diffusion coefficient (ADC) values might be correlated with the collagen content and tumour angiogenesis. The purpose of this study was to determine the correlation between ADC values of ESCC before treatment and oesophageal tumour stroma and angiogenesis. Seventeen patients with ESCC were enrolled. The ADC values were calculated from the DWI score. Seventeen patients who had undergone oesophagectomy were analysed for tumour stroma, vascular endothelial growth factor (VEGF) and CD34. Tissue collagen was stained with azocarmine and aniline blue to quantitatively analyse the extracellular matrix in cancer stroma. Tissues were stained with VEGF and CD34 to analyse the angiogenesis. The ADC values decreased with stromal collagen growth. We found a negative correlation between the tumour ADC and the amount of stromal collagen (r = -0.729, P = 0.001), i.e. the ADC values decreased with growth of VEGF. We also found a negative correlation between the ADC of the tumours and the amount of VEGF (r = 0.538, P = 0.026). Our results indicated that the ADC value may be a novel prognostic factor and contribute to the treatment of oesophageal cancer. circle Magnetic resonance apparent diffusion coefficient values inversely indicate tumour stromal collagen circle There is also negative correlation between ADCs and vascular endothelial growth factor circle ADC values may contribute to the treatment of oesophageal cancer. (orig.)

Estimating temporal and spatial variation of ocean surface pCO2 in the North Pacific using a self-organizing map neural network technique

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S. Nakaoka

2013-09-01

Full Text Available This study uses a neural network technique to produce maps of the partial pressure of oceanic carbon dioxide (pCO2sea in the North Pacific on a 0.25° latitude × 0.25° longitude grid from 2002 to 2008. The pCO2sea distribution was computed using a self-organizing map (SOM originally utilized to map the pCO2sea in the North Atlantic. Four proxy parameters – sea surface temperature (SST, mixed layer depth, chlorophyll a concentration, and sea surface salinity (SSS – are used during the training phase to enable the network to resolve the nonlinear relationships between the pCO2sea distribution and biogeochemistry of the basin. The observed pCO2sea data were obtained from an extensive dataset generated by the volunteer observation ship program operated by the National Institute for Environmental Studies (NIES. The reconstructed pCO2sea values agreed well with the pCO2sea measurements, with the root-mean-square error ranging from 17.6 μatm (for the NIES dataset used in the SOM to 20.2 μatm (for independent dataset. We confirmed that the pCO2sea estimates could be improved by including SSS as one of the training parameters and by taking into account secular increases of pCO2sea that have tracked increases in atmospheric CO2. Estimated pCO2sea values accurately reproduced pCO2sea data at several time series locations in the North Pacific. The distributions of pCO2sea revealed by 7 yr averaged monthly pCO2sea maps were similar to Lamont-Doherty Earth Observatory pCO2sea climatology, allowing, however, for a more detailed analysis of biogeochemical conditions. The distributions of pCO2sea anomalies over the North Pacific during the winter clearly showed regional contrasts between El Niño and La Niña years related to changes of SST and vertical mixing.

A gastrointestinal stromal tumor (GIST masquerading as an ovarian mass

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Beneduce Pasquale

2004-05-01

Full Text Available Abstract Background Malignant gastrointestinal stromal tumors (GIST are rare mesenchymal tumors originating in the wall of the gastrointestinal tract. Myogenic gastrointestinal stromal tumor, a distinctive morphologic variant is characterized by an unusually prominent myxoid stromal background. Case presentation We report a case of myxoid variant of GIST in a 42 years old woman presenting as an epigastric mass associated to an ovarian cyst and elevated CA-125. Histologically, the lesions was composed of a proliferation of spindle cells in an abundant myxoid stroma, without evidence of atypia or anaplasia. Immunohistochemical stains showed strong positive staining with muscle actin, positive staining with CD34 and weak positive staining with CD117, while showed negative for S-100. Conclusion At surgery every effort should be made to identify the origin of the tumor. A complete surgical removal of the tumor should be obtained, as this is the only established treatment that offers long term survival.

Resveratrol supplementation rescues pool of growing follicles and ovarian stroma from Cisplatin-induced toxicity on the ovary in Sprague-Dawley rats: An experimental study

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Gbotolorun Stella Chinwe

2018-02-01

Full Text Available Background: Cisplatin is a potent antineoplastic agent for many cancers but causes several levels of gonadal damage. Ovarian toxicity is a major concern of young cancer patients undergoing chemotherapy. Objective: This study sought to examine the effect of Cisplatin and Resveratrol supplementation on ovarian function in Sprague-Dawley rats. Materials and Methods: In this experimental study, 45 cyclic Sprague-Dawley rats with an average weight of 160 gr were divided into 9 groups (n=5/group. Group 1 was used as control and received distilled water. Groups 2 and 9 received Cisplatin only. Groups 3, 4, and 5 received different doses of Resveratrol after a single dose of Cisplatin. Groups 6, 7, and 8 received Resveratrol before Cisplatin. At sacrifice, the ovary was analyzed for histopathology, biochemical indices of oxidation and hormonal assay. Results: Relative and absolute organ weights were notably increased (p=0.001, 0.01 in the prophylactic groups relative to the groups that received Resveratrol after Cisplatin. Also, glutathione, superoxide dismutase and catalase were significantly increased (p=0.047, 0.01, 0.023 in a dose-dependent manner when compared to Cisplatin group only. Malondialdehyde decreased significantly (p=0.001 in the groups that received high dose Resveratrol compared with the control and Cisplatin alone groups. Although oestrogen showed no significant difference within the groups (p=0.48, Resveratrol significantly increased progesterone, follicle stimulating hormone and luteinizing hormone levels (p=0.007, 0.001, 0.006 at high doses when compared with Cisplatin alone groups. Ovarian histoarchitecture was best preserved in the prophylactic groups in a dose-dependent manner. Conclusion: Resveratrol supplementation confers protection and preserves ovarian follicles from Cisplatin toxicity in Sprague-Dawley rats.

Predictive factors of early moderate/severe ovarian hyperstimulation syndrome in non-polycystic ovarian syndrome patients: a statistical model.

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Ashrafi, Mahnaz; Bahmanabadi, Akram; Akhond, Mohammad Reza; Arabipoor, Arezoo

2015-11-01

To evaluate demographic, medical history and clinical cycle characteristics of infertile non-polycystic ovary syndrome (NPCOS) women with the purpose of investigating their associations with the prevalence of moderate-to-severe OHSS. In this retrospective study, among 7073 in vitro fertilization and/or intracytoplasmic sperm injection (IVF/ICSI) cycles, 86 cases of NPCO patients who developed moderate-to-severe OHSS while being treated with IVF/ICSI cycles were analyzed during the period of January 2008 to December 2010 at Royan Institute. To review the OHSS risk factors, 172 NPCOS patients without developing OHSS, treated at the same period of time, were selected randomly by computer as control group. We used multiple logistic regression in a backward manner to build a prediction model. The regression analysis revealed that the variables, including age [odds ratio (OR) 0.9, confidence interval (CI) 0.81-0.99], antral follicles count (OR 4.3, CI 2.7-6.9), infertility cause (tubal factor, OR 11.5, CI 1.1-51.3), hypothyroidism (OR 3.8, CI 1.5-9.4) and positive history of ovarian surgery (OR 0.2, CI 0.05-0.9) were the most important predictors of OHSS. The regression model had an area under curve of 0.94, presenting an allowable discriminative performance that was equal with two strong predictive variables, including the number of follicles and serum estradiol level on human chorionic gonadotropin day. The predictive regression model based on primary characteristics of NPCOS patients had equal specificity in comparison with two mentioned strong predictive variables. Therefore, it may be beneficial to apply this model before the beginning of ovarian stimulation protocol.

Gene expression profiling supports the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as ovarian cancer initiating cells

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Matyunina Lilya V

2009-12-01

Full Text Available Abstract Background Accumulating evidence suggests that somatic stem cells undergo mutagenic transformation into cancer initiating cells. The serous subtype of ovarian adenocarcinoma in humans has been hypothesized to arise from at least two possible classes of progenitor cells: the ovarian surface epithelia (OSE and/or an as yet undefined class of progenitor cells residing in the distal end of the fallopian tube. Methods Comparative gene expression profiling analyses were carried out on OSE removed from the surface of normal human ovaries and ovarian cancer epithelial cells (CEPI isolated by laser capture micro-dissection (LCM from human serous papillary ovarian adenocarcinomas. The results of the gene expression analyses were randomly confirmed in paraffin embedded tissues from ovarian adenocarcinoma of serous subtype and non-neoplastic ovarian tissues using immunohistochemistry. Differentially expressed genes were analyzed using gene ontology, molecular pathway, and gene set enrichment analysis algorithms. Results Consistent with multipotent capacity, genes in pathways previously associated with adult stem cell maintenance are highly expressed in ovarian surface epithelia and are not expressed or expressed at very low levels in serous ovarian adenocarcinoma. Among the over 2000 genes that are significantly differentially expressed, a number of pathways and novel pathway interactions are identified that may contribute to ovarian adenocarcinoma development. Conclusions Our results are consistent with the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as the origin of ovarian adenocarcinoma. While our findings do not rule out the possibility that ovarian cancers may also arise from other sources, they are inconsistent with claims that ovarian surface epithelia cannot serve as the origin of ovarian cancer initiating cells.

Ocean acidification effects on calcification in Caribbean scleractinian coral exposed to elevated pCO2: a potential for acclimation

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Hankins, C.

2016-02-01

Ocean acidification (OA) is projected to increase the acidity of coral reef habitats 2-3 times that of present day pCO2 levels. Many studies have shown the adverse effects on scleractinian calcification when exposed to elevated pCO2 levels, however, no such effects were seen in this study whereby corals were exposed for three months to elevated pCO2 levels. In this study, all corals were kept in culture for one year prior to being used in experimental trials. Data from culture systems shows coral experience a range of pCO2 from 300-600 µatm over the course of a day. This range is attributed to respiration and photosynthesis which also naturally occurs in a reef habitat. Montastrea cavernosa, Orbicella faveolata, and Pseudodiploria clivosa were exposed to their ambient culture conditions (control) or to elevated pCO2 levels of 1000 µatm (IPCC A1F1 scenario). By combining photographic analysis of live tissue area or exposed skeleton with the buoyant weight technique, an area density of each coral fragment was obtained to infer rates of calcification or erosion of skeleton. After three months of experimental exposure, preliminary results suggest that there is no significant difference in calcification or erosion in any of the species tested. Acclimation in the elevated pCO2 culture environment may have conditioned the coral to better withstand high pCO2 levels. Long acclimation periods of coral to near term future pCO2 levels may more accurately predict calcification responses in corals of the future.

Ovarian structure and oogenesis of the extremophile viviparous teleost Poecilia mexicana (Poeciliidae) from an active sulfur spring cave in Southern Mexico.

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Torres-Martínez, Aarón; Hernández-Franyutti, Arlette; Uribe, Mari Carmen; Contreras-Sánchez, Wilfrido Miguel

2017-12-01

The structure of the ovary and oogenesis of Poecilia mexicana from an active sulfur spring cave is documented. Poecilia mexicana is the only poeciliid adapted to a subterranean environment with high hydrogen sulfide levels and extreme hypoxic conditions. Twenty females were captured throughout one year at Cueva del Azufre, located in the State of Tabasco in Southern Mexico. Ovaries were processed with histological techniques. P. mexicana has a single, ovoid ovary with ovigerous lamella that project to the ovarian lumen. The ovarian wall presents abundant loose connective tissue, numerous melanomacrophage centers and large blood vessels, possibly associated with hypoxic conditions. The germinal epithelium bordering the ovarian lumen contains somatic and germ cells forming cell nests projecting into the stroma. P. mexicana stores sperm in ovarian folds associated with follicles at different developmental phases. Oogenesis in P. mexicana consisted of the following stages: (i) oogonial proliferation, (ii) chromatin nucleolus, (iii) primary growth, subdivided into: (a) one nucleolus, (b) multiple nucleoli, (c) droplet oils-cortical alveoli steps; (iv) secondary growth, subdivided in: (a) early secondary growth, (b) late secondary growth, and (c) full grown. Follicular atresia was present in all stages of follicular development; it was characterized by oocyte degeneration, where follicle cells hypertrophy and differentiate in phagocytes. The ovary and oogenesis are similar to these seen in other poeciliids, but we found frequent atretic follicles, melanomacrophage centers, reduced fecundity and increased of offspring size. © 2017 Wiley Periodicals, Inc.

An investigation of the calcification response of the scleractinian coral Astrangia poculata to elevated pCO2 and the effects of nutrients, zooxanthellae and gender

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Holcomb, M.; Cohen, A. L.; McCorkle, D. C.

2012-01-01

The effects of nutrients and pCO2 on zooxanthellate and azooxanthellate colonies of the temperate scleractinian coral Astrangia poculata (Ellis and Solander, 1786) were investigated at two different temperatures (16 °C and 24 °C). Corals exposed to elevated pCO2 tended to have lower relative calcification rates, as estimated from changes in buoyant weights. Experimental nutrient enrichments had no significant effect nor did there appear to be any interaction between pCO2 and nutrients. Elevated pCO2 appeared to have a similar effect on coral calcification whether zooxanthellae were present or absent at 16 °C. However, at 24 °C, the interpretation of the results is complicated by a significant interaction between gender and pCO2 for spawning corals. At 16 °C, gamete release was not observed, and no gender differences in calcification rates were observed - female and male corals showed similar reductions in calcification rates in response to elevated CO2 (15% and 19% respectively). Corals grown at 24 °C spawned repeatedly and male and female corals exhibited two different growth rate patterns - female corals grown at 24 °C and exposed to CO2 had calcification rates 39% lower than females grown at ambient CO2, while males showed a non-significant decline of 5% under elevated CO2. The increased sensitivity of females to elevated pCO2 may reflect a greater investment of energy in reproduction (egg production) relative to males (sperm production). These results suggest that both gender and spawning are important factors in determining the sensitivity of corals to ocean acidification, and considering these factors in future research may be critical to predicting how the population structures of marine calcifiers will change in response to ocean acidification.

Estimating surface pCO2 in the northern Gulf of Mexico: Which remote sensing model to use?

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Chen, Shuangling; Hu, Chuanmin; Cai, Wei-Jun; Yang, Bo

2017-12-01

Various approaches and models have been proposed to remotely estimate surface pCO2 in the ocean, with variable performance as they were designed for different environments. Among these, a recently developed mechanistic semi-analytical approach (MeSAA) has shown its advantage for its explicit inclusion of physical and biological forcing in the model, yet its general applicability is unknown. Here, with extensive in situ measurements of surface pCO2, the MeSAA, originally developed for the summertime East China Sea, was tested in the northern Gulf of Mexico (GOM) where river plumes dominate water's biogeochemical properties during summer. Specifically, the MeSAA-predicted surface pCO2 was estimated by combining the dominating effects of thermodynamics, river-ocean mixing and biological activities on surface pCO2. Firstly, effects of thermodynamics and river-ocean mixing (pCO2@Hmixing) were estimated with a two-endmember mixing model, assuming conservative mixing. Secondly, pCO2 variations caused by biological activities (ΔpCO2@bio) was determined through an empirical relationship between sea surface temperature (SST)-normalized pCO2 and MODIS (Moderate Resolution Imaging Spectroradiometer) 8-day composite chlorophyll concentration (CHL). The MeSAA-modeled pCO2 (sum of pCO2@Hmixing and ΔpCO2@bio) was compared with the field-measured pCO2. The Root Mean Square Error (RMSE) was 22.94 μatm (5.91%), with coefficient of determination (R2) of 0.25, mean bias (MB) of - 0.23 μatm and mean ratio (MR) of 1.001, for pCO2 ranging between 316 and 452 μatm. To improve the model performance, a locally tuned MeSAA was developed through the use of a locally tuned ΔpCO2@bio term. A multi-variate empirical regression model was also developed using the same dataset. Both the locally tuned MeSAA and the regression models showed improved performance comparing to the original MeSAA, with R2 of 0.78 and 0.84, RMSE of 12.36 μatm (3.14%) and 10.66 μatm (2.68%), MB of 0.00 μatm and - 0

Natural high pCO2 increases autotrophy in Anemonia viridis (Anthozoa) as revealed from stable isotope (C, N) analysis.

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Horwitz, Rael; Borell, Esther M; Yam, Ruth; Shemesh, Aldo; Fine, Maoz

2015-03-05

Contemporary cnidarian-algae symbioses are challenged by increasing CO2 concentrations (ocean warming and acidification) affecting organisms' biological performance. We examined the natural variability of carbon and nitrogen isotopes in the symbiotic sea anemone Anemonia viridis to investigate dietary shifts (autotrophy/heterotrophy) along a natural pCO2 gradient at the island of Vulcano, Italy. δ(13)C values for both algal symbionts (Symbiodinium) and host tissue of A. viridis became significantly lighter with increasing seawater pCO2. Together with a decrease in the difference between δ(13)C values of both fractions at the higher pCO2 sites, these results indicate there is a greater net autotrophic input to the A. viridis carbon budget under high pCO2 conditions. δ(15)N values and C/N ratios did not change in Symbiodinium and host tissue along the pCO2 gradient. Additional physiological parameters revealed anemone protein and Symbiodinium chlorophyll a remained unaltered among sites. Symbiodinium density was similar among sites yet their mitotic index increased in anemones under elevated pCO2. Overall, our findings show that A. viridis is characterized by a higher autotrophic/heterotrophic ratio as pCO2 increases. The unique trophic flexibility of this species may give it a competitive advantage and enable its potential acclimation and ecological success in the future under increased ocean acidification.

An analysis of pH, pO2 and pCO2 in the peritoneal fluid of dogs with ascites of various etiologies.

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Glińska-Suchocka, K; Sławuta, P; Jankowski, M; Kubiak, K; Spużak, J; Borusewicz, P

2016-01-01

The aim of the study was to assess pH, pO2 and pCO2 in peritoneal fluid. The study was conducted on a group of 22 dogs with symptoms of ascites. Group 1 consisted of 4 dogs with adenocarcinoma, group 2--of 6 dogs with glomerulonephritis, group 3 of 8 dogs with hepatic cirrhosis and group 4 of 4 dogs with bacterial peritonitis. An abdominal cavity puncture was performed in all dogs and the fluid was drawn into a heparinized syringe in order to assess pH, pO2 and pCO2 . The analysis of pH in the peritoneal fluid revealed statistically significant differences between group 4 and groups 1 (p=0.01), 2 (p=0.01), and 3 (p=0.01). The lowest pH value compared to the other studied groups was recorded in group 4. In group 4, the pO2 was the lowest compared to the other groups (group 1 p=0.01, group 2 p=0.01, group 3 p=0.01). The value of pCO2 was the highest in group 4 compared to groups 1, 2, and 3. The study found statistically significant differences in pH, pCO2 and pCO2 between group 4 (the group of dogs with bacterial peritonitis) and the other groups of dogs. This was probably linked to the pathogenesis of peritonitis. As a result of an inflammatory reaction within the peritoneal cavity, there is an increase in fibrin accumulations leading to a decreased oxygen supply causing the oxidative glucose metabolism to change into a non-oxidative glucose metabolism. This, in turn, causes a decrease in pH, acidosis, and a low oxidoreduction potential. It also impairs phagocytosis and activates proteolytic enzymes which create ideal conditions for the growth of anaerobic bacteria. The obtained results indicate that the pH, pO2 and pCO2 may be used to differentiate bacterial peritonitis from ascites of other etiologies.

Confocal microscopy of corneal stroma and endothelium after LASIK and PRK.

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Amoozadeh, Javad; Aliakbari, Soheil; Behesht-Nejad, Amir-Houshang; Seyedian, Mohammad-Amin; Rezvan, Bijan; Hashemi, Hassan

2009-10-01

To compare with confocal microscopy the changes in stromal keratocyte density and endothelial cell count due to photorefractive keratectomy (PRK) and LASIK. In this prospective study, 32 eyes (16 myopic patients) were examined with the NIDEK Confoscan 3 confocal microscope before and 6 months after PRK and LASIK. The preoperative mean myopia was -2.85+/-0.99 diopters (D) (range: -1.00 to -4.00 D) in 24 eyes that underwent PRK and -2.94+/-0.96 D (range: -2.00 to -4.25 D) in 8 eyes that underwent LASIK. Keratocyte density in the anterior and posterior stroma and the endothelial cell count were measured. Statistically significant changes were assessed using the t test. PPRK group. Postoperatively, the percentages were 52.96+/-7.55 and 53.34+/-10.2, respectively. Six months postoperatively, keratocyte density changed by 367.12+/-103.35 cells/mm(2) (34.7% reduction) in the anterior stroma (P.05) for the LASIK group. In the PRK group, these values were 319.71+/-83.45 cells/mm(2) (31.13% reduction) in the anterior stroma (P.05). The changes in keratocyte densities were not statistically significant between groups (P>.05). The mean number of keratocytes decreased by 37.2% in the retroablation zone of the LASIK group (PPRK groups (P>.05). Copyright 2009, SLACK Incorporated.

Effects of the Loss of Conjunctival Muc16 on Corneal Epithelium and Stroma in Mice

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Shirai, Kumi; Okada, Yuka; Cheon, Dong-Joo; Miyajima, Masayasu; Behringer, Richard R.; Yamanaka, Osamu; Saika, Shizuya

2014-01-01

Purpose. To examine the role of conjunctival Muc16 in the homeostasis of the ocular surface epithelium and stroma using Muc16-null knockout (KO) mice. Methods. We used KO mice (n = 58) and C57/BL6 (WT) mice (n = 58). Histology and immunohistochemistry were employed to analyze the phenotypes in the ocular surface epithelium. The expression of phospho-Stat3, AP-1 components, interleukin 6 (IL-6), and tumor necrosis factor-α (TNFα) in the cornea and conjunctiva was examined. The shape of the nuclei of corneal epithelial cells was examined to evaluate intraepithelial cell differentiation. Epithelial cell proliferation was studied using bromo-deoxyuridine labeling. Finally, the wound healing of a round defect (2-mm diameter) in the corneal epithelium was measured. The keratocyte phenotype and macrophage invasion in the stroma were evaluated after epithelial repair. Results. The loss of Muc16 activated Stat3 signal, affected JunB signal, and upregulated the expression of IL-6 in the conjunctiva. Basal-like cells were observed in the suprabasal layer of the corneal epithelium with an increase in proliferation. The loss of Muc16 accelerated the wound healing of the corneal epithelium. The incidence of myofibroblast appearance and macrophage invasion were more marked in KO stroma than in WT stroma after epithelial repair. Conclusions. The loss of Muc16 in the conjunctiva affected the homeostasis of the corneal epithelium and stroma. The mechanism might include the upregulation of the inflammatory signaling cascade (i.e., Stat3 signal, and IL-6 expression in the KO conjunctiva). Current data provides insight into the research of the pathophysiology of dry eye syndrome. PMID:24812549

Prophylactic salpingectomy in premenopausal low-risk women for ovarian cancer: primum non nocere.

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Morelli, Michele; Venturella, Roberta; Mocciaro, Rita; Di Cello, Annalisa; Rania, Erika; Lico, Daniela; D'Alessandro, Pietro; Zullo, Fulvio

2013-06-01

The objective of this study is to compare ovarian function and surgical outcomes between patients affected by benign uterine pathologies submitted to total laparoscopic hysterectomy (TLH) plus salpingectomy and women in which standard TLH with adnexal preservation was performed. We retrospectively compared data of 79 patients who underwent TLH plus bilateral salpingectomy (group A), with those of 79 women treated by standard TLH without adnexectomy (sTLH) (group B). Ovarian reserve modification, expressed as the difference between 3 months post-operative and pre-operative values of Anti-Müllerian Hormone (AMH), Follicle Stimulating Hormone (FSH), Antral Follicle Count (AFC), mean ovarian diameters and Peak Systolic Velocity (PSV), was recorded for each patient. For each surgical procedure, operative time, variation of hemoglobin level (ΔHb), postoperative hospital stay, postoperative return to normal activity, and complication rate were recorded as secondary outcomes. According to our post-hoc analysis, this equivalence study resulted to have a statistical power of 96.8%. Significant difference was not observed between groups with respect to ΔAMH (p=0.35), ΔFSH (p=0.15), ΔAFC (p=0.09), Δ mean ovarian diameters (p=0.57) and ΔPSV (p=0.61). In addition, secondary outcomes such as operative time (p=0.79), ΔHb (p=0.41), postoperative hospital stay (p=0.16), postoperative return to normal activity (p=0.11) and complication rate also did not show any significant difference. The addition of bilateral salpingectomy to TLH for prevention of ovarian cancer in women who do not carry a BRCA1/2 mutations do not show negative effects on the ovarian function. In addition, no perioperative complications are related to the salpingectomy step in TLH. Copyright © 2013 Elsevier Inc. All rights reserved.

Ovarian tubercular abscess mimicking ovarian carcinoma: A rare case report

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Abinash Agarwala

2015-01-01

Full Text Available Although genito-urinary tuberculosis is common, reports of isolated ovarian tubercular abscess are rare. Ovarian tubercular abscess may mimics that of an ovarian tumor, leading to diagnostic difficulties. We reported a case report of 35 years woman presented with chronic pain abdomen, weight loss, low-grade fever and a right ovarian mass on ultrasound, with a significantly elevated CA-125 level. On clinical and radiological evidence, diagnosis of ovarian carcinoma was made, and laparotomy was performed with resection of the ovary. Postoperative specimen sent for histological examination that revealed classic epithelioid granuloma and acid-fast bacilli were present in Ziehl-Neelsen stain. Patient was put on antitubercular regimen from our Dots center. She is improving clinical after taking antitubercular drug and is on regular follow up at our chest outpatient department. Ovarian tubercular abscess is common in young women living in endemic zones, but case report of isolated tubercular abscess is rarely reported. CA-125 can be raised in both ovarian tubercular abscess and ovarian carcinoma, and only imaging is not always conclusive. Laparotomy followed by tissue diagnosis can be helpful in this situation. As the prognosis and treatment outcome of ovarian tubercular abscess and ovarian carcinoma is different, proper diagnosis by laparotomy should be done. Early diagnosis of ovarian tubercular abscess is vital as untreated disease can lead to infertility.

A new model of development of the mammalian ovary and follicles.

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Katja Hummitzsch

Full Text Available Ovarian follicular granulosa cells surround and nurture oocytes, and produce sex steroid hormones. It is believed that during development the ovarian surface epithelial cells penetrate into the ovary and develop into granulosa cells when associating with oogonia to form follicles. Using bovine fetal ovaries (n = 80 we identified a novel cell type, termed GREL for Gonadal Ridge Epithelial-Like. Using 26 markers for GREL and other cells and extracellular matrix we conducted immunohistochemistry and electron microscopy and chronologically tracked all somatic cell types during development. Before 70 days of gestation the gonadal ridge/ovarian primordium is formed by proliferation of GREL cells at the surface epithelium of the mesonephros. Primordial germ cells (PGCs migrate into the ovarian primordium. After 70 days, stroma from the underlying mesonephros begins to penetrate the primordium, partitioning the developing ovary into irregularly-shaped ovigerous cords composed of GREL cells and PGCs/oogonia. Importantly we identified that the cords are always separated from the stroma by a basal lamina. Around 130 days of gestation the stroma expands laterally below the outermost layers of GREL cells forming a sub-epithelial basal lamina and establishing an epithelial-stromal interface. It is at this stage that a mature surface epithelium develops from the GREL cells on the surface of the ovary primordium. Expansion of the stroma continues to partition the ovigerous cords into smaller groups of cells eventually forming follicles containing an oogonium/oocyte surrounded by GREL cells, which become granulosa cells, all enclosed by a basal lamina. Thus in contrast to the prevailing theory, the ovarian surface epithelial cells do not penetrate into the ovary to form the granulosa cells of follicles, instead ovarian surface epithelial cells and granulosa cells have a common precursor, the GREL cell.

Variations in pCO2 during summer in the surface water of an unproductive lake in northern Sweden

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Jonsson, A.; Aaberg, J.; Jansson, M.

2007-01-01

Unproductive lakes are generally supersaturated with carbon dioxide (CO 2 ) and emit CO 2 to the atmosphere continuously during ice-free periods. However, temporal variation of the partial pressure of CO 2 (pCO 2 ) and thus of CO 2 evasion to atmosphere is poorly documented. We therefore carried out temporally high-resolution (every 6 h) measurements of the pCO 2 using an automated logger system in the surface water of a subarctic, unproductive, lake in the birch forest belt. The study period was June-September 2004. We found that the pCO 2 showed large seasonal variation, but low daily variation. The seasonal variation was likely mainly caused by variations in input and mineralization of allochthonous organic matter. Stratification depth probably also influenced pCO 2 of the surface water by controlling the volume in which mineralization of dissolved organic carbon (DOC) occurred. In lakes, with large variations in pCO 2 , as in our study lake a high (weekly) sampling intensity is recommended for obtaining accurate estimates of the evasion of CO 2

Expression of FK506 binding protein 65 (FKBP65) is decreased in epithelial ovarian cancer cells compared to benign tumor cells and to ovarian epithelium

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Henriksen, Rudi; Sørensen, Flemming Brandt; Orntoft, Torben Falck

2011-01-01

to be followed by a strongly increased risk of ovarian cysts. We performed the present study to reveal how FKBP65 is expressed in the ovary and in ovarian tumors and to see if this expression might be related to ovarian tumor development, a relationship we have found in colorectal cancer. Biopsies from...... prospectively collected samples from ovaries and benign, borderline, and invasive ovarian tumors were analyzed for expression of FKBP65 by immunohistochemistry. The expression was compared to survival and several clinicopathological parameters. FKBP65 is strongly expressed in ovarian epithelium and in benign...... ovarian tumor cells. In the ovary, a positive staining was also found in endothelial cells of blood vessels. In non-invasive and in invasive malignant tumor cells, a decreased staining was observed, which was not correlated to stage, histology, or survival. A significant inversed correlation to expression...

Qualitative analysis of connective tissue stroma in different grades of oral squamous cell carcinoma: A histochemical study

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Smitha Kullage

2017-01-01

Full Text Available Background: Detection of oral cancer at an early stage is of utmost importance to decrease morbidity and mortality. Tumor stroma plays a critical role during carcinogenesis. There is lack of information regarding the characteristics of the stroma in relation to the invading malignant epithelial cells and the interdependence between stroma and tumor cells in different grades of oral squamous cell carcinoma (OSCC. Aim: The present study was aimed to analyze and compare the nature of stroma in the vicinity of invading tumor islands in different grades of OSCC, using a histochemical technique picrosirius-polarization method. The present study also evaluated and correlated the possible role of inflammatory response in determining the nature of the stroma. Subjects and Methods: The study included thirty cases of different grades of histologically diagnosed OSCC and ten sections of normal buccal mucosa as a control group. Nature of collagen was analyzed using picrosirius-polarization method, and intensity of inflammatory cell infiltrate was recorded using ImageJ software (1.42q, NIH, USA. The results were tabulated and analyzed statistically. Results: Normal oral mucosa showed predominantly reddish birefringence. All cases of well-differentiated OSCC showed reddish-orange color. Nearly 70% moderately differentiated cases showed yellowish-orange (YO and 60% of poorly differentiated cases, showed greenish-yellow (GY. The mean inflammatory cell count was highest in well-differentiated group. There was shift to YO and GY collagen when the cell differentiation and inflammatory cell count decreased in moderate and poorly differentiated cases. Conclusion: Both inflammatory cells and tumor cells have a role in determining the nature of the collagen fibers in tumor stroma of OSCC, probably with opposing effects on stromal behavior and hence both are significant in predicting prognosis.

Adult body mass index and risk of ovarian cancer by subtype

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Dixon, Suzanne C; Nagle, Christina M; Thrift, Aaron P

2016-01-01

BACKGROUND: Observational studies have reported a positive association between body mass index (BMI) and ovarian cancer risk. However, questions remain as to whether this represents a causal effect, or holds for all histological subtypes. The lack of association observed for serous cancers may......, for instance, be due to disease-associated weight loss. Mendelian randomization (MR) uses genetic markers as proxies for risk factors to overcome limitations of observational studies. We used MR to elucidate the relationship between BMI and ovarian cancer, hypothesizing that genetically predicted BMI would...... be associated with increased risk of non-high grade serous ovarian cancers (non-HGSC) but not HGSC. METHODS: We pooled data from 39 studies (14 047 cases, 23 003 controls) in the Ovarian Cancer Association Consortium. We constructed a weighted genetic risk score (GRS, partial F-statistic = 172), summing alleles...

RNA-based ovarian cancer research from 'a gene to systems biomedicine' perspective.

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Gov, Esra; Kori, Medi; Arga, Kazim Yalcin

2017-08-01

Ovarian cancer remains the leading cause of death from a gynecologic malignancy, and treatment of this disease is harder than any other type of female reproductive cancer. Improvements in the diagnosis and development of novel and effective treatment strategies for complex pathophysiologies, such as ovarian cancer, require a better understanding of disease emergence and mechanisms of progression through systems medicine approaches. RNA-level analyses generate new information that can help in understanding the mechanisms behind disease pathogenesis, to identify new biomarkers and therapeutic targets and in new drug discovery. Whole RNA sequencing and coding and non-coding RNA expression array datasets have shed light on the mechanisms underlying disease progression and have identified mRNAs, miRNAs, and lncRNAs involved in ovarian cancer progression. In addition, the results from these analyses indicate that various signalling pathways and biological processes are associated with ovarian cancer. Here, we present a comprehensive literature review on RNA-based ovarian cancer research and highlight the benefits of integrative approaches within the systems biomedicine concept for future ovarian cancer research. We invite the ovarian cancer and systems biomedicine research fields to join forces to achieve the interdisciplinary caliber and rigor required to find real-life solutions to common, devastating, and complex diseases such as ovarian cancer. CAF: cancer-associated fibroblasts; COG: Cluster of Orthologous Groups; DEA: disease enrichment analysis; EOC: epithelial ovarian carcinoma; ESCC: oesophageal squamous cell carcinoma; GSI: gamma secretase inhibitor; GO: Gene Ontology; GSEA: gene set enrichment analyzes; HAS: Hungarian Academy of Sciences; lncRNAs: long non-coding RNAs; MAPK/ERK: mitogen-activated protein kinase/extracellular signal-regulated kinases; NGS: next-generation sequencing; ncRNAs: non-coding RNAs; OvC: ovarian cancer; PI3K

Metabolic profiles and lipoprotein lipid concentrations in non-obese and obese patients with polycystic ovarian disease.

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Mahabeer, S; Naidoo, C; Norman, R J; Jialal, I; Reddi, K; Joubert, S M

1990-10-01

Clinical parameters, androgen status and lipoprotein lipid profiles were assessed in 10 non-obese and 10 obese patients with polycystic ovarian disease (PCOD) and reference subjects matched for age, height and weight. Both obese and non-obese women with PCOD had significantly higher androgen levels when compared to the reference groups. When comparison of lipoprotein lipid profiles were made between groups, non-obese women with PCOD had significantly higher total cholesterol, triglycerides and LDL-cholesterol levels than non-obese reference subjects. Obese PCOD women manifested significantly higher total cholesterol, LDL-cholesterol, cholesterol/HDL, and LDL/HDL values than did obese reference subjects. Correlations between serum androgens and lipoprotein lipid concentrations in PCOD and normal women were unhelpful. Both non-obese and obese patients with PCOD had significantly higher systolic and diastolic blood pressures (BPs) than the reference groups. Thus, both non-obese and obese women with PCOD manifest hyperandrogenaemia which may result in a male pattern of lipoprotein lipid concentrations.

High nitrate to phosphorus regime attenuates negative effects of rising pCO2 on total population carbon accumulation

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S. A. Krug

2012-03-01

Full Text Available The ongoing rise in atmospheric pCO2 and consequent increase in ocean acidification have direct effects on marine calcifying phytoplankton, which potentially alters carbon export. To date it remains unclear, firstly, how nutrient regime, in particular by coccolithophores preferred phosphate limitation, interacts with pCO2 on particulate carbon accumulation; secondly, how direct physiological responses on the cellular level translate into total population response. In this study, cultures of Emiliania huxleyi were full-factorially exposed to two different N:P regimes and three different pCO2 levels. Cellular biovolume and PIC and POC content significantly declined in response to pCO2 in both nutrient regimes. Cellular PON content significantly increased in the Redfield treatment and decreased in the high N:P regime. Cell abundance significantly declined in the Redfield and remained constant in the high N:P regime. We hypothesise that in the high N:P regime severe phosphorous limitation could be compensated either by reduced inorganic phosphorous demand and/or by enzymatic uptake of organic phosphorous. In the Redfield regime we suggest that enzymatic phosphorous uptake to supplement enhanced phosphorous demand with pCO2 was not possible and thus cell abundance declined. These hypothesised different physiological responses of E. huxleyi among the nutrient regimes significantly altered population carrying capacities along the pCO2 gradient. This ultimately led to the attenuated total population response in POC and PIC content and biovolume to increased pCO2 in the high N:P regime. Our results point to the fact that the physiological (i.e. cellular PIC and POC response to ocean acidification cannot be linearly extrapolated to total population response and thus carbon export. It is therefore necessary to consider both effects of nutrient limitation on cell physiology and their consequences for population size when predicting the influence of

A 20 million year record of planktic foraminiferal B/Ca ratios: Systematics and uncertainties in pCO 2 reconstructions

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Tripati, Aradhna K.; Roberts, Christopher D.; Eagle, Robert A.; Li, Gaojun

2011-05-01

We use new and published data representing a 20 million long record to discuss the systematics of interpreting planktic foraminiferal B/Ca ratios. B/Ca-based reconstructions of seawater carbonate chemistry and atmospheric pCO 2 assume that the incorporation of boron into foraminiferal tests can be empirically described by an apparent partition coefficient, KD={B/Ca}/{B(OH4-/HCO)} ( Hemming and Hanson, 1992). It has also been proposed that there is a species-specific relationship between K D and temperature ( Yu et al., 2007). As we discuss, although these relationships may be robust, there remain significant uncertainties over the controls on boron incorporation into foraminifera. It is difficult to be certain that the empirically defined correlation between temperature and K D is not simply a result of covariance of temperature and other hydrographic variables in the ocean, including carbonate system parameters. There is also some evidence that K D may be affected by solution [HCO3-]/[CO32-] ratios (i.e., pH), or by [CO32-]. In addition, the theoretical basis for the definition of K D and for a temperature control on K D is of debate. We also discuss the sensitivity of pCO 2 reconstructions to different K D-temperature calibrations and seawater B/Ca. If a K D-temperature calibration is estimated using ice core pCO 2 values between 0 and 200 ka, B/Ca ratios can be used to reasonably approximate atmospheric pCO 2 between 200 and 800 ka; however, the absolute values of pCO 2 calculated are sensitive to the choice of K D-temperature relationship. For older time periods, the absolute values of pCO 2 are also dependent on the evolution of seawater B concentrations. However, we find that over the last 20 Ma, reconstructed changes in declining pCO 2 across the Mid-Pleistocene Transition, Pliocene glacial intensification, and the Middle Miocene Climate Transition are supported by the B/Ca record even if a constant coretop K D is used, or different K D

REG4 Is Highly Expressed in Mucinous Ovarian Cancer: A Potential Novel Serum Biomarker.

Directory of Open Access Journals (Sweden)

Laura Lehtinen

Full Text Available Preoperative diagnostics of ovarian neoplasms rely on ultrasound imaging and the serum biomarkers CA125 and HE4. However, these markers may be elevated in non-neoplastic conditions and may fail to identify most non-serous epithelial cancer subtypes. The objective of this study was to identify histotype-specific serum biomarkers for mucinous ovarian cancer. The candidate genes with mucinous histotype specific expression profile were identified from publicly available gene-expression databases and further in silico data mining was performed utilizing the MediSapiens database. Candidate biomarker validation was done using qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The expression level of the candidate gene in serum was compared to the serum CA125 and HE4 levels in a patient cohort of prospectively collected advanced ovarian cancer. Database searches identified REG4 as a potential biomarker with specificity for the mucinous ovarian cancer subtype. The specific expression within epithelial ovarian tumors was further confirmed by mRNA analysis. Immunohistochemical staining of ovarian tumor tissue arrays showed distinctive cytoplasmic expression pattern only in mucinous carcinomas and suggested differential expression between benign and malignant mucinous neoplasms. Finally, an ELISA based serum biomarker assay demonstrated increased expression only in patients with mucinous ovarian cancer. This study identifies REG4 as a potential serum biomarker for histotype-specific detection of mucinous ovarian cancer and suggests serum REG4 measurement as a non-invasive diagnostic tool for postoperative follow-up of patients with mucinous ovarian cancer.

Next Generation Hybrid Photo-Catalytic Oxidation (PCO) for Trace Contaminant Control

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National Aeronautics and Space Administration — Photocatalytic oxidation (PCO) is a primary candidate as an alternative to thermal-catalytic or sorbent- based technologies for VOC trace contaminant control due to...

MR imaging of malignant ovarian tumors

International Nuclear Information System (INIS)

Kim, Jun Ho; Kang, Heoung Keun; Moon, Woong Jae; Seo, Jeong Jin; Kim, Jae Kyu; Choi, Ho Sun

1994-01-01

To evaluate MRI findings of malignant ovarian tumors. MRI findings were retrospectively reviewed in 25 patients with surgically confirmed 30 malignant ovarian tumors(common epithelial tumor; 23, sex cord stromal tumor; 2, endo dermal sinus tumor; 1, metastatic tumor; 4). The findings evaluated were the lesion size, solid and/or cystic component, wall thickness, septal thickness, necrosis, invasion of adjacent organ, ascites, and adenopathy. MRI findings of the malignant ovarian tumors were as follow: Size of lesion was 5-35cm(mean 14cm); solid component was present in 80%(24/30); wall thickness was more than 3mm in 90%(27/30); septal thickness was more than 3mm in 70%(21/30); tumor necrosis was present in 40%(12/30%); invasion of adjacent organ was present in 76%(19/25); ascites was present in 56%(14/25); lymphadenopathy was present in 24% (6/25). MRI findings of absence of solid component(6/6), even wall and septal thickness(7/7, 19/19) were found only in epithelial tumors. Uneven septal thickness more than 3mm(7/11) was a predominant MRI findings of non-epithelial tumors. Well-defined cystic lesion within solid component was seen in Krukenberg tumors. Evaluation of the lesion size, internal architecture, invasion of adjacent organ, ascites, and lymphadenopathy in MRI would enable diagnosis of malignant ovarian tumors and could lead to possible differential diagnosis of epithelial tumors from non-epithelial tumors

Polycystic ovarian syndrome

OpenAIRE

Nina Madnani; Kaleem Khan; Phulrenu Chauhan; Girish Parmar

2013-01-01

Polycystic ovarian syndrome (PCOS) is a "multispeciality" disorder suspected in patients with irregular menses and clinical signs of hyperandrogenism such as acne, seborrhoea, hirsutism, irregular menses, infertility, and alopecia. Recently, PCOS has been associated with the metabolic syndrome. Patients may develop obesity, insulin resistance, acanthosis nigricans, Type 2 diabetes, dyslipidemias, hypertension, non-alcoholic liver disease, and obstructive sleep apnoea. Good clinical examinatio...

Mimicking corneal stroma using keratocyte-loaded photopolymerizable methacrylated gelatin hydrogels.

Science.gov (United States)

Kilic Bektas, Cemile; Hasirci, Vasif

2018-04-01

Cell-laden methacrylated gelatin (GelMA) hydrogels with high (approximately 90%) transparency were prepared to mimic the natural form and function of corneal stroma. They were synthesized from GelMA with a methacrylation degree of 70% as determined by nuclear magnetic resonance. Hydrogels were strong enough to withstand handling. Stability studies showed that 87% of the GelMA hydrogels remained after 21 days in phosphate buffered saline (PBS). Cell viability in the first 2 days was over 90% for the human keratocytes loaded in the gels as determined with the live-dead analysis. Cells in the hydrogel elongated and connected to each other as observed by confocal laser scanning microscopy (CLSM) images and scanning electron microscope analysis after 3 weeks in the culture medium and cells were seen to be distributed throughout the hydrogel bulk. Cells were found to synthesize collagen Types I and V, decorin, and biglycan (representative collagens and proteoglycans of human corneal stroma, respectively) showing that keratocytes maintained their functions and preserved their phenotypes in the hydrogels. Transparency of cell-loaded and cell-free hydrogels after 21 days was found to be over 90% at all time points in the visible light range and was comparable to the transparency of the native cornea. The corneal stroma equivalent produced in this study that has cells entrapped in it leads to a product with homogenous distribution of cells. It was transparent at the very beginning and is expected to allow better vision than nontransparent substrates. It, therefore, has a significant potential to be used as an alternative to the current products used to treat corneal blindness. Copyright © 2017 John Wiley & Sons, Ltd.

Effects of ocean acidification with pCO2 diurnal fluctuations on survival and larval shell formation of Ezo abalone, Haliotis discus hannai.

Science.gov (United States)

Onitsuka, Toshihiro; Takami, Hideki; Muraoka, Daisuke; Matsumoto, Yukio; Nakatsubo, Ayumi; Kimura, Ryo; Ono, Tsuneo; Nojiri, Yukihiro

2018-03-01

This study assessed the effects of constant and diurnally fluctuating pCO 2 on development and shell formation of larval abalone Haliotis discus hannai. The larvae was exposed to different pCO 2 conditions; constant [450, 800, or 1200 μatm in the first experiment (Exp. I), 450 or 780 μatm in the second experiment (Exp. II)] or diurnally fluctuating pCO 2 (800 ± 400 or 1200 ± 400 μatm in Exp. I, 450 ± 80, 780 ± 200 or 780 ± 400 μatm in Exp. II). Mortality, malformation rates or shell length of larval abalone were not significantly different among the 450, 800, and 800 ± 400 μatm pCO 2 treatments. Meanwhile, significantly higher malformation rates and smaller shells were detected in the 1200 and 1200 ± 400 μatm pCO 2 treatments than in the 450 μatm pCO 2 treatment. The negative impacts were greater in the 1200 ± 400 μatm than in the 1200 μatm. Shell length and malformation rate of larval abalone were related with aragonite saturation state (Ω-aragonite) in experimental seawater, and greatly changed around 1.1 of Ω-aragonite which corresponded to 1000-1300 μatm pCO 2 . These results indicate that there is a pCO 2 threshold associated with Ω-aragonite in the seawater, and that pCO 2 fluctuations produce additional negative impacts on abalone when above the threshold. Clear relationships were detected between abalone fitness and the integrated pCO 2 value over the threshold, indicating that the effects of OA on development and shell formation of larval abalone can be determined by intensity and time of exposure to pCO 2 over the threshold. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sensitivity to ocean acidification parallels natural pCO2 gradients experienced by Arctic copepods under winter sea ice

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Lewis, Ceri N.; Brown, Kristina A.; Edwards, Laura A.; Cooper, Glenn; Findlay, Helen S.

