CENTRAL SEROUS CHORIORETINOPATHY IN POSTMENOPAUSAL WOMEN RECEIVING EXOGENOUS TESTOSTERONE.

PubMed

Conway, Mandi D; Noble, Jason A; Peyman, Gholam A

2017-01-01

Central serous chorioretinopathy (CSR) is a serous detachment of the neurosensory retina commonly associated with male sex, Type-A personality and corticosteroid use. Exogenous administration of androgens and development of CSR in men has been reported. Only one case of CSR in a postmenopausal woman receiving exogenous androgen therapy has been reported. The authors describe three cases of chronic CSR in postmenopausal women receiving exogenous testosterone therapy. Diagnosis was based on characteristic clinical, fluorescein angiographic, and optical coherence tomography findings. The three women were being treated with exogenous testosterone and progesterone therapy for symptoms of menopause and libido loss. Average age at presentation was 54.7 years (53-56 years), average duration of exogenous androgen use was 61 months (36-87 months), with average 19.7-month follow-up. Resolution of symptoms seemed correlated with cessation of androgen use despite treatment with oscillatory photodynamic therapy and intravitreal pharmacotherapy with antivascular endothelial growth factor agents. Exogenous testosterone is increasingly prescribed for menopausal symptoms and libido loss. Treatment with oscillatory photodynamic therapy, supplemental bevacizumab intravitreal pharmacotherapy, and cessation of exogenous androgen therapy was successful in three cases of chronic, therapy-resistant CSR. Ophthalmologists should inquire about androgen usage in patients who present with CSR, especially in the setting of therapy resistance.

Imaging Polarimetry in Central Serous Chorioretinopathy

PubMed Central

MIURA, MASAHIRO; ELSNER, ANN E.; WEBER, ANKE; CHENEY, MICHAEL C.; OSAKO, MASAHIRO; USUI, MASAHIKO; IWASAKI, TAKUYA

2006-01-01

PURPOSE To evaluate a noninvasive technique to detect the leakage point of central serous chorioretinopathy (CSR), using a polarimetry method. DESIGN Prospective cohort study. METHODS SETTING Institutional practice. PATIENTS We examined 30 eyes of 30 patients with CSR. MAIN OUTCOME MEASURES Polarimetry images were recorded using the GDx-N (Laser Diagnostic Technologies). We computed four images that differed in their polarization content: a depolarized light image, an average reflectance image, a parallel polarized light image, and a birefringence image. Each polarimetry image was compared with abnormalities seen on fluorescein angiography. RESULTS In all eyes, leakage area could be clearly visualized as a bright area in the depolarized light images. Michelson contrasts for the leakage areas were 0.58 ± 0.28 in the depolarized light images, 0.17 ± 0.11 in the average reflectance images, 0.09 ± 0.09 in the parallel polarized light images, and 0.11 ± 0.21 in the birefringence images from the same raw data. Michelson contrasts in depolarized light images were significantly higher than for the other three images (P < .0001, for all tests, paired t test). The fluid accumulated in the retina was well-visualized in the average and parallel polarized light images. CONCLUSIONS Polarization-sensitive imaging could readily localize the leakage point and area of fluid in CSR. This may assist with the rapid, noninvasive assessment of CSR. PMID:16376644

Vision-related quality of life in patients with chronic central serous chorioretinopathy.

PubMed

Türkcü, Fatih Mehmet; Şahin, Alparslan; Bez, Yasin; Yüksel, Harun; Cinar, Yasin; Kürşat Cingü, Abdullah; Çaça, İhsan

2015-07-01

To evaluate vision-related quality of life in patients with chronic central serous chorioretinopathy (CSCR). Prospective, cross-sectional study. The interviewer-administered National Eye Institute visual function questionnaire (NEI-VFQ-25) was used in 30 adult consecutive patients with chronic CSCR patients. The controls were 30 gender- and age-matched people with normal visual function who came from the same socioeconomic and educational background as the participants. Patients with CSCR had statistically significant lower scores than controls for all the subscales, except for general health. In the study group, all subscale scores of vision-related quality of life, except general health, showed statistically significant negative correlations with the visual acuity. People with CSCR have worse vision-related quality of life than people without the condition.

Serum erythropoietin levels in patients with central serous chorioretinopathy.

PubMed

Turgut, Burak; Ilhan, Nevin; Uyar, Fatma Yayla; Celiker, Ulku; Demir, Tamer; Koca, Suleyman Serdar

2010-01-01

To evaluate the levels of erythropoietin (EPO) in the serum in patients with central serous chorioretinopathy (CSC). An institutional comperative clinical study. The serum EPO levels were measured with the enzyme-linked immunosorbent assay (ELISA) method, of 15 patients with active CSC (Group 1), 15 patients with inactive CSC (Group 2) and 15 healthy volunteers (Group 3). Kruskal-Wallis variance analysis and Mann-Whitney U test were used for statistical analysis. The patient and control groups were matched for age and sex. There was no statistically significant variation with regard to age and gender among the groups ( P > 0.05). The mean serum EPO concentrations in patients with active CSC (Group 1), inactive CSC (Group 2) and in healthy controls (Group 3) were 11.39 ± 3.01 mlU/mL, 11.79 ± 3.78 mlU/mL and 11.95 ± 3.27 mlU/mL, respectively. There was no significant variation among the serum EPO concentrations of the study groups ( P > 0.05). These findings suggest no role of serum EPO in pathogenesis of CSC.

In patients suffering from idiopathic central serous chorioretinopathy, anxiety scores are higher than in healthy controls, but do not vary according to sex or repeated central serous chorioretinopathy.

PubMed

Bazzazi, Nooshin; Ahmadpanah, Mohammad; Akbarzadeh, Siamak; Seif Rabiei, Mohammad Ali; Holsboer-Trachsler, Edith; Brand, Serge

2015-01-01

Idiopathic central serous chorioretinopathy (CSCR) is a relatively common ophthalmic disorder characterized by the development of a serous detachment of the sensory retina. Psychophysiological factors may trigger or maintain CSCR, though, surprisingly, the association between CSCR and anxiety has yet to be studied. The aims of the present study were threefold: to determine whether 1) Iranian patients with CSCR have higher scores for anxiety, 2) anxiety is lower, if CSCR has been experienced twice, and whether 3) anxiety scores differ between sexes. A total of 30 patients with CSCR and 30 healthy age-and sex-matched controls took part in the study. A brief face-to-face interview was conducted covering demographic variables and history and occurrence of CSCR and assessing anxiety. Compared to healthy controls, anxiety was significantly higher in both first-time and second-time CSCR patients. In CSCR patients, anxiety scores did not differ between sexes. Higher anxiety scores were observed in Iranian patients with CSCR, irrespective of whether this was the first or second occurrence of CSCR. This suggests there is no psychological adaptation in terms of reduced anxiety among patients with repeated CSCR.

In patients suffering from idiopathic central serous chorioretinopathy, anxiety scores are higher than in healthy controls, but do not vary according to sex or repeated central serous chorioretinopathy

PubMed Central

Bazzazi, Nooshin; Ahmadpanah, Mohammad; Akbarzadeh, Siamak; Seif Rabiei, Mohammad Ali; Holsboer-Trachsler, Edith; Brand, Serge

2015-01-01

Introduction Idiopathic central serous chorioretinopathy (CSCR) is a relatively common ophthalmic disorder characterized by the development of a serous detachment of the sensory retina. Psychophysiological factors may trigger or maintain CSCR, though, surprisingly, the association between CSCR and anxiety has yet to be studied. The aims of the present study were threefold: to determine whether 1) Iranian patients with CSCR have higher scores for anxiety, 2) anxiety is lower, if CSCR has been experienced twice, and whether 3) anxiety scores differ between sexes. Methods A total of 30 patients with CSCR and 30 healthy age-and sex-matched controls took part in the study. A brief face-to-face interview was conducted covering demographic variables and history and occurrence of CSCR and assessing anxiety. Results Compared to healthy controls, anxiety was significantly higher in both first-time and second-time CSCR patients. In CSCR patients, anxiety scores did not differ between sexes. Conclusion Higher anxiety scores were observed in Iranian patients with CSCR, irrespective of whether this was the first or second occurrence of CSCR. This suggests there is no psychological adaptation in terms of reduced anxiety among patients with repeated CSCR. PMID:25995637

Central chorioretinopathy associated with topical use of minoxidil 2% for treatment of baldness.

PubMed

Scarinci, Fabio; Mezzana, Paolo; Pasquini, Paola; Colletti, Michelle; Cacciamani, Andrea

2012-06-01

Minoxidil is one of the drugs approved for the treatment of androgenetic alopecia. This article presents a case of central serous chorioretinopathy after application of topical minoxidil solution. We examined a 37-year-old man who complained of a positive relative scotoma, metamorphopsia and impaired dark adaptation involving the right eye. The patient reported an 8 month history of daily topical use but denied previous treatment with other drugs. Dilated fundus examination of right eye revealed central swelling located over the macula. Optical coherence tomography showed the presence of subretinal fluid. Fluorescein angiography disclosed one focal hyperfluorescent spot in the foveal area with minimal pigmentary changes limitated to that area. The patient was diagnosed with central serous chorioretinopathy (CSC) potentially related to an 8 month topical minoxidil solution administration. One month after the drug was discontinued, normal findings were found upon reexamination. The patient reported no previous episode of CSC. Major systemic side effects from topical solution of minoxidil are rare. To our knowledge, this is the first reported case of a central serous chorioretinopathy associated with long-term use of this drug.

Serum erythropoietin levels in patients with central serous chorioretinopathy

PubMed Central

Turgut, Burak; Ilhan, Nevin; Uyar, Fatma Yayla; Celiker, Ulku; Demir, Tamer; Koca, Suleyman Serdar

2010-01-01

Objective To evaluate the levels of erythropoietin (EPO) in the serum in patients with central serous chorioretinopathy (CSC). Methods An institutional comperative clinical study. The serum EPO levels were measured with the enzyme-linked immunosorbent assay (ELISA) method, of 15 patients with active CSC (Group 1), 15 patients with inactive CSC (Group 2) and 15 healthy volunteers (Group 3). Kruskal–Wallis variance analysis and Mann–Whitney U test were used for statistical analysis. Results The patient and control groups were matched for age and sex. There was no statistically significant variation with regard to age and gender among the groups (P > 0.05). The mean serum EPO concentrations in patients with active CSC (Group 1), inactive CSC (Group 2) and in healthy controls (Group 3) were 11.39 ± 3.01 mlU/mL, 11.79 ± 3.78 mlU/mL and 11.95 ± 3.27 mlU/mL, respectively. There was no significant variation among the serum EPO concentrations of the study groups (P > 0.05). Conclusion These findings suggest no role of serum EPO in pathogenesis of CSC. PMID:28539767

Cushing disease revealed by bilateral atypical central serous chorioretinopathy: case report.

PubMed

Giovansili, Iama; Belange, Georeges; Affortit, Aude

2013-01-01

We report the case of a patient with Cushing disease revealed by bilateral central serous chorioretinopathy (CSCR). We present the clinical history, physical findings, laboratory results, and imaging studies of a 53-year-old Chinese woman with a Cushing disease revealed by bilateral CSCR. The association with CSCR and the pertinent literature are reviewed. A 53-year-old patient initially presented to the Department of Ophthalmology with a 4-week history of decreased vision in the left eye. Standard ophthalmologic examination and fluorescein angiography established the diagnosis of bilateral CSCR. Systemic clinical signs and biochemical analysis indicated hypercortisolism. Magnetic resonance imaging (MRI) of the pituitary gland showed a left-side lesion compatible with a microadenoma. The diagnosis of Adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome secondary to a pituitary microadenoma was selected. Endoscopic endonasal transsphenoidal surgery was performed and the pituitary adenoma was successfully removed. The histology confirmed the presence of ACTH-immunopositive pituitary adenoma. Early postoperative morning cortisol levels indicated early remission. At 6 weeks postoperatively, the patient's morning cortisol remains undetectable, and serous retinal detachments had regressed. CSCR is an uncommon manifestation of endogenous Cushing syndrome. It can be the first presentation of hypercortisolism caused by Cushing disease. CSCR should be considered when assessing patients with Cushing syndrome complaining of visual disorders. On the other hand, it is useful in patients with an atypical form of CSCR to exclude Cushing's syndrome.

Smokestack leak in central serous chorioretinopathy.

PubMed

Bujarborua, Dhiren; Nagpal, Pran N; Deka, Manab

2010-03-01

To study the demography, various morphological patterns and fluid dynamics of the smokestack leak by fluorescein angiography (FA) in central serous chorioretinopathy (CSC). Part I (clinical): review of the medical records and angiographic documents of 69 consecutive cases of CSC with smokestack leak. Part II (experimental): documentation of the movement of various concentrations of fluorescein dye due to convection currents in a laboratory model that roughly represents a closed chamber similar to that of CSC in human eyes. The clinical study (Part I) revealed that 14.40% of 479 consecutive cases had smokestack leak, of which 70% occurred in first acute episode (p-value: <0.001), 27.14% in acute recurrent episodes (50% fresh leak) and 2.85% in chronic stage. Patients were predominantly male (84.05%) with a median age of 34.00 +/- 8.14 years. The median symptom duration excluding the chronic cases was 15 +/- 34.28 days. This type of leak was mostly (48.57%) seen in medium-sized CSC, and the majority were in the parafoveal superonasal quadrant (31.42%). The ascending type of leak was predominant (94.28%). In four eyes, an atypical pattern and in two eyes more than one smokestack leak were seen within the same detached area. The experimental study (Part II) demonstrated that fluid containing a low concentration of fluorescein ascended due to convection currents, whereas highly concentrated dye descended. The clinical study revealed smokestack leaks to be significantly more common in a primary acute episode, and they usually develop in the early part of the acute phase of the disease (average duration 15 +/- 34.28 days). Rarely, this type of leak can occur in the chronic stage, and multiple leaks may develop in the same detached space. The various patterns of dye movement due to convection currents in the experimental model resembled the dye movement in certain cases of CSC of the present series. The experimental study also hinted at the probability of drainage of

Fundus autofluorescence imaging patterns in central serous chorioretinopathy according to chronicity.

PubMed

Lee, W J; Lee, J-H; Lee, B R

2016-10-01

PurposeTo investigate the time-period characteristics associated with morphologic changes in central serous chorioretinopathy (CSC) using fundus autofluorescence (FAF).Patients and methodsRetrospective, cross-sectional observational case series. Patients were classified into three groups: acute and chronic according to the onset of subjective symptoms of 6 weeks and sequelae patients who have history and symptoms but no serous retinal detachment (SRD). We compared FAF images to obtain characteristic findings according to the chronicity.ResultsA total of 52 eyes were included in this study. Acute CSC eyes were characterized by decreased FAF intensity at the leakage point in 13/22 eyes (56.5%) and staining patterns with various levels of fluorescence signal (hyperautofluorescent (10 eyes, 43.5%), hypoautofluorescent (1 eye, 4.3%), and minimal changes (12 eyes, 52.2%)) in the area of SRD. In chronic CSC eyes, hyperautofluorescent (14 eyes, 63.6%) or minimal changes (8 eyes, 36.4%) were observed in the area of SRD. Discrete dots with increased FAF intensity were observed in chronic CSC eyes (P<0.001). Eyes with sequelae of CSC had mixed FAF patterns over areas of retinal pigment epithelium (RPE) atrophy in seven eyes (100%, P<0.001)) and descending tracts which showed various FAF intensities according to the RPE and photoreceptor status (P<0.001).ConclusionFAF imaging patterns in CSC eyes differ according to the course of the disease, reflecting RPE and outer retinal changes. Detailed investigation using FAF could help to estimate the duration of CSC and determine the proper treatment modality.

Finasteride is effective for the treatment of central serous chorioretinopathy

PubMed Central

Moisseiev, E; Holmes, A J; Moshiri, A; Morse, L S

2016-01-01

Purpose To evaluate the safety and efficacy of finasteride treatment in patients with central serous chorioretinopathy (CSC). Methods Retrospective review of 29 eyes of 23 patients who were treated with finasteride for CSC. Previous medical and ocular history, steroid use, length of finasteride treatment, additional treatments for CSC, visual acuity (VA), central macular thickness (CMT), and presence of subretinal fluid (SRF) throughout the follow-up period, and the occurrence of any complications were recorded. Results Initial VA was 0.29±0.31 logMAR, and a trend towards improved VA was noted after 3 months (0.25±0.36 logMAR; P=0.07). VA was significantly improved at the final follow-up (0.23±0.27 logMAR; P=0.024). Initial CMT was 354±160 μm, and was significantly reduced after 1 month of treatment (284±77 μm; P=0.002) and this was maintained to the end of follow-up (247±85 μm; P=0.001). A significant reduction in SRF presence was found at all time points, with an overall 75.9% rate of complete resolution. Following discontinuation, SRF recurrence was noted in 37.5% of cases. No adverse events were recorded. Conclusions Finasteride is a safe and effective treatment for CSC. It may be a possible new option for the initial management of patient with CSC, and a suggested treatment approach is presented. PMID:27055675

Correlation between fundus autofluorescence and central visual function in chronic central serous chorioretinopathy.

PubMed

Eandi, Chiara M; Piccolino, Felice Cardillo; Alovisi, Camilla; Tridico, Federico; Giacomello, Daniela; Grignolo, Federico M

2015-04-01

To find possible correlations between the morphologic macular changes revealed by fundus autofluorescence (FAF) and the functional parameters such as visual acuity and retinal sensitivity in patients with chronic central serous chorioretinopathy (CSC). Prospective, cross-sectional study. Forty-six eyes (39 consecutive patients) with chronic CSC were studied with FAF and microperimetry (MP). Retinal sensitivity value maps were exactly superimposed over FAF images. The following microperimetric parameters were applied: central 10-degree visual field, 4-2-1 strategy, 61 stimulation spots, white monochromatic background, stimulation time 200 ms, stimulation spot size Goldmann III. A possible relationship between MP and FAF was investigated. Mean best-corrected visual acuity (BCVA) was 20/32 (median 20/25, range 20/20-20/200). BCVA was significantly correlated with FAF findings (Mann-Whitney test; P < .0001). A positive concordance between FAF and MP evaluation was also found (total concordance of 0.720 with a kappa of Cohen of 0.456). The hypo-autofluorescent areas showed decreased retinal sensitivity, while adjacent areas of increased FAF could be associated to both normal and decreased retinal sensitivity. Absolute scotoma, defined as 0 dB retinal sensitivity, corresponded with absence of autofluorescence. Altered FAF in chronic CSC patients has a functional correlation quantified by microperimetry. This study confirms the impact of FAF changes on retinal sensitivity and their value to reflect the functional impairment in chronic CSC. Copyright © 2015 Elsevier Inc. All rights reserved.

The relation of somatotypes and stress response to central serous chorioretinopathy.

PubMed

Schwartz, Roy; Rozenberg, Assaf; Loewenstein, Anat; Goldstein, Michaella

2017-12-01

To investigate a possible relationship between central serous chorioretinopathy (CSC) and specific body types and compositions (somatotypes), and to examine the cortisol stress response among CSC patients of different somatotypes in comparison with healthy subjects. Prospective case-control study. A group of 28 patients with a previous or current diagnosis of CSC was compared with a group of 26 healthy subjects. Anthropometric measurements were used to estimate somatotype ratings in all subjects. Serum cortisol was measured at rest and following a stress-inducing computerized test in order to estimate response to stress in both groups. The main outcome measures included somatotype categorization and the change in serum cortisol following stress in both groups. No significant difference in somatotype composition was found between the groups. There was no statistically significant difference between the groups in the elevation of cortisol following the stress-inducing test. The sample size was too small to exclude or find any significant difference between the different 13 subgroups of somatotype composition in the elevation of cortisol. Our study did not show a typical somatotype related to CSC. While previous studies showed higher cortisol values in CSC patients, we did not see a higher elevation in blood cortisol following a stress response in this group in comparison with healthy subjects.

Association of Helicobacter pylori with central serous chorioretinopathy: hypotheses regarding pathogenesis.

PubMed

Giusti, Cristiano

2004-01-01

Central serous chorioretinopathy (CSC) is a serous macular detachment that usually affects young people and leads fortunately to a spontaneous resolution and a good visual prognosis in most patients. Nevertheless, although in a small percentage of subjects only, it may also develop a chronic or progressive disease with widespread decompensation of the retinal pigment epithelium (RPE) and severe vision loss. The aetiopathogenesis of the disease is still not completely understood and no effective treatment is available at this time. However, an interesting association has been recently highlighted between CSC and the Helicobacter pylori infection. In particular, in a first case report recurrences of the disease were always associated with HP-positivity whereas improvements of both retinal findings and visual acuity were significantly correlated with a successful eradication of the bacterium using the conventional antimicrobial triple-therapy. In a second study, the prevalence of HP infection was found to be significantly higher in CSC-affected subjects compared to age- and sex-matched controls from the same country. Much speculation surrounds the role potentially played by HP in determining CSC. In particular, CSC seems not to be more a merely RPE disease but the final result of a general involvement of the choroidal microcirculation. In fact, several vascular abnormalities, such as localized vasoconstriction and impaired fibrinolysis, have been demonstrated during CSC whose "end-points" might be a focal occlusion of the choriocapillaries with decreased foveal choroidal blood flow, secondary RPE defects and serous macular detachment. Moreover, a HP-dependent immune mechanism, based on a "molecular mimicry" between pathogenic antigens expressed on the bacterium and homologous host proteins (e.g., those of the endothelial vascular wall), might also be involved in the pathophysiology of CSC. In this case, a genetically determined susceptibility of the subject could be

QT interval dispersion in the patients with central serous chorioretinopathy.

PubMed

Dagli, Necati; Turgut, Burak; Tanyildizi, Rumeysa; Kobat, Sabiha; Kobat, Mehmet Ali; Dogdu, Orhan

2015-01-01

To evaluate QT dispersion (QTD) in patients with central serous chorioretinopathy (CSC). This clinical, comperative, case-control study included 30 patients with CSC at acute phase (Group 1) and 30 age- and sex-matched healthy subjects (Group 2, the control group). From all subjects, a 12-lead surface electrocardiography was obtained. The heart rate (HR), QT maximum (QTmax), QT minimum (QTmin), QT corrected (QTc), QTD and Tmean were manually measured and analyzed. Student's t-test and Pearson's method of correlation were used for statistical analysis. The patient and control groups were matched for age, smoking status (rate and duration) and gender. There were no significant differences with regard to these among the groups (P>0.05). The participants included 19 men (63.3%) and 11 women (36.7%) in Group 1, 20 men (66.7%) and 10 women (33.3%) in Group 2. QTmax, QTD and QTc were significantly higher than those of healthy controls (P<0.001 for QTmax, P=0.01 for QTD and P=0.001 for QTc). QTmin, Tmean and HR did not differ significantly between the study groups (P=0.28 for QTmin, P=0.56 for Tmean and P>0.05 for HR). No significant correlation was found between duration of the disorder and QTD values (r=0.13, P>0.05). These findings suggest that CSC may be associated with an increase in QTD and that the patients might be at risk for ventricular arrhythmia.

Topical fundus pulsation measurement in patients with active central serous chorioretinopathy.

PubMed

Tittl, Michael; Polska, Elzbieta; Kircher, Karl; Kruger, Andreas; Maar, Noemi; Stur, Michael; Schmetterer, Leopold

2003-07-01

To determine regional pulsatile choroidal blood flow using laser interferometry in patients with active central serous chorioretinopathy (CSC). The study compared an equally sized age-, sex-, and refractive error-matched control group of healthy volunteers obtained from the Department of Clinical Pharmacology with 18 consecutive patients who had newly diagnosed active, unilateral CSC obtained from the University of Vienna Eye Clinic, Vienna, Austria. Regional fundus pulsation amplitude as assessed using laser interferometry. The median age of the patients was 40 years; the male-female ratio was 16:2. Foveal fundus pulsation amplitude was significantly higher in eyes with CSC (mean [SD], 5.5 [1.7] micro m) than in the eyes of the control subjects (4.1 [1.1] micro m; P =.005). In addition, eyes with CSC had a significantly higher variability in fundus pulsation amplitude (mean [SD], 48% [20%]) assessed at different fundus locations around the leak than the controls did (20% [9%]; P<.001). To our knowledge, this is the first study that measures topical fundus pulsations in patients who have active, unilateral CSC. These data indicate a generally increased foveal pulsatile choroidal blood flow and an abnormal distribution of fundus pulsation amplitude in the area close to the leak. Whether these findings reinforce the concept that choroidal perfusion abnormalities play a role in the pathogenesis of CSC remains to be established.

QT interval dispersion in the patients with central serous chorioretinopathy

PubMed Central

Dagli, Necati; Turgut, Burak; Tanyildizi, Rumeysa; Kobat, Sabiha; Kobat, Mehmet Ali; Dogdu, Orhan

2015-01-01

AIM To evaluate QT dispersion (QTD) in patients with central serous chorioretinopathy (CSC). METHODS This clinical, comperative, case-control study included 30 patients with CSC at acute phase (Group 1) and 30 age- and sex-matched healthy subjects (Group 2, the control group). From all subjects, a 12-lead surface electrocardiography was obtained. The heart rate (HR), QT maximum (QTmax), QT minimum (QTmin), QT corrected (QTc), QTD and Tmean were manually measured and analyzed. Student's t-test and Pearson's method of correlation were used for statistical analysis. RESULTS The patient and control groups were matched for age, smoking status (rate and duration) and gender. There were no significant differences with regard to these among the groups (P>0.05). The participants included 19 men (63.3%) and 11 women (36.7%) in Group 1, 20 men (66.7%) and 10 women (33.3%) in Group 2. QTmax, QTD and QTc were significantly higher than those of healthy controls (P<0.001 for QTmax, P=0.01 for QTD and P=0.001 for QTc). QTmin, Tmean and HR did not differ significantly between the study groups (P=0.28 for QTmin, P=0.56 for Tmean and P>0.05 for HR). No significant correlation was found between duration of the disorder and QTD values (r=0.13, P>0.05). CONCLUSION These findings suggest that CSC may be associated with an increase in QTD and that the patients might be at risk for ventricular arrhythmia. PMID:25709909

Bilateral simultaneous central serous chorioretinopathy in a teenage girl with systemic arterial hypertension.

PubMed

Alwassia, Ahmad A; Adhi, Mehreen; Duker, Jay S

2013-02-01

We present a case of bilateral simultaneous central serous chorioretinopathy (CSCR) in a teenage girl with a history of systemic arterial hypertension. A 19-year-old Caucasian female, with a history of systemic arterial hypertension, presented with gradual decrease in her central vision for 1 month. She was diagnosed with bilateral simultaneous CSCR, based on the findings of spectral domain optical coherence tomography (SD-OCT), indocyanine green angiography (ICG), fundus auto-fluorescence, fluorescein angiography and color fundus photographs, which are described. Blood pressure was 134/95 mmHg at presentation. Systemic evaluation failed to reveal a cause for the high blood pressure, and included a panel of blood tests, which were all normal. Her best-corrected visual acuity was 20/30 OD and 20/25 OS. Dilated fundus examination showed normal optic discs and retinal vasculature, with no evidence of hypertensive retinopathy. However, shallow retinal fluid associated with pigmentary changes was noted in the center of both maculae. OCT and ICG findings were consistent with the diagnosis of bilateral CSCR. CSCR can manifest in patients with demographics outside the range of those previously reported. This is the first report of CSCR occurring in a teenage girl, with a history of systemic arterial hypertension. It is important to consider this disease in any patient who has a clinically compatible presentation.

Characteristics of intraretinal deposits in acute central serous chorioretinopathy.

PubMed

Plateroti, Andrea M; Witmer, Matthew T; Kiss, Szilárd; D'Amico, Donald J

2014-01-01

To describe the temporal and spatial characteristics of intraretinal deposits in patients with acute central serous chorioretinopathy (CSC) using spectral domain optical coherence tomography (OCT). We retrospectively reviewed the medical records of all patients that presented with acute CSC to Weill Cornell Medical College from January 2012 to May 2013. Acute CSC was defined as a diagnosis of CSC within 4 months of the onset of symptoms. Only one eye per patient was included in the study. Each patient was imaged with spectral domain OCT at the initial office visit. The decision to reimage these patients was made by the treating physician. A total of 25 patients (25 eyes; 17 men and eight nonpregnant women) were included in this review. Seven of 25 patients (28%) demonstrated intraretinal deposits within the outer plexiform layer during the initial OCT, with deposits appearing as early as the same day as the onset of symptoms. A total of 25 of 25 patients (100%) demonstrated intraretinal deposits in the outer nuclear layer upon initial (76%) or follow-up OCT, as early as 2 days after the onset of symptoms. A total of 24 of 25 patients (96%) demonstrated deposits in the external limiting membrane upon a follow-up OCT, as early as 7 days from symptoms appearing. A total of 24 of 25 patients (96%) developed intraretinal deposits in the inner segment/outer segment layer upon follow-up OCT, appearing as early as 14 days after symptom onset. At the time of resolution of subretinal fluid, 20 of 25 patients (80%) demonstrated intraretinal deposits. Intraretinal deposits are present in the outer retinal layers in patients with acute CSC, with the deposits appearing progressively deeper within the retina as the condition evolves. Upon resolution of subretinal fluid, the deposits slowly resolve.

Massive Bilateral Serous Retinal Detachment in a Case of Hypertensive Chorioretinopathy

PubMed Central

Villalba-Pinto, Luis; Hernández-Ortega, M. Ángeles; de los Mozos, F. Javier Lavid; Pascual-Camps, Isabel; Dolz-Marco, Rosa; Arevalo, J. Fernando; Gallego-Pinazo, Roberto

2014-01-01

Introduction Systemic high blood pressure is related to a variety of retinal manifestations. We present an atypical case of hypertensive chorioretinopathy with massive bilateral serous retinal detachment. Case Report A 26-year-old male with a genitourinary malformation and secondary grade IV chronic kidney failure as well as high blood pressure complained of acute vision loss. Dilated fundus examination evidenced a bilateral serous retinal detachment with macular involvement. The patient was unresponsive to oral antihypertensive therapy and dialysis treatment. The serous retinal detachment progressively decreased after the restoration of dialysis and antihypertensive therapy. The final visual acuity was 0.50 in both eyes. Discussion In cases of serous macular detachment, it is mandatory to rule out different systemic and ocular diseases. The presence of uncontrolled high blood pressure may produce aggressive bilateral retinal changes, thus hypertension must be under early and strict control in order to improve the visual outcomes. PMID:25120474

PRESENTATION OF CENTRAL SEROUS CHORIORETINOPATHY IN TWO HUSBAND AND WIFE COUPLES.

PubMed

Kanesa-Thasan, Aditya; Fawzi, Amani A; Gill, Manjot K

2018-01-01

Central serous chorioretinopathy (CSC) is a disease in which serous detachment of the neurosensory retina occurs over an area of leakage from the choriocapillaris through the retinal pigment epithelium. Associations have been drawn between high-stress personality types and steroid exposure. This article aims to describe a unique case series of two husband and wife couples with CSC. All methods were approved by the authors' institution's institutional review board. History, physical examination, and imaging data were obtained from the electronic medical records of the patients in question and from the providers who cared for these patients. Couple 1: A 35-year-old man presented with "dark spots" in his right eye. He reported no recent steroid use. Visual acuity at presentation was 20/30 in the right eye and 20/20 in the left eye. On fundus examination, there was subretinal fluid in the right eye. His wife presented on the same day with a "wavy section" in the right eye for 6 weeks. She also had no recent steroid use. Visual acuity at presentation was 20/20 in both eyes with blunting of the foveal reflex in the right eye. Optical coherence tomography showed a thick choroid with a pigment epithelial detachment in the right eye. Couple 2: A 34-year-old man presented with "blurry vision" in his right eye for one month. He was taking oral and nasal steroids for chronic sinusitis. Visual acuity was 20/30 in the right eye and 20/20 in the left eye. Fluorescein angiography and indocyanine green confirmed the diagnosis of CSC. After 3 months of persistent subretinal fluid, he received photodynamic therapy in the right eye. Three days after his photodynamic therapy, his 38-year-old wife presented with subjective blurring in both eyes. Visual acuity was 20/20 in both eyes, but optical coherence tomography showed thick choroid in both eyes, a large central pigment epithelial detachment in the right eye, and 3 small pigment epithelial detachments in the left eye. She had no

Central serous chorioretinopathy and phosphodiesterase-5 inhibitors: a case-control postmarketing surveillance study.

PubMed

French, Dustin D; Margo, Curtis E

2010-02-01

The purpose of this study was to determine if there is an increased risk of central serous chorioretinopathy (CSC) associated with prescription exposure to phosphodiesterase-5 (PDE-5) inhibitors. A case-control study linking 2 National Veterans Health Administration databases (clinical and pharmacy) for fiscal years 2004 to 2005. The likelihood of past exposure to PDE-5 inhibitors among newly diagnosed patients with CSC, identified through International Classification of Diseases, 9th Edition, Clinical Modification codes, was compared with 2 age-matched control groups after excluding subjects with risk factors for CSC. Among 577 men, aged 59 years and younger with newly diagnosed CSC during the study year, 111 were prescribed a PDE-5 inhibitor (19.2%). The proportions of age-matched controls prescribed a PDE-5 inhibitor in the 2 groups were 18.5% and 21.5%. The odds ratio of exposure was 1.05 (95% confidence limit: 0.74-1.22) and 0.87 (95% confidence limit: 0.68-1.12). Patients with CSC had no increase in prescription exposure to PDE-5 inhibitors than did age-matched control subjects. Although the findings in this study do not support an association between CSC and PDE-5 inhibitors, postmarketing surveillance methods for drug-related side effects have acknowledged limitations.

[Selective retina therapy in central serous chorioretinopathy with detachment of the pigmentary epithelium].

PubMed

Klatt, C; Elsner, H; Pörksen, E; Brinkmann, R; Bunse, A; Birngruber, R; Roider, J

2006-10-01

Selective Retina Therapy (SRT) is a new and innovative laser treatment modality that selectively treats the retinal pigmentary epithelium while sparing the photoreceptors. This therapeutic concept appears to be particularly suitable for treating patients with acute or chronic central serous chorioretinopathy (CSC). We present preliminary results obtained in five patients who had CSC associated with pigmentary epithelium detachment (PED) and serous subretinal fluid (SRF) and who were treated with SRT. This case series was made up of five male patients (mean age 47 years) with chronic CSC and SRF resulting from PED. Examinations performed before and at 1 month and 3 months after the treatment were: BCVA, FLA, OCT (Zeiss OCT III). For SRT, confluent treatment of the PED (area of leakage) was carried out using a pulsed frequency-doubled, Q-switched Nd-YLF prototype laser (lambda=527 nm, t= 1.7 s, 100 Hz, energy = 150-250 J). Best corrected visual acuity at baseline was 0.53, while after 4 weeks it was 0.56 and after 12 weeks, 0.5. At baseline leakage was seen at the PED on fluorescein angiography in all patients. After 4 weeks leakage activity was no longer noted on angiography in 4 of 5 patients. OCT at baseline showed SRF at the edge of the PED in all patients, but in 4 of the 5 patients this was no longer detectable after 4 weeks. SRT is a safe and effective treatment for patients with CSC in which PED has caused SRF. Not a single case of rip syndrome was observed in this study, even though the PED was treated confluently. Since SRT spares the photoreceptors it is particularly suitable for the treatment of CSC, especially when the origin of leakage is located close to the fovea. The results indicate that SRT leads to reconstruction of the outer blood-retina barrier.

Restoration of outer segments of foveal photoreceptors after resolution of central serous chorioretinopathy.

PubMed

Ojima, Yumiko; Tsujikawa, Akitaka; Yamashiro, Kenji; Ooto, Sotaro; Tamura, Hiroshi; Yoshimura, Nagahisa

2010-01-01

To study morphologically and functionally the prognosis of damaged outer segments of the foveal photoreceptor layer in eyes with resolved central serous chorioretinopathy (CSC). We studied retrospectively the medical records of 70 patients (74 eyes) with resolved CSC. Optical coherence tomography was used to detect the junctions between inner and outer segments of the photoreceptors (IS/OS) as a hallmark of the integrity of the outer photoreceptor layer. In 53 eyes (71.6%), the IS/OS line was clearly detected beneath the fovea immediately after resolution of the retinal detachment, with good visual acuity (VA). In the remaining 21 eyes (28.4%), however, the foveal IS/OS line could not be detected shortly after resolution of CSC, and VA was variable, ranging from 0.1 to 1.5 (median, 0.9). Of these 21 eyes, 15 had a follow-up examination with OCT, and in four the foveal IS/OS line was not detected at the follow-up and vision in these eyes remained poor. However, nine eyes showed recovery of the foveal IS/OS line during follow-up, and these eyes had substantial visual recovery. Immediately after resolution of active CSC, although the IS/OS line cannot be detected beneath the fovea, it often shows restoration over time, with visual recovery, though in some eyes no restoration takes place and the prognosis remains poor.

Cushing's Syndrome and Hypothalamic-Pituitary-Adrenal Axis Hyperactivity in Chronic Central Serous Chorioretinopathy.

PubMed

van Haalen, Femke M; van Dijk, Elon H C; Dekkers, Olaf M; Bizino, Maurice B; Dijkman, Greet; Biermasz, Nienke R; Boon, Camiel J F; Pereira, Alberto M

2018-01-01

Central serous chorioretinopathy (CSC), a specific form of macular degeneration, has been reported as presenting manifestation of Cushing's syndrome. Furthermore, CSC has been associated with both exogenous hypercortisolism and endogenous Cushing's syndrome. It is important to know whether CSC patients should be screened for Cushing's syndrome. Although hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in CSC has been suggested, no detailed evaluation of the HPA axis has been performed in a large cohort of CSC patients. This study aimed to investigate whether Cushing's syndrome prevalence is increased among chronic CSC (cCSC) patients and whether detailed endocrinological phenotyping indicates hyperactivity of the HPA axis. Cross-sectional study. 86 cCSC patients and 24 controls. Prevalence of Cushing's syndrome, HPA axis activity. None of the cCSC patients met the clinical or biochemical criteria of Cushing's syndrome. However, compared to controls, HPA axis activity was increased in cCSC patients, reflected by higher 24 h urinary free cortisol, and accompanying higher waist circumference and diastolic blood pressure, whereas circadian cortisol rhythm and feedback were not different. Chronic CSC patients did not report more stress or stress-related problems on questionnaires. No case of Cushing's syndrome was revealed in a large cohort of cCSC patients. Therefore, we advise against screening for Cushing's syndrome in CSC patients, unless additional clinical features are present. However, our results indicate that cCSC is associated with hyperactivity of the HPA axis, albeit not accompanied with perception of more psychosocial stress.

Effects of smoking on visual acuity of central serous chorioretinopathy patients.

PubMed

Türkcü, Fatih Mehmet; Yüksel, Harun; Sahin, Alparslan; Cinar, Yasin; Cingü, Kürşat; Arı, Seyhmus; Sahin, Muhammed; Altındağ, Suat; Caça, Ihsan

2014-06-01

The aim of this study was to evaluate the differences, in terms of visual outcome and treatment needs, between smokers and non-smokers central serous chorioretinopathy (CSCR) patients. The files of 252 patients diagnosed with CSCR who had presented to the Retina Unit of the Ophthalmology Clinic at Dicle University Medical School in Turkey were retrospectively evaluated. Eighty-four smokers, with a known history of smoking of at least one pack-year, and 133 non-smokers were included, whereas 35 patients with additional pathologies were excluded from the study. Of the patients, 192 (88.5%) were male and 25 (11.5%) were female. The mean patient age was 38.8 ± 8.1 years (range: 20-68 years). Visual acuity (VA) of the smoker and non-smoker groups was measured as 0.45 ± 0.35 and 0.24 ± 0.28 logarithm of the minimum angle of resolution (logMar), respectively, at the first visit; 0.19 ± 0.29 and 0.06 ± 0.14 logMar at the sixth month; and 0.07 ± 0.14 and 0.02 ± 0.05 logMar at the ninth month. VA measurements at presentation and during all examinations (1th, 6th and 9th month) were significantly different for the two groups. VA was lower in the smoker group. In 27 patients (12.4%), an additional treatment modality was needed. Of the 27 patients, only 8 (6%) were non-smokers, whereas 19 (22.6%) were smokers. There was no difference between groups in the recurrence rate during follow-up (p = 0.907); 14 (16.7%) smokers and 8 (19.0%) non-smokers experienced a recurrence. This study has shown that patients selected and who are current smokers have poorer vision and need longer treatment.

Interventions for central serous chorioretinopathy: a network meta-analysis

PubMed Central

Salehi, Mahsa; Wenick, Adam S; Law, Hua Andrew; Evans, Jennifer R; Gehlbach, Peter

2016-01-01

Background Central serous chorioretinopathy (CSC) is characterized by serous detachment of the neural retina with dysfunction of the choroid and retinal pigment epithelium (RPE). The effects on the retina are usually self limited, although some people are left with irreversible vision loss due to progressive and permanent photoreceptor damage or RPE atrophy. There have been a variety of interventions used in CSC, including, but not limited to, laser treatment, photodynamic therapy (PDT), and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents. However, it is not known whether these or other treatments offer significant advantages over observation or other interventions. At present there is no evidence-based consensus on the management of CSC. Due in large part to the propensity for CSC to resolve spontaneously or to follow a waxing and waning course, the most common initial approach to treatment is observation. It remains unclear whether this is the best approach with regard to safety and efficacy. Objectives To compare the relative effectiveness of interventions for central serous chorioretinopathy. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2014), EMBASE (January 1980 to October 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 October 2015. Selection criteria Randomized controlled trials (RCTs) that compared any intervention for CSC with any other intervention for CSC or control. Data collection and analysis Two

Increased incidence of peptic ulcer disease in central serous chorioretinopathy patients: a population-based retrospective cohort study.

PubMed

Chen, San-Ni; Lian, Iebin; Chen, Yi-Chiao; Ho, Jau-Der

2015-02-01

To investigate peptic ulcer disease and other possible risk factors in patients with central serous chorioretinopathy (CSR) using a population-based database. In this population-based retrospective cohort study, longitudinal data from the Taiwan National Health Insurance Research Database were analyzed. The study cohort comprised 835 patients with CSR and the control cohort comprised 4175 patients without CSR from January 2000 to December 2009. Conditional logistic regression was applied to examine the association of peptic ulcer disease and other possible risk factors for CSR, and stratified Cox regression models were applied to examine whether patients with CSR have an increased chance of peptic ulcer disease and hypertension development. The identifiable risk factors for CSR included peptic ulcer disease (adjusted odd ratio: 1.39, P = 0.001) and higher monthly income (adjusted odd ratio: 1.30, P = 0.006). Patients with CSR also had a significantly higher chance of developing peptic ulcer disease after the diagnosis of CSR (adjusted odd ratio: 1.43, P = 0.009). Peptic ulcer disease and higher monthly income are independent risk factors for CSR. Whereas, patients with CSR also had increased risk for peptic ulcer development.

Serum dehydroepiandrosterone sulphate, total antioxidant capacity, and total oxidant status in central serous chorioretinopathy.

PubMed

Türkcü, Fatih Mehmet; Yüksel, Harun; Yüksel, Hatice; Sahin, Alparslan; Cinar, Yasin; Cingü, Abdullah Kürşat; Sahin, Muhammed; Caça, Ihsan

2014-01-01

The objective of this work is to evaluate plasma total antioxidant capacity (TAC), total oxidant status (TOS), and dehydroepiandrosterone sulphate (DHEA-S) levels in patients diagnosed with acute central serous chorioretinopathy (CSCR) and control samples. The TAC, TOS, and DHEA-S levels were assessed in the plasma of 46 CSCR patients and compared with 40 control samples. The TAC level was 1.16 ± 0.08 and 1.20 ± 0.09 mmol Trolox eq./l; TOS level was 28.77 ± 33.33 and 19.95 ± 10.42 μmol H202/l; DHEA-S level was 203.79 ± 84.75 μg/dl and 249.36 ± 122.93 μg/dl in the CSCR group and in the control group, respectively. The plasma TAC and DHEA-S values were significantly lower in the CSCR group than in the control group (p = 0.027 and p = 0.046, respectively). There was no significant difference between the CSCR and the control groups in terms of age, gender, and TOS levels (p > 0.05). We demonstrated that the levels of plasma DHEA-S and antioxidative parameters were reduced in CSCR. Our results suggest that the antioxidant defense system may be inadequate or corrupted in CSCR. Reduced DHEA-S level is one of the factors that trigger this insufficiency.

Ultra-widefield imaging with autofluorescence and indocyanine green angiography in central serous chorioretinopathy.

PubMed

Pang, Claudine E; Shah, Vinnie P; Sarraf, David; Freund, K Bailey

2014-08-01

To describe the spectrum of ultra-widefield autofluorescence (AF) and indocyanine green (ICG) angiographic findings in central serous chorioretinopathy (CSC). Retrospective observational case series. In 37 patients, 65 eyes with CSC from 2 vitreoretinal clinical practices were imaged using ultra-widefield AF and 24 of these eyes with ultra-widefield ICG angiography. Images were correlated with clinical findings and spectral-domain optical coherence tomography (OCT). In 37 (57%) eyes, a variety of altered AF patterns, including gravitational tracts, extended beyond the posterior 50 degrees of retina. Hyper-AF corresponded to areas of subretinal fluid (SRF) on spectral-domain OCT and was found to persist in 44 (70%) eyes for up to 8 years despite resolution of SRF. These areas corresponded to outer retinal atrophy with viable retinal pigment epithelium (RPE) on spectral-domain OCT and may be explained by the unmasking of normal background RPE AF. Ultra-widefield ICG angiography revealed dilated choroidal vessels and choroidal hyperpermeability in areas corresponding to altered AF on ultra-widefield AF in all 24 eyes. In 20 (83.3%) eyes, dilated vessels were observed in association with 1 or more congested vortex veins ampullas, suggesting that outflow congestion may be a contributing factor to the pathogenesis of CSC. Ultra-widefield AF and ICG angiography in CSC revealed more widespread disease in a single image than with standard field imaging and may be useful for identifying peripheral areas of previous or ongoing SRF and choroidal hyperpermeability that can assist in the diagnosis of CSC, surveillance of recurrent disease and treatment of active disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Central serous chorioretinopathy fundus autofluorescence comparison with two different confocal scanning laser ophthalmoscopes.