2013-01-01

The Arctic Ocean already experiences areas of low pH and high CO2, and it is expected to be most rapidly affected by future ocean acidification (OA). Copepods comprise the dominant Arctic zooplankton; hence, their responses to OA have important implications for Arctic ecosystems, yet there is little data on their current under-ice winter ecology on which to base future monitoring or make predictions about climate-induced change. Here, we report results from Arctic under-ice investigations of copepod natural distributions associated with late-winter carbonate chemistry environmental data and their response to manipulated pCO2 conditions (OA exposures). Our data reveal that species and life stage sensitivities to manipulated OA conditions were correlated with their vertical migration behavior and with their natural exposures to different pCO2 ranges. Vertically migrating adult Calanus spp. crossed a pCO2 range of >140 μatm daily and showed only minor responses to manipulated high CO2. Oithona similis, which remained in the surface waters and experienced a pCO2 range of <75 μatm, showed significantly reduced adult and nauplii survival in high CO2 experiments. These results support the relatively untested hypothesis that the natural range of pCO2 experienced by an organism determines its sensitivity to future OA and highlight that the globally important copepod species, Oithona spp., may be more sensitive to future high pCO2 conditions compared with the more widely studied larger copepods. PMID:24297880

Glucose, insulin and C-peptide secretion in obese and non obese women with polycystic ovarian disease.

Science.gov (United States)

Mahabeer, S; Naidoo, C; Joubert, S M

1990-06-01

Plasma glucose, immunoreactive insulin (IRI) and C-peptide responses during oral glucose tolerance testing (OGTT) were evaluated in 10 non obese women with polycystic ovarian disease (NOB-PCOD) and 10 obese women with polycystic ovarian disease (OB-PCOD). Mean plasma glucose response at 120 minutes in OB-PCOD showed impaired glucose tolerance. Also in this group, 1 patient had frank diabetes mellitus, whilst 3 other patients had impaired glucose tolerance 1 NOB-PCOD patient had impaired glucose tolerance. Mean plasma glucose levels and mean incremental glucose areas were higher in the OB-PCOD at all time intervals and reached statistical significance at 60 and 90 minutes. Mean plasma IRI levels were also higher in OB-PCOD at all time intervals, and reached statistically significant higher levels at 0, 60 and 90 minutes. Mean serum C-peptide valves were also higher at all time intervals in OB-PCOD. The relationship between acanthosis nigricans, obesity and PCOD was also analysed. It is evident from this study that obesity has a significant negative impact on the overall carbohydrate status in women with PCOD.

Insulin/IGF-driven cancer cell-stroma crosstalk as a novel therapeutic target in pancreatic cancer.

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Mutgan, Ayse Ceren; Besikcioglu, H Erdinc; Wang, Shenghan; Friess, Helmut; Ceyhan, Güralp O; Demir, Ihsan Ekin

2018-02-23

Pancreatic ductal adenocarcinoma (PDAC) is unrivalled the deadliest gastrointestinal cancer in the western world. There is substantial evidence implying that insulin and insulin-like growth factor (IGF) signaling axis prompt PDAC into an advanced stage by enhancing tumor growth, metastasis and by driving therapy resistance. Numerous efforts have been made to block Insulin/IGF signaling pathway in cancer therapy. However, therapies that target the IGF1 receptor (IGF-1R) and IGF subtypes (IGF-1 and IGF-2) have been repeatedly unsuccessful. This failure may not only be due to the complexity and homology that is shared by Insulin and IGF receptors, but also due to the complex stroma-cancer interactions in the pancreas. Shedding light on the interactions between the endocrine/exocrine pancreas and the stroma in PDAC is likely to steer us toward the development of novel treatments. In this review, we highlight the stroma-derived IGF signaling and IGF-binding proteins as potential novel therapeutic targets in PDAC.

Use of common analgesic medications and ovarian cancer survival

DEFF Research Database (Denmark)

Dixon, Suzanne C; Nagle, Christina M; Wentzensen, Nicolas

2017-01-01

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with improved survival in some cancers, but evidence for ovarian cancer is limited. METHODS: Pooling individual-level data from 12 Ovarian Cancer Association Consortium studies, we evaluated the association between self......-reported, pre-diagnosis use of common analgesics and overall/progression-free/disease-specific survival among 7694 women with invasive epithelial ovarian cancer (4273 deaths). RESULTS: Regular analgesic use (at least once per week) was not associated with overall survival (pooled hazard ratios, pHRs (95......% confidence intervals): aspirin 0.96 (0.88-1.04); non-aspirin NSAIDs 0.97 (0.89-1.05); acetaminophen 1.01 (0.93-1.10)), nor with progression-free/disease-specific survival. There was however a survival advantage for users of any NSAIDs in studies clearly defining non-use as less than once per week (pHR=0...

Mature Teratoma Associated with Bilateral Ovarian Carcinosarcoma - Accidental Association or Etiopathogenetic Determinism? - Case Report.

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Birla, Rodica; Catanescu, Elena-Roxana; Caragui, Andrei; Constantinoiu, Silviu

2016-01-01

Carcinosarcoma is a rare form of ovarian cancer with mixed origin, and its association with mature teratoma is extremely rare. We present the case of patient T. M. aged 67, admitted into our clinic on the 15/05/2016, F.O. 4877 for the increase of the abdominal volume. On admission, the patient was afebrile, conscious, cooperative, cardio-respiratory balanced, having the abdomen distended in volume, sharp dullness in the flanks, positive wave sign bioumoral within normal limits except: uric acid = 6.64 mg / dL, serum glucose = 113.7 mg / dl, serum total proteins = 8.65 g / dl, the albumin / globulin subunit, CRP 33.63 mg / l, sideremia 51 ug / dl, CA 125 = 588.4 IU. Abdominal ultrasound: high volume fluid and multiple perihepatic formations and multiple formations with cystic transformation in the abdomen and pelvis. CT exam describes multiple tissular masses localized intraperitoneal in the abdominal-pelvic region, sheath fluid effusion, infiltrative, with mass effect on the digestive lumens, without visible CT obstruction. Surgical treatment consisted in evacuation of the ascites fluid, excision of the tumoral lumps situated in the great omentum, omentectomy, excision of the lumps of the gastrocolic ligament, bilateral ovariectomy and hysterectomy. Postoperative simple evolution. Histopathology confirmed the diagnosis of bilateral ovarian carcinosarcoma associated with tridermic mature teratoma (presence of brain tissue areas associated with cartilage, transitional type epithelium, tubal type epithelium, endometrial stroma type and fatty tissue). IHC confirms the compatibility with the diagnosis of ovarian carcinosarcoma (mixed malignant Mullerian tumor). The patient followed adjuvant polichemotherapy. The association of teratoma with carcinosarcomatoase elements confers a poor prognosis case. Celsius.

Risk of borderline ovarian tumors among women with benign ovarian tumors

DEFF Research Database (Denmark)

Guleria, Sonia; Jensen, Allan; Kjær, Susanne K

2018-01-01

tumors among women with a benign ovarian tumor. METHODS: This nationwide cohort study included all Danish women diagnosed with a benign ovarian tumor (n=139,466) during 1978-2012. The cohort was linked to the Danish Pathology Data Bank and standardized incidence ratios (SIR) with 95% confidence intervals...... (CI) were calculated. RESULTS: Women with benign ovarian tumors had increased risks for subsequent borderline ovarian tumors (SIR 1.62, 95% CI 1.43-1.82), and this applied to both serous (SIR 1.69, 95% CI 1.39-2.03) and mucinous (SIR 1.75, 95% CI 1.45-2.10) histotypes of borderline ovarian tumors....... The risk for borderline ovarian tumors was primarily increased for women diagnosed with a benign ovarian tumor before 40years of age. The risk remained increased up to 9years after a benign ovarian tumor diagnosis. Finally, the associations did not change markedly when analyzed for the different histotypes...

Effect of temperature, hydraulic residence time and elevated PCO2 on acid neutralization within a pulsed limestone bed reactor

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Watten, B.J.; Lee, P.C.; Sibrell, P.L.; Timmons, M.B.

2007-01-01

Limestone has potential for reducing reagent costs and sludge volume associated with treatment of acid mine drainage, but its use is restricted by slow dissolution rates and the deposition of Fe, Al and Mn-based hydrolysis products on reactive surfaces. We evaluated a pulsed limestone bed (PLB) reactor (15 L/min capacity) that uses a CO2 pretreatment step to accelerate dissolution and hydraulic shearing forces provided by intermittent fluidization to abrade and carry away surface scales. We established the effects of hydraulic residence time (HRT, 5.1-15.9 min), temperature (T, 12-22 ??C) and CO2 tension (PCO2, 34.5-206.8 kPa) on effluent quality when inlet acidity (Acy) was fixed at 440 mg/L (pH=2.48) with H2SO4. The PLB reactor neutralized all H+ acidity (N=80) while concurrently providing unusually high levels of effluent alkalinity (247-1028 mg/L as CaCO3) that allow for side-stream treatment with blending. Alkalinity (Alk) yields rose with increases in PCO2, HRT and settled bed height (BH, cm) and decreased with T following the relationship (R2=0.926; p<0.001): (Alk)non-filtered=-548.726+33.571??(PCO2)0.5+33.671??(HRT)+7.734??(BH)-5.197??(T). Numerical modeling showed CO2 feed requirements for a target Alk yield decrease with increases in HRT, T and the efficiency of off-gas (CO2) recycling. ?? 2007 Elsevier Ltd. All rights reserved.

The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients

International Nuclear Information System (INIS)

Medrek, Catharina; Pontén, Fredrik; Jirström, Karin; Leandersson, Karin

2012-01-01

Tumor associated macrophages (TAMs) are alternatively activated macrophages that enhance tumor progression by promoting tumor cell invasion, migration and angiogenesis. TAMs have an anti-inflammatory function resembling M2 macrophages. CD163 is regarded as a highly specific monocyte/macrophage marker for M2 macrophages. In this study we evaluated the specificity of using the M2 macrophage marker CD163 as a TAM marker and compared its prognostic value with the more frequently used pan-macrophage marker CD68. We also analyzed the prognostic value of the localization of CD163 + and CD68 + myeloid cells in human breast cancer. The extent of infiltrating CD163 + or CD68 + myeloid cells in tumor nest versus tumor stroma was evaluated by immunohistochemistry in tissue microarrays with tumors from 144 breast cancer cases. Spearman’s Rho and χ 2 tests were used to examine the correlations between CD163 + or CD68 + myeloid cells and clinicopathological parameters. Kaplan Meier analysis and Cox proportional hazards modeling were used to assess the impact of CD163 + and CD68 + myeloid cells in tumor stroma and tumor nest, respectively, on recurrence free survival, breast cancer specific and overall survival. We found that infiltration of CD163 + and CD68 + macrophages into tumor stroma, but not into tumor nest, were of clinical relevance. CD163 + macrophages in tumor stroma positively correlated with higher grade, larger tumor size, Ki67 positivity, estrogen receptor negativity, progesterone receptor negativity, triple-negative/basal-like breast cancer and inversely correlated with luminal A breast cancer. Some CD163 + areas lacked CD68 expression, suggesting that CD163 could be used as a general anti-inflammatory myeloid marker with prognostic impact. CD68 + macrophages in tumor stroma positively correlated to tumor size and inversely correlated to luminal A breast cancer. More importantly, CD68 in tumor stroma was an independent prognostic factor for reduced breast cancer

Changes in ovarian reserve and ovarian blood flow in patients with polycystic ovary syndrome following laparoscopic ovarian drilling.

Science.gov (United States)

Kamal, Nasser; Sanad, Zakaria; Elkelani, Osama; Rezk, Mohamed; Shawky, Mohamed; Sharaf, Abd-Elbar

2018-04-10

This prospective cohort study was conducted on 80 patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome undergoing laparoscopic ovarian drilling (LOD). Pre- and post-LOD ovarian reserve parameters (anti-Mullerian hormone: AMH, ovarian volume: OV, and antral follicle count: AFC) and ovarian stromal blood flow indices (Vascularization index: VI, flow index: FI, and vascularization flow index: VFI) were measured to explore the effect of LOD and to find out the correlation between serum AMH and different clinical, hormonal, and ultrasonic variables. There was a highly significant reduction of the serum AMH (p ovarian reserve parameters (AMH, OV and AFC) and ovarian stromal blood flow indices (VI, FI and VFI) with no observed correlation between AMH levels and Doppler indices.

Corneal stroma microfibrils.

Science.gov (United States)

Hanlon, Samuel D; Behzad, Ali R; Sakai, Lynn Y; Burns, Alan R

2015-03-01

Elastic tissue was first described well over a hundred years ago and has since been identified in nearly every part of the body. In this review, we examine elastic tissue in the corneal stroma with some mention of other ocular structures which have been more thoroughly described in the past. True elastic fibers consist of an elastin core surrounded by fibrillin microfibrils. However, the presence of elastin fibers is not a requirement and some elastic tissue is comprised of non-elastin-containing bundles of microfibrils. Fibers containing a higher relative amount of elastin are associated with greater elasticity and those without elastin, with structural support. Recently it has been shown that the microfibrils, not only serve mechanical roles, but are also involved in cell signaling through force transduction and the release of TGF-β. A well characterized example of elastin-free microfibril bundles (EFMBs) is found in the ciliary zonules which suspend the crystalline lens in the eye. Through contraction of the ciliary muscle they exert enough force to reshape the lens and thereby change its focal point. It is believed that the molecules comprising these fibers do not turn-over and yet retain their tensile strength for the life of the animal. The mechanical properties of the cornea (strength, elasticity, resiliency) would suggest that EFMBs are present there as well. However, many authors have reported that, although present during embryonic and early postnatal development, EFMBs are generally not present in adults. Serial-block-face imaging with a scanning electron microscope enabled 3D reconstruction of elements in murine corneas. Among these elements were found fibers that formed an extensive network throughout the cornea. In single sections these fibers appeared as electron dense patches. Transmission electron microscopy provided additional detail of these patches and showed them to be composed of fibrils (∼10 nm diameter). Immunogold evidence clearly

Corneal stroma microfibrils

KAUST Repository

Hanlon, Samuel D.

2015-03-01

Elastic tissue was first described well over a hundred years ago and has since been identified in nearly every part of the body. In this review, we examine elastic tissue in the corneal stroma with some mention of other ocular structures which have been more thoroughly described in the past. True elastic fibers consist of an elastin core surrounded by fibrillin microfibrils. However, the presence of elastin fibers is not a requirement and some elastic tissue is comprised of non-elastin-containing bundles of microfibrils. Fibers containing a higher relative amount of elastin are associated with greater elasticity and those without elastin, with structural support. Recently it has been shown that the microfibrils, not only serve mechanical roles, but are also involved in cell signaling through force transduction and the release of TGF-β. A well characterized example of elastin-free microfibril bundles (EFMBs) is found in the ciliary zonules which suspend the crystalline lens in the eye. Through contraction of the ciliary muscle they exert enough force to reshape the lens and thereby change its focal point. It is believed that the molecules comprising these fibers do not turn-over and yet retain their tensile strength for the life of the animal. The mechanical properties of the cornea (strength, elasticity, resiliency) would suggest that EFMBs are present there as well. However, many authors have reported that, although present during embryonic and early postnatal development, EFMBs are generally not present in adults. Serial-block-face imaging with a scanning electron microscope enabled 3D reconstruction of elements in murine corneas. Among these elements were found fibers that formed an extensive network throughout the cornea. In single sections these fibers appeared as electron dense patches. Transmission electron microscopy provided additional detail of these patches and showed them to be composed of fibrils (~10nm diameter). Immunogold evidence clearly

Projected near-future levels of temperature and pCO2 reduce coral fertilization success.

Directory of Open Access Journals (Sweden)

Rebecca Albright

Full Text Available Increases in atmospheric carbon dioxide (pCO2 are projected to contribute to a 1.1-6.4°C rise in global average surface temperatures and a 0.14-0.35 reduction in the average pH of the global surface ocean by 2100. If realized, these changes are expected to have negative consequences for reef-building corals including increased frequency and severity of coral bleaching and reduced rates of calcification and reef accretion. Much less is known regarding the independent and combined effects of temperature and pCO2 on critical early life history processes such as fertilization. Here we show that increases in temperature (+3°C and pCO2 (+400 µatm projected for this century negatively impact fertilization success of a common Indo-Pacific coral species, Acropora tenuis. While maximum fertilization did not differ among treatments, the sperm concentration required to obtain 50% of maximum fertilization increased 6- to 8- fold with the addition of a single factor (temperature or CO2 and nearly 50- fold when both factors interact. Our results indicate that near-future changes in temperature and pCO2 narrow the range of sperm concentrations that are capable of yielding high fertilization success in A. tenuis. Increased sperm limitation, in conjunction with adult population decline, may have severe consequences for coral reproductive success. Impaired sexual reproduction will further challenge corals by inhibiting population recovery and adaptation potential.

Early detection of cardiac ischemia using a conductometric pCO2 sensor: real-time drift correction and parameterization

International Nuclear Information System (INIS)

Tronstad, Christian; Martinsen, Ørjan G; Grimnes, Sverre; Pischke, Soeren E; Holhjem, Lars; Tønnessen, Tor Inge

2010-01-01

For detection of cardiac ischemia based on regional pCO 2 measurement, sensor drift becomes a problem when monitoring over several hours. A real-time drift correction algorithm was developed based on utilization of the time-derivative to distinguish between physiological responses and the drift, customized by measurements from a myocardial infarction porcine model (6 pigs, 23 sensors). IscAlert(TM) conductometric pCO 2 sensors were placed in the myocardial regions supplied by the left anterior descending coronary artery (LAD) and the left circumflex artery (LCX) while the LAD artery was fully occluded for 1, 3, 5 and 15 min leading to ischemia in the LAD-dependent region. The measured pCO 2 , the drift-corrected pCO 2 (ΔpCO 2 ) and its time-derivative (TDpCO 2 ) were compared with respect to detection ability. Baseline stability in the ΔpCO 2 led to earlier, more accurate detection. The TDpCO 2 featured the earliest sensitivity, but with a lower specificity. Combining ΔpCO 2 and TDpCO 2 enables increased accuracy. Suggestions are given for the utilization of the parameters for an automated early warning and alarming system. In conclusion, early detection of cardiac ischemia is feasible using the conductometric pCO 2 sensor together with parameterization methods

Synergism between elevated pCO2 and temperature on the Antarctic sea ice diatom Nitzschia lecointei

Directory of Open Access Journals (Sweden)

A. Torstensson

2013-10-01

Full Text Available Polar oceans are particularly susceptible to ocean acidification and warming. Diatoms play a significant role in sea ice biogeochemistry and provide an important food source to grazers in ice-covered oceans, especially during early spring. However, the ecophysiology of ice-living organisms has received little attention in terms of ocean acidification. In this study, the synergism between temperature and partial pressure of CO2 (pCO2 was investigated in relationship to the optimal growth temperature of the Antarctic sea ice diatom Nitzschia lecointei. Diatoms were kept in cultures at controlled levels of pCO2 (∼390 and ∼960 μatm and temperature (−1.8 and 2.5 °C for 14 days. Synergism between temperature and pCO2 was detected in growth rate and acyl lipid fatty acid (FA content. Optimal growth rate was observed around 5 °C in a separate experiment. Carbon enrichment only promoted (6% growth rate closer to the optimal growth, but not at the control temperature (−1.8 °C. At −1.8 °C and at ∼960 μatm pCO2, the total FA content was reduced relative to the ∼390 μatm treatment, although no difference between pCO2 treatments was observed at 2.5 °C. A large proportion (97% of the total FAs comprised on average of polyunsaturated fatty acids (PUFA at −1.8 °C. Cellular PUFA content was reduced at ∼960 relative to ∼390 μatm pCO2. Effects of carbon enrichment may be different depending on ocean warming scenario or season, e.g. reduced cellular FA content in response to elevated CO2 at low temperatures only, reflected as reduced food quality for higher trophic levels. Synergy between warming and acidification may be particularly important in polar areas since a narrow thermal window generally limits cold-water organisms.

Evaluation of the ovarian reserve in women transplanted with frozen and thawed ovarian cortical tissue

DEFF Research Database (Denmark)

Greve, Tine; Schmidt, Kirsten Tryde; Kristensen, Stine Gry

2012-01-01

To investigate ovarian reserve and ovarian function in women transplanted with frozen/thawed ovarian tissue.......To investigate ovarian reserve and ovarian function in women transplanted with frozen/thawed ovarian tissue....

Modeling extracellular matrix (ECM) alterations in ovarian cancer by multiphoton excited fabrication of stromal models (Conference Presentation)

Science.gov (United States)

Campagnola, Paul J.; Ajeti, Visar; Lara, Jorge; Eliceiri, Kevin W.; Patankar, Mansh

2016-04-01

A profound remodeling of the extracellular matrix (ECM) occurs in human ovarian cancer but it unknown how this affects tumor growth, where this understanding could lead to better diagnostics and therapeutic approaches. We investigate the role of these ECM alterations by using multiphoton excited (MPE) polymerization to fabricate biomimetic models to investigate operative cell-matrix interactions in invasion/metastasis. First, we create nano/microstructured gradients mimicking the basal lamina to study adhesion/migration dynamics of ovarian cancer cells of differing metastatic potential. We find a strong haptotactic response that depends on both contact guidance and ECM binding cues. While we found enhanced migration for more invasive cells, the specifics of alignment and directed migration also depend on cell polarity. We further use MPE fabrication to create collagen scaffolds with complex, 3D submicron morphology. The stromal scaffold designs are derived directly from "blueprints" based on SHG images of normal, high risk, and malignant ovarian tissues. The models are seeded with different cancer cell lines and this allows decoupling of the roles of cell characteristics (metastatic potential) and ECM structure and composition (normal vs cancer) on adhesion/migration dynamics. We found the malignant stroma structure promotes enhanced migration and proliferation and also cytoskeletal alignment. Creating synthetic models based on fibers patterns further allows decoupling the topographic roles of the fibers themselves vs their alignment within the tissue. These models cannot be synthesized by other conventional fabrication methods and we suggest the MPE image-based fabrication method will enable a variety of studies in cancer biology.

[Peripubertal ovarian cyst torsion as an early complication of undiagnosed polycystic ovarian syndrome].

Science.gov (United States)

Ságodi, László; Schmidt, Ildikó; Vámosi, Ildikó; Barkai, László

2013-01-20

The aim of the authors is to present two cases which raise the possibility of an association between polycystic ovarian syndrome/hyperandrogenism and ovarian cyst torsion in peripubertal girls. Androgen excess may cause more frequently ovarian cyst formation in premenarcheal or young adolescents with undiagnosed polycystic ovarian syndrome than in adults. The authors recommend that polycystic ovarian syndrome as well as late onset congenital adrenal hyperplasia should be considered in peripubertal adolescents with ovarian cyst torsion. In case polycystic ovarian syndrome is confirmed, adequate management according to age and pubertal development of the patients should be commenced.

Subtypes of Ovarian Cancer and Ovarian Cancer Screening

Directory of Open Access Journals (Sweden)

Masafumi Koshiyama

2017-03-01

Full Text Available Ovarian cancer is the foremost cause of gynecological cancer death in the developed world, as it is usually diagnosed at an advanced stage. In this paper we discuss current issues, the efficacy and problems associated with ovarian cancer screening, and compare the characteristics of ovarian cancer subtypes. There are two types of ovarian cancer: Type I carcinomas, which are slow-growing, indolent neoplasms thought to arise from a precursor lesion, which are relatively common in Asia; and Type II carcinomas, which are clinically aggressive neoplasms that can develop de novo from serous tubal intraepithelial carcinomas (STIC and/or ovarian surface epithelium and are common in Europe and the USA. One of the most famous studies on the subject reported that annual screening using CA125/transvaginal sonography (TVS did not reduce the ovarian cancer mortality rate in the USA. In contrast, a recent study in the UK showed an overall average mortality reduction of 20% in the screening group. Another two studies further reported that the screening was associated with decreased stage at detection. Theoretically, annual screening using CA125/TVS could easily detect precursor lesions and could be more effective in Asia than in Europe and the USA. The detection of Type II ovarian carcinoma at an early stage remains an unresolved issue. The resolving power of CA125 or TVS screening alone is unlikely to be successful at resolving STICs. Biomarkers for the early detection of Type II carcinomas such as STICs need to be developed.

Subtypes of Ovarian Cancer and Ovarian Cancer Screening.

Science.gov (United States)

Koshiyama, Masafumi; Matsumura, Noriomi; Konishi, Ikuo

2017-03-02

Ovarian cancer is the foremost cause of gynecological cancer death in the developed world, as it is usually diagnosed at an advanced stage. In this paper we discuss current issues, the efficacy and problems associated with ovarian cancer screening, and compare the characteristics of ovarian cancer subtypes. There are two types of ovarian cancer: Type I carcinomas, which are slow-growing, indolent neoplasms thought to arise from a precursor lesion, which are relatively common in Asia; and Type II carcinomas, which are clinically aggressive neoplasms that can develop de novo from serous tubal intraepithelial carcinomas (STIC) and/or ovarian surface epithelium and are common in Europe and the USA. One of the most famous studies on the subject reported that annual screening using CA125/transvaginal sonography (TVS) did not reduce the ovarian cancer mortality rate in the USA. In contrast, a recent study in the UK showed an overall average mortality reduction of 20% in the screening group. Another two studies further reported that the screening was associated with decreased stage at detection. Theoretically, annual screening using CA125/TVS could easily detect precursor lesions and could be more effective in Asia than in Europe and the USA. The detection of Type II ovarian carcinoma at an early stage remains an unresolved issue. The resolving power of CA125 or TVS screening alone is unlikely to be successful at resolving STICs. Biomarkers for the early detection of Type II carcinomas such as STICs need to be developed.

Equilibrium p(CO) measurements over V-C-O system

International Nuclear Information System (INIS)

Sayi, Y.S.; Khan, M.I.; Radhakrishna, J.; Shankaran, P.S.; Yadav, C.S.; Chhapru, G.C.; Shukla, N.K.; Prasad, R.; Sood, D.D.

1986-01-01

The equilibrium partial pressure of (CO) over hyperstoichiometric U-C-O system has been measured in the temperature range 1300-1700degC. Slope of the curve log p(CO) vs.1/T(K) changed at about 1450degC indicating some change in the reaction involved in the formation of (CO). The enthalpy change for the possible reactions are also determined. (author)

Comparative transcriptome analysis links distinct peritoneal tumor spread types, miliary and non-miliary, with putative origin, tubes and ovaries, in high grade serous ovarian cancer.

Science.gov (United States)

Auer, Katharina; Bachmayr-Heyda, Anna; Aust, Stefanie; Grunt, Thomas W; Pils, Dietmar

2017-03-01

High grade serous ovarian cancer (HGSOC) is characterized by extensive local, i.e. peritoneal, tumor spread, manifested in two different clinical presentations, miliary (many millet sized peritoneal implants) and non-miliary (few large exophytically growing peritoneal nodes), and an overall unfavorable outcome. HGSOC is thought to arise from fallopian tube secretory epithelial cells, via so called serous tubal intraepithelial carcinomas (STICs) but an ovarian origin was never ruled out for at least some cases. Comparative transcriptome analyses of isolated tumor cells from fresh HGSOC tissues and (immortalized) ovarian surface epithelial and fallopian tube secretory epithelial cell lines revealed a close relation between putative origin and tumor spread characteristic, i.e. miliary from tubes and non-miliary from ovaries. The latter were characterized by more mesenchymal cell characteristics, more adaptive tumor immune infiltration, and a favorable overall survival. Several molecular sub-classification systems (Crijns' overall survival signature, Yoshihara's subclasses, and a collagen-remodeling signature) seem to already indicate origin. Putative origin alone is a significant independent predictor for HGSOC outcome, validated in independent patient cohorts. Characteristics of both spread types could guide development of new targeted therapeutics, which are urgently needed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hurricane Arthur and its effect on the short term variation of pCO2

Science.gov (United States)

Lemay, Jonathan; Thomas, Helmuth; Craig, Susanne; Greenan, Blair; Fennel, Katja

2016-04-01

Seasonal changes in carbon cycling over the years have become better understood on the Scotian Shelf, however little is resolved in short term variation. Hourly measurements were collected from an autonomous moored instrument (CARIOCA) stationed at Halifax Line 2 (HL2), roughly 30km off the coast of Halifax for the 2014 year. Data from the 2007 deployment of the SeaHorse vertical sampling mooring at HL2 was also collected. Focusing on the storm event, Hurricane Arthur, July 5th 2014 reveals a significant drop in pCO2. With the shelf having carbon rich deep water, a reduction of pCO2 due to mixing went against current understanding. It was revealed that slightly above the mixed layer there is a sustained population of phytoplankton. When wind mixing from storms occurs, this population moves to the surface allowing greater light and nutrients for short term growth. This growth then reduces pCO2 for a short period of time until wind speeds slow down reducing mixing of the water column.

Tubo-ovarian actinomycosis.

Directory of Open Access Journals (Sweden)

Shroff C

1981-01-01

Full Text Available Actinomycotic infection of the female genital tract is rare. Actinomycosis is a chronic suppurative granulomatous infection that is characterized by formation of abscesses, multiple draining sinuses and appearance of tangled mycelial masses or granules in the discharges and tissue sections. 2 cases of tubo-ovarian actinomycosis are reported. The 1st case presented clinical with gastrointestinal symptoms and a ventral scar hernia following an operation for a non-healing abdominal wound 6 months earlier. The 2nd case sought medical attention for backache and leucorrhea of 4 years′ duration. Exploratory laparotomy in the 1st case revealed tubo-ovarian masses; the vermiform appendix was not traceable. The uterine cavity in the 2nd case harbored a wooden stick. Direct extension from established ileocacal actinomycosis was believed to involve the female genital adnexae in the past. Association of tubo-ovarian actinomycosis with the presence of a foreign body in the female genital tract has been reported sporadically in the literature, yet an increase in the incidence may be expected because of the frequent use of intrauterine contraceptive devices in recent times. It is suggested that in women presenting clinically with vague abdominal symptoms, backache and discharge, actinomycosis should be considered and ruled out with the help of cytologic and proper microbial culture methods. Once the diagnosis is established, the infection can be treated with good results with penicillin.

Low pCO2 under sea-ice melt in the Canada Basin of the western Arctic Ocean

Science.gov (United States)

Kosugi, Naohiro; Sasano, Daisuke; Ishii, Masao; Nishino, Shigeto; Uchida, Hiroshi; Yoshikawa-Inoue, Hisayuki

2017-12-01

In September 2013, we observed an expanse of surface water with low CO2 partial pressure (pCO2sea) (Ocean. The large undersaturation of CO2 in this region was the result of massive primary production after the sea-ice retreat in June and July. In the surface of the Canada Basin, salinity was low ( 20 µmol kg-1) in the subsurface low pCO2sea layer in the Canada Basin indicated significant net primary production undersea and/or in preformed condition. If these low pCO2sea layers surface by wind mixing, they will act as additional CO2 sinks; however, this is unlikely because intensification of stratification by sea-ice melt inhibits mixing across the halocline.

Facile formation of 2D Co2P@Co3O4 microsheets through in-situ toptactic conversion and surface corrosion: Bifunctional electrocatalysts towards overall water splitting

Science.gov (United States)

Yao, Lihua; Zhang, Nan; Wang, Yin; Ni, Yuanman; Yan, Dongpeng; Hu, Changwen

2018-01-01

Exploring efficient non-precious electrocatalysts for both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is crucial for many renewable energy conversion processes. In this work, we report that 2D Co2P@Co3O4 microsheets can be prepared through an in-situ toptactic conversion from single-crystal β-Co(OH)2 microplatelets, associated with a surface phosphatization and corrosion process. The resultant Co2P@Co3O4 2D hybrid materials can further serve as self-supported bifunctional catalytic electrodes to drive the overall water splitting for HER and OER simultaneously, with low overpotentials and high long-term stability. Furthermore, a water electrolyzer based on Co2P@Co3O4 hybrid as both anode and cathode is fabricated, which achieves 10 mA cm-2 current at only 1.57 V during water splitting process. Therefore, this work provides a facile strategy to obtain 2D Co2P-based micro/nanostructures, which act as low-cost and highly active electrocatalysts towards overall water splitting application.

Polymorphism in the IL18 gene and epithelial ovarian cancer in non-Hispanic white women

DEFF Research Database (Denmark)

Palmieri, R.T.; Wilson, M.A.; Iversen, E.S.

2008-01-01

Over 22,000 cases of ovarian cancer were diagnosed in 2007 in the United States, but only a fraction of them can be attributed to mutations in highly penetrant genes such as BRCA1. To determine whether low-penetrance genetic variants contribute to ovarian cancer risk, we genotyped 1,536 single...

Brain parenchyma PO2, PCO2, and pH during and after hypoxic, ischemic brain insult in dogs.

Science.gov (United States)

McKinley, B A; Morris, W P; Parmley, C L; Butler, B D

1996-11-01

1) The investigation of fiberoptic PO2, PCO2, and pH sensor technology as a monitor of brain parenchyma during and after brain injury, and 2) the comparison of brain parenchyma PO2, PCO2, and pH with intracranial pressure during and after hypoxic, ischemic brain insult. Prospective, controlled, animal study in an acute experimental preparation. Physiology laboratory in a university medical school. Fourteen mongrel dogs (20 to 35 kg), anesthetized, room-air ventilated. Anesthesia was induced with thiopental and maintained after intubation using 1% to 1.5% halothane in room air (FiO2 0.21). Mechanical ventilation was established to maintain end-tidal PCO2 approximately 35 torr (-4.7 kPa). Intravenous, femoral artery, and pulmonary artery catheters were placed. The common carotid arteries were surgically exposed, and ultrasonic blood flow probes were applied. A calibrated intracranial pressure probe was placed through a right-side transcranial bolt, and a calibrated intracranial chemistry probe with optical sensors for PO2, PCO2, and pH was placed through a left-side bolt into brain parenchyma. Brain insult was induced in the experimental group (n = 6) by hypoxia (FiO2 0.1), ischemia (bilateral carotid artery occlusion), and hypotension (mean arterial pressure [MAP] approximately 40 mm Hg produced with isoflurane approximately 4%). After 45 mins, carotid artery occlusion was released, FiO2 was reset to 0.21, and anesthetic was returned to halothane (approximately 1.25%). The control group (n = 5) had the same surgical preparation and sequence of anesthetic agent exposure but no brain insult. Monitored variables included brain parenchyma PO2, PCO2, and pH, which were monitored at 1-min intervals, and intracranial pressure, MAP, arterial hemoglobin oxygen saturation (by pulse oximetry), end-tidal PCO2, and carotid artery blood flow rate, for which data were collected at 15-min intervals for 7 hrs. Arterial and mixed venous blood gas analyses were done at approximately 1

Mechanisms of Reactive Stroma-Induced Tumorigenesis in Prostate Cancer

Science.gov (United States)

2016-11-01

type I receptor blocker (SI Appendix, Fig. S9). Together, these results further support the concept that TGF-β1–expressing prostate cancer cells induce...of NBT-II bladder carcinoma cells to condi- tioned medium from normal fetal urogenital sinus. Cancer Res 47(11):2955–2960. 22. Nimmo R, Woollard A...AWARD NUMBER: W81XWH-12-1-0197 TITLE: Mechanisms of Reactive Stroma - Induced Tumorigenesis in Prostate Cancer PRINCIPAL INVESTIGATOR

Regulation of HGF and c-MET Interaction in Normal Ovary and Ovarian Cancer.

Science.gov (United States)

Kwon, Youngjoo; Godwin, Andrew K

2017-04-01

Binding of hepatocyte growth factor (HGF) to the c-MET receptor has mitogenic, motogenic, and morphogenic effects on cells. The versatile biological effects of HGF and c-MET interactions make them important contributors to the development of malignant tumors. We and others have demonstrated a therapeutic value in targeting the interaction of c-MET and HGF in epithelial ovarian cancer (EOC). However, both HGF and c-MET are expressed in the normal ovary as well. Therefore, it is important to understand the differences in mechanisms that control HGF signaling activation and its functional role in the normal ovary and EOC. In the normal ovary, HGF signaling may be under hormonal regulation. During ovulation, HGF-converting proteases are secreted and the subsequent activation of HGF signaling enhances the proliferation of ovarian surface epithelium in order to replenish the area damaged due to expulsion of the ovum. In contrast, EOC cells that exhibit epithelial characteristics constitutively express both c-MET and HGF-converting proteases such as urokinase-type plasminogen activator. In EOC, mechanisms to control the activation of HGF signaling are absent since HGF is provided locally from the tissue microenvironment as well as remotely throughout the body. Potential incessant HGF signaling in EOC may lead to an increase in proliferation, invasion through the stroma, and migration to other tissues of cancer cells. Therefore, targeting the interaction of c-MET and HGF would be beneficial in treating EOC.

Increased risk for ovarian cancer and borderline ovarian tumours in subfertile women with endometriosis

NARCIS (Netherlands)

Buis, C. C. M.; van Leeuwen, F. E.; Mooij, T. M.; Burger, C. W.; Lambalk, Cornelis B.; Kortman, Marian; Laven, Joop S. E.; Jansen, Cees A. M.; Helmerhorst, Frans M.; Cohlen, Ben J.; Willemsen, Wim N. P.; Smeenk, Jesper M. J.; Simons, Arnold H. M.; van der Veen, Fulco; Evers, Johannes L. H.; van Dop, Peter A.; Macklon, Nicholas S.

2013-01-01

Is ovarian or extra-ovarian endometriosis associated with an increased risk of ovarian cancer and borderline ovarian tumours (BOT)? We found a 3- to 8-fold increased risk of ovarian tumours associated with endometriosis: the magnitude of the risk increase depended on the definition of endometriosis.

Serum AMH Level to Predict the Hyper Response in Women with PCOS and Non-PCOS Undergoing Controlled Ovarian Stimulation in ART.

Science.gov (United States)

Vembu, Radha; Reddy, Nellepalli Sanjeeva

2017-01-01

It is essential to determine the cut-off value of serum anti-Mullerian hormone (AMH) to predict the hyper response in assisted reproductive technology (ART). There are few studies mentioning the cut-off value for the hyper response in infertile women but not specifically for polycystic ovary syndrome (PCOS) and non-PCOS groups. With this in background, this study was conducted. To determine the cut-off value of serum AMH to predict the hyper response in women with PCOS and non-PCOS undergoing a controlled ovarian stimulation (COS) in ART. To compare the outcome of stimulation in PCOS and non-PCOS groups. All 246 women enrolled for Intra Cytoplasmic Sperm Injection (ICSI) fulfilling the selection criteria were recruited. On the day 3 of the cycle, the serum AMH, Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), estradiol and antral follicle count (AFC) were measured. They underwent COS as per the unit protocol. They were divided into PCOS and non-PCOS groups as per the Rotterdam's criteria. The mean age, duration of infertility, Body Mass Index (BMI), Ovarian reserve markers and outcome of stimulation were compared. Using the Statistical Package for the Social Sciences version 16.0 software, the significant difference was measured by multivariate analysis, as well as a one-way analysis of variance with Tukey's post-hoc test was used. Among 246 women, 31.3% were in PCOS group, and 68.7% were in non-PCOS group. Comparison of PCOS and non-PCOS groups showed a significant difference in the age with the mean age being 29.2 and 31.5 years, respectively. The mean AMH and AFC were 2-fold higher in PCOS group. The mean number of follicles, oocytes retrieved, MII and oocytes fertilised were significantly higher in PCOS group. The pregnancy rate was 52.6% in PCOS and 30.9% in non-PCOS group. In the PCOS group, 22.1% had ovarian hyper stimulation syndrome (OHSS), and only 4.7% had OHSS in non-PCOS group ( P = 0.0005). Receiving Operator Curve (ROC) curve was plotted

Pancreatic Adenocarcinoma Therapeutic Targets Revealed by Tumor-Stroma Cross-Talk Analyses in Patient-Derived Xenografts

Directory of Open Access Journals (Sweden)

Rémy Nicolle

2017-11-01

Full Text Available Preclinical models based on patient-derived xenografts have remarkable specificity in distinguishing transformed human tumor cells from non-transformed murine stromal cells computationally. We obtained 29 pancreatic ductal adenocarcinoma (PDAC xenografts from either resectable or non-resectable patients (surgery and endoscopic ultrasound-guided fine-needle aspirate, respectively. Extensive multiomic profiling revealed two subtypes with distinct clinical outcomes. These subtypes uncovered specific alterations in DNA methylation and transcription as well as in signaling pathways involved in tumor-stromal cross-talk. The analysis of these pathways indicates therapeutic opportunities for targeting both compartments and their interactions. In particular, we show that inhibiting NPC1L1 with Ezetimibe, a clinically available drug, might be an efficient approach for treating pancreatic cancers. These findings uncover the complex and diverse interplay between PDAC tumors and the stroma and demonstrate the pivotal role of xenografts for drug discovery and relevance to PDAC.

Individualization of controlled ovarian stimulation in vitro fertilization using ovarian reserve markers.

Science.gov (United States)

Grisendi, Valentina; La Marca, Antonio

2017-06-01

In assisted reproduction technologies (ART) the controlled ovarian stimulation (COS) therapy is the starting point from which a good oocytes retrieval depends. Treatment individualization is based on ovarian response prediction, which largely depends on a woman's ovarian reserve. Anti-Müllerian hormone (AMH) and antral follicle count (AFC) are considered the most accurate and reliable markers of ovarian reserve. A literature search was carried out for studies that addressed the ability of AMH and AFC to predict poor and/or excessive ovarian response in IVF cycles. According to the predicted response to ovarian stimulation (poor- normal- or high-response) is today possible not only to personalize pre-treatment counseling with the couple, but also to individualize the ovarian stimulation protocol, choosing among GnRH-agonists or antagonists for endogenous follicle-stimulating hormone (FSH) suppression and formulating the FSH starting dose most adequate for the single patients. In this review we discuss how to choose the best COS therapy for the single patient, on the basis of the markers-guided ovarian response prediction.

Canine ovarian neoplasms: a clinicopathologic study of 71 cases, including histology of 12 granulosa cell tumors.

Science.gov (United States)

Patnaik, A K; Greenlee, P G

1987-11-01

In a retrospective study of 71 primary ovarian tumors in the dog, epithelial tumors (46%) were more common than sex cord stromal (34%) and germ cell tumors (20%). There were more adenocarcinomas (64%) than adenomas. Sex cord stromal tumors were equally divided into Sertoli-Leydig (12/24) and granulosa cell tumors (12/24). There were equal numbers (7/14) of dysgerminomas and teratomas among the germ cell tumors. Most teratomas (6/7) were malignant. Most granulosa cell tumors were solid; two were mostly cystic. Patterns included sheets of round and ovoid to spindle-shaped cells separated by thin, fibrovascular stroma; neoplastic cells formed rosettes or Call-Exner bodies. In some areas, neoplastic cells were in cords or columns and formed cyst-like structures. Four granulosa cell tumors were macrofollicular, having cysts lined with granulosa cells. Median ages of dogs with different ovarian neoplasms were similar; all were more than 10 years old, except the dogs with teratoma (mean age, 4 years). Most neoplasms were unilateral (84%), except the Sertoli-Leydig cell tumors, many of which were bilateral (36%). Size of ovarian neoplasms varied (2 cm3 to 15,000 cm3). Twenty-nine percent of neoplasms metastasized; adenocarcinomas (48%) and malignant teratomas (50%) had the highest rates, and distant metastasis was more common in malignant teratoma. Endometrial hyperplasia was in 67% of the dogs; it was most common in dogs with sex cord stromal tumors (95%). Uterine malignancy was not seen in dogs with granulosa cell tumors, although hyperplasia endometrium was in all dogs with this tumor. Cysts in the contralateral ovaries were most common in dogs with sex cord stromal tumors.

Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis

Science.gov (United States)

2015-08-01

exposure to the HFD or LFD, obese mice weighed significantly greater than lean mice (p=0.003, Table 1). There was no effect of HFD on non- fasted blood...AWARD NUMBER: W81XWH-13-1-0164 TITLE: Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis PRINCIPAL INVESTIGATOR: Victoria Bae...31 May 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis 5b. GRANT NUMBER

Random-start ovarian stimulation in women desiring elective cryopreservation of oocytes.

Science.gov (United States)

Pereira, Nigel; Voskuilen-Gonzalez, Anna; Hancock, Kolbe; Lekovich, Jovana P; Schattman, Glenn L; Rosenwaks, Zev

2017-10-01

The current study investigates the utility of random-start ovarian stimulation in women desiring elective oocyte cryopreservation. Women in the study cohort underwent random-start ovarian stimulation, and were subdivided based on the phase of the menstrual cycle that ovarian stimulation began, i.e. early follicular, late follicular or luteal phase. Women undergoing conventional cycle day (CD) 2/3 ovarian stimulation start were controls. A total of 1302 women were included - 859 (66.0%) conventional CD 2/3, 342 (26.3%) early follicular, 42 (3.2%) late follicular and 59 (4.5%) luteal ovarian stimulation starts. There was no difference in the demographics or baseline ovarian stimulation characteristics. The duration of ovarian stimulation (11 versus 9 days; P start group. The number of total and MII oocytes in the control and random-start groups was similar. A non-significant trend towards increased cycle cancellation was noted in the late follicular start group (7.1%). Study findings indicate the number of total and MII oocytes derived from random-start protocols initiated during any phase of the menstrual cycle is similar to conventional CD 2/3 ovarian stimulation start protocols in women desiring elective oocyte cryopreservation. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Increased cerebrovascular pCO2 reactivity in migraine with aura--a transcranial Doppler study during hyperventilation

DEFF Research Database (Denmark)

Thomsen, L L; Iversen, Helle Klingenberg; Olesen, J

1995-01-01

cerebral artery was measured with transcranial Doppler. In each subject a pCO2 reactivity index (RI) was calculated as (delta Vmean/baseline Vmean)/delta pCO2. Interictally, patients with migraine with aura showed higher RI (p ANOVA and multiple range test) than controls, whereas migraineurs without......-nitroglycerin-provoked healthy controls (p > 0.05, ANOVA and multiple range test). The exaggerated response in migraine with aura might predispose for the characteristic changes in rCBF seen during attacks....

Light-sheet microscopy for quantitative ovarian folliculometry

Science.gov (United States)

Lin, Hsiao-Chun Amy; Dutta, Rahul; Mandal, Subhamoy; Kind, Alexander; Schnieke, Angelika; Razansky, Daniel

2017-02-01

Determination of ovarian status and follicle monitoring are common methods of diagnosing female infertility. We evaluated the suitability of selective plane illumination microscopy (SPIM) for the study of ovarian follicles. Owing to the large field of view and fast acquisition speed of our newly developed SPIM system, volumetric image stacks from entire intact samples of pig ovaries have been rendered demonstrating clearly discernible follicular features like follicle diameters (70 μm - 2.5 mm), size of developing Cumulus oophorus complexes (COC ) (40 μm - 110 μm), and follicular wall thicknesses (90 μm-120 μm). The observation of clearly distinguishable COCs protruding into the follicular antrum was also shown possible, and correlation with the developmental stage of the follicles was determined. Follicles of all developmental stages were identified, and even the small primordial follicle clusters forming the egg nest could be observed. The ability of the system to non-destructively generate sub-cellular resolution 3D images of developing follicles, with excellent image contrast and high throughput capacity compared to conventional histology, suggests that it can be used to monitor follicular development and identify structural abnormalities indicative of ovarian ailments. Accurate folliculometric measurements provided by SPIM images can immensely help the understanding of ovarian physiology and provide important information for the proper management of ovarian diseases.

Effect of ovarian endometrioma on uterine and ovarian blood flow in infertile women

Directory of Open Access Journals (Sweden)

El-Mazny A

2016-11-01

Full Text Available Akmal El-Mazny, Ahmed Kamel, Wafaa Ramadan, Sherine Gad-Allah, Suzy Abdelaziz, Ahmed M Hussein Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt Background: Angiogenesis has been found to be among the most important factors in the pathogenesis of endometriosis. The formation of new blood vessels is critical for the survival of newly implanted endometriotic foci. The use of 3-D power Doppler allows for the demonstration of the dynamic vascular changes that occur during the process of in vitro fertilization (IVF. We aimed to evaluate the effect of ovarian endometrioma on uterine and ovarian blood flow in infertile women. Materials and methods: In a case–control study at a university teaching hospital, 138 women with unilateral ovarian endometrioma scheduled for IVF were compared to 138 women with male-factor or unexplained infertility. In the mid-luteal (peri-implantation phase of the cycle, endometrial thickness, uterine and ovarian artery pulsatility index and resistance index, endometrial and ovarian volume, 3-D power Doppler vascularization index (VI, flow index (FI, and vascularization FI (VFI values were measured in both groups. Results: There were no significant differences (P>0.05 in endometrial thickness, uterine ovarian artery pulsatility index and resistance index, endometrial and ovarian volume, or VI, FI, and VFI between the two groups. Furthermore, the endometrial and ovarian Doppler indices were not influenced by endometrioma size. No significant differences were observed in the ovarian Doppler indices between endometrioma-containing ovaries and contralateral ovaries. Conclusion: Ovarian endometrioma is not associated with impaired endometrial and ovarian blood flows in infertile women scheduled for IVF, and it is not likely to affect endometrial receptivity or ovarian function through a vascular mechanism. Keywords: 3-D power Doppler, endometrioma, IVF, uterine and ovarian blood flow

Seasonal controls on surface pCO2 in the central and eastern ...

Indian Academy of Sciences (India)

The mixed layer pCO2 relations with temperature, oxygen, chlorophyll a and primary production revealed ..... Temperature dependence of CO2 fugacity in sea water; Mar. Chem. ... 1996 Mechanism of the biological response to winter cooling.

Prognostic value of podoplanin expression in intratumoral stroma and neoplastic cells of uterine cervical carcinomas

Science.gov (United States)

Carvalho, Filomena M; Zaganelli, Fabricia L; Almeida, Bernardo G L; Goes, Joao Carlos Sampaio; Baracat, Edmund C; Carvalho, Jesus P

2010-01-01

OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2‐40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6%) cases, with 29/31 (93.5%) of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node‐positive cases was lower than that of node‐negative (18.9% vs. 22.6%, respectively). Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5% vs. 21.6%, respectively. In 27/143 (18.8%) cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5% vs. 3.7%, respectively), although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host‐tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas. PMID:21340215

Prognostic value of podoplanin expression in intratumoral stroma and neoplastic cells of uterine cervical carcinomas

Directory of Open Access Journals (Sweden)

Filomena M Carvalho

2010-01-01

Full Text Available OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2-40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6% cases, with 29/31 (93.5% of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node-positive cases was lower than that of node-negative (18.9% vs. 22.6%, respectively. Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5% vs. 21.6%, respectively. In 27/143 (18.8% cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5% vs. 3.7%, respectively, although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host-tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas.

The role of ovarian fossa evaluation in patients with ovarian endometriosis.

Science.gov (United States)

De Cicco Nardone, Carlo; Terranova, Corrado; Plotti, Francesco; Ricciardi, Roberto; Capriglione, Stella; Luvero, Daniela; Caserta, Donatella; Moscarini, Massimo; Benedetti Panici, Pierluigi; Angioli, Roberto

2015-10-01

The aim of this study is to evaluate prospectively the presence of endometriosis in the peritoneum of the ovarian fossa of patients affected by endometriomas and its correlation with the adhesion between this peritoneum and endometrioma. Patients presenting ovarian endometriomas and candidate to laparoscopy were considered for inclusion in the study. Patients underwent laparoscopic excision of endometriomas. The presence of adherence of the ovarian fossa to endometrioma was investigated. In all patients, the removal of a peritoneum fragment from the ovarian fossa of the affected ovary was carried out. 68 patients were enrolled in the study. 48 patients presented adhesions to the ovarian fossa. Histopathologic examination of the peritoneum of the ovarian fossa revealed the presence of endometriosis in 87 % of patients presenting adhesions of the endometriomas with ovarian fossa; surprisingly it was present only in 15 % of patients not presenting this condition (p endometriosis on the peritoneal surface of the fossa. This condition significantly correlates with pain symptoms and may predict endometrioma recurrence. The removal of this peritoneum in case of adherent endometrioma may potentially reduce the incidence of recurrence.

A non-synonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers

Science.gov (United States)

Ding, Yuan C.; McGuffog, Lesley; Healey, Sue; Friedman, Eitan; Laitman, Yael; Shani-Shimon–Paluch; Kaufman, Bella; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Gronwald, Jacek; Huzarski, Tomasz; Cybulski, Cezary; Byrski, Tomasz; Osorio, Ana; Cajal, Teresa Ramóny; Stavropoulou, Alexandra V; Benítez, Javier; Hamann, Ute; Rookus, Matti; Aalfs, Cora M.; de Lange, Judith L.; Meijers-Heijboer, Hanne E.J.; Oosterwijk, Jan C.; van Asperen, Christi J.; García, Encarna B. Gómez; Hoogerbrugge, Nicoline; Jager, Agnes; van der Luijt, Rob B.; Easton, Douglas F.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Lalloo, Fiona; Izatt, Louise; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Brewer, Carole; Tischkowitz, Marc; Godwin, Andrew K.; Pathak, Harsh; Stoppa-Lyonnet, Dominique; Sinilnikova, Olga M.; Mazoyer, Sylvie; Barjhoux, Laure; Léoné, Mélanie; Gauthier-Villars, Marion; Caux-Moncoutier, Virginie; de Pauw, Antoine; Hardouin, Agnès; Berthet, Pascaline; Dreyfus, Hélène; Ferrer, Sandra Fert; Collonge-Rame, Marie-Agnès; Sokolowska, Johanna; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy; John, Esther M; Southey, Melissa; Goldgar, David; Singer, Christian F; Maria, Muy-Kheng Tea; Gschwantler-Kaulich, Daphne; Fink-Retter, Anneliese; Hansen, Thomas v. O.; Ejlertsen, Bent; Johannsson, Oskar Th.; Offit, Kenneth; Sarrel, Kara; Gaudet, Mia M.; Vijai, Joseph; Robson, Mark; Piedmonte, Marion R; Andrews, Lesley; Cohn, David; DeMars, Leslie R.; DiSilvestro, Paul; Rodriguez, Gustavo; Toland, Amanda Ewart; Montagna, Marco; Agata, Simona; Imyanitov, Evgeny; Isaacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Ramus, Susan J; Sucheston, Lara; Karlan, Beth Y.; Gross, Jenny; Ganz, Patricia A.; Beattie, Mary S.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Meindl, Alfons; Arnold, Norbert; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Nevanlinna, Heli; Aittomäki, Kristiina; Simard, Jacques; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Tomlinson, Gail E.; Weitzel, Jeffrey; Garber, Judy E.; Olopade, Olufunmilayo I.; Rubinstein, Wendy S.; Tung, Nadine; Blum, Joanne L.; Narod, Steven A.; Brummel, Sean; Gillen, Daniel L.; Lindor, Noralane; Fredericksen, Zachary; Pankratz, Vernon S.; Couch, Fergus J.; Radice, Paolo; Peterlongo, Paolo; Greene, Mark H.; Loud, Jennifer T.; Mai, Phuong L.; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Gerdes, Anne-Marie; Thomassen, Mads; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A.; Lee, Andrew; Chenevix-Trench, Georgia; Antoniou, Antonis C; Neuhausen, Susan L.

2012-01-01

Background We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers. Methods IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers. Results Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 [Hazard ratio (HR) = 1.43; 95% CI: 1.06–1.92; p = 0.019] and BRCA2 mutation carriers (HR=2.21; 95% CI: 1.39–3.52, p=0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class 2 mutations than class 1 (mutations (class 2 HR=1.86, 95% CI: 1.28–2.70; class 1 HR=0.86, 95%CI:0.69–1.09; p-for difference=0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class 2 mutation carriers (HR = 2.42; p = 0.03). Conclusion The IRS1 Gly972Arg SNP, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class 2 mutation carriers. Impact These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers. PMID:22729394

Spatial and temporal variability of seawater pCO2 within the Canadian Arctic Archipelago and Baffin Bay during the summer and autumn 2011

Science.gov (United States)

Geilfus, N.-X.; Pind, M. L.; Else, B. G. T.; Galley, R. J.; Miller, L. A.; Thomas, H.; Gosselin, M.; Rysgaard, S.; Wang, F.; Papakyriakou, T. N.

2018-03-01

The partial pressure of CO2 in surface water (pCO2sw) measured within the Canadian Arctic Archipelago (CAA) and Baffin Bay was highly variable with values ranging from strongly undersaturated (118 μatm) to slightly supersaturated (419 μatm) with respect to the atmospheric levels ( 386 μatm) during summer and autumn 2011. During summer, melting sea ice contributed to cold and fresh surface water and enhanced the ice-edge bloom, resulting in strong pCO2sw undersaturation. Coronation Gulf was the only area with supersaturated pCO2sw, likely due to warm CO2-enriched freshwater input from the Coppermine River. During autumn, the entire CAA (including Coronation Gulf) was undersaturated, despite generally increasing pCO2sw. Coronation Gulf was the one place where pCO2sw decreased, likely due to seasonal reduction in discharge from the Coppermine River and the decreasing sea surface temperature. The seasonal summer-to-autumn increase in pCO2sw across the archipelago is attributed in part to the continuous uptake of atmospheric CO2 through both summer and autumn and to the seasonal deepening of the surface mixed layer, bringing CO2-rich waters to the surface. These observations demonstrate how freshwater from sea ice melt and rivers affect pCO2sw differently. The general pCO2sw undersaturation during summer-autumn 2011 throughout the CAA and Baffin Bay give an estimated net oceanic sink for atmospheric CO2 over the study period of 11.4 mmol CO2 m-2 d-1, assuming no sea-air CO2 flux exchange across the sea-ice covered areas.

Bone marrow stroma in idiopathic myelofibrosis and other haematological diseases. An immunohistochemical study

DEFF Research Database (Denmark)

Lisse, I; Hasselbalch, H; Junker, P

1991-01-01

Bone marrow stroma was investigated immunohistochemically in 31 patients with haematological diseases, mainly idiopathic myelofibrosis (n = 8) and related chronic myeloproliferative disorders (n = 14). The bone marrow from patients with idiopathic myelofibrosis and some CML patients showed marked...

The Relation between Diverse Phenotypes of PCOS with Clinical Manifestations, Anthropometric Indices and Metabolic Characteristics.

Science.gov (United States)

Shahrami, Seyedeh Hajar; Abbasi Ranjbar, Zahra; Milani, Forozan; Kezem-Nejad, Ehsan; Hassanzadeh Rad, Afagh; Dalil Heirat, Seyedeh Fatemeh

2016-02-01

Critical issue regarding to variation of findings based on different phenotypes led investigators to define whether they are distinct features or overlapping ones. Therefore, we aimed to investigate the association between diverse phenotypes of PCOS (Poly Cystic Ovary Syndrome) with clinical manifestations, anthropometric indices, and metabolic characteristics. This was a descriptive cross-sectional study conducted in 15-39 years old women with PCOS referred to infertility clinics in the north part of Iran, Rasht during 2010-2011. Data were gathered through an interview by a form consisted of demographic characteristics, laboratory findings, ovarian volume and anthropometric indices. A total of 214 patients consisted of 161 PCOS (cases) and 53 normal women (controls) participated in this study. The most prevalent phenotype in PCOS population was IM/PCO/HA (54%), followed by IM/HA (28%) and IM/PCO (13%). PCO/HA was present only in 6 PCOS patients (5%). PCOS patients were significantly younger than controls (P=0.07). Results showed that increased ovarian volume were higher in PCOS group in comparison with controls and IM/PCO/HA, and IM/PCO had respectively the largest ovarian volumes. Also, a significant relation was observed based on Cholesterol, 17OHP, LH, TG, 2hpp, and LH/FSH between patients with PCOS and control groups. There were significant differences in demographic, anthropometric, hormonal and ultrasound findings between PCOS and controls. Therefore, it seems that classification of the characteristics of each phenotype could offer an appropriate guide for screening risks of PCOS and may facilitate performing most favorable treatment for these complications.

Characterization and Structure Prediction of Partial Length Protein Sequences of pcoA, pcoR and chrB Genes from Heavy Metal Resistant Bacteria from the Klip River, South Africa

Directory of Open Access Journals (Sweden)

Patience Chihomvu

2015-04-01

Full Text Available The Klip River has suffered from severe anthropogenic effects from industrial activities such as mining. Long-term exposure to heavy metal pollution has led to the development of heavy metal resistant strains of Pseudomonas sp. KR23, Lysinibacillus sp. KR25, and E. coli KR29. The objectives of this study were to characterize the genetics of copper and chromate resistance of the isolates. Copper and chromate resistance determinants were cloned and sequenced. Open reading frames (ORFs related to the genes CopA and CopR were identified in E. coli KR29, PcoA in Lysinibacillus sp. KR25 and none related to chromate resistance were detected. The 3D-models predicted by I-TASSER disclose that the PcoA proteins consist of β-sheets, which form a part of the cupredoxin domain of the CopA copper resistance family of genes. The model for PcoR_29 revealed the presence of a helix turn helix; this forms part of a DNA binding protein, which is part of a heavy metal transcriptional regulator. The bacterial strains were cured using ethidium bromide. The genes encoding for heavy metal resistance and antibiotic resistance were found to be located on the chromosome for both Pseudomonas sp. (KR23 and E. coli (KR29. For Lysinibacillus (KR25 the heavy metal resistance determinants are suspected to be located on a mobile genetic element, which was not detected using gel electrophoresis.

Characterization and structure prediction of partial length protein sequences of pcoA, pcoR and chrB genes from heavy metal resistant bacteria from the Klip River, South Africa.

Science.gov (United States)

Chihomvu, Patience; Stegmann, Peter; Pillay, Michael

2015-04-01

The Klip River has suffered from severe anthropogenic effects from industrial activities such as mining. Long-term exposure to heavy metal pollution has led to the development of heavy metal resistant strains of Pseudomonas sp. KR23, Lysinibacillus sp. KR25, and E. coli KR29. The objectives of this study were to characterize the genetics of copper and chromate resistance of the isolates. Copper and chromate resistance determinants were cloned and sequenced. Open reading frames (ORFs) related to the genes CopA and CopR were identified in E. coli KR29, PcoA in Lysinibacillus sp. KR25 and none related to chromate resistance were detected. The 3D-models predicted by I-TASSER disclose that the PcoA proteins consist of β-sheets, which form a part of the cupredoxin domain of the CopA copper resistance family of genes. The model for PcoR_29 revealed the presence of a helix turn helix; this forms part of a DNA binding protein, which is part of a heavy metal transcriptional regulator. The bacterial strains were cured using ethidium bromide. The genes encoding for heavy metal resistance and antibiotic resistance were found to be located on the chromosome for both Pseudomonas sp. (KR23) and E. coli (KR29). For Lysinibacillus (KR25) the heavy metal resistance determinants are suspected to be located on a mobile genetic element, which was not detected using gel electrophoresis.

Ovarian Disorders

Science.gov (United States)

... a pregnancy can occur. Ovaries also make the female hormones estrogen and progesterone. When a woman goes through menopause, her ovaries stop making those hormones and releasing eggs. Problems with the ovaries include Ovarian cancer Ovarian ...

Temporal and spatial variations of oceanic pCO2 and air-sea CO2 flux in th Greenland Sea and the Barents Sea

International Nuclear Information System (INIS)

Nakaoka, Shin-Ichiro; Aoki, Shuji; Nakazawa, Takakiyo; Yoshikawa-Inoue, Hisayuki

2006-01-01

In order to elucidate the seasonal and inter annual variations of oceanic CO 2 uptake in the Greenland Sea and the Barents Sea, the partial pressure of CO 2 in the surface ocean (pCO 2 sea ) was measured in all seasons between 1992 and 2001. We derived monthly varying relationships between pCO 2 sea and sea surface temperature (SST) and combined them with the SST data from the NCEP/NCAR reanalysis to determine pCO 2 sea and air-sea CO 2 flux in these seas. The pCO 2 sea values were normalized to the year 1995 by assuming that pCO 2 sea increased at the same growth rate (1.5 μatm/yr) of the pCO 2 in the air (pCO 2 air ) between 1992 and 2001. In 1995, the annual net air-sea CO 2 fluxes were evaluated to be 52 ± 20 gC/m 2 /yr in the Greenland Sea and 46 ± 18 gC/m 2 /yr in the Barents Sea. The CO 2 flux into the ocean reached its maximum in winter and minimum in summer. The wind speed and (delta)pCO 2 (=pCO 2 air -pCO 2 sea ) exerted a greater influence on the seasonal variation than the sea ice coverage. The annual CO 2 uptake examined in this study (70-80 deg N, 20 deg W-40 deg E) was estimated to be 0.050 ± 0.020 GtC/yr in 1995. The inter annual variation in the annual CO 2 uptake was found to be positively correlated with the North Atlantic Oscillation Index (NAOI) via wind strength but negatively correlated with (delta)pCO 2 and the sea ice coverage. The present results indicate that the variability in wind speed and sea ice coverage play a major role, while that in (delta)pCO 2 plays a minor role, in determining the interannual variation of CO 2 uptake in this area

Determining the high variability of pCO2 and pO2 in the littoral zone of a subtropical coastal lake

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Denise Tonetta

2014-09-01

Full Text Available The aquatic metabolism comprises production and mineralization of organic matter through biological processes, such as primary production and respiration that can be estimated by gases concentration in the water column. AIM: The study aimed to assess the temporal variability of pCO2 and pO2 in the littoral zone of a subtropical coastal lake. Our hypotheses are i high variability in meteorological conditions, such as temperature and light, drive the high variability in pCO2 and pO2, and ii the lake is permanently heterotrophic due to the low phosphorus concentration. METHODS: We estimated pCO2 from pH-alkalinity method, and pO2 from dissolved oxygen concentration and water temperature measured in free-water during 24 hours in the autumn, winter, spring and summer. RESULTS: Our findings showed that limnological variables had low temporal variability, while the meteorological variables and pCO2 presented a high coefficient of variation, which is representative of each climatic season. In autumn and winter, it was recorded that the lake was supersaturated in CO2 relative to the atmosphere, while in spring and summer CO2 concentration was below the concentration found in the atmosphere. Over 24 hours, pCO2 also showed high variability, with autumn presenting higher concentration during the night when compared to daytime. Water temperature and chlorophyll a were negatively correlated with pCO2, while pO2 was positively correlated with wind and light. CONCLUSION: Agreeing with our first hypothesis, pCO2 showed an expressive temporal variation in a subtropical lake associated to the high variability in meteorological conditions. On the other hand, our second hypothesis was not confirmed, since Peri Lake exported CO2 to the atmosphere in some periods and in others, CO2 was removed from the atmosphere.

Impacts of food availability and pCO2 on planulation, juvenile survival, and calcification of the azooxanthellate scleractinian coral Balanophyllia elegans

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Crook, E. D.; Cooper, H.; Potts, D. C.; Lambert, T.; Paytan, A.

2013-11-01

Ocean acidification, the assimilation of atmospheric CO2 by the oceans that decreases the pH and CaCO3 saturation state (Ω) of seawater, is projected to have severe adverse consequences for calcifying organisms. While strong evidence suggests calcification by tropical reef-building corals containing algal symbionts (zooxanthellae) will decline over the next century, likely responses of azooxanthellate corals to ocean acidification are less well understood. Because azooxanthellate corals do not obtain photosynthetic energy from symbionts, they provide a system for studying the direct effects of acidification on energy available for calcification. The solitary azooxanthellate orange cup coral Balanophyllia elegans often lives in low-pH, upwelled waters along the California coast. In an 8-month factorial experiment, we measured the effects of three pCO2 treatments (410, 770, and 1220 μatm) and two feeding frequencies (3-day and 21-day intervals) on "planulation" (larval release) by adult B. elegans, and on the survival, skeletal growth, and calcification of newly settled juveniles. Planulation rates were affected by food level but not pCO2. Juvenile mortality was highest under high pCO2 (1220 μatm) and low food (21-day intervals). Feeding rate had a greater impact on calcification of B. elegans than pCO2. While net calcification was positive even at 1220 μatm (~3 times current atmospheric pCO2), overall calcification declined by ~25-45%, and skeletal density declined by ~35-45% as pCO2 increased from 410 to 1220 μatm. Aragonite crystal morphology changed at high pCO2, becoming significantly shorter but not wider at 1220 μatm. We conclude that food abundance is critical for azooxanthellate coral calcification, and that B. elegans may be partially protected from adverse consequences of ocean acidification in habitats with abundant heterotrophic food.

Context-Dependent Development of Lymphoid Stroma from Adult CD34+ Adventitial Progenitors

DEFF Research Database (Denmark)

Sitnik, Katarzyna Maria; Wendland, Kerstin; Weishaupt, Holger

2016-01-01

Despite the key role of primary and secondary lymphoid organ stroma in immunity, our understanding of the heterogeneity and ontogeny of these cells remains limited. Here, we identify a functionally distinct subset of BP3-PDPN+PDGFRβ+/α+CD34+ stromal adventitial cells in both lymph nodes (LNs...

End-tidal carbon dioxide (ETCO2) can replace methods for measuring partial pressure of carbon dioxide (PCO2) in pigs

DEFF Research Database (Denmark)

Alstrup, Aage Kristian Olsen

2017-01-01

We compared end-tidal carbon dioxide (ETCO2) with partial pressure of carbon dioxide (PCO2) in domestic pigs anesthetized for neuroscience. There was good agreement between ETCO2 and PCO2 under both hypocapnia, normocapnia, and hypercapnia conditions. ETCO2 saves time by continually providing...

Association between tumor-stroma ratio and prognosis in solid tumor patients: a systematic review and meta-analysis.

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Wu, Jiayuan; Liang, Caixia; Chen, Manyu; Su, Wenmei

2016-10-18

Tumor-related stroma plays an active role in tumor invasion and metastasis. The tumor-stroma ratio (TSR) in the pathologic specimen has drawn increasing attention from the field of predicting tumor prognosis. However, the prognostic value of TSR in solid tumors necessitates further elucidation. We conducted a meta-analysis on 14 studies with 4238 patients through a comprehensive electronic search on databases updated on May 2016 to explore the relationship between TSR and prognosis of solid tumors. The overall hazard ratio showed that rich stroma in tumor tissue was associated with poor overall survival (OS) (14 studies, 4238 patients) and disease-free survival (DFS) (9 studies, 2235 patients) of patients with solid tumors. The effect of low TSR on poor OS was observed among various cancer types, but not in the early stage of cervical caner. A significant relationship between low TSR and poor OS was also observed in the subgroup analyses based on study region, blinding status, and Newcastle-Ottawa Scale (NOS) score. Subgroup analyses indicated that cancer type, clinical stage, study region, blinding status, and NOS score did not affect the prognostic value of TSR for DFS. Moreover, low TSR was significantly correlated with the serious clinical stage, advanced depth of invasion, and positive lymph node metastasis. These findings indicate that a high proportion of stroma in cancer tissue is associated with poor clinical outcomes in cancer patients, and TSR may serve as an independent prognostic factor for solid tumors.

Temperature dependence of the relationship between pCO2 and dissolved organic carbon in lakes

KAUST Repository

Pinho, L.

2016-02-15

The relationship between the partial pressure of carbon dioxide (pCO2) and dissolved organic carbon (DOC) concentration in Brazilian lakes, encompassing 225 samples across a wide latitudinal range in the tropics, was tested. Unlike the positive relationship reported for lake waters, which was largely based on temperate lakes, we found no significant relationship for low-latitude lakes (< 33°), despite very broad ranges in both pCO2 and DOC levels. These results suggest substantial differences in the carbon cycling of low-latitude lakes, which must be considered when upscaling limnetic carbon cycling to global scales.

Temperature dependence of the relationship between pCO2 and dissolved organic carbon in lakes

KAUST Repository

Pinho, L.; Duarte, Carlos M.; Marotta, H.; Enrich-Prast, A.

2016-01-01

The relationship between the partial pressure of carbon dioxide (pCO2) and dissolved organic carbon (DOC) concentration in Brazilian lakes, encompassing 225 samples across a wide latitudinal range in the tropics, was tested. Unlike the positive relationship reported for lake waters, which was largely based on temperate lakes, we found no significant relationship for low-latitude lakes (< 33°), despite very broad ranges in both pCO2 and DOC levels. These results suggest substantial differences in the carbon cycling of low-latitude lakes, which must be considered when upscaling limnetic carbon cycling to global scales.

Hypolipidemic activity of P-methoxycinnamic diester (PCO-C) isolated from Copernicia prunífera against Triton WR-1339 and hyperlipidemic diet in mice.

Science.gov (United States)

Filho, A C V A; Rodrigues, P A S; Benjamin, S R; Paim, R T T; Holanda, M O; Silva, J Y G; Milo, T S; Vieira, I G P; Queiroz, M G R; Guedes, M I F

2017-12-01

Carnauba wax is extracted from the leaves of the Copernicia prunífera and contains approximately 80% of esters in its composition. The purpose of the present study was evaluate the hypolipidemic effect of p-methoxycinnamic diesters (PCO-C) extracted from Copernicia prunífera in a model of acute and chronic dyslipidemia in mice. The levels of total cholesterol and triglycerides were significantly reduced plasma levels in PCO-C at the dose of 100mg/kg in a model of acute and chronic dyslipidemia. Histological studies showed that PCO-C has no hepatotoxic effect and reduces hepatic steatosis in animals that consumed hyperlipidemic ration. Thus, it was concluded that PCO-C isolated from Copernicia Prunifera was effective in reducing total cholesterol and triglyceride levels in both dyslipidemia induction models. The finding indicates that PCO-C might be beneficial in treatment of hyperlipidemia and atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Spatial and temporal variability of seawater pCO2 within the Canadian Arctic Archipelago and Baffin Bay during the summer and autumn 2011

DEFF Research Database (Denmark)

Geilfus, N.-X.; Pind, M. L.; Else, B. G. T.

2018-01-01

The partial pressure of CO2 in surface water (pCO2sw) measured within the Canadian Arctic Archipelago (CAA) and Baffin Bay was highly variable with values ranging from strongly undersaturated (118 μatm) to slightly supersaturated (419 μatm) with respect to the atmospheric levels ( 386 μatm) during...... summer and autumn 2011. During summer, melting sea ice contributed to cold and fresh surface water and enhanced the ice-edge bloom, resulting in strong pCO2sw undersaturation. Coronation Gulf was the only area with supersaturated pCO2sw, likely due to warm CO2-enriched freshwater input from...... the Coppermine River. During autumn, the entire CAA (including Coronation Gulf) was undersaturated, despite generally increasing pCO2sw. Coronation Gulf was the one place where pCO2sw decreased, likely due to seasonal reduction in discharge from the Coppermine River and the decreasing sea surface temperature...

Tumor stroma-containing 3D spheroid arrays: A tool to study nanoparticle penetration

NARCIS (Netherlands)

Priwitaningrum, Dwi L.; Priwitaningrum, Dwi Lestari; Blondé, Jean-Baptiste Gabriel Marie; Blonde, Jean-Baptiste G.; Sridhar, Adithya; van Baarlen, Joop; Hennink, Wim E.; Storm, Gerrit; le Gac, Severine; Prakash, Jai

2016-01-01

Nanoparticle penetration through tumor tissue after extravasation is considered as a key issue for tumor distribution and therapeutic effects. Most tumors possess abundant stroma, a fibrotic tissue composed of cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM), which acts as a

Mixed effects of elevated pCO2 on fertilisation, larval and juvenile development and adult responses in the mobile subtidal scallop Mimachlamys asperrima (Lamarck, 1819.

Directory of Open Access Journals (Sweden)

Elliot Scanes

Full Text Available Ocean acidification is predicted to have severe consequences for calcifying marine organisms especially molluscs. Recent studies, however, have found that molluscs in marine environments with naturally elevated or fluctuating CO2 or with an active, high metabolic rate lifestyle may have a capacity to acclimate and be resilient to exposures of elevated environmental pCO2. The aim of this study was to determine the effects of near future concentrations of elevated pCO2 on the larval and adult stages of the mobile doughboy scallop, Mimachlamys asperrima from a subtidal and stable physio-chemical environment. It was found that fertilisation and the shell length of early larval stages of M. asperrima decreased as pCO2 increased, however, there were less pronounced effects of elevated pCO2 on the shell length of later larval stages, with high pCO2 enhancing growth in some instances. Byssal attachment and condition index of adult M. asperrima decreased with elevated pCO2, while in contrast there was no effect on standard metabolic rate or pHe. The responses of larval and adult M. asperrima to elevated pCO2 measured in this study were more moderate than responses previously reported for intertidal oysters and mussels. Even this more moderate set of responses are still likely to reduce the abundance of M. asperrima and potentially other scallop species in the world's oceans at predicted future pCO2 levels.

Successful vitrification and autografting of baboon (Papio anubis) ovarian tissue.

Science.gov (United States)

Amorim, Christiani A; Jacobs, Sophie; Devireddy, Ram V; Van Langendonckt, Anne; Vanacker, Julie; Jaeger, Jonathan; Luyckx, Valérie; Donnez, Jacques; Dolmans, Marie-Madeleine

2013-08-01

Can a vitrification protocol using an ethylene glycol/dimethyl sulphoxide-based solution and a cryopin successfully cryopreserve baboon ovarian tissue? Our results show that baboon ovarian tissue can be successfully cryopreserved with our vitrification protocol. Non-human primates have already been used as an animal model to test vitrification protocols for human ovarian tissue cryopreservation. Ovarian biopsies from five adult baboons were vitrified, warmed and autografted for 5 months. After grafting, follicle survival, growth and function and also the quality of stromal tissue were assessed histologically and by immunohistochemistry. The influence of the vitrification procedure on the cooling rate was evaluated by a computer model. After vitrification, warming and long-term grafting, follicles were able to grow and maintain their function, as illustrated by Ki67, anti-Müllerian hormone (AMH) and growth differentiation factor-9 (GDF-9) immunostaining. Corpora lutea were also observed, evidencing successful ovulation in all the animals. Stromal tissue quality did not appear to be negatively affected by our cryopreservation procedure, as demonstrated by vascularization and proportions of fibrotic areas, which were similar to those found in fresh ungrafted ovarian tissue. Despite our promising findings, before applying this technique in a clinical setting, we need to validate it by achieving pregnancies. In addition to encouraging results obtained with our vitrification procedure for non-human ovarian tissue, this study also showed, for the first time, expression of AMH and GDF-9 in ovarian follicles. This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (grant Télévie No. 7.4507.10, grant 3.4.590.08 awarded to Marie-Madeleine Dolmans), Fonds Spéciaux de Recherche, Fondation St Luc, Foundation Against Cancer, and Department of Mechanical Engineering at Louisiana State University (support to Ram Devireddy), and

Pelvic inflammatory disease and risk of invasive ovarian cancer and ovarian borderline tumors

DEFF Research Database (Denmark)

Rasmussen, Christina B; Faber, Mette T; Jensen, Allan

2013-01-01

PURPOSE: The aim of the study was to examine the potential association between a history of pelvic inflammatory disease (PID) and risk of epithelial ovarian cancer or ovarian borderline tumors. METHODS: In a population-based case-control study in Denmark, we included 554 women with invasive ovarian...... cancer, 202 with ovarian borderline tumors, and 1,564 controls aged 35-79 years. The analyses were performed in multiple logistic regression models. RESULTS: We found a significantly increased risk of ovarian borderline tumors among women with a history of PID (OR = 1.50; 95% CI 1.......08-2.08) but no apparent association between PID and risk of invasive ovarian cancer (OR = 0.83; 95% CI 0.65-1.05). We found no effect of age at time of first PID or time since first PID on the risk for either condition. CONCLUSION: Our results suggest that a history of PID is associated with an increased risk of ovarian...

ELF5 in epithelial ovarian carcinoma tissues and biological behavior in ovarian carcinoma cells.

Science.gov (United States)

Yan, Hongchao; Qiu, Linglin; Xie, Xiaolei; Yang, He; Liu, Yongli; Lin, Xiaoman; Huang, Hongxiang

2017-03-01

The expression of E74-like factor 5 (ELF5) in epithelial ovarian carcinoma tissues and its effects on biological behavior in ovarian carcinoma cells were assessed in search for a new approach for gene treatment of epithelial ovarian carcinoma. RT-PCR technology was applied to detect the expression of ELF5 mRNA in epithelial ovarian carcinoma (n=49), borderline ovarian epithelial tumor (n=19), benign ovarian epithelial tumor (n=31) and normal ovarian tissues (n=40). Then, we transfected recombinant plasmid pcDNA3.1‑ELF5+EGFP into human ovarian carcinoma SKOV3 cells (recombinant plasmid group) in vitro and screened out stably transfected cells to conduct multiplication culture. Western blot analysis was performed to detect the expression of ELF5 protein in the different groups. Flow cytometry was employed to detect cell apoptosis and cycles. ELF5 mRNA in epithelial ovarian carcinoma and borderline ovarian epithelial tumor tissues were significantly lower (Pepithelial tumor and normal ovarian tissues. ELF5 protein expression in the cells of recombinant plasmid group was significantly higher compared with empty plasmid and blank control groups. The capacity of cell reproductive recombinant plasmid group at each time point decreased (P<0.05). Flow cytometry detection showed that 67.03% of cells in recombinant plasmid group was blocked in G0/G1 phase (P<0.05), compared with empty plasmid group (37.17%) and blank control group (38.24%). Apoptotic rate of recombinant plasmid group was significantly lower (31.4±1.9%; P<0.05), compared with that of empty plasmid group (9.1±2.2%) and blank control group (8.7±1.5%), and the differences were statistically significant. In conclusion, ELF5 interfered with cell cycle of human ovarian carcinoma SKOV3 cells and promoted apoptosis of human ovarian carcinoma SKOV3 cells inhibiting their growth and invasive capacity; and thus providing a new approach to gene treatment of ovarian carcinoma.

Performance of a digital PCO2/SPO2 ear sensor.

Science.gov (United States)

Kocher, Serge; Rohling, Roman; Tschupp, Andres

2004-04-01

For determining the adequacy of ventilation, conventional pulse oximetry should be amended by PaCO2 (= arterial carbon dioxide partial pressure). This study investigates the precision of carbon dioxide measurements of the first digital ear-clip sensor providing continuous non-invasive monitoring of PaCO2, SpO2 (= functional arterial oxygen saturation as estimated with a pulse oximeter) and pulse rate and compares it to two conventional analog oximeters. 30 hypoxemia episodes in 6 adult volunteers were investigated in a standardized protocol. Masimo analog finger sensor, Nellcor analog ear sensor, SenTec digital ear sensor. The difference between PCO2 data (= PaCO2 estimated from the measured PcCO2 based on an algorithm by Severinghaus) (PcCO2 = cutaneous carbon dioxide pressure) and the PaCO2 is clinically unimportant. Therefore, we suggest, the two methods of estimating patient's carbon dioxide status can be used interchangeably. Combined digital SpO2/ PcCO2 ear sensors are very promising to allow for a fast and reliable monitoring of patient's oxygenation, hyper-/hypocapnia and ventilation with one single non-invasive probe. Optimal primary signal processing--amplification and digitalisation within the probe--allow for fast and reliable downstream signal processing algorithms. The resulting short SpO2 response times give the medical staff more time to take appropriate actions.

Coccolith calcite time capsules preserve a molecule-specific record of pCO2

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McClelland, H. L. O.; Pearson, A.; Hermoso, M.; Wilkes, E.; Lee, R. B. Y.; Rickaby, R. E. M.

2017-12-01

Coccolithophores are single-celled phytoplankton that have contributed organic matter and calcite to marine sediments since the Late Triassic. The carbon isotopic compositions of both the calcite, and the organic matter, constitute valuable archives of information about the interaction between these organisms and the environments in which they lived. The isotopic composition of alkenone lipids, a recalcitrant component of coccolithophore organic carbon produced by a single family of coccolithophores, has been widely used to reconstruct pCO2 in the geological past. However, the robustness of this approach has remained controversial, due in part to the difficulties associated with reproducing pCO2 changes across periods of known pCO2 change, and uncertainties in relevant physiological variables such as growth rate and cell size. Meanwhile the calcite, produced in the form of plates called coccoliths, and which has had limited utility in paleoclimate reconstructions due to its large and variable departures from the isotopic composition of abiogenic calcite, has garnered increasing attention in recent years for the environmental and physiological information it contains. Here we show that polysaccharides preserved within the calcite crystal lattice of near monospecific fractions of fossil coccoliths constitute an ancient pristine source of organic carbon that unlike alkenones is unambiguously associated with the coccolith1. The isotopic composition of these polysaccharides, in tandem with that of the host coccolith calcite, and morphometrics from the same coccoliths2, can be used simultaneously constrain a recently published cellular carbon isotope flux model3, embedded in a more complex nutrient limitation model, in a powerful new approach to simultaneously predict cellular parameters and pCO2. We demonstrate the validity of this approach across a glacial / interglacial cycle. Lee, R. B. Y., et al,, Nat. Commun. 7, 13144 (2016). McClelland, H. L. O. et al. Sci. Rep. 6

Estrogen receptor beta rs1271572 polymorphism and invasive ovarian carcinoma risk: pooled analysis within the Ovarian Cancer Association Consortium.

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Galina Lurie

Full Text Available The association of ovarian carcinoma risk with the polymorphism rs1271572 in the estrogen receptor beta (ESR2 gene was examined in 4946 women with primary invasive ovarian carcinoma and 6582 controls in a pooled analysis of ten case-control studies within the Ovarian Cancer Association Consortium (OCAC. All participants were non-Hispanic white women. Odds ratios (ORs and 95% confidence intervals (CIs were estimated using unconditional logistic regression adjusted for site and age. Women with the TT genotype were at increased risk of ovarian carcinoma compared to carriers of the G allele (OR = 1.10; 95%; CI: 1.01-1.21; p = 0.04; the OR was 1.09 (CI: 0.99-1.20; p = 0.07 after excluding data from the center (Hawaii that nominated this SNP for OCAC genotyping A stronger association of rs1271572 TT versus GT/GG with risk was observed among women aged ≤50 years versus older women (OR = 1.35; CI: 1.12-1.62; p = 0.002; p for interaction = 0.02 that remained statistically significant after excluding Hawaii data (OR = 1.34; CI: 1.11-1.61; p = 0.009. No heterogeneity of the association was observed by study, menopausal status, gravidity, parity, use of contraceptive or menopausal hormones, tumor histological type, or stage at diagnosis. This pooled analysis suggests that rs1271572 might influence the risk of ovarian cancer, in particular among younger women.

A comparison of multiple regression and neural network techniques for mapping in situ pCO2 data

International Nuclear Information System (INIS)

Lefevre, Nathalie; Watson, Andrew J.; Watson, Adam R.

2005-01-01

Using about 138,000 measurements of surface pCO 2 in the Atlantic subpolar gyre (50-70 deg N, 60-10 deg W) during 1995-1997, we compare two methods of interpolation in space and time: a monthly distribution of surface pCO 2 constructed using multiple linear regressions on position and temperature, and a self-organizing neural network approach. Both methods confirm characteristics of the region found in previous work, i.e. the subpolar gyre is a sink for atmospheric CO 2 throughout the year, and exhibits a strong seasonal variability with the highest undersaturations occurring in spring and summer due to biological activity. As an annual average the surface pCO 2 is higher than estimates based on available syntheses of surface pCO 2 . This supports earlier suggestions that the sink of CO 2 in the Atlantic subpolar gyre has decreased over the last decade instead of increasing as previously assumed. The neural network is able to capture a more complex distribution than can be well represented by linear regressions, but both techniques agree relatively well on the average values of pCO 2 and derived fluxes. However, when both techniques are used with a subset of the data, the neural network predicts the remaining data to a much better accuracy than the regressions, with a residual standard deviation ranging from 3 to 11 μatm. The subpolar gyre is a net sink of CO 2 of 0.13 Gt-C/yr using the multiple linear regressions and 0.15 Gt-C/yr using the neural network, on average between 1995 and 1997. Both calculations were made with the NCEP monthly wind speeds converted to 10 m height and averaged between 1995 and 1997, and using the gas exchange coefficient of Wanninkhof

Incipient ovarian failure and premature ovarian failure show the same immunological profile

NARCIS (Netherlands)

van Kasteren, YM; von Blomberg, M; Hoek, A; de Koning, C; Lambalk, N; van Montfrans, J; Kuik, J

PROBLEM: Incipient ovarian failure (IOF) is characterized by regular menstrual cycles, infertility and a raised early-follicular FSH in women under 40. IOF might be a precursor or a mitigated form of premature ovarian failure (POF). Disturbances in the immune system may play a role in ovarian

Premature ovarian failure

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Persani Luca

2006-04-01

Full Text Available Abstract Premature ovarian failure (POF is a primary ovarian defect characterized by absent menarche (primary amenorrhea or premature depletion of ovarian follicles before the age of 40 years (secondary amenorrhea. It is a heterogeneous disorder affecting approximately 1% of women e.g. Turner syndrome represent the major cause of primary amenorrhea associated with ovarian dysgenesis. Despite the description of several candidate genes, the cause of POF remains undetermined in the vast majority of the cases. Management includes substitution of the hormone defect by estrogen/progestin preparations. The only solution presently available for the fertility defect in women with absent follicular reserve is ovum donation.

Ovarian Reserve Assessment in Users of Oral Contraception Seeking Fertility Advice on their Reproductive Lifespan

DEFF Research Database (Denmark)

Petersen, K. Birch; Hvidman, H. W.; Forman, J. L.

2016-01-01

aged 19-46 attending the Fertility Assessment and Counselling Clinic (FACC) from 2011 to 2014 comparing ovarian reserve parameters in OC users with non-OC users. PARTICIPANTS/MATERIALS, SETTING, METHODS: The FAC Clinic was initiated to provide individual fertility assessment and counselling. All women...... follicles sized 5-7 mm (P groups (OC users versus non-users) were comparable regarding age, BMI, smoking and maternal age at menopause. LIMITATIONS, REASON FOR CAUTION......STUDY QUESTION: To what extent does oral contraception (OC) impair ovarian reserve parameters in women who seek fertility assessment and counselling to get advice on whether their remaining reproductive lifespan is reduced? SUMMARY ANSWER: Ovarian reserve parameters defined by anti...

Ovarian reserve assessment in users of oral contraception seeking fertility advice on their reproductive lifespan

DEFF Research Database (Denmark)

Birch Petersen, K; Hvidman, H W; Forman, J L

2015-01-01

aged 19-46 attending the Fertility Assessment and Counselling Clinic (FACC) from 2011 to 2014 comparing ovarian reserve parameters in OC users with non-OC users. PARTICIPANTS/MATERIALS, SETTING, METHODS: The FAC Clinic was initiated to provide individual fertility assessment and counselling. All women...... follicles sized 5-7 mm (P groups (OC users versus non-users) were comparable regarding age, BMI, smoking and maternal age at menopause. LIMITATIONS, REASON FOR CAUTION......STUDY QUESTION: To what extent does oral contraception (OC) impair ovarian reserve parameters in women who seek fertility assessment and counselling to get advice on whether their remaining reproductive lifespan is reduced? SUMMARY ANSWER: Ovarian reserve parameters defined by anti...