PubMed

Nam, Ki Tae; Yun, Cheol Min; Kim, Jee Taek; Yang, Kyung-Sook; Kim, Hyun Joo; Kim, Seong-Woo; Oh, Jaeryung; Huh, Kuhl

2015-12-01

To compare the lesion characteristics of two different types of confocal scanning laser ophthalmoscopy (cSLO) autofluorescence (AF) images in central serous chorioretinopathy (CSC). The study included 63 eyes of 61 patients; 63 pairs of fundus autofluorescence (FAF) images were compared before CSC resolution in 63 eyes, FAF images of 31 eyes were also compared after CSC resolution. The lesion characteristics (brightness and composite pattern) were compared between Heidelberg Retina Angiograph 2 (HRA2; Heidelberg Engineering, Germany) and Optomap Tx (Optomap; Optos, Scotland) FAF images. The lesion composite pattern was categorized as diffuse or granular. Diffuse AF was defined as homogenously increased or decreased AF, and granular AF was defined as dot-like, coarse changes in AF. The mean disease duration and subretinal fluid (SRF) height in the spectral domain optical coherence tomography were compared according to the FAF image characteristics. Lesion brightness before CSC resolution was hypo-AF in 48 eyes (76.2 %), hyper-AF in three (4.8 %), and mixed-AF in 12 (19.0 %) in HRA2 FAF images. In comparison, nine (14.3 %) images were hypo-AF, 44 (69.8 %) were hyper-AF, and 10 (15.9 %) were mixed-AF in Optomap FAF images (P < 0.0001). There was no significant difference in lesion composite pattern between the two FAF image wavelengths. Patients with lesions that were hyper-AF in Optomap FAF and hypo-AF in HRA2 FAF had a shorter disease duration and greater SRF height (1 month, 281 um) than those who were hyper-AF in both Optomap and HRA2 images (26 months, 153 um; P = 0.004, 0.001). The two types of FAF images of CSC showed different lesion brightness before and after CSC resolution but demonstrated similar lesion composite patterns.

Fundus autofluorescence findings in central serous chorioretinopathy using two different confocal scanning laser ophthalmoscopes: correlation with functional and structural status.

PubMed

Shin, Joo Youn; Choi, Hun Jin; Lee, Jonghyun; Choi, Moonjung; Chung, Byunghoon; Byeon, Suk Ho

2016-08-01

To compare autofluorescence (AF) findings using wide-field (Optomap) and conventional (HRA-AF) confocal scanning laser ophthalmoscopy (cSLO) systems in patients with central serous chorioretinopathy (CSC), and to investigate the correlations between AF findings and functional and anatomical status. Optical coherence tomography (OCT) and AF images were compared in 73 eyes with serous retinal detachment (SRD) (group A) and 30 eyes without SRD (group B). We evaluated AF findings from the SRD region, atrophic area, and foveola. Correlations between AF findings and outer retinal abnormalities in OCT and visual acuity (VA) were analyzed. Optomap-AF was more effective than HRA-AF in identifying the margins of a detached area (P = 0.001) in group A, and for monitoring mild outer retinal damage (P = 0.041) in group B. The foveolar AF grades in both instruments were significantly correlated with VA and central foveal thickness (CFT) in both group A (Optomap, VA r s = 0.33, P = 0.012; CFT r s = -0.38, P = 0.002; HRA, VA r s = 0.62, P < 0.001; CFT r s = -0.70, P < 0.001) and group B (Optomap, VA r s = 0.71, P < 0.001, CFT r s = -0.78, P < 0.001; HRA, VA r s = 0.40, P = 0.026, CFT r s = -0.40, P = 0.030). Optomap-AF was found to be advantageous for monitoring subretinal status in eyes with SRD, and more accurately reflected mild outer retinal changes in eyes without SRD. Foveolar AF grades of both imaging modalities were significantly correlated with functional and anatomical status.

The hyper-fluorescent transitional bands in ultra-late phase of indocyanine green angiography in chronic central serous chorioretinopathy.

PubMed

Hua, Rui; Yao, Kai; Xia, Fan; Li, Jun; Guo, Lei; Yang, Guoxing; Tao, Jun

2016-03-01

Chronic central serous chorioretinopathy (CSCR) is regarded as a type of severe diffuse retinal pigment epitheliopathy. There is an atrophic tract at level of retinal pigment epithelium (RPE) due to hyper-permeability of choroidal vessels, along with photoreceptor (PR) atrophy. Indocyanine green angiography (ICGA) is considered a gold standard for diagnosis. The purpose of this work is to investigate the hyper-fluorescent transitional bands (HFTB) between hypo-fluorescent and normal regions of the retina in the ultra-late phase of ICGA in CSCR. 26 chronic CSCR eyes and 12 relative normal eyes received spectral domain optical coherence tomography (SD-OCT), and ICGA at the 24th hour after indocyanine green (ICG) intravenous injection. In the ultra-late phase, images showed homogenous fluorescence in all normal eyes. On the contrary, geographical hypofluorescent lesions with atrophy of RPE was noted in 26 chronic CSCR eyes. Moreover, HFTB with intact RPE and disrupted PR was detected in 20 out of 26 chronic CSCR eyes (76.9%). The HFTB may indicate the early damage in chronic CSCR. Ultra-late ICGA can monitor not only metabolic status by endogenous melanin, but also membrane function in RPE by exogenous ICG molecule. © 2015 Wiley Periodicals, Inc.

Pneumatic Displacement with Perfluoropropane Gas and Intravitreal Tissue Plasminogen Activator for Subretinal Subfoveal Hemorrhage after Focal Laser Photocoagulation in Central Serous Chorioretinopathy

PubMed Central

Espinoza, Juan V.; Lasave, Andres F.; Savino-Zari, Dario; Arevalo, Fernando A.

2014-01-01

Objective. To report the visual and anatomic outcomes of pneumatic displacement with perfluoropropane (C3F8) gas and intravitreal tissue plasminogen activator (IVTPA) for subretinal subfoveal hemorrhage after focal laser photocoagulation in central serous chorioretinopathy (CSCR). Method. Interventional, retrospective case report of one eye (one patient). Outcome measures included visual acuity (VA), central macular thickness (CMT), and size of the lesion at two weeks of followup. Fluorescein angiography (FA) and optical coherent tomography (OCT) were used to measure anatomic outcomes. Results. A 35-year-old man with history of chronic CSCR received focal laser photocoagulation in the right eye two days before presentation. At initial examination, VA was 20/200 (ETDRS chart), CMT was 398 μ, and a subretinal subfoveal hemorrhage was seen. Tissue plasminogen activator (tPA) at a dose of 25 µg/0.1 mL was injected intravitreally before intravitreal C3F8 injection, and prone positioning was indicated postoperatively. At 24 hours, the hemorrhage had been displaced inferiorly and VA improved to 20/100. Two weeks later, VA improved to 20/80, CMT decreased to 225 μ, and the hemorrhage decreased without foveal involvement. Conclusions. The technique seems safe and effective in treating visually significant subretinal subfoveal hemorrhage. PMID:25485161

Long-term results and recurrence rates after spironolactone treatment in non-resolving central serous chorio-retinopathy (CSCR).

PubMed

Herold, Tina Rike; Rist, Kristina; Priglinger, Siegfried Georg; Ulbig, Michael Werner; Wolf, Armin

2017-02-01

To evaluate the long-term results of spironolactone in non-resolving central serous chorio-retinopathy (CSCR) and recurrence rates of CSCR. Interventional uncontrolled open-label prospective clinical trial of patients with non-resolving CSCR who were treated with spironolactone 50 mg daily (Spironolacton AL® 50 mg, ALIUD PHARMA) for up to 16 weeks. Follow-up visits were performed at 3, 6, 9, and 12 months. Retreatment criteria for recurrence were: gain in sub-retinal fluid (SRF) of more than 25 % plus/or increase of central retinal thickness (CRT) of more than 50 μm plus visual symptoms compared to last visit. 12-month efficacy of upload treatment with spironolactone. Secondary outcome measure was the recurrence rate at 6, 9, and 12 months. Of the 21 study eyes treated, 71 % (n = 15) showed significant improvement or complete regression on OCT examination over 12 months. Nineteen percent of the patients (n = 4) showed a stable course from visit 1 to visit 12. The overall reduction of sub-retinal fluid from visit 1 (156 μm ± 131 SD) to visit 12 (53 μm ± 93 SD) was statistically significant (p = 0.003). The change of mean visual acuity (log MAR) from 0.25 (± 0.17 SD) at baseline to 0.17 (± 0.18 SD) at visit 12 was statistically significant, with p = 0.044. Our results confirm a positive effect of spironolactone in non-resolving CSCR in 71 % of cases. Evaluation of recurrence rates and retreatments showed good results in patients who responded to spironolactone primarily. A prospective randomized trial may provide better data about this non-invasive treatment.

Half-Fluence Photodynamic Therapy for Chronic Central Serous Chorioretinopathy: Predisposing Factors for Visual Acuity Outcomes.

PubMed

Matušková, Veronika; Vysloužilová, Daniela; Uher, Michal

2017-12-18

Central serous chorioretinopathy (CSC) is characterised by a serous detachment of the neurosensory retina in the macula. Chronic CSC tends to affect older individuals with a less favourable visual outcome. Photodynamic therapy (PDT) with verteporfin is a possible therapeutic approach in cases of CSC with no tendency for spontaneous resorption. PDT has shown good anatomic and functional results in treating chronic CSC. For the purpose of diminishing side effects, modifications of the standard protocol were used. This is a retrospective study of 32 eyes with CSC of 32 patients treated by half-fluence PDT. The patients underwent complete ophthalmology examination. On optical coherence tomography (OCT) we measured central retinal thickness (CRT), the outer nuclear layer (ONL), presence of subfoveolar detachment of retinal pigment epithelium (PED), disturbance of external limiting membrane (ELM), morphological changes in the inner segment/outer segment (IS/OS) line and retinal pigment epithelium (RPE) atrophy. We evaluated at baseline, 3 and 12 months after PDT. The mean BCVA at baseline was 0.41 ± 0.23 log MAR, the mean BCVA at 3 months was 0.24 ± 0.20 and at the end of the follow-up it was 0.23 ± 0.200. We observed statistically significant improvements of visual acuity after 3 and 12 months (p < 0.001, Wilcoxon test). The mean central retinal thickness at baseline was 373 ± 87 µm, the mean CRT after 3 months was 234 ± 42 µm and after 12 months 223 ± 39 µm. A significant reduction from baseline was seen after 3 months and 12 months (p < 0.001, Wilcoxon test). Baseline ONL reached 80 ± 27 µm, after 3 months it was 78 ± 20 and after 12 months it was 74 ± 20 µm. We observed a statistically significant change in diminishing the amount of PED after PDT after 3 months and after 12 months (p = 0.021, McNemar's test). We observed that in patients with RPE ablation, there is lower chance for the restitution of the IS

Selective Retina Therapy in Acute and Chronic-Recurrent Central Serous Chorioretinopathy.

PubMed

Framme, Carsten; Walter, Andreas; Berger, Lieselotte; Prahs, Philipp; Alt, Clemens; Theisen-Kunde, Dirk; Kowal, Jens; Brinkmann, Ralf

2015-01-01

Selective retina therapy (SRT), the confined laser heating and destruction of retinal pigment epithelial cells, has been shown to treat acute types of central serous chorioretinopathy (CSC) successfully without damaging the photoreceptors and thus avoiding laser-induced scotoma. However, a benefit of laser treatment for chronic forms of CSC is questionable. In this study, the efficacy of SRT by means of the previously used 1.7-µs and shorter 300-ns pulse duration was evaluated for both types of CSC, also considering re-treatment for nonresponders. In a two-center trial, 26 patients were treated with SRT for acute (n = 10) and chronic-recurrent CSC (n = 16). All patients presented with subretinal fluid (SRF) in OCT and leakage in fluorescein angiography (FA). SRT was performed using a prototype SRT laser system (frequency-doubled Q-switched Nd:YLF-laser, wavelength 527 nm) with adjustable pulse duration. The following irradiation settings were used: a train of 30 laser pulses with a repetition rate of 100 Hz and pulse durations of 300 ns and 1.7 µs, pulse energy 120-200 µJ, retinal spot size 200 µm. Because SRT lesions are invisible, FA was always performed 1 h after treatment to demonstrate laser outcome (5-8 single spots in the area of leakage). In cases where energy was too low, as indicated by missing FA leakage, energy was adjusted and the patient re-treated immediately. Observation intervals were after 4 weeks and 3 months. In case of nonimprovement of the disease after 3 months, re-treatment was considered. Of 10 patients with active CSC that presents focal leakage in FA, 5 had completely resolved fluid after 4 weeks and all 10 after 3 months. Mean visual acuity increased from 76.6 ETDRS letters to 85.0 ETDRS letters 3 months after SRT. Chronic-recurrent CSC was characterized by less severe SRF at baseline in OCT and weaker leakage in FA than in acute types. Visual acuity changed from baseline 71.6 to 72.8 ETDRS letters after 3 months. At this time, SRF

Effect of Intravitreal Injection of Bevacizumab on Acute Central Serous Chorioretinopathy Patients Who Visited Feiz Hospital during 2014–2015 Period

PubMed Central

Akhlaghi, Mohamad Reza; Nasrollahi, Cobra; Namgar, Seyed Mohamad; Kianersi, Farzan; Dehghani, Ali Reza; Arefpour, Reza

2017-01-01

Background: Aim of this clinical trial is the evaluation of the effect of intravitreal injection of bevacizumab on acute central serous chorioretinopathy (CSC). Materials and Methods: In a nonrandomized clinical trial, 36 CSC eyes (with <1-month disease history) were examined. Initially, all the patients underwent posterior and anterior segment examinations as well as complete eye examination to evaluate the best spectacle-corrected visual acuity (BSCVA). Then, optical coherence tomography was performed to confirm the diagnosis. The patients were divided to the two groups each of 18 subjects, which 18 patients received intravitreal injection of bevacizumab (1.25 mg) and the rest of them did not receive any treatment (control group). The patients were health checked by the end of the 1st and 3rd months. Significance level was considered as P < 0.05. Results: In the BSCVA, no significant difference in visual improvement was observed in baseline vision compared to each other (P = 0.481). There was also no significant difference in the vision of intervention and control groups 1 and 3 months after injection (P = 0.379 and P = 0.557). A significant decrement existed in the intervention group compared with the control group in the maximum central macular thickness at 1 month after injection (P = 0.001); however, the difference was not significant when comparing the two groups at baseline and 3 months after injection (P = 0.925 and P = 0.338). Conclusion: In general, according to the results of this study, intravitreal injection of bevacizumab was not effective in improvement of patients with acute CSC, although it had no side effects. PMID:29142888

Alcohol- and light-induced electro-oculographic responses in age-related macular degeneration & central serous chorioretinopathy. alcohol- and light-induced EOG responses in ARMD & CSC.

PubMed

Wu, Kathy H C; Marmor, Michael F

2005-01-01

The non-photic electro-oculographic (EOG) response induced by alcohol has been proposed as an indicator of retinal pigment epithelial (RPE) integrity, and reported to be abnormal in age-related macular degeneration (ARMD). To evaluate this proposal, we have measured the alcohol-EOG as well as the ISCEV-standard EOG in patients with ARMD (n=11 patients, 4 eyes with drusen, 8 eyes with 'dry' and 7 eyes with 'wet' lesions) and central serous chorioretinopathy (CSC, n=11 patients, 7 eyes with active and 6 eyes with inactive lesions), compared with 29 normal controls. We recorded the alcohol-induced EOG response after a single oral administration of ethanol at 160 mg/kg, followed by an ISCEV-standard EOG. Blood alcohol levels were monitored with a breath analyzer. We found that neither the alcohol-EOG nor the light-induced EOG response showed any difference between either ARMD or CSC patients and normal controls. Nor was there difference among eyes of different ARMD or CSC subgroups. In addition, blood alcohol concentrations near the time of the alcohol-EOG peak showed no obvious relationship with peak/baseline ratios. These data suggest that neither the alcohol- nor the light-induced EOG is a sensitive indicator of these diseases.

Clinical application of optical coherence tomography in combination with functional diagnostics: advantages and limitations for diagnosis and assessment of therapy outcome in central serous chorioretinopathy.

PubMed

Schliesser, Joshua A; Gallimore, Gary; Kunjukunju, Nancy; Sabates, Nelson R; Koulen, Peter; Sabates, Felix N

2014-01-01

While identifying functional and structural parameters of the retina in central serous chorioretinopathy (CSCR) patients, this study investigated how an optical coherence tomography (OCT)-based diagnosis can be significantly supplemented with functional diagnostic tools and to what degree the determination of disease severity and therapy outcome can benefit from diagnostics complementary to OCT. CSCR patients were evaluated prospectively with microperimetry (MP) and spectral domain optical coherence tomography (SD-OCT) to determine retinal sensitivity function and retinal thickness as outcome measures along with measures of visual acuity (VA). Patients received clinical care that involved focal laser photocoagulation or pharmacotherapy targeting inflammation and neovascularization. Correlation of clinical parameters with a focus on functional parameters, VA, and mean retinal sensitivity, as well as on the structural parameter mean retinal thickness, showed that functional measures were similar in diagnostic power. A moderate correlation was found between OCT data and the standard functional assessment of VA; however, a strong correlation between OCT and MP data showed that diagnostic measures cannot always be used interchangeably, but that complementary use is of higher clinical value. The study indicates that integrating SD-OCT with MP provides a more complete diagnosis with high clinical relevance for complex, difficult to quantify diseases such as CSCR.

En face choroidal vascular feature imaging in acute and chronic central serous chorioretinopathy using swept source optical coherence tomography.

PubMed

Lee, Won June; Lee, Jung Wook; Park, Seung Hun; Lee, Byung Ro

2017-05-01

To evaluate the variable depth tomographic features of choroidal vasculature in acute and chronic central serous chorioretinopathy (CSC) using swept source optical coherence tomography (SS-OCT) en face imaging. We retrospectively reviewed the en face SS-OCT images of 29 patients that presented with acute (12 eyes) or chronic (17 eyes) CSC. All of the patient eyes underwent 6×6 macular scans with SS-OCT (DRI OCT-1, Topcon, Tokyo, Japan), fluorescein angiography and indocyanine green angiography. The en face image was used to investigate the choroidal vasculature of each layer. Moreover, we determined that some parts corresponded to choriocapillaris and Sattler's layer attenuation, whereas choroidal vessel dilatation was associated with Haller's layer. At Haller's layer level, choroidal vessel dilatation was observed in 11 of 12 acute CSC (91.7%) and 15 of 17 chronic CSC (88.2%). In acute CSC, choroidal vessel dilatation was divided into focal (9/11; 81.8%) and diffuse (2/11; 18.2%) patterns. The chronic CSC cases demonstrated different patterns of choroidal vessel dilatation: focal (5/15; 33.3%) and diffuse (10/15; 66.6%). Ten of the acute CSC eyes (83.3%) and 14 of the chronic CSC eyes (82.4%) were found to have obscured choriocapillaris and Sattler's layers on en face imaging. En face imaging of SS-OCT is useful when combined with angiography in CSC for evaluating choroidal vessel dilatation at Haller's layer and to identify obscured upper layers. We identified different choroidal vessel dilatation patterns between acute and chronic CSC. These findings might be useful for pathophysiological understanding of CSC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Correlation between morphological characteristics in spectral-domain-optical coherence tomography, different functional tests and a patient's subjective handicap in acute central serous chorioretinopathy.

PubMed

Gerendas, Bianca S; Kroisamer, Julia-Sophie; Buehl, Wolf; Rezar-Dreindl, Sandra M; Eibenberger, Katharina M; Pablik, Eleonore; Schmidt-Erfurth, Ursula; Sacu, Stefan

2018-01-16

The purpose of this study was to identify quantitatively measurable morphologic optical coherence tomography (OCT) characteristics in patients with an acute episode of central serous chorioretinopathy (CSC) and evaluate their correlation to functional and psychological variables for their use in daily clinical practice. Retinal thickness (RT), the height, area and volume of subretinal fluid (SRF)/pigment epithelium detachments were evaluated using the standardized procedures of the Vienna Reading Center. These morphologic characteristics were compared with functional variables [best-corrected visual acuity (BCVA), contrast sensitivity (CS), retinal sensitivity/microperimetry, fixation stability], and patients' subjective handicap from CSC using the National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25). Data from 39 CSC patients were included in this analysis. Three different SRF height measures showed a high negative correlation (r = -0.7) to retinal sensitivity within the central 9°, which was also negatively correlated with SRF area and volume (r = -0.6). The CS score and fixation stability (fixation points within 2°) showed a moderate negative correlation (r = -0.4) with SRF height variables. Comparison of the subjective handicap with morphological characteristics in spectral-domain (SD)-OCT showed SRF height had the highest correlation (r = -0.4) with the subjective problems reported and overall NEI VFQ-25 score. In conclusion, SRF height measured in SD-OCT showed the best correlation with functional variables and patients' subjective handicap caused by the disease and therefore seems to be the best variable to look at in daily clinical routine. Even though area and volume also show a correlation, these cannot be so easily measured as height and are therefore not suggested for daily clinical routine. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Risk Factors for Central Serous Chorioretinopathy: Multivariate Approach in a Case-Control Study.

PubMed

Chatziralli, Irini; Kabanarou, Stamatina A; Parikakis, Efstratios; Chatzirallis, Alexandros; Xirou, Tina; Mitropoulos, Panagiotis

2017-07-01

The purpose of this prospective study was to investigate the potential risk factors associated independently with central serous retinopathy (CSR) in a Greek population, using multivariate approach. Participants in the study were 183 consecutive patients diagnosed with CSR and 183 controls, matched for age. All participants underwent complete ophthalmological examination and information regarding their sociodemographic, clinical, medical and ophthalmological history were recorded, so as to assess potential risk factors for CSR. Univariate and multivariate analysis was performed. Univariate analysis showed that male sex, high educational status, high income, alcohol consumption, smoking, hypertension, coronary heart disease, obstructive sleep apnea, autoimmune disorders, H. pylori infection, type A personality and stress, steroid use, pregnancy and hyperopia were associated with CSR, while myopia was found to protect from CSR. In multivariate analysis, alcohol consumption, hypertension, coronary heart disease and autoimmune disorders lost their significance, while the remaining factors were all independently associated with CSR. It is important to take into account the various risk factors for CSR, so as to define vulnerable groups and to shed light into the pathogenesis of the disease.

Central serous choroidopathy in the Hallermann-Streiff Syndrome.

PubMed

Blair, N P; Brockhurst, R J; Lee, W

1981-08-01

Central serous choroidopathy was observed in a young patient with the Hallermann-Streiff syndrome. Typical features of this syndrome include microphthalmos, proportionate dwarfism, dyscephaly with birdlike facies, dental abnormalities, and hypotrichosis. Exceptional aspects of this case include age of onset (11 years), high hyperopic refractive error (+ 13.00 sphere), and multiple recurrences caused by six separate documented leaks from the choroid. Fundus changes previously reported in the Hallermann-Streiff syndrome, interpreted as chorioretinal pigmentary changes, may have been secondary to previous undiagnosed central serous choroidopathy. Periodic ophthalmoscopy should be performed and may detect unrecognized episodes of central serous choroidopathy for which photocoagulation would be beneficial.

Comparing half-dose photodynamic therapy with high-density subthreshold micropulse laser treatment in patients with chronic central serous chorioretinopathy (the PLACE trial): study protocol for a randomized controlled trial.

PubMed

Breukink, Myrte B; Downes, Susan M; Querques, Giuseppe; van Dijk, Elon H C; den Hollander, Anneke I; Blanco-Garavito, Rocio; Keunen, Jan E E; Souied, Eric H; MacLaren, Robert E; Hoyng, Carel B; Fauser, Sascha; Boon, Camiel J F

2015-09-21

Chronic central serous chorioretinopathy (cCSC) is an eye disease characterized by an accumulation of serous fluid under the retina. It is postulated that this fluid accumulation results from hyperpermeability and swelling of the choroid, the underlying vascular tissue of the eye, causing a dysfunction of the retinal pigment epithelium. This fluid accumulation causes neuroretinal detachment. A prolonged neuroretinal detachment in the macula can lead to permanent vision loss. Therefore, treatment is aimed primarily at achieving resolution of subretinal fluid, preferably within the first 4 months after diagnosis of the disease. A broad spectrum of treatment modalities has been investigated in cCSC, but no consensus exists on the optimal treatment of cCSC. Currently, photodynamic therapy (PDT) and high-density subthreshold micropulse laser treatment (HSML) are among the most frequently cited treatments in obtaining successful neuroretinal reattachment. This is a randomized, controlled, open-label, multicenter trial comparing the efficacy of half-dose PDT to HSML in treating patients with cCSC. A total of 156 patients will be recruited, 78 patients in each treatment arm, with a maximum follow-up duration of 8 months after the first treatment. A complete ophthalmological examination with vision-related quality of life (NEI VFQ-25) and stress questionnaires, will be performed at baseline, 6 to 8 weeks after the first treatment, 6 to 8 weeks after a second treatment (if necessary), and at the final follow-up visit at 7 to 8 months after the first treatment. Treatment visits will be scheduled within 3 weeks after the baseline visit, and within 3 weeks after the first control visit, if a second treatment is required. Both half-dose PDT and HSML may be effective treatments in cCSC, but because of the lack of prospective randomized controlled trials, which treatment should be the first choice remains unclear. The aim of this study is to compare the efficacy of half-dose PDT

EN FACE IMAGING OF PACHYCHOROID SPECTRUM DISORDERS WITH SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY.

PubMed

Dansingani, Kunal K; Balaratnasingam, Chandrakumar; Naysan, Jonathan; Freund, K Bailey

2016-03-01

To correlate clinical manifestations with choroidal morphology in pachychoroid disorders, including central serous chorioretinopathy, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, and polypoidal choroidal vasculopathy, using en face swept-source optical coherence tomography (OCT). Patients with pachychoroid spectrum diagnoses were identified nonconsecutively through a review of charts and multimodal imaging. Each eye was categorized as uncomplicated pachychoroid, pachychoroid pigment epitheliopathy, central serous chorioretinopathy, pachychoroid neovasculopathy, or polypoidal choroidal vasculopathy. All patients included in this series then underwent bilateral swept-source OCT. Sixty-six eyes of 33 patients were included. Numbers assigned to diagnostic categories were 8 uncomplicated pachychoroid, 13 pachychoroid pigment epitheliopathy, 27 central serous chorioretinopathy, 15 pachychoroid neovasculopathy, and 3 polypoidal choroidal vasculopathy. One eye was classified as normal. Swept-source OCT choroidal thickness maps confirmed increased thickness under the areas of pachychoroid pigment epitheliopathy, central serous chorioretinopathy, type 1 NV (pachychoroid neovasculopathy), or polyps (polypoidal choroidal vasculopathy). En face swept-source OCT showed dilated outer choroidal vessels in all eyes. In several eyes with a chronic disease, focal choriocapillaris atrophy with inward displacement of deep choroidal vessels was noted. Although clinical manifestations of pachychoroid spectrum disorders vary considerably, these entities share morphologic findings in the choroid, including increased thickness and dilated outer choroidal vessels. En face swept-source OCT localizes these changes to disease foci and shows additional findings that may unify our understanding of disease pathogenesis.

Yellow (577 nm) micropulse laser versus half-dose verteporfin photodynamic therapy in eyes with chronic central serous chorioretinopathy: results of the Pan-American Collaborative Retina Study (PACORES) Group.

PubMed

Roca, Jose A; Wu, Lihteh; Fromow-Guerra, Jans; Rodríguez, Francisco J; Berrocal, Maria H; Rojas, Sergio; Lima, Luiz H; Gallego-Pinazo, Roberto; Chhablani, Jay; Arevalo, J Fernando; Lozano-Rechy, David; Serrano, Martin

2018-02-08

To compare the functional and anatomical outcomes of eyes with chronic central serous chorioretinopathy treated with yellow micropulse (MP) laser versus half-dose verteporfin photodynamic therapy (PDT). This is a multicentre, retrospective comparative study of 92 eyes treated with yellow MP laser (duty cycle of 5%, zero spacing between spots, spot size varied from 100 to 200 µm, power varied from 320 to 660 mW, and the pulse burst duration was 200 ms) and 67 eyes treated with PDT (half-dose verteporfin (3 mg/m 2 ) infused over 10 min), followed by laser activation for 83 s. Spot sizes varied from 400 to 2000 µm. In the MP group, at 12 months of follow-up, the mean best corrected visual acuity (BCVA) improved from the logarithm of the minimum angle of resolution (logMAR) of 0.41±0.27 at baseline to 0.21±0.26 (P<0.0001), 48.9% (45/92) of eyes had an improvement of ≥3 lines of BCVA from baseline, 48.9% (45/92) of eyes remained within 2 lines of baseline BCVA, and only 2.2% (2/92) of eyes lost ≥3 lines of BCVA from baseline. In the PDT group, at 12 months of follow-up, the mean BCVA changed from logMAR of 0.50±0.34 at baseline to 0.47±0.34 (P=0.89), 19% (13/67) of eyes had an improvement of ≥3 lines of BCVA from baseline, 73% (49/67) of eyes remained within 2 lines of baseline BCVA, and 7% (5/67) of eyes lost ≥3 lines of BCVA from baseline. There were no adverse events attributable to the yellow MP laser treatment. One eye in the PDT group developed choroidal neovascularisation, which was treated with three intravitreal bevacizumab injections. Both PDT and MP are effective in restoring the macular anatomy. In places where PDT is not available, yellow MP laser may be an adequate treatment alternative. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Intravitreal Bevacizumab vs.Combination Therapy for CNV Due to Other Than AMD

ClinicalTrials.gov

2014-01-13

Choroidal Neovascularization; Myopia; Punctate Inner Choroidopathy (PIC); Multifocal Choroiditis; Ocular Histoplasmosis Syndrome; Central Serous Chorioretinopathy (CSC); Angioid Streaks; Trauma, or Hereditary Eye Diseases

The prevalence of 4G/5G polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene in central serous chorioretinopathy and its association with plasma PAI-1 levels.

PubMed

Sogutlu Sari, Esin; Yazici, Alper; Eser, Betül; Erol, Muhammet Kazim; Kilic, Adil; Ermis, Sitki Samet; Koytak, Arif; Akşit, Hasan; Yakut, Tahsin

2014-12-01

Central serous chorioretinopathy (CSCR) is a poorly understood disease and the choroidal circulation abnormality induced by the plasminogen activator inhibitor type 1 (PAI-1) seems to be associated with the pathogenesis. There are many reports indicating that 4 G/5 G polymorphism of the PAI-1 gene is a risk factor for several diseases related to the elevated serum levels of PAI-1. To evaluate the 4 G/5 G polymorphism of the PAI-1 gene and its association with serum levels of PAI-1 in acute CSCR patients. Sixty CSCR patients and 50 healthy control patients were included. The PAI-1 4 G/5 G was genotyped using the polymerase chain reaction-restriction technique. Serum PAI-1 level was measured using enzyme-linked immunosorbent assay. Demographic data consisting of age, sex, body mass index (BMI) as well as genotype disturbances and serum PAI-1 levels were compared between the groups. Statistical significance for differences in the serum PAI-1 levels of each group with different genotypes was also analyzed. The CSCR group consisted of 40 male (66.7%) and 20 female (33.3%) patients with a mean age of 46.7 ± 8.39 years. The control group consisted of 32 male (64%) and 18 female (36%) healthy subjects with a mean age of 45.8 ± 8.39 years. There was no statistically significant difference between the groups in terms of age, sex and BMI. In the CSCR group the genotype frequencies were 4 G/4G: 30% (n = 18), 4G/5 G: 50% (n = 30), 5 G/5G: 20% (n = 12) and in the control group genotype frequencies were 34% (n = 17), 42% (n = 21) and 24% (n = 12), respectively. There was no statistically significant difference in the distribution of genotypes among the groups (chi-squared, p = 0.70). The CSCR group had a significantly higher serum PAI-1 concentration than the control group (p = 0.001). In both groups the mean plasma PAI-1 concentration did not vary significantly among the different genotypes (p > 0.05). Although our results demonstrated that the patients with acute CSCR have

A nationwide study of ovarian serous borderline tumors in Denmark 1978-2002. Risk of recurrence, and development of ovarian serous carcinoma.

PubMed

Hannibal, Charlotte Gerd; Vang, Russell; Junge, Jette; Frederiksen, Kirsten; Kurman, Robert J; Kjaer, Susanne K

2017-01-01

Absolute risk and risk factors for recurrence and ovarian serous carcinoma following ovarian serous borderline tumors (SBTs) is not well-established. We included all women with SBTs in Denmark, 1978-2002. Diagnoses were confirmed by centralized pathology review and classified as atypical proliferative serous tumor (APST) or noninvasive low-grade serous carcinoma (LGSC). Implants were classified as noninvasive or invasive. Medical records were collected and reviewed, and follow-up was obtained. Subsequent diagnoses were also confirmed by centralized pathology review. We examined absolute risk and risk factors for recurrent APST and serous carcinoma using Cox regression. The absolute serous carcinoma risk after, respectively, 5 and 20years was 5.0% and 13.9% for noninvasive LGSC, and 0.9% and 3.7% for APST. Serous carcinoma risk was significantly higher following noninvasive LGSC compared with APST among stage I patients/patients without implants (HR=5.3; 95% CI: 1.7-16.3), whereas no significant association with tumor type was found in advanced stage patients/patients with implants. Advanced stage - notably invasive implants - bilaterality, surface involvement, and residual disease increased serous carcinoma risk. However, women with stage I APST also had a higher risk than the general population. This largest population-based cohort of verified SBTs revealed that women with noninvasive LGSC are significantly more likely to develop serous carcinoma than women with APST, which could not entirely be explained by invasive implants. Although invasive implants was a strong risk factor for serous carcinoma, even women with stage I APST were at increased risk compared with the general population. Copyright © 2016 Elsevier Inc. All rights reserved.

Microperimetry in patients with central serous retinopathy.

PubMed

Toonen, F; Remky, A; Janssen, V; Wolf, S; Reim, M

1995-09-01

In patients with acute central serous retinopathy (CSR), evaluation of visual acuity alone may not represent visual function. In patients with acute CSR, visual function may be disturbed by localized scotomas, distortion, and waviness. For the assessment of localized light sensitivity and stability of fixation, patients with CSR were evaluated by fundus perimetry with a scanning laser ophthalmoscope (SLO 101, Rodenstock Instruments). In all, 21 patients with acute CSR and 19 healthy volunteers were included in the study. Diagnosis of CSR was established by ophthalmoscopy and digital video fluorescein angiography. All patients and volunteers underwent static suprathreshold perimetry with the SLO. Light sensitivity was quantified by presenting stimuli with different light intensities (intensity, 0-27.9 dB above background; size, Goldmann III; wavelength, 633 nm) using an automatic staircase strategy. Stimuli were presented with simultaneous real-time monitoring of the retina. Fixation stability was quantified by measuring the area encompassing 75% of all points of fixation. Light sensitivity was 18-20 dB in affected areas, whereas in healthy eyes and outside the affected area, values of 22-24 dB were obtained. Fixation stability was significantly decreased in the affected eye as compared with normal eyes (33 +/- 12 versus 21 +/- 4 min of arc; P < 0.01). Static perimetry with an SLO is a useful technique for the assessment of localized light sensitivity and fixation stability in patients with macular disease. This technique could provide helpful information in the management of CSR.

HLA-A29-POSITIVE BIRDSHOT CHORIORETINOPATHY IN AN AFRICAN AMERICAN PATIENT.

PubMed

Knezevic, Alexander; Munk, Marion R; Pappas, Frankie; Merrill, Pauline T; Goldstein, Debra A

2016-01-01

To report the first documented case of HLA-A29-positive birdshot chorioretinopathy in an African American patient. A 51-year-old African American woman presented with a 10-year history of photopsia, progressive decrease in visual acuity, metamorphopsia, and new nyctalopia. Both fundi showed evidence of periphlebitis, arterial attenuation, macular edema, and diffuse chorioretinal atrophy. Fluorescein angiography revealed diffuse vascular leakage, and indocyanine green showed evenly distributed and symmetrical hypofluorescent spots, which were difficult to appreciate on fundoscopy. Workup revealed a positive HLA-A29 and was negative for sarcoid, tuberculosis, and syphilis. Birdshot chorioretinopathy overwhelmingly affects non-Hispanic Caucasians, but there have been rare reported cases in other ethnicities including Hispanics and African Americans. This patient's ethnicity may have contributed to the 10-year delay in diagnosis. To our knowledge, this is the first documented HLA-A29 positive case of birdshot chorioretinopathy in an African American. HLA-A29 may be a useful supportive test in cases with classic clinical presentation in non-Caucasian patients to enable the correct diagnose in a timely manner.

Prognostic indicators in ovarian serous borderline tumours.

PubMed

Malpica, Anais; Longacre, Teri A

2018-02-01

There have been great strides in our understanding of the serous group of borderline and malignant pelvic epithelial neoplasms in the past decade. While most serous borderline tumours have a favourable prognosis, recurrences and progression to carcinoma occur, often following a protracted clinical course. Clinical and pathological risk factors tend to co-vary, but the presence and type of extraovarian disease is the most important predictor for progression. Progression usually takes the form of low-grade serous carcinoma, although transformation to high-grade carcinoma is occasionally seen. A serous borderline - low-grade serous carcinoma pathway analogous to neoplastic transformation pathways seen in other organ systems has been proposed, based on global gene expression profiling, shared mutations in KRAS or BRAF, and in most cases, the presence of serous borderline tumour in de novo low-grade serous carcinoma. This discussion focuses on the key prognostic factors that predispose to disease progression and/or transformation to carcinoma in serous borderline tumours. Published by Elsevier B.V.

Evaluation of focal choroidal excavation in the macula using swept-source optical coherence tomography.

PubMed

Lim, F P M; Loh, B K; Cheung, C M G; Lim, L S; Chan, C M; Wong, D W K

2014-09-01

To evaluate imaging findings of patients with focal choroidal excavation (FCE) in the macula using swept-source optical coherence tomography (SS-OCT) and correlate it clinically. Prospective observational case series. Eleven consecutive patients (12 eyes) with FCE were described. Data on demographics and clinical presentation were collected and imaging findings (including color photography, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and SS-OCT) were analyzed. The primary diagnosis was epiretinal membrane (two eyes), choroidal neovascularization (one eye), polypoidal choroidal vasculopathy (three eyes), central serous chorioretinopathy (one eye), and dry age-related macular degeneration (two eyes). Eleven out of 12 of the lesions were conforming. One presented with a non-conforming lesion that progressed to a conforming lesion. One eye had multiFCE and two had two overlapping choroidal excavations. Using the SS-OCT, we found the choroid to be thinned out at the area of FCE but sclera remained normal. The choroidal tissue beneath the FCE was abnormal, with high internal reflectivity and poor visualization of choroidal vessels. There was loss of contour of the outer choroidal boundary that appeared to be pulled inward by this abnormal choroidal tissue. A suprachoroidal space was noted beneath this choroidal tissue and the choroidal-scleral interface was smooth. Repeat SS-OCT 6 months after presentation showed the area of excavation to be stable in size. FCE can be associated with epiretinal membrane, central serous chorioretinopathy, and age-related macular degeneration. The choroid was thinned out in the area of FCE.

Evaluation of focal choroidal excavation in the macula using swept-source optical coherence tomography

PubMed Central

Lim, F P M; Loh, B K; Cheung, C M G; Lim, L S; Chan, C M; Wong, D W K

2014-01-01

Purpose To evaluate imaging findings of patients with focal choroidal excavation (FCE) in the macula using swept-source optical coherence tomography (SS-OCT) and correlate it clinically. Methods Prospective observational case series. Eleven consecutive patients (12 eyes) with FCE were described. Data on demographics and clinical presentation were collected and imaging findings (including color photography, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and SS-OCT) were analyzed. Results The primary diagnosis was epiretinal membrane (two eyes), choroidal neovascularization (one eye), polypoidal choroidal vasculopathy (three eyes), central serous chorioretinopathy (one eye), and dry age-related macular degeneration (two eyes). Eleven out of 12 of the lesions were conforming. One presented with a non-conforming lesion that progressed to a conforming lesion. One eye had multiFCE and two had two overlapping choroidal excavations. Using the SS-OCT, we found the choroid to be thinned out at the area of FCE but sclera remained normal. The choroidal tissue beneath the FCE was abnormal, with high internal reflectivity and poor visualization of choroidal vessels. There was loss of contour of the outer choroidal boundary that appeared to be pulled inward by this abnormal choroidal tissue. A suprachoroidal space was noted beneath this choroidal tissue and the choroidal–scleral interface was smooth. Repeat SS-OCT 6 months after presentation showed the area of excavation to be stable in size. Conclusion FCE can be associated with epiretinal membrane, central serous chorioretinopathy, and age-related macular degeneration. The choroid was thinned out in the area of FCE. PMID:24946847

Low-grade serous ovarian cancer: A review.

PubMed

Kaldawy, Anis; Segev, Yakir; Lavie, Ofer; Auslender, Ron; Sopik, Victoria; Narod, Steven A

2016-11-01

Epithelial ovarian cancers can be divided into the more common, aggressive type II cancers and the less common, slow-growing type I cancers. Under this model, serous ovarian carcinomas can be subdivided into high-grade (type II) and low-grade (type I) tumours. The two-tier system for grading serous ovarian carcinomas is superior to more detailed grading systems in terms of predicting survival. Low-grade serous carcinomas typically present in young women and have a relatively good prognosis, despite being resistant to chemotherapy. Low-grade serous cancers have a high prevalence of KRAS and BRAF mutations, but a low prevalence of TP53 mutations (which are characteristic of high-grade serous cancers). Among women with low-grade serous ovarian cancer, the presence of a KRAS/BRAF mutation is a favorable prognostic factor. Studies of the mitogen-activated protein kinase (MAPK) inhibitor in low-grade serous ovarian cancer suggest that identifying MAPK mutations might eventually be useful in guiding treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Central serous retinopathy with permanent visual deficit in a commercial air transport pilot: a case report.

PubMed

Newman, David G

2002-11-01

This report describes a case of central serous retinopathy (CSR) in the right eye of a commercial air transport pilot which resulted in a permanent reduction in visual acuity and the loss of his license. The previously fit and well pilot developed sudden loss of central vision, which resolved spontaneously. He then went on to experience recurrent episodes of fluctuating visual acuity (down to 6/60) and visual dysfunction in the right eye. His left eye remained unaffected. Eventually his condition stabilized, and he was left with a permanent reduction in right visual acuity (6/36) with intact peripheral visual fields and a completely normal left eye. After a period of grounding of 12 mo, he sought to have his license reinstated. He was considered to be a functionally monocular pilot, and as such was granted a conditional Class 1 medical category. The aeromedical disposition of this pilot and the issues involved in determining the fitness to fly of pilots with permanent visual defects arising from CSR are discussed.

Myelin Oligodendrocyte Glycoprotein-IgG-positive Recurrent Bilateral Optic Papillitis with Serous Retinal Detachment: A Case Report.

PubMed

Kon, Tomoya; Hikichi, Hiroki; Ueno, Tatsuya; Suzuki, Chieko; Nunomura, Jinichi; Kaneko, Kimihiko; Takahashi, Toshiyuki; Nakashima, Ichiro; Tomiyama, Masahiko

2018-05-18

Autoantibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been detected in inflammatory demyelinating central nervous system diseases. A 30-year-old woman had blurred vision, marked optic nerve disc swelling, serous retinal detachment at the macular on optic coherence tomography, and MOG-IgG seropositivity. The patient was thought to have optic papillitis associated with MOG-IgG. Her symptoms rapidly improved after high-dose methylprednisolone therapy. We hypothesize that serous retinal detachment was secondary, arising from optic papillitis. This is the first report of the concurrence of optic papillitis with MOG-IgG and serous retinal detachment. MOG-IgG should be tested in patients with marked optic disc swelling.

Serous endometrial intraepithelial carcinoma: a case series and literature review.

PubMed

Pathiraja, P; Dhar, S; Haldar, K

2013-01-01

Minimal uterine serous cancer (MUSC) or serous endometrial intraepithelial carcinoma (EIC) has been described by many different names since 1998. There have been very few cases reported in literature since EIC/MUSC was recognized as a separate entity. The World health Organization (WHO) Classification favors the term serous EIC. Although serous EIC is confined to the uterine endometrium at initial histology diagnosis, a significant number of patients could have distal metastasis at diagnosis, without symptoms. Serous EIC is considered as being the precursor of uterine serous cancer (USC), but pure serous EIC also has an aggressive behavior similar to USC. It is therefore prudent to have an accurate diagnosis and appropriate surgical staging. There are very few published articles in literature that discuss the pure form of serous EIC. The aim of this series is to share our experience and review evidence for optimum management of serous EIC. We report a series of five women treated in our institute in the last 3 years. We reviewed the relevant literature on serous EIC and various management strategies, to recommend best clinical practice. Pure serous EIC is a difficult histopathological diagnosis, which requires ancillary immunohistochemical staining. It can have an aggressive clinical behavior with early recurrence and poor survival. Optimum surgical staging, with appropriate adjuvant treatment, should be discussed when treating these patients.

Does a p53 "Wild-type" Immunophenotype Exclude a Diagnosis of Endometrial Serous Carcinoma?