A Molecularly Targeted Theranostic Probe for Ovarian Cancer

Science.gov (United States)

Chen, Wenxue; Bardhan, Rizia; Bartels, Marc; Perez-Torres, Carlos; Pautler, Robia G.; Halas, Naomi J.; Joshi, Amit

2014-01-01

Overexpression of the human epidermal growth factor receptor (HER) family has been implicated in ovarian cancer because of its participation in signaling pathway regulating cellular proliferation, differentiation, motility, and survival. Currently, effective diagnostic and therapeutic schemes are lacking for treating ovarian cancer and consequently ovarian cancer has a high mortality rate. While HER2 receptor expression does not usually affect the survival rates of ovarian cancer to the same extent as in breast cancer, it can be employed as a docking site for directed nanotherapies in cases with de novo or acquired chemotherapy resistance. In this study, we have exploited a novel gold nanoshell-based complex (nanocomplex) for targeting, dual modal imaging, and photothermal therapy of HER2 overexpressing and drug resistant ovarian cancer OVCAR3 cells in vitro. The nanocomplexes are engineered to simultaneously provide contrast as fluorescence optical imaging probe and a magnetic resonance imaging (MRI) agent. Both immunofluorescence staining and MRI successfully demonstrate that nanocomplex-anti-HER2 conjugates specifically bind to OVCAR3 cells as opposed to the control, MDA-MB-231 cells, which have low HER2 expression. In addition, nanocomplexes targeted to OVCAR3 cells, when irradiated with near infrared (NIR) laser result in selective destruction of cancer cells through photothermal ablation. We also demonstrate that NIR light therapy and the nanocomplexes by themselves are non-cytotoxic in vitro. To the best of our knowledge, this is the first demonstration of a successful integration of dual modal bioimaging with photothermal cancer therapy for treatment of ovarian cancer. Based on their efficacy in vitro, these nanocomplexes are highly promising for image guided photo-thermal therapy of ovarian cancer as well as other HER2 overexpressing cancers. PMID:20371708

pO2 and pCO2 increment in post-dialyzer blood: the role of dialysate.

Science.gov (United States)

Sombolos, Kostas I; Bamichas, Gerasimos I; Christidou, Fotini N; Gionanlis, Lazaros D; Karagianni, Anna C; Anagnostopoulos, Theodoros C; Natse, Taïsir A

2005-11-01

Blood returning from a dialyzer during hemodialysis has a higher pO2 and pCO2 content than blood entering the dialyzer, and this has been attributed to the dialysate. The present study investigates this phenomenon. Acid-base and blood-gas parameters (pH, pO2, pCO2 and HCO3) were measured in three groups of stable chronic hemodialysis patients (A, B, and C) undergoing high-flux hemodialysis. In group A (n = 15), "arterial" (a) and "venous" (v) samples were withdrawn simultaneously before dialysis (samples A0), 5 min after circulation of the blood with the dialysate in the by-pass mode (samples A5), and 5 min after high-flux hemodialysis at a zero ultrafiltration rate (samples A10). In group B (n = 11) (a) and (v) samples were withdrawn simultaneously before dialysis (samples B0), 5 min after isolated-ultrafiltration with closed dialysate ports ("isolated-closed" ultrafiltration) (samples B5), and 5 min after high-flux hemodialysis at a zero ultrafiltration rate (samples B10). In group C (n = 14), after an initial arterial blood sample withdrawal before hemodialysis (sample C0), high-flux hemodialysis at a zero ultrafiltration rate was initiated. Five minutes later, blood and dialysate samples were withdrawn simultaneously from the hemodialysis lines (samples C5). In all cases blood and dialysate (bicarbonate) flow rates were set at 0.300 and 0.700 L/min, respectively. FLX-18 hemodialyzers (membrane PEPA 1.8 m2) were used in this study. Analysis of variance revealed significant changes only in venous samples. A comparison of arterial and venous samples revealed no differences between groups A and B before the initiation of dialysis (A0a vs. A0v and B0a vs. B0v, P = NS). The pO2 content was higher in A5v samples than in A5a samples (83.5 +/- 11.2 vs. 88.8 +/- 14.0 mm Hg, P pO2, pCO2, and HCO3 in comparison to A10v samples (P pO2 and pCO2 values in A5v and A10v samples increased by 6.3% and 12.1% and by 1.29% and 52% in comparison to corresponding values of A5a and A10

Impaired endothelial progenitor cell mobilization and dysfunctional bone marrow stroma in diabetes mellitus.

Science.gov (United States)

Westerweel, Peter E; Teraa, Martin; Rafii, Shahin; Jaspers, Janneke E; White, Ian A; Hooper, Andrea T; Doevendans, Pieter A; Verhaar, Marianne C

2013-01-01

Circulating Endothelial Progenitor Cell (EPC) levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired -at least partly- due to dysfunction of the bone marrow stromal compartment. Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1(+)Flk-1(+) EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34(+) hematopoietic progenitor cells (HPC) and supporting stroma was assessed by co-cultures. To study progenitor cell-endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed. In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro. EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients.

Impaired endothelial progenitor cell mobilization and dysfunctional bone marrow stroma in diabetes mellitus.

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Peter E Westerweel

Full Text Available Circulating Endothelial Progenitor Cell (EPC levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired -at least partly- due to dysfunction of the bone marrow stromal compartment.Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1(+Flk-1(+ EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34(+ hematopoietic progenitor cells (HPC and supporting stroma was assessed by co-cultures. To study progenitor cell-endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed.In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro.EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients.

Premature ovarian failure/dysfunction following surgical treatment of polycystic ovarian syndrome: A case series

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T.K. Al-Hussaini

2017-09-01

Full Text Available Polycystic ovarian syndrome (PCOS is one of the most common causes of infertility in women. Surgical treatment of PCOS, either by the antiquated wedge resection or ovarian drilling, is one of the commonly used lines in developing countries due to its low-cost. Premature ovarian failure and diminished ovarian reserve are serious complications of the surgical treatment but no published reports sufficiently highlighted these hazards. In this case series, we report on twenty one women aged between 19–39 years, presented to Infertility Clinic, Assiut Women Health Hospital with ovarian dysfunction, diagnosed within 6–36 months after surgical management of PCOS. Nineteen of them had laparoscopic bilateral ovarian drilling using electrocauterization, and the last two had bilateral wedge resection of the ovaries through minilaparotomy. Accurate and documented diagnosis of PCOS, appropriate surgical training, adjusted thermal injury and adjusted number of punctures are essential for the avoidance of excessive damage to the ovaries. Under treatment (failure of drilling is much better than premature ovarian failure or diminishing ovarian reserve.

Overexpression of SnoN/SkiL, amplified at the 3q26.2 locus, in ovarian cancers: A role in ovarian pathogenesis

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Nanjundan, Meera; Cheng, Kwai Wa; Zhang, Fan; Lahad, John; Kuo, Wen-Lin; Schmandt, Rosemarie; Smith-McCune, Karen; Fishman, David; Gray, Joe W.; Mills, Gordon B.

2008-07-18

High-resolution array comparative genomic hybridization of 235 serous epithelial ovarian cancers demonstrated a regional increase at 3q26.2 encompassing SnoN/SkiL, a coregulator of SMAD/TGF{beta} signaling. SnoN RNA transcripts were elevated in {approx}80% of advanced stage serous epithelial ovarian cancers. In both immortalized normal (TIOSE) and ovarian carcinoma cell lines (OVCA), SnoN RNA levels were increased by TGF{beta} stimulation and altered by LY294002 and JNK II inhibitor treatment suggesting that the PI3K and JNK signaling pathways may regulate TGF{beta}-induced increases in SnoN RNA. In TIOSE, SnoN protein levels were reduced 15min post TGF{beta}-stimulation, likely by proteosome-mediated degradation. In contrast, in OVCA, SnoN levels were elevated 3h post-stimulation potentially as a result of inhibition of the proteosome. To elucidate the role of SnoN in ovarian tumorigenesis, we explored the effects of both increasing and decreasing SnoN levels. In both TIOSE and OVCA, SnoN siRNA decreased cell growth between 20 and 50% concurrent with increased p21 levels. In TIOSE, transient expression of SnoN repressed TGF{beta} induction of PAI-1 promoters with little effect on the p21 promoter or resultant cell growth. In contrast to the effects of transient expression, stable expression of SnoN in TIOSE led to growth arrest through induction of senescence. Collectively, these results implicate SnoN levels in multiple roles during ovarian carcinogenesis: promoting cellular proliferation in ovarian cancer cells and as a positive mediator of cell cycle arrest and senescence in non-transformed ovarian epithelial cells.

Species-Specific Responses of Juvenile Rockfish to Elevated pCO2: From Behavior to Genomics.

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Scott L Hamilton

Full Text Available In the California Current ecosystem, global climate change is predicted to trigger large-scale changes in ocean chemistry within this century. Ocean acidification-which occurs when increased levels of atmospheric CO2 dissolve into the ocean-is one of the biggest potential threats to marine life. In a coastal upwelling system, we compared the effects of chronic exposure to low pH (elevated pCO2 at four treatment levels (i.e., pCO2 = ambient [500], moderate [750], high [1900], and extreme [2800 μatm] on behavior, physiology, and patterns of gene expression in white muscle tissue of juvenile rockfish (genus Sebastes, integrating responses from the transcriptome to the whole organism level. Experiments were conducted simultaneously on two closely related species that both inhabit kelp forests, yet differ in early life history traits, to compare high-CO2 tolerance among species. Our findings indicate that these congeners express different sensitivities to elevated CO2 levels. Copper rockfish (S. caurinus exhibited changes in behavioral lateralization, reduced critical swimming speed, depressed aerobic scope, changes in metabolic enzyme activity, and increases in the expression of transcription factors and regulatory genes at high pCO2 exposure. Blue rockfish (S. mystinus, in contrast, showed no significant changes in behavior, swimming physiology, or aerobic capacity, but did exhibit significant changes in the expression of muscle structural genes as a function of pCO2, indicating acclimatization potential. The capacity of long-lived, late to mature, commercially important fish to acclimatize and adapt to changing ocean chemistry over the next 50-100 years is likely dependent on species-specific physiological tolerances.

Experimental evidence of nitrogen control on pCO2 in phosphorus-enriched humic and clear coastal lagoon waters

Science.gov (United States)

Peixoto, Roberta B.; Marotta, Humberto; Enrich-Prast, Alex

2013-01-01

Natural and human-induced controls on carbon dioxide (CO2) in tropical waters may be very dynamic (over time and among or within ecosystems) considering the potential role of warmer temperatures intensifying metabolic responses and playing a direct role on the balance between photosynthesis and respiration. The high magnitude of biological processes at low latitudes following eutrophication by nitrogen (N) and phosphorus (P) inputs into coastal lagoons waters may be a relevant component of the carbon cycle, showing controls on partial pressure of CO2 (pCO2) that are still poorly understood. Here we assessed the strength of N control on pCO2 in P-enriched humic and clear coastal lagoons waters, using four experimental treatments in microcosms: control (no additional nutrients) and three levels of N additions coupled to P enrichments. In humic coastal lagoons waters, a persistent CO2 supersaturation was reported in controls and all nutrient-enriched treatments, ranging from 24- to 4-fold the atmospheric equilibrium value. However, both humic and clear coastal lagoons waters only showed significant decreases in pCO2 in relation to the controlled microcosms in the two treatments with higher N addition levels. Additionally, clear coastal lagoons water microcosms showed a shift from CO2 sources to CO2 sinks, in relation to the atmosphere. Only in the two more N-enriched treatments did pCO2 substantially decrease, from 650 µatm in controls and less N-enriched treatments to 10 µatm in more N-enriched microcosms. Humic substrates and N inputs can modulate pCO2 even in P-enriched coastal lagoons waters, thereby being important drivers on CO2 outgassing from inland waters. PMID:23390422

Experimental evidence of nitrogen control on pCO2 in phosphorus-enriched humic and clear coastal lagoon waters

Directory of Open Access Journals (Sweden)

Roberta Bittencourt Peixoto

2013-02-01

Full Text Available Natural and human-induced controls on carbon dioxide (CO2 in tropical waters may be very dynamic (over time and among or within ecosystems considering the potential role of warmer temperatures intensifying metabolic responses and playing a direct role on the balance between photosynthesis and respiration. The high magnitude of biological processes at low latitudes following eutrophication by nitrogen (N and phosphorus (P inputs into inland waters may be a relevant component of the C cycle, showing controls on partial pressure of CO2 (pCO2 that are still poorly understood. Here we assessed the strength of N control on pCO2 in P-enriched humic and clear coastal lagoons waters, using four experimental treatments in microcosms: control (no additional nutrients and three levels of N additions coupled to P enrichments. In humic coastal lagoon waters, a persistent CO2 supersaturation was reported in controls and all nutrient-enriched treatments, ranging from 24-fold to fourfold the atmospheric equilibrium value. However, both humic and clear coastal lagoon waters only showed significant decreases in pCO2 in relation to the controlled microcosms in the two treatments with higher N addition levels. Additionally, clear coastal lagoon water microcosms showed a shift from CO2 sources to CO2 sinks, in relation to the atmosphere. Only in the two more N-enriched treatments did pCO2 substantially decrease, from 650 µatm in controls and less N-enriched treatments to 10 µatm in more N-enriched microcosms. Humic substrates and N inputs can modulate pCO2 even in P-enriched coastal lagoon waters, thereby being important drivers on CO2 outgassing from inland waters.

Validation of the Performance of International Ovarian Tumor Analysis (IOTA) Methods in the Diagnosis of Early Stage Ovarian Cancer in a Non-Screening Population.

Science.gov (United States)

Froyman, Wouter; Wynants, Laure; Landolfo, Chiara; Bourne, Tom; Valentin, Lil; Testa, Antonia; Sladkevicius, Povilas; Franchi, Dorella; Fischerova, Daniela; Savelli, Luca; Van Calster, Ben; Timmerman, Dirk

2017-06-02

The aim of this study was to assess and compare the performance of different ultrasound-based International Ovarian Tumor Analysis (IOTA) strategies and subjective assessment for the diagnosis of early stage ovarian malignancy. This is a secondary analysis of a prospective multicenter cross-sectional diagnostic accuracy study that included 1653 patients recruited at 18 centers from 2009 to 2012. All patients underwent standardized transvaginal ultrasonography by experienced ultrasound investigators. We assessed test performance of the IOTA Simple Rules (SRs), Simple Rules Risk (SRR), the Assessment of Different NEoplasias in the adneXa (ADNEX) model and subjective assessment to discriminate between stage I-II ovarian cancer and benign disease. Reference standard was histology after surgery. 230 (13.9%) patients proved to have stage I-II primary invasive ovarian malignancy, and 1423 (86.1%) had benign disease. Sensitivity and specificity with respect to malignancy (95% confidence intervals) of the original SRs (classifying all inconclusive cases as malignant) were 94.3% (90.6% to 96.7%) and 73.4% (71.0% to 75.6%). Subjective assessment had a sensitivity and specificity of 90.0% (85.4% to 93.2%) and 86.7% (84.9% to 88.4%), respectively. The areas under the receiver operator characteristic curves of SRR and ADNEX were 0.917 (0.902 to 0.933) and 0.905 (0.920 to 0.934), respectively. At a 1% risk cut-off, sensitivity and specificity for SRR were 100% (98.4% to 100%) and 38.0% (35.5% to 40.6%), and for ADNEX were 100% (98.4% to 100%) and 19.4% (17.4% to 21.5%). At a 30% risk cut-off, sensitivity and specificity for SRR were 88.3% (83.5% to 91.8%) and 81.1% (79% to 83%), and for ADNEX were 84.5% (80.5% to 89.6%) and 84.5% (82.6% to 86.3%). This study shows that all three IOTA strategies have good ability to discriminate between stage I-II ovarian malignancy and benign disease.

Pelvic Inflammatory Disease and the Risk of Ovarian Cancer and Borderline Ovarian Tumors

DEFF Research Database (Denmark)

Rasmussen, Christina B; Kjaer, Susanne K; Albieri, Vanna

2017-01-01

Inflammation has been implicated in ovarian carcinogenesis. However, studies investigating the association between pelvic inflammatory disease (PID) and ovarian cancer risk are few and inconsistent. We investigated the association between PID and the risk of epithelial ovarian cancer according to...

Multivariate Analysis of Reproductive Risk Factors for Ovarian Cancer in Alexandria, Egypt

International Nuclear Information System (INIS)

El-Khwsky, F.S.; Maghraby, H.K.; Rostom, Y.A.; Abdel-Rahman, A.H.

2006-01-01

Background: Ovarian cancer is the eighth leading cancer in women, as it accounts for 4% of all malignant tumors in females. The incidence of ovarian cancer is up to 10 times higher in western countries than in rural Asian and Africa ones. Different reproductive characteristics, life styles and specific medical conditions are responsible for different pattern and incidence of ovarian cancer worldwide. Material and Methods: A case control study was conducted during the time period from 2000 to 2003 including 172 cases of epithelial ovarian cancer, recently diagnosed and confirmed by histopathology. The patients were accessed at the hospitals currently covered by Alexandria Cancer Registry. In addition, 441 control subjects, comparable by age and address, were randomly selected from patients admitted to the same hospitals for non gynecological, non endocrinal acute diseases. Both cases and controls were subjected to a specific predesigned questionnaire to cover menstrual, reproductive and lifestyle indicators. Univariate and multivariate analysis were conducted and 5% level of significance was adopted. Results: Significantly increased risks were reported with increased number of abortions and increased number of ovarian cycles (OR=1.8, 95% CI (1.7-2.8), and 2.8, 95% CI 2.8 (1.5-5.2), respectively. Similarly, high risks were also reported for increased number of pregnancies, OR= 1.6, 95% CI 1.1-2.4) for I to three pregnancies and 4.2,95% CI 1.2-15.9) for more than four pregnancies On the other hand, decreased risks were reported for those with increased parity compared to nulliparous. Conclusion: Although ovarian cancer is less frequent in our community, yet the significant positive and negative associations between risk factors and ovarian cancer were similar to the results of other studies, apart from the primary prevention program that should be outlined according to prevalence of significant risk factors in the studied local community

Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium

DEFF Research Database (Denmark)

Pearce, C L; Near, A M; Van Den Berg, D J

2009-01-01

The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had...... been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P... and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted....

Dual targeting of TNF-α and free radical toxic stress as a promising strategy to manage experimental polycystic ovary.

Science.gov (United States)

Rezvanfar, Mohammad Amin; Saeedi, Sarah; Mansoori, Parisa; Saadat, Sepideh; Goosheh, Maziar; Shojaei Saadi, Habib A; Baeeri, Maryam; Abdollahi, Mohammad

2016-01-01

It is now clear that oxidative stress (OS) and chronic low-grade inflammation are two main pathways involved in polycystic ovary syndrome (PCOS) pathogenesis. Therefore, simultaneous targeting of these pathways by means of carvedilol and Semelil (ANGIPARS™), as established medicines with dual anti-cytokine and anti-oxidant potential may be a therapeutic alternative approach to the current treatments. The objective of this study is to study the protective effects of carvedilol and ANGIPARS™ on inflammatory and oxidative response in hyperandrogenism-induced polycystic ovary (PCO). The murine model of PCO was induced by letrozole (1 mg/kg/d; orally) and effective doses of carvedilol (10 mg/kg/d; orally) and ANGIPARS™ (2.1 mg/kg/d; orally) were administrated for 21 d in PCO and non-PCO healthy rats. Ovarian folliculogenesis, sex hormones concentrations, OS, inflammatory, and metabolic biomarkers were assessed in serum and ovaries. PCO rats exhibited ovarian cystogenesis which was preserved by the application of carvedilol and ANGIPARS™. In comparison with controls, decreased level of the total antioxidant power (TAP) and higher levels of reactive oxygen species (ROS) and lipid peroxidation (LPO) in serum and ovaries (2.41 ± 0.67 versus 0.72 ± 0.11; and 0.17 ± 0.04 versus 0.05 ± 0.01; 5.48 ± 1.30 versus 10.56 ± 0.77; and 7.06 ± 1.94 versus 17.98 ± 0.98; p < 0.05, respectively) were detected in PCO rats. Moreover, the PCO rats exhibited hyperandrogenism due to a 3.7-fold increase in serum testosterone concentration (35.04 ± 3.17 versus 131.09 ± 13.24; p < 0.05) along with a 2.98-fold decrease in serum progesterone (6.19 ± 0.40 versus 18.50 ± 1.03; p < 0.05) and 5.2-fold decrease in serum estradiol (9.30 ± 0.61 versus 48.3 ± 2.10; p < 0.05) when compared with those of the control group. However, similar to the control group, normal levels of OS markers and sex hormones were detected in ANGIPARS™ and carvedilol co-treated PCO rats. Besides, when

Carcinoid Syndrome and Carcinoid Heart Disease as Manifestations of Non-Metastatic Ovarian Neuroendocrine Tumour

Directory of Open Access Journals (Sweden)

Joana Simões-Pereira

2017-05-01

Full Text Available The carcinoid syndrome is rare but it is associated with carcinoid heart disease in more than a half of the cases. Carcinoid heart disease is typically characterised by morphological and functional modifications of right-sided valves. Its aetiology is probable multifactorial but serotonin appears to play a key role in the development of this valvular disease. Unlike gastrointestinal neuroendocrine tumours, ovarian neuroendocrine tumours can present with carcinoid syndrome and carcinoid heart disease in the absence of liver metastases; such ovarian neuroendocrine tumours are a unique clinical entity. The additional burden of cardiac impairment in these patients represents a significant reduction in survival. Early recognition and surgical valve replacement before advanced heart failure is established may improve the clinical outcome. We report the case of a woman with an ovarian neuroendocrine tumour and highly symptomatic carcinoid heart disease who was submitted to tumour resection followed by valvuloplasty. She demonstrated an outstanding clinical improvement and has remained free of tumour and symptomatology.

Ovarian volume throughout life

DEFF Research Database (Denmark)

Kelsey, Thomas W; Dodwell, Sarah K; Wilkinson, A Graham

2013-01-01

conception to 82 years of age. This model shows that 69% of the variation in ovarian volume is due to age alone. We have shown that in the average case ovarian volume rises from 0.7 mL (95% CI 0.4-1.1 mL) at 2 years of age to a peak of 7.7 mL (95% CI 6.5-9.2 mL) at 20 years of age with a subsequent decline...... to about 2.8 mL (95% CI 2.7-2.9 mL) at the menopause and smaller volumes thereafter. Our model allows us to generate normal values and ranges for ovarian volume throughout life. This is the first validated normative model of ovarian volume from conception to old age; it will be of use in the diagnosis......The measurement of ovarian volume has been shown to be a useful indirect indicator of the ovarian reserve in women of reproductive age, in the diagnosis and management of a number of disorders of puberty and adult reproductive function, and is under investigation as a screening tool for ovarian...

Lateral supraorbital approach to ipsilateral PCA-P1 and ICA-PCoA aneurysms.

Science.gov (United States)

Goehre, Felix; Jahromi, Behnam Rezai; Elsharkawy, Ahmed; Lehto, Hanna; Shekhtman, Oleg; Andrade-Barazarte, Hugo; Munoz, Francisco; Hijazy, Ferzat; Makhkamov, Makhkam; Hernesniemi, Juha

2015-01-01

Aneurysms of the posterior cerebral artery (PCA) are rare and often associated with anterior circulation aneurysms. The lateral supraorbital approach allows for a very fast and safe approach to the ipsilateral lesions Circle of Willis. A technical note on the successful clip occlusion of two aneurysms in the anterior and posterior Circle of Willis via this less invasive approach has not been published before. The objective of this technical note is to describe the simultaneous microsurgical clip occlusion of an ipsilateral PCA-P1 and an internal carotid artery - posterior communicating artery (ICA-PCoA) aneurysm via the lateral supraorbital approach. The authors present a technical report of successful clip occlusions of ipsilateral located PCA-P1 and ICA-PCoA aneurysms. A 59-year-old female patient was diagnosed with a PCA-P1 and an ipsilateral ICA-PCoA aneurysm by computed tomography angiography (CTA) after an ischemic stroke secondary to a contralateral ICA dissection. The patient underwent microsurgical clipping after a lateral supraorbital craniotomy. The intraoperative indocyanine green (ICG) videoangiography and the postoperative CTA showed a complete occlusion of both aneurysms; the parent vessels (ICA and PCA) were patent. The patient presents postoperative no new neurologic deficit. The lateral supraorbital approach is suitable for the simultaneous microsurgical treatment of proximal anterior circulation and ipsilateral proximal PCA aneurysms. Compared to endovascular treatment, direct visual control of brainstem perforators is possible.

Endometrial carcinoma occuring from polycystic ovary disease : A case report

International Nuclear Information System (INIS)

Seong, Su Ok; Jeon, Woo Ki

1996-01-01

Endometrial carcinoma usually occurs in postmenopausal women ; less than 5% occurs in women under the age of 40. Up to one quarter of endometrial carcinoma patients below this age have PCO(polycystic ovary disease, Stein-Leventhal syndrome). The increased incidence of endometrial carcinoma in patients with PCO is related to chronic estrogenic stimulation. We report MR imaging in one case of endometrial carcinoma occuring in a 23 year old woman with PCO and had complained of hypermenorrhea for about three years. On T2-weighted MR image the endometrial cavity was seen to be distended with protruded endometrial masses of intermediate signal intensity, and the junctional zone was disrupted beneath the masses. Both ovaries were best seen on T2-weighted MR imaging and showed multiple small peripheral cysts and low signal-intensity central stroma

Endometrial carcinoma occuring from polycystic ovary disease : A case report

Energy Technology Data Exchange (ETDEWEB)

Seong, Su Ok; Jeon, Woo Ki [Inje Univ. College of Medicine, Seoul (Korea, Republic of)

1996-12-01

Endometrial carcinoma usually occurs in postmenopausal women ; less than 5% occurs in women under the age of 40. Up to one quarter of endometrial carcinoma patients below this age have PCO(polycystic ovary disease, Stein-Leventhal syndrome). The increased incidence of endometrial carcinoma in patients with PCO is related to chronic estrogenic stimulation. We report MR imaging in one case of endometrial carcinoma occuring in a 23 year old woman with PCO and had complained of hypermenorrhea for about three years. On T2-weighted MR image the endometrial cavity was seen to be distended with protruded endometrial masses of intermediate signal intensity, and the junctional zone was disrupted beneath the masses. Both ovaries were best seen on T2-weighted MR imaging and showed multiple small peripheral cysts and low signal-intensity central stroma.

Epithelium-Stroma Classification via Convolutional Neural Networks and Unsupervised Domain Adaptation in Histopathological Images.

Science.gov (United States)

Huang, Yue; Zheng, Han; Liu, Chi; Ding, Xinghao; Rohde, Gustavo K

2017-11-01

Epithelium-stroma classification is a necessary preprocessing step in histopathological image analysis. Current deep learning based recognition methods for histology data require collection of large volumes of labeled data in order to train a new neural network when there are changes to the image acquisition procedure. However, it is extremely expensive for pathologists to manually label sufficient volumes of data for each pathology study in a professional manner, which results in limitations in real-world applications. A very simple but effective deep learning method, that introduces the concept of unsupervised domain adaptation to a simple convolutional neural network (CNN), has been proposed in this paper. Inspired by transfer learning, our paper assumes that the training data and testing data follow different distributions, and there is an adaptation operation to more accurately estimate the kernels in CNN in feature extraction, in order to enhance performance by transferring knowledge from labeled data in source domain to unlabeled data in target domain. The model has been evaluated using three independent public epithelium-stroma datasets by cross-dataset validations. The experimental results demonstrate that for epithelium-stroma classification, the proposed framework outperforms the state-of-the-art deep neural network model, and it also achieves better performance than other existing deep domain adaptation methods. The proposed model can be considered to be a better option for real-world applications in histopathological image analysis, since there is no longer a requirement for large-scale labeled data in each specified domain.

Ovarian cancer and smoking

DEFF Research Database (Denmark)

Beral, V; Gaitskell, K; Hermon, C

2012-01-01

Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence....

Reference values in ovarian response to controlled ovarian stimulation throughout the reproductive period.

Science.gov (United States)

La Marca, Antonio; Grisendi, Valentina; Spada, Elena; Argento, Cindy; Milani, Silvano; Plebani, Maddalena; Seracchioli, Renato; Volpe, Annibale

2014-01-01

Abstract The age-related decline in ovarian response to gonadotropins has been well known since the beginning of ovarian stimulation in IVF cycles and has been considered secondary to the age-related decline in ovarian reserve. The objective of this study was to establish reference values and to construct nomograms of ovarian response for any specific age to gonadotropins in IVF/ICSI cycles. We analyzed our database containing information on IVF cycles. According to inclusion and exclusion criteria, a total of 703 patients were selected. Among inclusion criteria, there were regular menstrual cycle, treatment with a long GnRH agonist protocol and starting follicle-stimulating hormone (FSH) dose of at least 200 IU per day. To estimate the reference values of ovarian response, the CG-LMS method was used. A linear decline in the parameters of ovarian response with age was observed: the median number of oocytes decreases approximately by one every three years, and the median number of follicles >16 mm by one every eight years. The number of oocytes and growing follicles corresponding to the 5th, 25th, 50th, 75th and 95th centiles has been calculated. This study confirmed the well known negative relationship between ovarian response to FSH and female ageing and permitted the construction of nomograms of ovarian response.

Transvaginal ultrasound assessment of myometrial and cervical stroma invasion in women with endometrial cancer -interobserver reproducibility among ultrasound experts and gynaecologists

DEFF Research Database (Denmark)

Eriksson, LS; Lindqvist, PG; Flöter Rådestad, A

2014-01-01

OBJECTIVES: To assess interobserver reproducibility among ultrasound experts and gynaecologists in the prediction of deep myometrial- and cervical stroma invasion by transvaginal ultrasound in women with endometrial cancer. METHODS: Video-clips of the corpus- and cervix uteri of 53 women...... with endometrial cancer, examined preoperatively by the same ultrasound expert, were integrated in a digitalized survey. Nine ultrasound experts and 9 gynaecologists evaluated presence or absence of deep myometrial- and cervical stroma invasion. Histopathology from hysterectomy specimen was used as gold standard.......001). CONCLUSION: Preoperative ultrasound assessment of deep myometrial- and cervical stroma invasion in endometrial cancer is best performed by ultrasound experts, as they show a higher degree of agreement to histopathology and higher interobserver reproducibility in the assessment of cervical stromal invasion....

Epithelial ovarian cancer and the occurrence of skin cancer in the Netherlands: histological type connotations

NARCIS (Netherlands)

Niekerk, G.C. van; Bulten, J.; Verbeek, A.L.M.

2011-01-01

Background. Patients with epithelial ovarian cancer have a high risk of (non-)melanoma skin cancer. The association between histological variants of primary ovarian cancer and skin cancer is poorly documented. Objectives. To further evaluate the risk of skin cancer based on the histology of the

Prevention of ovarian cancer.

Science.gov (United States)

Hanna, Louise; Adams, Malcolm

2006-04-01

Ovarian cancer is the leading cause of death from gynaecological malignancy. The incidence is high in the Western world. The incidence of ovarian cancer is reduced by pregnancy, lactation, the oral contraceptive pill and tubal ligation. Lifestyle factors are important in the aetiology of ovarian cancer and current evidence suggests the risk can be reduced by eating a diet rich in fruit and vegetables, taking regular exercise, avoiding smoking, avoiding being overweight and avoiding long-term use of hormonal replacement therapy (HRT). Familial ovarian cancer is responsible for about 10% of ovarian cancer cases. Strategies available to high-risk women include screening (covered elsewhere) and prophylactic salpingo-oophorectomy. The precise role of chemoprevention for high-risk women in the form of the oral contraceptive pill is unclear.

Engineered gold nanoparticles for identification of novel ovarian biomarkers

Science.gov (United States)

Giri, Karuna

multiple proteins not detected by mass spectrometry alone. Differential expression analysis of proteins in cancer vs. non-cancer cells identified many proteins exclusively expressed in ovarian cancer. Hepatoma derived growth factor (HDGF) was one of the identified proteins that became the focus of the second part of the study. Understanding the role of HDGF in ovarian cancer would uncover its potential as a diagnostic and/or therapeutic marker. HDGF was found to be overexpressed in multiple ovarian cancer cell lines and xenograft models of ovarian cancer. Intracellular HDGF promoted cell proliferation, cell cycle progression and survival of ovarian cancer cell lines. While HDGF was exclusively localized in the nucleus, the protein was passively released from ovarian non-cancer and cancer cells during late apoptosis and necrosis. Extracellular HDGF activated MAP kinase pathways through a yet unknown receptor and promoted cell migration. Overall, the results presented in this study provide considerable support for the use of AuNPs for protein enrichment and detection of low abundance proteins. The functional study of HDGF, which revealed the importance of its expression in cancer cell, provides additional validation for AuNPs based cancer biomarker discovery. Further studies regarding the release of HDGF by cancer cells will help evaluate its utility in detecting and monitoring ovarian cancer. Additionally, initial results with knock down experiments indicate that HDGF has the potential to be a therapeutic target for inhibition of cancer progression.

Comparison of Interstitial Fluid pH, PCO2, PO2 with Venous Blood Values During Repetitive Handgrip Exercise

Science.gov (United States)

Hagan, Ronald Donald; Soller, Babs R.; Shear, Michael; Walz, Matthias; Landry, Michelle; Heard, Stephen

2006-01-01

We evaluated the use of a small, fiber optic sensor to measure pH, PCO2 and PO2 from forearm muscle interstitial fluid (IF) during handgrip dynamometry. PURPOSE: Compare pH, PCO2 and PO2 values obtained from venous blood with those from the IF of the flexor digitorum superficialis (FDS) during three levels of exercise intensity. METHODS: Six subjects (5M/1F), average age 29+/-5 yrs, participated in the study. A venous catheter was placed in the retrograde direction in the antecubital space and a fiber optic sensor (Paratrend, Diametrics Medical, Inc.) was placed through a 22 G catheter into the FDS muscle under ultrasound guidance. After a 45 min rest period, subjects performed three 5-min bouts of repetitive handgrip exercise (2s contraction/1 s relaxation) at attempted levels of 15%, 30% and 45% of maximal voluntary contraction. The order of the exercise bouts was random with the second and third bouts started after blood lactate had returned to baseline. Venous blood was sampled every minute during exercise and analyzed with an I-Stat CG-4+ cartridge, while IF fiber optic sensor measurements were obtained every 2 s. Change from pre-exercise baseline to end of exercise was computed for pH, PCO2 and PO2. Blood and IF values were compared with a paired t-test. RESULTS: Baseline values for pH, PCO2 and PO2 were 7.37+/-0.02, 46+/-4 mm Hg, and 36+/-6 mm Hg respectively in blood and 7.39+/-0.02, 44+/-6 mm Hg, and 35+/-14 mm Hg in IF. Average changes over all exercise levels are noted in the Table below. For each parameter the exercise-induced change was at least twice as great in IF as in blood. In blood and IF, pH and PCO2 increases were directly related to exercise intensity. Change in venous PO2 was unrelated to exercise intensity, while IF PO2 decreased with increases in exercise intensity. CONCLUSIONS: Measurement of IF pH, PCO2 and PO2 is more sensitive to exercise intensity than measurement of the same parameters in venous blood and provides continuous

Exposure to elevated pCO2 does not exacerbate reproductive suppression of Aurelia aurita jellyfish polyps in low oxygen environments

KAUST Repository

Treible, LM

2017-08-15

Eutrophication-induced hypoxia is one of the primary anthropogenic threats to coastal ecosystems. Under hypoxic conditions, a deficit of O2 and a surplus of CO2 will concurrently decrease pH, yet studies of hypoxia have seldom considered the potential interactions with elevated pCO2 (reduced pH). Previous studies on gelatinous organisms concluded that they are fairly robust to low oxygen and reduced pH conditions individually, yet the combination of stressors has only been examined for ephyrae. The goals of this study were to determine the individual and interactive effects of hypoxia and elevated pCO2 on the asexual reproduction and aerobic respiration rates of polyps of the scyphozoan Aurelia aurita during a manipulative experiment that ran for 36 d. pCO2 and pO2 were varied on a diel basis to closely mimic the diel conditions observed in the field. Exposure to low dissolved oxygen (DO) reduced asexual budding of polyps by ~50% relative to control conditions. Under hypoxic conditions, rates of respiration were elevated during an initial acclimation period (until Day 8), but respiration rates did not differ between DO levels under prolonged exposure. There was no significant effect of increased pCO2 on either asexual reproduction or aerobic respiration, suggesting that elevated pCO2 (reduced pH) did not exacerbate the negative reproductive effects of hypoxia on A. aurita polyps.

Exposure to elevated pCO2 does not exacerbate reproductive suppression of Aurelia aurita jellyfish polyps in low oxygen environments

KAUST Repository

Treible, LM; Pitt, KA; Klein, SG; Condon, RH

2017-01-01

Eutrophication-induced hypoxia is one of the primary anthropogenic threats to coastal ecosystems. Under hypoxic conditions, a deficit of O2 and a surplus of CO2 will concurrently decrease pH, yet studies of hypoxia have seldom considered the potential interactions with elevated pCO2 (reduced pH). Previous studies on gelatinous organisms concluded that they are fairly robust to low oxygen and reduced pH conditions individually, yet the combination of stressors has only been examined for ephyrae. The goals of this study were to determine the individual and interactive effects of hypoxia and elevated pCO2 on the asexual reproduction and aerobic respiration rates of polyps of the scyphozoan Aurelia aurita during a manipulative experiment that ran for 36 d. pCO2 and pO2 were varied on a diel basis to closely mimic the diel conditions observed in the field. Exposure to low dissolved oxygen (DO) reduced asexual budding of polyps by ~50% relative to control conditions. Under hypoxic conditions, rates of respiration were elevated during an initial acclimation period (until Day 8), but respiration rates did not differ between DO levels under prolonged exposure. There was no significant effect of increased pCO2 on either asexual reproduction or aerobic respiration, suggesting that elevated pCO2 (reduced pH) did not exacerbate the negative reproductive effects of hypoxia on A. aurita polyps.

Dexrazoxane Diminishes Doxorubicin-Induced Acute Ovarian Damage and Preserves Ovarian Function and Fecundity in Mice.

Directory of Open Access Journals (Sweden)

Jenna Kropp

Full Text Available Advances in cancer treatment utilizing multiple chemotherapies have dramatically increased cancer survivorship. Female cancer survivors treated with doxorubicin (DXR chemotherapy often suffer from an acute impairment of ovarian function, which can persist as long-term, permanent ovarian insufficiency. Dexrazoxane (Dexra pretreatment reduces DXR-induced insult in the heart, and protects in vitro cultured murine and non-human primate ovaries, demonstrating a drug-based shield to prevent DXR insult. The present study tested the ability of Dexra pretreatment to mitigate acute DXR chemotherapy ovarian toxicity in mice through the first 24 hours post-treatment, and improve subsequent long-term fertility throughout the reproductive lifespan. Adolescent CD-1 mice were treated with Dexra 1 hour prior to DXR treatment in a 1:1 mg or 10:1 mg Dexra:DXR ratio. During the acute injury period (2-24 hours post-injection, Dexra pretreatment at a 1:1 mg ratio decreased the extent of double strand DNA breaks, diminished γH2FAX activation, and reduced subsequent follicular cellular demise caused by DXR. In fertility and fecundity studies, dams pretreated with either Dexra:DXR dose ratio exhibited litter sizes larger than DXR-treated dams, and mice treated with a 1:1 mg Dexra:DXR ratio delivered pups with birth weights greater than DXR-treated females. While DXR significantly increased the "infertility index" (quantifying the percentage of dams failing to achieve pregnancy through 6 gestations following treatment, Dexra pretreatment significantly reduced the infertility index following DXR treatment, improving fecundity. Low dose Dexra not only protected the ovaries, but also bestowed a considerable survival advantage following exposure to DXR chemotherapy. Mouse survivorship increased from 25% post-DXR treatment to over 80% with Dexra pretreatment. These data demonstrate that Dexra provides acute ovarian protection from DXR toxicity, improving reproductive health

Altered Proteomic Polymorphisms in the Caterpillar Body and Stroma of Natural Cordyceps sinensis during Maturation

Science.gov (United States)

Wu, Zi-Mei; Gao, Ling; Yao, Yi-Sang; Tan, Ning-Zhi; Wu, Jian-Yong; Ni, Luqun; Zhu, Jia-Shi

2014-01-01

Objective To examine the maturational changes in proteomic polymorphisms resulting from differential expression by multiple intrinsic fungi in the caterpillar body and stroma of natural Cordyceps sinensis (Cs), an integrated micro-ecosystem. Methods The surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) biochip technique was used to profile the altered protein compositions in the caterpillar body and stroma of Cs during its maturation. The MS chromatograms were analyzed using density-weighted algorithms to examine the similarities and cluster relationships among the proteomic polymorphisms of the Cs compartments and the mycelial products Hirsutella sinensis (Hs) and Paecilomyces hepiali (Ph). Results: SELDI-TOF MS chromatograms displayed dynamic proteomic polymorphism alterations among samples from the different Cs compartments during maturation. More than 1,900 protein bands were analyzed using density-weighted ZUNIX similarity equations and clustering methods, revealing integral polymorphism similarities of 57.4% between the premature and mature stromata and 42.8% between the premature and mature caterpillar bodies. The across-compartment similarity was low, ranging from 10.0% to 18.4%. Consequently, each Cs compartment (i.e., the stroma and caterpillar body) formed a clustering clade, and the 2 clades formed a Cs cluster. The polymorphic similarities ranged from 0.51% to 1.04% between Hs and the Cs compartments and were 2.8- to 4.8-fold higher (1.92%–4.34%) between Ph and the Cs compartments. The Hs and Ph mycelial samples formed isolated clades outside of the Cs cluster. Conclusion Proteomic polymorphisms in the caterpillar body and stroma of Cs change dynamically during maturation. The proteomic polymorphisms in Hs and Ph differ from those in Cs, suggesting the presence of multiple Cs-associated fungi and multiple Ophiocordyceps sinensis genotypes with altered differential protein expression in the Cs compartments

Cancer-associated stroma affects FDG uptake in experimental carcinomas. Implications for FDG-PET delineation of radiotherapy target

Energy Technology Data Exchange (ETDEWEB)

Farace, Paolo; Merigo, Flavia; Galie, Mirco; Sbarbati, Andrea; Marzola, Pasquina [University of Verona, Department of Morphological-Biomedical Sciences, Section of Anatomy and Histology, Verona (Italy); D' Ambrosio, Daniela; Nanni, Cristina; Spinelli, Antonello; Fanti, Stefano [Policlinico ' S. Orsola-Malpighi' , Department of Nuclear Medicine, Bologna (Italy); Degrassi, Anna [Nerviano Medical Sciences, Milan (Italy); Rubello, Domenico [' S. Maria della Misericordia' Hospital, PET Centre, Department of Nuclear Medicine, Rovigo (Italy)

2009-04-15

To analyse the influence of cancer-associated stroma on FDG-uptake in two carcinoma models characterized by different stromal degrees. Eight nude mice were subcutaneously injected with DU-145 prostate cancer cells or BXPC-3 pancreatic cancer cells, and underwent FDG-PET imaging about 2 weeks after implantation. After the mice were killed, histology, and CD31 and GLUT1 immunohistochemistry were performed. To further evaluate the highly stromalized carcinoma using perfusion-sensitive imaging, four BXPC-3 tumours underwent two successive albumin-binding (MS-325) MRI scans during tumour growth. FDG uptake was significantly higher in the DU-145 than in the BXPC-3 tumours, which were hardly distinguishable from adjacent normal tissue. In the BXPC-3 tumours, histology confirmed the widespread presence of aberrant infiltrated stroma, embedded with numerous vessels marked by CD31. In both tumour types, the stromal matrix was negative for GLUT1. In DU-145 tumour cells, GLUT1 immunostaining was greater than in BXPC-3 tumour cells, but not homogeneously, since it was less evident in the tumour cells which were nearer to vessels and stroma. Finally, MS-325 MRI always clearly showed areas of enhancement in the BXPC-3 tumours. Cancer-associated stroma has been reported to be capable of aerobic metabolism with low glucose consumption. Furthermore, it has been proposed that regions with high vascular perfusion exhibit a significantly lower FDG uptake, suggesting some vascular/metabolic reciprocity. Since our results are consistent with these recent findings, they signal a risk of tumour volume underestimation in radiotherapy if FDG uptake alone is used for target delineation of carcinomas, which suggests that additional evaluation should be performed using vasculature/perfusion-sensitive imaging. (orig.)

Cancer-associated stroma affects FDG uptake in experimental carcinomas. Implications for FDG-PET delineation of radiotherapy target.

Science.gov (United States)

Farace, Paolo; D'Ambrosio, Daniela; Merigo, Flavia; Galiè, Mirco; Nanni, Cristina; Spinelli, Antonello; Fanti, Stefano; Degrassi, Anna; Sbarbati, Andrea; Rubello, Domenico; Marzola, Pasquina

2009-04-01

To analyse the influence of cancer-associated stroma on FDG-uptake in two carcinoma models characterized by different stromal degrees. Eight nude mice were subcutaneously injected with DU-145 prostate cancer cells or BXPC-3 pancreatic cancer cells, and underwent FDG-PET imaging about 2 weeks after implantation. After the mice were killed, histology, and CD31 and GLUT1 immunohistochemistry were performed. To further evaluate the highly stromalized carcinoma using perfusion-sensitive imaging, four BXPC-3 tumours underwent two successive albumin-binding (MS-325) MRI scans during tumour growth. FDG uptake was significantly higher in the DU-145 than in the BXPC-3 tumours, which were hardly distinguishable from adjacent normal tissue. In the BXPC-3 tumours, histology confirmed the widespread presence of aberrant infiltrated stroma, embedded with numerous vessels marked by CD31. In both tumour types, the stromal matrix was negative for GLUT1. In DU-145 tumour cells, GLUT1 immunostaining was greater than in BXPC-3 tumour cells, but not homogeneously, since it was less evident in the tumour cells which were nearer to vessels and stroma. Finally, MS-325 MRI always clearly showed areas of enhancement in the BXPC-3 tumours. Cancer-associated stroma has been reported to be capable of aerobic metabolism with low glucose consumption. Furthermore, it has been proposed that regions with high vascular perfusion exhibit a significantly lower FDG uptake, suggesting some vascular/metabolic reciprocity. Since our results are consistent with these recent findings, they signal a risk of tumour volume underestimation in radiotherapy if FDG uptake alone is used for target delineation of carcinomas, which suggests that additional evaluation should be performed using vasculature/perfusion-sensitive imaging.

Cancer-associated stroma affects FDG uptake in experimental carcinomas. Implications for FDG-PET delineation of radiotherapy target

International Nuclear Information System (INIS)

Farace, Paolo; Merigo, Flavia; Galie, Mirco; Sbarbati, Andrea; Marzola, Pasquina; D'Ambrosio, Daniela; Nanni, Cristina; Spinelli, Antonello; Fanti, Stefano; Degrassi, Anna; Rubello, Domenico

2009-01-01

To analyse the influence of cancer-associated stroma on FDG-uptake in two carcinoma models characterized by different stromal degrees. Eight nude mice were subcutaneously injected with DU-145 prostate cancer cells or BXPC-3 pancreatic cancer cells, and underwent FDG-PET imaging about 2 weeks after implantation. After the mice were killed, histology, and CD31 and GLUT1 immunohistochemistry were performed. To further evaluate the highly stromalized carcinoma using perfusion-sensitive imaging, four BXPC-3 tumours underwent two successive albumin-binding (MS-325) MRI scans during tumour growth. FDG uptake was significantly higher in the DU-145 than in the BXPC-3 tumours, which were hardly distinguishable from adjacent normal tissue. In the BXPC-3 tumours, histology confirmed the widespread presence of aberrant infiltrated stroma, embedded with numerous vessels marked by CD31. In both tumour types, the stromal matrix was negative for GLUT1. In DU-145 tumour cells, GLUT1 immunostaining was greater than in BXPC-3 tumour cells, but not homogeneously, since it was less evident in the tumour cells which were nearer to vessels and stroma. Finally, MS-325 MRI always clearly showed areas of enhancement in the BXPC-3 tumours. Cancer-associated stroma has been reported to be capable of aerobic metabolism with low glucose consumption. Furthermore, it has been proposed that regions with high vascular perfusion exhibit a significantly lower FDG uptake, suggesting some vascular/metabolic reciprocity. Since our results are consistent with these recent findings, they signal a risk of tumour volume underestimation in radiotherapy if FDG uptake alone is used for target delineation of carcinomas, which suggests that additional evaluation should be performed using vasculature/perfusion-sensitive imaging. (orig.)

MR findings of ruptured endometrial cyst: Comparison with tubo-ovarian abscess

International Nuclear Information System (INIS)

Suzuki, Shigeru; Yasumoto, Mayumi; Matsumoto, Reiko; Andoh, Akihiko

2012-01-01

Objective: To evaluate the MR findings of ruptured endometrial cyst, focusing on the differentiation from tubo-ovarian abscess (TOA). Patients and methods: We reviewed the records of 21 patients who underwent preoperative MR examinations for TOAs (n = 15) or ruptured endometrial cysts (n = 6). We evaluated the presence of hyper-intense ascites and hyper-intense peritoneum in T1-weighted sequences, strong enhancement of the peritoneum, hyper-intense content and hyper-intense rim of the ovarian lesion in T1-weighted sequences, and strong wall enhancement of the ovarian lesion. χ 2 test was used to assess the relationship between TOA cases versus cases with ruptured endometrial cysts, and the three MR peritoneal findings. We evaluated the relationship between TOA versus non-infected endometrial cysts, and the ovarian MR peritoneal findings, too. Results: Hyper-intense ascites was found in all of the patients with ruptured endometrial cyst and none with TOA (p < 0.0001). Hyper-intense peritoneum was observed in only TOAs cases (4 of 8). Strong peritoneal enhancement was seen in 3 of the 3 patients with ruptured endometrial cyst and 7 of the 13 patients with TOA (p = 0.1366). Hyper-intense content of the ovarian lesion was seen more often in the non-infected endometrial cysts than in the TOAs (p = 0.001607), while hyper-intense rim was more frequent in TOAs (p = 0.000402). Strong wall enhancement was observed only in TOAs (11 of 15) (p = 0.001355). Conclusions: MR images are useful to differentiate ruptured endometrial cyst from TOA.

MR findings of ruptured endometrial cyst: Comparison with tubo-ovarian abscess

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Suzuki, Shigeru, E-mail: shig.suz@gmail.com [Department of Radiology, Saitama Red Cross Hospital, 8-3-33 Kamiochiai, Chuo-ku, Saitama, 338-8553 (Japan); Yasumoto, Mayumi, E-mail: Mayumihoo@yahoo.co.jp [Department of Radiology, Saitama Red Cross Hospital, 8-3-33 Kamiochiai, Chuo-ku, Saitama, 338-8553 (Japan); Matsumoto, Reiko, E-mail: rad@saitama-med.jrc.or.jp [Department of Radiology, Saitama Red Cross Hospital, 8-3-33 Kamiochiai, Chuo-ku, Saitama, 338-8553 (Japan); Andoh, Akihiko, E-mail: a-andoh@silk.plala.or.jp [Department of Obstetrics and Gynecology, Saitama Red Cross Hospital, 8-3-33 Kamiochiai, Chuo-ku, Saitama, 338-8553 (Japan)

2012-11-15

Objective: To evaluate the MR findings of ruptured endometrial cyst, focusing on the differentiation from tubo-ovarian abscess (TOA). Patients and methods: We reviewed the records of 21 patients who underwent preoperative MR examinations for TOAs (n = 15) or ruptured endometrial cysts (n = 6). We evaluated the presence of hyper-intense ascites and hyper-intense peritoneum in T1-weighted sequences, strong enhancement of the peritoneum, hyper-intense content and hyper-intense rim of the ovarian lesion in T1-weighted sequences, and strong wall enhancement of the ovarian lesion. {chi}{sup 2} test was used to assess the relationship between TOA cases versus cases with ruptured endometrial cysts, and the three MR peritoneal findings. We evaluated the relationship between TOA versus non-infected endometrial cysts, and the ovarian MR peritoneal findings, too. Results: Hyper-intense ascites was found in all of the patients with ruptured endometrial cyst and none with TOA (p < 0.0001). Hyper-intense peritoneum was observed in only TOAs cases (4 of 8). Strong peritoneal enhancement was seen in 3 of the 3 patients with ruptured endometrial cyst and 7 of the 13 patients with TOA (p = 0.1366). Hyper-intense content of the ovarian lesion was seen more often in the non-infected endometrial cysts than in the TOAs (p = 0.001607), while hyper-intense rim was more frequent in TOAs (p = 0.000402). Strong wall enhancement was observed only in TOAs (11 of 15) (p = 0.001355). Conclusions: MR images are useful to differentiate ruptured endometrial cyst from TOA.

IL-33 activates tumor stroma to promote intestinal polyposis.

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Maywald, Rebecca L; Doerner, Stephanie K; Pastorelli, Luca; De Salvo, Carlo; Benton, Susan M; Dawson, Emily P; Lanza, Denise G; Berger, Nathan A; Markowitz, Sanford D; Lenz, Heinz-Josef; Nadeau, Joseph H; Pizarro, Theresa T; Heaney, Jason D

2015-05-12

Tumor epithelial cells develop within a microenvironment consisting of extracellular matrix, growth factors, and cytokines produced by nonepithelial stromal cells. In response to paracrine signals from tumor epithelia, stromal cells modify the microenvironment to promote tumor growth and metastasis. Here, we identify interleukin 33 (IL-33) as a regulator of tumor stromal cell activation and mediator of intestinal polyposis. In human colorectal cancer, IL-33 expression was induced in the tumor epithelium of adenomas and carcinomas, and expression of the IL-33 receptor, IL1RL1 (also referred to as IL1-R4 or ST2), localized predominantly to the stroma of adenoma and both the stroma and epithelium of carcinoma. Genetic and antibody abrogation of responsiveness to IL-33 in the Apc(Min/+) mouse model of intestinal tumorigenesis inhibited proliferation, induced apoptosis, and suppressed angiogenesis in adenomatous polyps, which reduced both tumor number and size. Similar to human adenomas, IL-33 expression localized to tumor epithelial cells and expression of IL1RL1 associated with two stromal cell types, subepithelial myofibroblasts and mast cells, in Apc(Min/+) polyps. In vitro, IL-33 stimulation of human subepithelial myofibroblasts induced the expression of extracellular matrix components and growth factors associated with intestinal tumor progression. IL-33 deficiency reduced mast cell accumulation in Apc(Min/+) polyps and suppressed the expression of mast cell-derived proteases and cytokines known to promote polyposis. Based on these findings, we propose that IL-33 derived from the tumor epithelium promotes polyposis through the coordinated activation of stromal cells and the formation of a protumorigenic microenvironment.

Insulin resistance and endocrine-metabolic abnormalities in polycystic ovarian syndrome: Comparison between obese and non-obese PCOS patients.

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Layegh, Parvin; Mousavi, Zohreh; Farrokh Tehrani, Donya; Parizadeh, Seyed Mohammad Reza; Khajedaluee, Mohammad

2016-04-01

Insulin resistance has an important role in pathophysiology of polycystic ovarian syndrome (PCOS). Yet there are certain controversies regarding the presence of insulin resistance in non-obese patients. The aim was to compare the insulin resistance and various endocrine and metabolic abnormalities in obese and non-obese PCOS women. In this cross-sectional study which was performed from 2007-2010, 115 PCOS patients, aged 16-45 years were enrolled. Seventy patients were obese (BMI ≥25) and 45 patients were non-obese (BMI 2.3) between two groups (p=0.357). Waist circumference (pPCOS patients. There was no significant difference in total testosterone (p=0.634) and androstenedione (p=0.736) between groups whereas Dehydroepiandrotendione sulfate (DHEAS) was significantly higher in non-obese PCOS women (p=0.018). There was no case of fatty liver and metabolic syndrome in non-obese patients, whereas they were seen in 31.3% and 39.4% of obese PCOS women, respectively. Our study showed that metabolic abnormalities are more prevalent in obese PCOS women, but adrenal axis activity that is reflected in higher levels of DHEAS was more commonly pronounced in our non-obese PCOS patients.

Pancreatic Metastasis of High-Grade Papillary Serous Ovarian Carcinoma Mimicking Primary Pancreas Cancer: A Case Report

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Yusuf Gunay

2012-01-01

Full Text Available Introduction. Reports of epithelial ovarian carcinomas metastatic to the pancreas are very rare. We herein present a metastasis of high grade papillary serous ovarian cancer to mid portion of pancreas. Case. A 42-year-old patient was admitted with a non-specified malignant cystic lesion in midportion of pancreas. She had a history of surgical treatment for papillary serous ovarian adenocarcinoma. A cystic lesion was revealed by an abdominal computerized tomography (CT performed in her follow up . It was considered as primary mid portion of pancreatic cancer and a distal pancreatectomy was performed. The final pathology showed high-grade papillary serous adenocarcinoma morphologically similar to the previously diagnosed ovarian cancer. Discussion. Metastatic pancreatic cancers should be considered in patients who present with a solitary pancreatic mass and had a previous non-pancreatic malignancy. Differential diagnosis of primary pancreatic neoplasm from metastatic malignancy may be very difficult. A biopsy for tissue confirmation is required to differentiate primary and secondary pancreatic tumors. Although, the value of surgical resection is poorly documented, resection may be considered in selected patients. Conclusion. Pancreatic metastasis of ovarian papillary serous adenocarcinoma has to be kept in mind when a patient with pancreatic mass has a history of ovarian malignancy.

[Association between obesity and ovarian cancer].

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Valladares, Macarena; Corsini, Gino; Romero, Carmen

2014-05-01

Obesity is a risk factor for cancer. Epidemiological evidences associate ovarian cancer with obesity. Epithelial ovarian cancer (EOC) is the most common type of ovarian cancer and accounts for a high rate of mortality. The association between ovarian cancer and obesity could be explained by molecular factors secreted by adipose tissue such as leptin. In EOC, leptin increases cell proliferation and inhibits apoptosis. Additionally, adipose tissue synthesizes endogenous estrogens, which increase cell proliferation of epithelial ovarian cells. Also, obesity associated hyperinsulinism could increase ovarian estrogen secretion.

Radioimmunoassay of the normal serum glycoprotein (CX1) in monitoring ovarian malignancy

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Wass, M.; Searle, F.; Bagshawe, K.D.

1981-01-01

A glycoprotein designated CX 1, of molecular weight 80,000, has been extracted from adenocarcinomas of the ovary and its measurement by radioimmunoassay established. CX 1 is present in the normal ovary and in normal serum. It is present in various non-ovarian carcinomas but in much greater amount in ovarian adenocarcinoma and in ascitic fluid associated with this cancer. Increased concentrations are found in the serum of patients with various cancers. In about 60% of patients with Stage III and IV ovarian adenocarcinoma, serum values are elevated and they correlate with the course of the disease, providing information which probably has clinical value. (author)

Drugs with potential chemopreventive properties in relation to epithelial ovarian cancer--a nationwide case-control study.

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Baandrup, Louise

2015-07-01

Ovarian cancer has a poor prognosis because the disease in the majority of patients is diagnosed at an advanced stage as a result of nonspecific symptoms and lack of efficient screening methods. Because of the poor prognosis of ovarian cancer and the challenge of early detection of the disease, identification of protective factors is important. It has been suggested that some commonly used drugs may have a protective effect against cancer, including ovarian cancer; however, the literature on chemopreventive measures for ovarian cancer is sparse and the results are inconclusive. Most previous studies have substantial methodological constraints, including limited study size and self-reporting of drug use, which introduces potential recall bias and misclassification. This PhD thesis includes a nationwide case-control study to evaluate associations between use of drugs with potential chemopreventive properties and risk of epithelial ovarian cancer. The study is nested in the entire Danish female population using data from the following nationwide registries: the Danish Cancer Registry, the Danish Civil Registration System, the Danish Prescription Registry, the Danish National Patient Register, and registries in Statistics Denmark on fertility, education, and income. Information from the included registries is linked by use of the unique personal identification number assigned to all Danish citizens. The cases were all women in Denmark with epithelial ovarian cancer diagnosed during 2000-2009 (Paper 1) and 2000-2011 (Papers 2 and 3), identified in the Cancer Registry. Age-matched female population controls were randomly selected from the Civil Registration System by risk-set sampling. We required that cases and controls have no history of cancer (except non-melanoma skin cancer) and that controls not previously have undergone bilateral oophorectomy or salpingo-oophorectomy. The total study population comprised 3741 epithelial ovarian cancer cases and 50,576 controls in

Tubal ligation and salpingectomy and the risk of epithelial ovarian cancer and borderline ovarian tumors

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Madsen, C; Baandrup, Louise; Dehlendorff, Christian

2015-01-01

OBJECTIVE: According to the recent theories on the ovarian cancer origin, any protective effect of tubal ligation may vary with histologic subtype of ovarian cancer. Furthermore, bilateral salpingectomy may represent an opportunity for surgical prevention of serous ovarian cancer. DESIGN: Nationw......OBJECTIVE: According to the recent theories on the ovarian cancer origin, any protective effect of tubal ligation may vary with histologic subtype of ovarian cancer. Furthermore, bilateral salpingectomy may represent an opportunity for surgical prevention of serous ovarian cancer. DESIGN...... sampling. We required that cases and controls have no previous cancer and that controls have no previous bilateral oophorectomy. METHODS: Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals, adjusting for potential confounders. MAIN OUTCOME MEASURES: Epithelial...

In situ developmental responses of tropical sea urchin larvae to ocean acidification conditions at naturally elevated pCO2 vent sites.

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Lamare, Miles D; Liddy, Michelle; Uthicke, Sven

2016-11-30

Laboratory experiments suggest that calcifying developmental stages of marine invertebrates may be the most ocean acidification (OA)-sensitive life-history stage and represent a life-history bottleneck. To better extrapolate laboratory findings to future OA conditions, developmental responses in sea urchin embryos/larvae were compared under ecologically relevant in situ exposures on vent-elevated pCO 2 and ambient pCO 2 coral reefs in Papua New Guinea. Echinometra embryos/larvae were reared in meshed chambers moored in arrays on either venting reefs or adjacent non-vent reefs. After 24 and 48 h, larval development and morphology were quantified. Compared with controls (mean pH (T) = 7.89-7.92), larvae developing in elevated pCO 2 vent conditions (pH (T) = 7.50-7.72) displayed a significant reduction in size and increased abnormality, with a significant correlation of seawater pH with both larval size and larval asymmetry across all experiments. Reciprocal transplants (embryos from vent adults transplanted to control conditions, and vice versa) were also undertaken to identify if adult acclimatization can translate resilience to offspring (i.e. transgenerational processes). Embryos originating from vent adults were, however, no more tolerant to reduced pH. Sea temperature and chlorophyll-a concentrations (i.e. larval nutrition) did not contribute to difference in larval size, but abnormality was correlated with chlorophyll levels. This study is the first to examine the response of marine larvae to OA scenarios in the natural environment where, importantly, we found that stunted and abnormal development observed in situ are consistent with laboratory observations reported in sea urchins, in both the direction and magnitude of the response. © 2016 The Author(s).

Histopathological and Follicular Atresia Assessment of Rat’s Ovarian Tissue Following Experimental Chronic Spinal Cord Injury

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Sam Zarbakhsh

2017-06-01

Full Text Available Background One of the important side effects in spinal cord injuries in both genders is sexual dysfunction. This study aimed at investigating histopathological changes of ovaries in the chronic phase after spinal cord injury. Methods Animals (adult female rats were divided to the following groups, Control (Co, Sham (Sh, and Spinal Cord Injury (SCI; each group contained 18 rats. The spinal cord of SCI animals was transected by the bilateral laminectomy method on level T9, while the rats of the sham group were incised in the same location without any spinal cord injury. Animals were sacrified at 7th, 14th and 21st day postsurgical intervention, then the body weight, and the weight and volume of ovaries were measured. The slices were stained by hematoxylin and eosin and periodic acid Schiff methods. The histomorphometric changes of the diameter of the follicle and ovum, and the thickness of granulosa layer were measured in different kinds of follicles including, Unilaminar Primary Follicle (UPF, Multilaminar Primary Follicle (MPF, Secondary Follicle (SF, and Tertiary Follicle (TF. Results The results showed that the animal weights were decreased in three SCI groups (P = 0.018. In the SCI groups, the diameter of follicle and ovum and the thickness of granulosa layer were significantly decreased in different kinds of follicles (P = 0.012. Also the thickness of zona pellucida and theca interna were significantly decreased in UPF, SF, and TF in the SCI groups on 14th and 21st day (P = 0.024. The histopathologic examination revealed widespread ovarian follicle atresia in the SCI groups on the 14th and 21st day, including numerous cell debris and inflammatory cells in the antrum atretic follicles. The ovarian stroma showed edema, fibrosis, hypercellularity, and vasodilation in the SCI group, compared to the sham or control groups. Conclusions The histopathlogic data indicated that after spinal cord injury many histologic parameter changes occurred and

Autoimmune premature ovarian failure

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Beata Komorowska

2017-02-01

Full Text Available Premature ovarian failure (POF, also termed as primary ovarian insufficiency (POI, is a highly heterogenous condition affecting 0.5-3.0% of women in childbearing age. These young women comprise quite a formidable group with unique physical and psychological needs that require special attention. Premature ovarian senescence (POS in all of its forms evolves insidiously as a basically asymptomatic process, leading to complete loss of ovarian function, and POI/POF diagnoses are currently made at relatively late stages. Well-known and well-documented risk factors exist, and the presence or suspicion of autoimmune disorder should be regarded as an important one. Premature ovarian failure is to some degree predictable in its occurrence and should be considered while encountering young women with loss of menstrual regularity, especially when there is a concomitant dysfunction in the immune system.

Air-ice CO2 fluxes and pCO2 dynamics in the Arctic coastal area (Amundsen Gulf, Canada)

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Geilfus, Nicolas-Xavier; Tison, Jean Louis; Carnat, Gauthier; Else, Brent; Borges, Alberto V.; Thomas, Helmuth; Shadwick, Elizabeth; Delille, Bruno

2010-05-01

Sea ice covers about 7% of the Earth surface at its maximum seasonal extent. For decades sea ice was assumed to be an impermeable and inert barrier for air - sea exchange of CO2 so that global climate models do not include CO2 exchange between the oceans and the atmosphere in the polar regions. However, uptake of atmospheric CO2 by sea ice cover was recently reported raising the need to further investigate pCO2 dynamics in the marine cryosphere realm and related air-ice CO2 fluxes. In addition, budget of CO2 fluxes are poorly constrained in high latitudes continental shelves [Borges et al., 2006]. We report measurements of air-ice CO2 fluxes above the Canadian continental shelf and compare them to previous measurements carried out in Antarctica. We carried out measurements of pCO2 within brines and bulk ice, and related air-ice CO2 fluxes (chamber method) in Antarctic first year pack ice ("Sea Ice Mass Balance in Antarctica -SIMBA" drifting station experiment September - October 2007) and in Arctic first year land fast ice ("Circumpolar Flaw Lead" - CFL, April - June 2008). These 2 experiments were carried out in contrasted sites. SIMBA was carried out on sea ice in early spring while CFL was carried out in from the middle of the winter to the late spring while sea ice was melting. Both in Arctic and Antarctic, no air-ice CO2 fluxes were detected when sea ice interface was below -10°C. Slightly above -10°C, fluxes toward the atmosphere were observed. In contrast, at -7°C fluxes from the atmosphere to the ice were significant. The pCO2 of the brine exhibits a same trend in both hemispheres with a strong decrease of the pCO2 anti-correlated with the increase of sea ice temperature. The pCO2 shifted from a large over-saturation at low temperature to a marked under-saturation at high temperature. These air-ice CO2 fluxes are partly controlled by the permeability of the air-ice interface, which depends of the temperature of this one. Moreover, air-ice CO2 fluxes are

Restoring Ovarian Endocrine Function with Encapsulated Ovarian Allograft in Immune Competent Mice.

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David, Anu; Day, James Ronald; Cichon, Alexa Leigh; Lefferts, Adam; Cascalho, Marilia; Shikanov, Ariella

2017-07-01

Premature ovarian insufficiency (POI) is a major complication of cytotoxic treatments due to extreme ovarian sensitivity to chemotherapy and radiation. In pediatric cancer patients modern therapy has improved the long-term survival to over 80% in the United States. However, these cancer survivors face long-term health problems related to treatment toxicity. In female cancer survivors POI leads to sterility, along with the consequences of estrogen deficiency such as premature osteopenia, muscle wasting, accelerated cardiovascular diseases and a vast array of other health and developmental problems. These long-lasting effects are particularly significant for young girls reaching puberty. As such, restoring ovarian endocrine function is paramount in this population. In the present study, we evaluated the feasibility of restoring ovarian endocrine function in ovariectomized mice by transplanting syngeneic and allogeneic ovarian tissue encapsulated in alginate capsules or TheraCyte ® . Histological analysis of the implants retrieved after 7 and 30 days' post implantation showed follicular development up to the secondary and antral stages in both syngeneic and allogeneic implants. Implantation of syngeneic and allogeneic ovarian grafts encapsulated in TheraCyte devices restored ovarian endocrine function, which was confirmed by decreased serum FSH levels from 60 to 70 ng/mL in ovariectomized mice to 30-40 ng/mL 30 days after implantation. Absence of allo-MHC-specific IgG and IgM antibodies in the sera of implanted mice with allogeneic ovarian tissue encapsulated in TheraCyte indicate that the implants did not evoke an allo-immune response, while the allogeneic controls were rejected 21 days after implantation. Our results show that TheraCyte effectively isolates the graft from immune recognition but also supports follicular growth.

Effect of elevated pCO2 on metabolic responses of porcelain crab (Petrolisthes cinctipes) Larvae exposed to subsequent salinity stress.

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Miller, Seth H; Zarate, Sonia; Smith, Edmund H; Gaylord, Brian; Hosfelt, Jessica D; Hill, Tessa M

2014-01-01

Future climate change is predicted to alter the physical characteristics of oceans and estuaries, including pH, temperature, oxygen, and salinity. Investigating how species react to the influence of such multiple stressors is crucial for assessing how future environmental change will alter marine ecosystems. The timing of multiple stressors can also be important, since in some cases stressors arise simultaneously, while in others they occur in rapid succession. In this study, we investigated the effects of elevated pCO2 on oxygen consumption by larvae of the intertidal porcelain crab Petrolisthes cinctipes when exposed to subsequent salinity stress. Such an exposure mimics how larvae under future acidified conditions will likely experience sudden runoff events such as those that occur seasonally along portions of the west coast of the U.S. and in other temperate systems, or how larvae encounter hypersaline waters when crossing density gradients via directed swimming. We raised larvae in the laboratory under ambient and predicted future pCO2 levels (385 and 1000 µatm) for 10 days, and then moved them to seawater at ambient pCO2 but with decreased, ambient, or elevated salinity, to monitor their respiration. While larvae raised under elevated pCO2 or exposed to stressful salinity conditions alone did not exhibit higher respiration rates than larvae held in ambient conditions, larvae exposed to elevated pCO2 followed by stressful salinity conditions consumed more oxygen. These results show that even when multiple stressors act sequentially rather than simultaneously, they can retain their capacity to detrimentally affect organisms.

Primary ovarian leiomyoma

International Nuclear Information System (INIS)

Mathew, Marian; Krolikowski, Anderzj; Al-Haddabi, Ibrahim; Nirmala, Vadakkepat

2005-01-01

Ovarian leiomyoma is a rare and incidentally detected neoplasm, clinically indistinguishable from subserous leiomyomas and ovarian fibromas, until histopathological confirmation. We present a case of leiomyoma arising primarily from the ovary in a 35 year old woman. (author)

Cell cycle genes and ovarian cancer susceptibility: a tagSNP analysis

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Cunningham, J M; Vierkant, R A; Sellers, T A

2009-01-01

BACKGROUND: Dysregulation of the cell cycle is a hallmark of many cancers including ovarian cancer, a leading cause of gynaecologic cancer mortality worldwide. METHODS: We examined single nucleotide polymorphisms (SNPs) (n=288) from 39 cell cycle regulation genes, including cyclins, cyclin......-dependent kinases (CDKs) and CDK inhibitors, in a two-stage study. White, non-Hispanic cases (n=829) and ovarian cancer-free controls (n=941) were genotyped using an Illumina assay. RESULTS: Eleven variants in nine genes (ABL1, CCNB2, CDKN1A, CCND3, E2F2, CDK2, E2F3, CDC2, and CDK7) were associated with risk...... of ovarian cancer in at least one genetic model. Seven SNPs were then assessed in four additional studies with 1689 cases and 3398 controls. Association between risk of ovarian cancer and ABL1 rs2855192 found in the original population [odds ratio, OR(BB vs AA) 2.81 (1.29-6.09), P=0.01] was also observed...

Monoclonal Antibody Therapy in Treating Patients With Ovarian Epithelial Cancer, Melanoma, Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Non-Small Cell Lung Cancer

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2013-01-09

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Melanoma; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer

Evaluation of unilateral versus bilateral ovarian drilling in clomiphene citrate resistant cases of polycystic ovarian syndrome.

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Roy, K K; Baruah, Jinee; Moda, Nidhi; Kumar, Sunesh

2009-10-01

Laparoscopic ovarian drilling (LOD) has been put forward as the treatment of choice in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS), with tubo-ovarian adhesion formation as the major disadvantage. Our study proposed to compare the efficacy of laparoscopic unilateral ovarian drilling with bilateral ovarian drilling in terms of ovulation and pregnancy rate with the expected advantage of decreasing postoperative adhesion rate and change in fimbiro ovarian relationship with unilateral drilling. This prospective randomized study included 44 patients with anovulatory infertility due to PCOS. Twenty-two patients underwent unilateral ovarian drilling in group-I and 22 patients underwent bilateral ovarian drilling in group-II between June 2005 and June 2007. The number of drilling site in each ovary was limited to five. The clinical and biochemical response, ovulation and pregnancy rates over a follow-up period of 1 year were compared. Tubo-ovarian adhesion rate was compared during cesarean section or during repeat laparoscopy. There was no statistical difference between the two groups in terms of clinical and biochemical response, ovulation rate and pregnancy rate. Postoperatively, tubo-ovarian adhesions could be assessed in 36.3% of the patients and no adhesions were found in a single case in either group. Unilateral drilling cauterization of ovary is equally efficacious as bilateral drilling in inducing ovulation and achieving pregnancy. Unilateral ovarian drilling may be a suitable option in clomiphene citrate resistant infertility patient of PCOS which can replace bilateral ovarian drilling with the potential advantage of decreasing the chances of adhesion formation.

Cytogenetic abnormalities in Tunisian women with premature ovarian failure.

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Ayed, Wiem; Amouri, Ahlem; Hammami, Wajih; Kilani, Olfa; Turki, Zinet; Harzallah, Fatma; Bouayed-Abdelmoula, Nouha; Chemkhi, Imen; Zhioua, Fethi; Slama, Claude Ben

2014-12-01

To identify the distribution of chromosome abnormalities among Tunisian women with premature ovarian failure (POF) referred to the department of Cytogenetic at the Pasteur Institute of Tunis (Tunisia), standard cytogenetic analysis was carried out in a total of 100 women younger than 40 affected with premature ovarian failure. We identified 18 chromosomal abnormalities, including seven X-numerical anomalies in mosaic and non-mosaic state (45,X; 47,XXX), four sex reversal, three X-structural abnormalities (terminal deletion and isochromosomes), one autosomal translocation and one supernumerary marker. The overall prevalence of chromosomal abnormalities was 18% in our cohort. X chromosome aneuploidy was the most frequent aberration. This finding confirms the essential role of X chromosome in ovarian function and underlies the importance of cytogenetic investigations in the routine management of POF. Copyright © 2014 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Drivers of pCO2 dynamics in two contrasting coral reef lagoons: The influence of submarine groundwater discharge (Invited)

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Cyronak, T.; Santos, I. R.; Erler, D.; Maher, D. T.; Eyre, B.

2013-12-01

The carbon chemistry of coral reef lagoons can be highly variable over short time scales. While much of the diel variability in seawater carbon chemistry is explained by biological processes, external sources such as river and groundwater seepage may deliver large amounts of organic and inorganic carbon to coral reefs and represent a poorly understood feedback to ocean acidification. Here, we assess the impact of submarine groundwater discharge (SGD) on pCO2 variability in two coral reef lagoons with distinct SGD driving mechanisms. Diel variability of pCO2 in the two ecosystems was explained by a combination of biological drivers and SGD inputs. In Rarotonga, a South Pacific volcanic island, SGD was driven primarily by a steep terrestrial hydraulic gradient, and the lagoon was influenced by the high pCO2 (5,501 μatm) of the fresh groundwater. In Heron Island, a Great Barrier Reef coral cay, SGD was dominated by seawater recirculation through sediments (i.e. tidal pumping) and pCO2 was mainly impacted through the stimulation of biological processes. The Rarotonga water column had a relatively higher average pCO2 (549 μatm) than Heron Island (471 μatm). However, pCO2 exhibited a greater diel range in Heron Island (778 μatm) than in Rarotonga (507 μatm). The Rarotonga lagoon received 31.2 mmol CO2 m-2 d-1 from SGD, while the Heron Island lagoon received 12.3 mmol CO2 m-2 d-1. Over the course of this study both systems were sources of CO2 to the atmosphere (3.00 to 9.67 mmol CO2 m-2 d-1), with SGD-derived CO2 contributing a large portion to the air-sea CO2 flux. The relationship between both water column pH and aragonite saturation state (ΩAr) and radon (222Rn) concentrations indicate that SGD may enhance the local acidification of some coral reef lagoons. Studies measuring the carbon chemistry of coral reefs (e.g. community metabolism, calcification rates) may need to consider SGD-derived CO2.

Digital histologic analysis reveals morphometric patterns of age-related involution in breast epithelium and stroma.

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Sandhu, Rupninder; Chollet-Hinton, Lynn; Kirk, Erin L; Midkiff, Bentley; Troester, Melissa A

2016-02-01

Complete age-related regression of mammary epithelium, often termed postmenopausal involution, is associated with decreased breast cancer risk. However, most studies have qualitatively assessed involution. We quantitatively analyzed epithelium, stroma, and adipose tissue from histologically normal breast tissue of 454 patients in the Normal Breast Study. High-resolution digital images of normal breast hematoxylin and eosin-stained slides were partitioned into epithelium, adipose tissue, and nonfatty stroma. Percentage area and nuclei per unit area (nuclear density) were calculated for each component. Quantitative data were evaluated in association with age using linear regression and cubic spline models. Stromal area decreased (P = 0.0002), and adipose tissue area increased (P epithelium. Epithelial nuclear density is a quantitative measure of age-related breast involution that begins to decline in the early premenopausal period. Copyright © 2015 Elsevier Inc. All rights reserved.

Game Theory of Tumor–Stroma Interactions in Multiple Myeloma: Effect of Nonlinear Benefits

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Javad Salimi Sartakhti

2018-05-01

Full Text Available Cancer cells and stromal cells often exchange growth factors with paracrine effects that promote cell growth: a form of cooperation that can be studied by evolutionary game theory. Previous models have assumed that interactions between cells are pairwise or that the benefit of a growth factor is a linear function of its concentration. Diffusible factors, however, affect multiple cells and generally have nonlinear effects, and these differences are known to have important consequences for evolutionary dynamics. Here, we study tumor–stroma paracrine signaling using a model with multiplayer collective interactions in which growth factors have nonlinear effects. We use multiple myeloma as an example, modelling interactions between malignant plasma cells, osteoblasts, and osteoclasts. Nonlinear benefits can lead to results not observed in linear models, including internal mixed stable equilibria and cyclical dynamics. Models with linear effects, therefore, do not lead to a meaningful characterization of the dynamics of tumor–stroma interactions. To understand the dynamics and the effect of therapies it is necessary to estimate the shape of the benefit functions experimentally and parametrize models based on these functions.

Management of ovarian cysts in infants.

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Xue-Qiang, Yan; Nan-Nan, Zheng; Lei, Yu; Wei, Lu; Hong-Qiang, Bian; Jun, Yang; Xu-Fei, Duan; Xin-Ke, Qin

2015-12-01

To discuss the experience of diagnosis and treatment of ovarian cyst in infants. A retrospective review was conducted on 20 infants who suffered from ovarian cyst. There were no dysplasia ovarian was found in children which were preoperatively diagnosed simplex cyst. Within thirteen children preoperatively detected mixed cystic-solid lesion, six cases ovarian cysts disappeared and two cases underwent poor blood supply in the following time. Adverse effects for ovarian cyst in infants can be prevented by agressive surgical intervention. Harmful effects of ovarian cyst can be prevented by positive surgical intervention despite the diagnostic difficulties in children with clinical symptoms of this condition.

Polycystic ovaries at ultrasound: normal variant or silent polycystic ovary syndrome?

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Catteau-Jonard, S; Bancquart, J; Poncelet, E; Lefebvre-Maunoury, C; Robin, G; Dewailly, D

2012-08-01

It is not known whether polycystic ovaries (PCO) are an ovarian appearance without pathological meaning or whether they share with polycystic ovary syndrome (PCOS) the same ovarian follicle abnormality. There are few studies including strictly selected women with PCO but without other criteria of PCOS. In order to address these issues, we compared hormonal, metabolic and ultrasound parameters obtained from patients with PCO only, patients with PCOS and controls. This was a comparative analysis including three age-matched groups of 95 patients, who were included consecutively in a database: controls, patients with sonographic PCO but no symptoms (PCO group) and patients with PCOS. A clinical examination, fasting serum sampling and pelvic ultrasound examination were performed between cycle days 2 and 5 and results were compared between groups. The median serum anti-Mullerian hormone (AMH) level in the PCO group was intermediate between that in controls and that in the PCOS group (33.6 pmol/L, 19.8 pmol/L and 63.3 pmol/L, respectively), the differences being significant after adjustment for follicle number (P < 0.05), while the mean androgen serum level in the PCO group was similar to that in the control group and significantly lower than that in the PCOS group (P < 0.05) (median serum testosterone levels: 0.90 nmol/L, 0.79 nmol/L and 1.39 nmol/L; median androstenedione levels: 5.25 nmol/L, 4.37 nmol/L and 6.09 nmol/L, respectively). Body mass index, waist circumference and insulin levels had no effect on these differences. PCO is an abnormal condition, affected women showing no evidence of hyperandrogenism but having higher AMH serum levels compared with controls, suggesting a granulosa cell abnormality in PCO similar to that observed in PCOS. The absence of hyperandrogenism in PCO does not seem linked to the metabolic status. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Comparison of the iPCoD and DEPONS models for modelling population consequences of noise on harbour porpoises

DEFF Research Database (Denmark)

Nabe-Nielsen, Jacob; Harwood, John

Two different frameworks have been developed to assess the potential effects of noise associated with offshore renewable energy developments on harbour porpoise populations: The Interim Population Consequences of Disturbance (iPCoD) and Disturbance Effects of Noise on the Harbour Porpoise...... Population in the North Sea (DEPONS). Although both models simulate population dynamics based on the birth and survival rates of individual animals, they model survival in a different way. iPCoD uses average survival rates derived from data from North Sea animals. In the DEPONS model, survival emerges from...

MicroRNA: a new and promising potential biomarker for diagnosis and prognosis of ovarian cancer

International Nuclear Information System (INIS)

Pal, Manish K.; Jaiswar, Shyam P.; Dwivedi, Vinaya N.; Tripathi, Amit K.; Dwivedi, Ashish; Sankhwar, Pushplata

2015-01-01

Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecological malignancies. Despite the technological and medical advances over the past four decades, such as the development of several biological markers (mRNA and proteins biomarkers), the mortality rate of ovarian cancer remains a challenge because of its late diagnosis, which is specifically attributed to low specificities and sensitivities. Under this compulsive scenario, recent advances in expression biology have shifted in identifying and developing specific and sensitive biomarkers, such as microRNAs (miRNAs) for cancer diagnosis and prognosis. MiRNAs are a novel class of small non-coding RNAs that deregulate gene expression at the posttranscriptional level, either by translational repression or by mRNA degradation. These mechanisms may be involved in a complex cascade of cellular events associated with the pathophysiology of many types of cancer. MiRNAs are easily detectable in tissue and blood samples of cancer patients. Therefore, miRNAs hold good promise as potential biomarkers in ovarian cancer. In this review, we attempted to provide a comprehensive profile of key miRNAs involved in ovarian carcinoma to establish miRNAs as more reliable non-invasive clinical biomarkers for early detection of ovarian cancer compared with protein and DNA biomarkers

Laparoscopic ovarian drilling: An alternative but not the ultimate in the management of polycystic ovary syndrome

Science.gov (United States)

Mitra, Subarna; Nayak, Prasanta Kumar; Agrawal, Sarita

2015-01-01

Since its introduction in 1984, laparoscopic ovarian drilling has evolved into a safe and effective surgical treatment for anovulatory, infertile women with polycystic ovary syndrome (PCOS), unresponsive to clomiphene citrate. It is as effective as gonadotropins in terms of pregnancy and live birth rates, but without the risks of ovarian hyperstimulation syndrome and multiple pregnancies. It improves ovarian responsiveness to successive ovulation induction agents. Its favorable reproductive and endocrinal effects are sustained long. Despite its advantages, its use in unselected cases of PCOS or for non-fertility indications is not prudent owing to the potential risks of iatrogenic adhesions and ovarian insufficiency. PMID:25810633

Efficacy of a non-hypercalcemic vitamin-D2 derived anti-cancer agent (MT19c and inhibition of fatty acid synthesis in an ovarian cancer xenograft model.

Directory of Open Access Journals (Sweden)

Richard G Moore

Full Text Available BACKGROUND: Numerous vitamin-D analogs exhibited poor response rates, high systemic toxicities and hypercalcemia in human trials to treat cancer. We identified the first non-hypercalcemic anti-cancer vitamin D analog MT19c by altering the A-ring of ergocalciferol. This study describes the therapeutic efficacy and mechanism of action of MT19c in both in vitro and in vivo models. METHODOLOGY/PRINCIPAL FINDING: Antitumor efficacy of MT19c was evaluated in ovarian cancer cell (SKOV-3 xenografts in nude mice and a syngenic rat ovarian cancer model. Serum calcium levels of MT19c or calcitriol treated animals were measured. In-silico molecular docking simulation and a cell based VDR reporter assay revealed MT19c-VDR interaction. Genomewide mRNA analysis of MT19c treated tumors identified drug targets which were verified by immunoblotting and microscopy. Quantification of cellular malonyl CoA was carried out by HPLC-MS. A binding study with PPAR-Y receptor was performed. MT19c reduced ovarian cancer growth in xenograft and syngeneic animal models without causing hypercalcemia or acute toxicity. MT19c is a weak vitamin-D receptor (VDR antagonist that disrupted the interaction between VDR and coactivator SRC2-3. Genome-wide mRNA analysis and western blot and microscopy of MT19c treated xenograft tumors showed inhibition of fatty acid synthase (FASN activity. MT19c reduced cellular levels of malonyl CoA in SKOV-3 cells and inhibited EGFR/phosphoinositol-3kinase (PI-3K activity independently of PPAR-gamma protein. SIGNIFICANCE: Antitumor effects of non-hypercalcemic agent MT19c provide a new approach to the design of vitamin-D based anticancer molecules and a rationale for developing MT19c as a therapeutic agent for malignant ovarian tumors by targeting oncogenic de novo lipogenesis.

pCO2 effects on species composition and growth of an estuarine phytoplankton community.

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The effects of ongoing changes in ocean carbonate chemistry on plankton ecology have important implications for food webs and biogeochemical cycling. However, conflicting results have emerged regarding species-specific responses to pCO2 enrichment and thus community responses hav...

Influence of ovarian manipulation on reproductive endocrinology in polycystic ovarian syndrome and regularly cycling women

NARCIS (Netherlands)

Hendriks, M.L.; König, T.E.; Soleman, R.S.; Korsen, T.; Schats, R.; Hompes, P.G.A.; Homburg, R.R.; Lambalk, C.B.

2013-01-01

Objective: Little is known about the function of the ovarian neuronal network in humans. In many species, copulation influences endocrinology through this network. As a first step, the possible influence of ovarian mechanical manipulation on pituitary and ovarian hormones was evaluated in polycystic

Radiolabeled pertuzumab for imaging of human epidermal growth factor receptor 2 expression in ovarian cancer

Energy Technology Data Exchange (ETDEWEB)

Jiang, Dawei [Shenzhen University, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen (China); University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); Im, Hyung-Jun [University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); Seoul National University, Graduate School of Convergence Science and Technology, Seoul (Korea, Republic of); Sun, Haiyan; Cho, Steve Y. [University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); Valdovinos, Hector F.; England, Christopher G.; Ehlerding, Emily B.; Nickles, Robert J. [University of Wisconsin - Madison, Department of Medical Physics, Madison, WI (United States); Lee, Dong Soo [Seoul National University, Graduate School of Convergence Science and Technology, Seoul (Korea, Republic of); Huang, Peng [Shenzhen University, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen (China); Cai, Weibo [University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); University of Wisconsin - Madison, Department of Medical Physics, Madison, WI (United States); University of Wisconsin Carbone Cancer Center, Madison, WI (United States)

2017-08-15

Human epidermal growth factor receptor 2 (HER2) is over-expressed in over 30% of ovarian cancer cases, playing an essential role in tumorigenesis and metastasis. Non-invasive imaging of HER2 is of great interest for physicians as a mean to better detect and monitor the progression of ovarian cancer. In this study, HER2 was assessed as a biomarker for ovarian cancer imaging using {sup 64}Cu-labeled pertuzumab for immunoPET imaging. HER2 expression and binding were examined in three ovarian cancer cell lines (SKOV3, OVCAR3, Caov3) using in vitro techniques, including western blot and saturation binding assays. PET imaging and biodistribution studies in subcutaneous models of ovarian cancer were performed for non-invasive in vivo evaluation of HER2 expression. Additionally, orthotopic models were employed to further validate the imaging capability of {sup 64}Cu-NOTA-pertuzumab. HER2 expression was highest in SKOV3 cells, while OVCAR3 and Caov3 displayed lower HER2 expression. {sup 64}Cu-NOTA-pertuzumab showed high specificity for HER2 (K{sub a} = 3.1 ± 0.6 nM) in SKOV3. In subcutaneous tumors, PET imaging revealed tumor uptake of 41.8 ± 3.8, 10.5 ± 3.9, and 12.1 ± 2.3%ID/g at 48 h post-injection for SKOV3, OVCAR3, and Caov3, respectively (n = 3). In orthotopic models, PET imaging with {sup 64}Cu-NOTA-pertuzumab allowed for rapid and clear delineation of both primary and small peritoneal metastases in HER2-expressing ovarian cancer. {sup 64}Cu-NOTA-pertuzumab is an effective PET tracer for the non-invasive imaging of HER2 expression in vivo, rendering it a potential tracer for treatment monitoring and improved patient stratification. (orig.)

The Interrelationship of pCO2, Soil Moisture Content, and Biomass Fertilization Expressed in the Carbon Isotope Signature of C3 Plant Tissue

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Schubert, B.; Jahren, A. H.