PubMed

Fadare, Oluwole; Roma, Andres A; Parkash, Vinita; Zheng, Wenxin; Walavalkar, Vighnesh

2018-01-01

combined with p53-wild-type immunophenotype, including analytic limitations, a nonserous histotype displaying morphologic mimicry of serous carcinoma, and true biological phenomena (including the possibility of a TP53-independent pathway of endometrial serous carcinogenesis). Ultimately, our central thematic question is provisionally answered in the negative. At present, the available data would not support a categorical conclusion that a p53 alteration is a necessary and obligate component in the genesis and/or diagnosis of endometrial serous carcinoma. On the basis of their collective experience, the authors proffer some recommendations on the use of p53 immunohistochemistry in the histotyping of endometrial carcinomas.

Testing for NRAS Mutations in Serous Borderline Ovarian Tumors and Low-Grade Serous Ovarian Carcinomas

PubMed Central

Grzanka, Dariusz; Grabiec, Marek

2018-01-01

The Idylla NRAS Mutation Test, performed on the Biocartis Idylla system, is an in vitro diagnostic tool for the qualitative assessment of 18 NRAS mutations in codons 12, 13, 59, 61, 117, and 146. Low-grade serous ovarian cancer (LGSC) represents less than 10% of all serous ovarian carcinomas. LGSCs are believed to arise from preexisting cystadenomas or serous borderline tumors (SBOTs) that eventually progress to an invasive carcinoma. The molecular analysis of cancer-causing mutations and the development of targeted biological therapies constitute a milestone in the diagnosis and therapy of ovarian malignancies. According to some authors, NRAS may be an important oncogene for the progression of SBOT to a frankly invasive disease. The primary aim of this study was to verify if a fully integrated, real-time PCR-based Idylla system can be used for the rapid determination of the NRAS mutation status in patients with serous borderline ovarian tumors and low-grade serous ovarian carcinomas. The study included tissue specimens from 12 patients with histopathologically verified ovarian masses, operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz (Poland), between January 2009 and June 2012. The mean age of the study patients was 52.5 years (range 27–80 years). NRAS mutation in codon 13 (G13D, p.Gly13Asp; nucleotide: c.38G>A) was found in one patient, a woman with low-grade serous ovarian carcinoma. To the best of our knowledge, our experiment was the first published study using the novel Idylla NRAS Mutation Test for the evaluation of ovarian tumors in a clinical setting. The Idylla platform is an interesting ancillary first-line rapid and fully automated instrument to detect NRAS mutations in SBOTs and LGSCs. However, the clinical usefulness of this method still needs to be verified in larger groups of cancer patients. PMID:29682098

Incidence of Serous Tubal Intraepithelial Carcinoma (STIC) by Algorithm Classification in Serous Ovarian Tumor Associated with PAX8 Expression in Tubal Epithelia: A Study of Single Institution in Japan

PubMed Central

Yamamoto, Toshiya

2015-01-01

Serous ovarian carcinoma is now hypothesized to originate from fallopian tube epithelium (FTE). We investigated the FTE abnormalities in the patients with epithelial ovarian tumors. Our study included 55 cases of serous tumors (24 carcinomas, 8 borderline tumors, and 23 adenomas), 14 mucinous carcinomas, 22 endometrioid carcinomas, 5 clear cell carcinomas, and 2 malignant Brenner tumors. FTE was diagnosed by the diagnostic algorithm, which combines the data of morphology, and p53, Ki-67 immunostaining, as serous tubal intraepithelial carcinoma, serous tubal intraepithelial lesion, p53 signature, and normal/reactive. Serous tubal intraepithelial carcinoma, serous tubal intraepithelial lesion, p53 signature, and normal/reactive were observed in 5, 3, 0, and 16 cases in serous carcinoma; 0, 3, 0, and 5 cases in serous borderline tumor; 0, 1, 1, and 21 cases in serous adenoma; 0, 0, 1, and 13 cases in mucinous carcinoma; 0, 0, 3, and 19 cases in endometrioid carcinoma; 0, 0, 0, and 5 cases in clear cell carcinoma; and 0, 1, 0, and 1 case in malignant Brenner tumor. Among tumors of serous histology and between carcinomas, FTE abnormalities differed significantly (P<0.05). Serous tubal intraepithelial carcinomas were only found in serous carcinoma. The incidence of secretory cell proliferation (SCP) was examined by PAX8 expression. The rate of SCP was extremely high in serous carcinoma (96%). Among tumors of serous histology and between carcinomas, an incidence of SCP differed significantly (P<0.05). Patients with SCP were significantly older (P<0.0001). Our observations were concordant with the hypothesis of serous ovarian carcinogenesis. The SCP has a meaningful association with serous ovarian cancer. PMID:25473747

Serous Tubal Carcinogenesis: The Recent Concept of Origin of Ovarian, Primary Peritoneal and Fallopian Tube High-Grade Serous Carcinoma.

PubMed

Kar, Tushar; Kar, Asaranti; Dhal, Ipsita; Panda, Sasmita; Biswal, Priyadarshini; Nayak, Bhagyalaxmi; Rout, Niranjan; Samantray, Sagarika

2017-12-01

Pelvic (non-uterine) high-grade serous carcinomas (PHGSC) including ovarian, tubal and primary peritoneal serous carcinomas have increased death: incidence ratio due to presentation at advanced stage, rapid progression, poor prognosis and high morbidity. Ambiguity regarding their pathogenesis and lack of a proper screening method is the cause of their late detection and high fatality rate. This study was undertaken to assess the fallopian tube for the presence of precursor lesions in pelvic serous carcinoma. This was a prospective case-control study carried out in a tertiary care center. Consecutive specimens of 55 cases of pelvic high-grade serous carcinoma and 41 controls inclusive of 21 low-grade serous carcinoma, 10 benign adnexal masses and 10 normal adnexa were included in the study. Both side fallopian tubes in each case were subjected to histopathological examination and p53, Ki67 immunohistochemistry. There were 55 cases of PHGSC comprising of 50 cases of ovarian HGSC, two cases of primary peritoneal carcinoma (PPC) and three cases of tubal carcinoma. Serous tubal intraepithelial carcinoma (STIC) was detected in 14 cases (28%), p53 signature in 13 cases (26%) and tubal intraepithelial lesion in transition in 10 cases (20%) of ovarian HGSC. One case (50%) of PPC and one (33%) case of tubal carcinoma revealed the presence of STIC. None of the controls exhibited any precursor lesion except ovarian low-grade serous carcinoma where p53 was detected in 20% of cases. This revelation concludes that fallopian tubes are the sites of precursors of PHGSC to a large extent. In the absence of a proper screening method of HGSC, prophylactic bilateral salpingectomy at hysterectomy for benign diseases can achieve ultimate goal of reduction in incidence of PHGSC.

[Multiple retinal pigment epithelial detachments: a case report].

PubMed

González-Escobar, A B; González de Gor-Crooke, J L; López-Egea-Bueno, M A; García-Campos, J M

2014-05-01

A 47 year-old female who presented with a bilateral idiopathic multiple pigment epithelial detachment (PED) in a routine visit. This pathology is shown as a rare clinical manifestation, where the outcome is resolution of localized atrophy of the pigment epithelium, with a good functional prognosis. PED is a common clinical manifestation in several chorioretinal diseases, particularly in macular degeneration associated with age. Idiopathic PED can be considered as a kind of central type II serous chorioretinopathy. Fundus fluorescein angiography (FFA) and optical coherence tomography (OCT) are complementary tests to study the number, extension, and nature of these PED. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Transconjunctival drainage of serous and hemorrhagic choroidal detachment.

PubMed

Rezende, Flávio A; Kickinger, Mônica C; Li, Gisèle; Prado, Renata F; Regis, Luiz Gustavo T

2012-02-01

To describe a novel surgical technique for drainage of bullous serous and hemorrhagic choroidal detachments. A prospective, consecutive case series of 6 eyes with serous and/or hemorrhagic choroidal detachments secondary to intraocular surgery was documented to evaluate the feasibility of using the 25-gauge and 20-gauge transconjunctival trocar/cannula systems to drain choroidal detachments. Two eyes had expulsive hemorrhagic choroidal detachments and 4 eyes had serous choroidal detachments after glaucoma surgeries. A 25-gauge infusion line was placed in the anterior chamber. A 20-gauge (in eyes with hemorrhagic choroidal detachments) or a 25-gauge (in eyes with serous detachments) trocar/cannula system was inserted into the suprachoroidal space 7.0 mm from limbus. After drainage, the cannulas were removed and no sutures were placed. Pars plana vitrectomy was performed only in eyes with concomitant pathology that demanded the additional procedure. The primary outcome measure was presence of choroidal detachment at 1 week, 2 weeks, and 1 month postoperatively. Secondary outcome measures were visual acuity at 6 months and intraocular pressure at 1 week and 1, 3, and 6 months postoperatively. Drainage of hemorrhagic choroidal detachments resulted in resolution of the detachments by 1 month postoperatively. In eyes with serous detachments, resolution was achieved by 1 week postdrainage. In both groups, intraocular pressure increased to at least 10 mmHg by postoperative Week 1. The visual acuity improved in all eyes. No complications related to the transconjunctival technique were noted. Transconjunctival drainage of serous and hemorrhagic choroidal detachments seems to be a feasible and simple surgical option with minimal scleral and conjunctival damage. Pars plana vitrectomy may not be necessary when draining choroidal detachments in this manner.

Spectral domain optical coherence tomography imaging of retinal diseases in Singapore.

PubMed

Singh, Mandeep; Chee, Caroline K L

2009-01-01

In this retrospective case series, the authors reviewed cases of patients with macular disorders whose eyes had been imaged using spectral domain optical coherence tomography (SD-OCT) (Cirrus HD-OCT; Carl Zeiss Meditec, Inc., Dublin, CA). SD-OCT images were obtained from patients with a variety of ocular conditions attending a tertiary retinal clinic in Singapore from August 2007 to December 2007, according to standardized protocols. Images of 428 eyes from 301 patients were reviewed. Ocular diagnoses included diabetic macular edema, exudative age-related macular degeneration, central serous chorioretinopathy, cystoid macular edema, retinal vein and artery occlusions, infective chorioretinitis, and others. The authors present four cases of particular interest to illustrate how SD-OCT was useful in complementing the clinician's assessment of macular disease.

Automated segmentation of serous pigment epithelium detachment in SD-OCT images

NASA Astrophysics Data System (ADS)

Sun, Zhuli; Shi, Fei; Xiang, Dehui; Chen, Haoyu; Chen, Xinjian

2015-03-01

Pigment epithelium detachment (PED) is an important clinical manifestation of multiple chorio-retinal disease processes, which can cause the loss of central vision. A 3-D method is proposed to automatically segment serous PED in SD-OCT images. The proposed method consists of five steps: first, a curvature anisotropic diffusion filter is applied to remove speckle noise. Second, the graph search method is applied for abnormal retinal layer segmentation associated with retinal pigment epithelium (RPE) deformation. During this process, Bruch's membrane, which doesn't show in the SD-OCT images, is estimated with the convex hull algorithm. Third, the foreground and background seeds are automatically obtained from retinal layer segmentation result. Fourth, the serous PED is segmented based on the graph cut method. Finally, a post-processing step is applied to remove false positive regions based on mathematical morphology. The proposed method was tested on 20 SD-OCT volumes from 20 patients diagnosed with serous PED. The average true positive volume fraction (TPVF), false positive volume fraction (FPVF), dice similarity coefficient (DSC) and positive predictive value (PPV) are 97.19%, 0.03%, 96.34% and 95.59%, respectively. Linear regression analysis shows a strong correlation (r = 0.975) comparing the segmented PED volumes with the ground truth labeled by an ophthalmology expert. The proposed method can provide clinicians with accurate quantitative information, including shape, size and position of the PED regions, which can assist diagnose and treatment.

Prediction of chemo-response in serous ovarian cancer.

PubMed

Gonzalez Bosquet, Jesus; Newtson, Andreea M; Chung, Rebecca K; Thiel, Kristina W; Ginader, Timothy; Goodheart, Michael J; Leslie, Kimberly K; Smith, Brian J

2016-10-19

Nearly one-third of serous ovarian cancer (OVCA) patients will not respond to initial treatment with surgery and chemotherapy and die within one year of diagnosis. If patients who are unlikely to respond to current standard therapy can be identified up front, enhanced tumor analyses and treatment regimens could potentially be offered. Using the Cancer Genome Atlas (TCGA) serous OVCA database, we previously identified a robust molecular signature of 422-genes associated with chemo-response. Our objective was to test whether this signature is an accurate and sensitive predictor of chemo-response in serous OVCA. We first constructed prediction models to predict chemo-response using our previously described 422-gene signature that was associated with response to treatment in serous OVCA. Performance of all prediction models were measured with area under the curves (AUCs, a measure of the model's accuracy) and their respective confidence intervals (CIs). To optimize the prediction process, we determined which elements of the signature most contributed to chemo-response prediction. All prediction models were replicated and validated using six publicly available independent gene expression datasets. The 422-gene signature prediction models predicted chemo-response with AUCs of ~70 %. Optimization of prediction models identified the 34 most important genes in chemo-response prediction. These 34-gene models had improved performance, with AUCs approaching 80 %. Both 422-gene and 34-gene prediction models were replicated and validated in six independent datasets. These prediction models serve as the foundation for the future development and implementation of a diagnostic tool to predict response to chemotherapy for serous OVCA patients.

Is the two-tier ovarian serous carcinoma grading system potentially useful in stratifying uterine serous carcinoma? A large multi-institutional analysis.

PubMed

Ahmed, Quratulain; Hussein, Yaser; Hayek, Kinda; Bandyopadhyay, Sudeshna; Semaan, Assaad; Abdul-Karim, Fadi; Al-Wahab, Zaid; Munkarah, Adnan R; Elshaikh, Mohamed A; Alosh, Baraa; Nucci, Marisa R; Van de Vijver, Koen K; Morris, Robert T; Oliva, Esther; Ali-Fehmi, Rouba

2014-02-01

A subset of uterine serous carcinoma (USC) may have better clinical behavior bringing up the possibility that there may be morphologic features, which would help in their categorization. The aim of this study is to evaluate the potential use of the MD Anderson Cancer Center 2-tier grading system for ovarian carcinoma in USC. Tumors assigned a combined score included in this analysis were 1) low-grade: tumors without marked atypia and 12 mitoses/10 high power field (HPF) and 2) high grade: tumors with severe nuclear atypia and >12 mitoses/10 HPF. Clinicopathologic parameters evaluated included patients' age, tumor size, myometrial invasion (MI), lymphovascular invasion (LVI), lymph node (LN), FIGO stage, and patient outcome. 140 patients with USC were included, 30 low grade uterine serous carcinoma (LGUSC) and 110 high grade uterine serous carcinoma (HGUSC). Of all parameters only 2 (MI and stage IA) reached statistical significance. 67% of LGUSC cases showed myometrial invasion versus 93.6% HGUSC cases (p = 0.003). A higher percentage of LGUSC (63.3%) versus HGUSC (32.7%) were in stage IA (p = 0.01). However, by multivariate analysis including age, LVI, stage and tumor grade only stage was an independent prognostic factor. The presence of atypia and mitosis across a uterine serous carcinoma is notoriously variable in magnitude and extent, potentially making evaluation of these features difficult and subsequent grading subjective. Our findings thus show that actual prognostic utility of application of MDACC two-tier grading system to uterine serous carcinoma may not be applicable. Copyright © 2013 Elsevier Inc. All rights reserved.

Are all pelvic (nonuterine) serous carcinomas of tubal origin?

PubMed

Przybycin, Christopher G; Kurman, Robert J; Ronnett, Brigitte M; Shih, Ie-Ming; Vang, Russell

2010-10-01

It has been proposed that the presence of tubal intraepithelial carcinoma (TIC), in association with one-third to nearly half of pelvic serous carcinomas, is evidence of fallopian tube origin for high-grade serous carcinomas that would have been otherwise classified as primary ovarian or peritoneal. To address this hypothesis, we evaluated a series of 114 consecutive pelvic (nonuterine) gynecologic carcinomas at our institution (2006 to 2008) to determine the frequency of TIC in 52 cases in which all the resected fallopian tube tissue was examined microscopically. These 52 cases were classified as ovarian (n=37), peritoneal (n=8), or fallopian tube (n=7) in origin as per conventional criteria based on disease distribution. The presence of TIC and its location and relationship to invasive carcinoma in the fallopian tubes and ovaries were assessed. Among the 45 cases of ovarian/peritoneal origin, carcinoma subtypes included 41 high-grade serous, 1 endometrioid, 1 mucinous, 1 high-grade, not otherwise specified, and 1 malignant mesodermal mixed tumor. TIC was identified in 24 cases (59%) of high-grade serous carcinoma but not among any of the other subtypes; therefore, the term serous TIC (STIC) is a more specific appellation. STICs were located in the fimbriated end of the tube in 22 cases (92%) and in the ampulla in 2 (8%); they were unilateral in 21 (88%) and bilateral in 3 (13%). STICs in the absence of an associated invasive carcinoma in the same tube were detected in 7 cases (30%) and with invasive carcinoma in the same tube in 17 (71%). Unilateral STICs were associated with bilateral ovarian involvement in 15 cases and unilateral (ipsilateral) ovarian involvement in 5 (the remaining case with a unilateral STIC had a primary peritoneal tumor with no ovarian involvement); the bilateral STICs were all associated with bilateral ovarian involvement. Six of the 7 primary tubal tumors were high-grade serous carcinomas, and 4 of these 6 (67%) had STICs. Based on

Keratin 5 overexpression is associated with serous ovarian cancer recurrence and chemotherapy resistance.

PubMed

Ricciardelli, Carmela; Lokman, Noor A; Pyragius, Carmen E; Ween, Miranda P; Macpherson, Anne M; Ruszkiewicz, Andrew; Hoffmann, Peter; Oehler, Martin K

2017-03-14

This study investigated the clinical significance of keratin 5 and 6 expression in serous ovarian cancer progression and chemotherapy resistance. KRT5 and KRT6 (KRT6A, KRT6B & KRT6C) gene expression was assessed in publically available serous ovarian cancer data sets, ovarian cancer cell lines and primary serous ovarian cancer cells. Monoclonal antibodies which detect both K5/6 or only K5 were used to assess protein expression in ovarian cancer cell lines and a cohort of high grade serous ovarian carcinomas at surgery (n = 117) and after neoadjuvant chemotherapy (n = 21). Survival analyses showed that high KRT5 mRNA in stage III/IV serous ovarian cancers was significantly associated with reduced progression-free (HR 1.38, P < 0.0001) and overall survival (HR 1.28, P = 0.013) whilst high KRT6 mRNA was only associated with reduced progression-free survival (HR 1.2, P = 0.031). Both high K5/6 (≥ 10%, HR 1.78 95% CI; 1.03-2.65, P = 0.017) and high K5 (≥ 10%, HR 1.90, 95% CI; 1.12-3.19, P = 0.017) were associated with an increased risk of disease recurrence. KRT5 but not KRT6C mRNA expression was increased in chemotherapy resistant primary serous ovarian cancer cells compared to chemotherapy sensitive cells. The proportion of serous ovarian carcinomas with high K5/6 or high K5 immunostaining was significantly increased following neoadjuvant chemotherapy. K5 can be used to predict serous ovarian cancer prognosis and identify cancer cells that are resistant to chemotherapy. Developing strategies to target K5 may therefore improve serous ovarian cancer survival.

Risk factors for benign serous and mucinous epithelial ovarian tumors.

PubMed

Jordan, Susan J; Green, Adèle C; Whiteman, David C; Webb, Penelope M

2007-03-01

To investigate the risk factors for benign serous and mucinous epithelial ovarian tumors. Cases were women newly diagnosed with benign serous ovarian tumors (n=230) or benign mucinous tumors (n=133) between 2002 and 2005. Control women were selected at random from the general population (n=752). All participants completed a comprehensive reproductive and lifestyle questionnaire. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) and to simultaneously adjust for potential confounding factors. Current smoking was associated with a three-fold increase in risk of benign mucinous tumors (OR 3.25, 95% CI 1.97-5.34), and there was a trend of increasing risk with increasing amount smoked (P<.001). Both recent obesity (OR 1.93, 95% CI 1.30-2.88) and obesity at age 20 (OR 4.38, 95% CI 1.88-10.20) were associated with increased risk of benign serous ovarian tumors, and having had a hysterectomy was also related to increased risk of serous (OR 2.75, 95% CI 1.90-3.96), but not mucinous tumors. Ever having had a term pregnancy was inversely associated with both tumor types (combined OR 0.65, 95% CI 0.43-0.97), although greater numbers of pregnancies did not decrease risk further. Use of hormonal contraceptives was unrelated to risk. Our results suggest some differences in risk factors between benign serous and mucinous epithelial ovarian tumors and that risk factors for benign serous tumors differ from those well established for ovarian cancer. The results also suggest that there is potential for prevention of these common conditions through avoidance of smoking and obesity. II.

The frequency and significance of WT-1 expression in serous endometrial carcinoma.

PubMed

Hedley, Catherine; Sriraksa, Ruethairat; Showeil, Rania; Van Noorden, Susan; El-Bahrawy, Mona

2014-09-01

Serous endometrial carcinoma is an aggressive type of endometrial carcinoma. Wilms tumor gene 1 (WT-1) is commonly expressed in ovarian serous carcinomas and considered a diagnostic marker of these tumors. However, it is generally believed that WT-1 is rarely expressed by endometrial serous carcinoma. The aim of this study was to evaluate the frequency and significance of WT-1 expression in endometrial serous carcinoma. We studied the expression of WT-1 in formalin-fixed, paraffin-embedded tumor sections from 77 cases of endometrial serous carcinoma. Thirty-four tumors showed positive expression for WT-1 (44%). There was a statistically significant association between the presence of WT-1 expression and disease-free survival (DFS), where patients with tumors expressing WT-1 had a shorter DFS compared with those with no WT-1 expression (P = .031; median DFS, 15 and 38 months, respectively). By multivariate Cox regression analysis, DFS was independent from other clinicopathological data (tumor stage, presence of lymphovascular space invasion, cervical involvement, and extrauterine spread), indicating that WT-1 expression is independently associated with DFS. Our study shows that WT-1 is expressed in a considerable percentage of endometrial serous carcinomas, suggesting a role for WT-1 in the pathology of these tumors. This has therapeutic significance, as WT-1 is an emerging target for immunotherapy. Moreover, our results show that WT-1 has prognostic value, being predictive of DFS. As a potential prognostic marker and therapeutic target, we recommend that WT-1 expression should be included in histopathologic reports of endometrial serous carcinoma. Copyright © 2014 Elsevier Inc. All rights reserved.

[Why and how should serous otitis media be treated?].

PubMed

François, M; Bonfils, P; Van Haver, K; Narcy, P

1992-10-01

Serous otitis media is an extremely commonplace condition in pediatric patients and tends to resolve spontaneously. Only some forms warrant treatment. Indications for treatment include frequent superinfections, lasting hearing impairment with adverse consequences on socialization, or debilitation of the tympanic membrane carrying a risk for the ear. Tympanostomy tubes are a palliative treatment for serous otitis which restores hearing within a few hours and eliminates unfixated retractions of the tympanic membrane within a few weeks. Tympanostomy tubes may lead to complications including otorrhea and perforation of the tympanic membrane and should therefore be used only in patients with severe otitis media. Etiologic treatment of serous otitis rests on restoration of satisfactory nasal ventilation (education to improve nose-blowing, adenoidectomy), improvement of eustachian tube patency (corticosteroids), and modification of the characteristics of middle ear secretions (mucolytic agents and mucomodifying agents).

Multimodal imaging of the disease progression of birdshot chorioretinopathy.

PubMed

Teussink, Michel M; Huis In Het Veld, Paulien I; de Vries, Lieuwe A M; Hoyng, Carel B; Klevering, B Jeroen; Theelen, Thomas

2016-12-01

To study outer retinal deterioration in relation to clinical disease activity in patients with birdshot chorioretinopathy using fundus autofluorescence and spectral-domain optical coherence tomography (OCT). A single-centre retrospective cohort study was carried out on 42 eyes of 21 patients with birdshot disease, using a multimodal imaging approach including fundus autofluorescence, OCT, fluorescein angiography and indocyanine green angiography in combination with a patient chart review. The patients' overall clinical activity of retinal vasculitis during the follow-up period was determined by periods of clinical activity as indicated by fluorescein angiography and associated treatment decisions. Image analysis was performed to examine the spatial correspondence between autofluorescence changes and disruption of the photoreceptor inner segment ellipsoid zone on OCT. Three common types of outer retinal lesions were observed in fovea-centred images of 43% of patients: circular patches of chorioretinal atrophy, ellipsoid zone disruption on OCT, and outer retinal atrophy on autofluorescence and OCT. There was good spatial correspondence between ellipsoid zone disruption and areas of diffuse hyper-autofluorescence outside the fovea. Interestingly, the ellipsoid zone disruption recovered in four out of seven patients upon intensified therapeutic immunosuppression. Most patients only developed peripapillary atrophy and occasional perivascular hypo-autofluorescence. A multimodal imaging approach with autofluorescence imaging and OCT may help to detect ellipsoid zone disruption in the central retina of patients with birdshot disease. Our results suggest that ellipsoid zone disruption may be related to both the activity and duration of retinal vasculitis, and could help to determine therapeutic success in birdshot disease. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Comparison of tumor markers and clinicopathological features in serous and mucinous borderline ovarian tumors.

PubMed

Alanbay, I; Aktürk, E; Coksuer, H; Ercan, C M; Karaşahin, E; Dede, M; Yenen, M C; Ozan, H; Dilek, S

2012-01-01

The aim of this study was to assess tumor markers and clinicopathological findings of patients with serous and mucinous borderline ovarian tumor (BOT) features. The study consisted of 50 patients that were diagnosed with and treated for BOT between 2005-2010 in three centers. CA125, CA19-9, and CA125+CA19-9 levels and clinicopathological features were compared in serous and mucinous histotypes. In serous and mucinous BOTs, correlations between tumor markers and demographics such as age, menopausal status, parity, clinical findings (stage, relapse, adjuvant chemotherapy, cytology, lymph node involvement and tumoral morphology (cystic-solid content, papilla, septation) were evaluated. There were no significant differences between serous and mucinous tumors in the clinicopathological features such as stage, tumor markers, age, menopausal status, or cytology. In serous BOTs we found a significant relation between elevated CA125+ CA19-9, CA19-9 and recurrence (p < 0.05). Also there was a significant relation between elevated CA125+ CA19-9, CA19-9 and cytology positivity (p < 0.05). We found a significant relation in serous BOTs between elevated CA125+CA19-9, adjuvant chemotherapy and lymph node metastases (p < 0.05). Also In mucinous BOTs with papilla formation we found a significant relation between elevated CA125 and CA125+ CA19-9 (p < 0.05). There was significant relation between cytology positivity and elevated CA19-9 in mucinous BOTs (p < 0.05). Serum tumor markers of serous and mucinous BOTs were different in relation to their clinicopathological features. This may reflect differences of serous and mucinous BOTs.

Revisiting the role of radiation treatment for non-serous subtypes of epithelial ovarian cancer.

PubMed

Thomas, G

2013-01-01

Except for its palliative use, radiation has been largely abandoned in the management of ovarian cancers because of the recognized efficacy of chemotherapy agents. Whole abdominal irradiation (WAR), however, has been shown to be of adjuvant and curative value in ovarian cancer with microscopic or minimal residual disease in the pelvis, the so-called "intermediate risk group." Recent hypothesis generating data from the use of adjuvant radiation following adjuvant chemotherapy in ovarian cancer has shown an incremental survival benefit for the rarer non-serous ovarian subtypes including clear cell, endometrioid, and mucinous. No incremental benefit was observed for the more common serous subtype. A retrospective examination of early trials using WAR as the sole postoperative treatment in ovarian cancer has determined that the majority of patients in these studies and cured by radiation actually had the non-serous subtypes. The recognition that the non-serous subtypes differ from the serous cancers in their stage of presentation, their molecular characteristics, their response to classic chemotherapy, and their outcomes suggest the non-serous subtypes should be treated as rare and different cancers. In addition to specific targeting therapies that may be developed, radiation should be reconsidered as part of the treatment armamentarium for these diseases.

Prognosis for advanced-stage primary peritoneal serous papillary carcinoma and serous ovarian cancer in Taiwan.

PubMed

Chao, Kuan-Chong; Chen, Yi-Jen; Juang, Chi-Mou; Lau, Hei-Yu; Wen, Kuo-Chang; Sung, Pi-Lin; Fang, Feng-Ying; Twu, Nae-Fang; Yen, Ming-Shyen

2013-03-01

To compare the prognosis of patients with advanced-stage primary peritoneal serous papillary carcinoma (PSPC) or papillary serous ovarian cancer (PSOC). This was a retrospective case-control study and included two study groups: one with stage III/IV PSPC (n = 38) patients and the other with PSOC (n = 53) patients. Patients were matched for histologic subtype (serous tumor), tumor stage, tumor grade, residual disease at the end of debulking surgery (primary or interval), and age (±5 years). Mean age was significantly greater for patients with PSPC (63.03 ± 11.88 years) than for patients with PSOC (55.92 ± 12.56 years, p = 0.008). Optimal debulking surgery was performed initially in 71.9% of PSPC patients and 66.0% of PSOC patients. In addition, 93.9% of PSPC patients and 92.3% of PSOC patients were treated with platinum-paclitaxel chemotherapy. The frequency of high-grade tumors was significantly higher in the PSPC (100%) than in the PSOC group (68.3%; p < 0.001). Progression-free survival (PFS) was similar in the PSPC [median 12 months, 95% confidence interval (CI) 7.3-16.7] and PSOC groups (median 16.7 months, 95% CI 12.9-20.4; p = 0.470). Overall survival was shorter in the PSPC (median 62 months, 95% CI 19.6-104.4) than in the PSOC group (median 77.5 months, 95% CI 69.7-85.2; p = 0.006, log-rank statistic). PFS was similar for advanced-stage PSPC and PSOC patients. Since the PSPC patients tended to be older and have more high-grade tumors, OS was shorter for PSPC than for POSC patients. Thus, management of the two types of cancer should not differ. Copyright © 2013. Published by Elsevier B.V.

Overexpression and oncogenic function of HMGA2 in endometrial serous carcinogenesis

PubMed Central

Wei, Linxuan; Liu, Xiaolin; Zhang, Wenjing; Wei, Yuyan; Li, Yingwei; Zhang, Qing; Dong, Ruifen; Kwon, Jungeun Sarah; Liu, Zhaojian; Zheng, Wenxin; Kong, Beihua

2016-01-01

The high-mobility group A protein 2 (HMGA2) is a non-histone chromatin factor highly expressed in fetal tissue and malignant tumors but rarely detected within normal adult tissues. The clinical implications and biological functions of HMGA2 in endometrial carcinoma are largely unknown. Here we report that HMGA2 expression was barely detected in benign endometrium samples (2 of 28 samples). However, HMGA2 expression increased significantly from precancerous lesion endometrial glandular dysplasia (7 of 17, 41.2%), to serous endometrial intraepithelial carcinoma (5 of 8, 62.5%) and to full blown endometrial serous carcinoma (39 of 59, 66.1%). Functional characterization of HMGA2 revealed that the gene has both tumor growth promotion and metastasis. In addition, HMGA2 induced epithelial-mesenchymal transition (EMT) through modulation vimentin and β-catenin. Furthermore, HMGA2 overexpression started from endometrial serous precancers, non-invasive cancers, as well as in full blown carcinomas in a p53 knockout mouse model we recently established in our laboratory. Our findings suggest that HMGA2 may serve as a useful diagnostic marker in the assessment of endometrial serous cancer and its precursor lesions. PMID:27186400

Identification and Characterization of Genomic Amplifications in Ovarian Serous Carcinoma

DTIC Science & Technology

2008-01-01

lower cost. As a result, we have analyzed more than 40 affinity purified ovarian serous tumors and our results demonstrated that CCNE1, Notch3 , Rsf-1...serous tumors. In addition, we have further characterized the biological functions of the two of the commonly amplified genes, Notch3 and Rsf-1, in...analyses, we have focused on two of the most frequently amplified regions, 11q13.2 (Rsf-1 locus) and 19p13 ( Notch3 locus), for detailed mapping and

Neuropeptides degranulate serous cells of ferret tracheal glands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gashi, A.A.; Borson, D.B.; Finkbeiner, W.E.

1986-08-01

To determine whether serous or mucous cells in tracheal submucosal glands respond to the neuropeptides substance P (SP) and vasoactive intestinal peptide (VIP). The authors studied the peptide-induced changes in gland cell morphology accompanying release of TVSO4-labeled macromolecules from tracheal explants of ferrets. Explants were labeled for 1 h in medium containing TVSO4 and washed for 3.5 additional hours. Base-line secretion in the absence of drugs declined between 1.5 and 3.5 h after the pulse. Between 2.5 and 3.5 h, the average percent change in counts per minute recovered per sample period was not significantly different from zero. Substance Pmore » and VIP added 4 h after labeling each increased greatly the release of TVSO4-labeled macromolecules above base line. Bethanechol, a muscarinic-cholinergic agonist, increased secretion by an average of 142% above base line. Light and electron microscopy of the control tissues showed glands with narrow lumens and numerous secretory granules. Glands treated with SP or VIP had enlarged lumens and the serous cells were markedly degranulated. These phenomena were documented by morphometry and suggest that SP and VIP cause secretion from glands at least partially by stimulating exocytosis from serous cells.« less

Effect of Tubal Sterilization Technique on Risk of Serous Ovarian and Primary Peritoneal Carcinoma

PubMed Central

LESSARD-ANDERSON, Collette R.; HANDLOGTEN, Kathryn S.; MOLITOR, Rochelle J.; DOWDY, Sean C.; CLIBY, William A.; WEAVER, Amy L.; SAUVER, Jennifer ST.; BAKKUM-GAMEZ, Jamie N.

2014-01-01

Objective To determine the effect of excisional tubal sterilization on subsequent development of serous epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC). Methods We performed a population-based, nested case-control study using the Rochester Epidemiology Project. We identified all patients with a diagnosis of serous EOC or PPC from 1966 through 2009. Each case was age-matched to 2 controls without either diagnosis. Odds ratios (ORs) and corresponding 95% CIs were estimated from conditional logistic regression models. Models were adjusted for prior hysterectomy, prior salpingo-oophorectomy, oral contraceptive use, endometriosis, infertility, gravidity, and parity. Results In total, we identified 194 cases of serous EOC and PPC during the study period and matched them with 388 controls (mean [SD] age, 61.4 [15.2] years). Fourteen cases (7.2%) and 46 controls (11.9%) had undergone tubal sterilization. Adjusted risk of serous EOC or PPC was slightly lower after any tubal sterilization (OR, 0.59 [95% CI, 0.29–1.17]; P=.13). The rate of excisional tubal sterilization was lower in cases than controls (2.6% vs 6.4%). Adjusted risk of serous EOC and PPC was decreased by 64% after excisional tubal sterilization (OR, 0.36 [95% CI, 0.13–1.02]; P=.054) compared with those without sterilization or with nonexcisional tubal sterilization. Conclusions We present a population-based investigation of the effects of excisional tubal sterilization on the risk of serous EOC and PPC. Excisional methods may confer greater risk reduction than other sterilization methods. PMID:25316178

Molecular Analysis of Mixed Endometrioid and Serous Adenocarcinoma of the Endometrium

PubMed Central

Lawrenson, Kate; Pakzamir, Elham; Liu, Biao; Lee, Janet M.; Delgado, Melissa K.; Duncan, Kara; Gayther, Simon A.; Liu, Song; Roman, Lynda; Mhawech-Fauceglia, Paulette

2015-01-01

Background The molecular biology and cellular origins of mixed type endometrial carcinomas (MT-ECs) are poorly understood, and a Type II component of 10 percent or less may confer poorer prognoses. Methodology/Principal Findings We studied 10 cases of MT-EC (containing endometrioid and serous differentiation), 5 pure low-grade endometrioid adenocarcinoma (EAC) and 5 pure uterine serous carcinoma (USC). Endometrioid and serous components of the MT-ECs were macrodissected and the expression of 60 candidate genes compared between MT-EC, pure USC and pure EAC. We found that four genes were differentially expressed when MT-ECs were compared to pure low-grade EAC: CDKN2A (P = 0.006), H19 (P = 0.010), HOMER2 (P = 0.009) and TNNT1 (P = 0.006). Also while we found that even though MT-ECs closely resembled the molecular profiles of pure USCs, they also exhibit lower expression of PAX8 compared to all pure cases combined (P = 0.035). Conclusion Our data suggest that MT-EC exhibits the closest molecular and epidemiological similarities to pure USC and supports clinical observations that suggest patients with MT-EC should receive the same treatment as patients with pure serous carcinoma. Novel specific markers of MT-EC could be of diagnostic utility and could represent novel therapeutic targets in the future. PMID:26132201

Pancreatic mixed serous neuroendocrine neoplasm with clear cells leading to diagnosis of von Hippel Lindau disease.

PubMed

Kakkar, Aanchal; Sharma, Mehar C; Yadav, Rajni; Panwar, Rajesh; Mathur, Sandeep R; Iyer, Venkateswaran K; Sahni, Peush

2016-08-01

Mixed serous neuroendocrine neoplasms are extremely rare tumors that are usually seen in female patients and are often associated with von Hippel Lindau (VHL) disease. We describe the case of a 38-year-old male who presented with complaints of anorexia, weight loss, and abdominal pain. CT abdomen showed a mass in the head of the pancreas, multiple small nodules in the body of pancreas, and bilateral adrenal masses. Fine needle aspiration cytology (FNAC) from the mass showed features of a neuroendocrine tumor, with many of the cells demonstrating abundant clear cytoplasm. Histopathological examination of the pancreaticoduodenectomy specimen showed a mixed serous neuroendocrine neoplasm with two components viz. serous cystadenoma and neuroendocrine tumor (NET) World Health Organization (WHO) grade 2. In addition, he was diagnosed to have bilateral pheochromocytomas and a paraganglioma. The synchronicity of these tumors suggested the possibility of VHL disease. Thus, identification of a NET with clear cells or of a mixed serous neuroendocrine neoplasm should raise suspicion of VHL disease. In a mixed tumor, FNAC may identify only one of the two components. Thorough processing of all pancreatic serous tumors for pathological examination is recommended, as NET may occur as a small nodule within the serous cystadenoma. Copyright © 2016 Elsevier GmbH. All rights reserved.

Micropulsed diode laser therapy: evolution and clinical applications.

PubMed

Sivaprasad, Sobha; Elagouz, Mohammed; McHugh, Dominic; Shona, Olajumoke; Dorin, Giorgio

2010-01-01

Many clinical trials have demonstrated the clinical efficacy of laser photocoagulation in the treatment of retinal vascular diseases, including diabetic retinopathy. There is, however, collateral iatrogenic retinal damage and functional loss after conventional laser treatment. Such side effects may occur even when the treatment is appropriately performed because of morphological damage caused by the visible endpoint, typically a whitening burn. The development of the diode laser with micropulsed emission has allowed subthreshold therapy without a visible burn endpoint. This greatly reduces the risk of structural and functional retinal damage, while retaining the therapeutic efficacy of conventional laser treatment. Studies using subthreshold micropulse laser protocols have reported successful outcomes for diabetic macular edema, central serous chorioretinopathy, macular edema secondary to retinal vein occlusion, and primary open angle glaucoma. The report includes the rationale and basic principles underlying micropulse diode laser therapy, together with a review of its current clinical applications. Copyright © 2010 Elsevier Inc. All rights reserved.

Enhanced Depth SD-OCT Images Reveal Characteristic Choroidal Changes in Patients With Vogt-Koyanagi-Harada Disease.

PubMed

Li, Mei; Liu, Qiuhui; Luo, Yan; Li, Yonghao; Lin, Shaofen; Lian, Ping; Yang, Qiufen; Li, Xiaofang; Liu, Xialin; Sadda, SriniVas; Lu, Lin

2016-11-01

To identify characteristic choroidal changes of patients with Vogt-Koyanagi-Harada (VKH) disease at different stages. Fifty-four patients with VKH in the acute uveitic or convalescent stages, 24 patients with central serous chorioretinopathy (CSC), and 54 normal participants were enrolled in this prospective, observational study. Enhanced depth imaging spectral-domain optical coherence tomography scans were captured for all subjects to allow for comparison of choroidal morphological findings. Numerous round or oval hyperreflective profiles with hyporeflective cores, corresponding to choroidal vessels, were observed in the choroid of control participants and patients with CSC; whereas the numbers of these profiles were markedly decreased in the choroid of VKH patients in both the acute uveitic and convalescent stages. A reduction in vascular profiles in the choroid is observed in VKH and may aid in the differentiation with disorders such as CSC. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:1004-1012.]. Copyright 2016, SLACK Incorporated.

A nationwide study of serous "borderline" ovarian tumors in Denmark 1978-2002: centralized pathology review and overall survival compared with the general population.

PubMed

Hannibal, Charlotte Gerd; Vang, Russell; Junge, Jette; Frederiksen, Kirsten; Kjaerbye-Thygesen, Anette; Andersen, Klaus Kaae; Tabor, Ann; Kurman, Robert J; Kjaer, Susanne K

2014-08-01

To describe the study population and estimate overall survival of women with a serous "borderline" ovarian tumor (SBT) in Denmark over 25 years relative to the general population. The Danish Pathology Data Bank and the Danish Cancer Registry were used to identify 1487 women diagnosed with SBTs from 1978 to 2002. The histologic slides were collected from Danish pathology departments and reviewed by expert pathologists and classified as SBT/atypical proliferative serous tumor (APST) or noninvasive low-grade serous carcinoma (LGSC). Associated implants were classified as noninvasive or invasive. Medical records were collected from hospital departments and reviewed. Data were analyzed using Kaplan-Meier and relative survival was estimated with follow-up through September 2, 2013. A cohort of 1042 women with a confirmed SBT diagnosis was identified. Women with stage I had an overall survival similar to the overall survival expected from the general population (p=0.3), whereas women with advanced stage disease had a poorer one (p<0.0001). This was evident both in women with noninvasive (p<0.0001) and invasive implants (p<0.0001). Only among women with advanced stage, overall survival of women with SBT/APST (p<0.0001) and noninvasive LGSC (p<0.0001) was poorer than expected from the general population. To date this is the largest nationwide cohort of SBTs where all tumors have been verified by expert pathologists. Only in women with advanced stage SBT, overall survival is poorer than in the general population which applies both to women with noninvasive and invasive implants as well as to women with SBT/APST and noninvasive LGSC. Copyright © 2014. Published by Elsevier Inc.

BILATERAL SEROUS MACULAR DETACHMENT IN A PATIENT WITH NEPHROTIC SYNDROME.

PubMed

Bilge, Ayse D; Yaylali, Sevil A; Yavuz, Sara; Simsek, İlke B

2018-01-01

The purpose of this study was to report a case of a woman with nephrotic syndrome who presented with blurred vision because of bilateral serous macular detachment. Case report and literature review. A 55-year-old woman with a history of essential hypertension, diabetes, and nephrotic syndrome was presented with blurred vision in both eyes. Her fluorescein angiography revealed dye leakage in the early and subretinal pooling in the late phases, and optical coherence tomography scans confirmed the presence of subretinal fluid in the subfovel area. In nephrotic syndrome cases especially with accompaniment of high blood pressure, fluid accumulation in the retina layer may occur. Serous macular detachment must be kept in mind when treating these patients.

Polymorphisms in the FGF2 gene and risk of serous ovarian cancer: results from the Ovarian Cancer Association Consortium

PubMed Central

Johnatty, Sharon E.; Beesley, Jonathan; Chen, Xiaoqing; Spurdle, Amanda B.; deFazio, Anna; Webb, Penelope M; Goode, Ellen L.; Rider, David N.; Vierkant, Robert A.; Anderson, Stephanie; Wu, Anna H.; Pike, Malcolm; Van Den Berg, David; Moysich, Kirsten; Ness, Roberta; Doherty, Jennifer; Rossing, Mary-Anne; Pearce, Celeste Leigh; Chenevix-Trench, Georgia

2009-01-01

Fibroblast growth factor (FGF)-2 (basic) is a potent angiogenic molecule involved in tumour progression, and is one of several growth factors with a central role in ovarian carcinogenesis. We hypothesised that common single nucleotide polymorphisms (SNPs) in the FGF2 gene may alter angiogenic potential and thereby susceptibility to ovarian cancer. We analysed 25 FGF2 tgSNPs using five independent study populations from the United States and Australia. Analysis was restricted to non-Hispanic White women with serous ovarian carcinoma (1269 cases and 2829 controls). There were no statistically significant associations between any FGF2 SNPs and ovarian cancer risk. There were two nominally statistically significant associations between heterozygosity for two FGF2 SNPs (rs308379 and rs308447; p<0.05) and serous ovarian cancer risk in the combined dataset, but rare homozygous estimates did not achieve statistical significance, nor were they consistent with the log additive model of inheritance. Overall genetic variation in FGF2 does not appear to play a role in susceptibility to ovarian cancer. PMID:19456219

Serous tubal intraepithelial carcinomas associated with high-grade serous ovarian carcinomas: a systematic review.