2017-12-01

Hundreds of chamber and field experiments have shown an increase in C3 plant biomass in response to elevated atmospheric carbon dioxide (pCO2); however, secondary water and nutrient deficits are thought to limit this response. Some have hypothesized that secondary limitation might be self-alleviating under elevated pCO2 as greater root biomass imparts enhanced access to water and nutrients. Here we present results of growth chamber experiments designed to test this hypothesis: we grew 206 Arabidopsis thaliana plants within 5 growth chambers, each set at a different level of pCO2: 390, 685, 1075, 1585, and 2175 ppmv. Within each growth chamber, soil moisture content (θm) was maintained across a spectrum: 1.50, 0.83, 0.44, and 0.38 g g-1. After 3 weeks of total growth, tissues were analyzed for both biomass and net carbon isotope discrimination (Δ13C) value. From these values, we calculated Δresidual, which represents the residual effect of water stress after subtraction of the effect of pCO2 due to photorespiration. Across the full range of moisture content, Δresidual displayed a significant 2.5‰ increase with increasing pCO2. This further implies a 0.1 unit increase in ci/ca, consistent with decreased water stress at elevated pCO2. The influence of CO2 fertilization on the alleviation of water stress was further evidenced in a positive correlation between percent biomass change and Δresidual, such that a doubling of plant biomass yielded a 1.85‰ increase in carbon isotope discrimination. In addition to providing new insight into water uptake in plants growing under elevated carbon dioxide, these data underscore the importance of separating the effects of increased pCO2 (via photorespiration) and altered ci/ca (via stomatal conductance) when considering changes in the Δ13C value of C3 land plants during the Anthropocene, or across any geological period that includes a marked change in global carbon cycling.

The role of pCO2 in astronomically-paced climate and carbon cycle variations in the Middle Miocene

Science.gov (United States)

Penman, D. E.; Hull, P. M.; Scher, H.; Kirtland Turner, S.; Ridgwell, A.

2017-12-01

The pace of Earth's background climate variability is known to be driven by the Milankovitch cycles, variations in Earth's orbital parameters and axial tilt. While the Milankovitch (orbital) theory of climate change is very nearly universally accepted, the climate system mechanisms and feedbacks responsible for amplifying orbital cycles preserved in the geologic record remain uncertain. For the late Pleistocene, the ice core-derived record of atmospheric carbon dioxide (pCO2) is strongly coupled with global temperature on orbital time scales, indicating that internal feedbacks involving the carbon cycle amplify or even cause the large changes in global temperature during orbitally driven glacial-interglacial cycles. However, for earlier time periods beyond the range of ice cores (the last 800 kyr), it is not possible to directly compare records of pCO2 to orbital climate cycles because there are no high-resolution (orbitally resolved) records of pCO2 before the Pliocene. We address this deficiency with a high-resolution ( 5-10 kyr spacing) record of planktonic foraminiferal d11B-derived surface seawater pH (as well as d13C and trace metal analyses) over a 500 kyr time window in a sedimentary record with known Milankovitch-scale climate and carbon cycle oscillations: the Middle Miocene (14.0 - 14.5 Ma) at ODP Site 926 (subtropical North Atlantic). The resulting pH record can be used to constrain atmospheric pCO2, allowing comparison of the timescale and magnitude of carbon cycle changes during a period of eccentricity-dominated variability in the response of the global climate system (the Late Pleistocene) with a period of obliquity-dominance (the middle Miocene). These new records of planktic d11B and d13C will then be used to guide simulations of astronomical climate forcing in Earth System models, resulting in refined estimates of pCO2 changes over orbital cycles and providing quantitative constraints on the mechanisms and feedbacks responsible for the

Autotransplantation of cryopreserved ovarian tissue in 12 women with chemotherapy-induced premature ovarian failure: the Danish experience

DEFF Research Database (Denmark)

Schmidt, Kirsten Tryde; Rosendahl, Mikkel; Ernst, Erik

2011-01-01

To describe a cohort of 12 Danish women who received autotransplantation of frozen-thawed cryopreserved ovarian tissue because of premature ovarian failure after cancer treatment.......To describe a cohort of 12 Danish women who received autotransplantation of frozen-thawed cryopreserved ovarian tissue because of premature ovarian failure after cancer treatment....

Progesterone signaling mediated through progesterone receptor membrane component-1 in ovarian cells with special emphasis on ovarian cancer.

Science.gov (United States)

Peluso, John J

2011-08-01

Various ovarian cell types including granulosa cells and ovarian surface epithelial cells express the progesterone (P4) binding protein, progesterone receptor membrane component-1 (PGRMC1). PGRMC1 is also expressed in ovarian tumors. PGRMC1 plays an essential role in promoting the survival of both normal and cancerous ovarian cell in vitro. Given the clinical significance of factors that regulate the viability of ovarian cancer, this review will focus on the role of PGRMC1 in ovarian cancer, while drawing insights into the mechanism of PGRMC1's action from cell lines derived from healthy ovaries as well as ovarian tumors. Studies using PGRMC1siRNA demonstrated that P4's ability to inhibit ovarian cells from undergoing apoptosis in vitro is dependent on PGRMC1. To confirm the importance of PGRMC1, the ability of PGRMC1-deplete ovarian cancer cell lines to form tumors in intact nude mice was assessed. Compared to PGRMC1-expressing ovarian cancer cells, PGRMC1-deplete ovarian cancer cells formed tumors in fewer mice (80% compared to 100% for controls). Moreover, the number of tumors derived from PGRMC1-deplete ovarian cancer cells was 50% of that observed in controls. Finally, the tumors that formed from PGRMC1-deplete ovarian cancer cells were about a fourth the size of tumors derived from ovarian cancer cells with normal levels of PGRMC1. One reason for PGRMC1-deplete tumors being smaller is that they had a poorly developed microvasculature system. How PGRMC1 regulates cell viability and in turn tumor growth is not known but part of the mechanism likely involves the regulation of genes that promote cell survival and inhibit apoptosis. Copyright © 2011 Elsevier Inc. All rights reserved.

Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer.

Science.gov (United States)

Knapp, Paweł; Bodnar, Lubomir; Błachnio-Zabielska, Agnieszka; Świderska, Magdalena; Chabowski, Adrian

2017-10-01

The role of lipids in carcinogenesis through induction of abnormal cell lines in the human body is currently undisputable. Based on the literature, bioactive sphingolipids play an essential role in the development and progression of cancer and are involved in the metastatic process. The aim of this study was to determine the concentration of selected sphingolipids in patients with advanced ovarian cancer (AOC, FIGO III/IV, high grade ovarian cancer). Seventy-four patients with ovarian cancer were enrolled. Plasma concentrations of C16-Cer, C18:1-Cer and C18-Cer were assessed by LC/MS/MS. The content of tissue sphingolipids was measured using a UHPLC/MS/MS. Plasma concentration of 3 ceramides: C16-Cer, C18:1-Cer and C18-Cer was significantly elevated in women with advanced ovarian cancer compared to control group (P=0.031; 0.022; 0.020; respectively). There were increases in concentration of 5 ceramides: C16-Cer, C18:1-Cer, C18-Cer, C24:1-Cer, C24-Cer (P=0.025; 0.049; 0.032; 0.005; 0.013, respectively) and S1P (P=0.004) in ovarian tissue of women with advanced ovarian cancer compared to healthy individuals. Importantly, significantly higher risk of ovarian cancer when the plasma concentration of C16-Cer>311.88ng/100μl (AUC: 0.76, P=0.0261); C18:1-Cer>4.75ng/100μl (AUC: 0.77, P=0.0160) and C18-Cer>100.76ng/100μl (AUC:0.77, P=0.0136) was noticed. Bioactive sphingolipids play an essential role in the development and progression of cancer and they also take part in the process of metastasizing. This study suggests that some sphingolipids can be used as potential biomarkers of advanced ovarian cancer and that they can play an important role in the pathogenesis of this disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Hormone therapy and ovarian cancer

DEFF Research Database (Denmark)

Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms

2009-01-01

CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal and postmenopau......CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal...... and postmenopausal women receiving different hormone therapies. DESIGN AND SETTING: Nationwide prospective cohort study including all Danish women aged 50 through 79 years from 1995 through 2005 through individual linkage to Danish national registers. Redeemed prescription data from the National Register...... bands included hormone exposures as time-dependent covariates. PARTICIPANTS: A total of 909,946 women without hormone-sensitive cancer or bilateral oophorectomy. MAIN OUTCOME MEASURE: Ovarian cancer. RESULTS: In an average of 8.0 years of follow-up (7.3 million women-years), 3068 incident ovarian...

Insulin and C-peptide secretion in non-obese patients with polycystic ovarian disease.

Science.gov (United States)

Mahabeer, S; Jialal, I; Norman, R J; Naidoo, C; Reddi, K; Joubert, S M

1989-09-01

Plasma glucose, immunoreactive insulin (IRI) and C-peptide responses during an oral glucose tolerance test (oGTT) were assessed in 11 non-obese patients with polycystic ovarian disease (PCOD) and 11 reference subjects matched for age, height and weight. Also, 6 patients with PCOD and 6 normal women were subjected to intravenous glucose tolerance testing (ivGTT) On oGTT, all subjects exhibited normal glucose tolerance; however, PCOD patients had significantly higher mean plasma glucose levels at 30, 60, 90 and 120 min and higher mean incremental glucose areas. In addition the patients with polycystic ovaries showed higher mean basal IRI and C-peptide levels, higher mean glucose stimulated IRI and C-peptide levels and higher mean incremental IRI and C-peptide values. The molar ratios of C-peptide/IRI were significantly lower in the PCOD group at all time intervals after glucose stimulation when compared to the normal women. During ivGTT, there were significantly higher mean glucose levels at 5, 40, 50 and 60 min in the PCOD group when compared to the reference group. The IRI response to intravenous glucose in the PCOD women was similar to the reference group. The findings on oGTT suggest that non-obese patients with PCOD have increased pancreatic IRI secretion as well as impaired hepatic extraction of the hormone.

Management of ovarian cysts in infants

Directory of Open Access Journals (Sweden)

Yan Xue-qiang

2015-01-01

Full Text Available Background: To discuss the experience of diagnosis and treatment of ovarian cyst in infants. Materials and Methods: A retrospective review was conducted on 20 infants who suffered from ovarian cyst. Results: There were no dysplasia ovarian was found in children which were preoperatively diagnosed simplex cyst. Within thirteen children preoperatively detected mixed cystic-solid lesion, six cases ovarian cysts disappeared and two cases underwent poor blood supply in the following time. Conclusion: Adverse effects for ovarian cyst in infants can be prevented by agressive surgical intervention. Harmful effects of ovarian cyst can be prevented by positive surgical intervention despite the diagnostic difficulties in children with clinical symptoms of this condition.

Morphological and immunohistochemical pattern of tubo-ovarian dysplasia and serous tubal intraepithelial carcinoma.

Science.gov (United States)

Chene, Gautier; Cayre, Anne; Raoelfils, Ines; Lagarde, Nicole; Dauplat, Jacques; Penault-Llorca, Frederique

2014-12-01

Histopathological examination of material from prophylactic salpingo-oophorectomies performed in patients at genetic risk of ovarian cancer can reveal abnormalities interpreted as possible pre-cancerous "ovarian dysplasia" and tubal precursors lesions. We sought to study the morphological features and immunohistochemical expression patterns of neoplasia-associated markers in prophylactically removed ovaries and fallopian tubes (pBSO) in comparison with a group of serous tubal intraepithelial carcinoma (STIC) and non-cancerous controls. Morphological features and immunohistochemical expression patterns of Ki-67 (for proliferation biomarker), p53 (key pathway of mullerian serous tumorogenesis), Bcl2 (anti-apoptotic), γH2AX (a double-strand breaks marker) and ALDH1 (a stem cell marker significantly associated with early-stage ovarian cancer) were blindly evaluated by two pathologists in 111 pBSO, 12 STICs and 116 non-cancerous salpingo-oophorectomies (control group) (nBSO). Morphological ovarian and tubal dysplasia scores were significantly higher in the pBSO than in controls (respectively, 8.8 vs 3.12, pSTICs compared with the controls whereas expression patterns of Ki67, p53 and bcl2 were low to moderate in the pBSO group. STICs overexpressed Ki67 and p53 while bcl2 expression was low; Interestingly, ALDH1 expression was low in non dysplastic epithelium, high in dysplasia and constantly low in STICs. The morphological and immunohistochemical profile of tubo-ovarian dysplasia and STICs might be consistent with progression toward neoplastic transformation in the Serous Carcinogenesis Sequence. These changes may be pre-malignant and could represent an important phase in early neoplasia. ALDH1 activation in pBSO samples and its extinction in STICs should be considered as a target for prevention. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Consortium analysis of 7 candidate SNPs for ovarian cancer

DEFF Research Database (Denmark)

Ramus, S.J.; Vierkant, R.A.; Johnatty, S.E.

2008-01-01

The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H...... (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5' flanking CDKN2A, rs523349 in the 3' UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin...... was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded...

3D is not enough: Building up a cell instructive microenvironment for tumoral stroma microtissues.

Science.gov (United States)

Brancato, Virginia; Garziano, Alessandro; Gioiella, Filomena; Urciuolo, Francesco; Imparato, Giorgia; Panzetta, Valeria; Fusco, Sabato; Netti, Paolo A

2017-01-01

We fabricated three-dimensional microtissues with the aim to replicate in vitro the composition and the functionalities of the tumor microenvironment. By arranging either normal fibroblasts (NF) or cancer-activated fibroblasts (CAF) in two different three dimensional (3D) configurations, two kinds of micromodules were produced: spheroids and microtissues. Spheroids were obtained by means of the traditional cell aggregation technique resulting in a 3D model characterized by high cell density and low amount of extracellular proteins. The microtissues were obtained by culturing cells into porous gelatin microscaffolds. In this latter configuration, cells assembled an intricate network of collagen, fibronectin and hyaluronic acid. We investigated the biophysical properties of both 3D models in terms of cell growth, metabolic activity, texture and composition of the extracellular matrix (via histological analysis and multiphoton imaging) and cell mechanical properties (via Particle Tracking Microrheology). In the spheroid models such biophysical properties remained unchanged regardless to the cell type used. In contrast, normal-microtissues and cancer-activated-microtissues displayed marked differences. CAF-microtissues possessed higher proliferation rate, superior contraction capability, different micro-rheological properties and an extracellular matrix richer in collagen fibronectin and hyaluronic acid. At last, multiphoton investigation revealed differences in the collagen network architecture. Taken together, these results suggested that despite to cell spheroids, microtissues better recapitulate the important differences existing in vivo between normal and cancer-activated stroma representing a more suitable system to mimic in vitro the stromal element of the tumor tissues. This work concerns the engineering of tumor tissue in vitro. Tumor models serve as biological equivalent to study pathologic progression and to screen or validate the drugs efficacy. Tumor

Characterization of novel tumor stroma markers identified by gene expression profiling of human cancer tissues and 3D co-culture models

International Nuclear Information System (INIS)

Rupp, C.

2010-01-01

The tumor stroma plays an important role in tumorigenesis. During cancer progression it undergoes changes in architecture, gene expression and secretion of proteolytic enzymes that are essential for the invasive and metastatic phenotype of malignant tumors. Cancer associated fibroblasts (Cafes) represent the major cellular component of the stroma and recent studies demonstrated the prognostic and therapeutic significance of CaF-related molecular signatures. The identification and characterization of genes and signaling pathways involved in the molecular interactions between tumor and stromal cells has been the focus of this study. For that purpose we have used two complementary approaches: the identification of novel tumor stroma targets in human colon cancer samples using whole genome Affymetrix GeneChip analysis and the validation of theses targets in a newly established of 3D co-culture model that mimics the cellular and molecular heterogeneity of human cancers. We have demonstrated increased expression of gene sets related to hypoxia, epithelial-to-mesenchymal transition (EMT) and TGFβ pathway activation in CAFs vs their normal counterparts in both systems. The putative TGFβ target IGFBP7 (insulin-like growth factor binding protein 7) was identified as a tumor stroma marker of epithelial cancers and as a tumor antigen in mesenchyme-derived sarcomas. IGFPB7 was shown to promote anchorage-independent growth in malignant mesenchymal cells and malignant epithelial cells with an EMT-phenotype, whereas a tumor suppressor function was observed in tumor epithelial cells. In summary, we have demonstrated that a number of important signaling pathways involved in cancer progression and metastasis are specifically dysregulated in the tumor stroma both in our in vivo screen and in the in vitro 3D model, illustrating the value of these approaches for the identification and characterization of novel stromal markers. (author) [de

Ectopic ovarian pregnancy

International Nuclear Information System (INIS)

Sachdev, P.S.; Jatoi, N.; Memon, R.A.; Sachdev, C.S.

2003-01-01

A case of ectopic ovarian pregnancy is presented occurring in a 24 years old woman after natural conception. The clinical diagnosis was ruptured tubal pregnancy. Gross findings were suggestive of ruptured corpus luteum cyst on exploration. The histopathological examination of specimen brought forward the diagnosis of ovarian pregnancy. (author)

Hyaluronan and hyaluronectin in the extracellular matrix of human brain tumour stroma.

Science.gov (United States)

Delpech, B; Maingonnat, C; Girard, N; Chauzy, C; Maunoury, R; Olivier, A; Tayot, J; Creissard, P

1993-01-01

Hyaluronan (HA) and the hyaluronan-binding glycoprotein hyaluronectin (HN) were measured in 23 gliomas and 8 meningiomas and their location was revisited in 35 tumours. A clear-cut difference was found in the HN/HA ratio values of glioblastomas (below 0.5) and that of astrocytomas (above 0.5 P edification of the extracellular matrix. In meningiomas only the stroma would be responsible for HA and HN production.

Appendiceal and ovarian Burkitt's lymphoma presenting as acute appendicitis

Directory of Open Access Journals (Sweden)

Donovan Hui

2018-05-01

Full Text Available Burkitt's lymphoma is an extremely aggressive B-cell non-Hodgkin lymphoma. Patients with the sporadic form of Burkitt's lymphoma typically present with a rapidly growing abdominal mass, pain and distension. Involvement of either the appendix and/or ovaries in females is a rare manifestation of the disease. We present an unusual case of a 13 year old girl with appendiceal and ovarian Burkitt's lymphoma presenting with signs of acute appendicitis. This case demonstrates the potential for secondary involvement of the appendix and/or ovaries from Burkitt's lymphoma as well as the importance of the histopathology. Keywords: Appendicitis, Appendix, Burkitt's lymphoma, Lymphoma, Ovarian tumor

Effects of seawater pCO2 and temperature on calcification and productivity in the coral genus Porites spp.: an exploration of potential interaction mechanisms

Science.gov (United States)

Cole, C.; Finch, A. A.; Hintz, C.; Hintz, K.; Allison, N.

2018-06-01

Understanding how rising seawater pCO2 and temperatures impact coral aragonite accretion is essential for predicting the future of reef ecosystems. Here, we report 2 long-term (10-11 month) studies assessing the effects of temperature (25 and 28 °C) and both high and low seawater pCO2 (180-750 μatm) on the calcification, photosynthesis and respiration of individual massive Porites spp. genotypes. Calcification rates were highly variable between genotypes, but high seawater pCO2 reduced calcification significantly in 4 of 7 genotypes cultured at 25 °C but in only 1 of 4 genotypes cultured at 28 °C. Increasing seawater temperature enhanced calcification in almost all corals, but the magnitude of this effect was seawater pCO2 dependent. The 3 °C temperature increase enhanced calcification rate on average by 3% at 180 μatm, by 35% at 260 μatm and by > 300% at 750 μatm. The rate increase at high seawater pCO2 exceeds that observed in inorganic aragonites. Responses of gross/net photosynthesis and respiration to temperature and seawater pCO2 varied between genotypes, but rates of all these processes were reduced at the higher seawater temperature. Increases in seawater temperature, below the thermal stress threshold, may mitigate against ocean acidification in this coral genus, but this moderation is not mediated by an increase in net photosynthesis. The response of coral calcification to temperature cannot be explained by symbiont productivity or by thermodynamic and kinetic influences on aragonite formation.

An update on the role of PET/CT and PET/MRI in ovarian cancer

International Nuclear Information System (INIS)

Khiewvan, Benjapa; Torigian, Drew A.; Emamzadehfard, Sahra; Paydary, Koosha; Salavati, Ali; Houshmand, Sina; Werner, Thomas J.; Alavi, Abass

2017-01-01

This review article summarizes the role of PET/CT and PET/MRI in ovarian cancer. With regard to the diagnosis of ovarian cancer, the presence of FDG uptake within the ovary of a postmenopausal woman raises the concern for ovarian cancer. Multiple studies show that FDG PET/CT can detect lymph node and distant metastasis in ovarian cancer with high accuracy and may, therefore, alter the management to obtain better clinical outcomes. Although PET/CT staging is superior for N and M staging of ovarian cancer, its role is limited for T staging. Additionally, FDG PET/CT is of great benefit in evaluating treatment response and has prognostic value in patients with ovarian cancer. FDG PET/CT also has value to detect recurrent disease, particularly in patients with elevated serum CA-125 levels and negative or inconclusive conventional imaging test results. PET/MRI may beneficial for tumor staging because MRI has higher soft tissue contrast and no ionizing radiation exposure compared to CT. Some non-FDG PET radiotracers such as 18 F-fluorothymidine (FLT) or 11 C-methionine (MET) have been studied in preclinical and clinical studies as well and may play a role in the evaluation of patients with ovarian cancer. (orig.)

An update on the role of PET/CT and PET/MRI in ovarian cancer

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Khiewvan, Benjapa [Hospital of the University of Pennsylvania, Department of Radiology, Philadelphia, PA (United States); Mahidol University, Division of Nuclear Medicine, Department of Radiology, Faculty of Medicine Siriraj Hospital, Bangkok (Thailand); Torigian, Drew A.; Emamzadehfard, Sahra; Paydary, Koosha; Salavati, Ali; Houshmand, Sina; Werner, Thomas J.; Alavi, Abass [Hospital of the University of Pennsylvania, Department of Radiology, Philadelphia, PA (United States)

2017-06-15

This review article summarizes the role of PET/CT and PET/MRI in ovarian cancer. With regard to the diagnosis of ovarian cancer, the presence of FDG uptake within the ovary of a postmenopausal woman raises the concern for ovarian cancer. Multiple studies show that FDG PET/CT can detect lymph node and distant metastasis in ovarian cancer with high accuracy and may, therefore, alter the management to obtain better clinical outcomes. Although PET/CT staging is superior for N and M staging of ovarian cancer, its role is limited for T staging. Additionally, FDG PET/CT is of great benefit in evaluating treatment response and has prognostic value in patients with ovarian cancer. FDG PET/CT also has value to detect recurrent disease, particularly in patients with elevated serum CA-125 levels and negative or inconclusive conventional imaging test results. PET/MRI may beneficial for tumor staging because MRI has higher soft tissue contrast and no ionizing radiation exposure compared to CT. Some non-FDG PET radiotracers such as {sup 18}F-fluorothymidine (FLT) or {sup 11}C-methionine (MET) have been studied in preclinical and clinical studies as well and may play a role in the evaluation of patients with ovarian cancer. (orig.)

Impact of transvaginal hydrolaparoscopy ovarian drilling on ovarian stromal blood flow and ovarian volume in clomiphene citrate-resistant PCOS patients: a case-control study.

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Giampaolino, Pierluigi; Morra, Ilaria; De Rosa, Nicoletta; Cagnacci, Angelo; Pellicano, Massimiliano; Di Carlo, Costantino; Nappi, Carmine; Bifulco, Giuseppe

2017-09-01

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in gynecology. In PCOS patients vascularization parameters are altered. Transvaginal hydrolaparoscopy (THL) is a mini-invasive approach for ovarian drilling in PCOS patients. In this study, we assessed the effect of ovarian drilling using THL on ovarian volume (OV) and vascularization index (VI) using 3D power Doppler ultrasonography in CC-resistant PCOS patients. A case-control study on 123 CC-resistant PCOS women who underwent THL ovarian drilling was performed. Patients underwent 3D ultrasound and power Doppler to measure VI, flow index (FI), vascularization flow index (VFI) and to evaluate OV before and after the procedure, at six months, and on the early follicular phase of the menstrual cycle. After THL ovarian drilling, OV and power Doppler flow indices were significantly reduced compared to pre-operative values (OV: 7.85 versus 11.72 cm 3 , p drilling seems to reduce OV and 3D power Doppler indices, and could therefore be a viable alternative to LOD in PCOS patients resistant to medical therapy.

Ovarian Cancer and Comorbidity

DEFF Research Database (Denmark)

Noer, Mette Calundann; Sperling, Cecilie Dyg; Ottesen, Bent

2017-01-01

OBJECTIVES: Comorbidity influences survival in ovarian cancer, but the causal relations between prognosis and comorbidity are not well characterized. The aim of this study was to investigate the associations between comorbidity, system delay, the choice of primary treatment, and survival in Danish...... ovarian cancer patients. METHODS: This population-based study was conducted on data from 5317 ovarian cancer patients registered in the Danish Gynecological Cancer Database. Comorbidity was classified according to the Charlson Comorbidity Index and the Ovarian Cancer Comorbidity Index. Pearson χ test...... and multivariate logistic regression analyses were used to investigate the association between comorbidity and primary outcome measures: primary treatment ("primary debulking surgery" vs "no primary surgery") and system delay (more vs less than required by the National Cancer Patient Pathways [NCPPs]). Cox...

[Study on the oxidative stress in the ovaries of a rat model of polycystic ovary].

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Gong, Jin; Wu, Dong-bo; Zhang, Lan-lan; Li, Jia; Zhao, Xing; Zhang, Dan

2015-03-01

To establish a pathological animal model of polycystic ovary (PCO) by letrozole in rats. Investigate whether PCO were mediated by the effect of oxidative stress by measuring oxidative stress levels in this cohort of rats with PCO, and proceed a new way of treatment for polycystic ovary syndrom (PCOS). 90 SD female rats aged 6 weeks were randomly divided into two groups, including a control group of 45 rats that received vehicle only [19% aqueous solution of carboxmethlycellulose (CMC), 1 mL/d] once daily orally (p.o.), and an experimental group of 45 rats, which were administered letrozole at concentrations of 1 mg/kg p.o. dissolved in 1% CMC (1 mL/d) once daily. The treatment period was 28 d. During this period, vaginal smears were collected daily for estrus cycle determination and body masses were measured every 7 d. On the day subsequent to the last letrozole dose administration, rats were killed; Uteri and ovaries were then excised and weighed for the calculation of organ indexes. Serum hormone levels, SHBG and histologic changes in the ovaries were examined. Then testosterone free index (FAD) was calculated. Oxidant status was evaluated by determination of ovarian total oxidant status (TOS), malondialdehyde (MDA) concentration and intracellular reactive oxygen species (ROS) level, while antioxidant status was evaluated by determination of total antioxidant status (TAS) and superoxide dismutase (SOD) concentration. Vaginal smear test showed the estrus cycle began to disappear from day 12 to day 15. A statistically significant difference in growth curves, ovarian weights, uterine weights and organ indexes between the groups were also observed. In rats with PCO serum testosterone (T), follicle-stimulating hormone (FSH) concentrations and free androgen index (FADI) were significantly increased compared with the control group (rats without PCO). However, rats with PCO had decreased levels of estrogen (E2), luteinizing hormone (LH), and progesterone (P) compared

Cumulative live-birth rate in women with polycystic ovary syndrome or isolated polycystic ovaries undergoing in-vitro fertilisation treatment.

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Li, Hang Wun Raymond; Lee, Vivian Chi Yan; Lau, Estella Yee Lan; Yeung, William Shu Biu; Ho, Pak Chung; Ng, Ernest Hung Yu

2014-02-01

This retrospective cohort study evaluated the cumulative live birth rate in women with polycystic ovary syndrome (PCOS) and isolated polycystic ovaries (PCO) undergoing in-vitro fertilisation (IVF) treatment. We studied 104 women with PCOS, 184 with PCO and 576 age-matched controls undergoing the first IVF treatment cycle between 2002 and 2009. The main outcome measure was cumulative live birth in the fresh plus all the frozen embryo transfers combined after the same stimulation cycle. Women in both the PCOS (n = 104) and isolated PCO groups (n = 184) had higher ovarian response parameters compared to age-matched controls (n = 576), and higher rates of withholding fresh embryo transfer for risk of ovarian hyperstimulation syndrome (OHSS). The actual incidence of moderate to severe OHSS was significantly higher in the PCOS (11.5 %) but not the isolated PCO group (8.2%) compared to controls (4.9%). The live birth rates in the fresh cycle were comparable among the 3 groups, but the PCOS group had a significantly higher miscarriage rate compared to the other 2 groups. Cumulative live birth rate was significantly higher in the isolated PCO group (60.3%), but not the PCOS group (50.0%), compared to controls (47.5%). Women in the isolated PCO group, but not the PCOS group, had a significantly higher cumulative live birth rate compared to controls. This could be explained by the quantitative effect of the higher number of transferable embryos obtained per stimulation cycle, which is uncompromised by the unfavourable embryo competence otherwise observed in PCOS.

Primary ovarian insufficiency: an update

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Cox L

2014-02-01

Full Text Available Leticia Cox, James H LiuUH Case Medical Center, MacDonald Women's Hospital, Department of Obstetrics and Gynecology, Case Western Reserve University School of Medicine, Department of Reproductive Biology, Cleveland, OH, USAAbstract: Primary ovarian insufficiency is a condition that represents impaired ovarian function on a continuum with intermittent ovulation. This condition commonly leads to premature menopause, defined as cessation of ovulation prior to the age of 40 years. Because there are potential immediate and long-term consequences of hypoestrogenism, a timely diagnosis is invaluable. This comprehensive review will discuss identifiable causes for primary ovarian insufficiency, including genetic disorders and metabolic abnormalities, as well as review current strategies for diagnosis, evaluation, and management of women with this condition.Keywords: premature ovarian failure, premature menopause, ovarian dysfunction

Rag defects and thymic stroma: lessons from animal models

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Veronica eMarrella

2014-06-01

Full Text Available Thymocytes and thymic epithelial cells (TECs cross-talk is essential to support T-cell development and preserve thymic architecture and maturation of TECs and Foxp3+ natural regulatory T (nTreg cells. Accordingly, disruption of thymic lymphostromal cross-talk may have major implications on the thymic mechanisms that govern T cell tolerance. Several genetic defects have been described in humans that affect early stages of T cell development (leading to Severe Combined Immune Deficiency, SCID or late stages in thymocyte maturation (resulting in combined immunodeficiency. Hypomorphic mutations in SCID-causing genes may allow for generation of a limited pool of T lymphocytes with a restricted repertoire. These conditions are often associated with infiltration of peripheral tissues by activated T cells and immune dysregulation, as best exemplified by Omenn syndrome (OS. In this review, we will discuss our recent findings on abnormalities of thymic microenvironment in OS with a special focus of defective maturation of TECs, altered distribution of thymic dendritic cells (DCs and impairment of deletional and non-deletional mechanisms of central tolerance. Here, taking advantage of mouse models of OS and atypical SCID, we will discuss how modifications in stromal compartment impact and shape lymphocyte differentiation, and vice versa how inefficient T cell signalling results in defective stromal maturation. These findings are instrumental to understand the extent to which novel therapeutic strategies should act on thymic stroma to achieve full immune reconstitution.

Food availability and pCO2 impacts on planulation, juvenile survival, and calcification of the azooxanthellate scleractinian coral, Balanophyllia elegans

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Crook, E. D.; Cooper, H.; Potts, D. C.; Lambert, T.; Paytan, A.

2013-05-01

Ocean acidification, the assimilation of atmospheric CO2 by the oceans that decreases the pH and CaCO3 saturation state (Ω) of seawater, is projected to have severe consequences for calcifying organisms. Strong evidence suggests that tropical reef-building corals containing algal symbionts (zooxanthellae) will experience dramatic declines in calcification over the next century. The responses of azooxanthellate corals to ocean acidification are less well understood, and because they cannot obtain extra photosynthetic energy from symbionts, they provide a system for studying the direct effects of acidification on the energy available for calcification. The orange cup coral Balanophyllia elegans is a solitary, azooxanthellate scleractinian species common on the California coast where it thrives in the low pH waters of an upwelling regime. During an 8 month study, we addressed the effects of three pCO2 treatments (410, 770, and 1230 μatm) and two feeding frequencies (High Food and Low Food) on adult Balanophyllia elegans planulation (larval release) rates, and on the survival, growth, and calcification of their juvenile offspring. Planulation rates were affected by food level but not pCO2, while juvenile survival was highest under 410 μatm and High Food conditions. Our results suggest that feeding rate has a greater impact on calcification of B. elegans than pCO2. Net calcification was positive even at 1230 μatm (~ 3 times current atmospheric pCO2), although the increase from 410 to 1230 μatm reduced overall calcification by ~ 25-45%, and reduced skeletal density by ~ 35-45%. Higher pCO2 also altered aragonite crystal morphology significantly. We discuss how feeding frequency affects azooxanthellate coral calcification, and how B. elegans may respond to ocean acidification in coastal upwelling waters.

Ovarian transposition in young women and fertility sparing.

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Mossa, B; Schimberni, M; Di Benedetto, L; Mossa, S

2015-09-01

Ovarian transposition is a highly effective surgical procedure used to preserve ovarian function in premenopausal patients with cancers requiring postoperative or primary pelvic radiotherapy. Pelvic irradiation determines severe damage of ovarian DNA and iatrogenic ovarian failure with premature menopause, necessity of long-term hormone replacement therapy and infertility. We conducted an extensive research of the literature in Medline between January 2000 and April 2015 using the key-words "ovarian transposition radiotherapy", "radiotherapy gonadal function", radiotherapy fertility sparing". The population included young women with normal ovarian function affected by cancers that required pelvic radiotherapy. We have examined 32 articles reporting on 1189 women undergoing ovarian transposition. Median age was 32.5 years, follow up was median 48 months. The procedure has been performed in patients less than 40 years of age. Surgery has been achieved by laparotomy or laparoscoy. We have analyzed effects of radiotherapy on ovarian function. The proportion of women treated by ovarian transposition preserved ovarian function was 70%. About 86% of patients did not develop ovarian cysts and in 98-99% of cases did not occur any metastatic disease. Ovarian transposition is associated with significant preservation of ovarian function and a low frequency of complications as cysts and metastasis. In 31% of cases the procedure can fail. Further studies are needed to evaluate the efficacy of ovarian transposition and the follow up. Ovarian transposition should be discussed at the time of cancer diagnosis in every premenopausal woman requiring pelvic radiotherapy.

Plexin-B1 silencing inhibits ovarian cancer cell migration and invasion

International Nuclear Information System (INIS)

Ye, Shuangmei; Chen, Yin; You, Lanying; Zhang, Yiqun; Xu, Gang; Zhou, Jianfeng; Ma, Ding; Wang, Shixuan; Hao, Xing; Zhou, Ting; Wu, Mingfu; Wei, Juncheng; Wang, Yongjun; Zhou, Li; Jiang, Xuefeng; Ji, Li

2010-01-01

Elevated Plexin-B1 expression has been found in diverse human cancers and in non-neoplastic tissues, and it mediates diverse biological and pathological activities. However, whether or not Plexin-B1 expression is involved in human ovarian tumors remains unclear. In the present study, Plexin-B1 expression was explored in benign and malignant human ovarian tumor tissues. In addition, the impact of Plexin-B1 expression on ovarian cancer cell proliferation, migration and invasion were investigated in vitro. Plexin-B1 expression was analyzed in normal and benign ovarian tissues and serous ovarian tumors (both borderline and malignant) by immunohistochemical staining, as well as in four human ovarian cancer cell lines (A2780, C13*, SKOV3, and OV2008) by RT-PCR and western blot analyses. Furthermore, endogenous Plexin-B1 expression was suppressed by Plexin-B1 siRNA in SKOV3 cells, which overexpress Plexin-B1. Protein levels of Plexin-B1, AKT and AKT Ser473 were examined by western blot analysis. Cell proliferation, migration and invasion were measured with MTT, wound healing and boyden chamber assays, respectively, and the cytoskeleton was monitored via F-actin staining. Expression levels of Plexin-B1 protein were significantly higher in serous ovarian carcinomas than in normal ovaries or benign ovarian neoplasms, and in the former, Plexin-B1 expression was positively correlated with lymphatic metastasis, and the membrane and cytoplasm of cancer cells stained positively. SKOV3 cells displayed the highest Plexin-B1 expression at both the mRNA and protein levels among the four tested human ovarian cancer cell lines and was selected as a cell model for further in vitro experiments. Plexin-B1 siRNA significantly suppressed phosphorylation of AKT at Ser473 in SKOV3 cells, but it did not alter total AKT expression. In addition, silencing of Plexin-B1 in SKOV3 cells inhibited cell migration and invasion and reorganized the cytoskeleton, whereas cell proliferation was not

Comparison of Expression Profiles in Ovarian Epithelium In Vivo and Ovarian Cancer Identifies Novel Candidate Genes Involved in Disease Pathogenesis

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Emmanuel, Catherine; Gava, Natalie; Kennedy, Catherine; Balleine, Rosemary L.; Sharma, Raghwa; Wain, Gerard; Brand, Alison; Hogg, Russell; Etemadmoghadam, Dariush; George, Joshy; Birrer, Michael J.; Clarke, Christine L.; Chenevix-Trench, Georgia; Bowtell, David D. L.; Harnett, Paul R.; deFazio, Anna

2011-01-01

Molecular events leading to epithelial ovarian cancer are poorly understood but ovulatory hormones and a high number of life-time ovulations with concomitant proliferation, apoptosis, and inflammation, increases risk. We identified genes that are regulated during the estrous cycle in murine ovarian surface epithelium and analysed these profiles to identify genes dysregulated in human ovarian cancer, using publically available datasets. We identified 338 genes that are regulated in murine ovarian surface epithelium during the estrous cycle and dysregulated in ovarian cancer. Six of seven candidates selected for immunohistochemical validation were expressed in serous ovarian cancer, inclusion cysts, ovarian surface epithelium and in fallopian tube epithelium. Most were overexpressed in ovarian cancer compared with ovarian surface epithelium and/or inclusion cysts (EpCAM, EZH2, BIRC5) although BIRC5 and EZH2 were expressed as highly in fallopian tube epithelium as in ovarian cancer. We prioritised the 338 genes for those likely to be important for ovarian cancer development by in silico analyses of copy number aberration and mutation using publically available datasets and identified genes with established roles in ovarian cancer as well as novel genes for which we have evidence for involvement in ovarian cancer. Chromosome segregation emerged as an important process in which genes from our list of 338 were over-represented including two (BUB1, NCAPD2) for which there is evidence of amplification and mutation. NUAK2, upregulated in ovarian surface epithelium in proestrus and predicted to have a driver mutation in ovarian cancer, was examined in a larger cohort of serous ovarian cancer where patients with lower NUAK2 expression had shorter overall survival. In conclusion, defining genes that are activated in normal epithelium in the course of ovulation that are also dysregulated in cancer has identified a number of pathways and novel candidate genes that may contribute

Prevalence of metabolic syndrome is higher among non-obese PCOS women with hyperandrogenism and menstrual irregularity in Korea.

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Min-Ju Kim

Full Text Available BACKGROUND: Hyperandrogenism (HA has been linked with several components of metabolic syndrome (MetS. Few studies in Asian women have evaluated the important risk factors for and prevalence of MetS according to PCOS subtype. In this study, we investigated differences in metabolic parameters and the prevalence of MetS in two major phenotypic subgroups of PCOS in Korea. Furthermore, we investigated the relationship between HA-associated parameters and MetS. MATERIALS AND METHODS: This cross-sectional observational study was conducted from May 2010 to December 2011 in Korea. A total of 837 females with PCOS, aged 15-40, were recruited from Departments of Obstetrics and Gynecology at 13 hospitals. Of those, 700 subjects with either polycystic ovaries (PCO+HA+oligomenorrhea/amenorrhea (O or PCO+O were eligible for this study. MetS was diagnosed according to the modified National Cholesterol Education Program (NCEP Adult Treatment Panel (ATP III guidelines and the International Diabetes Federation (IDF criteria. RESULTS: MetS was more prevalent in the PCO+HA+O group (19.7% than in the PCO+O (11.9% group. There were statistically significant trends for an increased risk of MetS in the PCO+HA+O group compared to the PCO+O group. After adjustment for age, the odds ratio of MetS was 2.192 in non-obese subjects with PCO+HA+O compared to those with PCO+O, whereas the risk of MetS was not different in obese patients. Multivariate logistic regression analysis showed that high free androgen index and low sex hormone-binding globulin were significantly associated with MetS in non-obese women with PCOS, with odds ratios of 4.234 (95% CI, 1.893-9.474 and 4.612 (95% CI, 1.978-10.750, respectively. However, no associations were detected between MetS and SHBG and FAI in obese PCOS subjects. CONCLUSIONS: Our results indicate that HA and its associated parameters (FAI and SHBG are significantly associated with MetS in non-obese PCOS subjects, whereas this association

History of Comorbidities and Survival of Ovarian Cancer Patients, Results from the Ovarian Cancer Association Consortium

DEFF Research Database (Denmark)

Minlikeeva, Albina N; Freudenheim, Jo L; Eng, Kevin H

2017-01-01

carcinoma who participated in 23 studies included in the Ovarian Cancer Association Consortium, we explored associations between histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, and neurological diseases and overall and progression-free survival...... with ovarian cancer outcome in the overall sample nor in strata defined by histologic subtype, weight status, age at diagnosis, or stage of disease (local/regional vs. advanced).Conclusions: Histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, or neurologic......Background: Comorbidities can affect survival of ovarian cancer patients by influencing treatment efficacy. However, little evidence exists on the association between individual concurrent comorbidities and prognosis in ovarian cancer patients.Methods: Among patients diagnosed with invasive ovarian...

Ovarian volume and antral follicle count assessed by MRI and transvaginal ultrasonography: a methodological study.

Science.gov (United States)

Leonhardt, Henrik; Gull, Berit; Stener-Victorin, Elisabet; Hellström, Mikael

2014-03-01

Ultrasonographic measurements of ovarian volume and antral follicle count are of clinical importance as diagnostic features of polycystic ovarian syndrome (PCOS), and as a parameter in estimation of ovarian follicular reserve in infertility care. To compare two-dimensional (2D)/three-dimensional (3D) transvaginal ultrasonography (TVUS) and magnetic resonance imaging (MRI) for estimation of ovarian volume and antral follicle count, and to assess reproducibility and inter-observer agreement of MRI measurements. Volumes of 172 ovaries in 99 women aged 21-37 years were calculated (length x width x height x 0.523) with conventional 2D TVUS and 2D MRI. Semi-automatic estimates of ovarian volumes were obtained by 3D MRI. Antral follicles were counted manually on 2D MRI and automatically by 3D TVUS (SonoAVC), and stratified according to follicle size. Mean ovarian volume assessed by 2D TVUS (13.1 ± 6.4 mL) was larger than assessed by 2D MRI (9.6 ± 4.1) and 3D MRI (11.4 ± 4.5) (P 0.77. 2D MRI reveals more antral follicles, especially of small size, than 3D TVUS. Ovarian volume estimation by MRI provides smaller volumes than by the reference standard 2D TVUS. Ovarian volume estimation by 3D MRI, allowing independence of non-ellipsoid ovarian shape measurement errors, provides volumes closer to 2D TVUS values than does 2D MRI. Reproducibility and inter-observer agreement of 2D MRI measurements of ovarian volume and total follicle count are good.

Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG): clinical trial design for rare ovarian tumours

NARCIS (Netherlands)

Leary, A. F.; Quinn, M.; Fujiwara, K.; Coleman, R. L.; Kohn, E.; Sugiyama, T.; Glasspool, R.; Ray-Coquard, I.; Colombo, N.; Bacon, M.; Zeimet, A.; Westermann, A.; Gomez-Garcia, E.; Provencher, D.; Welch, S.; Small, W.; Millan, D.; Okamoto, A.; Stuart, G.; Ochiai, K.

2017-01-01

This manuscript reports the consensus statements on designing clinical trials in rare ovarian tumours reached at the fifth Ovarian Cancer Consensus Conference (OCCC) held in Tokyo, November 2015. Three important questions were identified concerning rare ovarian tumours (rare epithelial ovarian

Immunological comparison of ovarian and colonic CEA

International Nuclear Information System (INIS)

Burtin, P.; Gendron, M.C.; Maunoury, M.T.; Lamerz, R.; Schnabel, G.

1982-01-01

Ovarian and colonic CEA were compared immunologically by means of antisera prepared against each of them. CEAs of both origins were found identical by immunodiffusion methods. In radioimmunological experiments, slight differences were observed between some but not all ovarian CEAs and colonic CEAs and also between different preparations of colonic CEA: no organ specificity of ovarian CEA could be demonstrated. Finally, CEA level was measured in 41 sera of patients with ovarian carcinoma by two radioimmunoassays, one using colonic CEA as tracer and standard and anti-colonic CEA serum, the other using ovarian CEA and anti-ovarian CEA serum: the values given by the two assays were highly correlated (rsub(s) = 0.8107), meaning that an organ specific assay for ovarian CEA is not needed. (Auth.)

A combined transcutaneous PO2-PCO2 electrode with electrochemical HCO3- stabilization.

Science.gov (United States)

Severinghaus, J W

1981-10-01

Combined transcutaneous PO2-PCO2 electrodes are described in which the interaction between the two electrodes due to OH- production at the O2 cathode has been eliminated. An anode of either anodized aluminum or platinum has been driven at a current equal to cathode current to force stoichiometric consumption of OH- at its rate of production. The AgCl reference electrode operates at zero current. O2 sensitivity was not significantly altered by electrolyte pH variation from 6.7 to 9.0 with variations by PCO2. These electrodes have been found stable both with and without spacers, and with electrolytes dissolved in 50-100% ethylene glycol. In 22 anesthetized patients, with electrode temperature of 43 degrees C (s refers to skin surface, a to arterial blood); PsO2 = 0.52PaO2 + 15 (range 54-300) (r = 0.66; Sy . x = 29.6; n = 46); and PsCO2 = 1.39PaCO2 + 2.1 (range 24-98) (r = 0.99; Sy . x = 2.28; n = 48).

Ovarian dynamics and milk progesterone concentrations in cycling and non-cycling buffalo-cows (Bubalus bubalis) during Ovsynch program.

Science.gov (United States)

Ali, A; Fahmy, S

2007-07-01

The objective was to evaluate ovarian dynamics and progesterone concentrations in cyclic (CYC, n=10) and non-cyclic (NCY, n=8) buffalo-cows during Ovsynch program. All cows received GnRH on day 0, PGF2alpha on day 7, and GnRH on day 9, and AI 14 h later. Ovarian structures were monitored by ultrasound and milk samples were collected for progesterone (P4) analysis. The first GnRH resulted in ovulation in CYC (90%) and NCY (62.5%) cows. By day 7, almost all cows had large follicle and lutein tissue. Luteolytic responses to PGF2alpha were 80 and 87.5% for CYC and NCY cows, respectively. Following second GnRH, ovulation occurred in 80% of CYC and 100% of NCY cows. Ovulation began earlier (12 h following second GnRH) and extended for longer (36 h) in NCY cows, when compared to CYC cows (36 and 12 h, respectively). The mean P4 levels increased from days 0 through 7 in CYC and NCY cows and levels were higher in CYC group. Conception rates were 60 and 37.5% in CYC and NYC cows, respectively. Early and asynchronous ovulation and luteal sub-function seemed to be a problem in NCY cows. Inseminating NCY cows twice, at 0 and 24 h of the second GnRH is recommended.

Local lymphocytes and nitric oxide synthase in the uterine cervical stroma of patients with grade III cervical intraepithelial neoplasia

Directory of Open Access Journals (Sweden)

Cléber Sergio da Silva

2010-01-01

Full Text Available OBJECTIVES: Precancerous and cancerous cells can trigger an immune response that may limit tumor development and can be used as a prognostic marker. The aims of the present study were to quantify the presence of B and T lymphocytes, macrophages and cells expressing inducible nitric oxide synthase (iNOS in the cervical stroma of women with grade III cervical intraepithelial neoplasia (CIN III or in the intratumoral and peritumoral tissue of women with stage I invasive carcinoma. METHODS: Cervical tissue specimens were obtained from 60 women (20 each from control tissues, CIN III and invasive carcinomas. The average ages in the control, CIN III and invasive groups were 43.9 (± 4.3, 35.5 (± 9.5, and 50 (± 11.2 years, respectively. The specimens were immunohistochemically labeled with antibodies to identify T lymphocytes (CD3, cytotoxic lymphocytes (CD8, B lymphocytes (CD20, macrophages (CD68 and iNOS. We evaluated the markers in the stroma above the squamocolumnar junction (control, at the intraepithelial lesion (CIN cases, and in the nfiltrating tumor. Two independent observers performed the immunohistochemical analysis. RESULTS: T lymphocytes, B lymphocytes, macrophages and iNOS were present more frequently (P<0.05 in the stroma of peritumoral invasive tumors compared to the controls and intratumoral invasive cancer samples. CD3+ and CD20+ lymphocytes were present more frequently in CIN III patients compared to samples from patients with intratumoral invasive cancer (P<0.05. CONCLUSION: High numbers of T and B lymphocytes, macrophages and iNOS-expressing cells in the peritumoral stroma of the invasive tumors were observed. Cell migration appeared to be proportional to the progression of the lesion.

Fertility drugs and ovarian cancer.

Science.gov (United States)

Ali, Aus Tariq

2017-06-20

The aetiology of ovarian cancer is multifactorial with both endogenous and exogenous risk factors playing an important role. The exact pathogenesis of ovarian cancer is still not well understood, despite the number of hypotheses published. Due to an increase in the number of women using fertility drugs, much attention has been focused on the long-term health effects of such drugs. Although fertility drugs facilitate the ovulation process, it is however associated with a significant increase in hormone concentrations, placing exposed women at increased risk of gynaecological cancer. Many clinical and epidemiological studies have examined the association between fertility drugs and ovarian cancer risk. Results from these studies have been contradictory, as some studies have reported an increased risk of ovarian cancer while others reported no increased risk. Nevertheless, recent studies have shown that women who used fertility drugs and did not conceive had a higher risk of developing ovarian cancer, compared to women who used fertility drugs and conceived and delivered successfully. This review discusses the effect of fertility drugs on the risk of developing ovarian cancer, providing details on four possible scenarios associated with fertility treatment. In addition, the limitations of previous studies and their impact on our understanding of the association between fertility drugs and ovarian cancer also have been highlighted. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Clinicopathologic significance of HLA-G and HLA-E molecules in Tunisian patients with ovarian carcinoma.

Science.gov (United States)

Babay, Wafa; Ben Yahia, Hamza; Boujelbene, Nadia; Zidi, Nour; Laaribi, Ahmed Baligh; Kacem, Dhikra; Ben Ghorbel, Radhia; Boudabous, Abdellatif; Ouzari, Hadda-Imene; Rizzo, Roberta; Rebmann, Vera; Mrad, Karima; Zidi, Inès

2018-06-01

The human leukocyte antigen (HLA)-G and HLA-E, non classical HLA class I molecules, have been highly implicated in immune tolerance. HLA-G and HLA-E molecules were proposed as putative markers of several advanced cancers. As a step towards a better understanding of ovarian carcinoma, we evaluated the expression of both HLA-G and HLA-E molecules and explored their prognostic implication. HLA-G and HLA-E expression were studied by immunohistochemistry on ovarian carcinoma tissues. This expression was semi-quantitatively scored into four expression groups and correlated to clinicopathological parameters and patients' survival. HLA-G and HLA-E have been found to be highly expressed in ovarian carcinoma tissues (Respectively, 72.4% and 96.8%). They are frequently co-expressed. Univariate and multivariate analysis revealed that a positive HLA-G expression status in tumor tissue is a promising candidate parameter to predict disease recurrence in addition to the disease status in Tunisian patients with ovarian carcinoma. Moreover, the elevated HLA-E expression was associated with serous ovarian carcinoma subtype as well as with advanced stages of ovarian carcinoma. HLA-G and HLA-E are highly represented in ovarian carcinoma suggesting a potential association with progressive disease mechanism. HLA-G and HLA-E molecules might be new candidates' markers for ovarian carcinoma progression. Copyright © 2018 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

An Update on Ovarian Aging and Ovarian Reserve Tests

Directory of Open Access Journals (Sweden)

Migraci Tosun

2016-12-01

Full Text Available Ovaries are the female organs that age more quickly than other tissues such as the uterus, the pituitary gland or pancreas. Different from males, an interesting question is why and how the females lose fertility so rapidly. During the aging process, both the number and quality of the oocytes in the ovaries decrease and reach to a point beyond that no more viable offspring may be produced and the associated cyclic endocrinological activities cease, entering the menopause in females at an average age of 50 years. Females who delayed childbearing with or without their willing until their 30 years or 40 years constitute the largest portion of the total infertility population. Ovarian reserve tests (ORTs provide an indirect estimate of a female�s diminishing ovarian reserve or remaining follicular pool. This article briefly reviews recent progresses in relation to ovarian aging and ORTs.

Laparoscopic ovarian drilling by diathermy for ovulation induction in infertile women with polycystic ovarian syndrome

International Nuclear Information System (INIS)

Butt, F.

2011-01-01

Background: Polycystic ovarian syndrome (PCOS) is the commonest cause of secondary infertility. Laparoscopic ovarian drilling has widely been used for induction of ovulation in polycystic ovarian syndrome patients resistant to clomiphene citrate. 80% patients ovulated after treatment and 60% patient conceived either spontaneously or after treatment with medication to which they are previously resistant. Purpose: The aim of the present study was to see the effectiveness of laparoscopic ovarian drilling (LOD) with monopolar diathermy on pregnancy outcome in infertile women with polycystic ovarian syndrome (PCOS). Design: Descriptive cross sectional study. Intervention: Laparoscopic ovarian drilling. Main Outcome Measures: Pregnancy, ovulation rate. Material and Methods: This study was carried out in the department of Gynae and Obstetrics in Sharif Medical City Hospital from January, 2007 to January, 2009. The inclusion criteria for laparoscopy ovarian drilling (LOD) were those infertile women between the age group of 25 - 38 years who meet the criteria for PCOS and who are resistant to clomiphene citrate and injectable gonadotrophins. A total of 30 women were booked for laparoscopic ovarian drilling after having informed consent for procedure. Response to therapy was assessed in term of pregnancy outcome and ovulation rate for 1 year after therapy. Results: A total of 30 patients were booked for laparoscopic ovarian drilling from January, 2007 to January, 2009. The mean age of study group was 30 years +- SD 4.7791. Cumulative ovulation rate was observed in 22 patients (73%), out of which spontaneous ovulation occurred in 18 patients (80%), and after ovulation induction therapy in 4 patients (18%). Eleven patients (37%) conceived in two year duration. Spontaneous conception without any treatment was observed in 7 patients (63%); however 4 patients (37%) require further assistance with combined therapy of clomiphene citrate and injectable gonadotrophins after failure

Polymorphism in the GALNT1 gene and epithelial ovarian cancer in non-Hispanic white women: the Ovarian Cancer Association Consortium

DEFF Research Database (Denmark)

Phelan, Catherine M; Tsai, Ya-Yu; Goode, Ellen L

2010-01-01

Aberrant glycosylation is a well-described hallmark of cancer. In a previous ovarian cancer case control study that examined polymorphisms in 26 glycosylation-associated genes, we found strong statistical evidence (P = 0.00017) that women who inherited two copies of a single-nucleotide polymorphism...... sites but significant differences compared with the original study population (P = 0.03). This study underscores the need for replication of putative findings in genetic association studies....

DETECTION OF OXIDATIVE STRESS, APOPTOSIS AND MOLECULAR LESIONS IN HUMAN OVARIAN CANCER CELLS

Directory of Open Access Journals (Sweden)

H. I. Falfushynska

2016-05-01

Full Text Available Background. Ovarian cancer has the highest mortality rate of gynaecological cancers. This is partly due to the lack of effective screening markers. Indices of oxidative stress are well-recognized prognostic criteria for tumorous transformation of tissue, but their value depends on the type of tumor and the stage of its development. Objective. The aim of this study is to clarify the relationship between antioxidant/pro-oxidant ratio and the signs of molecular lesions and apoptosis rate in blood of ovarian cancer patients and non-cancer ones. Results. The ovarian cancer group is marked by antioxidant/prooxidant balance shifting to oxidative damage in blood as the consequence of overexpression of oxyradicals (by 300%. Higher level of glutathione (by 366%, lower level of metallothioneins (by 65% as well as higher level of lipid peroxidation (by 174% and protein carbonyls (by 186% in blood of ovarian cancer patients compared to the normal ovarian group have been observed. The signs of cytotoxicity are determined in blood of ovarian cancer patients: an increased (compared to control level of DNA fragmentation (by 160%, choline esterase (up to twice, higher rate of both caspase dependent and caspase independent lysosomal mediated apoptosis. Conclusions. Cathepsin D activity both total and free, choline esterase activity, TBA-reactive substance and protein carbonyls level in blood could be used as the predictive markers of worse prognosis and the signs of human ovarian cancer.

Diffusion-weighted imaging features of breast tumours and the surrounding stroma reflect intrinsic heterogeneous characteristics of molecular subtypes in breast cancer

KAUST Repository

Fan, Ming; He, Ting; Zhang, Peng; Cheng, Hu; Zhang, Juan; Gao, Xin; Li, Lihua

2017-01-01

Breast cancer heterogeneity is the main obstacle preventing the identification of patients with breast cancer with poor prognoses and treatment responses; however, such heterogeneity has not been well characterized. The purpose of this retrospective study was to reveal heterogeneous patterns in the apparent diffusion coefficient (ADC) signals in tumours and the surrounding stroma to predict molecular subtypes of breast cancer. A dataset of 126 patients with breast cancer, who underwent preoperative diffusion-weighted imaging (DWI) on a 3.0-T image system, was collected. Breast images were segmented into regions comprising the tumour and surrounding stromal shells in which features that reflect heterogeneous ADC signal distribution were extracted. For each region, imaging features were computed, including the mean, minimum, variance, interquartile range (IQR), range, skewness, kurtosis and entropy of ADC values. Univariate and stepwise multivariate logistic regression modelling was performed to identify the magnetic resonance imaging features that optimally discriminate luminal A, luminal B, human epidermal growth factor 2 (HER2)-enriched and basal-like molecular subtypes. The performance of the predictive models was evaluated using the area under the receiver operating characteristic curve (AUC). Univariate logistic regression analysis showed that the skewness in the tumour boundary achieved an AUC of 0.718 for discrimination between luminal A and non-luminal A tumours, whereas the IQR of the ADC value in the tumour boundary had an AUC of 0.703 for classification of the HER2-enriched subtype. Imaging features in the tumour boundary and the proximal peritumoral stroma corresponded to a higher overall prediction performance than those in other regions. A multivariate logistic regression model combining features in all the regions achieved an overall AUC of 0.800 for the classification of the four tumour subtypes. These findings suggest that features in the tumour

Diffusion-weighted imaging features of breast tumours and the surrounding stroma reflect intrinsic heterogeneous characteristics of molecular subtypes in breast cancer

KAUST Repository

Fan, Ming

2017-12-16

Breast cancer heterogeneity is the main obstacle preventing the identification of patients with breast cancer with poor prognoses and treatment responses; however, such heterogeneity has not been well characterized. The purpose of this retrospective study was to reveal heterogeneous patterns in the apparent diffusion coefficient (ADC) signals in tumours and the surrounding stroma to predict molecular subtypes of breast cancer. A dataset of 126 patients with breast cancer, who underwent preoperative diffusion-weighted imaging (DWI) on a 3.0-T image system, was collected. Breast images were segmented into regions comprising the tumour and surrounding stromal shells in which features that reflect heterogeneous ADC signal distribution were extracted. For each region, imaging features were computed, including the mean, minimum, variance, interquartile range (IQR), range, skewness, kurtosis and entropy of ADC values. Univariate and stepwise multivariate logistic regression modelling was performed to identify the magnetic resonance imaging features that optimally discriminate luminal A, luminal B, human epidermal growth factor 2 (HER2)-enriched and basal-like molecular subtypes. The performance of the predictive models was evaluated using the area under the receiver operating characteristic curve (AUC). Univariate logistic regression analysis showed that the skewness in the tumour boundary achieved an AUC of 0.718 for discrimination between luminal A and non-luminal A tumours, whereas the IQR of the ADC value in the tumour boundary had an AUC of 0.703 for classification of the HER2-enriched subtype. Imaging features in the tumour boundary and the proximal peritumoral stroma corresponded to a higher overall prediction performance than those in other regions. A multivariate logistic regression model combining features in all the regions achieved an overall AUC of 0.800 for the classification of the four tumour subtypes. These findings suggest that features in the tumour

The effect of bipolar electrocoagulation during ovarian cystectomy on ovarian reserve: a systematic review.

Science.gov (United States)

Pergialiotis, Vasilios; Prodromidou, Anastasia; Frountzas, Maximos; Bitos, Konstantinos; Perrea, Despina; Doumouchtsis, Stergios K

2015-11-01

The aim of the present systematic review was to study the effect of bipolar electrocoagulation during ovarian cystectomy on ovarian reserve. We searched Medline (1966-2015), Scopus (2004-2015), ClinicalTrials.gov (2008-2015), and Cochrane Central Register (CENTRAL) databases along with reference lists of electronically retrieved studies. The levels of antimullerian hormone (AMH) and antral follicle count (AFC) at 1, 3, 6, and 12 months following the excision of the benign ovarian cyst were defined as primary outcomes. Eight studies were finally included in our systematic review, which recruited 545 women. A metaanalysis was precluded because of significant heterogeneity in the methodological characteristics of the included studies. Data from the included studies suggest that the use of bipolar coagulation compared with ovarian sutures seems to result in significantly lower AMH and AFC during the first 3 months following the excision of the ovarian cyst. Two studies reported that this effect seems to persist at 6 and 12 months postoperatively. Bipolar electrodiathermy seems to be accompanied by increased damage to ovarian reserve, which is indicated by the lower levels of AMH and AFC. However, definitive results are precluded because of the significant heterogeneity of included studies and the potential bias. Copyright © 2015 Elsevier Inc. All rights reserved.

Pediatric ovarian torsion: an uncommon clinical entity

OpenAIRE

Rajwani, Kapil M; Mahomed, Anies

2014-01-01

Key Clinical Message Pediatric ovarian torsion is an infrequent diagnosis and it often mimics acute appendicitis. Most cases are due to underlying ovarian pathology and if left untreated, ovarian torsion may eventually cause peritonitis. Emergency exploratory laparoscopy represents a valuable diagnostic and therapeutic tool in suspected ovarian torsion.

Vanishing large ovarian cyst with thyroxine therapy.

Science.gov (United States)

Dharmshaktu, Pramila; Kutiyal, Aditya; Dhanwal, Dinesh

2013-01-01

A 21-year-old female patient recently diagnosed with severe hypothyroidism was found to have a large ovarian cyst. In view of the large ovarian cyst, she was advised to undergo elective laparotomy in the gynaecology department. She was further evaluated in our medical out-patient department (OPD), and elective surgery was withheld. She was started on thyroxine replacement therapy, and within a period of 4 months, the size of the cyst regressed significantly, thereby improving the condition of the patient significantly. This case report highlights the rare and often missed association between hypothyroidism and ovarian cysts. Although very rare, profound hypothyroidism that can cause ovarian cysts in an adult should always be kept in the differential diagnosis to avoid unnecessary ovarian surgery. Hypothyroidism should be considered in the differential diagnosis of adult females presenting with multicystic ovarian tumours.Adequate thyroid hormone replacement therapy can prevent these patients from undergoing unnecessary and catastrophic ovarian resection.Surgical excision should be considered only when adequate thyroid replacement therapy fails to resolve ovarian enlargement.In younger women with ovarian cysts, it is also desirable to avoid unnecessary surgery so as to not compromise fertility in the future.

The capacity of peripheral blood stem cells mobilised with chemotherapy plus G-CSF to repopulate irradiated marrow stroma in vitro is similar to that of bone marrow

International Nuclear Information System (INIS)

Demuynck, H.; Dexter, T.M.; Testa, N.G.; Pettengell, R.; Campos, E. de

1992-01-01

After treatment of patients with intermediate or high grade non-Hodgkin lymphoma with chemotherapy plus G-CSF the numbers of haemopoietic progenitor cells in the circulation increased to a mean of 226-fold for mixed CFC (Mix-CFC), 278-fold for GM-CFC and 29-fold for erythroid burst forming unit (BFU-E). The mean increase was modest (7-12-fold) for patients treated with chemotherapy alone. Peripheral blood mononuclear cells harvested at the time of the peak in the numbers of progenitors, or 2-4 days before the peak, seeded onto irradiated marrow stroma in vitro, repopulated the stroma and generated active haemopoiesis at least as effectively as bone marrow cells on a cell per cell basis. This is in contrast to the poor repopulating capacity of pretreatment blood. The results indicate that not only the progenitor cells, but also the repopulating stem cells migrated into the blood after chemotherapy plus G-CSF in sufficient numbers to allow harvesting and successful grafting without the possible complication of late haemopoietic failure. (author)

Inverse relationship between TCTP/RhoA and p53/ /cyclin A/actin expression in ovarian cancer cells Inverse relationship between TCTP/RhoA and p53/ /cyclin A/actin expression in ovarian cancer cells

Directory of Open Access Journals (Sweden)

Malgorzata Kloc

2012-10-01

Full Text Available The translationally controlled tumor protein (TCTP plays a role in cell growth, cell cycle and cancer
progression. TCTP controls negatively the stability of the p53 tumor suppressor protein and interacts with the
cellular cytoskeleton. The deregulation of the actin and cytokeratin cytoskeleton is responsible for the increased
migratory activity of tumor cells and is linked with poor patient outcome. Recent studies indicate that cyclin A,
a key regulator of cell cycle, controls actin organization and negatively regulates cell motility via regulation of RhoA
expression. We studied the organization of actin and cytokeratin cytoskeleton and the expression of TCTP, p53,
cyclin A, RhoA and actin in HIO180 non-transformed ovarian epithelial cells, and OVCAR3 and SKOV3 (expressing
low level of inducible p53 ovarian epithelial cancer cells with different metastatic potential. Immunostaining
and ultrastructural analyses illustrated a dramatic difference in the organization of the cytokeratin and actin
filaments in non-transformed versus cancer cell lines. We also determined that there is an inverse relationship between
the level of TCTP/RhoA and actin/p53/cyclin A expression in ovarian cancer cell lines. This previously unidentified
negative relationship between TCTP/RhoA and actin/p53/cyclin A may suggest that this interaction is linked
with the high aggressiveness of ovarian cancers.The translationally controlled tumor protein (TCTP plays a role in cell growth, cell cycle and cancer
progression. TCTP controls negatively the stability of the p53 tumor suppressor protein and interacts with the
cellular cytoskeleton. The deregulation of the actin and cytokeratin cytoskeleton is responsible for the increased
migratory activity of tumor cells and is linked with poor patient outcome. Recent studies indicate that cyclin A,
a key regulator of cell cycle, controls actin organization

Effect of ovarian dermoid cyst excision on ovarian reserve and response: Insights from in vitro fertilization

OpenAIRE

Lei Yan; Miao Li; Bing-Qian Zhang; Xin-Xin Xu; Zhen Xu; Ting Han; Zi-Jiang Chen

2016-01-01

Study objective: To investigate the impact of an ovarian dermoid cyst or dermoid cyst surgery on ovarian reserve in patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Design: We performed a retrospective cohort study by using the records of patients with a history of ovarian dermoid cyst who underwent IVF/ICSI between 2009 and 2013. The antral follicle count (AFC) obtained by transvaginal ultrasound during controlled ovarian hyperstimulation of IVF/ICSI...

New perspectives on targeted therapy in ovarian cancer

Directory of Open Access Journals (Sweden)

Coward JIG

2015-02-01

Full Text Available Jermaine IG Coward,1–3 Kathryn Middleton,1 Felicity Murphy1 1Mater Health Services, Raymond Terrace, South Brisbane, QLD, Australia; 2Inflammtion and Cancer Therapeutics Group, Mater Research, University of Queensland, Translational Research Institute, Woolloongabba, Brisbane, QLD, Australia; 3School of Medicine, University of Queensland, Brisbane, QLD, Australia Abstract: Epithelial ovarian cancer remains the most lethal gynecologic malignancy. During the last 15 years, there has been only marginal improvement in 5 year overall survival. These daunting statistics are compounded by the fact that despite all subtypes exhibiting striking heterogeneity, their systemic management remains identical. Although changes to the scheduling and administration of chemotherapy have improved outcomes to a degree, a therapeutic ceiling is being reached with this approach, resulting in a number of trials investigating the efficacy of targeted therapies alongside standard treatment algorithms. Furthermore, there is an urge to develop subtype-specific studies in an attempt to improve outcomes, which currently remain poor. This review summarizes the key studies with antiangiogenic agents, poly(adenosine diphosphate [ADP]-ribose inhibitors, and epidermal growth factor receptor/human epidermal growth factor receptor family targeting, in addition to folate receptor antagonists and insulin growth factor receptor inhibitors. The efficacy of treatment paradigms used in non-ovarian malignancies for type I tumors is also highlighted, in addition to recent advances in appropriate patient stratification for targeted therapies in epithelial ovarian cancer. Keywords: antiangiogenic therapy, high-grade serous, low grade ovarian cancer, PARP inhibition, cancer-related inflammation

Effects of previous ovarian surgery for endometriosis on the outcome of assisted reproduction treatment.

Science.gov (United States)

Geber, Selmo; Ferreira, Daniela Parreiras; Spyer Prates, Luis Felipe Víctor; Sales, Liana; Sampaio, Marcos

2002-01-01

Endometriosis affects 2-50% of women at reproductive age. Surgery is an option for treatment, but there is no convincing evidence that it promotes a significant improvement in fertility. Also, the removal of ovarian endometrioma might lead to a reduction in the follicular reserve and response to stimulation. Therefore, the aim of this study was to evaluate the effect of previous ovarian surgery for endometriosis on the ovarian response in assisted reproduction treatment cycles and its pregnancy outcome. A total of 61 women, with primary infertility and previously having undergone ovarian surgery for endometriosis, who had received 74 IVF/intracytoplasmic sperm injection (ICSI) cycles, were studied (study group). A further 74 patients with primary infertility who underwent 77 IVF/ICSI cycles within#10; the same period of time, at the same clinic and without previous ovarian surgery or endometriosis were studied as a control group. Patients were matched for age and treatment performed. Patients 35 years with previous ovarian surgery needed more ampoules for ovulation induction (P = 0.017) and had fewer follicles and oocytes than women in the control group (P = 0.001). Duration of folliculogenesis was similar in both groups, as was fertilization rate. A total of 10 patients achieved pregnancy in the study group (34.5%) and 14 (48.3%) in the control group. Although a lower pregnancy rate was observed in patients who had undergone previous ovarian surgery, this difference was not statistically significant (P = 0.424). In conclusion, ovarian surgery for the treatment of endometriosis reduces the ovarian outcome in IVF/ICSI cycles in women >35 years old, and might also decrease pregnancy rates. Therefore, for infertile patients, non-surgical treatment might be a better option to avoid reduction of the ovarian response.

Anti-Mullerian hormone and ovarian dysfunction

NARCIS (Netherlands)

Broekmans, Frank J.; Visser, Jenny A.; Laven, Joop S. E.; Broer, Simone L.; Themmen, Axel P. N.; Fauser, Bart C.

2008-01-01

Anti-Mullerian hormone (AMH) has important roles in postnatal ovarian function. Produced by ovarian granulosa cells, AMH is involved in initial follicle development. In fact, serum AMH level correlates with ovarian follicle number. In patients with polycystic ovary syndrome (PCOS), AMH levels are

Ovarian and tubal cancer in Denmark

DEFF Research Database (Denmark)

Gottschau, Mathilde; Mellemkjaer, Lene; Hannibal, Charlotte G

2016-01-01

INTRODUCTION: The Nordic countries are areas with a high-incidence of ovarian cancer; however, differences between the countries exist. MATERIAL AND METHODS: We used the Danish Cancer Registry to identify 11 264 cases of ovarian cancer and 363 cases of tubal cancer during 1993-2013. We calculated...... age-standardized (world standard population) incidence rates for overall and subtype-specific ovarian cancer, and for tubal cancer. We compared age-standardized incidence rates, and 1- and 5-year age-standardized relative survival rates, respectively, for ovarian and tubal cancer combined in four...... Nordic countries using the NORDCAN database. RESULTS: The incidence rate of ovarian cancer overall in Denmark decreased statistically significantly by approximately 2.3% per year among women aged

Reduced supportive capacity of bone marrow stroma upon chemotherapy is mediated via changes in glycosaminoglycan profile

NARCIS (Netherlands)

Zweegman, Sonja; Kessler, Floortje L.; Kerkhoven, Ron M.; Heimerikx, Mike; Celie, Johanna W. A. M.; Janssen, Jeroen J. W. M.; Huijgens, Peter C.; Drager, Angelika M.; van den Born, Jacob

High dose chemotherapy and radiation have been found to impair the hematopoiesis-supportive capacity of bone marrow stroma. We now provide evidence for an important role of chemotherapy-induced alterations in stromal glycosaminoglycans (GAGs) in reduction of the supportive properties of stromal

Bidirectional Signaling of Mammary Epithelium and Stroma: Implications for Breast Cancer—Preventive Actions of Dietary Factors

Science.gov (United States)

The mammary gland is composed of two major cellular compartments: a highly dynamic epithelium that undergoes cycles of proliferation, differentiation, and apoptosis in response to local and endocrine signals and the underlying stroma comprised of fibroblasts, endothelial cells, and adipocytes that c...

Coffee, tea, and caffeine consumption and risk of epithelial ovarian cancer and borderline ovarian tumors

DEFF Research Database (Denmark)

Gosvig, Camilla F; Kjaer, Susanne K; Blaakær, Jan

2015-01-01

BACKGROUND: Epidemiological studies that have investigated the association between coffee, tea and caffeine consumption and ovarian cancer risk have produced conflicting results. Furthermore, only few studies have examined the role of coffee and tea consumption separately for borderline ovarian...... tumors. By use of data from a large Danish population-based case-control study, we examined the risk of ovarian tumors associated with coffee, tea, and caffeine consumption with a particular focus on characterizing risks by tumor behavior and histology. MATERIAL AND METHODS: From 1995 through 1999, we....... RESULTS: Both coffee (OR = 0.90; 95% CI 0.84-0.97 per cup/day) and total caffeine consumption from coffee and tea combined (OR = 0.93; 95% CI 0.88-0.98 per 100 mg/day) decreased the risk of ovarian cancer. These associations were significant only for the serous and "other" subtypes of ovarian cancer...

Proteomic and metabolomic responses of Pacific oyster Crassostrea gigas to elevated pCO2 exposure.

Science.gov (United States)

Wei, Lei; Wang, Qing; Wu, Huifeng; Ji, Chenglong; Zhao, Jianmin

2015-01-01

The gradually increased atmospheric CO2 partial pressure (pCO2) has thrown the carbonate chemistry off balance and resulted in decreased seawater pH in marine ecosystem, termed ocean acidification (OA). Anthropogenic OA is postulated to affect the physiology of many marine calcifying organisms. However, the susceptibility and metabolic pathways of change in most calcifying animals are still far from being well understood. In this work, the effects of exposure to elevated pCO2 were characterized in gills and hepatopancreas of Crassostrea gigas using integrated proteomic and metabolomic approaches. Metabolic responses indicated that high CO2 exposure mainly caused disturbances in energy metabolism and osmotic regulation marked by differentially altered ATP, glucose, glycogen, amino acids and organic osmolytes in oysters, and the depletions of ATP in gills and the accumulations of ATP, glucose and glycogen in hepatopancreas accounted for the difference in energy distribution between these two tissues. Proteomic responses suggested that OA could not only affect energy and primary metabolisms, stress responses and calcium homeostasis in both tissues, but also influence the nucleotide metabolism in gills and cytoskeleton structure in hepatopancreas. This study demonstrated that the combination of proteomics and metabolomics could provide an insightful view into the effects of OA on oyster C. gigas. The gradually increased atmospheric CO2 partial pressure (pCO2) has thrown the carbonate chemistry off balance and resulted in decreased seawater pH in marine ecosystem, termed ocean acidification (OA). Anthropogenic OA is postulated to affect the physiology of many marine calcifying organisms. However, the susceptibility and metabolic pathways of change in most calcifying animals are still far from being understood. To our knowledge, few studies have focused on the responses induced by pCO2 at both protein and metabolite levels. The pacific oyster C. gigas, widely distributed

How to personalize ovarian stimulation in clinical practice.

Science.gov (United States)

Sighinolfi, Giovanna; Grisendi, Valentina; La Marca, Antonio

2017-09-01

Controlled ovarian stimulation (COS) in in vitro fertilization (IVF) cycles is the starting point from which couple's prognosis depends. Individualization in follicle-stimulating hormone (FSH) starting dose and protocol used is based on ovarian response prediction, which depends on ovarian reserve. Anti-Müllerian hormone levels and the antral follicle count are considered the most accurate and reliable markers of ovarian reserve. A literature search was performed for studies that addressed the ability of ovarian reserve markers to predict poor and high ovarian response in assisted reproductive technology cycles. According to the predicted response to ovarian stimulation (poor- normal- or high- response), it is possible to counsel couples before treatment about the prognosis, and also to individualize ovarian stimulation protocols, choosing among GnRH-agonists or antagonists for endogenous FSH suppression, and the FSH starting dose in order to decrease the risk of cycle cancellation and ovarian hyperstimulation syndrome. In this review we discuss how to choose the best COS therapy, based on ovarian reserve markers, in order to enhance chances in IVF.

Characterization of the Chicken Ovarian Cancer Model

National Research Council Canada - National Science Library

Rodriguez, Gustavo

2002-01-01

.... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

Characterization of the Chicken Ovarian Cancer Model

National Research Council Canada - National Science Library

Rodriguez, Gustavo C

2004-01-01

.... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

Characterization of the Chicken Ovarian Cancer Model

National Research Council Canada - National Science Library

Rodriguez, Gustavo C

2005-01-01

.... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

Characterization of the Chicken Ovarian Cancer Model

National Research Council Canada - National Science Library

Rodriguez, Gustavo

2003-01-01

.... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

Characterization of the Chicken Ovarian Cancer Model

National Research Council Canada - National Science Library

Rodriquez, Gustavo

2001-01-01

.... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

Cell-type-specific enrichment of risk-associated regulatory elements at ovarian cancer susceptibility loci.

Science.gov (United States)

Coetzee, Simon G; Shen, Howard C; Hazelett, Dennis J; Lawrenson, Kate; Kuchenbaecker, Karoline; Tyrer, Jonathan; Rhie, Suhn K; Levanon, Keren; Karst, Alison; Drapkin, Ronny; Ramus, Susan J; Couch, Fergus J; Offit, Kenneth; Chenevix-Trench, Georgia; Monteiro, Alvaro N A; Antoniou, Antonis; Freedman, Matthew; Coetzee, Gerhard A; Pharoah, Paul D P; Noushmehr, Houtan; Gayther, Simon A

2015-07-01

Understanding the regulatory landscape of the human genome is a central question in complex trait genetics. Most single-nucleotide polymorphisms (SNPs) associated with cancer risk lie in non-protein-coding regions, implicating regulatory DNA elements as functional targets of susceptibility variants. Here, we describe genome-wide annotation of regions of open chromatin and histone modification in fallopian tube and ovarian surface epithelial cells (FTSECs, OSECs), the debated cellular origins of high-grade serous ovarian cancers (HGSOCs) and in endometriosis epithelial cells (EECs), the likely precursor of clear cell ovarian carcinomas (CCOCs). The regulatory architecture of these cell types was compared with normal human mammary epithelial cells and LNCaP prostate cancer cells. We observed similar positional patterns of global enhancer signatures across the three different ovarian cancer precursor cell types, and evidence of tissue-specific regulatory signatures compared to non-gynecological cell types. We found significant enrichment for risk-associated SNPs intersecting regulatory biofeatures at 17 known HGSOC susceptibility loci in FTSECs (P = 3.8 × 10(-30)), OSECs (P = 2.4 × 10(-23)) and HMECs (P = 6.7 × 10(-15)) but not for EECs (P = 0.45) or LNCaP cells (P = 0.88). Hierarchical clustering of risk SNPs conditioned on the six different cell types indicates FTSECs and OSECs are highly related (96% of samples using multi-scale bootstrapping) suggesting both cell types may be precursors of HGSOC. These data represent the first description of regulatory catalogues of normal precursor cells for different ovarian cancer subtypes, and provide unique insights into the tissue specific regulatory variation with respect to the likely functional targets of germline genetic susceptibility variants for ovarian cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Tumor-Associated Macrophages as Incessant Builders and Destroyers of the Cancer Stroma

International Nuclear Information System (INIS)

Liguori, Manuela; Solinas, Graziella; Germano, Giovanni; Mantovani, Alberto; Allavena, Paola

2011-01-01

Tumor-Associated Macrophages (TAM) are key components of the reactive stroma of tumors. In most, although not all cancers, their presence is associated with poor patient prognosis. In addition to releasing cytokines and growth factors for tumor and endothelial cells, a distinguished feature of TAM is their high-rate degradation of the extra-cellular matrix. This incessant stroma remodelling favours the release of matrix-bound growth factors and promotes tumor cell motility and invasion. In addition, TAM produce matrix proteins, some of which are typical of the neoplastic tissues. The gene expression profile of TAM isolated from human tumors reveals a matrix-related signature with the up-regulation of genes coding for different matrix proteins, as well as several proteolytic enzymes. Among ECM components are: osteopontin, osteoactivin, collagens and fibronectin, including also a truncated isoform of fibronectin termed migration stimulation factor. In addition to serve as structural proteins, these matrix components have key functions in the regulation of the vessel network, in the inductionof tumor cell motility and degradation of cellular debris. Among proteolytic enzymes are: matrix metalloproteases, cathepsins, lysosomal and ADAM proteases, and the urokinase-type plasminogen activator. The degrading activity of TAM, coupled to the production of bio-active ECM proteins, co-operate to the build-up and maintenance of an inflammatory micro-environment which eventually promotes tumor progression

Tumor-Associated Macrophages as Incessant Builders and Destroyers of the Cancer Stroma

Energy Technology Data Exchange (ETDEWEB)

Liguori, Manuela; Solinas, Graziella; Germano, Giovanni [Department of Immunology and Inflammation Istituto Clinico Humanitas, Via Manzoni 113, Rozzano-Milano 20089 (Italy); Mantovani, Alberto [Department of Immunology and Inflammation Istituto Clinico Humanitas, Via Manzoni 113, Rozzano-Milano 20089 (Italy); Department of Translational Medicine, University of Milano, Milano 20089 (Italy); Allavena, Paola, E-mail: paola.allavena@humanitasresearch.it [Department of Immunology and Inflammation Istituto Clinico Humanitas, Via Manzoni 113, Rozzano-Milano 20089 (Italy)

2011-09-28

Tumor-Associated Macrophages (TAM) are key components of the reactive stroma of tumors. In most, although not all cancers, their presence is associated with poor patient prognosis. In addition to releasing cytokines and growth factors for tumor and endothelial cells, a distinguished feature of TAM is their high-rate degradation of the extra-cellular matrix. This incessant stroma remodelling favours the release of matrix-bound growth factors and promotes tumor cell motility and invasion. In addition, TAM produce matrix proteins, some of which are typical of the neoplastic tissues. The gene expression profile of TAM isolated from human tumors reveals a matrix-related signature with the up-regulation of genes coding for different matrix proteins, as well as several proteolytic enzymes. Among ECM components are: osteopontin, osteoactivin, collagens and fibronectin, including also a truncated isoform of fibronectin termed migration stimulation factor. In addition to serve as structural proteins, these matrix components have key functions in the regulation of the vessel network, in the inductionof tumor cell motility and degradation of cellular debris. Among proteolytic enzymes are: matrix metalloproteases, cathepsins, lysosomal and ADAM proteases, and the urokinase-type plasminogen activator. The degrading activity of TAM, coupled to the production of bio-active ECM proteins, co-operate to the build-up and maintenance of an inflammatory micro-environment which eventually promotes tumor progression.

The number and microlocalization of tumor-associated immune cells are associated with patient's survival time in non-small cell lung cancer

International Nuclear Information System (INIS)

Dai, Fuqiang; Liu, Lunxu; Che, Guowei; Yu, Nanbin; Pu, Qiang; Zhang, Shangfu; Ma, Junliang; Ma, Lin; You, Zongbing

2010-01-01

Tumor microenvironment is composed of tumor cells, fibroblasts, endothelial cells, and infiltrating immune cells. Tumor-associated immune cells may inhibit or promote tumor growth and progression. This study was conducted to determine whether the number and microlocalization of macrophages, mature dendritic cells and cytotoxic T cells in non-small cell lung cancer are associated with patient's survival time. Ninety-nine patients with non-small cell lung cancer (NSCLC) were included in this retrospective study. Paraffin-embedded NSCLC specimens and their clinicopathological data including up to 8-year follow-up information were used. Immunohistochemical staining for CD68 (marker for macrophages), CD83 (marker for mature dendritic cells), and CD8 (marker for cytotoxic T cells) was performed and evaluated in a blinded fashion. The numbers of immune cells in tumor islets and stroma, tumor islets, or tumor stroma were counted under a microscope. Correlation of the cell numbers and patient's survival time was analyzed using the Statistical Package for the Social Sciences (version 13.0). The numbers of macrophages, mature dendritic cells and cytotoxic T cells were significantly more in the tumor stroma than in the tumor islets. The number of macrophages in the tumor islets was positively associated with patient's survival time, whereas the number of macrophages in the tumor stroma was negatively associated with patient's survival time in both univariate and multivariate analyses. The number of mature dendritic cells in the tumor islets and stroma, tumor islets only, or tumor stroma only was positively associated with patient's survival time in a univariate analysis but not in a multivariate analysis. The number of cytotoxic T cells in the tumor islets and stroma was positively associated with patient's survival time in a univariate analysis but not in a multivariate analysis. The number of cytotoxic T cells in the tumor islets only or stroma

Isolation and characterization of tumor cells from the ascites of ovarian cancer patients: molecular phenotype of chemoresistant ovarian tumors.

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Ardian Latifi

Full Text Available Tumor cells in ascites are a major source of disease recurrence in ovarian cancer patients. In an attempt to identify and profile the population of ascites cells obtained from ovarian cancer patients, a novel method was developed to separate adherent (AD and non-adherent (NAD cells in culture. Twenty-five patients were recruited to this study; 11 chemonaive (CN and 14 chemoresistant (CR. AD cells from both CN and CR patients exhibited mesenchymal morphology with an antigen profile of mesenchymal stem cells and fibroblasts. Conversely, NAD cells had an epithelial morphology with enhanced expression of cancer antigen 125 (CA125, epithelial cell adhesion molecule (EpCAM and cytokeratin 7. NAD cells developed infiltrating tumors and ascites within 12-14 weeks after intraperitoneal (i.p. injections into nude mice, whereas AD cells remained non-tumorigenic for up to 20 weeks. Subsequent comparison of selective epithelial, mesenchymal and cancer stem cell (CSC markers between AD and NAD populations of CN and CR patients demonstrated an enhanced trend in mRNA expression of E-cadherin, EpCAM, STAT3 and Oct4 in the NAD population of CR patients. A similar trend of enhanced mRNA expression of CD44, MMP9 and Oct4 was observed in the AD population of CR patients. Hence, using a novel purification method we demonstrate for the first time a distinct separation of ascites cells into epithelial tumorigenic and mesenchymal non-tumorigenic populations. We also demonstrate that cells from the ascites of CR patients are predominantly epithelial and show a trend towards increased mRNA expression of genes associated with CSCs, compared to cells isolated from the ascites of CN patients. As the tumor cells in the ascites of ovarian cancer patients play a dominant role in disease recurrence, a thorough understanding of the biology of the ascites microenvironment from CR and CN patients is essential for effective therapeutic interventions.

Blood type, ABO genetic variants, and ovarian cancer survival.

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Gabriella D Cozzi

Full Text Available Blood type A and the A1 allele have been associated with increased ovarian cancer risk. With only two small studies published to date, evidence for an association between ABO blood type and ovarian cancer survival is limited.We conducted a retrospective cohort study of Tumor Registry confirmed ovarian cancer cases from the Vanderbilt University Medical Center with blood type from linked laboratory reports and ABO variants from linked Illumina Exome BeadChip data. Associations with overall survival (OS were quantified by hazard ratios (HR and confidence intervals (CI from proportional hazards regression models; covariates included age, race, stage, grade, histologic subtype, and year of diagnosis.ABO phenotype (N = 694 and/or genotype (N = 154 data were available for 713 predominantly Caucasian (89.3% cases. In multivariable models, blood type A had significantly better OS compared to either O (HR: 0.75, 95% CI: 0.60-0.93 or all non-A (HR: 0.77, 95% CI: 0.63-0.94 cases. Similarly, missense rs1053878 minor allele carriers (A2 had better OS (HR: 0.50, 95% CI: 0.25-0.99. Among Caucasians, this phenotype association was strengthened, but the genotype association was attenuated; instead, four variants sharing moderate linkage disequilibrium with the O variant were associated with better OS (HR: 0.62, 95% CI: 0.39-0.99 in unadjusted models.Blood type A was significantly associated with longer ovarian cancer survival in the largest such study to date. This finding was supported by genetic analysis, which implicated the A2 allele, although O related variants also had suggestive associations. Further research on ABO and ovarian cancer survival is warranted.

Preliminary observations and clinical value of N-acetyl resonances in ovarian tumours using in-vivo proton MR spectroscopy at 3T

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Takeuchi, Mayumi; Matsuzaki, Kenji; Harada, Masafumi [University of Tokushima, Department of Radiology, Tokushima (Japan)

2011-12-15

To retrospectively evaluate the clinical significance of N-acetyl resonances at 2 ppm in in-vivo proton magnetic resonance (MR) spectroscopy for distinguishing mucinous and non-mucinous tumours in patients with ovarian masses. MR spectroscopy was performed in patients with pathologically diagnosed ovarian tumours at 3T-MR imaging. Single-voxel MR spectroscopy data were collected from a single square volume of interest that encompassed the ovarian masses. The metabolite resonance peak areas at 2 ppm were quantified relative to unsuppressed water using a software package (LCModel). A total of 32 ovarian lesions in 32 patients were evaluated in this study. High metabolite peak at 2 ppm was observed in all nine mucinous tumours (9.71 +/- 7.46 mM), whereas low peak was observed in 14 of 23 non-mucinous tumours (3.12 +/- 1.42 mM) (p < 0.001). Using a cut off value of 4.45 mM for mucinous tumours had a sensitivity of 89%, specificity of 86%, PPV of 80%, and NPV of 92%. Proton MR spectroscopy with quantitative evaluation of the metabolite at 2 ppm concentration, which may suggest the presence of mucinous material containing N-acetyl mucinous compounds, can provide helpful information in distinguishing mucinous and non-mucinous ovarian tumours. (orig.)