PubMed

Chen, F; Gaitskell, K; Garcia, M J; Albukhari, A; Tsaltas, J; Ahmed, A A

2017-05-01

Serous tubal intraepithelial carcinomas (STICs) have been documented in high-grade serous ovarian carcinomas (HGSOCs). However, the rate of association between STICs and HGSOCs and, therefore, the fraction of HGSOCs that are likely to have originated from the fallopian tube (FT), has remained unclear. To appraise the literature describing the association between STICs and established HGSOCs. Ovid MEDLINE and EMBASE were searched. Studies were included if they evaluated the frequency of STICs in HGSOCs, and were published in an English peer-reviewed journal. Appropriate studies were evaluated for their compliance with the 'Strengthening and Reporting of Observational Studies in Epidemiology (STROBE)' criteria. Ten articles met the study selection criteria. The reported coexistence between STICs and HGSOCs ranged from 11% to 61% (mean: 31%, 95% CI: 17-46%). STICs were rarely found in other gynaecological cancers. Small sample size, lack of objective criteria to identify STICs and the retrospective nature of the studies contributed to the variability in reporting the rate of the association. STICs were identified commonly in the FTs of women with HGSOC. Finding the true rate of association between STICs and HGSOCs will require further investigations. While there is evidence that a fraction of HGSOCs arise from the FTs, an accurate estimate of that fraction remains to be determined. The lack of an accurate estimate of the association makes it difficult to evaluate the potential magnitude of reduction of HGSOCs following prophylactic salpingectomy. A systematic review of the incidence of STICs in HGSOCs identifies significant methodological inconsistencies. © 2017 Royal College of Obstetricians and Gynaecologists.

Pattern of HER-2 Gene Amplification and Protein Expression in Benign, Borderline, and Malignant Ovarian Serous and Mucinous Neoplasms.

PubMed

Mohammed, Rabab A A; Makboul, Rania; Elsers, Dalia A H; Elsaba, Tarek M A M; Thalab, Abeer M A B; Shaaban, Omar M

2017-01-01

Amplification of HER-2 gene and overexpression of HER-2 receptor play a significant role in the progression of a number of malignancies such as breast cancer. Trastuzumab (anti-HER-2 therapeutic agent) has been used successfully in treatment of breast cancer. The aim of this study was to assess the pattern of HER-2 gene amplification and of HER-2 receptor expression in a spectrum of serous and mucinous ovarian tumors to determine whether HER-2 is altered in these neoplasms similar to that occurring in breast cancer. Formalin-fixed paraffin-embedded microarray tissue sections from 212 specimens were stained with HER-2 antibody using immunohistochemistry and with anti-HER-2 DNA probe using chromogenic in situ hybridization. Specimens consisted of 65 benign tumors (50 serous and 15 mucinous), 26 borderline (13 serous and 13 mucinous), 73 malignant tumors (53 serous carcinoma and 20 mucinous carcinoma), 18 metastatic deposits (13 serous and 5 mucinous), in addition to 30 normal tissues (16 ovarian surface and 14 normal fallopian tube). HER-2 protein-positive expression was not detected in the normal or the benign tissues. Borderline neoplasms showed positive staining, but no overexpression. HER-2 overexpression was seen only in 4 carcinoma specimens: 1/53 (1.8%) primary serous carcinomas and 3/20 (15%) primary mucinous carcinomas. HER-2 gene amplification was seen in 4 specimens: 2 primary mucinous carcinomas and 2 malignant deposits of these 2 mucinous carcinomas. In conclusion, alteration of HER-2 was not detected in ovarian serous neoplasms; however, in mucinous carcinoma, HER-2 amplification and overexpression occur.

Evolution of platinum resistance in high-grade serous ovarian cancer.

PubMed

Cooke, Susanna L; Brenton, James D

2011-11-01

High-grade serous ovarian cancers account for most ovarian-cancer mortality. Although this disease initially responds well to platinum-based chemotherapy, relapse and progression to chemotherapy resistance are frequently seen. Time to relapse after first-line therapy is a predictor of response to secondary platinum treatment: more than 12 months is associated with high chance of a secondary response, whereas relapses within 6 months generally indicate platinum resistance. In this Personal View we discuss whether patterns of response, relapse, and the development of drug resistance in high-grade serous ovarian cancers are related to distinct underlying molecular and cellular biological characteristics. In particular, we propose that rapid relapse with platinum-resistant disease is due to minor subpopulations of intrinsically resistant cancer cells at presentation. Copyright © 2011 Elsevier Ltd. All rights reserved.

High Grade Serous Cystadenocarcinoma of Testis-Case Report of a Rare Ovarian Epithelial Type Tumour

PubMed Central

Nayanar, Sangeetha K; Varadharajaperumal, R; Satheeshbabu, TV; Balasubramanian, Satheesan

2017-01-01

Ovarian epithelial type tumour of testis are extremely rare tumours that resemble ovarian surface epithelial tumours. They usually present as testicular or paratesticular tumours and can be serous, mucinous, endometrioid or Brenner tumour. Serous and mucinous types account for the majority of tumours. The tumours are benign, borderline or malignant, commonly borderline. Here, we report a case of high grade serous cyst adenocarcinoma of testis which manifested as extensive metastasis in supraclavicular, mediastinal and abdominopelvic groups of lymph nodes, lung and adrenal gland without clinical evidence of an overt primary tumour. We report this case so as to make clinicians and pathologists aware of this rare entity and to stress on the fact that this rare entity should be kept in mind when evaluating cases of metastatic adenocarcinoma in male patients. PMID:28764180

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

PubMed

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.

Granular cutaneous glands in the frog Physalaemus biligonigerus (Anura, Leptodactylidae): comparison between ordinary serous and 'inguinal' glands.

PubMed

Delfino, G; Brizzi, R; Alvarez, B B; Gentili, M

1999-12-01

Beside the ordinary granular (or serous) glands, the skin of the leptodactylid frog Physalaemus biligonigerus possesses peculiar clusters of large granular units, the 'inguinal' glands, located in the dorsolateral areas of the pelvic girdle. Both gland types store their specific products within the syncytial cytoplasm of the secretory unit. These secretory materials consist of spheroidal or ellipsoidal bodies (granules) with a repeating substructure. The subcellular features of the immature products of the ordinary serous and inguinal glands are identical. However, these products undergo divergent maturative processes, leading to fluidation on the one hand and condensation on the other. Secretory release into the small gland lumen was observed in both cases, involving merocrine mechanisms. On the basis of the analysis of cutaneous serous gland polymorphism in anurans, the inguinal units in P. biligonigerus do not appear to be an independent line. Rather, these large units belong to the ordinary serous type and represent a gland population specialized in the storage of remarkable amounts of product used in chemical defence of the skin.

Mapping of photoreceptor dysfunction using high resolution three-dimensional spectral optical coherence tomography

NASA Astrophysics Data System (ADS)

Sikorski, B. L.; Szkulmowski, M.; Kałużny, J. J.; Bajraszewski, T.; Kowalczyk, A.; Wojtkowski, M.

2008-02-01

The ability to obtain reliable information on functional status of photoreceptor layer is essential for assessing vision impairment in patients with macular diseases. The reconstruction of three-dimensional retinal structure in vivo using Spectral Optical Coherence Tomography (Spectral OCT) became possible with a recent progress of the OCT field. Three-dimensional data collected by Spectral OCT devices comprise information on light intensity back-reflected from the junction between photoreceptor outer and inner segments (IS/OS) and thus can be used for evaluating photoreceptors impairment. In this paper, we introduced so called Spectral OCT reflectivity maps - a new method of selecting and displaying the spatial distribution of reflectivity of individual retinal layers. We analyzed the reflectivity of the IS/OS layer in various macular diseases. We have measured eyes of 49 patients with photoreceptor dysfunction in course of age-related macular degeneration, macular holes, central serous chorioretinopathy, acute zonal occult outer retinopathy, multiple evanescent white dot syndrome, acute posterior multifocal placoid pigment epitheliopathy, drug-induced retinopathy and congenital disorders.

Analysis of autofluorescence pattern in birdshot chorioretinopathy.

PubMed

Semécas, R; Mauget-Faÿsse, M; Aptel, F; Mailhac, A; Salmon, L; Vasseur, V; Bouillet, L; Chiquet, C

2017-07-01

To characterize and correlate the different patterns of fundus autofluorescence (FAF) in patients with birdshot chorioretinopathy (BSCR), with functional and anatomical parameters. Twenty-one BSCR patients were prospectively studied in 2013 and 2014. Each patient underwent visual acuity (VA) and visual field (SITA standard 30.2) testing as well as fluorescein and indocyanine green angiography, spectral-domain optical coherence tomography (SD-OCT) B scan, enhanced depth imaging (EDI), and fundus autofluorescence (FAF) imaging. The disease was classified as active, chronic, or quiescent. The patients' mean age was 60.3 ± 9.2 years and 60% were female. Disease duration was 5.7 ± 3.7 years. Autofluorescence imaging showed punctiform hyper-FAF spots in 23 out of the 29 eyes (79%), which was significantly associated with a greater visual field mean deviation (-7 ± 7 versus -3 ± 2 dB, p = 0.04). Hypo-FAF was defined as peripapillary (n = 25; 86.2%), macular (n = 10; 34.5%), lichenoid (n = 17; 58.6%), and/or diffuse (n = 13; 44.8%). Lichenoid hypo-FAF was significantly associated with worse VA (0.18 ± 0.24 vs. 0.05 ± 0.07 LogMAR, p = 0.04). Macular hypo-FAF was associated with a history of macular edema (62.5%; p = 0.06). Diffuse hypo-FAF was observed more frequently (p = 0.01) in chronic disease (66.7%) than in active (0%) or quiescent disease (27.3%). Autofluorescence analysis in BRSC patients contributes to evaluating disease activity and could be useful to guide follow-up and treatment.

Papillary Tubal Hyperplasia. The Putative Precursor of Ovarian Atypical Proliferative (Borderline) Serous Tumors, Noninvasive Implants and Endosalpingiosis

PubMed Central

Kurman, Robert J.; Vang, Russell; Junge, Jette; Hannibal, Charlotte Gerd; Kjaer, Susanne K.; Shih, Ie-Ming

2011-01-01

In contrast to the controversy regarding the terminology and behavior of ovarian noninvasive low-grade serous tumors (atypical proliferative serous tumor [APST] and serous borderline tumor [SBT]), little attention has been directed to their origin. Similarly, until recently, proliferative lesions in the fallopian tube have not been extensively studied. The recent proposal that ovarian high-grade serous carcinomas are derived from intraepithelial carcinoma in the fallopian tube prompted us to evaluate the possible role of the fallopian tube in the genesis of low-grade serous tumors. We have identified a lesion, designated “papillary tubal hyperplasia (PTH)”, characterized by small rounded clusters of tubal epithelial cells and small papillae, with or without associated psammoma bodies, that are present within the tubal lumen and which are frequently associated with APSTs. Twenty-two cases in this study were selected from a population-based study in Denmark of approximately 1000 patients with low-grade ovarian serous tumors in whom implants were identified on the fallopian tube. Seven additional cases were seen recently in consultation at The Johns Hopkins Hospital (JHH). These 7 cases were not associated with an ovarian tumor. Papillary tubal hyperplasia was found in 20 (91%) of the 22 cases in the Danish study. Based on this association of PTH with APSTs with implants and the close morphologic resemblance of PTH, not only to the primary ovarian APSTs but also to the noninvasive epithelial implants and endosalpingiosis, we speculate that the small papillae and clusters of cells from the fallopian tubes implant on ovarian and peritoneal surfaces to produce these lesions. The 7 JHH cases of PTH that were not associated with an ovarian tumor support the view that PTH is the likely precursor lesion. We propose a model for the development of ovarian and extraovarian low-grade serous proliferations (APST, noninvasive epithelial implants and endosalpingiosis) that

GRAFT-VERSUS-HOST DISEASE PANUVEITIS AND BILATERAL SEROUS DETACHMENTS: MULTIMODAL IMAGING ANALYSIS.

PubMed

Jung, Jesse J; Chen, Michael H; Rofagha, Soraya; Lee, Scott S

2017-01-01

To report the multimodal imaging findings and follow-up of a case of graft-versus-host disease-induced bilateral panuveitis and serous retinal detachments after allogenic bone marrow transplant for acute myeloid leukemia. A 75-year-old black man presented with acute decreased vision in both eyes for 1 week. Clinical examination and multimodal imaging, including spectral domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and swept-source optical coherence tomography angiography (Investigational Device; Carl Zeiss Meditec Inc) were performed. Clinical examination of the patient revealed anterior and posterior inflammation and bilateral serous retinal detachments. Ultra-widefield fundus autofluorescence demonstrated hyperautofluorescence secondary to subretinal fluid; and fluorescein angiography revealed multiple areas of punctate hyperfluorescence, leakage, and staining of the optic discs. Spectral domain and enhanced depth imaging optical coherence tomography demonstrated subretinal fluid, a thickened, undulating retinal pigment epithelium layer, and a thickened choroid in both eyes. En-face swept-source optical coherence tomography angiography did not show any retinal vascular abnormalities but did demonstrate patchy areas of decreased choriocapillaris flow. An extensive systemic infectious and malignancy workup was negative and the patient was treated with high-dose oral prednisone immunosuppression. Subsequent 6-month follow-up demonstrated complete resolution of the inflammation and bilateral serous detachments after completion of the prednisone taper over a 3-month period. Graft-versus-host disease panuveitis and bilateral serous retinal detachments are rare complications of allogenic bone marrow transplant for acute myeloid leukemia and can be diagnosed with clinical and multimodal imaging analysis. This form of autoimmune inflammation may occur after the recovery of T-cell activity within the donor graft targeting the host

Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer.

PubMed

Moran-Jones, Kim; Gloss, Brian S; Murali, Rajmohan; Chang, David K; Colvin, Emily K; Jones, Marc D; Yuen, Samuel; Howell, Viive M; Brown, Laura M; Wong, Carol W; Spong, Suzanne M; Scarlett, Christopher J; Hacker, Neville F; Ghosh, Sue; Mok, Samuel C; Birrer, Michael J; Samimi, Goli

2015-12-29

Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer.

Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer

PubMed Central

Moran-Jones, Kim; Gloss, Brian S.; Murali, Rajmohan; Chang, David K.; Colvin, Emily K.; Jones, Marc D.; Yuen, Samuel; Howell, Viive M.; Brown, Laura M.; Wong, Carol W.; Spong, Suzanne M.; Scarlett, Christopher J.; Hacker, Neville F.; Ghosh, Sue; Mok, Samuel C.; Birrer, Michael J.; Samimi, Goli

2015-01-01

Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer. PMID:26575166

Primary peritoneal serous carcinoma presenting as inflammatory breast cancer.

PubMed

Khalifeh, Ibrahim; Deavers, Michael T; Cristofanilli, Massimo; Coleman, Robert L; Malpica, Anais; Gilcrease, Michael Z

2009-01-01

Metastasis to the breast from extramammary malignancies is rare. Nevertheless, its recognition is important because the prognosis and treatment differ from that of primary breast cancer. We report a unique case of primary peritoneal serous carcinoma that initially presented as inflammatory breast cancer. The patient received neoadjuvant chemotherapy for breast cancer and subsequently underwent bilateral total mastectomy and bilateral sentinel lymph node biopsy. She was found to have extensive intralymphatic carcinoma in both breasts, with only focal minimal breast parenchymal involvement, and residual metastatic carcinoma in bilateral sentinel lymph nodes. Further work-up revealed pelvic ascites and omental nodularities. The patient underwent laparoscopic bilateral salpingo-oophorectomy, which revealed high-grade serous carcinoma involving both ovaries and fallopian tubes. Molecular testing of tumor from the ovary and axillary lymph node showed an identical pattern of allelic loss, confirming a common origin for both tumors. To our knowledge, this is the first reported case of an extramammary primary malignancy that not only presented as inflammatory breast cancer but also was diagnosed and initially treated as such.

CT Features of Ovarian Tumors: Defining Key Differences Between Serous Borderline Tumors and Low-Grade Serous Carcinomas.

PubMed

Nougaret, Stephanie; Lakhman, Yulia; Molinari, Nicolas; Feier, Diana; Scelzo, Chiara; Vargas, Hebert A; Sosa, Ramon E; Hricak, Hedvig; Soslow, Robert A; Grisham, Rachel N; Sala, Evis

2018-04-01

The objective of our study was to investigate whether the CT features of serous borderline tumors (SBTs) differ from those of low-grade serous carcinomas (LGSCs) and to evaluate if mutation status is associated with distinct CT phenotypes. This retrospective study included 59 women, 37 with SBT and 22 with LGSC, who underwent CT before primary surgical resection. Thirty of 59 patients were genetically profiled. Two radiologists (readers 1 and 2) independently and retrospectively reviewed CT examinations for qualitative features and quantified total tumor volumes (TTVs), solid tumor volumes (STVs), and solid proportion of ovarian masses. Univariate and multivariate associations of the CT features with histopathologic diagnoses and mutations were evaluated, and interreader agreement was determined. At multivariate analysis, the presence of bilateral ovarian masses (p = 0.03), the presence of peritoneal disease (PD) (p = 0.002), and higher STV of ovarian masses (p = 0.002) were associated with LGSC. The presence of nodular PD pattern (p < 0.001 each reader) and the presence of PD calcifications (reader 1, p = 0.02; reader 2, p = 0.003) were associated with invasive peritoneal lesions (i.e., LGSC). The presence of bilateral ovarian masses (p = 0.04 each reader), PD (reader 1, p = 0.01; reader 2, p = 0.004), and higher STV (p = 0.03 for each reader) were associated with the absence of BRAF mutation (i.e., wild type [wt]-BRAF). The CT features of LGSCs were distinct from those of SBTs. The CT manifestations of LGSC and the wt-BRAF phenotype were similar.

Pathways to Genome-targeted Therapies in Serous Ovarian Cancer.

PubMed

Axelrod, Joshua; Delaney, Joe

2017-07-01

Genome sequencing technologies and corresponding oncology publications have generated enormous publicly available datasets for many cancer types. While this has enabled new treatments, and in some limited cases lifetime management of the disease, the treatment options for serous ovarian cancer remain dismal. This review summarizes recent advances in our understanding of ovarian cancer, with a focus on heterogeneity, functional genomics, and actionable data.

Impact of the Ovarian Microenvironment on Serous Cancer

DTIC Science & Technology

2016-10-01

Collagen is a well-established matrix utilized by serous cancer cells, of unknown origin, to seed metastatic sites, such as the mesothelium. An RNAseq...analysis will be performed between human TEC adhered to collagen matrix compared to tissue culture plastic and used to identify gene expression...changes responsible for adhesion on collagen . Ovarian conditioned medium (OCM) with and without H2O2 treatment will be added to normal and our series of

Giant ovarian serous cystadenoma in a postmenopausal woman: a case report

PubMed Central

Babu, Sunkavalli Chinna

2009-01-01

A case of 66-year-old South Indian post menopausal woman presenting a giant ovarian serous cyst adenoma weighing 23 kg is reported here. A 66-year-old woman was referred to our clinic from a local medical center. When she was seen first at our outpatient clinic, she had gross abdominal distension since 2 years and she was unable to walk. On abdominal ultrasound, a giant cyst was found which encompassed the whole abdomen. At laparotomy, a giant, totally cystic, vascularized and smooth mass attached to the right ovary was encountered. Staging laparotomy was performed. On the postoperative tenth day, she was discharged without any problem. Her pathology report disclosed a 60×47×30 cm serous cyst adenoma weighing 23 kg. This is the largest ovarian cyst that ever reported from our hospital and one of the largest among the reported cases in the literature. PMID:19830023

Femoral metastases from ovarian serous/endometroid adenocarcinoma

PubMed Central

Beresford–Cleary, NJA; Mehdi, SA; Magowan, B

2012-01-01

Bony metastases from ovarian cancer are rare, tend to affect the axial skeleton and are associated with abdomino-pelvic disease. The median time interval between diagnosis of ovarian carcinoma and presentation of bony metastases is 44 months (1). We describe a rare case of high grade left ovarian serous / endometrioid adenocarcinoma presenting with a pathological right femoral fracture 4 weeks following diagnosis and optimal debulking of the ovarian tumour. Orthopaedic surgeons must be vigilant when planning treatment of fractures presenting in patients with a history of ovarian cancer. PMID:24960734

CDKN2D-WDFY2 is a cancer-specific fusion gene recurrent in high-grade serous ovarian carcinoma.

PubMed

Kannan, Kalpana; Coarfa, Cristian; Rajapakshe, Kimal; Hawkins, Shannon M; Matzuk, Martin M; Milosavljevic, Aleksandar; Yen, Laising

2014-03-01

Ovarian cancer is the fifth leading cause of cancer death in women. Almost 70% of ovarian cancer deaths are due to the high-grade serous subtype, which is typically detected only after it has metastasized. Characterization of high-grade serous cancer is further complicated by the significant heterogeneity and genome instability displayed by this cancer. Other than mutations in TP53, which is common to many cancers, highly recurrent recombinant events specific to this cancer have yet to be identified. Using high-throughput transcriptome sequencing of seven patient samples combined with experimental validation at DNA, RNA and protein levels, we identified a cancer-specific and inter-chromosomal fusion gene CDKN2D-WDFY2 that occurs at a frequency of 20% among sixty high-grade serous cancer samples but is absent in non-cancerous ovary and fallopian tube samples. This is the most frequent recombinant event identified so far in high-grade serous cancer implying a major cellular lineage in this highly heterogeneous cancer. In addition, the same fusion transcript was also detected in OV-90, an established high-grade serous type cell line. The genomic breakpoint was identified in intron 1 of CDKN2D and intron 2 of WDFY2 in patient tumor, providing direct evidence that this is a fusion gene. The parental gene, CDKN2D, is a cell-cycle modulator that is also involved in DNA repair, while WDFY2 is known to modulate AKT interactions with its substrates. Transfection of cloned fusion construct led to loss of wildtype CDKN2D and wildtype WDFY2 protein expression, and a gain of a short WDFY2 protein isoform that is presumably under the control of the CDKN2D promoter. The expression of short WDFY2 protein in transfected cells appears to alter the PI3K/AKT pathway that is known to play a role in oncogenesis. CDKN2D-WDFY2 fusion could be an important molecular signature for understanding and classifying sub-lineages among heterogeneous high-grade serous ovarian carcinomas.

Aurora-A overexpression and aneuploidy predict poor outcome in serous ovarian carcinoma.

PubMed

Lassus, Heini; Staff, Synnöve; Leminen, Arto; Isola, Jorma; Butzow, Ralf

2011-01-01

Aurora-A is a potential oncogene and therapeutic target in ovarian carcinoma. It is involved in mitotic events and overexpression leads to centrosome amplification and chromosomal instability. The objective of this study was to evaluate the clinical significance of Aurora-A and DNA ploidy in serous ovarian carcinoma. Serous ovarian carcinomas were analysed for Aurora-A protein by immunohistochemistry (n=592), Aurora-A copy number by CISH (n=169), Aurora-A mRNA by real-time PCR (n=158) and DNA ploidy by flowcytometry (n=440). Overexpression of Aurora-A was found in 27% of the tumors, cytoplasmic overexpression in 11% and nuclear in 17%. The cytoplasmic and nuclear overexpression were nearly mutually exclusive. Both cytoplasmic and nuclear overexpression were associated with shorter survival, high grade, high proliferation index and aberrant p53. Interestingly, only cytoplasmic expression was associated with aneuploidy and expression of phosphorylated Aurora-A. DNA ploidy was associated with poor patient outcome as well as aggressive clinicopathological parameters. In multivariate analysis, Aurora-A overexpression appeared as an independent prognostic factor for disease-free survival, together with grade, stage and ploidy. Aurora-A protein expression is strongly linked with poor patient outcome and aggressive disease characteristics, which makes Aurora-A a promising biomarker and a potential therapeutic target in ovarian carcinoma. Cytoplasmic and nuclear Aurora-A protein may have different functions. DNA aneuploidy is a strong predictor of poor prognosis in serous ovarian carcinoma. Copyright © 2010 Elsevier Inc. All rights reserved.

Surgical staging and prognosis in serous borderline ovarian tumours (BOT): A subanalysis of the AGO ROBOT study

PubMed Central

Trillsch, F; Mahner, S; Vettorazzi, E; Woelber, L; Reuss, A; Baumann, K; Keyver-Paik, M-D; Canzler, U; Wollschlaeger, K; Forner, D; Pfisterer, J; Schroeder, W; Muenstedt, K; Richter, B; Fotopoulou, C; Schmalfeldt, B; Burges, A; Ewald-Riegler, N; de Gregorio, N; Hilpert, F; Fehm, T; Meier, W; Hillemanns, P; Hanker, L; Hasenburg, A; Strauss, H-G; Hellriegel, M; Wimberger, P; Kommoss, S; Kommoss, F; Hauptmann, S; du Bois, A

2015-01-01

Background: Incomplete surgical staging is a negative prognostic factor for patients with borderline ovarian tumours (BOT). However, little is known about the prognostic impact of each individual staging procedure. Methods: Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 at 24 German AGO centres were analysed. In 559 patients with serous BOT and adequate ovarian surgery, further recommended staging procedures (omentectomy, peritoneal biopsies, cytology) were evaluated applying Cox regression models with respect to progression-free survival (PFS). Results: For patients with one missing staging procedure, the hazard ratio (HR) for recurrence was 1.25 (95%-CI 0.66–2.39; P=0.497). This risk increased with each additional procedure skipped reaching statistical significance in case of two (HR 1.95; 95%-CI 1.06–3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI 1.22–4.64; P=0.011). The most crucial procedure was omentectomy which retained a statistically significant impact on PFS in multiple analysis (HR 1.91; 95%-CI 1.15–3.19; P=0.013) adjusting for previously established prognostic factors as FIGO stage, tumour residuals, and fertility preservation. Conclusion: Individual surgical staging procedures contribute to the prognosis for patients with serous BOT. In this analysis, recurrence risk increased with each skipped surgical step. This should be considered when re-staging procedures following incomplete primary surgery are discussed. PMID:25562434

Surgical staging and prognosis in serous borderline ovarian tumours (BOT): a subanalysis of the AGO ROBOT study.

PubMed

Trillsch, F; Mahner, S; Vettorazzi, E; Woelber, L; Reuss, A; Baumann, K; Keyver-Paik, M-D; Canzler, U; Wollschlaeger, K; Forner, D; Pfisterer, J; Schroeder, W; Muenstedt, K; Richter, B; Fotopoulou, C; Schmalfeldt, B; Burges, A; Ewald-Riegler, N; de Gregorio, N; Hilpert, F; Fehm, T; Meier, W; Hillemanns, P; Hanker, L; Hasenburg, A; Strauss, H-G; Hellriegel, M; Wimberger, P; Kommoss, S; Kommoss, F; Hauptmann, S; du Bois, A

2015-02-17

Incomplete surgical staging is a negative prognostic factor for patients with borderline ovarian tumours (BOT). However, little is known about the prognostic impact of each individual staging procedure. Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 at 24 German AGO centres were analysed. In 559 patients with serous BOT and adequate ovarian surgery, further recommended staging procedures (omentectomy, peritoneal biopsies, cytology) were evaluated applying Cox regression models with respect to progression-free survival (PFS). For patients with one missing staging procedure, the hazard ratio (HR) for recurrence was 1.25 (95%-CI 0.66-2.39; P=0.497). This risk increased with each additional procedure skipped reaching statistical significance in case of two (HR 1.95; 95%-CI 1.06-3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI 1.22-4.64; P=0.011). The most crucial procedure was omentectomy which retained a statistically significant impact on PFS in multiple analysis (HR 1.91; 95%-CI 1.15-3.19; P=0.013) adjusting for previously established prognostic factors as FIGO stage, tumour residuals, and fertility preservation. Individual surgical staging procedures contribute to the prognosis for patients with serous BOT. In this analysis, recurrence risk increased with each skipped surgical step. This should be considered when re-staging procedures following incomplete primary surgery are discussed.

Anti-VEGF therapy in symptomatic peripheral exudative hemorrhagic chorioretinopathy (PEHCR) involving the macula.

PubMed

Seibel, Ira; Hager, Annette; Duncker, Tobias; Riechardt, Aline I; Nürnberg, Daniela; Klein, Julian P; Rehak, Matus; Joussen, Antonia M

2016-04-01

The purpose of this study was to describe the anatomical and functional outcome of vascular endothelial growth factor inhibitor (anti-VEGF) treatment in symptomatic peripheral exudative hemorrhagic chorioretinopathy (PEHCR) involving the macula. Clinical records from patients seen between 2012 and 2013 at a single academic center were reviewed to identify PEHCR patients receiving anti-VEGF therapy due to disease-associated changes involving the macula. Affected eyes were either treated with consecutive intravitreal injections of anti-VEGF or vitrectomy combined with anti-VEGF followed by pro re nata injections. The mean age of the patients was 76 years (range 70-89 years). In all nine eyes, visual acuity was reduced due to central subretinal fluid. On average, three anti-VEGF injections (range 2-5 injections) were required initially to achieve complete resolution of macular subretinal fluid. In three eyes, subretinal fluid reappeared after an average of 10 months (range 5-16 months), and an average of 2.5 anti-VEGF injections (range 2-3 injections) were necessary to attain complete resolution of macular subretinal fluid a second time. Median visual acuity at the visit before the first injection was 1.0 logMAR (range 2.1-0.4 logMAR) and increased to 0.8 logMAR (range 2-0.1 logMAR) at the last visit. Results of this study show that for cases in which PEHCR becomes symptomatic due to macular involvement, anti-VEGF treatment may have drying potential. Although vision was improved in some patients, it remained limited in cases with long-term macular involvement, precluding any definitive functional conclusion. However, we believe that the use of anti-VEGF agents should be recommended in PEHCR that threatens the macula. Due to its often self-limiting course, peripheral lesions should be closely observed. Larger studies are needed in order to provide clear evidence of the efficacy of anti-VEGF therapy in PEHCR.

Adrenal Metastasis from Uterine Papillary Serous Carcinoma.

PubMed

Singh Lubana, Sandeep; Singh, Navdeep; Tuli, Sandeep S; Seligman, Barbara

2016-04-27

Uterine papillary serous carcinoma (UPSC) is a highly malignant form of endometrial cancer with a high propensity for metastases and recurrences even when there is minimal or no myometrial invasion. It usually metastasizes to the pelvis, retroperitoneal lymph nodes, upper abdomen, and peritoneum. However, adrenal metastases from UPSC is extremely rare. Here, we present a case of UPSC with adrenal metastasis that occurred 6 years after the initial diagnosis. A 60-year-old woman previously diagnosed with uterine papillary serous carcinoma at an outside facility presented in September of 2006 with postmenopausal bleeding. She underwent comprehensive surgical staging with FIGO (International Federation of Gynecology and Obstetrics) stage 2. Post-operatively, the patient was treated with radiation and chemotherapy. The treatment was completed in April of 2007. The patient had no evidence of disease until July 2009 when she was found to have a mass highly suspicious for malignancy. Subsequently, she underwent right upper lobectomy. The morphology of the carcinoma was consistent with UPSC. She refused chemotherapy due to a previous history of chemotherapy-induced neuropathy. The patient was followed up with regular computed tomography (CT) scans. In October 2012 a new right adrenal nodule was seen on CT, which showed intense metabolic uptake on positron emission tomography (PET)/CT scan. The patient underwent right adrenalectomy. Pathology of the surgical specimen was consistent with UPSC. UPSC is an aggressive variant of endometrial cancer associated with high recurrence rate and poor prognoses. Long-term follow-up is needed because there is a possibility of late metastases, as in this case.

Ultrastructural Evidence of Serous Gland Polymorphism in the Skin of the Tungara Frog Engystomops pustulosus (Anura Leptodactylidae).

PubMed

Delfino, Giovanni; Giachi, Filippo; Malentacchi, Cecilia; Nosi, Daniele

2015-09-01

Three types of serous products were detected in the syncytial cutaneous glands of the leptodactylid tungara frog, Engystomops pustulosus: type Ia, granules with wide halos and variable density cores; type Ib, high density granules without halos; and type II, vesicles containing a finely dispersed product. Ultrastructural evidence revealed that these products were manufactured by different serous gland types and excluded that they represented different steps in the secretory cycle of a single gland type. Indeed, secretory maturation affecting the products released by the Golgi apparatus proceeded through different mechanisms: confluence (vesicles), interactions between syncytium and secretory product (type Ib granules), and a combination of both processes (type Ia granules). In conclusion, this investigation of secretory maturation was shown to be a suitable approach for the identification of serous gland polymorphism and demonstrated that the tungara frog belongs to the minority of anuran species characterized by this peculiar morpho-functional trait. © 2015 Wiley Periodicals, Inc.

[Pancreatic serous cystadenoma associated with pancreatic heterotopia].

PubMed

Mohamed, Hedfi; Dorra, Belghachem; Hela, Bouhafa; Cherif, Abdelhedi; Azza, Sridi; Karim, Sassi; Khadija, Bellil; Adnen, Chouchene

2016-01-01

Pancreatic heterotopias (HP) are rare. They can occur at any age with a slight male predominance. These lesions are usually asymptomatic and they are often found incidentally during upper or lower GI endoscopy or during the anatomo-pathological examination of an organ which was resected for other reasons; they can be isolated or associated with a digestive pathology. We report, through observation, the association of HP with serous cystadenoma of the pancreas discovered during examinations to identify the etiology of isolated abdominal pain. The aim of this study is to analyse clinical and histological features of this rare pathology.

Prevention of Ovarian High Grade Serous Carcinoma by Elucidating Its Early Changes

DTIC Science & Technology

2015-10-01

journals including J Pathol (PMID: 23378270), Am J Surg Pathol (PMID: 22892598) and Mod Pathology (PMID: 25216223). Task 2d. Telomere FISH on STICs...STICs have shorter telomere length and lower degree of centrosome amplification than the adjacent high- grade serous carcinomas (HGSC). Therefore, our

Mucosal Proliferations in Completely Examined Fallopian Tubes Accompanying Ovarian Low-grade Serous Tumors: Neoplastic Precursor Lesions or Normal Variants of Benign Mucosa?

PubMed

Wolsky, Rebecca J; Price, Matt A; Zaloudek, Charles J; Rabban, Joseph T

2018-05-01

Malignant transformation of the fallopian tube mucosa, followed by exfoliation of malignant cells onto ovarian and/or peritoneal surfaces, has been implicated as the origin of most pelvic high-grade serous carcinoma. Whether a parallel pathway exists for pelvic low-grade serous tumors [ovarian serous borderline tumor (SBT) and low-grade serous carcinoma (LGSC)] remains to be fully elucidated. The literature is challenging to interpret due to variation in the diagnostic criteria and terminology for cytologically low-grade proliferations of the fallopian tube mucosa, as well as variation in fallopian tube specimen sampling. Recently, a candidate fallopian tube precursor to ovarian SBT, so-called papillary tubal hyperplasia, was described in advanced stage patients. The current study was designed to identify fallopian tube mucosal proliferations unique to patients with low-grade serous ovarian tumors (serous cystadenoma, SBT, LGSC) and to determine if they may represent precursors to the ovarian tumors. Fallopian tubes were thinly sliced and entirely examined microscopically, including all of the fimbriated and nonfimbriated portions of the tubes, from patients with ovarian serous cystadenoma (35), SBT (61), and LGSC (11) and from a control population of patients with ovarian mucinous cystadenoma (28), mature cystic teratoma (18) or uterine leiomyoma (14). The slides of the fallopian tubes were examined in randomized order, without knowledge of the clinical history or findings in the ovaries or other organs. Alterations of the mucosa of the fallopian tube were classified as type 1: nonpapillary proliferation of cytologically bland tubal epithelium exhibiting crowding, stratification, and/or tufting without papillary fibrovascular cores or as type 2: papillary alterations consisting of a fibrovascular core lined by a cytologically bland layer of tubal epithelium. A third abnormality, type 3, consisted of detached intraluminal papillae, buds, or nests of epithelium that

Comparison of subfoveal choroidal thickness in healthy pregnancy and pre-eclampsia

PubMed Central

Kim, J W; Park, M H; Kim, Y J; Kim, Y T

2016-01-01

Purpose Pregnancy is a known predisposing factor for central serous chorioretinopathy (CSC). Choroidal thickness (CT) increases in patients with CSC. This study was designed to evaluate CT in pregnant women. Patients and methods This was a prospective study. Fourteen healthy pregnant women and seven patients with pre-eclampsia were included. Twenty-one normal subjects were also recruited. CT was measured using enhanced-depth imaging optical coherence tomography. Results The mean CT of normal subjects, healthy pregnant women and patients with pre-eclampsia were 264.95±21.03, 274.23±29.30 and 389.79±25.13 μm, respectively (normal subjects vs healthy gravidas: P>0.05; normal subjects vs pre-eclampsia: P<0.001; healthy gravidas vs pre-eclampsia: P<0.001). CT decreased from 381.05±22.96 μm to 335.17±9.97 μm 1 week after delivery in patients with pre-eclampsia. Conclusions Pregnancy itself did not increase CT, whereas pre-eclampsia did appear to result in increased CT. This suggests that additional unknown factors induce hyperpermeability in pregnant women. PMID:26541086

Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk.

PubMed

Kar, Siddhartha P; Tyrer, Jonathan P; Li, Qiyuan; Lawrenson, Kate; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia; Chenevix-Trench, Georgia; Baker, Helen; Bandera, Elisa V; Bean, Yukie T; Beckmann, Matthias W; Berchuck, Andrew; Bisogna, Maria; Bjørge, Line; Bogdanova, Natalia; Brinton, Louise; Brooks-Wilson, Angela; Butzow, Ralf; Campbell, Ian; Carty, Karen; Chang-Claude, Jenny; Chen, Yian Ann; Chen, Zhihua; Cook, Linda S; Cramer, Daniel; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas F; Edwards, Robert P; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goode, Ellen L; Goodman, Marc T; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus K; Hosono, Satoyo; Iversen, Edwin S; Jakubowska, Anna; Paul, James; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kjaer, Susanne K; Kelemen, Linda E; Kellar, Melissa; Kelley, Joseph; Kiemeney, Lambertus A; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; McNeish, Iain A; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B; Narod, Steven A; Nedergaard, Lotte; Ness, Roberta B; Nevanlinna, Heli; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Pearce, Celeste Leigh; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jennifer; Phelan, Catherine M; Pike, Malcolm C; Poole, Elizabeth M; Ramus, Susan J; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schildkraut, Joellen M; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C; Sucheston-Campbell, Lara E; Tangen, Ingvild L; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Timorek, Agnieszka; Tsai, Ya-Yu; Tworoger, Shelley S; van Altena, Anne M; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Sellers, Thomas A; Monteiro, Alvaro N A; Freedman, Matthew L; Gayther, Simon A; Pharoah, Paul D P

2015-10-01

Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations. We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network. We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization. ©2015 American Association for Cancer Research.

Central serous choroidopathy

MedlinePlus

... is unknown. Men are affected more often than women, and the condition is most common at around age 45. However, anyone can be affected. Stress appears to be a risk factor. Early studies found that people with aggressive, "type A" personalities who are under a lot ...

Chromosome 3 Anomalies Investigated by Genome Wide SNP Analysis of Benign, Low Malignant Potential and Low Grade Ovarian Serous Tumours

PubMed Central

Birch, Ashley H.; Arcand, Suzanna L.; Oros, Kathleen K.; Rahimi, Kurosh; Watters, A. Kevin; Provencher, Diane; Greenwood, Celia M.; Mes-Masson, Anne-Marie; Tonin, Patricia N.

2011-01-01

Ovarian carcinomas exhibit extensive heterogeneity, and their etiology remains unknown. Histological and genetic evidence has led to the proposal that low grade ovarian serous carcinomas (LGOSC) have a different etiology than high grade carcinomas (HGOSC), arising from serous tumours of low malignant potential (LMP). Common regions of chromosome (chr) 3 loss have been observed in all types of serous ovarian tumours, including benign, suggesting that these regions contain genes important in the development of all ovarian serous carcinomas. A high-density genome-wide genotyping bead array technology, which assayed >600,000 markers, was applied to a panel of serous benign and LMP tumours and a small set of LGOSC, to characterize somatic events associated with the most indolent forms of ovarian disease. The genomic patterns inferred were related to TP53, KRAS and BRAF mutations. An increasing frequency of genomic anomalies was observed with pathology of disease: 3/22 (13.6%) benign cases, 40/53 (75.5%) LMP cases and 10/11 (90.9%) LGOSC cases. Low frequencies of chr3 anomalies occurred in all tumour types. Runs of homozygosity were most commonly observed on chr3, with the 3p12-p11 candidate tumour suppressor region the most frequently homozygous region in the genome. An LMP harboured a homozygous deletion on chr6 which created a GOPC-ROS1 fusion gene, previously reported as oncogenic in other cancer types. Somatic TP53, KRAS and BRAF mutations were not observed in benign tumours. KRAS-mutation positive LMP cases displayed significantly more chromosomal aberrations than BRAF-mutation positive or KRAS and BRAF mutation negative cases. Gain of 12p, which harbours the KRAS gene, was particularly evident. A pathology review reclassified all TP53-mutation positive LGOSC cases, some of which acquired a HGOSC status. Taken together, our results support the view that LGOSC could arise from serous benign and LMP tumours, but does not exclude the possibility that HGOSC may derive

Chromosome 3 anomalies investigated by genome wide SNP analysis of benign, low malignant potential and low grade ovarian serous tumours.

PubMed

Birch, Ashley H; Arcand, Suzanna L; Oros, Kathleen K; Rahimi, Kurosh; Watters, A Kevin; Provencher, Diane; Greenwood, Celia M; Mes-Masson, Anne-Marie; Tonin, Patricia N

2011-01-01

Ovarian carcinomas exhibit extensive heterogeneity, and their etiology remains unknown. Histological and genetic evidence has led to the proposal that low grade ovarian serous carcinomas (LGOSC) have a different etiology than high grade carcinomas (HGOSC), arising from serous tumours of low malignant potential (LMP). Common regions of chromosome (chr) 3 loss have been observed in all types of serous ovarian tumours, including benign, suggesting that these regions contain genes important in the development of all ovarian serous carcinomas. A high-density genome-wide genotyping bead array technology, which assayed >600,000 markers, was applied to a panel of serous benign and LMP tumours and a small set of LGOSC, to characterize somatic events associated with the most indolent forms of ovarian disease. The genomic patterns inferred were related to TP53, KRAS and BRAF mutations. An increasing frequency of genomic anomalies was observed with pathology of disease: 3/22 (13.6%) benign cases, 40/53 (75.5%) LMP cases and 10/11 (90.9%) LGOSC cases. Low frequencies of chr3 anomalies occurred in all tumour types. Runs of homozygosity were most commonly observed on chr3, with the 3p12-p11 candidate tumour suppressor region the most frequently homozygous region in the genome. An LMP harboured a homozygous deletion on chr6 which created a GOPC-ROS1 fusion gene, previously reported as oncogenic in other cancer types. Somatic TP53, KRAS and BRAF mutations were not observed in benign tumours. KRAS-mutation positive LMP cases displayed significantly more chromosomal aberrations than BRAF-mutation positive or KRAS and BRAF mutation negative cases. Gain of 12p, which harbours the KRAS gene, was particularly evident. A pathology review reclassified all TP53-mutation positive LGOSC cases, some of which acquired a HGOSC status. Taken together, our results support the view that LGOSC could arise from serous benign and LMP tumours, but does not exclude the possibility that HGOSC may derive

[Serous cysts of the spleen treated by laparoscopic surgery].

PubMed

Alecu, L; Deacu, Adriana; Costan, I; Viţalariu, Adriana; Gulinescu, L

2002-01-01

The authors present two case of a 25 years and 32 years old male patients with serous cysts of spleen that were detected on an random abdominal ultrasonography. Abdominal pain in the left hypocondrium was only symptom of this patients. The patients was operated by laparoscopic method, with Ultra-Shears and intraoperative ultrasonography examination. This kind of techniques give us the opportunity to performed the ablation of the cysts with preservation of the spleen with fast full recovery.

Network-based integration of GWAS and gene expression identifies a HOX-centric network associated with serous ovarian cancer risk

PubMed Central

Kar, Siddhartha P.; Tyrer, Jonathan P.; Li, Qiyuan; Lawrenson, Kate; Aben, Katja K.H.; Anton-Culver, Hoda; Antonenkova, Natalia; Chenevix-Trench, Georgia; Baker, Helen; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias W.; Berchuck, Andrew; Bisogna, Maria; Bjørge, Line; Bogdanova, Natalia; Brinton, Louise; Brooks-Wilson, Angela; Butzow, Ralf; Campbell, Ian; Carty, Karen; Chang-Claude, Jenny; Chen, Yian Ann; Chen, Zhihua; Cook, Linda S.; Cramer, Daniel; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas F.; Edwards, Robert P.; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goode, Ellen L.; Goodman, Marc T.; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus K.; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Paul, James; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kjaer, Susanne K.; Kelemen, Linda E.; Kellar, Melissa; Kelley, Joseph; Kiemeney, Lambertus A.; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Iain A.; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B.; Narod, Steven A.; Nedergaard, Lotte; Ness, Roberta B.; Nevanlinna, Heli; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Pearce, Celeste Leigh; Pejovic, Tanja; Pelttari, Liisa M.; Permuth-Wey, Jennifer; Phelan, Catherine M.; Pike, Malcolm C.; Poole, Elizabeth M.; Ramus, Susan J.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schildkraut, Joellen M.; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Sucheston-Campbell, Lara E.; Tangen, Ingvild L.; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J; Timorek, Agnieszka; Tsai, Ya-Yu; Tworoger, Shelley S.; van Altena, Anne M.; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A.; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Sellers, Thomas A.; Monteiro, Alvaro N. A.; Freedman, Matthew L.; Gayther, Simon A.; Pharoah, Paul D. P.

2015-01-01

Background Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by co-expression may also be enriched for additional EOC risk associations. Methods We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly co-expressed with each selected TF gene in the unified microarray data set of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this data set were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). Results Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P<0.05 and FDR<0.05). These results were replicated (P<0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network. Conclusion We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. Impact Network analysis integrating large, context-specific data sets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization. PMID:26209509

Feasibility and clinical utility of ultra-widefield indocyanine green angiography.

PubMed

Klufas, Michael A; Yannuzzi, Nicolas A; Pang, Claudine E; Srinivas, Sowmya; Sadda, Srinivas R; Freund, K Bailey; Kiss, Szilárd

2015-03-01

To evaluate the feasibility and clinical utility of a novel noncontact scanning laser ophthalmoscope-based ultra-widefield indocyanine green angiographic system. Ultra-widefield indocyanine green angiographic images were captured using a modified Optos P200Tx that produced high-resolution images of the choroidal vasculature with up to a 200° field. Ultra-widefield indocyanine green angiography was performed on patients with a variety of retinal conditions to assess utility of this imaging technique for diagnostic purposes and disease treatment monitoring. Ultra-widefield indocyanine green angiography was performed on 138 eyes of 69 patients. Mean age was 58 ± 16.9 years (range, 24-85 years). The most common ocular pathologies imaged included central serous chorioretinopathy (24 eyes), uveitis (various subtypes, 16 eyes), age-related macular degeneration (12 eyes), and polypoidal choroidal vasculopathy (4 eyes). In all eyes evaluated with ultra-widefield indocyanine green angiography, high-resolution images of choroidal and retinal circulation were obtained with sufficient detail out to 200° of the fundus. In this series of 138 eyes, scanning laser ophthalmoscope-based ultra-widefield indocyanine green angiography was clinically practical and provided detailed images of both the central and peripheral choroidal circulation. Future studies are needed to refine the clinical value of this imaging modality and the significance of peripheral choroidal vascular changes in the diagnosis, monitoring, and treatment of ocular diseases.

A binary histologic grading system for ovarian serous carcinoma is an independent prognostic factor: a population-based study of 4317 women diagnosed in Denmark 1978-2006.

PubMed

Hannibal, Charlotte Gerd; Vang, Russell; Junge, Jette; Kjaerbye-Thygesen, Anette; Kurman, Robert J; Kjaer, Susanne K

2012-06-01

To evaluate the prognostic significance of histologic grade on survival of ovarian serous cancer in Denmark during nearly 30 years. Using the nationwide Danish Pathology Data Bank, we evaluated 4317 women with ovarian serous carcinoma in 1978-2006. All pathology reports were scrutinized and tumors classified as either low-grade serous carcinomas (LGSC) or high-grade serous carcinomas (HGSC). Tumors in which the original pathology reports were described as well-differentiated were classified as LGSC, and those that were described as moderately or poorly differentiated were classified as HGSC. We obtained histologic slides from the pathology departments for women with a diagnosis of well-differentiated serous carcinoma during 1997-2006, which were then reviewed by expert gynecologic pathologists. Data were analyzed using Kaplan-Meier methods and Cox proportional hazards regression analysis with follow-up through June 2009. Women with HGSC had a significantly increased risk of dying (HR=1.9; 95% CI: 1.6-2.3) compared with women with LGSC while adjusting for age and stage. Expert review of 171 women originally classified as well-differentiated in 1997-2006 were interpreted as LGSC in 30% of cases, whereas 12% were interpreted as HGSC and 50% as serous borderline ovarian tumors (SBT). Compared with women with confirmed LGSC, women with SBT at review had a significantly lower risk of dying (HR=0.5; 95% CI: 0.22-0.99), and women with HGSC at review had a non-significantly increased risk of dying (HR=1.6; 95% CI: 0.7-3.4). A binary grading system is a significant predictor of survival for ovarian serous carcinoma. Copyright © 2012 Elsevier Inc. All rights reserved.

Primary Papillary Serous Carcinoma of the Fallopian Tube Presenting as a Vaginal Mass: A Case Report and Review of the Literature.

PubMed

Kadour-Peero, Einav; Sagi-Dain, Lena; Cohen, Gil; Korobochka, Roman; Agbarya, Abed; Bejar, Jacob; Sagi, Shlomi

2018-05-07

BACKGROUND There is now evidence to support that some cases of high-grade serous papillary carcinoma arise from the fallopian tubes rather than the ovaries. Common symptoms at presentation include abdominal pain and swelling, vomiting, altered bowel habit and urinary symptoms. To our knowledge, this is the first case of serous papillary carcinoma presenting as a vaginal mass lesion. CASE REPORT A 41-year-old woman was referred to the Bnai-Zion Medical Center with the main complaint of irregular vaginal bleeding, vaginal mucous discharge, and suspected pelvic mass. Physical examination showed a soft, painless mass, measuring about 10 cm in diameter located mainly in the recto-vaginal septum, but not involving the uterus. Ultrasound examination showed no abnormal ovarian or uterine findings. Transvaginal biopsies of the mass showed a poorly differentiated serous papillary carcinoma of ovarian, tubal, or peritoneal origin. The physical examination and imaging findings strongly indicated an inoperable tumor, and the patient was treated with neoadjuvant (pre-surgical) chemotherapy. Pre-operative computed tomography (CT) imaging showed the partial involvement of the colon, and so surgical treatment included total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, partial vaginectomy, anterior rectal resection, and lymph node dissection. Histopathology of the surgical specimens showed a poorly differentiated serous carcinoma originating from the fimbria of the right fallopian tube. CONCLUSIONS To the best of our knowledge, this is the first report to describe primary fallopian tube papillary serous carcinoma presenting as a vaginal mass. Therefore, physicians should be aware of this possible diagnosis.

Photoreceptor layer map using spectral-domain optical coherence tomography.

PubMed

Lee, Ji Eun; Lim, Dae Won; Bae, Han Yong; Park, Hyun Jin

2009-12-01

To develop a novel method for analysis of the photoreceptor layer map (PLM) generated using spectral-domain optical coherence tomography (OCT). OCT scans were obtained from 20 eyes, 10 with macular holes (MH) and 10 with central serous chorioretinopathy (CSC) using the Macular Cube (512 x 128) protocol of the Cirrus HD-OCT (Carl Zeiss). The scanned data were processed using embedded tools of the advanced visualization. A partial thickness OCT fundus image of the photoreceptor layer was generated by setting the region of interest to a 50-microm thick layer that was parallel and adjacent to the retinal pigment epithelium. The resulting image depicted the photoreceptor layer as a map of the reflectivity in OCT. The PLM was compared with fundus photography, auto-fluorescence, tomography, and retinal thickness map. The signal from the photoreceptor layer of every OCT scan in each case was demonstrated as a single image of PLM in a fundus photograph fashion. In PLM images, detachment of the sensory retina is depicted as a hypo-reflective area, which represents the base of MH and serous detachment in CSC. Relative hypo-reflectivity, which was also noted at closed MH and at recently reattached retina in CSC, was associated with reduced signal from the junction between the inner and outer segments of photoreceptors in OCT images. Using PLM, changes in the area of detachment and reflectivity of the photoreceptor layer could be efficiently monitored. The photoreceptor layer can be analyzed as a map using spectral-domain OCT. In the treatment of both MH and CSC, PLM may provide new pathological information about the photoreceptor layer to expand our understanding of these diseases.

Is a More Comprehensive Surgery Necessary in Patients With Uterine Serous Carcinoma?

PubMed

Touhami, Omar; Trinh, Xuan-Bich; Gregoire, Jean; Sebastianelli, Alexandra; Renaud, Marie-Claude; Grondin, Katherine; Plante, Marie

2015-09-01

Uterine serous carcinoma (USC) is an aggressive histologic subtype of endometrial cancer that shares similarities to serous ovarian cancer, with a propensity for spread to the upper abdomen, a high recurrence rate, and a poor prognosis. The aim of this study was to determine whether the traditional surgical staging procedure for endometrial cancer was adequate for USC or whether a more extensive surgery, similar to the staging procedure for ovarian cancer, needs to be performed. Specifically, the roles of omentectomy and sentinel lymph node (SLN) mapping were evaluated. We retrospectively identified cases of presumed clinical stage I USC at our institution from April 2005 to March 2014. Medical records were reviewed for the following information: age at diagnosis, preoperative imaging, operative findings, surgical procedure, and final histology with definitive International Federation of Gynecology and Obstetrics stage. A total of 39 patients with presumed clinical stage I USC were identified. According to the final pathology report, the surgical stage was as follows: 17 stage IA (44%), 8 stage IB (20%), 3 stage II (8%), 2 stage IIIA (5%), 6 stage IIIC1 (15%), 1 IIIC2 (3%), and 2 stage IVB (5%). Therefore, 14 patients (36%) were surgically upstaged, but none of the patients had their clinical disease upstaged by virtue of finding microscopic metastatic disease in an otherwise normal-looking omentum. Sentinel lymph node mapping was performed in 19 patients (42%). Sensitivity and negative predictive value of SLN mapping were 100% when at least 1 SLN was identified. The detection of microscopic disease in radiologically and clinically normal-appearing omentum seems to be rare in USC. Sentinel lymph node mapping seems to be valuable in the serous subtype of endometrial cancer. A less extensive surgery may be possible in patients with USC as it seems to provide the same information as a more extensive surgery.

Megamitochondria in the serous acinar cells of the submandibular gland of the neotropical fruit bat, Artibeus obscurus.

PubMed

Tandler, B; Nagato, T; Phillips, C J

1997-05-01

As part of a continuing investigation of the comparative ultrastructure of chiropteran salivary glands, we examined the submandibular glands of eight species of neotropical fruit bats in the genus Artibeus. We previously described secretory granules of unusual substructure in the seromucous demilunar cells of this organ in some species in this genus. In the present study, we turned our attention to the serous acinar cells in the same glands. Specimens of eight species of Artibeus were collected in neotropical localities. Salivary glands were extirpated in the field and thin slices were fixed by immersion in triple aldehyde-DMSO or in modified half-strength Karnovsky's fixative. Tissues were further processed for electron microscopy by conventional means. In contrast to seromucous cells, which exhibit species-specific diversification in bats of this genus, the secretory apparatus and secretory granules in the serous acinar cells are highly conserved across all seven species. The single exception involves the mitochondria in one species. In this instance, some of the serous cell mitochondria in Artibeus obscurus are modified into megamitochondria. Such organelles usually have short, peripheral cristae; a laminar inclusion is present in the matrix compartment of every outsized organelle. Inclusions of this nature never are present in normal-size mitochondria in the serous cells. None of the megamitochondria were observed in the process of degeneration. The giant mitochondria in A. obscurus have a matrical structure that is radically different from that of the only other megamitochondria reported to occur in bat salivary glands. The factors that lead to variation in megamitochondrial substructure in different species, as well as the functional capacities of such giant organelles, are unknown.

Mixed endometrial carcinomas with a "low-grade serous"-like component: a clinicopathologic, immunohistochemical, and molecular genetic study.

PubMed

Espinosa, Iñigo; D'Angelo, Emanuela; Corominas, Marina; Gonzalez, Alan; Prat, Jaime

2018-01-01

Recently, we reported 2 mixed endometrioid endometrial carcinomas with a "low-grade serous"-like component, which does not fit into any of the 4 molecular groups described by The Cancer Genome Atlas. To understand the nature of these tumors, we have done an immunohistochemical and molecular genetic study of these 2 cases and added a third case. Immunoreactivity for p53, ER, Ki67, WT1, MLH1, PMS2, MSH2, and MSH6 was assessed. Targeted next-generation sequencing for somatic mutations, including genes commonly implicated in carcinogenesis including TP53, KRAS, and PIK3CA, and Sanger sequencing for PTEN and POLE were also performed. All patients were nulliparous and had morbid obesity. Their tumors showed a micropapillary component that resembled that of ovarian low-grade serous carcinoma and merged with villoglandular endometrioid carcinoma. The invasive tumor glands exhibited a microcystic, elongated, or fragmented pattern and contained psammoma bodies. Two tumors showed aberrant p53 expression, and all 3 were positive for ER. All showed KRAS mutations, and TP53 mutations were found in 2 cases. One patient developed peritoneal carcinomatosis, one patient is alive with disease, and another died of a brain tumor. The third patient, whose tumor was confined to the uterus (stage IA), is alive without evidence of disease, but she has been followed for only 6 months. Mixed endometrial carcinomas with a "low-grade" serous-like component exhibit a morphologic spectrum of endometrioid and serous differentiation with microcystic, elongated, or fragmented features; ER expression; KRAS and TP53 mutations; and aggressive behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

Epinephrine stimulation of anion secretion in the Calu-3 serous cell model

PubMed Central

Banga, Amiraj; Flaig, Stephanie; Lewis, Shanta; Winfree, Seth

2014-01-01

Calu-3 is a well-differentiated human bronchial cell line with the characteristics of the serous cells of airway submucosal glands. The submucosal glands play a major role in mucociliary clearance because they secrete electrolytes that facilitate airway hydration. Given the significance of both long- and short-term β-adrenergic receptor agonists in the treatment of respiratory diseases, it is important to determine the role of these receptors and their ligands in normal physiological function. The present studies were designed to characterize the effect of epinephrine, the naturally occurring β-adrenergic receptor agonist, on electrolyte transport of the airway serous cells. Interestingly, epinephrine stimulated two anion secretory channels, the cystic fibrosis transmembrane conductance regulator and a Ca2+-activated Cl− channel, with the characteristics of transmembrane protein 16A, thereby potentially altering mucociliary clearance via multiple channels. Consistent with the dual channel activation, epinephrine treatment resulted in increases in both intracellular cAMP and Ca2+. Furthermore, the present results extend previous reports indicating that the two anion channels are functionally linked. PMID:24705724

A Case of Endometrioid Adenocarcinoma Originating from the Serous Surface of the Small Intestine.

PubMed

Makihara, Natsuko; Fujita, Ichiro; Soudaf, Hiroo; Yamamoto, Takahisa; Sashikata, Terumasa; Mukohara, Toru; Maeda, Tetsuo

2015-09-07

Malignant transformation of endometriosis has been extensively described in the literature. However, extragonadal endometrioid adenocarcinoma, either de novo or arising from malignant transformation of endometriosis, is rare. The present case report describes a patient with endometrioid adenocarcinoma on the serous surface of the small intestine. A 25-year-old female with no history of endometriosis was referred to our hospital with an intrapelvic tumor. An internal examination, ultrasound, and magnetic resonance imaging revealed a round mass approximately 80 mm in diameter; however, identification of the affected organ was difficult. Because we could not rule out malignancy based on the non-specific radiologic findings, laparotomy was performed. A mass with ileal adhesions was detected intraoperatively. In addition, the uterus and bilateral adnexa appeared normal. The tumor was resected with part of the ileum. Histopathology confirmed a diagnosis of endometrioid adenocarcinoma originating from the serous surface of the small intestine.

The Ovary Is an Alternative Site of Origin for High-Grade Serous Ovarian Cancer in Mice

PubMed Central

Coffey, Donna M.; Ma, Lang; Matzuk, Martin M.

2015-01-01

Although named “ovarian cancer,” it has been unclear whether the cancer actually arises from the ovary, especially for high-grade serous carcinoma (HGSC), also known as high-grade serous ovarian cancer, the most common and deadliest ovarian cancer. In addition, the tumor suppressor p53 is the most frequently mutated gene in HGSC. However, whether mutated p53 can cause HGSC remains unknown. In this study, we bred a p53 mutation, p53R172H, into conditional Dicer-Pten double-knockout (DKO) mice, a mouse model duplicating human HGSC, to generate triple-mutant (TKO) mice. Like DKO mice, these TKO mice develop metastatic HGSCs originating from the fallopian tube. Unlike DKO mice, however, even after fallopian tubes are removed in TKO mice, ovaries alone can develop metastatic HGSCs, indicating that a p53 mutation can drive HGSC arising from the ovary. To confirm this, we generated p53R172H-Pten double-mutant mice, one of the genetic control lines for TKO mice. As anticipated, these double-mutant mice also develop metastatic HGSCs from the ovary, verifying the HGSC-forming ability of ovaries with a p53 mutation. Our study therefore shows that ovaries harboring a p53 mutation, as well as fallopian tubes, can be a distinct tissue source of high-grade serous ovarian cancer in mice. PMID:25815421

The ovary is an alternative site of origin for high-grade serous ovarian cancer in mice.

PubMed

Kim, Jaeyeon; Coffey, Donna M; Ma, Lang; Matzuk, Martin M

2015-06-01

Although named "ovarian cancer," it has been unclear whether the cancer actually arises from the ovary, especially for high-grade serous carcinoma (HGSC), also known as high-grade serous ovarian cancer, the most common and deadliest ovarian cancer. In addition, the tumor suppressor p53 is the most frequently mutated gene in HGSC. However, whether mutated p53 can cause HGSC remains unknown. In this study, we bred a p53 mutation, p53(R172H), into conditional Dicer-Pten double-knockout (DKO) mice, a mouse model duplicating human HGSC, to generate triple-mutant (TKO) mice. Like DKO mice, these TKO mice develop metastatic HGSCs originating from the fallopian tube. Unlike DKO mice, however, even after fallopian tubes are removed in TKO mice, ovaries alone can develop metastatic HGSCs, indicating that a p53 mutation can drive HGSC arising from the ovary. To confirm this, we generated p53(R172H)-Pten double-mutant mice, one of the genetic control lines for TKO mice. As anticipated, these double-mutant mice also develop metastatic HGSCs from the ovary, verifying the HGSC-forming ability of ovaries with a p53 mutation. Our study therefore shows that ovaries harboring a p53 mutation, as well as fallopian tubes, can be a distinct tissue source of high-grade serous ovarian cancer in mice.

Optimal management for surgically Stage 1 serous cancer of the uterus.

PubMed

Elit, L; Kwon, J; Bentley, J; Trim, K; Ackerman, I; Carey, M

2004-01-01

To describe the outcomes of patients who have undergone well-conducted surgery and found to have Stage 1 serous uterine cancer. This retrospective cohort study includes women who have been treated for Stage 1 serous cancer of the uterus from 1985 to 2001. Cases were included from the regional cancer centers in Hamilton, London, Sunnybrook Toronto and Cancer Care Manitoba. Forty-three women met the inclusion criteria: Complete surgical staging (n = 27), surgery followed by pelvic radiation therapy (n = 4), surgery followed by whole abdominal radiation therapy (n = 6), surgery followed by adjuvant chemotherapy (n = 6). Patient age or depth of invasion did not influence survival. Progression free interval was 22 months (SD = 14.29). Recurrence rate was highest for adjuvant chemotherapy (66%). Survival was assessed by treatment modality and a statistically significant poorer survival was seen in the adjuvant chemotherapy group (OR 17.5; 95% CI 1.3-227.6). No comment can be made on a superior treatment regimen given the small numbers in each treatment strata. This study supports the findings of others in the literature. In a group of patients where surgical staging shows limited disease (i.e., surgically Stage 1 disease), then surgery alone appears to be adequate treatment.

Small Foci of Serous Component as a Predictor of Recurrence and Prognosis for Stage IA Endometrial Carcinomas.

PubMed

Miyamoto, Morikazu; Takano, Masashi; Tsuda, Hitoshi; Soyama, Hiroaki; Aoyama, Tadashi; Ishibashi, Hiroki; Kato, Kento; Iwahashi, Hideki; Matuura, Hiroko; Yoshikawa, Tomoyuki; Suzuki, Ayako; Hirata, Junko; Furuya, Kenichi

2017-01-01

Most of the endometrial carcinomas are detected in early stages and have a better prognosis; however, predictive factors for recurrence have not been determined. Patients with grade 1 endometrioid carcinoma (EG1) according to the 2014 WHO criteria at FIGO 2009 stage IA that were identified through scanning medical charts were included, and we assessed whether the presence of uterine serous carcinoma (SC) component which comprised less than 5% of the total volume using the ovarian two-tiered grading system could be a recurrent risk factor in these patients. Among 126 cases which met inclusion criteria, 12 cases had SC. SC tumors were divided into 2 groups: SC resembling high-grade serous carcinoma (HGSC) and SC resembling low-grade serous carcinoma (LGSC). Five (3.9%) cases had HGSC and 7 (5.6%) cases had LGSC. Recurrence was observed in 3 of all cases (2.3%): 2 cases with HGSC, and 1 case with LGSC. Regarding several clinicopathological factors, only the presence of SC was associated with recurrence. The sensitivity and specificity to predict recurrence using this system were 100 and 93%, respectively. The identification of SC using the ovarian two-tiered grading system could be an accurate predictor of recurrence in stage IA EG1. © 2017 S. Karger AG, Basel.

APOBEC3B upregulation and genomic mutation patterns in serous ovarian carcinoma

PubMed Central

Leonard, Brandon; Hart, Steven N.; Burns, Michael B.; Carpenter, Michael A.; Temiz, Nuri A.; Rathore, Anurag; Vogel, Rachel Isaksson; Nikas, Jason B.; Law, Emily K.; Brown, William L.; Li, Ying; Zhang, Yuji; Maurer, Matthew J.; Oberg, Ann L.; Cunningham, Julie M.; Shridhar, Viji; Bell, Debra A.; April, Craig; Bentley, David; Bibikova, Marina; Cheetham, R. Keira; Fan, Jian-Bing; Grocock, Russell; Humphray, Sean; Kingsbury, Zoya; Peden, John; Chien, Jeremy; Swisher, Elizabeth M.; Hartmann, Lynn C.; Kalli, Kimberly R.; Goode, Ellen L.; Sicotte, Hugues; Kaufmann, Scott H.; Harris, Reuben S.

2013-01-01

Ovarian cancer is a clinically and molecularly heterogeneous disease. The driving forces behind this variability are unknown. Here we report wide variation in expression of the DNA cytosine deaminase APOBEC3B, with elevated expression in a majority of ovarian cancer cell lines (3 standard deviations above the mean of normal ovarian surface epithelial cells) and high grade primary ovarian cancers. APOBEC3B is active in the nucleus of several ovarian cancer cell lines and elicits a biochemical preference for deamination of cytosines in 5′TC dinucleotides. Importantly, examination of whole-genome sequence from 16 ovarian cancers reveals that APOBEC3B expression correlates with total mutation load as well as elevated levels of transversion mutations. In particular, high APOBEC3B expression correlates with C-to-A and C-to-G transversion mutations within 5′TC dinucleotide motifs in early-stage high grade serous ovarian cancer genomes, suggesting that APOBEC3B-catalyzed genomic uracil lesions are further processed by downstream DNA ‘repair’ enzymes including error-prone translesion polymerases. These data identify a potential role for APOBEC3B in serous ovarian cancer genomic instability. PMID:24154874

Coexistence of BRAF V600E and TERT Promoter Mutations in Low-grade Serous Carcinoma of Ovary Recurring as Carcinosarcoma in a Lymph Node: Report of a Case.

PubMed

Tavallaee, Mahkam; Steiner, David F; Zehnder, James L; Folkins, Ann K; Karam, Amer K

2018-04-03

Low-grade serous carcinomas only rarely coexist with or progress to high-grade tumors. We present a case of low-grade serous carcinoma with transformation to carcinosarcoma on recurrence in the lymph node. Identical BRAF V600E and telomerase reverse transcriptase promoter mutations were identified in both the original and recurrent tumor. Given that telomerase reverse transcriptase promotor mutations are thought to play a role in progression of other tumor types, the function of telomerase reverse transcriptase mutations in BRAF mutated low-grade serous carcinoma deserves investigation.

The O-Linked Glycome and Blood Group Antigens ABO on Mucin-Type Glycoproteins in Mucinous and Serous Epithelial Ovarian Tumors

PubMed Central

Vitiazeva, Varvara; Kattla, Jayesh J.; Flowers, Sarah A.; Lindén, Sara K.; Premaratne, Pushpa; Weijdegård, Birgitta; Sundfeldt, Karin; Karlsson, Niclas G.

2015-01-01

Background Mucins are heavily O-glycosylated proteins where the glycosylation has been shown to play an important role in cancer. Normal epithelial ovarian cells do not express secreted mucins, but their abnormal expression has previously been described in epithelial ovarian cancer and may relate to tumor formation and progression. The cyst fluids were shown to be a rich source for acidic glycoproteins. The study of these proteins can potentially lead to the identification of more effective biomarkers for ovarian cancer. Methods In this study, we analyzed the expression of the MUC5AC and the O-glycosylation of acidic glycoproteins secreted into ovarian cyst fluids. The samples were obtained from patients with serous and mucinous ovarian tumors of different stages (benign, borderline, malignant) and grades. The O-linked oligosaccharides were released and analyzed by negative-ion graphitized carbon Liquid Chromatography (LC) coupled to Electrospray Ionization tandem Mass Spectrometry (ESI-MSn). The LC-ESI-MSn of the oligosaccharides from ovarian cyst fluids displayed differences in expression of fucose containing structures such as blood group ABO antigens and Lewis-type epitopes. Results The obtained data showed that serous and mucinous benign adenomas, mucinous low malignant potential carcinomas (LMPs, borderline) and mucinous low-grade carcinomas have a high level of blood groups and Lewis type epitopes. In contrast, this type of fucosylated structures were low abundant in the high-grade mucinous carcinomas or in serous carcinomas. In addition, the ovarian tumors that showed a high level of expression of blood group antigens also revealed a strong reactivity towards the MUC5AC antibody. To visualize the differences between serous and mucinous ovarian tumors based on the O-glycosylation, a hierarchical cluster analysis was performed using mass spectrometry average compositions (MSAC). Conclusion Mucinous benign and LMPs along with mucinous low-grade carcinomas

Serous goblet cells: the protein secreting cells in the oral cavity of a catfish, Rita rita (Hamilton, 1822) (Bagridae, Siluriformes).

PubMed

Yashpal, Madhu; Mittal, Ajay Kumar

2014-02-01

Serous goblet cells in the oral epithelium of Rita rita are characterized by the presence of distinct eosinophilic granules occupying large parts of the cytoplasm. In R. rita, a range of histochemical results reveal that these cells are involved in proteinaceous secretions, and thus likely contribute to various functions analogous to those of mammalian saliva. The secretions of these cells have also been associated with specific functions and are discussed in relation to their physiological importance with special reference to their roles in lubrication, alteration in viscosity, various functions of mucus such as handling, maneuvering and driving of food items toward the esophagus, maintaining taste sensitivity and protection of the oral epithelium. In addition, the serous goblet cells may also be considered as the primary defensive cell of the oral epithelium of R. rita. The results significantly add to very limited set of literature on the serous goblet cells and provide noteworthy information on the mucous secretions in the oral cavity of fish. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Vitrectomy and gas-fluid exchange for the treatment of serous macular detachment due to optic disc pit: long-term evaluation].

PubMed

Moreira Neto, Carlos Augusto; Moreira Junior, Carlos Augusto

2013-01-01

To evaluate 5 patients with serous macular detachment due to optic disc pit that were submitted to pars plana vitrectomy and were followed for at least 7 years. Patients were submitted to pars plana vitrectomy, posterior hyaloid removal, autologous serum injection and gas-fluid exchange, without laser photocoagulation, and were evaluated pre and post-operatively with visual acuity and Amsler grid testing, retinography, and recently, with autofluorescence imaging and high resolution OCT. All 5 eyes improved visual acuity significantly following the surgical procedure maintaining good vision throughout the follow-up period. Mean pre-operative visual acuity was 20/400 and final visual acuity was 20/27 with a mean follow-up time of 13.6 years. No recurrences of serous detachments were observed. OCT examinations demonstrated an attached retina up to the margin of the pit. Serous macular detachments due to optic disc pits were adequately treated with pars plana vitrectomy and gas fluid exchange, without the need for laser photocoagulation, maintaining excellent visual results for a long period of time.

Automated choroidal segmentation method in human eye with 1050nm optical coherence tomography

NASA Astrophysics Data System (ADS)

Liu, Cindy; Wang, Ruikang K.

2014-02-01

Choroidal thickness (ChT), defined as the distance between the retinal pigment epithelium (RPE) and the choroid-sclera interface (CSI), is highly correlated with various ocular disorders like high myopia, diabetic retinopathy, and central serous chorioretinopathy. Long wavelength Optical Coherence Tomography (OCT) has the ability to penetrate deep to the CSI, making the measurement of the ChT possible. The ability to accurately segment the CSI and RPE is important in extracting clinical information. However, automated CSI segmentation is challenging due to the weak boundary in the lower choroid and inconsistent texture with varied blood vessels. We propose a K-means clustering based automated algorithm, which is effective in segmenting the CSI and RPE. The performance of the method was evaluated using 531 frames from 4 normal subjects. The RPE and CSI segmentation time was about 0.3 seconds per frame, and the average time was around 0.5 seconds per frame with correction among frames, which is faster than reported algorithms. The results from the proposed method are consistent with the manual segmentation results. Further investigation includes the optimization of the algorithm to cover more OCT images captured from patients and the increase of the processing speed and robustness of the segmentation method.

Optical coherence tomography – current and future applications

PubMed Central

Adhi, Mehreen; Duker, Jay S.

2013-01-01

Purpose of review Optical coherence tomography (OCT) has revolutionized the clinical practice of ophthalmology. It is a noninvasive imaging technique that provides high-resolution, cross-sectional images of the retina, retinal nerve fiber layer and the optic nerve head. This review discusses the present applications of the commercially available spectral-domain OCT (SD-OCT) systems in the diagnosis and management of retinal diseases, with particular emphasis on choroidal imaging. Future directions of OCT technology and their potential clinical uses are discussed. Recent findings Analysis of the choroidal thickness in healthy eyes and disease states such as age-related macular degeneration, central serous chorioretinopathy, diabetic retinopathy and inherited retinal dystrophies has been successfully achieved using SD-OCT devices with software improvements. Future OCT innovations such as longer-wavelength OCT systems including the swept-source technology, along with Doppler OCT and en-face imaging, may improve the detection of subtle microstructural changes in chorioretinal diseases by improving imaging of the choroid. Summary Advances in OCT technology provide for better understanding of pathogenesis, improved monitoring of progression and assistance in quantifying response to treatment modalities in diseases of the posterior segment of the eye. Further improvements in both hardware and software technologies should further advance the clinician’s ability to assess and manage chorioretinal diseases. PMID:23429598

Uterine Serous Carcinomas Frequently Metastasize to the Fallopian Tube and Can Mimic Serous Tubal Intraepithelial Carcinoma.

PubMed

Kommoss, Friedrich; Faruqi, Asma; Gilks, C Blake; Lamshang Leen, Sarah; Singh, Naveena; Wilkinson, Nafisa; McCluggage, W Glenn

2017-02-01

We investigated the frequency, histopathologic, and immunohistochemical characteristics of tubal involvement in uterine serous carcinoma (USC) and aimed to clarify the relationship between "serous tubal intraepithelial carcinoma (STIC)" and USC in these cases. Cases of USC with complete tubal examination were prospectively collected and reviewed for the presence of tubal involvement. Immunohistochemical analysis for p53 and WT1 was performed on the endometrial and tubal tumor in cases with tubal involvement. Of 161 USC cases (pure USC or a component of a mixed carcinoma or a carcinosarcoma), 32 (20%) showed tubal involvement (unilateral: n=19; bilateral: n=13). The uterine tumors in cases with tubal involvement showed a trend toward increased likelihood of deep myometrial and lymphovascular invasion (LVI) compared with those without tubal involvement. The tubal fimbriae were involved in 15/32 cases. Tubal involvement was mucosal in 30/32 cases, mural in 14/32, serosal in 5/32, invasive in 22/32, and there was LVI in the tube in 13/32. STIC-like features were seen in 17/32 cases (7 as the only pattern of involvement, 9 with associated invasive carcinoma, and 5 with LVI). Immunostaining showed complete concordance of p53 and WT1 between the endometrial and tubal tumors in 26/32 cases, the majority being WT1 negative or only focally positive (19/26), and all exhibiting mutation-type p53 staining. On the basis of the histologic and immunohistochemical features, the tubal tumor was considered to represent metastatic USC in 26/32 cases, most likely metastatic USC in 2/32 cases, an independent tubal primary tumor in 3/32 cases, and to be of uncertain origin in the 1 remaining case. STIC-like lesions were considered to represent metastatic USC in 12/17 cases, most likely metastatic USC in 2/17 cases, an independent tubal primary in 2/17 cases, and of uncertain origin in the 1 remaining case. Tubal involvement, including STIC-like lesions, is seen in one fifth of USC when

MAINTENANCE OF GOOD VISUAL ACUITY IN BEST DISEASE ASSOCIATED WITH CHRONIC BILATERAL SEROUS MACULAR DETACHMENT.

PubMed

Gattoussi, Sarra; Boon, Camiel J F; Freund, K Bailey

2017-08-10

We describe the long-term follow-up of a patient with multifocal Best disease with chronic bilateral serous macular detachment and unusual peripheral findings associated with a novel mutation in the BEST1 gene. Case report. A 59-year-old white woman was referred for an evaluation of her macular findings in 1992. There was a family history of Best disease in the patient's mother and a male sibling. Her medical history was unremarkable. Best-corrected visual acuity was 20/20 in her right eye and 20/25 in her left eye. The anterior segment examination was normal in both eyes. Funduscopic examination showed multifocal hyperautofluorescent vitelliform deposits with areas of subretinal fibrosis in both eyes. An electrooculogram showed Arden ratios of 1.32 in the right eye and 1.97 in the left eye. Ultra-widefield color and fundus autofluorescence imaging showed degenerative retinal changes in areas throughout the entire fundus in both eyes. Optical coherence tomography, including annual eye-tracked scans from 2005 to 2016, showed persistent bilateral serous macular detachments. Despite chronic foveal detachment, visual acuity was 20/25 in her right eye and 20/40 in her left eye, 24 years after initial presentation. Genetic testing showed a novel c.238T>A (p.Phe80Ile) missense mutation in the BEST1 gene. Some patients with Best disease associated with chronic serous macular detachment can maintain good visual acuity over an extended follow-up. To our knowledge, this is the first report of Best disease associated with this mutation in the BEST1 gene.

Detection of Silent Type I Choroidal Neovascular Membrane in Chronic Central Serous Chorioretinopathy Using En Face Swept-Source Optical Coherence Tomography Angiography.

PubMed

Moussa, Magdy; Leila, Mahmoud; Khalid, Hagar; Lolah, Mohamed

2017-01-01

To evaluate the efficacy of SS-OCTA in the detection of silent CNV secondary to chronic CSCR compared to that of FFA and SS-OCT. A retrospective observational case series reviewing the clinical data, FFA, SS-OCT, and SS-OCTA images of patients with chronic CSCR, and comparing the findings. SS-OCTA detects the CNV complex and delineates it from the surrounding pathological features of chronic CSCR by utilizing the blood flow detection algorithm, OCTARA, and the ultrahigh-definition B-scan images of the retinal microstructure generated by swept-source technology. The bivariate correlation procedure was used for the calculation of the correlation matrix of the variables tested. The study included 60 eyes of 40 patients. Mean age was 47.6 years. Mean disease duration was 14.5 months. SS-OCTA detected type 1 CNV in 5 eyes (8.3%). In all 5 eyes, FFA and SS-OCT were inconclusive for CNV. The presence of foveal thinning, opaque material beneath irregular flat PED, and increased choroidal thickness in chronic CSCR constitutes a high-risk profile for progression to CNV development. Silent type 1 CNV is an established complication of chronic CSCR. SS-OCTA is indispensable in excluding CNV especially in high-risk patients and whenever FFA and SS-OCT are inconclusive.

Down-regulation of HECTD3 by HER2 inhibition makes serous ovarian cancer cells sensitive to platinum treatment.

PubMed

Shu, Tong; Li, Yi; Wu, Xiaowei; Li, Bin; Liu, Zhihua

2017-12-28

Resistance to platinum-based chemotherapy is a major cause of treatment failure in patients with epithelial ovarian cancer and predicts a poor prognosis. Previously, we found that HECTD3 confers cancer cell resistance to apoptosis. However, the significance of HECTD3 expression in ovarian cancer and its regulatory mechanisms were unknown. Here, we found that HECTD3 depletion promotes carboplatin-induced apoptosis in both an ovarian cancer cell model and a xenograft mouse model. Moreover, high HECTD3 expression is significantly associated with poor platinum response and prognosis in ovarian cancer patients. We further demonstrated that HER2 can up-regulate HECTD3 expression through activating STAT3. Furthermore, HER2 inhibitors, such as lapatinib, down-regulate HECTD3 expression and thus promote the chemosensitivity of ovarian cancer cells to carboplatin. Lapatinib combined with carboplatin also significantly inhibits serous ovarian carcinoma growth compared with each drug alone in a xenograft mouse model. HECTD3 may be considered a promising molecular predictor of platinum chemosensitivity and prognosis for serous ovarian cancer. Through decreasing HECTD3, lapatinib possesses significantly increased anti-tumor activity when combined with carboplatin compared with each agent alone, which provides an optional therapeutic regimen for serous ovarian cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Metastatic serous carcinoma presenting as inflammatory carcinoma over the breast-Report of two cases and literature review.

PubMed

Panse, Gauri; Bossuyt, Veerle; Ko, Christine J

2018-03-01

Non-mammary metastases involving breast are rare and most commonly involve the breast parenchyma. Infrequently, metastasis from an extramammary primary site presents as inflammatory carcinoma over the breast. Diagnosis of such lesions can be challenging, especially in patients with coexisting primary breast carcinoma. Few such cases have been described in literature; however, none of the previously reported cases had a prior history of primary breast carcinoma. We present 2 patients with history of breast carcinoma and serous carcinoma of ovarian/peritoneal origin that presented with inflammatory carcinoma over the breast. Biopsies from breast tissue showed atypical cells in the dermis forming cords and papillary structures. Histopathologic differential diagnosis included infiltrating ductal carcinoma of breast origin and metastatic serous carcinoma. Immunohistochemical studies showed that the tumor cells were positive for markers of ovarian origin such as PAX-8 and CA-125 and negative for breast markers such as GATA-3, thus supporting the diagnosis. In summary, we describe the unusual presentation of metastatic serous carcinoma as inflammatory carcinoma over breast and discuss the diagnostic challenges in patients with coexisting primary breast and ovarian malignancies. We also review the morphologic features of tumors of breast and ovarian origin and the immunohistochemical stains to differentiate these 2 entities. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer

PubMed Central

Bowtell, David D.; Böhm, Steffen; Ahmed, Ahmed A.; Aspuria, Paul-Joseph; Bast, Robert C.; Beral, Valerie; Berek, Jonathan S.; Birrer, Michael J.; Blagden, Sarah; Bookman, Michael A.; Brenton, James; Chiappinelli, Katherine B.; Martins, Filipe Correia; Coukos, George; Drapkin, Ronny; Edmondson, Richard; Fotopoulou, Christina; Gabra, Hani; Galon, Jérôme; Gourley, Charlie; Heong, Valerie; Huntsman, David G.; Iwanicki, Marcin; Karlan, Beth Y.; Kaye, Allyson; Lengyel, Ernst; Levine, Douglas A.; Lu, Karen H.; McNeish, Iain A.; Menon, Usha; Narod, Steve A.; Nelson, Brad H.; Nephew, Kenneth P.; Pharoah, Paul; Powell, Daniel J.; Ramos, Pilar; Romero, Iris L.; Scott, Clare L.; Sood, Anil K.; Stronach, Euan A.; Balkwill, Frances R.

2016-01-01

High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of ovarian cancer deaths, and overall survival has not changed significantly for several decades. In this Opinion article, we outline a set of research priorities that we believe will reduce incidence and improve outcomes for women with this disease. This ‘roadmap’ for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015. PMID:26493647

Prevention of Ovarian High-Grade Serous Carcinoma by Elucidating its Early Changes

DTIC Science & Technology

We will determine the early molecular changes in STIC and their biological significance in developing high-grade serous carcinoma. marker selection...and sample preparation will begin in the next coming months. Project 2 We will evaluate whether the presence of a STIC is associated with different...clinical manifestations and/or outcome compare to those patients in whom a STIC was not identified. Molecular profiling will be initiated after quality

Quantification of photoreceptor layer thickness in different macular pathologies using ultrahigh-resolution optical coherence tomography

NASA Astrophysics Data System (ADS)

Drexler, Wolfgang; Hermann, Boris; Unterhuber, Angelika; Sattmann, Harald; Wirtitsch, Matthias; Stur, Michael; Scholda, Christoph; Ergun, Erdem; Anger, Elisabeth; Ko, Tony H.; Schubert, Christian; Ahnelt, Peter K.; Fujimoto, James G.; Fercher, Adolf F.

2004-07-01

In vivo ultrahigh resolution ophthalmic OCT has been performed in more than 300 eyes of 200 patients with several retinal pathologies, demonstrating unprecedented visualization of all major intraretinal layers, in particular the photoreceptor layer. Visualization as well as quantification of the inner and outer segment of the photoreceptor layer especially in the foveal region has been acvhieved. In normal subjects the photoreceptor layer thickness in the center of the fovea is about of 90 μm, approximately equally distributed to the inner and the outer photoreceptor segment. In the parafoveal region this thickness is reduced to ~50 μm (~30 μm for the inner and ~20 μm for the outer segment). This is in good agreement with well known increase of cone outer segments in the central foveal region. Photoreceptor layer impairment in different macular pathologies like macular hole, central serous chorioretinopathy, age related macular degeneration, foveomacular dystrophies, Stargardt dystrophy as well as retinitis pigmentosa has been investigated. Photoreceptor layer loss significantly correlated with visual acuity (R2 = 0.6, p < 0.001) and microperimetry findings for the first time in 22 eyes with Stargardt dystrophy. Visualization and quantification of photoreceptor inner and outer segment using ultrahigh resolution OCT has the potential to improve early ophthalmic diagnosis, contributes to a better understanding of pathogenesis of retinal diseases as well as might have impact in the development and monitoring of novel therapy approaches.

Central Serous Retinopathy Treatment

MedlinePlus

... Plastic Surgery Center Laser Surgery Education Center Redmond Ethics Center Global Ophthalmology Guide Academy Publications EyeNet Ophthalmology ... Plastic Surgery Center Laser Surgery Education Center Redmond Ethics Center Global Ophthalmology Guide Find an Ophthalmologist Advanced ...

Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary.

PubMed

Ahmed, Ahmed Ashour; Etemadmoghadam, Dariush; Temple, Jillian; Lynch, Andy G; Riad, Mohamed; Sharma, Raghwa; Stewart, Colin; Fereday, Sian; Caldas, Carlos; Defazio, Anna; Bowtell, David; Brenton, James D

2010-05-01

Numerous studies have tested the association between TP53 mutations in ovarian cancer and prognosis but these have been consistently confounded by limitations in study design, methodology, and/or heterogeneity in the sample cohort. High-grade serous (HGS) carcinoma is the most clinically important histological subtype of ovarian cancer. As these tumours may arise from the ovary, Fallopian tube or peritoneum, they are collectively referred to as high-grade pelvic serous carcinoma (HGPSC). To identify the true prevalence of TP53 mutations in HGPSC, we sequenced exons 2-11 and intron-exon boundaries in tumour DNA from 145 patients. HGPSC cases were defined as having histological grade 2 or 3 and FIGO stage III or IV. Surprisingly, pathogenic TP53 mutations were identified in 96.7% (n = 119/123) of HGPSC cases. Molecular and pathological review of mutation-negative cases showed evidence of p53 dysfunction associated with copy number gain of MDM2 or MDM4, or indicated the exclusion of samples as being low-grade serous tumours or carcinoma of uncertain primary site. Overall, p53 dysfunction rate approached 100% of confirmed HGPSCs. No association between TP53 mutation and progression-free or overall survival was found. From this first comprehensive mapping of TP53 mutation rate in a homogeneous group of HGPSC patients, we conclude that mutant TP53 is a driver mutation in the pathogenesis of HGPSC cancers. Because TP53 mutation is almost invariably present in HGPSC, it is not of substantial prognostic or predictive significance. Copyright (c) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

GATA3: a promising marker for metastatic breast carcinoma in serous effusion specimens.

PubMed

Shield, Paul W; Papadimos, David J; Walsh, Michael D

2014-04-01

The usefulness of GATA3 (GATA-binding protein 3 to DNA sequence [A/T]GATA[A/G]) as a marker for metastatic breast carcinoma in serous effusion specimens was investigated. Cell block sections from 74 serous effusion specimens (32 ascitic, 2 pericardial, and 40 pleural fluids) were stained with an anti-GATA3 murine monoclonal antibody. The specimens included 62 confirmed metastatic carcinomas from the breast (30 specimens), female genital tract (13 specimens), gastrointestinal tract (7 specimens), lung adenocarcinoma (9 specimens), pancreas (1 specimen), kidney (1 specimen), and bladder (1 specimen). The breast carcinoma cases included 15 ductal carcinomas and 8 lobular carcinomas; the histology subtype was not available for 7 specimens. Twelve cases containing florid reactive mesothelial cells were also stained. The breast carcinoma cases were also stained for mammaglobin and gross cystic disease fluid protein of 15 kilodaltons (GCDFP-15) to compare their sensitivity with GATA3. Positive nuclear staining for GATA3 was found to be present in 90% of metastatic breast carcinoma specimens (27 of 30 specimens). All nonbreast metastatic carcinomas tested were negative with the exception of the single case of metastatic urothelial carcinoma. No staining was observed in any of the benign reactive cases or in benign mesothelial cells present in the malignant cell block preparations. Two cases demonstrated weak positivity of benign lymphoid cells. Staining results were unambiguous because all positive cases demonstrated intense nuclear staining in > 50% of tumor cells. Mammaglobin (57% staining; 17 of 30 cases) and GCDFP-15 (33% staining; 10 of 30 cases) were found to be less sensitive markers of breast carcinoma. If used in a panel, mammaglobin and GCFP-15 staining would have identified only 1 additional case compared with those stained with GATA3. GATA3 may be a useful addition to immunostaining panels for serous effusion specimens when metastatic breast carcinoma is a

BRCA1, TP53, and CHEK2 germline mutations in uterine serous carcinoma.