Overexpression of human sperm protein 17 increases migration and decreases the chemosensitivity of human epithelial ovarian cancer cells

International Nuclear Information System (INIS)

Li, Fang-qiu; Han, Yan-ling; Liu, Qun; Wu, Bo; Huang, Wen-bin; Zeng, Su-yun

2009-01-01

Most deaths from ovarian cancer are due to metastases that are resistant to conventional therapies. But the factors that regulate the metastatic process and chemoresistance of ovarian cancer are poorly understood. In the current study, we investigated the aberrant expression of human sperm protein 17 (HSp17) in human epithelial ovarian cancer cells and tried to analyze its influences on the cell behaviors like migration and chemoresistance. Immunohistochemistry and immunocytochemistry were used to identify HSp17 in paraffin embedded ovarian malignant tumor specimens and peritoneal metastatic malignant cells. Then we examined the effect of HSp17 overexpression on the proliferation, migration, and chemoresistance of ovarian cancer cells to carboplatin and cisplatin in a human ovarian carcinoma cell line, HO8910. We found that HSp17 was aberrantly expressed in 43% (30/70) of the patients with primary epithelial ovarian carcinomas, and in all of the metastatic cancer cells of ascites from 8 patients. The Sp17 expression was also detected in the metastatic lesions the same as in ovarian lesions. None of the 7 non-epithelial tumors primarily developed in the ovaries was immunopositive for HSp17. Overexpression of HSp17 increased the migration but decreased the chemosensitivity of ovarian carcinoma cells to carboplatin and cisplatin. HSp17 is aberrantly expressed in a significant proportion of epithelial ovarian carcinomas. Our results strongly suggest that HSp17 plays a role in metastatic disease and resistance of epithelial ovarian carcinoma to chemotherapy

Ovarian cancer mortality and industrial pollution

International Nuclear Information System (INIS)

García-Pérez, Javier; Lope, Virginia; López-Abente, Gonzalo; González-Sánchez, Mario

2015-01-01

We investigated whether there might be excess ovarian cancer mortality among women residing near Spanish industries, according to different categories of industrial groups and toxic substances. An ecologic study was designed to examine ovarian cancer mortality at a municipal level (period 1997–2006). Population exposure to pollution was estimated by means of distance from town to facility. Using Poisson regression models, we assessed the relative risk of dying from ovarian cancer in zones around installations, and analyzed the effect of industrial groups and pollutant substances. Excess ovarian cancer mortality was detected in the vicinity of all sectors combined, and, principally, near refineries, fertilizers plants, glass production, paper production, food/beverage sector, waste treatment plants, pharmaceutical industry and ceramic. Insofar as substances were concerned, statistically significant associations were observed for installations releasing metals and polycyclic aromatic chemicals. These results support that residing near industries could be a risk factor for ovarian cancer mortality. - Highlights: • We studied excess mortality due to ovarian cancer near Spanish industries. • Integrated nested Laplace approximations were used as a Bayesian inference tool. • We found excess ovarian cancer mortality near all industrial groups as a whole. • Risk also was found in towns near industries releasing carcinogens and metals. • Risk was associated with plants releasing polycyclic aromatic chemicals and POPs. - Our results support that residing in the vicinity of pollutant industries could be a risk factor for ovarian cancer mortality

Targeting of follicle stimulating hormone peptide-conjugated dendrimers to ovarian cancer cells

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Modi, Dimple A.; Sunoqrot, Suhair; Bugno, Jason; Lantvit, Daniel D.; Hong, Seungpyo; Burdette, Joanna E.

2014-02-01

Ovarian cancer is the most lethal gynecological malignancy. Current treatment modalities include a combination of surgery and chemotherapy, which often lead to loss of fertility in premenopausal women and a myriad of systemic side effects. To address these issues, we have designed poly(amidoamine) (PAMAM) dendrimers to selectively target the follicle stimulating hormone receptor (FSHR), which is overexpressed by tumorigenic ovarian cancer cells but not by immature primordial follicles and other non-tumorigenic cells. Fluorescein-labeled generation 5 (G5) PAMAM dendrimers were conjugated with the binding peptide domain of FSH (FSH33) that has a high affinity to FSHR. The targeted dendrimers exhibited high receptor selectivity to FSHR-expressing OVCAR-3 cells, resulting in significant uptake and downregulation of an anti-apoptotic protein survivin, while showing minimal interactions with SKOV-3 cells that do not express FSHR. The selectivity of the FSH33-targeted dendrimers was further validated in 3D organ cultures of normal mouse ovaries. Immunostaining of the conjugates revealed their selective binding and uptake by ovarian surface epithelium (OSE) cells that express FSHR, while sparing the immature primordial follicles. In addition, an in vivo study monitoring tissue accumulation following a single intraperitoneal (i.p.) injection of the conjugates showed significantly higher accumulation of FSH33-targeted dendrimers in the ovary and oviduct compared to the non-targeted conjugates. These proof-of-concept findings highlight the potential of these FSH33-targeted dendrimers to serve as a delivery platform for anti-ovarian cancer drugs, while reducing their systemic side effects by preventing nonspecific uptake by the primordial follicles.Ovarian cancer is the most lethal gynecological malignancy. Current treatment modalities include a combination of surgery and chemotherapy, which often lead to loss of fertility in premenopausal women and a myriad of systemic side

Direct and indirect effects of high pCO2 on algal grazing by coral reef herbivores from the Gulf of Aqaba (Red Sea)

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Borell, E. M.; Steinke, M.; Fine, M.

2013-12-01

Grazing on marine macroalgae is a key structuring process for coral reef communities. However, ocean acidification from rising atmospheric CO2 concentrations is predicted to adversely affect many marine animals, while seaweed communities may benefit and prosper. We tested how exposure to different pCO2 (400, 1,800 and 4,000 μatm) may affect grazing on the green alga Ulva lactuca by herbivorous fish and sea urchins from the coral reefs in the northern Gulf of Aqaba (Red Sea), either directly, by changing herbivore behaviour, or indirectly via changes in algal palatability. We also determined the effects of pCO2 on algal tissue concentrations of protein and the grazing-deterrent secondary metabolite dimethylsulfoniopropionate (DMSP). Grazing preferences and overall consumption were tested in a series of multiple-choice feeding experiments in the laboratory and in situ following exposure for 14 d (algae) and 28 d (herbivores). 4,000 μatm had a significant effect on the biochemical composition and palatability of U. lactuca. No effects were observed at 1,800 relative to 400 μatm (control). Exposure of U. lactuca to 4,000 μatm resulted in a significant decrease in protein and increase in DMSP concentration. This coincided with a reduced preference for these algae by the sea urchin Tripneustes gratilla and different herbivorous fish species in situ (Acanthuridae, Siganidae and Pomacanthidae). No feeding preferences were observed for the rabbitfish Siganus rivulatus under laboratory conditions. Exposure to elevated pCO2 had no direct effect on the overall algal consumption by T. gratilla and S. rivulatus. Our results show that CO2 has the potential to alter algal palatability to different herbivores which could have important implications for algal abundance and coral community structure. The fact that pCO2 effects were observed only at a pCO2 of 4,000 μatm, however, indicates that algal-grazer interactions may be resistant to predicted pCO2 concentrations in the

Does methotrexate administration for ectopic pregnancy after in vitro fertilization impact ovarian reserve or ovarian responsiveness?

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Boots, Christina E; Gustofson, Robert L; Feinberg, Eve C

2013-12-01

To evaluate the effects of methotrexate (MTX) on the future fertility of women undergoing IVF by comparing ovarian reserve and ovarian responsiveness in the IVF cycle before and after an ectopic pregnancy (EP) treated with MTX. Retrospective cohort study. Private reproductive endocrinology and infertility practice. Sixty-six women undergoing IVF before and after receiving MTX for an EP. Methotrexate administration and ovarian stimulation. Markers of ovarian reserve (day 3 FSH, antral follicle count), measures of ovarian responsiveness (duration of stimulation, peak E2 level, total dose of gonadotropins, number of oocytes retrieved, fertilization rate), and time from MTX administration to subsequent IVF cycle. There were no differences after MTX administration in body mass index (BMI), FSH, or antral follicle count. A greater dose of gonadotropins was used in the cycle after MTX, but there were no differences in numbers of oocytes retrieved or high quality embryos transferred. As expected, there was a slight increase in age in the subsequent IVF cycle. The pregnancy rates (PR) were comparable to the average PRs within the practice when combining all age groups. Methotrexate remains the first line of therapy for medical management of asymptomatic EP and does not compromise ovarian reserve, ovarian responsiveness, or IVF success in subsequent cycles. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Primary ovarian malignant melanoma

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Kostov Miloš

2010-01-01

Full Text Available Background. Primary ovarian malignant melanoma is extremely rare. It usually appears in the wall of a dermoid cyst or is associated with another teratomatous component. Metastatic primary malignant melanoma to ovary from a primary melanoma elsewhere is well known and has been often reported especially in autopsy studies. Case report. We presented a case of primary ovarian malignant melanoma in a 45- year old woman, with no evidence of extraovarian primary melanoma nor teratomatous component. The tumor was unilateral, macroscopically on section presented as solid mass, dark brown to black color. Microscopically, tumor cells showed positive immunohistochemical reaction for HMB-45, melan-A and S-100 protein, and negative immunoreactivity for estrogen and progesteron receptors. Conclusion. Differentiate metastatic melanoma from rare primary ovarian malignant melanoma, in some of cases may be a histopathological diagnostic problem. Histopathological diagnosis of primary ovarian malignant melanoma should be confirmed by immunohistochemical analyses and detailed clinical search for an occult primary tumor.

MoPCoM Methodology: Focus on Models of Computation

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Koudri, Ali; Champeau, Joël; Le Lann, Jean-Christophe; Leilde, Vincent

Today, developments of Real Time Embedded Systems have to face new challenges. On the one hand, Time-To-Market constraints require a reliable development process allowing quick design space exploration. On the other hand, rapidly developing technology, as stated by Moore's law, requires techniques to handle the resulting productivity gap. In a previous paper, we have presented our Model Based Engineering methodology addressing those issues. In this paper, we make a focus on Models of Computation design and analysis. We illustrate our approach on a Cognitive Radio System development implemented on an FPGA. This work is part of the MoPCoM research project gathering academic and industrial organizations (http://www.mopcom.fr).

Examination of diagnostic features in multiphoton microscopy and optical coherence tomography images of ovarian tumorigenesis in a mouse model

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Watson, Jennifer M.

Ovarian cancer is a deadly disease owing to the non-specific symptoms and suspected rapid progression, leading to frequent late stage detection and poor prognosis. Medical imaging methods such as CT, MRI and ultrasound as well as serum testing for cancer markers have had extremely poor performance for early disease detection. Due to the poor performance of available screening methods, and the impracticality and ineffectiveness of taking tissue biopsies from the ovary, women at high risk for developing ovarian cancer are often advised to undergo prophylactic salpingo-oophorectomy. This surgery results in many side effects and is most often unnecessary since only a fraction of high risk women go on to develop ovarian cancer. Better understanding of the early development of ovarian cancer and characterization of morphological changes associated with early disease could lead to the development of an effective screening test for women at high risk. Optical imaging methods including optical coherence tomography (OCT) and multiphoton microscopy (MPM) are excellent tools for studying disease progression owing to the high resolution and depth sectioning capabilities. Further, these techniques are excellent for optical biopsy because they can image in situ non-destructively. In the studies described in this dissertation OCT and MPM are used to identify cellular and tissue morphological changes associated with early tumor development in a mouse model of ovarian cancer. This work is organized into three specific aims. The first aim is to use the images from the MPM phenomenon of second harmonic generation to quantitatively examine the morphological differences in collagen structure in normal mouse ovarian tissue and mouse ovarian tumors. The second aim is to examine the differences in endogenous two-photon excited fluorescence in normal mouse ovarian tissue and mouse ovarian tumors. The third and final aim is to identify changes in ovarian microstructure resulting from early

Does the peritumoral stroma of basal cell carcinoma recapitulate the follicular connective tissue sheath?

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Sellheyer, Klaus; Krahl, Dieter

2011-07-01

There are compelling embryologic and anatomic relationships within adnexal tumors. However, these are mostly perceived within the epithelial component while the stromal component of the tumors is frequently overlooked. In postnatal skin, nestin is almost exclusively expressed in the perifollicular mesenchyme. This study examines the expression of this neuroepithelial stem cell protein in trichoblastoma/trichoepithelioma and in basal cell carcinoma (BCC), which is increasingly being viewed as follicular in nature. We employed standard immunohistochemical methods with three different antibodies to examine the expression of nestin in 25 BCCs and compared the staining pattern with that of 7 trichoblastomas and 11 trichoepitheliomas. Nestin is expressed in the peritumoral stroma of all tumors examined and is limited to the immediate layer of mesenchymal cells surrounding the tumor epithelium. In BCC, nestin-immunoreactive cells are found as a sheath of thin, spindled fibroblasts, while reactive cells are plump in trichoepitheliomas/trichoblastomas. We postulate that the peritumoral stroma of BCC imitates the perifollicular connective tissue sheath, while in contrast that of trichoepithelioma/trichoblastoma is similar to the papillary and immediate peripapillary follicular mesenchyme. Further functional and animal experimental studies are needed to test this hypothesis. Copyright © 2011 John Wiley & Sons A/S.

Novel protein phosphorylation site identification in spinach stroma membranes by titanium dioxide microcolumns and tandem mass spectrometry

DEFF Research Database (Denmark)

Rinalducci, Sara; Larsen, Martin Røssel; Mohammed, Shabaz

2006-01-01

In this work, spinach stroma membrane, instead of thylakoid, has been investigated for the presence of phosphorylated proteins. We identified seven previously unknown phosphorylation sites by taking advantage of TiO(2) phosphopeptides enrichment coupled to mass spectrometric analysis. Upon...

Seasonal variation of air-sea CO2 fluxes in the Terra Nova Bay of the Ross Sea, Antarctica, based on year-round pCO2 observations

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Zappa, C. J.; Rhee, T. S.; Kwon, Y. S.; Choi, T.; Yang, E. J.; Kim, J.

2017-12-01

The polar oceans are rapidly changing in response to climate variability. In particular, augmented inflow of glacial melt water and shrinking sea-ice extent impacts the polar coastal oceans, which may in turn shift the biogeochemistry into an unprecedented paradigm not experienced previously. Nonetheless, most research in the polar oceans is limited to the summer season. Here, we present the first direct observations of ocean and atmospheric pCO2 measured near the coast of Terra Nova Bay in the Ross Sea, Antarctica, ongoing since February, 2015 at Jang Bogo Station. The coastal area is covered by landfast sea-ice from spring to fall while continually exposed to the atmosphere during summer season only. The pCO2 in seawater swung from 120 matm in February to 425 matm in early October. Although sea-ice still covers the coastal area, pCO2 already started decreasing after reaching the peak in October. In November, the pCO2 suddenly dropped as much as 100 matm in a week. This decrease of pCO2 continued until late February when the sea-ice concentration was minimal. With growing sea ice, the pCO2 increased logarithmically reaching the atmospheric concentration in June/July, depending on the year, and continued to increase until October. Daily mean air-sea CO2 flux in the coastal area widely varied from -70 mmol m-2 d-1 to 20 mmol m-2 d-1. Based on these observations of pCO2 in Terra Nova Bay, the annual uptake of CO2 is 8 g C m-2, estimated using the fraction of sea-ice concentration estimated from AMSR2 microwave emission imagery. Extrapolating to all polynyas surrounding Antarctica, we expect the annual uptake of 8 Tg C in the atmosphere. This is comparable to the amount of CO2 degassed into the atmosphere south of the Antarctic Polar Front (62°S).

Acclimation of bloom-forming and perennial seaweeds to elevated pCO2 conserved across levels of environmental complexity.

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Xu, Dong; Schaum, Charlotte-Elisa; Lin, Fan; Sun, Ke; Munroe, James R; Zhang, Xiao W; Fan, Xiao; Teng, Lin H; Wang, Yi T; Zhuang, Zhi M; Ye, Naihao

2017-11-01

Macroalgae contribute approximately 15% of the primary productivity in coastal marine ecosystems, fix up to 27.4 Tg of carbon per year, and provide important structural components for life in coastal waters. Despite this ecological and commercial importance, direct measurements and comparisons of the short-term responses to elevated pCO 2 in seaweeds with different life-history strategies are scarce. Here, we cultured several seaweed species (bloom forming/nonbloom forming/perennial/annual) in the laboratory, in tanks in an indoor mesocosm facility, and in coastal mesocosms under pCO 2 levels ranging from 400 to 2,000 μatm. We find that, across all scales of the experimental setup, ephemeral species of the genus Ulva increase their photosynthesis and growth rates in response to elevated pCO 2 the most, whereas longer-lived perennial species show a smaller increase or a decrease. These differences in short-term growth and photosynthesis rates are likely to give bloom-forming green seaweeds a competitive advantage in mixed communities, and our results thus suggest that coastal seaweed assemblages in eutrophic waters may undergo an initial shift toward communities dominated by bloom-forming, short-lived seaweeds. © 2017 John Wiley & Sons Ltd.

Polycystic Ovary Syndrome, Oligomenorrhea, and Risk of Ovarian Cancer Histotypes: Evidence from the Ovarian Cancer Association Consortium.

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Harris, Holly R; Babic, Ana; Webb, Penelope M; Nagle, Christina M; Jordan, Susan J; Risch, Harvey A; Rossing, Mary Anne; Doherty, Jennifer A; Goodman, Marc T; Modugno, Francesmary; Ness, Roberta B; Moysich, Kirsten B; Kjær, Susanne K; Høgdall, Estrid; Jensen, Allan; Schildkraut, Joellen M; Berchuck, Andrew; Cramer, Daniel W; Bandera, Elisa V; Wentzensen, Nicolas; Kotsopoulos, Joanne; Narod, Steven A; Phelan, Catherine M; McLaughlin, John R; Anton-Culver, Hoda; Ziogas, Argyrios; Pearce, Celeste L; Wu, Anna H; Terry, Kathryn L

2018-02-01

Background: Polycystic ovary syndrome (PCOS), and one of its distinguishing characteristics, oligomenorrhea, have both been associated with ovarian cancer risk in some but not all studies. However, these associations have been rarely examined by ovarian cancer histotypes, which may explain the lack of clear associations reported in previous studies. Methods: We analyzed data from 14 case-control studies including 16,594 women with invasive ovarian cancer ( n = 13,719) or borderline ovarian disease ( n = 2,875) and 17,718 controls. Adjusted study-specific ORs were calculated using logistic regression and combined using random-effects meta-analysis. Pooled histotype-specific ORs were calculated using polytomous logistic regression. Results: Women reporting menstrual cycle length >35 days had decreased risk of invasive ovarian cancer compared with women reporting cycle length ≤35 days [OR = 0.70; 95% confidence interval (CI) = 0.58-0.84]. Decreased risk of invasive ovarian cancer was also observed among women who reported irregular menstrual cycles compared with women with regular cycles (OR = 0.83; 95% CI = 0.76-0.89). No significant association was observed between self-reported PCOS and invasive ovarian cancer risk (OR = 0.87; 95% CI = 0.65-1.15). There was a decreased risk of all individual invasive histotypes for women with menstrual cycle length >35 days, but no association with serous borderline tumors ( P heterogeneity = 0.006). Similarly, we observed decreased risks of most invasive histotypes among women with irregular cycles, but an increased risk of borderline serous and mucinous tumors ( P heterogeneity ovarian cancer risk differentially based on histotype. Impact: These results highlight the importance of examining ovarian cancer risk factors associations by histologic subtype. Cancer Epidemiol Biomarkers Prev; 27(2); 174-82. ©2017 AACR . ©2017 American Association for Cancer Research.

Progress in understanding human ovarian folliculogenesis and its implications in assisted reproduction.

Science.gov (United States)

Yang, Dong Zi; Yang, Wan; Li, Yu; He, Zuanyu

2013-02-01

To highlight recent progress in understanding the pattern of follicular wave emergence of human menstrual cycle, providing a brief overview of the new options for human ovarian stimulation and oocyte retrieval by making full use of follicular physiological waves of the patients either with normal or abnormal ovarian reserve. Literature review and editorial commentary. There has been increasing evidence to suggest that multiple (two or three) antral follicular waves are recruited during human menstrual cycle. The treatment regimens designed based on the theory of follicular waves, to promote increased success with assisted reproduction technology (ART) and fertility preservation have been reported. These new options for human ovarian stimulation and oocyte retrieval by making full use of follicular waves of the patients either with normal or abnormal ovarian reserve lead to new thinking about the standard protocols in ART and challenge the traditional theory that a single wave of antral follicles grows only during the follicular phase of the menstrual cycle. The understanding of human ovarian folliculogenesis may have profound implications in ART and fertility preservation. Further studies are needed to evaluate the optimal regimens in ART based on the theory of follicular waves and to identify non-invasive markers for predicting the outcome and the potential utilities of follicles obtained from anovulatory follicular waves in ART.

Novel genetic variants in miR-191 gene and familial ovarian cancer

International Nuclear Information System (INIS)

Shen, Jie; DiCioccio, Richard; Odunsi, Kunle; Lele, Shashikant B; Zhao, Hua

2010-01-01

Half of the familial aggregation of ovarian cancer can't be explained by any known risk genes, suggesting the existence of other genetic risk factors. Some of these unknown factors may not be traditional protein encoding genes. MicroRNA (miRNA) plays a critical role in tumorigenesis, but it is still unknown if variants in miRNA genes lead to predisposition to cancer. Considering the fact that miRNA regulates a number of tumor suppressor genes (TSGs) and oncogenes, genetic variations in miRNA genes could affect the levels of expression of TSGs or oncogenes and, thereby, cancer risk. To test this hypothesis in familial ovarian cancer, we screened for genetic variants in thirty selected miRNA genes, which are predicted to regulate key ovarian cancer genes and are reported to be misexpressed in ovarian tumor tissues, in eighty-three patients with familial ovarian cancer. All of the patients are non-carriers of any known BRCA1/2 or mismatch repair (MMR) gene mutations. Seven novel genetic variants were observed in four primary or precursor miRNA genes. Among them, three rare variants were found in the precursor or primary precursor of the miR-191 gene. In functional assays, the one variant located in the precursor of miR-191 resulted in conformational changes in the predicted secondary structures, and consequently altered the expression of mature miR-191. In further analysis, we found that this particular variant exists in five family members who had ovarian cancer. Our findings suggest that there are novel genetic variants in miRNA genes, and those certain genetic variants in miRNA genes can affect the expression of mature miRNAs and, consequently, might alter the regulation of TSGs or oncogenes. Additionally, the variant might be potentially associated with the development of familial ovarian cancer

Neoadjuvant Chemotherapy for Advanced Epithelial Ovarian Cancer

International Nuclear Information System (INIS)

Avendano Juan; Buitrago, Giancarlo; Ramos, Pedro; Suescun Oscar

2010-01-01

Objective: To describe the experience at the National Cancer Institute (NCI) on the use of neoadjuvant chemotherapy as primary treatment for epithelial ovarian cancer among patients in stages IIIC and IV. Methods: We conducted a descriptive retrospective study (case series type) of patients diagnosed with epithelial ovarian cancer in stages IIIC and IV, treated at the NCI from January 1, 2003 to December 31,2006, who underwent neoadjuvant chemotherapy as primary treatment. Demographic characteristics and clinical outcomes are described. Results: Seventeen patients who fulfilled the above mentioned criteria were selected. Once neoadjuvant chemotherapy ended, 5 patients (29.4%) achieved complete or partial clinical response; 4 (23.8%) remained in stable condition, and 8 (47.6%) showed signs of progressive illness. Interval debulking surgery was performed on objective response patients. Maximum cytoreduction was achieved in 5 patients (100%); first relapse was reported at month 18 of follow-up; 2 disease-free survivors were identified in December, 2007; 8 (49%) reported some degree of non-severe chemotherapy-related toxicity. No mortality was related to chemotherapy, no post surgical complications were observed and no patient required advanced support management. Conclusions: Neoadjuvant chemotherapy, followed by optimal interval debulking surgery among selected patients, can be an alternative treatment for advanced epithelial ovarian cancer among women with irresecability or the critically ill. Further studies with improved design are required to confirm these findings.

Interlobular and intralobular mammary stroma: Genotype may not reflect phenotype

Directory of Open Access Journals (Sweden)

Meltzer PS

2008-08-01

Full Text Available Abstract Background The normal growth and function of mammary epithelial cells depend on interactions with the supportive stroma. Alterations in this communication can lead to the progression or expansion of malignant growth. The human mammary gland contains two distinctive types of fibroblasts within the stroma. The epithelial cells are surrounded by loosely connected intralobular fibroblasts, which are subsequently surrounded by the more compacted interlobular fibroblasts. The different proximity of these fibroblasts to the epithelial cells suggests distinctive functions for these two subtypes. In this report, we compared the gene expression profiles between the two stromal subtypes. Methods Fresh normal breast tissue was collected from reduction mammoplasty patients and immediately placed into embedding medium and frozen on dry ice. Tissue sections were subjected to laser capture microscopy to isolate the interlobular from the intralobular fibroblasts. RNA was prepared and subjected to microarray analysis using the Affymetrix Human Genome U133 GeneChip®. Data was analyzed using the Affy and Limma packages available from Bioconductor. Findings from the microarray analysis were validated by RT-PCR and immunohistochemistry. Results No statistically significant difference was detected between the gene expression profiles of the interlobular and intralobular fibroblasts by microarray analysis and RT-PCR. However, for some of the genes tested, the protein expression patterns between the two subtypes of fibroblasts were significantly different. Conclusion This study is the first to report the gene expression profiles of the two distinct fibroblast populations within the human mammary gland. While there was no significant difference in the gene expression profiles between the groups, there was an obvious difference in the expression pattern of several proteins tested. This report also highlights the importance of studying gene regulation at both the

Clomiphene citrate versus high doses of gonadotropins for in vitro fertilisation in women with compromised ovarian reserve: a randomised controlled non-inferiority trial

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Ragni Guido

2012-12-01

Full Text Available Abstract Background The aim of the present randomised controlled non-inferiority trial is to test whether in women with compromised ovarian reserve requiring in vitro fertilisation, a protocol of ovarian stimulation using exclusively clomiphene citrate performs similarly to a regimen with high doses of gonadotropins. Methods Women with day 3 serum FSH > 12 IU/ml on at least two occasions or previous poor response to hyper-stimulation were recruited at four Italian infertility units. Selected women were allocated to clomiphene citrate 150 mg/day from day 3 to day 7 of the cycle (n=145 or to a short protocol with GnRH agonist 0.1 mg and recombinant FSH 450 IU daily (n=146. They were randomised by means of a computer-generated list into two groups. The study was not blinded. The main outcome of the study was the delivery rate per started cycle. Results The study was interrupted after the scheduled two years of recruitment before reaching the sample size. 148 women were allocated to clomiphene citrate and 156 to the short protocol with high doses of gonadotropins; 124 and 125 participants were analysed in the groups, respectively. Women allocated to high doses of gonadotropins retrieved more oocytes and had a higher probability to perform embryo-transfer. However, the chances of success were similar. The delivery rate per started cycle in women receiving clomiphene citrate and high-dose gonadotropins was 3% (n=5 and 5% (n=7, respectively (p=0.77. The mean estimated cost per delivery in the two groups was 81,294 and 113,107 Euros, respectively. No side-effects or adverse events were observed. Conclusions In women with compromised ovarian reserve selected for in vitro fertilisation, ovarian stimulation with clomiphene citrate or high-dose gonadotropins led to similar chances of pregnancy but the former is less expensive. Trial registration Trial registered on http://www.clinicaltrials.gov (NCT01389713

Mucinous cystadenoma of the ovary with stromal luteinization and hilar cell hyperplasia during pregnancy.

Science.gov (United States)

Pascal, R R; Grecco, L A

1988-02-01

A 32-year-old woman was delivered of a healthy, full-term infant by cesarean section, at which time a large ovarian cyst was removed. The cyst proved to be a mucinous cystadenoma with prominent luteinization of the stroma subtending the epithelium and with numerous foci of hyperplastic Leydig cells in the cyst wall and ovarian hilum. These hormonally induced changes must be recognized in order to avoid mistaking them for invasive epithelial components.

Persistent ovarian masses and pregnancy outcomes.

Science.gov (United States)

Goh, William A; Rincon, Monica; Bohrer, Justin; Tolosa, Jorge E; Sohaey, Roya; Riaño, Rene; Davis, James; Zalud, Ivica

2013-07-01

To determine if persistent ovarian masses in pregnancy are associated with increased adverse outcomes. This is a retrospective cohort of 126 pregnant women with a persistent ovarian mass measuring 5 cm or greater who delivered at two university hospitals between 2001 and 2009. Maternal outcomes included gestational age (GA) at diagnosis, delivery and surgery as well as miscarriage, preterm birth (PTB), ovarian torsion and hospital admission for pain. Neonatal outcomes included birth weight, respiratory distress syndrome (RDS), intra-ventricular hemorrhage (IVH), death and sepsis. A total of 1225 ovarian masses were identified (4.9%) in 24,868 patients. A persistent ovarian mass was found in 0.7%. Average GA at diagnosis was 17.8 weeks. Miscarriage rate was 3.3%. Average GA at delivery was 37.9 weeks. Of the patients, 8.5% had ovarian torsion, 10.3% had admission for pain and 9.3% had PTBs. The mean cesarean delivery rate was 46.3%. The average neonatal weight was 3273 g. There was one neonatal death in this cohort. The rate of RDS was 2.8%, IVH 0.9% and neonatal sepsis 1.9%. The most common surgical pathologic diagnosis was dermoids (37.6%). No overt malignancies were seen. A persistent ovarian mass in pregnancy does not confer an increased risk of adverse pregnancy outcomes.

MRI of ovarian torsion: Correlation of imaging features with the presence of perifollicular hemorrhage and ovarian viability

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Petkovska, Iva, E-mail: dr.iva.petkovska@gmail.com [Department of Medical Imaging, University of Arizona College of Medicine, Tucson, AZ (United States); Duke, Eugene; Martin, Diego R.; Irani, Zeenia [Department of Medical Imaging, University of Arizona College of Medicine, Tucson, AZ (United States); Geffre, Christopher P. [Department of Pathology, University of Arizona College of Public Health, Tucson, AZ (United States); Cragun, Janiel M. [Department of Obstetrics & Gynecology, University of Arizona College of Medicine, Tucson, AZ (United States); Costello, James R.; Arif-Tiwari, Hina; Czeyda-Pommersheim, Ferenc; Udayasankar, Unni [Department of Medical Imaging, University of Arizona College of Medicine, Tucson, AZ (United States); Kalb, Bobby, E-mail: bkalb@radiology.arizona.edu [Department of Medical Imaging, University of Arizona College of Medicine, Tucson, AZ (United States)

2016-11-15

Purpose: The purpose of our study is to test for: (a) correlation between the presence of a perifollicular T2-hypointense rim on MRI with the presence of perifollicular hemorrhage on histology; and (b) correlation between this finding and diminished ovarian viability after intra-operative detorsion. Methods and materials: Our IRB-approved, retrospective study evaluated 780 patients between August 2012 and February 2016 with ovarian torsion as a diagnostic consideration on the emergency department note. Patients were included if they had preoperative MRI and intraoperatively confirmed case of ovarian torsion. MRIs were retrospectively reviewed for presence of perifollicular T2 hypointense rim in the torsed ovary. Two arms of analysis were performed: (a) assessment of perifollicular hemorrhage on histological exam; and (b) assessment of ovarian viability after intra-operative detorsion. Sensitivity, specificity, positive predictive value, and negative predictive value of MRI for predicting ovarian viability in the setting of torsion was performed. κ test assessed level of agreement between readers. Results: 24 patients included in one of the two arms; 20 in viability analysis and 12 in perifollicular hemorrhage analysis (8 in both). The presence of T2-hypointense rim on MRI demonstrated 88.9% sensitivity and 66.7% specificity for the diagnosis of perifollicular hemorrhage on histology, and 91.7% sensitivity and 100% specificity for predicting intraoperative viability. Conclusion: The presence of a perifollicular T2 hypointense rim on MRI in the setting of ovarian torsion correlates with perifollicular hemorrhage on histopathologic exam, and may also be a useful predictor of ovarian viability in patients presenting with ovarian torsion.

Multiple metastases from ovarian cancer

African Journals Online (AJOL)

Ovarian cancer affects women in the age group >60 years much ... ovarian cancer presenting with liver and thoracic vertebral metastases 4 months after ... manifested by parenchymal liver or lung ... categorised as stage Ic as per International.

Blood type, ABO genetic variants, and ovarian cancer survival

Science.gov (United States)

Cozzi, Gabriella D.; Levinson, Rebecca T.; Toole, Hilary; Snyder, Malcolm-Robert; Deng, Angie; Crispens, Marta A.; Khabele, Dineo; Beeghly-Fadiel, Alicia

2017-01-01

Objective Blood type A and the A1 allele have been associated with increased ovarian cancer risk. With only two small studies published to date, evidence for an association between ABO blood type and ovarian cancer survival is limited. Methods We conducted a retrospective cohort study of Tumor Registry confirmed ovarian cancer cases from the Vanderbilt University Medical Center with blood type from linked laboratory reports and ABO variants from linked Illumina Exome BeadChip data. Associations with overall survival (OS) were quantified by hazard ratios (HR) and confidence intervals (CI) from proportional hazards regression models; covariates included age, race, stage, grade, histologic subtype, and year of diagnosis. Results ABO phenotype (N = 694) and/or genotype (N = 154) data were available for 713 predominantly Caucasian (89.3%) cases. In multivariable models, blood type A had significantly better OS compared to either O (HR: 0.75, 95% CI: 0.60–0.93) or all non-A (HR: 0.77, 95% CI: 0.63–0.94) cases. Similarly, missense rs1053878 minor allele carriers (A2) had better OS (HR: 0.50, 95% CI: 0.25–0.99). Among Caucasians, this phenotype association was strengthened, but the genotype association was attenuated; instead, four variants sharing moderate linkage disequilibrium with the O variant were associated with better OS (HR: 0.62, 95% CI: 0.39–0.99) in unadjusted models. Conclusions Blood type A was significantly associated with longer ovarian cancer survival in the largest such study to date. This finding was supported by genetic analysis, which implicated the A2 allele, although O related variants also had suggestive associations. Further research on ABO and ovarian cancer survival is warranted. PMID:28448592

Environmental and developmental origins of ovarian reserve.

Science.gov (United States)

Richardson, M C; Guo, M; Fauser, B C J M; Macklon, N S

2014-01-01

BACKGROUND Oocyte number is established early in life before a gradual loss of this ovarian reserve during reproductive life until oocyte availability becomes limiting at the menopause. Although there is a large genetic component to the ovarian reserve achieved before birth, other influences including the maternal endocrine and nutritional milieu, and environmental factors may represent important developmental determinants. Environmental and nutritional factors may also modify the downward trajectory of ovarian reserve in adult life. The combination of these early and later life influences has the potential to lead to diminished ovarian reserve, compromising fertility in later reproductive years and altering age at natural menopause. METHODS Literature searches of the ISI Web of Knowledge database were carried out using the main terms 'ovarian reserve' and 'menopause AND age' in conjunction with a range of other terms encompassing a variety of factors with potential effects on ovarian reserve. The various searches were inspected manually and the relevant papers selected for critical analysis and interpretation. RESULTS Evidence was identified supporting the view that elevated prenatal androgens have an adverse effect on the early establishment of ovarian reserve, although the implications for ovarian reserve in the polycystic ovary syndrome (which may also be programmed through prenatal androgen exposure) remain uncertain. Recent evidence is cited suggesting that effects of maternal nutrient restriction on ovarian reserve may also involve changes in prenatal androgen exposure. A general rationale is developed through examination of evidence which emphasizes the roles of the aryl hydrocarbon receptor (AHR) and the estrogen receptor (ER) systems in ovarian reserve modulation. Because of their similarity to the natural ligands, many environmental compounds have the ability to bind to these receptors (albeit at lower affinities) and thereby have the potential to

Ovarian function and growth performance of indigenous goats in Malaysia

International Nuclear Information System (INIS)

Adnan, S.; Jainudeen, M.R.; Alimon, A.R.; Sharifuddin, W.

1991-01-01

Ovarian activity and factors influencing it were studied in the Malaysian indigenous goat using plasma progesterone radioimmunoassay technique and laparoscopic examination of the ovaries. Laparoscopy, complemented by progesterone assay, was found to be a reliable technique for diagnosing the presence of corpora lutea (CL). However, progesterone assay had the limitation that it could not detect the presence of early developing CL. Two morphological types of CL were observed, either protruding or embedded. The mean plasma progesterone concentrations for pregnant, dioestrous and postpartum anoestrous goats were 4.8 ± 0.72, 4.7 ± 1.60 and <0.7 ng/mL respectively. An inhibitory effect of suckling on the resumption of postpartum ovarian activity was also observed. Removal of kids tended to hasten the onset of postpartum ovarian activity. Continuous confinement of goats was suspected to contribute to conception failure and non-regression of the CL. Kids fed improved diet showed higher average daily weight gain than those suckling their dams. (author). 12 refs, 3 figs, 7 tabs

Premature ovarian failure and ovarian autoimmunity

NARCIS (Netherlands)

J.A. Schoemaker (Joop); H.A. Drexhage (Hemmo); A. Hoek (Annemieke)

1997-01-01

textabstractPremature ovarian failure (POF) is defined as a syndrome characterized by menopause before the age of 40 yr. The patients suffer from anovulation and hypoestrogenism. Approximately 1% of women will experience menopause before the age of 40 yr. POF is a

Ovarian neoplasms in atomic bomb survivors

International Nuclear Information System (INIS)

Tokuoka, Shoji

1986-01-01

A recent pathological and epidemiological study on females with ovarian neoplasms among the Radiation Effects Research Foundation (RERF) Life Span Study (LSS) Extended Sample ascertained 194 malignant and 106 benign ovarian tumor cases which had occurred during the period 1950 - 80. Of the 194 cases of ovarian cancer, 128 (66 %) were reviewed microscopically and the age-adjusted incidence of ovarian cancer revealed a statistically significant linear increase with increasing exposure dose, both in microscopically reviewed and in all cases. The radiation-related excess of ovarian cancer appeared to be highest in women less than 20 years of age when exposed, with these women having the longest latent period for tumor development, compared to the older age groups. The histological distribution of cancer types among exposed individuals appeared not very different from that seen in the general population. The analysis of 106 autopsy subjects with benign ovarian tumors, of which 89 were reviewed microscopically, depicted a trend of increasing radiation-related tumor excess with increasing exposure dose among exposed cases, though the trend is not statistically significant when observation was limited to microscopically reviewed subjects. The histological distribution of benign tumor types among exposed cases appeared not very different from that seen in the general population. The findings are consistent with a hypothesis that radiation-injured ovaries in association with secondary excess of gonadotrophic hormones are important causative factors in the development of ovarian tumors, which has been suggested by experimental findings concerning the induction of ovarian tumors by ionizing radiation and by a recent analysis of breast carcinogenesis in exposed females of Hiroshima and Nagasaki. (author)

The postmenopausal ovary as an androgen-producing gland; hypothesis on the etiology of endometrial cancer

NARCIS (Netherlands)

Jongen, V. H. W. M.; Sluijmer, A. V.; Heineman, M. J.

2002-01-01

Postmenopausal estrogens originate from the peripheral conversion of androgens, which are produced by the adrenal glands and the ovaries. Estrogens are considered to contribute to the neoplastic development of endometrium. Hyperplasia of ovarian stroma is associated with an increased androgen

Malignant tumour stroma gonads Sertoli-Leydig:a communication clinic case and bibliographic review

International Nuclear Information System (INIS)

Krygier Waltier, G.; Rodriguez Lemes, R.; Carlevaro Elizondo, T.

1995-01-01

The malignant tumors of the stroma gonads represent 0.2% of all the tumors of the testicle, and they are almost exclusive of the relatively refractory to the radiotherapy and the chemotherapy, and the medium survive of the illness is of two years. it presents a clinical case of tumour to cells of Sertoli-Leydig in a 45 year-old man that heI consulted for sterility . A review of the literature it is made for finish [es

Ovarian activity before and after gonadal suppression by GnRH-a in patients with polycystic ovary syndrome, hyperandrogenism, hyperinsulinism and acanthosis nigricans Atividade ovariana antes e após supressão gonadal por GnRH-a em pacientes com síndrome dos ovários policísticos, hiperandrogenismo, hiperinsulinismo e acantose nigricante

Directory of Open Access Journals (Sweden)

E.L.A. Motta

1998-06-01

Full Text Available OBJECTIVE: To investigate the ovarian activity before and after gonadal suppression with GnRH-analog in patients with PCO, hyperandrogenism, hyperinsulinism and acanthosis nigricans. DESIGN: Controlled clinical study. SETTING: Tertiary academic medical center. PATIENTS: Six patients with clinical findings of PCO, hirsutism and acanthosis nigricans. INTERVENTIONS: Morning blood samples in the follicular phase to determine the steroid levels, glucose and insulin curve, comparing to a control group. Administration for 2 consecutive months of a GnRH-analog, comparing, in the study group, the free testosterone levels before and after ovarian suppression. MAIN OUTCOME MEASURE: Determination of insulin levels in PCO, hirsutism and acanthotic patients and the free-testosterone levels before and after gonadal suppression. RESULTS: Insulin levels were significantly higher in the study group when compared to normal women during the glycemic test. We also found a significant decrease in the free-testosterone levels after 2 months of gonadal suppression with GnRH-analog when compared to the initial time. CONCLUSIONS: Patients with PCO, hirsutism and acanthosis nigricans present high levels of insulin, suggesting an ovarian hyperesponsiveness, which is not sustained when gonadotrophic blockage was achieved.OBJETIVO: Investigar a atividade ovariana antes e após a supressão gonadal com análogo de GnRH em pacientes com síndrome dos ovários policísticos (SOP, hiperandrogenismo, hiperinsulinismo e acantose nigricante. DESENHO: Estudo clínico prospectivo. LOCAL: Centro médico-acadêmico nível terciário. PACIENTES: Seis pacientes com sinais clínicos de SOP, hirsutismo e acantose nigricante. INTERVENÇÕES: Colheita de amostras sanguíneas matinais na fase folicular para determinar os valores séricos de esteróides, curva glicêmica e insulínica, comparando esta última à do grupo controle. Administração por dois meses consecutivos de análogo de Gn

Ovarian cancer immunotherapy: opportunities, progresses and challenges

Directory of Open Access Journals (Sweden)

Stevens Richard

2010-02-01

Full Text Available Abstract Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer. We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strategies. Finally, we will summarize our own experience on the use of patient-specific tumor-derived heat shock protein-peptide complex for the treatment of advanced ovarian cancer.

Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial

Science.gov (United States)

Jacobs, Ian J; Menon, Usha; Ryan, Andy; Gentry-Maharaj, Aleksandra; Burnell, Matthew; Kalsi, Jatinderpal K; Amso, Nazar N; Apostolidou, Sophia; Benjamin, Elizabeth; Cruickshank, Derek; Crump, Danielle N; Davies, Susan K; Dawnay, Anne; Dobbs, Stephen; Fletcher, Gwendolen; Ford, Jeremy; Godfrey, Keith; Gunu, Richard; Habib, Mariam; Hallett, Rachel; Herod, Jonathan; Jenkins, Howard; Karpinskyj, Chloe; Leeson, Simon; Lewis, Sara J; Liston, William R; Lopes, Alberto; Mould, Tim; Murdoch, John; Oram, David; Rabideau, Dustin J; Reynolds, Karina; Scott, Ian; Seif, Mourad W; Sharma, Aarti; Singh, Naveena; Taylor, Julie; Warburton, Fiona; Widschwendter, Martin; Williamson, Karin; Woolas, Robert; Fallowfield, Lesley; McGuire, Alistair J; Campbell, Stuart; Parmar, Mahesh; Skates, Steven J

2016-01-01

Summary Background Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality. Methods In this randomised controlled trial, we recruited postmenopausal women aged 50–74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer-generated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032. Findings Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202 638 women: 50 640 (25·0%) to MMS, 50 639 (25·0%) to USS, and 101 359 (50·0%) to no screening. 202 546 (>99·9%) women were eligible for analysis: 50 624 (>99·9%) women in the MMS group, 50 623 (>99·9%) in the USS group, and 101 299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345 570 MMS and 327 775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0–12·0), we diagnosed ovarian cancer in

Targeted Therapies in Epithelial Ovarian Cancer

Directory of Open Access Journals (Sweden)

Jurjees Hasan

2010-02-01

Full Text Available Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer.

Targeted Therapies in Epithelial Ovarian Cancer

Energy Technology Data Exchange (ETDEWEB)

Dean, Emma; El-Helw, Loaie; Hasan, Jurjees, E-mail: jurjees.hasan@christie.nhs.uk [Christie Hospital NHS Foundation Trust / Wilmslow Road, Manchester, M20 4BX (United Kingdom)

2010-02-23

Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer.

Ovarian chocolate cysts

International Nuclear Information System (INIS)

Sugimura, Kazuro; Ishida, Tetsuya; Takemori, Masayuki; Kitagaki, Hajime; Tanaka, Yutaka; Yamasaki, Katsuhito; Shimizu, Tadafumi; Kono, Michio.

1988-01-01

Accurate preoperative staging of ovarian chocolate cysts is very important because recent hormonal therapy has been effective in low stage patients. However, it has been difficult to assess the preoperative stage of ovarian chocolate cysts. We evaluated the diagnostic potential of MRI in preoperative staging of 15 overian chocolate cysts. It was well known that the older the ovarian chocolate cyst was the more iron content it had. We examined the iron contents effect on T1 and T2 relaxation times in surgically confirmed chocolate cysts (stage II: 3 cases, stage III: 3 cases and stage IV: 9 cases by AFS classification, 1985) employing the 0.15-T MR system and 200 MHz spectrometer. There was a positive linear relation between T1 of the lesion using the MR system (T1) and T1 of the resected contents using the spectrometer (sp-T1); r = 0.93. The same relation was revealed between T2 and sp-T2; r = 0.87. It was indicated that T1 and T2 using the MR system was accurate. There was a negative linear relation between T1 and the iron contents ( r = -0.81) but no relation between T2 and the iron contents. T1 was 412 ± 91 msec for stage II, 356 ± 126 msec for stage III and 208 ± 30 msec for stage IV. T1 for stage IV was shorter than that for stage II and III, statistically significant differences were noted (p < 0.05). Thus, T1 was useful in differentiating a fresh from an old ovarian chocolate cyst. We concluded that T1 relaxation time using the MR system was useful for the staging of an ovarian chocolate cyst without surgery. (author)