PubMed

Pennington, Kathryn P; Walsh, Tom; Lee, Ming; Pennil, Christopher; Novetsky, Akiva P; Agnew, Kathy J; Thornton, Anne; Garcia, Rochelle; Mutch, David; King, Mary-Claire; Goodfellow, Paul; Swisher, Elizabeth M

2013-01-15

Uterine serous carcinoma (USC) is not recognized as part of any defined hereditary cancer syndrome, and its association with hereditary breast and ovarian carcinoma and Lynch syndrome are uncertain. Using targeted capture and massively parallel genomic sequencing, 151 subjects with USC were assessed for germline mutations in 30 tumor suppressor genes, including BRCA1 (breast cancer 1, early onset), BRCA2, the DNA mismatch repair genes (MLH1 [mutL homolog 1], MSH2 [mutS homolog 2], MSH6, PMS2 [postmeiotic segregation increased 2]), TP53 (tumor protein p53), and 10 other genes in the Fanconi anemia-BRCA pathway. Ten cases with < 10% serous histology were also assessed. Seven subjects (4.6%) carried germline loss-of-function mutations: 3 subjects (2.0%) with mutations in BRCA1, 2 subjects (1.3%) with mutations in TP53, and 2 subjects (1.3%) with mutations in CHEK2 (checkpoint kinase 2). One subject with < 10% serous histology had an MSH6 mutation. Subjects with MSH6 and TP53 mutations had neither personal nor family histories suggestive of Lynch or Li-Fraumeni syndromes. Of the 22 women with USC and a personal history of breast carcinoma, the frequency of BRCA1 mutations was 9%, compared to 0.9% in 119 women with no such history. Approximately 5% of women with USC have germline mutations in 3 different tumor suppressor genes: BRCA1, CHEK2, and TP53. Mutations in DNA mismatch repair genes that cause Lynch syndrome are rare in USC. The germline BRCA1 mutation rate in USC subjects of 2% is higher than expected in a nonfounder population, suggesting that USC is associated with hereditary breast and ovarian carcinoma in a small proportion of cases. Women with USC and breast cancer should be offered genetic testing for BRCA1 and BRCA2 mutations. Copyright © 2012 American Cancer Society.

HtrA3 Is Downregulated in Cancer Cell Lines and Significantly Reduced in Primary Serous and Granulosa Cell Ovarian Tumors.

PubMed

Singh, Harmeet; Li, Ying; Fuller, Peter J; Harrison, Craig; Rao, Jyothsna; Stephens, Andrew N; Nie, Guiying

2013-01-01

Objective. The high temperature requirement factor A3 (HtrA3) is a serine protease homologous to bacterial HtrA. Four human HtrAs have been identified. HtrA1 and HtrA3 share a high degree of domain organization and are downregulated in a number of cancers, suggesting a widespread loss of these proteases in cancer. This study examined how extensively the HtrA (HtrA1-3) proteins are downregulated in commonly used cancer cell lines and primary ovarian tumors.Methods. RT-PCR was applied to various cancer cell lines (n=17) derived from the ovary, endometrium, testes, breast, prostate, and colon, and different subtypes of primary ovarian tumors [granulosa cell tumors (n=19), mucinous cystadenocarcinomas (n=6), serous cystadenocarcinomas (n=8)] and normal ovary (n = 9). HtrA3 protein was localized by immunohistochemistry.Results. HtrA3 was extensively downregulated in the cancer cell lines examined including the granulosa cell tumor-derived cell lines. In primary ovarian tumors, the HtrA3 was significantly lower in serous cystadenocarcinoma and granulosa cell tumors. In contrast, HtrA1 and HtrA2 were expressed in all samples with no significant differences between the control and tumors. In normal postmenopausal ovary, HtrA3 protein was localized to lutenizing stromal cells and corpus albicans. In serous cystadenocarcinoma, HtrA3 protein was absent in the papillae but detected in the mesenchymal cyst wall.Conclusion. HtrA3 is more extensively downregulated than HtrA1-2 in cancer cell lines. HtrA3, but not HtrA1 or HtrA2, was decreased in primary ovarian serous cystadenocarcinoma and granulosa cell tumors. This study provides evidence that HtrA3 may be the most relevant HtrA associated with ovarian malignancy.

Reclassification of serous ovarian carcinoma by a 2-tier system: a Gynecologic Oncology Group Study.

PubMed

Bodurka, Diane C; Deavers, Michael T; Tian, Chunqiao; Sun, Charlotte C; Malpica, Anais; Coleman, Robert L; Lu, Karen H; Sood, Anil K; Birrer, Michael J; Ozols, Robert; Baergen, Rebecca; Emerson, Robert E; Steinhoff, Margaret; Behmaram, Behnaz; Rasty, Golnar; Gershenson, David M

2012-06-15

A study was undertaken to use the 2-tier system to reclassify the grade of serous ovarian tumors previously classified using the International Federation of Gynecology and Obstetrics (FIGO) 3-tier system and determine the progression-free survival (PFS) and overall survival (OS) of patients treated on Gynecologic Oncology Group (GOG) Protocol 158. The authors retrospectively reviewed demographic, pathologic, and survival data of 290 patients with stage III serous ovarian carcinoma treated with surgery and chemotherapy on GOG Protocol 158, a cooperative multicenter group trial. A blinded pathology review was performed by a panel of 6 gynecologic pathologists to verify histology and regrade tumors using the 2-tier system. The association of tumor grade with PFS and OS was assessed. Of 241 cases, both systems demonstrated substantial agreement when combining FIGO grades 2 and 3 (overall agreement, 95%; kappa statistic, 0.68). By using the 2-tier system, patients with low-grade versus high-grade tumors had significantly longer PFS (45.0 vs 19.8 months, respectively; P = .01). By using FIGO criteria, median PFS for patients with grade 1, 2, and 3 tumors was 37.5, 19.8, and 20.1 months, respectively (P = .07). There was no difference in clinical outcome in patients with grade 2 or 3 tumors in multivariate analysis. Woman with high-grade versus low-grade tumors demonstrated significantly higher risk of death (hazard ratio, 2.43; 95% confidence interval, 1.17-5.04; P = .02). Women with high-grade versus low-grade serous carcinoma of the ovary are 2 distinct patient populations. Adoption of the 2-tier grading system provides a simple yet precise framework for predicting clinical outcomes. Copyright © 2011 American Cancer Society.

HCO3(-) secretion by murine nasal submucosal gland serous acinar cells during Ca2+-stimulated fluid secretion.

PubMed

Lee, Robert J; Harlow, Janice M; Limberis, Maria P; Wilson, James M; Foskett, J Kevin

2008-07-01

Airway submucosal glands contribute to airway surface liquid (ASL) composition and volume, both important for lung mucociliary clearance. Serous acini generate most of the fluid secreted by glands, but the molecular mechanisms remain poorly characterized. We previously described cholinergic-regulated fluid secretion driven by Ca(2+)-activated Cl(-) secretion in primary murine serous acinar cells revealed by simultaneous differential interference contrast (DIC) and fluorescence microscopy. Here, we evaluated whether Ca(2+)-activated Cl(-) secretion was accompanied by secretion of HCO(3)(-), possibly a critical ASL component, by simultaneous measurements of intracellular pH (pH(i)) and cell volume. Resting pH(i) was 7.17 +/- 0.01 in physiological medium (5% CO(2)-25 mM HCO(3)(-)). During carbachol (CCh) stimulation, pH(i) fell transiently by 0.08 +/- 0.01 U concomitantly with a fall in Cl(-) content revealed by cell shrinkage, reflecting Cl(-) secretion. A subsequent alkalinization elevated pH(i) to above resting levels until agonist removal, whereupon it returned to prestimulation values. In nominally CO(2)-HCO(3)(-)-free media, the CCh-induced acidification was reduced, whereas the alkalinization remained intact. Elimination of driving forces for conductive HCO(3)(-) efflux by ion substitution or exposure to the Cl(-) channel inhibitor niflumic acid (100 microM) strongly inhibited agonist-induced acidification by >80% and >70%, respectively. The Na(+)/H(+) exchanger (NHE) inhibitor dimethylamiloride (DMA) increased the magnitude (greater than twofold) and duration of the CCh-induced acidification. Gene expression profiling suggested that serous cells express NHE isoforms 1-4 and 6-9, but pharmacological sensitivities demonstrated that alkalinization observed during both CCh stimulation and pH(i) recovery from agonist-induced acidification was primarily due to NHE1, localized to the basolateral membrane. These results suggest that serous acinar cells secrete HCO(3

Parity, infertility, oral contraceptives, and hormone replacement therapy and the risk of ovarian serous borderline tumors: A nationwide case-control study.

PubMed

Rasmussen, Emma L Kaderly; Hannibal, Charlotte Gerd; Dehlendorff, Christian; Baandrup, Louise; Junge, Jette; Vang, Russell; Kurman, Robert J; Kjaer, Susanne K

2017-03-01

Few studies have examined the risk of an ovarian serous borderline tumor (SBT) associated with parity, infertility, oral contraceptives (OCs), or hormone replacement therapy (HRT), which was the study aim. This nationwide case-control study included all women with an SBT diagnosis in Denmark, 1978-2002. SBTs were confirmed by centralized expert pathology review. For each case, 15 age-matched female controls were randomly selected using risk-set sampling. Cases and controls with previous cancer (except for non-melanoma skin cancer) and controls with bilateral oophorectomy or salpingo-oophorectomy were excluded. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). We found a strongly decreased risk of SBTs among parous women which decreased with increasing number of children (p<0.01). Older age at first birth also decreased the SBT risk (p=0.03). An increased SBT risk was associated with infertility (OR=3.31; 95% CI: 2.44-4.49), which was present both among parous and nulliparous women. HRT use increased the SBT risk (OR=1.32; 95% CI: 1.02-1.72), whereas OC use decreased the risk (OR=0.40; 95% CI: 0.26-0.62). Our nationwide study with expert histopathologic review of all SBTs showed that parity, infertility, use of HRT, and use of OCs, respectively, were strongly associated with the risk of SBTs. This is the first study to report a strong and significantly decreased SBT risk associated with OC use and a significantly increased risk with infertility, and HRT use. This supports that SBTs and serous ovarian cancer share similar risk factors. Copyright © 2017 Elsevier Inc. All rights reserved.

Wilms tumor gene product: sensitive and contextually specific marker of serous carcinomas of ovarian surface epithelial origin.

PubMed

Hwang, Harry; Quenneville, Louise; Yaziji, Hadi; Gown, Allen M

2004-06-01

Carcinomas of ovarian surface epithelial origin can arise from, and often present at, extraovarian sites. There are few available markers for the positive identification of carcinomas of ovarian surface epithelial origin, which might aid in distinguishing them from metastatic carcinomas, such as of breast, colon, or lung origin. Recently, the Wilms tumor gene product (WT-1) has been shown to be expressed in ovarian surface and mesothelial epithelium. We tested the hypothesis that WT-1 would be a sensitive and specific marker of ovarian surface epithelium carcinomas. An archived series of 116 ovarian carcinomas (57 serous [43 ovarian, 14 extraovarian], 31 mucinous, 15 clear cell, 13 endometrioid), 118 breast carcinomas, 46 colonic carcinomas, and 45 nonsmall cell lung cancers were selected. A polyclonal antibody to the WT-1 gene product was applied to deparaffinized, formalin-fixed tissue sections after epitope retrieval. Fifty-two of 57 (93%) serous carcinomas of ovarian surface epithelial origin were WT-1-positive, in a nuclear pattern, with virtually all the tumor cell population positive in the majority of cases. None of the mucinous, clear cell, or endometrioid ovarian cancers were positive, and only 8 of 118 breast, 0 of 46 colonic, and 0 of 45 lung nonsmall cell carcinomas were WT-1-positive. These findings demonstrate that WT-1 is a highly sensitive and specific marker of serous carcinomas of ovarian surface epithelial origin (both ovarian and extraovarian). These results also contradict recent reports demonstrating WT-1 expression in both breast and lung carcinomas.

Molecular alterations of EGFR and PIK3CA in uterine serous carcinoma.

PubMed

Hayes, Monica Prasad; Douglas, Wayne; Ellenson, Lora Hedrick

2009-06-01

Uterine serous carcinoma (USC) is an aggressive endometrial cancer associated with poor prognosis despite comprehensive surgical staging and adjuvant chemotherapy and radiation therapy. Biologic targets have yet to be fully explored in this disease and research on such targets could lead to clinical trials utilizing a new class of therapeutics. This study sought to evaluate primary USC tumors for molecular alterations in epidermal growth factor receptor (EGFR) and the recently characterized oncogene PIK3CA, which encodes the catalytic p110-alpha subunit of phosphatidylinositol 3-kinase (PI3K) and thus activates the AKT-mTOR oncogenic pathway. Paraffin-embedded archival tissue of 45 primary USC tumors was utilized in this study. Immunohistochemical analysis of EGFR was performed and cases given a score of 0 to 12 calculated as the product of staining intensity (0 to 3+) and the percentage of positively stained cells (0-4), with 1=1-25%, 2=26-50%, 3=51-75%, and 4=76-100%. For mutational analysis, neoplastic tissue was microdissected and DNA was extracted with phenol-chloroform. Exons 18 through 21 of EGFR and exons 9 and 20 of PIK3CA, the most commonly mutated exons of these genes, were amplified and directly sequenced. When EGFR was evaluated, moderate or strong EGFR membranous staining was observed in 25/45 (56%) USC cases. Thus, a mutational analysis was performed on 35 cases, including all cases with moderate and strong EGFR staining. No mutations were identified in EGFR. In contrast, PIK3CA mutations were confirmed in 5/34 (15%) of USC cases. Four cases were mutated in exon 20 and one case was mutated in exon 9. Since optimal treatment of uterine serous carcinoma remains unknown, novel therapeutic approaches need to be actively pursued. In the current study of primary USC tumors, oncogenic mutations of the PIK3CA gene were seen in 15% of USC cases. This represents the first report of this gene mutation in USC. In addition, EGFR stained positively in the majority

HCO3− Secretion by Murine Nasal Submucosal Gland Serous Acinar Cells during Ca2+-stimulated Fluid Secretion

PubMed Central

Lee, Robert J.; Harlow, Janice M.; Limberis, Maria P.; Wilson, James M.; Foskett, J. Kevin

2008-01-01

Airway submucosal glands contribute to airway surface liquid (ASL) composition and volume, both important for lung mucociliary clearance. Serous acini generate most of the fluid secreted by glands, but the molecular mechanisms remain poorly characterized. We previously described cholinergic-regulated fluid secretion driven by Ca2+-activated Cl− secretion in primary murine serous acinar cells revealed by simultaneous differential interference contrast (DIC) and fluorescence microscopy. Here, we evaluated whether Ca2+-activated Cl− secretion was accompanied by secretion of HCO3−, possibly a critical ASL component, by simultaneous measurements of intracellular pH (pHi) and cell volume. Resting pHi was 7.17 ± 0.01 in physiological medium (5% CO2–25 mM HCO3−). During carbachol (CCh) stimulation, pHi fell transiently by 0.08 ± 0.01 U concomitantly with a fall in Cl− content revealed by cell shrinkage, reflecting Cl− secretion. A subsequent alkalinization elevated pHi to above resting levels until agonist removal, whereupon it returned to prestimulation values. In nominally CO2–HCO3−-free media, the CCh-induced acidification was reduced, whereas the alkalinization remained intact. Elimination of driving forces for conductive HCO3− efflux by ion substitution or exposure to the Cl− channel inhibitor niflumic acid (100 μM) strongly inhibited agonist-induced acidification by >80% and >70%, respectively. The Na+/H+ exchanger (NHE) inhibitor dimethylamiloride (DMA) increased the magnitude (greater than twofold) and duration of the CCh-induced acidification. Gene expression profiling suggested that serous cells express NHE isoforms 1–4 and 6–9, but pharmacological sensitivities demonstrated that alkalinization observed during both CCh stimulation and pHi recovery from agonist-induced acidification was primarily due to NHE1, localized to the basolateral membrane. These results suggest that serous acinar cells secrete HCO3− during Ca2+-evoked fluid

Through the glass darkly: intraepithelial neoplasia, top-down differentiation and the road to pelvic serous cancer

PubMed Central

Crum, Christopher P; Herfs, Michael; Ning, Gang; Bijron, Jonathan G.; Howitt, Brooke E.; Jimenez, Cynthia A.; Hanamornroongruang, Suchanan; McKeon, Frank D.; Xian, Wa

2014-01-01

The origins of pelvic high grade serous cancer (HGSC) have become a subject of intense scrutiny in view of proposals to reduce the incidence of the disease via opportunistic salpingectomy in healthy women. Accumulated data implicates the fimbria as a site of origin and descriptive molecular pathology and experimental evidence strongly support a serous carcinogenic sequence in the fallopian tube. Both direct and indirect ("surrogate") precursors suggest the benign tube undergoes important biologic changes after menopause, acquiring abnormalities in gene expression that are shared with malignancy. However, the tube can be linked to only some HGSCs, recharging arguments that nearby peritoneum/ovarian surface epithelium (POSE) also hosts progenitors to this malignancy. A major sticking point is the difference in immunophenotype between POSE and Müllerian epithelium, essentially requiring mesothelial to Müllerian differentiation prior to or during malignant transformation to HGSC. However, there is emerging evidence that an embryonic or progenitor phenotype exists in the adult female genital tract with the capacity to differentiate, normally or during neoplastic transformation. Recently, a putative cell of origin to cervical cancer has been identified in the squamo-columnar (SC) junction, projecting a model whereby embryonic progenitors give rise to immuno-phenotypically distinct neoplastic progeny under stromal influences via "top down" differentiation. A similar pattern of differentiation is implied in the endometrium and the juxtaposition of disparate epithelial immuno-phenotypes (POSE and underlying Müllerian inclusions) recapitulates this in the ovary. While a sudden mesothelial-Mullerian transition remains to be proven, it would explain the rapid evolution, short asymptomatic interval, and absence of a defined epithelial starting point in many HGSCs. Resolving this question will be critical to both expectations from prophylactic salpingectomy and future

Papillary syncytial metaplasia associated with endometrial breakdown exhibits an immunophenotype that overlaps with uterine serous carcinoma.

PubMed

McCluggage, W Glenn; McBride, Hilary A

2012-05-01

Uterine serous carcinoma (USC) is an aggressive variant of Type 2 endometrial carcinoma, which in most cases exhibits, at least focally, a papillary architecture. Occasionally, especially in small biopsy specimens, it may be difficult to distinguish between USC and a variety of metaplastic or reactive processes. In particular, papillary syncytial metaplasia (PSM), as a result of endometrial breakdown, may be confused with USC or its precursor serous endometrial intraepithelial carcinoma. In such cases, immunohistochemistry is often undertaken, the panel of markers usually including estrogen receptor (ER), p53, p16, and MIB1. The expected immunoprofile of USC is ER negative, p53 and p16 positive, and a high MIB1 proliferation index, although studies have shown that significant numbers of cases deviate from this immunophenotype. With regard to the aforementioned markers, PSM has not been studied extensively, but intuitively, the expected immunophenotype would be ER positive, p53 and p16 negative, and a low MIB1 proliferation index. After 2 index cases in which breaking down menstrual endometrium with florid PSM was misdiagnosed on an endometrial biopsy as USC or suspected USC, in part due to the observed immunophenotype, we studied the expression of ER, p53, p16, MIB1, and HMGA2 (a recently described useful marker of USC) in 10 further cases of PSM associated with endometrial breakdown. We illustrate that compared with a nonbreaking down endometrium, PSM is characterized by a decreased expression of ER and an increased expression of p53 (although still wild-type staining) and p16, the latter marker typically being diffusely positive. HMGA2 is negative, and there is a low MIB1 proliferation index. In cases of PSM, which are morphologically problematic, the immunophenotype may further heighten the suspicion of serous malignancy and potentially result in a misdiagnosis.

The association of Helicobacter pylori with choroidal and retinal nerve fiber layer thickness.

PubMed

Can, Mehmet Erol; Kaplan, Fatma Efe; Uzel, Mehmet Murat; Kiziltoprak, Hasan; Ergun, Mustafa Cagri; Koc, Mustafa; Simsek, Gülcin

2017-08-05

To investigate the effect of Helicobacter pylori (H. pylori) infection on choroidal thickness (CT) and retinal nerve fiber layer thickness (RNFLT). The study included 25 patients with H. pylori infection and 25 healthy individuals as the control group. Helicobacter pylori patients were classified as the pre-treatment (Group 1; n: 25) and the post-treatment (Group 2; n: 25). RNFLT and CT were measured before and after treatment of H. pylori infection, using enhanced depth imaging (EDI) spectral-domain optical coherence tomography (Spectralis, Heidelberg Engineering, Heidelberg, Germany). The axial length and intraocular pressure were also measured. The mean subfoveal CT was 320.96 ± 29.15 μm in Group 1 and 287.48 ± 49.17 in the control group (p = 0.007), while the mean subfoveal CT did not show any difference between Group 2 and the control group (p > 0.05). No statistically significant difference was determined between the H. pylori patients and the control group in respect of RNFLT values (p > 0.05). CT increases during H. pylori infection and returns to the normal range within 6 weeks of treatment. RNFLT does not show any change during H. pylori infection. The data related to the subfoveal CT may be useful in understanding the pathogenesis of central serous chorioretinopathy developing in H. pylori patients.

Fluorescence lifetime imaging ophthalmoscopy.

PubMed

Dysli, Chantal; Wolf, Sebastian; Berezin, Mikhail Y; Sauer, Lydia; Hammer, Martin; Zinkernagel, Martin S

2017-09-01

Imaging techniques based on retinal autofluorescence have found broad applications in ophthalmology because they are extremely sensitive and noninvasive. Conventional fundus autofluorescence imaging measures fluorescence intensity of endogenous retinal fluorophores. It mainly derives its signal from lipofuscin at the level of the retinal pigment epithelium. Fundus autofluorescence, however, can not only be characterized by the spatial distribution of the fluorescence intensity or emission spectrum, but also by a characteristic fluorescence lifetime function. The fluorescence lifetime is the average amount of time a fluorophore remains in the excited state following excitation. Fluorescence lifetime imaging ophthalmoscopy (FLIO) is an emerging imaging modality for in vivo measurement of lifetimes of endogenous retinal fluorophores. Recent reports in this field have contributed to our understanding of the pathophysiology of various macular and retinal diseases. Within this review, the basic concept of fluorescence lifetime imaging is provided. It includes technical background information and correlation with in vitro measurements of individual retinal metabolites. In a second part, clinical applications of fluorescence lifetime imaging and fluorescence lifetime features of selected retinal diseases such as Stargardt disease, age-related macular degeneration, choroideremia, central serous chorioretinopathy, macular holes, diabetic retinopathy, and retinal artery occlusion are discussed. Potential areas of use for fluorescence lifetime imaging ophthalmoscopy will be outlined at the end of this review. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Optical Biomarkers of Serous and Mucinous Human Ovarian Tumor Assessed with Nonlinear Optics Microscopies

PubMed Central

Adur, Javier; Pelegati, Vitor B.; de Thomaz, Andre A.; Baratti, Mariana O.; Almeida, Diogo B.; Andrade, L. A. L. A.; Bottcher-Luiz, Fátima; Carvalho, Hernandes F.; Cesar, Carlos L.

2012-01-01

Background Nonlinear optical (NLO) microscopy techniques have potential to improve the early detection of epithelial ovarian cancer. In this study we showed that multimodal NLO microscopies, including two-photon excitation fluorescence (TPEF), second-harmonic generation (SHG), third-harmonic generation (THG) and fluorescence lifetime imaging microscopy (FLIM) can detect morphological and metabolic changes associated with ovarian cancer progression. Methodology/Principal Findings We obtained strong TPEF + SHG + THG signals from fixed samples stained with Hematoxylin & Eosin (H&E) and robust FLIM signal from fixed unstained samples. Particularly, we imaged 34 ovarian biopsies from different patients (median age, 49 years) including 5 normal ovarian tissue, 18 serous tumors and 11 mucinous tumors with the multimodal NLO platform developed in our laboratory. We have been able to distinguish adenomas, borderline, and adenocarcinomas specimens. Using a complete set of scoring methods we found significant differences in the content, distribution and organization of collagen fibrils in the stroma as well as in the morphology and fluorescence lifetime from epithelial ovarian cells. Conclusions/Significance NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns for serous and mucinous ovarian tumors. The results provide a basis to interpret future NLO images of ovarian tissue and lay the foundation for future in vivo optical evaluation of premature ovarian lesions. PMID:23056557

Odorous secretions in anurans: morphological and functional assessment of serous glands as a source of volatile compounds in the skin of the treefrog Hypsiboas pulchellus (Amphibia: Anura: Hylidae).

PubMed

Brunetti, Andrés E; Hermida, Gladys N; Iurman, Mariana G; Faivovich, Julián

2016-03-01

Serous (granular or venom) glands occur in the skin of almost all species of adult amphibians, and are thought to be the source of a great diversity of chemical compounds. Despite recent advances in their chemistry, odorous volatile substances are compounds that have received less attention, and until now no study has attempted to associate histological data with the presence of these molecules in amphibians, or in any other vertebrate. Given the recent identification of 40 different volatile compounds from the skin secretions of H. pulchellus (a treefrog species that releases a strong odour when handled), we examined the structure, ultrastructure, histochemistry, and distribution of skin glands of this species. Histological analysis from six body regions reveals the presence of two types of glands that differ in their distribution. Mucous glands are homogeneously distributed, whereas serous glands are more numerous in the scapular region. Ultrastructural results indicate that electron-translucent vesicles observed within granules of serous glands are similar to those found in volatile-producing glands from insects and also with lipid vesicles from different organisms. Association among lipids and volatiles is also evidenced from chemical results, which indicate that at least some of the volatile components in H. pulchellus probably originate within the metabolism of fatty acids or the mevalonate pathway. As odorous secretions are often considered to be secreted under stress situations, the release of glandular content was assessed after pharmacological treatments, epinephrine administrated in vivo and on skin explants, and through surface electrical stimulation. Serous glands responded to all treatments, generally through an obvious contraction of myoepithelial cells that surround their secretory portion. No response was observed in mucous glands. Considering these morpho-functional results, along with previous identification of volatiles from H. pulchellus and H

Unique presentation of giant metastatic microcystic serous adenocarcinoma of the pancreas.

PubMed

Philips, Cyriac Abby; Kalal, Chetan Ramesh; Bihari, Chhagan; Sahney, Amrish; Kumar, Kn Chandan; Rastogi, Archana

2014-01-01

Tumors of the pancreas that contain substantial cystic components include mainly mucinous cystic neoplasm, intraductal papillary mucinous neoplasm, solid pseudopapillary tumor, and cystadenomas (which encompass microcystic, macrocystic/oligocystic, and rare solid serous adenomas). Microcystic adenoma of the pancreas is a tumor that is benign in nature. Malignant transformation in the tumor with metastases is rare and only about 26 cases have been reported so far. Here we present a giant microcystic adenoma of the pancreas, possibly the largest ever malignant type in this group ever reported in the literature with extensive metastases to the liver and causing extensive compression and encasement on surrounding structures.

Unique Presentation of Giant Metastatic Microcystic Serous Adenocarcinoma of the Pancreas

PubMed Central

Kalal, Chetan Ramesh; Bihari, Chhagan; Sahney, Amrish; Kumar, KN Chandan; Rastogi, Archana

2014-01-01

Tumors of the pancreas that contain substantial cystic components include mainly mucinous cystic neoplasm, intraductal papillary mucinous neoplasm, solid pseudopapillary tumor, and cystadenomas (which encompass microcystic, macrocystic/oligocystic, and rare solid serous adenomas). Microcystic adenoma of the pancreas is a tumor that is benign in nature. Malignant transformation in the tumor with metastases is rare and only about 26 cases have been reported so far. Here we present a giant microcystic adenoma of the pancreas, possibly the largest ever malignant type in this group ever reported in the literature with extensive metastases to the liver and causing extensive compression and encasement on surrounding structures. PMID:24782930

Population-based study of survival for women with serous cancer of the ovary, fallopian tube, peritoneum or undesignated origin - on behalf of the Swedish gynecological cancer group (SweGCG).

PubMed

Dahm-Kähler, Pernilla; Borgfeldt, Christer; Holmberg, Erik; Staf, Christian; Falconer, Henrik; Bjurberg, Maria; Kjölhede, Preben; Rosenberg, Per; Stålberg, Karin; Högberg, Thomas; Åvall-Lundqvist, Elisabeth

2017-01-01

The aim of the study was to determine survival outcome in patients with serous cancer in the ovary, fallopian tube, peritoneum and of undesignated origin. Nation-wide population-based study of women≥18years with histologically verified non-uterine serous cancer, included in the Swedish Quality Registry for primary cancer of the ovary, fallopian tube and peritoneum diagnosed 2009-2013. Relative survival (RS) was estimated using the Ederer II method. Simple and multivariable analyses were estimated by Poisson regression models. Of 5627 women identified, 1246 (22%) had borderline tumors and 4381 had malignant tumors. In total, 2359 women had serous cancer; 71% originated in the ovary (OC), 9% in the fallopian tube (FTC), 9% in the peritoneum (PPC) and 11% at an undesignated primary site (UPS). Estimated RS at 5-years was 37%; for FTC 54%, 40% for OC, 34% for PPC and 13% for UPS. In multivariable regression analyses restricted to women who had undergone primary or interval debulking surgery for OC, FTC and PPC, site of origin was not independently associated with survival. Significant associations with worse survival were found for advanced stages (RR 2.63, P<0.001), moderate (RR 1.90, P<0.047) and poor differentiation (RR 2.20, P<0.009), neoadjuvant chemotherapy (RR1.33, P<0.022), residual tumor (RR 2.65, P<0.001) and platinum single (2.34, P<0.001) compared to platinum combination chemotherapy. Survival was poorer for serous cancer at UPS than for ovarian, fallopian tube and peritoneal cancer. Serous cancer at UPS needs to be addressed when reporting and comparing survival rates of ovarian cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Linking uterine serous carcinoma to BRCA1/2-associated cancer syndrome: A meta-analysis and case report.

PubMed

de Jonge, M M; Mooyaart, A L; Vreeswijk, M P G; de Kroon, C D; van Wezel, T; van Asperen, C J; Smit, V T H B M; Dekkers, O M; Bosse, T

2017-02-01

Uterine serous carcinoma (USC) shows greater morphological, clinical and molecular similarities to high-grade ovarian tubal serous carcinoma than to other types of endometrial cancer. As high-grade ovarian tubal serous carcinoma is known to be associated with BRCA1/2 pathogenic germline mutations (PMs), we aimed to explore whether USC is also a constituent of hereditary breast and ovarian cancer syndrome. Pubmed, EMBASE and Web of Science were searched in July 2016 for articles assessing the association between USC and germline BRCA1/2-PMs. Pooled analysis and comparisons were performed using a random effects logistic model, stratifying for ethnicity (Ashkenazi versus non-Ashkenazi). In addition, tumour tissue from an USC case with a hereditary BRCA1-PM was analysed for loss of heterozygosity at the BRCA1 locus and was functionally analysed for homologous recombination proficiency. The search yielded 1893 citations, 10 studies were included describing 345 USC patients. For Ashkenazi Jews, the pooled odds ratio of having a germline BRCA1/2-PM was increased in USC patients compared with the general Ashkenazi population: odds ratio 5.4 (95%confidence interval: 2.2-13.1). In the patient with USC, we identified the known germline BRCA1-PM in the tumour DNA. Furthermore, we showed both loss of heterozygosity of the wild-type allele and a deficiency of homologous recombination. This study suggests that USC may be an overlooked component of BRCA1/2-associated hereditary breast and ovarian cancer syndrome. Screening for germline BRCA1/2-PMs should be considered in patients diagnosed with USC, especially in cases with a positive first-degree family history for breast and/or ovarian cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

Validation of a two-tier grading system in an unselected, consecutive cohort of serous ovarian cancer patients.

PubMed

Battista, Marco Johannes; Cotarelo, Cristina; Almstedt, Katrin; Heimes, Anne-Sophie; Makris, Georgios-Marios; Weyer, Veronika; Schmidt, Marcus

2016-09-01

New insights into the carcinogenesis of ovarian cancer (OC) lead to the definition of low-grade and high-grade serous OC. In this study, we validated the MD Anderson Cancer Center (MDACC) two-tier grading system and compared it with the traditional three-tier grading system as suggested by the International Federation of Gynecology and Obstetrics (FIGO). Consecutive patients with serous OC were enrolled. These two grading systems were assessed independently from each other. Kaplan-Meier estimates and Cox-regression analyses were performed to validate and compare their prognostic impact. 143 consecutive patients entered the study. According to the Kaplan-Meier estimates, the MDACC grading system (p = 0.001) predicted the progression free survival (PFS) more precisely than the FIGO system (p = 0.025). The MDACC grading system (p = 0.008) but not the FIGO system (p = 0.329) showed a statistically significant difference in terms of disease specific survival (DSS). Multivariable Cox-regression analyses revealed an independent prognostic impact of the MDACC grading system but not of the FIGO system for PFS (HR 1.570; 95 % CI 1.007-2.449; p = 0.047, and HR 0.712; 95 % CI 0.476-1.066; p = 0.099, respectively). Concerning DSS, the two-tier grading system but not the FIGO system showed a prognostic impact in a univariable Cox-regression analysis (HR 2.152; 95 % CI 1.207-3.835; p = 0.009, and HR 1.258; 95 % CI 0.801-1.975; p = 0.319, respectively). We were able to validate the MDACC grading system in serous OC. Moreover, this grading system was stronger associated with survival than the FIGO system.

[MANIFESTATIONS OF EPIDEMIC PROCESS AND TRANSMISSION ROUTES OF CAUSATIVE AGENT OF ENTEROVIRUS SEROUS MENINGITIS].

PubMed

Sergevnin, V I; Tryasolobova, M A; Kudrevatykh, E V; Kuzovnikova, E Zh

2015-01-01

Study the manifestations of epidemic process and leading transmission routes of causative agents of enterovirus serous meningitis (SM) by results of laboratory studies and epidemiologic examination of epidemic nidi. During 2010 - 2014 a study for enterovirus was carried out in cerebrospinal fluid in 743 patients, hospitalized into medical organizations of Perm with primary diagnosis "serous meningitis", feces of 426 individuals, that had communicated with patients with SM of enterovirus etiology; 827 water samples from the distribution network, 295 water samples from open water and 57 washes from surface of vegetables and fruits. All the samples were studied in polymerase chain reaction, part--by a virological method. Epidemiologic examination of 350 epidemic nidi of SM was carried out. Enterovirus and (or) its RNA were detected in 62.0% of patients and 61.9% of individuals that had communicated with patients with enteroviris SM. ECHO 6 serotype enterovirus dominated among the causative agents. Maximum intensity of epidemic process of enterovirus SM, based on data from laboratory examination of patients, was detected in a group of organized pre-school and school age children during summer-autumn period. . Examination of epidemic nidi and laboratory control of environmental objects have shown that CV causative agent transmission factors are, in particular, unboiled water from decentralized sources (boreholes, wells, springs), water from open waters during bathing, as well as fresh vegetables, fruits, berries and meals produced from them. .

Quantification of fluid resorption from diabetic macular oedema with foveal serous detachment after dexamethasone intravitreal implant (Ozurdex® ) in a pregnant diabetic.

PubMed

Hodzic-Hadzibegovic, Delila; Ba-Ali, Shakoor; Valerius, Marianne; Lund-Andersen, Henrik

2017-05-01

To quantify the fluid resorption from the centre of the fovea in a pregnant woman with diabetic macular oedema by daily optical coherence tomography (OCT) measurements after the administration of intravitreal dexamethasone implant (Ozurdex ® ). A 36-year-old pregnant woman with type 1 diabetes for 33 years presented with diabetic macular oedema with foveal serous detachment and symptomatic vision loss at 16 gestational weeks. Best-corrected visual acuity (BCVA) in Snellen notation and central retinal volume assessed by optical coherence tomography (OCT, Topcon Corporation) were measured almost on a daily basis the first five weeks after implantation and then 2-3 times per month until childbirth. The pretreatment BCVA was 0.6/1.0, and pretreatment central retinal volume was 0.32 mm 3 . Near elimination of the oedema was achieved 3 days after treatment. One week after treatment, BCVA improved to preconception level, and full regression of the oedema was achieved. The rate of fluid resorption from the centre of the fovea was highest 3 days after treatment 0.00139 μL/hr and decreasing to 0.00065 μL/hr 1 week after treatment. Intravitreal dexamethasone implant Ozurdex reduces promptly central retinal volume in diabetic macular oedema involving the centre of the fovea in pregnancy with highest rate of fluid resorption 3 days after treatment initiation. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Serous retinal detachment accompanied by MEWDS in a myopic patient with dome-shaped macula.

PubMed

Shin, Min Kyu; Byon, Ik Soo; Park, Sung Who; Lee, Ji Eun

2014-01-01

Macular serous retinal detachment (MSRD) is a rare complication in highly myopic patients with an inferior staphyloma, tilted disc, or dome-shaped macula. Multiple evanescent white dot syndrome (MEWDS) presents with sudden visual loss and multiple yellowish dots that resolve spontaneously within several weeks. The authors report the development and spontaneous resolution of subretinal fluid accompanied by MEWDS in a myopic patient with a dome-shaped macula. Dysfunction of the retinal pigment epithelium due to MEWDS likely induced temporary MSRD in this patient. Copyright 2014, SLACK Incorporated.

Monoclonal antibody DS6 detects a tumor-associated sialoglycotope expressed on human serous ovarian carcinomas.

PubMed

Kearse, K P; Smith, N L; Semer, D A; Eagles, L; Finley, J L; Kazmierczak, S; Kovacs, C J; Rodriguez, A A; Kellogg-Wennerberg, A E

2000-12-15

A newly developed murine monoclonal antibody, DS6, immunohistochemically reacts with an antigen, CA6, that is expressed by human serous ovarian carcinomas but not by normal ovarian surface epithelium or mesothelium. CA6 has a limited distribution in normal adult tissues and is most characteristically detected in fallopian tube epithelium, inner urothelium and type 2 pneumocytes. Pre-treatment of tissue sections with either periodic acid or neuraminidase from Vibrio cholerae abolishes immunoreactivity with DS6, indicating that CA6 is a neuraminidase-sensitive and periodic acid-sensitive sialic acid glycoconjugate ("sialoglycotope"). SDS-PAGE of OVCAR5 cell lysates has revealed that the CA6 epitope is expressed on an 80 kDa non-disulfide-linked glycoprotein containing N-linked oligosaccharides. Two-dimensional non-equilibrium pH gradient gel electrophoresis indicates an isoelectric point of approximately 6.2 to 6.5. Comparison of the immunohistochemical distribution of CA6 in human serous ovarian adenocarcinomas has revealed similarities to that of CA125; however, distinct differences and some complementarity of antigen expression were revealed by double-label, 2-color immunohistochemical studies. The DS6-detected CA6 antigen appears to be distinct from other well-characterized tumor-associated antigens, including MUC1, CA125 and the histo-blood group-related antigens sLea, sLex and sTn. Copyright 2000 Wiley-Liss, Inc.

Prognostic significance of normal-sized ovary in advanced serous epithelial ovarian cancer.

PubMed

Paik, E Sun; Kim, Ji Hye; Kim, Tae Joong; Lee, Jeong Won; Kim, Byoung Gie; Bae, Duk Soo; Choi, Chel Hun

2018-01-01

We compared survival outcomes of advanced serous type epithelial ovarian cancer (EOC) patients with normal-sized ovaries and enlarged-ovarian tumors by propensity score matching analysis. The medical records of EOC patients treated at Samsung Medical Center between 2002 and 2015 were reviewed retrospectively. We investigated EOC patients with high grade serous type histology and International Federation of Gynecology and Obstetrics (FIGO) stage IIIB, IIIC, or IV who underwent primary debulking surgery (PDS) and adjuvant chemotherapy to identify patients with normal-sized ovaries. Propensity score matching was performed to compare patients with normal-sized ovaries to patients with enlarged-ovarian tumors (ratio, 1:3) according to age, FIGO stage, initial cancer antigen (CA)-125 level, and residual disease status after PDS. Of the 419 EOC patients, 48 patients had normal-sized ovary. Patients with enlarged-ovarian tumor were younger (54.0±10.3 vs. 58.4±9.2 years, p=0.005) than those with normal-sized ovary, and there was a statistically significant difference in residual disease status between the 2 groups. In total cohort with a median follow-up period of 43 months (range, 3-164 months), inferior overall survival (OS) was shown in the normal-sized ovary group (median OS, 71.2 vs. 41.4 months; p=0.003). After propensity score matching, the group with normal-sized ovary showed inferior OS compared to the group with enlarged-ovarian tumor (median OS, 72.1 vs. 41.4 months; p=0.031). In multivariate analysis for OS, normal-sized ovary remained a significant factor. Normal-sized ovary was associated with poor OS compared with the common presentation of enlarged ovaries in EOC, independent of CA-125 level or residual disease. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

Akt2/ZEB2 may be a biomarker for exfoliant cells in ascitic fluid in advanced grades of serous ovarian carcinoma.

PubMed

Liu, Changmei; Yang, Fangmei

2015-09-01

Ovarian cancers present a mild clinical course when diagnosed early but an aggressive pathway when diagnosed in the peri- and postmenopausal periods. However, the predictability of tumor progression is stochastic and is difficult to predict. In the present study, we hypothesized to examine the key pathways that are dysregulated to promote epithelial-mesenchymal transition in serous ovarian carcinoma. Examination of these steps would help to identify ascitic fluid with cells poised for metastasis or otherwise. We focused on examining the Akt2 expression, mainly because of its report as being overamplified in the aggressive variants of ovarian cancer, as well as TGFbeta-sensitivity of Akt2 that forms the key basis for metastasis initiation of most kinds of carcinoma. We obtained primary ovarian carcinoma samples as well as ascitic fluid and distantly metastatic ovarian carcinoma to examine the expression of Akt2. The results of the study demonstrated that in malignant exfoliated ovarian cancer cells, Smad4 expression was tremendously increased in the nuclei, suggesting nuclear translocation of Smad, which thereafter may have activated ZEB2, and thereafter genomically affected the expression of E-cadherin, myosin II, and vimentin, key components for initiating and sustaining metastasis. All of these may have been stimulated by increased cellular expression of Akt2 in metastatic variants of the serous ovarian carcinoma. The reliance on Akt2 and TGF beta signaling may also potentiate the case for Akt inhibitors or small molecule inhibitors of TGFbeta signaling like doxycycline as adjunct chemotherapy in serous ovarian carcinoma, especially the metastatic variants.

A comparative analysis of conventional cytopreparatory and liquid based cytological techniques (Sure Path) in evaluation of serous effusion fluids.

PubMed

Dadhich, Hrishikesh; Toi, Pampa Ch; Siddaraju, Neelaiah; Sevvanthi, Kalidas

2016-11-01

Clinically, detection of malignant cells in serous body fluids is critical, as their presence implies the upstaging of the disease. Cytology of body cavity fluids serves as an important tool when other diagnostic tests cannot be performed. In most laboratories, currently, the effusion fluid samples are analysed chiefly by the conventional cytopreparatory (CCP) technique. Although, there are several studies comparing the liquid-based cytology (LBC), with CCP technique in the field of cervicovaginal cytology; the literature on such comparison with respect to serous body fluid examination is sparse. One hundred samples of serous body fluids were processed by both CCP and LBC techniques. Slides prepared by these techniques were studied using six parameters. A comparative analysis of the advantages and disadvantages of the techniques in detection of malignant cells was carried out with appropriate statistical tests. The samples comprised 52 pleural, 44 peritoneal and four pericardial fluids. No statistically significant difference was noted with respect to cellularity (P values = 0.22), cell distribution (P values = 0.39) and diagnosis of malignancy (P values = 0.20). As for the remaining parameters, LBC provided statistically significant clearer smear background (P values < 0.0001) and shorter screening time (P values < 0.0001), while CPP technique provided a significantly better staining quality (P values 0.01) and sharper cytomorphologic features (P values 0.05). Although, a reduced screening time and clearer smear background are the two major advantages of LBC; the CCP technique provides the better staining quality with sharper cytomorphologic features which is more critical from the cytologic interpretation point of view. Diagn. Cytopathol. 2016;44:874-879. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Cigarette smoking and the association with serous ovarian cancer in African American women: African American Cancer Epidemiology Study (AACES).

PubMed

Kelemen, Linda E; Abbott, Sarah; Qin, Bo; Peres, Lauren Cole; Moorman, Patricia G; Wallace, Kristin; Bandera, Elisa V; Barnholtz-Sloan, Jill S; Bondy, Melissa; Cartmell, Kathleen; Cote, Michele L; Funkhouser, Ellen; Paddock, Lisa E; Peters, Edward S; Schwartz, Ann G; Terry, Paul; Alberg, Anthony J; Schildkraut, Joellen M

2017-07-01

Smoking is a risk factor for mucinous ovarian cancer (OvCa) in Caucasians. Whether a similar association exists in African Americans (AA) is unknown. We conducted a population-based case-control study of incident OvCa in AA women across 11 geographic locations in the US. A structured telephone interview asked about smoking, demographic, health, and lifestyle factors. Odds ratios and 95% confidence intervals (OR, 95% CI) were estimated from 613 cases and 752 controls using unconditional logistic regression in multivariable adjusted models. Associations were greater in magnitude for serous OvCa than for all OvCa combined. Compared to never smokers, increased risk for serous OvCa was observed for lifetime ever smokers (1.46, 1.11-1.92), former smokers who quit within 0-2 years of diagnosis (5.48, 3.04-9.86), and for total pack-years smoked among lifetime ever smokers (0-5 pack-years: 1.79, 1.23-2.59; >5-20 pack-years: 1.52, 1.05-2.18; >20 pack-years: 0.98, 0.61-1.56); however, we observed no dose-response relationship with increasing duration or consumption and no significant associations among current smokers. Smoking was not significantly associated with mucinous OvCa. Associations for all OvCa combined were consistently elevated among former smokers. The proportion of ever smokers who quit within 0-2 years was greater among cases (23%) than controls (7%). Cigarette smoking may be associated with serous OvCa among AA, which differs from associations reported among Caucasians. Exposure misclassification or reverse causality may partially explain the absence of increased risk among current smokers and lack of dose-response associations. Better characterization of smoking patterns is needed in this understudied population.

Fundus autofluorescence: applications and perspectives.

PubMed

Cuba, J; Gómez-Ulla, F

2013-02-01

To describe the findings of the study of autofluorescence of the different retinal diseases included in the study. To determine in which diseases autofluorescence may be more, or just as, useful as fluorescein angiography (FAG) in terms of diagnostic information. We studied the retinal autofluorescence of 123 eyes of 93 patients, including various diseases of the eye fundus. In all cases we explored the fundus, retinal autofluorescence, and, if indicated, FAG was performed. Analysis of the autofluorescence was performed using the Heidelberg Retina angiography Angiograph 2 (HRA2) Heidelberg Engineering (Germany). The autofluorescence information provided was equal or better (than FAG) in: 68.18% of cases of macular edema, 50% of pigment epithelium detachments, 100% of pigment epithelium atrophies, 100% of central serous chorioretinopathy; 55.55% of choroidal neovascularization, 100% of retinal dystrophies with deposition of lipofuscin, 100% of hard exudates and pre-retinal hemorrhages. Autofluorescence is a quick and non-invasive examination method, comfortable for both patient and examiner, and with a very short learning curve. It provides diagnostic information about many eye fundus diseases. While more studies and more experience with its use are needed, its interest lies in the possibility of avoiding the performing of angiography in patients with these diseases, and in the additional information autofluorescence provides about the functional situation of cells and retinal pigments. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Autofluorescence from the outer retina and subretinal space: hypothesis and review.

PubMed

Spaide, Richard

2008-01-01

To review the pathophysiologic principles underlying increased autofluorescence from the outer retina and subretinal space using selected diseases as examples. The ocular imaging information and histopathologic features, when known, were integrated for diseases causing increased autofluorescence from the outer retina and subretinal space. Inferences were taken from this information and used to create a classification scheme. These diseases are principally those that cause separation of the outer retina from the retinal pigment epithelium, thereby preventing proper phagocytosis of photoreceptor outer segments. The separation can arise from increased exudation into the subretinal space or inadequate removal of fluid from the subretinal space. Lack of normal outer segment processing initially leads to increased accumulation of outer segments on the outer retina and subretinal space. Over time, this material is visible as an increasingly thick coating on the outer retina, is yellow, and is autofluorescent. Over time, atrophy develops with thinning of the deposited material and decreasing autofluorescence. The accumulated material is ultimately capable of inducing damage to the retinal pigment epithelium. Diseases causing accumulation of the material include central serous chorioretinopathy, vitelliform macular dystrophy, acute exudative polymorphous vitelliform maculopathy, choroidal tumors, and vitreomacular traction syndrome. The physical separation of the retinal outer segments from the retinal pigment epithelium hinders proper phagocytosis of the outer segments. Accumulation of the shed but not phagocytized outer segments plays a role in disease manifestations for a number of macular diseases.

Choroidal neovascularisation triggered multiple evanescent white dot syndrome (MEWDS) in predisposed eyes.

PubMed

Mathis, Thibaud; Delaunay, Benoit; Cahuzac, Armelle; Vasseur, Vivien; Mauget-Faÿsse, Martine; Kodjikian, Laurent

2017-09-28

Multiple evanescent white dot syndrome (MEWDS) is an inflammatory disease that can be associated with choroidalneovascularisation (CNV). However, few studies in the literature have described the occurrence of MEWDS in association with CNV. This paper discusses whether CNV can trigger MEWDS in a predisposed eye. A retrospective multicentric case series of six eyes in six patients with acute onset of MEWDS and evidence of previous CNV was conducted between January 2015 and January 2017. All patients underwent ophthalmic examination including multimodal imaging at baseline and during follow-up. The mean age was 32.2±12.2 years. The majority of patients were women (5/1). In each case, MEWDS was diagnosed during a recurrence or occurrence of CNV secondary to choriocapillaritis, central serous chorioretinopathy or atrophic scar, presumably due to congenital toxoplasmosis. All patients were treated with intravitreal injections of antivascular endothelial growth factor (anti-VEGF) with good anatomical and functional responses (mean gain of 0.3±0.31 logMAR). The mean duration of follow-up was 13.5±10.65 months. This study highlights a sequence in the development of MEWDS, following the occurrence or recurrence of CNV. CNV may trigger MEWDS, possibly due to the proinflammatory environment created by the retinal tissue surrounding the CNV. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Pancreatic neuroendocrine tumor with complete replacement of the pancreas by serous cystic neoplasms in a patient with von Hippel-Lindau disease: a case report.

PubMed

Maeda, Shimpei; Motoi, Fuyuhiko; Oana, Shuhei; Ariake, Kyohei; Mizuma, Masamichi; Morikawa, Takanori; Hayashi, Hiroki; Nakagawa, Kei; Kamei, Takashi; Naitoh, Takeshi; Unno, Michiaki

2017-09-25

von Hippel-Lindau disease is a dominantly inherited multi-system syndrome with neoplastic hallmarks. Pancreatic lesions associated with von Hippel-Lindau include serous cystic neoplasms, simple cysts, and neuroendocrine tumors. The combination of pancreatic neuroendocrine tumors and serous cystic neoplasms is relatively rare, and the surgical treatment of these lesions must consider both preservation of pancreatic function and oncological clearance. We report a patient with von Hippel-Lindau disease successfully treated with pancreas-sparing resection of a pancreatic neuroendocrine tumor where the pancreas had been completely replaced by serous cystic neoplasms, in which pancreatic function was preserved. A 39-year-old female with von Hippel-Lindau disease was referred to our institution for treatment of a pancreatic neuroendocrine tumor. Abdominal computed tomography demonstrated a well-enhanced mass, 4 cm in diameter in the tail of the pancreas, and two multilocular tumors with several calcifications, 5 cm in diameter, in the head of the pancreas. There was complete replacement of the pancreas by multiple cystic lesions with diameters ranging from 1 to 3 cm. Magnetic resonance cholangiopancreatography showed innumerable cystic lesions on the whole pancreas and no detectable main pancreatic duct. Endoscopic ultrasound-guided fine-needle aspiration of the mass in the pancreatic tail showed characteristic features of a neuroendocrine tumor. A diagnosis of pancreatic neuroendocrine tumor in the tail of the pancreas and mixed-type serous cystic neoplasms replacing the whole pancreas was made and she underwent distal pancreatectomy while avoiding total pancreatectomy. The stump of the pancreas was sutured as firm as possible using a fish-mouth closure. The patient made a good recovery and was discharged on postoperative day 9. She is currently alive and well with no symptoms of endocrine or exocrine pancreatic insufficiency 8 months after surgery. A pancreas

[Expansion of secretory cells in the fallopian tubal epithelium in the early stages of the pathogenesis of ovarian serous carcinomas].

PubMed

Asaturova, A V; Ezhova, L S; Faizullina, N M; Adamyan, L V; Khabas, G N; Sannikova, M V

to investigate the frequency of the types of fallopian tubal secretory cell expansion (SCE) in diseases of the reproductive organs and to determine the immunophenotype and biological role of the cells in the early stages of the pathogenesis of high-grade ovarian serous carcinomas (HGOSC). The investigation enrolled 287 patients with extraovarian diseases and ovarian serous tumors varying in grade, whose fallopian tubes were morphologically and immunohistochemically examined using p53, Ki-67, PAX2, Bcl-2, beta-catenin, and ALDH1 markers. The material was statistically processed applying the Mann-Whitney test and χ2 test. The rate of secretory cell proliferation (SCP) (more than 10 consecutive secretory cells) and that of secretory cell overgrowth (SCO) (more than 30 consecutive secretory cells) increase with age in all investigated reproductive system diseases. The rate of SCP in the corpus fimbriatum of the patients with HGOSC was 5.9 times higher than that in those with extraovarian disease (p<0.01); when comparing the same patient groups, that of SCO was 3.4 times higher (p<0.05). The immunohistochemical characteristics of the investigated lesions (in scores) were as follows: PAX2 was expressed in the intact epithelium (2.8), in SCP (1.3), in SCO (1.2), in serous tubal intraepithelial carcinoma (STIC) (1.0), and in HGOSC (0.9); Bcl-2 was in the intact epithelium (2.2), in SCP (2.1), STIC (0.9), and in HGOSC (0.6), β-catenin was in the intact epithelium (0.5), in SCP (2.85), in SCO (2.95), in STIC (0.6), and in HGOSC (0.5); ALDH1 was in the intact epithelium (0.5), in SCP (2.91), in SCO (2.92), in STIC (1.2), and in HGOSC (0.6). There were statistically significant differences with a 95% confidence interval (p<0.05) for: 1) PAX2 between the intact epithelium and pathology (fallopian tube lesions and HGOSC); 2) Bcl-2 between the intact epithelium and SCE (SCP and SCO) and between SCE and HGOSC; 3) beta-catenin between the intact epithelium and SCE (SCP and SCO

Integrated proteogenomic characterization of human high grade serous ovarian cancer

PubMed Central

Zhang, Bai; McDermott, Jason E; Zhou, Jian-Ying; Petyuk, Vladislav A; Chen, Li; Ray, Debjit; Sun, Shisheng; Yang, Feng; Chen, Lijun; Wang, Jing; Shah, Punit; Cha, Seong Won; Aiyetan, Paul; Woo, Sunghee; Tian, Yuan; Gritsenko, Marina A; Clauss, Therese R; Choi, Caitlin; Monroe, Matthew E; Thomas, Stefani; Nie, Song; Wu, Chaochao; Moore, Ronald J; Yu, Kun-Hsing; Tabb, David L; Fenyö, David; Bafna, Vineet; Wang, Yue; Rodriguez, Henry; Boja, Emily S; Hiltke, Tara; Rivers, Robert C; Sokoll, Lori; Zhu, Heng; Shih, Ie-Ming; Cope, Leslie; Pandey, Akhilesh; Zhang, Bing; Snyder, Michael P; Levine, Douglas A; Smith, Richard D

2016-01-01

SUMMARY To provide a detailed analysis of the molecular components and underlying mechanisms associated with ovarian cancer, we performed a comprehensive mass spectrometry-based proteomic characterization of 174 ovarian tumors previously analyzed by The Cancer Genome Atlas (TCGA), of which 169 were high-grade serous carcinomas (HGSC). Integrating our proteomic measurements with the genomic data yielded a number of insights into disease such as how different copy number alternations influence the proteome, the proteins associated with chromosomal instability, the sets of signaling pathways that diverse genome rearrangements converge on, as well as the ones most associated with short overall survival. Specific protein acetylations associated with homologous recombination deficiency suggest a potential means for stratifying patients for therapy. In addition to providing a valuable resource, these findings provide a view of how the somatic genome drives the cancer proteome and associations between protein and post-translational modification levels and clinical outcomes in HGSC. PMID:27372738

Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer.

PubMed

Zhang, Hui; Liu, Tao; Zhang, Zhen; Payne, Samuel H; Zhang, Bai; McDermott, Jason E; Zhou, Jian-Ying; Petyuk, Vladislav A; Chen, Li; Ray, Debjit; Sun, Shisheng; Yang, Feng; Chen, Lijun; Wang, Jing; Shah, Punit; Cha, Seong Won; Aiyetan, Paul; Woo, Sunghee; Tian, Yuan; Gritsenko, Marina A; Clauss, Therese R; Choi, Caitlin; Monroe, Matthew E; Thomas, Stefani; Nie, Song; Wu, Chaochao; Moore, Ronald J; Yu, Kun-Hsing; Tabb, David L; Fenyö, David; Bafna, Vineet; Wang, Yue; Rodriguez, Henry; Boja, Emily S; Hiltke, Tara; Rivers, Robert C; Sokoll, Lori; Zhu, Heng; Shih, Ie-Ming; Cope, Leslie; Pandey, Akhilesh; Zhang, Bing; Snyder, Michael P; Levine, Douglas A; Smith, Richard D; Chan, Daniel W; Rodland, Karin D

2016-07-28

To provide a detailed analysis of the molecular components and underlying mechanisms associated with ovarian cancer, we performed a comprehensive mass-spectrometry-based proteomic characterization of 174 ovarian tumors previously analyzed by The Cancer Genome Atlas (TCGA), of which 169 were high-grade serous carcinomas (HGSCs). Integrating our proteomic measurements with the genomic data yielded a number of insights into disease, such as how different copy-number alternations influence the proteome, the proteins associated with chromosomal instability, the sets of signaling pathways that diverse genome rearrangements converge on, and the ones most associated with short overall survival. Specific protein acetylations associated with homologous recombination deficiency suggest a potential means for stratifying patients for therapy. In addition to providing a valuable resource, these findings provide a view of how the somatic genome drives the cancer proteome and associations between protein and post-translational modification levels and clinical outcomes in HGSC. VIDEO ABSTRACT. Copyright © 2016 Elsevier Inc. All rights reserved.

MUS81 is associated with cell proliferation and cisplatin sensitivity in serous ovarian cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xie, Suhong; Zheng, Hui; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai

The dysfunction of DNA damage repair (DDR) pathway contributes to tumorigenesis and drug-resistance in cancer. MUS81 is a member of the conserved xeroderma pigmentosum group F (XPF) family protein of endonucleases, which is important to the DDR pathway. However, the role of MUS81 in the development of ovarian cancer remains uncertain. To explore the expression of MUS81 and its association to serous ovarian cancer (SOC), 43 biopsies of SOC patients were detected by qRT-PCR, and 29 specimens were further performed by immunohistochemistry analysis. Here, we observed that MUS81 was over-expressed in SOC tissues at both transcript and protein levels, andmore » the expression level of MUS81 protein in ovarian cancer cell lines was also higher than that in human normal ovarian surface epithelial cell line (HOSEpiC). We also found that down-regulation of MUS81 expression in ovarian cancer cells inhibited cell proliferation and colony formation ability, and influenced cell cycle progression. Moreover, inhibition of MUS81 expression induced cellular senescence and enhanced the antitumor effect of cisplatin. Down-regulation of MUS81 expression could suppress the growth and development of SOC. These results indicate that MUS81 might play important roles in the progression of SOC and influence the antitumor effect of cisplatin. - Highlights: • MUS81 was overexpression in serous ovarian cancer (SOC). • Meanwhile down-regulation of inhibited cell proliferation and influenced cell cycle progression. • Inhibition of MUS81 induced cell cellular senescence and enhanced the antitumor effect of cisplatin. • Down-regulation of MUS81 expression could suppress the growth and development of SOC.« less

Amplification of the NSD3-BRD4-CHD8 pathway in pelvic high-grade serous carcinomas of tubo-ovarian and endometrial origin.

PubMed

Jones, Derek H; Lin, Douglas I

2017-08-01

Identification of novel therapeutics in pelvic high-grade serous carcinoma (HGSC) has been hampered by a paucity of actionable point mutations in target genes. The aim of the present study was to investigate the extent of amplification of the therapeutically targetable NSD3-CHD8-BRD4 pathway in pelvic HGSC, and to determine whether amplification is associated with worse prognosis. The Cancer Genome Atlas (TCGA) ovarian and endometrial cancer cohorts were retrospectively analyzed via online data-mining tools to test the association of NSD3 , CHD8 and BRD4 genomic alterations with survival of pelvic HGSC patients. It was demonstrated that amplification of the NSD3-CHD8-BRD4 pathway in the ovarian HGSC cohort (observed in 18% of the cases, 88/489) was significantly associated with worse overall and progression-free survival compared with non-amplified cases. In addition, amplification of NSD3 , CHD8 and BRD4 also occurred in 9% (21/232) of overall endometrial cancer TCGA cases, which was associated with worse overall survival. In the endometrial cancer TCGA cohort, NSD3 , CHD8 and BRD4 amplification occurred specifically in the serous carcinoma (25%, 13/53) and 'serous-like' copy number high endometrial carcinoma (33%, 20/60) subgroups, compared with the polymerase e (0%, 0/17), microsatellite instability high (0%, 0/65) or low copy number (1%, 1/90) subgroups. These findings support the hypothesis that amplification of the NSD3-BRD4-CDH8 axis is frequent in pelvic HGSC of both ovarian and endometrial origin, and that this pathway is potentially targetable in a subset of HGSC patients.

Inhibition of nuclear factor-kappa B enhances the tumor growth of ovarian cancer cell line derived from a low-grade papillary serous carcinoma in p53-independent pathway.

PubMed

Xiao, Xue; Yang, Gong; Bai, Peng; Gui, Shunping; Nyuyen, Tri M Bui; Mercado-Uribe, Imelda; Yang, Mei; Zou, Juan; Li, Qintong; Xiao, Jianguo; Chang, Bin; Liu, Guangzhi; Wang, He; Liu, Jinsong

2016-08-02

NF-kB can function as an oncogene or tumor suppressor depending on cancer types. The role of NF-kB in low-grade serous ovarian cancer, however, has never been tested. We sought to elucidate the function of NF-kB in the low-grade serous ovarian cancer. The ovarian cancer cell line, HOC-7, derived from a low-grade papillary serous carcinoma. Introduction of a dominant negative mutant, IkBαM, which resulted in decrease of NF-kB function in ovarian cancer cell lines. The transcription ability, tumorigenesis, cell proliferation and apoptosis were observed in derivative cell lines in comparison with parental cells. Western blot analysis indicated increased expression of the anti-apoptotic proteins Bcl-xL and reduced expression of the pro-apoptotic proteins Bax, Bad, and Bid in HOC-7/IĸBαM cell. Further investigations validate this conclusion in KRAS wildtype cell line SKOV3. Interesting, NF-kB can exert its pro-apoptotic effect by activating mitogen-activated protein kinase (MAPK) phosphorylation in SKOV3 ovarian cancer cell, whereas opposite changes detected in p-MEK in HOC-7 ovarian cancer cell, the same as some chemoresistant ovarian cancer cell lines. In vivo animal assay performed on BALB/athymic mice showed that injection of HOC-7 induced subcutaneous tumor growth, which was completely regressed within 7 weeks. In comparison, HOC-7/IĸBαM cells caused sustained tumor growth and abrogated tumor regression, suggesting that knock-down of NF-kB by IĸBαM promoted sustained tumor growth and delayed tumor regression in HOC-7 cells. Our results demonstrated that NF-kB may function as a tumor suppressor by facilitating regression of low grade ovarian serous carcinoma through activating pro-apoptotic pathways.

BRAF mutation is associated with a specific cell-type with features suggestive of senescence in ovarian serous borderline (atypical proliferative) tumors

PubMed Central

Zeppernick, Felix; Ardighieri, Laura; Hannibal, Charlotte G.; Vang, Russell; Junge, Jette; Kjaer, Susanne K.; Zhang, Rugang; Kurman, Robert J.; Shih, Ie-Ming

2014-01-01

Serous borderline tumor (SBT) also known as atypical proliferative serous tumor (APST) is the precursor of ovarian low-grade serous carcinoma (LGSC). In this study, we correlated the morphologic and immunohistochemical phenotypes of 71 APSTs and 18 LGSCs with the mutational status of KRAS and BRAF, the most common molecular genetic changes in these neoplasms. A subset of cells characterized by abundant eosinophilic cytoplasm (EC), discrete cell borders and bland nuclei was identified in all (100%) 25 BRAF mutated APSTs but in only 5 (10%) of 46 APSTs without BRAF mutations (p<0.0001). Among the 18 LGSCs, EC cells were found in only 2 and both contained BRAF mutations. The EC cells were present admixed with cuboidal and columnar cells lining the papillae and appeared to be budding from the surface, resulting in individual cells and clusters of detached cells “floating” above the papillae. Immunohistochemistry showed that the EC cells always expressed p16, a senescence-associated marker, and had a significantly lower Ki-67 labeling index than adjacent cuboidal and columnar cells (p=0.02). In vitro studies supported the interpretation that these cells were undergoing senescence as the same morphologic features could be reproduced in cultured epithelial cells by ectopic expression of BRAFV600E. Senescence was further established by markers such as SA-β-gal staining, expression of p16 and p21, and reduction in DNA synthesis. In conclusion, this study sheds light on the pathogenesis of this unique group of ovarian tumors by showing that BRAF mutation is associated with cellular senescence and the presence of a specific cell type characterized by abundant eosinophilic cytoplasm. This “oncogene-induced senescence” phenotype may represent a mechanism that prevents impedes progression of APSTs to LGSC. PMID:25188864

Connective tissue growth factor mediates TGF-β1-induced low-grade serous ovarian tumor cell apoptosis.

PubMed

Cheng, Jung-Chien; Chang, Hsun-Ming; Leung, Peter C K

2017-10-17

Ovarian low-grade serous carcinoma (LGSC) is a rare disease and is now considered to be a distinct entity from high-grade serous carcinoma (HGSC), which is the most common and malignant form of epithelial ovarian cancer. Connective tissue growth factor (CTGF) is a secreted matricellular protein that has been shown to modulate many biological functions by interacting with multiple molecules in the microenvironment. Increasing evidence indicates that aberrant expression of CTGF is associated with cancer development and progression. Transforming growth factor-β1 (TGF-β1) is a well-known molecule that can strongly up-regulate CTGF expression in different types of normal and cancer cells. Our previous study demonstrated that TGF-β1 induces apoptosis of LGSC cells. However, the effect of TGF-β1 on CTGF expression in LGSC needs to be defined. In addition, whether CTGF mediates TGF-β1-induced LGSC cell apoptosis remains unknown. In the present study, we show that TGF-β1 treatment up-regulates CTGF expression by activating SMAD3 signaling in two human LGSC cell lines. Additionally, siRNA-mediated CTGF knockdown attenuates TGF-β1-induced cell apoptosis. Moreover, our results show that the inhibitory effect of the CTGF knockdown on TGF-β1-induced cell apoptosis is mediated by down-regulating SMAD3 expression. This study demonstrates an important role for CTGF in mediating the pro-apoptotic effects of TGF-β1 on LGCS.

Serous cutaneous glands in new world hylid frogs: an ultrastructural study on skin poisons confirms phylogenetic relationships between Osteopilus septentrionalis and Phrynohyas venulosa.

PubMed

Delfino, Giovanni; Brizzi, Rossana; Nosi, Daniele; Terreni, Alessandro

2002-08-01

Transmission electron microscope investigations of the serous (poison) skin glands in the New World tree frogs Osteopilus septentrionalis and Phrynohyas venulosa revealed that they produce granules with closely similar substructures, namely, a dense cortex and pale medulla. In both species these features, that contrast the complex, sometimes repeating patterns described in other hylid frogs, derive from similar secretory and maturational processes starting from the Golgi phase of poison biosynthesis. Observations on secretory discharge showed that the two species share common release mechanisms, based on bulk discharge (holocrine) processes. Our data provide novel evidence of the extensive ultrastructural polymorphism of serous skin products in Hylidae and agree with phylogenies that regard this family as polyphyletic in origin. Assuming that ultrastructural features of cutaneous poison biosynthesis and maturation are adequate clues for tracking anuran phylogeny, the present findings also support a close relationship between Osteopilus and Phrynohyas taxa as previously suggested by osteological evidence. Copyright 2002 Wiley-Liss, Inc.

Age and sex distribution in malignant and tuberculous serous effusions: A study of 127 patients and review of the literature.

PubMed

Das, Dilip K

2015-09-01

Tuberculosis and carcinomatosis are the two most frequent causes of pleural effusion and exudative ascites, and both are characterized by lymphocyte-rich effusion. We attempted to discover if there is any significant difference in the age and sex distribution between patients presenting with these two conditions. A total of 161 serous effusion samples from 127 patients (89 with pleural effusion and 38 with ascites) having follow-up biopsy and histopathological examination were included in the present study. Three groups - malignancy (47 patients), tuberculosis (47) and non-tuberculous benign lesions (26) as per histopathological diagnoses - were compared in respect to age and sex distribution. A total of 29 (61.7%) patients with malignancy were aged ≥50 years as compared with three (6.4%) tuberculosis patients with serous effusions (P = 0.00000). A similar trend was observed in the ≥60 years age group (18 or 38.3% malignancy vs none with tuberculosis, P = 0.00000). A total of 36 (76.6%) tuberculous effusion patients were aged less than 40 years as opposed to eight (17.0%) patients with malignant effusions (P = 0.00000). There was also s significant difference between tuberculous and non-tuberculous benign lesions in the ≥50 years age group (6.4% vs 69.2%, P = 0.00000), but no significant difference between malignancy and non-tuberculous benign lesions (P = 0.61385). There were 31 female (66.0%) patients with malignancy, which was significantly higher than that of patients with tuberculosis (16, [34%], P = 0.00365) and non-specific inflammation/benign lesions (23.1%, P = 0.00059). However, the difference between tuberculosis and non-tuberculous benign lesions was not significant (P = 0.42756). Whereas malignancy in serous effusions is found in older and middle-aged people, tuberculous effusion is a disease of younger people. © 2014 Japan Geriatrics Society.

Nondamaging Retinal Laser Therapy: Rationale and Applications to the Macula.

PubMed

Lavinsky, Daniel; Wang, Jenny; Huie, Philip; Dalal, Roopa; Lee, Seung Jun; Lee, Dae Yeong; Palanker, Daniel

2016-05-01

Retinal photocoagulation and nondamaging laser therapy are used for treatment of macular disorders, without understanding of the response mechanism and with no rationale for dosimetry. To establish a proper titration algorithm, we measured the range of tissue response and damage threshold. We then evaluated safety and efficacy of nondamaging retinal therapy (NRT) based on this algorithm for chronic central serous chorioretinopathy (CSCR) and macular telangiectasia (MacTel). Retinal response to laser treatment below damage threshold was assessed in pigmented rabbits by expression of the heat shock protein HSP70 and glial fibrillary acidic protein (GFAP). Energy was adjusted relative to visible titration using the Endpoint Management (EpM) algorithm. In clinical studies, 21 eyes with CSCR and 10 eyes with MacTel were treated at 30% EpM energy with high spot density (0.25-diameter spacing). Visual acuity, retinal and choroidal thickness, and subretinal fluid were monitored for 1 year. At 25% EpM energy and higher, HSP70 was expressed acutely in RPE, and GFAP upregulation in Müller cells was observed at 1 month. Damage appeared starting at 40% setting. Subretinal fluid resolved completely in 81% and partially in 19% of the CSCR patients, and visual acuity improved by 12 ± 3 letters. Lacunae in the majority of MacTel patients decreased while preserving the retinal thickness, and vision improved by 10 letters. Heat shock protein expression in response to hyperthermia helps define the therapeutic window for NRT. Lack of tissue damage enables high-density treatment to boost clinical efficacy, therapy in the fovea, and retreatments to manage chronic diseases.

Hypermethylated APC in serous carcinoma based on a meta-analysis of ovarian cancer.

PubMed

Shen, Chunyan; Sheng, Qifang; Zhang, Xiaojie; Fu, Yuling; Zhu, Kemiao

2016-09-26

The reduced expression of the Adenomatous polyposis coli (APC) gene, a tumor suppressor gene, through promoter hypermethylation has been reported to play a key role in the carcinogenesis. However, the correlation between APC promoter hypermethylation and ovarian cancer (OC) remains to be clarified. A comprehensive literature search was carried out in related research databases. The overall odds ratio (OR) and corresponding 95 % confidence interval (CI) were used to evaluate the effects of APC promoter hypermethylation on OC and clinicopathological characteristics. Ultimately, 12 eligible studies were used in our study, including 806 OC samples, 429 normal controls, 109 benign lesions and 75 LMP samples. The pooled OR showed that APC promoter hypermethylation was significantly higher in OC than in normal and benign controls (OR = 6.18 and OR = 3.26, respectively). No significant correlation was observed between OC and low malignant potential (LMP) tumors (P = 0.436). In the comparison of OC and normal controls, subgroup analysis based on race showed that the overall OR of APC promoter hypermethylation was significant and similar in Asians and Caucasians (OR = 8.34 and OR = 5.39, respectively). A subgroup analysis based on sample type found that the pooled OR was significantly higher in blood than in tissue (OR = 18.71 and OR = 5.74, respectively). A significant association was not observed between APC promoter hypermethylation and tumor grade or tumor stage. The pooled OR indicated that APC promoter hypermethylation was significantly lower in serous carcinoma than in non-serous carcinoma (OR = 0.56, P = 0.02). No obvious publication bias was detected by Egger's test (all P > 0.05). APC promoter hypermethylation may be linked to the increased risk of OC. It was associated with histological type, but not with tumor grade or tumor stage. Moreover, hypermethylated APC may be a noninvasive biomarker using blood samples. Future

Bevacizumab Therapy and Multimodal Ultra-widefield Imaging in Immunogammopathy Maculopathy Secondary to Waldenstrom’s Macroglobulinemia

PubMed Central

Xu, Lucy T.; Courtney, Robert J.; Ehlers, Justis P

2015-01-01

Waldenstrom’s macroglobulinemia (WM) is associated with retinal findings of hyperviscosity such as venous dilation, and findings of immunogammopathy maculopathy such as serous macular detachment. The report describes a case of bilateral serous macular detachment with intraretinal schisis-like fluid in a patient with WM. Enhanced depth imaging OCT revealed a thickened choroid with hyper-reflective accumulations in the RPE layer. The ultra-widefield fundus autofluorescence demonstrated a central area of hyperautofluorescence corresponding to the area of serous macular detachment. Ultra-widefield fluorescein angiography was characteristically silent. Intravitreal bevacizumab therapy resulted in significant reduction in intraretinal fluid, but minimal change in subretinal fluid. Long-term follow-up demonstrated alterations in retinal architecture and improved serous detachments. PMID:25707055

Characterization of three new serous epithelial ovarian cancer cell lines

PubMed Central

Ouellet, Véronique; Zietarska, Magdalena; Portelance, Lise; Lafontaine, Julie; Madore, Jason; Puiffe, Marie-Line; Arcand, Suzanna L; Shen, Zhen; Hébert, Josée; Tonin, Patricia N; Provencher, Diane M; Mes-Masson, Anne-Marie

2008-01-01

Background Cell lines constitute a powerful model to study cancer, and here we describe three new epithelial ovarian cancer (EOC) cell lines derived from poorly differentiated serous solid tumors (TOV-1946, and TOV-2223G), as well as the matched ascites for one case (OV-1946). Methods In addition to growth parameters, the cell lines were characterized for anchorage independent growth, migration and invasion potential, ability to form spheroids and xenografts in SCID mice. Results While all cell lines were capable of anchorage independent growth, only the TOV-1946 and OV-1946 cell lines were able to form spheroid and produce tumors. Profiling of keratins, p53 and Her2 protein expression was assessed by immunohistochemistry and western blot analyses. Somatic TP53 mutations were found in all cell lines, with TOV-1946 and OV-1946 harboring the same mutation, and none harbored the commonly observed somatic mutations in BRAF, KRAS or germline BRCA1/2 mutations found to recur in the French Canadian population. Conventional cytogenetics and spectral karyotype (SKY) analyses revealed complex karyotypes often observed in ovarian disease. Conclusion This is the first report of the establishment of matched EOC cell lines derived from both solid tumor and ascites of the same patient. PMID:18507860

Polarimetric imaging of retinal disease by polarization sensitive SLO

NASA Astrophysics Data System (ADS)

Miura, Masahiro; Elsner, Ann E.; Iwasaki, Takuya; Goto, Hiroshi

2015-03-01

Polarimetry imaging is used to evaluate different features of the macular disease. Polarimetry images were recorded using a commercially- available polarization-sensitive scanning laser opthalmoscope at 780 nm (PS-SLO, GDx-N). From data sets of PS-SLO, we computed average reflectance image, depolarized light images, and ratio-depolarized light images. The average reflectance image is the grand mean of all input polarization states. The depolarized light image is the minimum of crossed channel. The ratio-depolarized light image is a ratio between the average reflectance image and depolarized light image, and was used to compensate for variation of brightness. Each polarimetry image is compared with the autofluorescence image at 800 nm (NIR-AF) and autofluorescence image at 500 nm (SW-AF). We evaluated four eyes with geographic atrophy in age related macular degeneration, one eye with retinal pigment epithelium hyperplasia, and two eyes with chronic central serous chorioretinopathy. Polarization analysis could selectively emphasize different features of the retina. Findings in ratio depolarized light image had similarities and differences with NIR-AF images. Area of hyper-AF in NIR-AF images showed high intensity areas in the ratio depolarized light image, representing melanin accumulation. Areas of hypo-AF in NIR-AF images showed low intensity areas in the ratio depolarized light images, representing melanin loss. Drusen were high-intensity areas in the ratio depolarized light image, but NIR-AF images was insensitive to the presence of drusen. Unlike NIR-AF images, SW-AF images showed completely different features from the ratio depolarized images. Polarization sensitive imaging is an effective tool as a non-invasive assessment of macular disease.

Clinical Features of Pregnancy-associated Retinal and Choroidal Diseases Causing Acute Visual Disturbance.

PubMed

Park, Young Joo; Park, Kyu Hyung; Woo, Se Joon

2017-08-01

To report clinical features of patients with retinal and choroidal diseases presenting with acute visual disturbance during pregnancy. In this retrospective case series, patients who developed acute visual loss during pregnancy (including puerperium) and visited a tertiary hospital from July 2007 to June 2015, were recruited by searching electronic medical records. Patients were categorized according to the cause of visual loss. Clinical features and required diagnostic modalities were analyzed in the retinal and choroidal disease group. Acute visual loss occurred in 147 patients; 49 (38.9%) were classified into the retinal and choroidal group. The diagnoses included central serous chorioretinopathy (22.4%), hypertensive retinopathy with or without pre-eclampsia (22.4%), retinal tear with or without retinal detachment (18.4%), diabetic retinopathy progression (10.2%), Vogt-Koyanagi-Harada disease (4.1%), retinal artery occlusion (4.1%), multiple evanescent white dot syndrome (4.1%), and others (14.3%). Visual symptoms first appeared at gestational age 25.9 ± 10.3 weeks. The initial best-corrected visual acuity (BCVA) was 0.27 ± 0.39 logarithm of the minimum angle of resolution (logMAR); the final BCVA after delivery improved to 0.13 ± 0.35 logMAR. Serious visual deterioration (BCVA worth than 20 / 200) developed in two patients. Differential diagnoses were established with characteristic fundus and spectral-domain optical coherence tomography findings in all cases. In pregnant women with acute visual loss, retinal and choroidal diseases are common and could be vision threatening. Physicians should be aware of pregnancy-associated retinal and choroidal diseases and their clinical features. The differential diagnosis can be established with non-invasive techniques. © 2017 The Korean Ophthalmological Society

High resolution OCT image generation using super resolution via sparse representation

NASA Astrophysics Data System (ADS)

Asif, Muhammad; Akram, Muhammad Usman; Hassan, Taimur; Shaukat, Arslan; Waqar, Razi

2017-02-01

In this paper we propose a technique for obtaining a high resolution (HR) image from a single low resolution (LR) image -using joint learning dictionary - on the basis of image statistic research. It suggests that with an appropriate choice of an over-complete dictionary, image patches can be well represented as a sparse linear combination. Medical imaging for clinical analysis and medical intervention is being used for creating visual representations of the interior of a body, as well as visual representation of the function of some organs or tissues (physiology). A number of medical imaging techniques are in use like MRI, CT scan, X-rays and Optical Coherence Tomography (OCT). OCT is one of the new technologies in medical imaging and one of its uses is in ophthalmology where it is being used for analysis of the choroidal thickness in the eyes in healthy and disease states such as age-related macular degeneration, central serous chorioretinopathy, diabetic retinopathy and inherited retinal dystrophies. We have proposed a technique for enhancing the OCT images which can be used for clearly identifying and analyzing the particular diseases. Our method uses dictionary learning technique for generating a high resolution image from a single input LR image. We train two joint dictionaries, one with OCT images and the second with multiple different natural images, and compare the results with previous SR technique. Proposed method for both dictionaries produces HR images which are comparatively superior in quality with the other proposed method of SR. Proposed technique is very effective for noisy OCT images and produces up-sampled and enhanced OCT images.

Side effects of corticosteroid injections: what's new?

PubMed

Berthelot, Jean-Marie; Le Goff, Benoît; Maugars, Yves

2013-07-01

The risk of sepsis with a hip or knee implant does not seem to be increased by prior joint injections, as long as the injection and surgery are separated by at least two months. Calcifications have been reported after intradiscal injection in the coccygeal region for coccydynia. Complete rest for 24 hours after injection of triamcinolone hexacetonide into the knee had no effect on systemic diffusion of the product. Patients infected by HIV who are treated with ritonavir are at much greater risk for Cushing syndrome after epidural injection. Problems with menstruation after corticosteroid injection seem to be related to a transient decrease in estradiol levels, without alterations in FSH and LH levels. The risk of central serous chorioretinopathy and acute necrosis of the retina after injection is not known, even by ophthalmologists. Transient dysphonia occurs in 12% of patients receiving corticosteroid injections. The impressive Tachon's syndrome seems to be the venous counterpart to Nicolau's syndrome for arteries. Injections into C1-C2 should be abandoned because of the neurological risks. Since serious neurological events after foraminal injections could be the result of an overly fast injection into the arterialized radicular veins rather than in the arteries, only slow injections with products having a low risk of embolism or vascular complications should be allowed. Dexamethasone-based preparations seem to contain no particles or crystals, and have not induced any neurological accidents in various animal models, even after direct administration into vertebral or carotid arteries. Copyright © 2012 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Micropulse laser for persistent optic disc pit maculopathy. A case report.

PubMed

Valdés-Lara, Carlos Andrés; Crim, Nicolás; García-Aguirre, Gerardo; Lule, Ismael Ávila; Morales-Cantón, Virgilio

2018-06-01

Optic disc pits (ODP) are rare and congenital anomalies of the optic disc, sometimes remaining asymptomatic. However, serous macular detachment or optic disc maculopathy is the most common complication, causing significant visual deterioration, without a current consensus about treatment. We describe a case of ODP maculopathy that was treated successfully with micropulse laser. A patient with ODP maculopathy remained with macular serous detachment after nine months of follow up after pars plana vitrectomy. Subthreshold micropulse laser was used to treat macular serous detachment, achieving a significant improvement in central macular thickness after one session. Subthreshold micropulse laser is designed to stimulate the retinal pigment epithelium without damage to the photoreceptors, resulting in absorption of subretinal and intraretinal fluid. Macular serous detachment in patients with ODP requires a prompt diagnosis and treatment to avoid damage to photoreceptors. Subthreshold micropulse laser is a potential treatment for eyes with ODP and macular serous detachment complication.

Impact of Adjuvant External-Beam Radiation Therapy in Early-Stage Uterine Papillary Serous and Clear Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Anne, E-mail: akim2@health-quest.org; Schreiber, David; Rineer, Justin

2011-11-15

Purpose: Adjuvant radiation therapy (RT) in early-stage high- to intermediate-risk endometrioid adenocarcinoma is well established and has been shown to improve locoregional control. Its role in the management of early-stage clear cell carcinoma and uterine papillary serous carcinoma (UPSC) remains controversial. Methods and Materials: Using the Surveillance Epidemiology and End Results database, we identified women with American Joint Committee on Cancer Stage Sixth Edition. Stage IA-IIB clear cell carcinoma or UPSC who underwent hysterectomy with or without adjuvant RT between 1988 and 2003. We used Kaplan-Meier and Cox regression analysis to compare overall survival (OS) for all patients. Results: Wemore » identified 1,333 women of whom 451 had clear cell carcinoma and 882 had UPSC. Of those patients, 775 underwent surgery alone and 558 received adjuvant RT as well. For Stages I-IIB disease, the median OS with surgery alone was 106 months, vs. 151 months with adjuvant RT (p = 0.006). On subgroup analysis, we saw the benefit from adjuvant RT only in Stage IB-C patients. For Stage IB disease, patients undergoing surgery alone had a median OS of 117 months, vs. median survival not reached with the addition of RT (p = 0.006). For Stage IC disease, surgery alone had a median OS of 35 months vs. 120 months with RT (p = 0.001). Although the apparent benefit of RT diminished when measured via multivariate analysis, the impact of RT on survival did show a trend toward significance (hazard ration 0.808, confidence interval 95% 0.651-1.002, p = 0.052) Conclusion: In FIGO Stage IB-C papillary serous and clear cell uterine carcinoma, adjuvant RT seems to play an important role in improving survival.« less

[Surgical therapy of giant tubulovillous adenoma of the duodenum and incidental serous cystadenoma of the head of the pancreas].

PubMed

Knoop, M; Vorwerk, T; Lüders, P; Hendrich, F

2001-01-01

A villous giant adenoma of the duodenum was diagnosed in a 56-year-old female patient with uncharacteristic upper abdominal discomfort after multiple previous laparotomies for various indications. A partial pancreaticoduodenectomy was performed as radical oncological procedure since the dignity of the neoplasm was uncertain. Histopathologic examination revealed medium-grade cell dysplasia of the villous adenoma but an incidental serous cystadenoma of the pancreatic head as well. The postoperative course was uneventful. The coincidence of these both rare neoplastic entities has yet not been described in the literature. The surgical options for treatment of both neoplasms are discussed.

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.

PubMed

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.

Ovarian transitional cell carcinoma represents a poorly differentiated form of high-grade serous or endometrioid adenocarcinoma.

PubMed

Takeuchi, Tadahisa; Ohishi, Yoshihiro; Imamura, Hiroko; Aman, Murasaki; Shida, Kaai; Kobayashi, Hiroaki; Kato, Kiyoko; Oda, Yoshinao

2013-07-01

Ovarian transitional cell tumors include Brenner tumors (BTs) and transitional cell carcinoma (TCC; non-BTs) according to the most recent World Health Organization classification. However, it remains a matter of debate whether TCC represents a distinct entity or a morphologic variant of high-grade serous adenocarcinoma (HG-SC). The purpose of this study was to resolve the above question by clarifying the morphologic, immunohistochemical, and molecular features of TCC. We reviewed 488 cases of epithelial ovarian carcinomas and reclassified them on the basis of the most recent World Health Organization classification with the modifications proposed by Köbel and colleagues, and 35 cases of TCC were identified; 25 and 6 TCCs were admixed with HG-SC and endometrioid adenocarcinoma (EC), respectively, and the remaining 4 cases were pure TCC. TCC components were not observed in any clear cell carcinomas or mucinous adenocarcinomas. Only 2 cases of malignant BT were identified. In addition to TCCs, malignant BTs, and related adenocarcinomas, benign and borderline BTs were included in the following immunohistochemical and molecular analyses. Immunohistochemically, pure TCCs, TCCs admixed with HG-SC, and pure HG-SCs were characterized by frequent aberrant p53 expression (diffuse or null pattern) and WT1+/ER+/PR+/IMP2+ immunophenotype, whereas BTs, including benign, borderline, and malignant BTs, were characterized by lack of aberrant p53 expression and WT1-/ER-/PR-/IMP2- immunophenotype. In contrast to the BTs, pure ECs and TCCs admixed with EC showed an ER+/PR+ immunophenotype. Nearly all the tumors with a TP53 gene mutation by molecular analysis showed aberrant p53 staining patterns. In conclusion, TCC is not a distinct entity but a poorly differentiated form of serous or EC, as (1) most TCCs coexist with HG-SC (mostly) or EC (occasionally), and (2) the immunophenotype and molecular features are similar to those of HG-SC or EC but different from those of BTs.

Immunohistochemical characterization of endometrial carcinomas: endometrioid, serous and clear cell adenocarcinomas in association with genetic analysis.

PubMed

Yasuda, Masanori

2014-12-01

Developments in immunohistochemistry, which are closely linked with the advances in the analyses of genetic abnormalities and their associated molecular disorders as early and late histogenetic events, have contributed greatly to the improvement of pathological diagnostic confirmation and validation. Immunohistochemistry has also generated great benefit to the innovation of therapeutic strategies for various kinds of cancers. In this article, the three representative histological types of corpus cancer, namely, endometrioid adenocarcinoma, serous adenocarcinoma and clear cell adenocarcinoma, will be histologically approached in association with their immunohistochemical profiles as well as genetic disorders. First, the focus will be on 'Conventional/prototypic features,' followed by 'Controversy over conventional histological subclassification,' and subsequently 'Tumorigenesis and re-subclassification'. © 2014 The Author. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Post-translational amino acid racemization in the frog skin peptide deltorphin I in the secretion granules of cutaneous serous glands.

PubMed

Auvynet, Constance; Seddiki, Nabila; Dunia, Irene; Nicolas, Pierre; Amiche, Mohamed; Lacombe, Claire

2006-01-01

The dermal glands of the South American hylid frog Phyllomedusa bicolor synthesize and expel huge amounts of cationic, alpha-helical, 24- to 33-residue antimicrobial peptides, the dermaseptins B. These glands also produce a wide array of peptides that are similar to mammalian hormones and neuropeptides, including a heptapeptide opioid containing a D-amino acid, deltorphin I (Tyr-DAla-Phe-Asp-Val-Val-Gly NH2). Its biological activity is due to the racemization of L-Ala2 to D-Ala. The dermaseptins B and deltorphins are all derived from a single family of precursor polypeptides that have an N-terminal preprosequence that is remarkably well conserved, although the progenitor sequences giving rise to mature opioid or antimicrobial peptides are markedly different. Monoclonal and polyclonal antibodies were used to examine the cellular and ultrastructural distributions of deltorphin I and dermaseptin B in the serous glands by immunofluoresence confocal microscopy and immunogold-electron microscopy. Preprodeltorphin I and preprodermaseptins B are sorted into the regulated pathway of secretion, where they are processed to give the mature products. Deltorphin I, [l-Ala2]-deltorphin I and dermaseptin B are all stored together in secretion granules which accumulate in the cytoplasm of all serous glands. We conclude that the L- to D-amino acid isomerization of the deltorphin I occurs in the secretory granules as a post-translational event. Thus the specificity of isomerization depends on the presence of structural and/or conformational determinants in the peptide N-terminus surrounding the isomerization site.

Phenformin has anti-tumorigenic effects in human ovarian cancer cells and in an orthotopic mouse model of serous ovarian cancer.

PubMed

Jackson, Amanda L; Sun, Wenchuan; Kilgore, Joshua; Guo, Hui; Fang, Ziwei; Yin, Yajie; Jones, Hannah M; Gilliam, Timothy P; Zhou, Chunxiao; Bae-Jump, Victoria L

2017-11-21

Obesity and diabetes have been associated with increased risk and worse outcomes in ovarian cancer (OC). The biguanide metformin is used in the treatment of type 2 diabetes and is also believed to have anti-tumorigenic benefits. Metformin is highly hydrophilic and requires organic cation transporters (OCTs) for entry into human cells. Phenformin, another biguanide, was taken off the market due to an increased risk of lactic acidosis over metformin. However, phenformin is not reliant on transporters for cell entry; and thus, may have increased potency as both an anti-diabetic and anti-tumorigenic agent than metformin. Thus, our goal was to evaluate the effect of phenformin on established OC cell lines, primary cultures of human OC cells and in an orthotopic mouse model of high grade serous OC. In three OC cell lines, phenformin significantly inhibited cellular proliferation, induced cell cycle G1 arrest and apoptosis, caused cellular stress, inhibited adhesion and invasion, and activation of AMPK and inhibition of the mTOR pathway. Phenformin also exerted anti-proliferative effects in seven primary cell cultures of human OC. Lastly, phenformin inhibited tumor growth in an orthotopic mouse model of serous OC, coincident with decreased Ki-67 staining and phosphorylated-S6 expression and increased expression of caspase 3 and phosphorylated-AMPK. Our findings demonstrate that phenformin has anti-tumorigenic effects in OC as previously demonstrated by metformin but it is yet to be determined if it is superior to metformin for the potential treatment of this disease.

Phenformin has anti-tumorigenic effects in human ovarian cancer cells and in an orthotopic mouse model of serous ovarian cancer

PubMed Central

Jackson, Amanda L.; Sun, Wenchuan; Kilgore, Joshua; Guo, Hui; Fang, Ziwei; Yin, Yajie; Jones, Hannah M.; Gilliam, Timothy P.; Zhou, Chunxiao; Bae-Jump, Victoria L.

2017-01-01

Obesity and diabetes have been associated with increased risk and worse outcomes in ovarian cancer (OC). The biguanide metformin is used in the treatment of type 2 diabetes and is also believed to have anti-tumorigenic benefits. Metformin is highly hydrophilic and requires organic cation transporters (OCTs) for entry into human cells. Phenformin, another biguanide, was taken off the market due to an increased risk of lactic acidosis over metformin. However, phenformin is not reliant on transporters for cell entry; and thus, may have increased potency as both an anti-diabetic and anti-tumorigenic agent than metformin. Thus, our goal was to evaluate the effect of phenformin on established OC cell lines, primary cultures of human OC cells and in an orthotopic mouse model of high grade serous OC. In three OC cell lines, phenformin significantly inhibited cellular proliferation, induced cell cycle G1 arrest and apoptosis, caused cellular stress, inhibited adhesion and invasion, and activation of AMPK and inhibition of the mTOR pathway. Phenformin also exerted anti-proliferative effects in seven primary cell cultures of human OC. Lastly, phenformin inhibited tumor growth in an orthotopic mouse model of serous OC, coincident with decreased Ki-67 staining and phosphorylated-S6 expression and increased expression of caspase 3 and phosphorylated-AMPK. Our findings demonstrate that phenformin has anti-tumorigenic effects in OC as previously demonstrated by metformin but it is yet to be determined if it is superior to metformin for the potential treatment of this disease. PMID:29245964

[Maxillary swing approach in the management of tumors in the central and lateral cranial base].

PubMed

Liao, Hua; Hua, Qing-quan; Wu, Zhan-yuan

2006-04-01

patients developed serous otitis media (58.8%), and four patients developed a certain degree of trismus (23.5%). Cerebrospinal fluid leak occurred in two patients. They subsequently healed with conservative management. The maxillary swing approach is a proven method for access to the central and lateral skull base with good exposure and acceptable morbidity. Complications and sequelae associated with this approach include facial scarring, transaction of the infraorbital nerve, impaired lacrimal drainage, eustachian tube dysfunction and serous otitis, palatal fistula, trismus etc. Some procedures should be performed for reducing the incidence and severity of complications in the maxillary swing approach.

Systematic analyses reveal long non-coding RNA (PTAF)-mediated promotion of EMT and invasion-metastasis in serous ovarian cancer.

PubMed

Liang, Haihai; Zhao, Xiaoguang; Wang, Chengyu; Sun, Jian; Chen, Yingzhun; Wang, Guoyuan; Fang, Lei; Yang, Rui; Yu, Mengxue; Gu, Yunyan; Shan, Hongli

2018-06-21

A deeper mechanistic understanding of epithelial-to-mesenchymal transition (EMT) regulation is needed to improve current anti-metastasis strategies in ovarian cancer (OvCa). This study was designed to investigate the role of lncRNAs in EMT regulation during process of invasion-metastasis in serous OvCa to improve current anti-metastasis strategies for OvCa. We systematically analyzes high-throughput gene expression profiles of both lncRNAs and protein-coding genes in OvCa samples with integrated epithelial (iE) subtype and integrated mesenchymal (iM) subtype labels. Mouse models, cytobiology, molecular biology assays and clinical samples were performed to elucidate the function and underlying mechanisms of lncRNA PTAF-mediated promotion of EMT and invasion-metastasis in serous OvCa. We constructed a lncRNA-mediated competing endogenous RNA (ceRNA) regulatory network that affects the expression of many EMT-related protein-coding genes in mesenchymal OvCa. Using a combination of in vitro and in vivo studies, we provided evidence that the lncRNA PTAF-miR-25-SNAI2 axis controlled EMT in OvCa. Our results revealed that up-regulated PTAF induced elevated SNAI2 expression by competitively binding to miR-25, which in turn promoted OvCa cell EMT and invasion. Moreover, we found that silencing of PTAF inhibited tumor progression and metastasis in an orthotopic mouse model of OvCa. We then observed a significant correlation between PTAF expression and EMT markers in OvCa patients. The lncRNA PTAF, a mediator of TGF-β signaling, can predispose OvCa patients to metastases and may serve as a potential target for anti-metastatic therapies for mesenchymal OvCa patients.

Are the uterine serous carcinomas underdiagnosed? Histomorphologic and immunohistochemical correlates and clinical follow up in high-grade endometrial carcinomas initially diagnosed as high-grade endometrioid carcinoma.

PubMed

Hu, Shaomin; Hinson, Jeff L; Matnani, Rahul; Cibull, Michael L; Karabakhtsian, Rouzan G

2018-02-01

Histologic subclassification of high-grade endometrial carcinomas can sometimes be a diagnostic challenge when based on histomorphology alone. Here we utilized immunohistochemical markers to determine the immunophenotype in histologically ambiguous high-grade endometrial carcinomas that were initially diagnosed as pure or mixed high-grade endometrioid carcinoma, aiming to determine the utility of selected immunohistochemical panel in accurate classification of these distinct tumor types, while correlating these findings with the clinical outcome. A total of 43 high-grade endometrial carcinoma cases initially classified as pure high-grade endometrioid carcinoma (n=32), mixed high-grade endometrioid carcinoma/serous carcinoma (n=9) and mixed high-grade endometrioid carcinoma/clear cell carcinoma (n=2) were retrospectively stained with a panel of immunostains, including antibodies for p53, p16, estrogen receptor, and mammaglobin. Clinical follow-up data were obtained, and stage-to-stage disease outcomes were compared for different tumor types. Based on aberrant staining for p53 and p16, 17/43 (40%) of the high-grade endometrial carcinoma cases initially diagnosed as high-grade endometrioid carcinoma were re-classified as serous carcinoma. All 17 cases showed negative staining for mammaglobin, while estrogen receptor was positive in only 6 (35%) cases. The remaining 26 cases of high-grade endometrioid carcinoma showed wild-type staining for p53 in 25 (96%) cases, patchy staining for p16 in 20 (77%) cases, and were positive for mammaglobin and estrogen receptor in 8 (31%) and 19 (73%) cases, respectively, thus the initial diagnosis of high-grade endometrioid carcinoma was confirmed in these cases. In addition, the patients with re-classified serous carcinoma had advanced clinical stages at diagnosis and poorer overall survival on clinical follow-up compared to that of the remaining 26 high-grade endometrioid carcinoma cases. These results indicate that selected

75 FR 4623 - Qualification of Drivers; Exemption Applications; Vision

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-28

... reasons, including amblyopia, optic nerve hyperplasia, retinopathy of prematurity, macular hole, central serous retinopathy, prosthesis, macular degeneration, cataract, extropia, diabetic retinopathy, aphakia...

A Postmenopausal Woman with Giant Ovarian Serous Cyst Adenoma: A Case Report with Brief Literature Review

PubMed Central

Mubarak Al Badi, Muna

2018-01-01

Giant (>10 cm) ovarian cyst is a rare finding. In the literature, a few cases of giant ovarian cysts have been mentioned sporadically, especially in elderly patients. We report a 57-year-old postmenopausal woman with a giant left ovarian cyst measuring 43 × 15 × 9 cm. She was referred to us from the local health center in view of palpable pelvic mass for six-month period. Considering the age and menopausal state, we performed a total abdominal hysterectomy and bilateral salpingo-oophorectomy with excision of the giant left ovarian cyst intact and successfully without any significant complication. On histopathological examination, the cyst was confirmed as benign serous cystadenoma of the ovary. During the management of these high-risk cases of multidisciplinary approach, intraoperative and postoperative strict vigilance is necessary to avoid unwanted complications. PMID:29850314

PIK3CA missense mutation is associated with unfavorable outcome in grade 3 endometrioid carcinoma but not in serous endometrial carcinoma.

PubMed

McIntyre, John B; Nelson, Gregg S; Ghatage, Prafull; Morris, Don; Duggan, Máire A; Lee, Cheng-Han; Doll, Corinne M; Köbel, Martin

2014-01-01

To evaluate the outcome association of PIK3CA mutational status within histological types of rigorously classified high-grade endometrial carcinomas. We assessed PIK3CA mutational status in exon 9 and exon 20 hot spots by Sanger sequencing of DNA derived from formalin fixed paraffin embedded tissue of 57 grade 3 endometrioid, 26 serous, 11 clear cell and 5 dedifferentiated carcinomas. We correlated PIK3CA mutation status with clinicopathological and other molecular parameters. Univariate and multivariate disease specific survival analysis was performed using Kaplan-Meier and Cox regression analyses. PIK3CA exon 9 or exon 20 missense mutations were identified in 20 of 99 (20%) high-grade endometrial carcinomas without significant difference across histological types (p=0.22). Presence of PIK3CA exon 9 or exon 20 missense mutations was associated with shorter disease specific survival within grade 3 endometrioid (p=0.0029) but not endometrial serous (p=0.57) carcinoma based on univariate analysis. Within grade 3 endometrioid carcinoma, PIK3CA exon 9 or exon 20 missense mutations were more commonly observed in cases that were deficient for mismatch repair protein expression (p=0.0058) and showed loss of ARID1A expression (p=0.037). PIK3CA exon 9 or exon 20 missense mutations are present across all histological types of high-grade endometrial carcinomas but a significant outcome association is only seen in grade 3 endometrioid carcinoma, suggesting a greater biological importance in this tumor type. Copyright © 2013 Elsevier Inc. All rights reserved.

Mutational analysis of BRAF and KRAS in ovarian serous borderline (atypical proliferative) tumours and associated peritoneal implants

PubMed Central

Ardighieri, Laura; Zeppernick, Felix; Hannibal, Charlotte G; Vang, Russell; Cope, Leslie; Junge, Jette; Kjaer, Susanne K; Kurman, Robert J; Shih, Ie-Ming

2014-01-01

There is debate as to whether peritoneal implants associated with serous borderline tumours/atypical proliferative serous tumours (SBT/APSTs) of the ovary are derived from the primary ovarian tumour or arise independently in the peritoneum. We analysed 57 SBT/APSTs from 45 patients with advanced-stage disease identified from a nation-wide tumour registry in Denmark. Mutational analysis for hotspots in KRAS and BRAF was successful in 55 APSTs and demonstrated KRAS mutations in 34 (61.8%) and BRAF mutations in eight (14.5%). Mutational analysis was successful in 56 peritoneal implants and revealed KRAS mutations in 34 (60.7%) and BRAF mutations in seven (12.5%). Mutational analysis could not be performed in two primary tumours and in nine implants, either because DNA amplification failed or because there was insufficient tissue for mutational analysis. For these specimens we performed VE1 immunohistochemistry, which was shown to be a specific and sensitive surrogate marker for a V600E BRAF mutation. VE1 staining was positive in one of two APSTs and seven of nine implants. Thus, among 63 implants for which mutation status was known (either by direct mutational analysis or by VE1 immunohistochemistry), 34 (53.9%) had KRAS mutations and 14 (22%) had BRAF mutations, of which identical KRAS mutations were found in 34 (91%) of 37 SBT/APST–implant pairs and identical BRAF mutations in 14 (100%) of 14 SBT/APST–implant pairs. Wild-type KRAS and BRAF (at the loci investigated) were found in 11 (100%) of 11 SBT/APST–implant pairs. Overall concordance of KRAS and BRAF mutations was 95% in 59 of 62 SBT/APST–implant (non-invasive and invasive) pairs (p < 0.00001). This study provides cogent evidence that the vast majority of peritoneal implants, non-invasive and invasive, harbour the identical KRAS or BRAF mutations that are present in the associated SBT/APST, supporting the view that peritoneal implants are derived from the primary ovarian tumour. PMID:24307542

Extreme Outlier Analysis Identifies Occult Mitogen-Activated Protein Kinase Pathway Mutations in Patients With Low-Grade Serous Ovarian Cancer

PubMed Central

Grisham, Rachel N.; Sylvester, Brooke E.; Won, Helen; McDermott, Gregory; DeLair, Deborah; Ramirez, Ricardo; Yao, Zhan; Shen, Ronglai; Dao, Fanny; Bogomolniy, Faina; Makker, Vicky; Sala, Evis; Soumerai, Tara E.; Hyman, David M.; Socci, Nicholas D.; Viale, Agnes; Gershenson, David M.; Farley, John; Levine, Douglas A.; Rosen, Neal; Berger, Michael F.; Spriggs, David R.; Aghajanian, Carol A.; Solit, David B.; Iyer, Gopa

2015-01-01

Purpose No effective systemic therapy exists for patients with metastatic low-grade serous (LGS) ovarian cancers. BRAF and KRAS mutations are common in serous borderline (SB) and LGS ovarian cancers, and MEK inhibition has been shown to induce tumor regression in a minority of patients; however, no correlation has been observed between mutation status and clinical response. With the goal of identifying biomarkers of sensitivity to MEK inhibitor treatment, we performed an outlier analysis of a patient who experienced a complete, durable, and ongoing (> 5 years) response to selumetinib, a non-ATP competitive MEK inhibitor. Patients and Methods Next-generation sequencing was used to analyze this patient's tumor as well as an additional 28 SB/LGS tumors. Functional characterization of an identified novel alteration of interest was performed. Results Analysis of the extraordinary responder's tumor identified a 15-nucleotide deletion in the negative regulatory helix of the MAP2K1 gene encoding for MEK1. Functional characterization demonstrated that this mutant induced extracellular signal-regulated kinase pathway activation, promoted anchorage-independent growth and tumor formation in mice, and retained sensitivity to selumetinib. Analysis of additional LGS/SB tumors identified mutations predicted to induce extracellular signal-regulated kinase pathway activation in 82% (23 of 28), including two patients with BRAF fusions, one of whom achieved an ongoing complete response to MEK inhibitor–based combination therapy. Conclusion Alterations affecting the mitogen-activated protein kinase pathway are present in the majority of patients with LGS ovarian cancer. Next-generation sequencing analysis revealed deletions and fusions that are not detected by older sequencing approaches. These findings, coupled with the observation that a subset of patients with recurrent LGS ovarian cancer experienced dramatic and durable responses to MEK inhibitor therapy, support additional

Evaluation of the Precision of the Microperimetry Function of the Spectral OCT/SLO

ClinicalTrials.gov

2017-04-03

Age-Related Macular Degeneration; Geographic Atrophy; Diabetic Retinopathy; Macular Edema; Retinal Vein Occlusion; Central Serous Retinopathy; Pattern Dystrophy of Macula; Epiretinal Membrane; Macular Hole

Pregnancy-associated retinal diseases and their management.

PubMed

Errera, Marie-Hélène; Kohly, Radha P; da Cruz, Lyndon

2013-01-01

Pregnancy-associated retinal diseases are conditions that may occur uniquely in pregnancy or, more commonly, general conditions that may worsen or alter during pregnancy as a result of hematologic, hormonal, metabolic, cardiovascular, and immunologic changes. Diabetic retinopathy (DR) is by far the most common retinal condition that is altered by pregnancy. However, there are currently no widely accepted, precise clinical guidelines regarding its management during pregnancy. At present it is not possible to predict who will regress and who will progress without treatment. Some of the variation in progression of DR in pregnancy may be a result of well-known risk factors such as hypertension or inadequate glycemic control prior to pregnancy. Other pregnancy-associated retinal diseases are relatively uncommon, and their treatments are poorly characterized. Pre-existing conditions include the white dot syndromes, such as punctuate inner choroidopathy and ocular histoplasmosis syndrome, as well as chorioretinal neovascularization from many other etiologies. Retinal and chorioretinal disorders that can arise during pregnancy include central serous chorioretinopathy and occlusive vasculopathy such as retinal artery occlusion (Purtschers-like retinopathy) and retinal vein occlusion. There remains a small group that appear to be unique to pregnancy, with pre-eclampsia- and eclampsia-associated retinopathy, disseminated intravascular coagulopathy, or amniotic fluid embolism being the best described. In angiogenic retinal diseases outside of pregnancy, the use of anti-vascular endothelial growth factor (anti-VEGF agents) has proven helpful. There are no safety data about the use of anti-VEGF agents during pregnancy, and conventionally the proposed interventions have been laser photocoagulation and systemic or intravitreal injections of steroids. Most of the literature on the treatment of pregnancy associated-chorioretinal neovascularization is anecdotal. Copyright © 2013

Giant serous cystadenoma arising from an accessory ovary in a morbidly obese 11-year-old girl: a case report.

PubMed

Sharatz, Steven M; Treviño, Taína A; Rodriguez, Luís; West, Jared H

2008-01-18

Ectopic ovarian tissue is an unusual entity, especially if it is an isolated finding thought to be of embryological origin. An 11-year-old, morbidly obese female presented with left flank pain, nausea, and irregular menses. Various diagnostic procedures suggested a large ovarian cyst, and surgical resection was performed. Histologically, the resected mass was not of tubal origin as suspected, but a serous cystadenoma arising from ovarian tissue. The patient's two normal, eutopic ovaries were completely uninvolved and unaffected. A tumor arising from ectopic ovarian tissue of embryological origin seems the most likely explanation. We suggest refining the descriptive nomenclature so as to more precisely characterize the various presentations of ovarian ectopia.

Prognostic Factors of Uterine Serous Carcinoma-A Multicenter Study.

PubMed

Zhong, Xiaozhu; Wang, Jianliu; Kaku, Tengen; Wang, Zhiqi; Li, Xiaoping; Wei, Lihui

2018-04-04

The prognostic factors of uterine serous carcinoma (USC) vary among studies, and there is no report of Chinese USC patients. The aim of this study was to investigate the clinicopathological characteristics and prognostic factors in Chinese patients with USC. Patients with USC from 13 authoritative university hospitals in China and treated between 2004 and 2014 were retrospectively reviewed. Three-year disease-free survival rate (DFSR), cumulative recurrence, and cumulative mortality were estimated by Kaplan-Meier analyses and log-rank tests. Multivariate Cox regression analysis was used to model the association of potential prognostic factors with clinical outcomes. Data of a total of 241 patients were reviewed. The median follow-up was 26 months (range, 1-128 months). Median age was 60 years (range, 39-84 years), and 58.0% had stages I-II disease. The 3-year DFSR and cumulative recurrence were 46.8% and 27.7%. Advanced stage (III and IV) (P = 0.004), myometrial invasion (P = 0.001), adnexal involvement (P < 0.001), lymph node metastasis (P = 0.025), and positive peritoneal cytology (P = 0.007) were independently associated with 3-year DFSR. Advanced stage (P = 0.017), myometrial invasion (P = 0.008), adnexal involvement (odds ratio, 2.987; P = 0.001), lymph node metastasis (P = 0.031), and positive peritoneal cytology (P = 0.001) were independently associated with the cumulative recurrence. Myometrial invasion (P = 0.004) and positive peritoneal cytology (P = 0.025) were independently associated with 3-year cumulative mortality. Peritoneal cytology and myometrial invasion could be independent prognostic factors for 3-year DFSR, cumulative recurrence, and cumulative mortality of patients with USC. Prospective studies are needed to confirm these results.

Objective, domain-specific HER2 measurement in uterine and ovarian serous carcinomas and its clinical significance.

PubMed

Carvajal-Hausdorf, Daniel E; Schalper, Kurt A; Bai, Yalai; Black, Jonathan; Santin, Alessandro D; Rimm, David L

2017-04-01

HER2 overexpression/amplification is identified in up to 40% of uterine serous carcinomas (USC) and 10% of ovarian serous carcinomas (OSC). However, clinical trials using various HER2-targeted agents failed to show significant responses. FDA-approved HER2 assays target only the protein's intracellular domain (ICD) and not the extracellular domain (ECD). Previous quantitative studies in breast cancer by our group have shown that ICD of HER2 is expressed in some cases that do not express the HER2 ECD. We measured HER2 ICD and ECD in USC and OSC samples, and determined their relationship with clinico-pathologic characteristics and survival. We measured HER2 ICD and ECD levels in 2 cohorts of USC and OSC comprising 102 and 175 patients, respectively. HER2 antibodies targeting ICD (CB11) and ECD (SP3) were validated and standardized using the AQUA® method of quantitative immunofluorescence (QIF) and a previously reported HER2 standardization tissue microarray (TMA). Objective, population-based cut-points were used to stratify patients according to HER2 ICD/ECD status. In USC, 8% of patients with high HER2 ICD had low ECD levels (6/75 patients). In OSC, 42% of patients with high HER2 ICD had low ECD levels (29/69 patients). HER2 ICD/ECD status in USC and OSC was not significantly associated with major clinico-pathological features or survival. Using objective, domain-specific HER2 measurement, 8% of USC and 42% of OSC patients with high HER2 ICD levels do not show uniform overexpression of the ECD. This may be related to the presence of p95 HER2, an oncogenic fragment generated by full protein cleavage or alternative initiation of translation. These observations raise the possibility that USC/OSCs expressing low ECD despite being HER2-positive by ICD measurement, may benefit from therapies directed against the intracellular domain (e.g. lapatinib or afatinib) alone or in combination with extracellular domain-directed drugs (e.g. trastuzumab, pertuzumab, T-DM1

The Potential of Targeting Ribosome Biogenesis in High-Grade Serous Ovarian Cancer

PubMed Central

Yan, Shunfei; Frank, Daniel; Son, Jinbae; Hannan, Katherine M.; Hannan, Ross D.; Chan, Keefe T.; Pearson, Richard B.; Sanij, Elaine

2017-01-01

Overall survival for patients with ovarian cancer (OC) has shown little improvement for decades meaning new therapeutic options are critical. OC comprises multiple histological subtypes, of which the most common and aggressive subtype is high-grade serous ovarian cancer (HGSOC). HGSOC is characterized by genomic structural variations with relatively few recurrent somatic mutations or dominantly acting oncogenes that can be targeted for the development of novel therapies. However, deregulation of pathways controlling homologous recombination (HR) and ribosome biogenesis has been observed in a high proportion of HGSOC, raising the possibility that targeting these basic cellular processes may provide improved patient outcomes. The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib has been approved to treat women with defects in HR due to germline BRCA mutations. Recent evidence demonstrated the efficacy of targeting ribosome biogenesis with the specific inhibitor of ribosomal RNA synthesis, CX-5461 in v-myc avian myelocytomatosis viral oncogene homolog (MYC)-driven haematological and prostate cancers. CX-5461 has now progressed to a phase I clinical trial in patients with haematological malignancies and phase I/II trial in breast cancer. Here we review the currently available targeted therapies for HGSOC and discuss the potential of targeting ribosome biogenesis as a novel therapeutic approach against HGSOC. PMID:28117679

Similar protein expression profiles of ovarian and endometrial high-grade serous carcinomas.

PubMed

Hiramatsu, Kosuke; Yoshino, Kiyoshi; Serada, Satoshi; Yoshihara, Kosuke; Hori, Yumiko; Fujimoto, Minoru; Matsuzaki, Shinya; Egawa-Takata, Tomomi; Kobayashi, Eiji; Ueda, Yutaka; Morii, Eiichi; Enomoto, Takayuki; Naka, Tetsuji; Kimura, Tadashi

2016-03-01

Ovarian and endometrial high-grade serous carcinomas (HGSCs) have similar clinical and pathological characteristics; however, exhaustive protein expression profiling of these cancers has yet to be reported. We performed protein expression profiling on 14 cases of HGSCs (7 ovarian and 7 endometrial) and 18 endometrioid carcinomas (9 ovarian and 9 endometrial) using iTRAQ-based exhaustive and quantitative protein analysis. We identified 828 tumour-expressed proteins and evaluated the statistical similarity of protein expression profiles between ovarian and endometrial HGSCs using unsupervised hierarchical cluster analysis (P<0.01). Using 45 statistically highly expressed proteins in HGSCs, protein ontology analysis detected two enriched terms and proteins composing each term: IMP2 and MCM2. Immunohistochemical analyses confirmed the higher expression of IMP2 and MCM2 in ovarian and endometrial HGSCs as well as in tubal and peritoneal HGSCs than in endometrioid carcinomas (P<0.01). The knockdown of either IMP2 or MCM2 by siRNA interference significantly decreased the proliferation rate of ovarian HGSC cell line (P<0.01). We demonstrated the statistical similarity of the protein expression profiles of ovarian and endometrial HGSC beyond the organs. We suggest that increased IMP2 and MCM2 expression may underlie some of the rapid HGSC growth observed clinically.

Germline whole exome sequencing and large-scale replication identifies FANCM as a likely high grade serous ovarian cancer susceptibility gene.

PubMed

Dicks, Ed; Song, Honglin; Ramus, Susan J; Oudenhove, Elke Van; Tyrer, Jonathan P; Intermaggio, Maria P; Kar, Siddhartha; Harrington, Patricia; Bowtell, David D; Group, Aocs Study; Cicek, Mine S; Cunningham, Julie M; Fridley, Brooke L; Alsop, Jennifer; Jimenez-Linan, Mercedes; Piskorz, Anna; Goranova, Teodora; Kent, Emma; Siddiqui, Nadeem; Paul, James; Crawford, Robin; Poblete, Samantha; Lele, Shashi; Sucheston-Campbell, Lara; Moysich, Kirsten B; Sieh, Weiva; McGuire, Valerie; Lester, Jenny; Odunsi, Kunle; Whittemore, Alice S; Bogdanova, Natalia; Dürst, Matthias; Hillemanns, Peter; Karlan, Beth Y; Gentry-Maharaj, Aleksandra; Menon, Usha; Tischkowitz, Marc; Levine, Douglas; Brenton, James D; Dörk, Thilo; Goode, Ellen L; Gayther, Simon A; Pharoah, D P Paul

2017-08-01

We analyzed whole exome sequencing data in germline DNA from 412 high grade serous ovarian cancer (HGSOC) cases from The Cancer Genome Atlas Project and identified 5,517 genes harboring a predicted deleterious germline coding mutation in at least one HGSOC case. Gene-set enrichment analysis showed enrichment for genes involved in DNA repair (p = 1.8×10 -3 ). Twelve DNA repair genes - APEX1, APLF, ATX, EME1, FANCL, FANCM, MAD2L2, PARP2, PARP3, POLN, RAD54L and SMUG1 - were prioritized for targeted sequencing in up to 3,107 HGSOC cases, 1,491 cases of other epithelial ovarian cancer (EOC) subtypes and 3,368 unaffected controls of European origin. We estimated mutation prevalence for each gene and tested for associations with disease risk. Mutations were identified in both cases and controls in all genes except MAD2L2 , where we found no evidence of mutations in controls. In FANCM we observed a higher mutation frequency in HGSOC cases compared to controls (29/3,107 cases, 0.96 percent; 13/3,368 controls, 0.38 percent; P=0.008) with little evidence for association with other subtypes (6/1,491, 0.40 percent; P=0.82). The relative risk of HGSOC associated with deleterious FANCM mutations was estimated to be 2.5 (95% CI 1.3 - 5.0; P=0.006). In summary, whole exome sequencing of EOC cases with large-scale replication in case-control studies has identified FANCM as a likely novel susceptibility gene for HGSOC, with mutations associated with a moderate increase in risk. These data may have clinical implications for risk prediction and prevention approaches for high-grade serous ovarian cancer in the future and a significant impact on reducing disease mortality.

A Clinical and Pathologic Comparison Between Stage-Matched Endometrial Intraepithelial Carcinoma and Uterine Serous Carcinoma

PubMed Central

Hou, June Y.; McAndrew, Thomas C.; Goldberg, Gary L.; Whitney, Kathleen

2014-01-01

Endometrial intraepithelial carcinoma (EIC) is a rare pathologic variant of uterine serous carcinoma (USC). Our aim is to distinguish patterns of clinic–pathologic outcomes in patients with EIC and USC for disease limited to the endometrium (stage 1A) as well as with distant metastasis (stage 4B). Surgically staged patients were retrospectively identified and relevant variables were extracted and compared. Kaplan-Meier was used to generate the survival data. More USC (n = 29) exhibited lymphovascular invasion (stage 4, P = .01) and expressed higher levels of estrogen receptor-α than EIC (P = .0009 and .063 for stages 1 and 4, respectively). The survival is comparable, with 1 recurrence in each group for stage 1A disease. For stage 4 EIC and USC, the progression-free survival (14 vs10 months) and overall survival (19 vs 20 months) are similar to what is previously published. In conclusion, EIC, whether limited to the endometrium, or widely metastatic, imparts similar outcomes and should be treated comparably with stage-matched USC. PMID:24023030

Genomic analysis of genetic heterogeneity and evolution in high-grade serous ovarian carcinoma

PubMed Central

Cooke, Susanna L; Ng, Charlotte KY; Melnyk, Nataliya; Garcia, Maria J; Hardcastle, Tom; Temple, Jillian; Langdon, Simon; Huntsman, David; Brenton, James D

2010-01-01

Resistance to chemotherapy in ovarian cancer is poorly understood. Evolutionary models of cancer predict that, following treatment, resistance emerges either due to outgrowth of an intrinsically resistant sub-clone, or evolves in residual disease under the selective pressure of treatment. To investigate genetic evolution in high-grade serous (HGS) ovarian cancers we first analysed cell line series derived from three cases of HGS carcinoma before and after platinum resistance had developed (PEO1, PEO4 and PEO6, PEA1 and PEA2, and PEO14 and PEO23). Analysis with 24-colour fluorescence in situ hybridisation and SNP array comparative genomic hybridisation (CGH) showed mutually exclusive endoreduplication and loss of heterozygosity events in clones present at different timepoints in the same individual. This implies that platinum sensitive and resistant disease was not linearly related but shared a common ancestor at an early stage of tumour development. Array CGH analysis of six paired pre- and post-neoadjuvant treatment HGS samples from the CTCR-OV01 clinical study did not show extensive copy number differences, suggesting that one clone was strongly dominant at presentation. These data show that cisplatin resistance in HGS carcinoma develops from pre-existing minor clones but that enrichment for these clones is not apparent during short-term chemotherapy treatment. PMID:20581869

Regulatory network involving miRNAs and genes in serous ovarian carcinoma

PubMed Central

Zhao, Haiyan; Xu, Hao; Xue, Luchen

2017-01-01

Serous ovarian carcinoma (SOC) is one of the most life-threatening types of gynecological malignancy, but the pathogenesis of SOC remains unknown. Previous studies have indicated that differentially expressed genes and microRNAs (miRNAs) serve important functions in SOC. However, genes and miRNAs are identified in a disperse form, and limited information is known about the regulatory association between miRNAs and genes in SOC. In the present study, three regulatory networks were hierarchically constructed, including a differentially-expressed network, a related network and a global network to reveal associations between each factor. In each network, there were three types of factors, which were genes, miRNAs and transcription factors that interact with each other. Focus was placed on the differentially-expressed network, in which all genes and miRNAs were differentially expressed and therefore may have affected the development of SOC. Following the comparison and analysis between the three networks, a number of signaling pathways which demonstrated differentially expressed elements were highlighted. Subsequently, the upstream and downstream elements of differentially expressed miRNAs and genes were listed, and a number of key elements (differentially expressed miRNAs, genes and TFs predicted using the P-match method) were analyzed. The differentially expressed network partially illuminated the pathogenesis of SOC. It was hypothesized that if there was no differential expression of miRNAs and genes, SOC may be prevented and treatment may be identified. The present study provided a theoretical foundation for gene therapy for SOC. PMID:29113276

Serous Carcinoma of the Uterine Cervix, an Extremely Rare Aggressive Entity: A Literature Review.

PubMed

Jonska-Gmyrek, Joanna; Zolciak-Siwinska, Agnieszka; Gmyrek, Leszek; Michalski, Wojciech; Poniatowska, Grazyna; Fuksiewicz, Malgorzata; Wiechno, Pawel; Kucharz, Jakub; Kowalska, Maria; Kotowicz, Beata

2018-01-01

Serous carcinoma of the uterine cervix (USCC) is an extremely rare subtype. To establish the treatment strategy in patients with USCC is an important issue. MEDLINE (PubMed) was searched for all articles published after the first publication by Lurie et al. [Eur J Obstet Gynecol Reprod Biol 1991; 40: 79-81], reporting woman diagnosed with USCC. Because of limited numbers of studies on the topic of the study, we could not keep a restriction of eliminating smaller sample sizes. A search of PubMed demonstrated that 113 cases of USCC have been reported in the literature since the first publication. The current treatment modality adopted for early cervical cancer is hysterectomy with bilateral iliac-obturator lymphadenectomy and postoperative radiotherapy (RT) or radiochemotherapy (RT-CT) if risk factors for cervical carcinoma appear. The treatment strategy for locally advanced USCC is preoperative RT-CT or chemotherapy (CHTH) with the intention to treat the patient surgically. The treatment option for disseminated disease is CHTH with paclitaxel and carboplatin. Risk factors and a more advanced clinical stage of USCC have an impact on poor outcomes despite the use of standard treatment methods, adapted for cervical cancer. The outside-pelvic failures tend to seek effective systemic treatment. © 2018 S. Karger AG, Basel.

Photopsias: A Key to Diagnosis.

PubMed

Brown, Gary C; Brown, Melissa M; Fischer, David H

2015-10-01

To assess the character and cause of photopsias in vitreoretinal patients. Cross-sectional study. A total of 169 consecutive patients (217 eyes) with vitreoretinal disease presenting with a history of photopsias. A total of 217 eyes with photopsias in 169 patients were evaluated. Photopsia assessment included (1) laterality (unilateral, bilateral but not simultaneous, bilateral, and simultaneous); (2) morphology (flash, zig-zag, strobe, scintillating scotoma, twinkling, other); (3) color (white, silver, yellow, combination, other); (4) location (temporal, central, other); (5) duration (quick, prolonged, constant, other); (6) frequency; (7) diurnal appearance (day, night, both); (8) stimuli (turning head or eyes, hypoglycemia, hyperglycemia, other); and (9) associated systemic or ocular signs and symptoms (headache, numbness, weakness, vertigo, syncope, diplopia, hypotension, floaters, other). Clinical photopsia features correlated with the causes of photopsias. Thirty-two photopsia causes were identified. The top 16 included posterior vitreous detachment (PVD) in 39.7% of eyes; retinal tear in 8.9% of eyes; neovascular age-related macular degeneration (AMD) in 7.9% of eyes; rhegmatogenous retinal detachment (RRD) in 7.5% of eyes; classic and ophthalmic migraine in 6.5% of eyes; hypoglycemia in 2.8% of eyes; vertebrobasilar insufficiency in 2.8% of eyes; non-AMD choroidal neovascularization in 2.3% of eyes; retinitis pigmentosa in 1.9% of eyes; severe cough in 1.9% of eyes; central serous chorioretinopathy in 1.4% of eyes; intraocular lens reflections in 0.9% of eyes; blue field entoptic phenomenon in 0.9% of eyes; Charles Bonnet syndrome in 0.9% of eyes; digitalis in 0.9% of eyes; and metastatic adenocarcinoma to the brain in 0.9% of eyes. The photopsias associated with PVD are typically quick (96%), with lightning/flash morphology (96%), white (87%), temporally located (86%), associated with new-onset floaters (85%), preferentially seen in dark (90%) rather than

INTRAVITREAL DEXAMETHASONE IMPLANTATION IN PATIENTS WITH DIFFERENT MORPHOLOGICAL DIABETIC MACULAR EDEMA HAVING INSUFFICIENT RESPONSE TO RANIBIZUMAB.

PubMed

Kaldırım, Havva; Yazgan, Serpil; Atalay, Kursat; Gurez, Ceren; Savur, Fatma

2018-05-01

To evaluate the effectiveness of a single intravitreal injection of dexamethasone implant in resistant diabetic macular edema that have different morphological types. In this retrospective study, 31 patients (35 eyes) with persistent diabetic macular edema, who underwent a single injection of dexamethasone implant, were evaluated. Diabetic macular edema was classified into three types: diffuse retinal thickening (n = 10), cystoid macular edema (n = 13), and serous retinal detachment (n = 12). Primary outcome measures were best corrected visual acuity, and central macular thickness. The three subgroups were similar in terms of age and gender (P > 0.05). Total duration of diabetes was significantly less in the serous retinal detachment subgroup (P = 0.01). There were no differences in the best corrected visual acuity between the three subgroups until the sixth month. However, the best corrected visual acuity was significantly better in the diffuse retinal thickness subgroup at the sixth month (P = 0.008). Regarding the central macular thickness values, it was statistically better in serous retinal detachment than in diffuse retinal thickening and cystoid macular edema subgroups till the sixth month (P = 0.001). However, at the sixth month, there was not any statistical difference between subgroups regarding central macular thickness values. Antiglaucomatous agents were required in 4 (11.4%) patients throughout the study. Treatment algorithms should differ according to the morphology of diabetic macular edema; however, more data is needed to give specific recommendations.

Melatonin Reduces Angiogenesis in Serous Papillary Ovarian Carcinoma of Ethanol-Preferring Rats

PubMed Central

Zonta, Yohan Ricci; Martinez, Marcelo; Camargo, Isabel Cristina C.; Domeniconi, Raquel F.; Lupi Júnior, Luiz Antonio; Pinheiro, Patricia Fernanda F.; Reiter, Russel J.; Martinez, Francisco Eduardo; Chuffa, Luiz Gustavo A.

2017-01-01

Angiogenesis is a hallmark of ovarian cancer (OC); the ingrowth of blood vessels promotes rapid cell growth and the associated metastasis. Melatonin is a well-characterized indoleamine that possesses important anti-angiogenic properties in a set of aggressive solid tumors. Herein, we evaluated the role of melatonin therapy on the angiogenic signaling pathway in OC of an ethanol-preferring rat model that mimics the same pathophysiological conditions occurring in women. OC was chemically induced with a single injection of 7,12-dimethylbenz(a)anthracene (DMBA) under the ovarian bursa. After the rats developed serous papillary OC, half of the animals received intraperitoneal injections of melatonin (200 µg/100 g body weight/day) for 60 days. Melatonin-treated animals showed a significant reduction in OC size and microvessel density. Serum levels of melatonin were higher following therapy, and the expression of its receptor MT1 was significantly increased in OC-bearing rats, regardless of ethanol intake. TGFβ1, a transforming growth factor-beta1, was reduced only after melatonin treatment. Importantly, vascular endothelial growth factor (VEGF) was severely reduced after melatonin therapy in animals given or not given ethanol. Conversely, the levels of VEGF receptor 1 (VEGFR1) was diminished after ethanol consumption, regardless of melatonin therapy, and VEGFR2 was only reduced following melatonin. Hypoxia-inducible factor (HIF)-1α was augmented with ethanol consumption, and, notably, melatonin significantly reduced their levels. Collectively, our results suggest that melatonin attenuates angiogenesis in OC in an animal model of ethanol consumption; this provides a possible complementary therapeutic opportunity for concurrent OC chemotherapy. PMID:28398226

High-Grade Serous Ovarian Cancer: Use of Machine Learning to Predict Abdominopelvic Recurrence on CT on the Basis of Serial Cancer Antigen 125 Levels.

PubMed

Shinagare, Atul B; Balthazar, Patricia; Ip, Ivan K; Lacson, Ronilda; Liu, Joyce; Ramaiya, Nikhil; Khorasani, Ramin

2018-05-19

The aim of this study was to use machine learning to predict abdominal recurrence on CT on the basis of serial cancer antigen 125 (CA125) levels in patients with advanced high-grade serous ovarian cancer on surveillance. This institutional review board-approved, HIPAA-compliant, retrospective, hypothesis-generating study included all 57 patients (mean age, 61 ± 11.2 years) with advanced high-grade serous ovarian cancer who underwent cytoreductive surgery from January to December 2012, followed by surveillance abdominopelvic CT and corresponding CA125 levels. A blinded radiologist reviewed abdominopelvic CT studies until recurrence was noted. Four measures of CA125 were assessed: actual CA125 levels at the time of CT, absolute change since prior CT, relative change since prior CT, and rate of change since prior CT. Using machine learning, support vector machine models were optimized and evaluated using 10-fold cross-validation to determine the CA125 measure most predictive of abdominal recurrence. The association of the most accurate CA125 measure was further analyzed using Cox proportional-hazards model along with age, tumor size, stage, and degree of cytoreduction. Rate of change in CA125 was most predictive of abdominal recurrence in a linear kernel support vector machine model and was significantly higher preceding CT studies showing abdominal recurrence (median 13.2 versus 0.6 units/month; P = .007). On multivariate analysis, a higher rate of CA125 increase was significantly associated with recurrence (hazard ratio, 1.02 per 10 units change; 95% confidence interval, 1.0006-1.04; P = .04). A higher rate of CA125 increase is associated with abdominal recurrence. The rate of increase of CA125 may help in the selection of patients who are most likely to benefit from abdominopelvic CT in surveillance of ovarian cancer. Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Establishment and characterization of a platinum- and paclitaxel-resistant high grade serous ovarian carcinoma cell line.

PubMed

Teng, Pang-Ning; Bateman, Nicholas W; Wang, Guisong; Litzi, Tracy; Blanton, Brian E; Hood, Brian L; Conrads, Kelly A; Ao, Wei; Oliver, Kate E; Darcy, Kathleen M; McGuire, William P; Paz, Keren; Sidransky, David; Hamilton, Chad A; Maxwell, G Larry; Conrads, Thomas P

2017-07-01

High grade serous ovarian cancer (HGSOC) patients have a high recurrence rate after surgery and adjuvant chemotherapy due to inherent or acquired drug resistance. Cell lines derived from HGSOC tumors that are resistant to chemotherapeutic agents represent useful pre-clinical models for drug discovery. Here, we describe establishment of a human ovarian carcinoma cell line, which we term WHIRC01, from a patient-derived mouse xenograft established from a chemorefractory HGSOC patient who did not respond to carboplatin and paclitaxel therapy. This newly derived cell line is platinum- and paclitaxel-resistant with cisplatin, carboplatin, and paclitaxel half-maximal lethal doses of 15, 130, and 20 µM, respectively. Molecular characterization of this cell line was performed using targeted DNA exome sequencing, transcriptomics (RNA-seq), and mass spectrometry-based proteomic analyses. Results from exomic sequencing revealed mutations in TP53 consistent with HGSOC. Transcriptomic and proteomic analyses of WHIRC01 showed high level of alpha-enolase and vimentin, which are associated with cell migration and epithelial-mesenchymal transition. WHIRC01 represents a chemorefractory human HGSOC cell line model with a comprehensive molecular profile to aid future investigations of drug resistance mechanisms and screening of chemotherapeutic agents.

Endometrial Serous Carcinoma With Clear-Cell Change: Frequency and Immunohistochemical Analysis.

PubMed

Hariri, Nosaibah; Qarmali, Morad; Fadare, Oluwole

2018-04-01

The diagnostic distinction between endometrial serous carcinoma (ESC) and endometrial clear-cell carcinoma (CCC) may occasionally be problematic, and one potentially contributing factor is the finding of clear cells in otherwise classic cases of ESC. This study aimed to define the frequency of this finding and comparatively assessed the immunophenotype of the clear cells. A review of 56 cases of ESC identified 8 (14.28%) with clear cells, representing 1% to 20% (median 7.5) of tumoral volume in these cases. In only 3 cases were clear cells discernible at low (×20) magnification. There was no significant difference in stage distribution or age between ESC patients with and without clear cells. The immunophenotypes of ESC-associated clear cells (group 1) were compared with foci of conventional ESC on another tissue block within the same case (group 2; n = 8) as well as a randomly selected cohort of CCC cases (group 3; n = 8). Groups 1 and 2 showed no significant differences regarding p53, ER, PR, Napsin-A, p504S, and hepatocyte nuclear factor 1β (HNF1β) expression, or regarding mitotic indices or Ki67 proliferation rate. In contrast, group 1 cases showed an immunophenotypic profile that was notably different from that of group 3 cases, with the former showing statistically significantly higher/more frequent expression of ER, PR, Ki67, and p53 and lower/less frequent expression of Napsin-A, p504S, and HNF1β. We conclude that clear-cell change is seen in 14% of ESCs and is discernible at low magnification in only 5%; these areas show an immunophenotype that is essentially identical to the associated background conventional ESC and are phenotypically dissimilar to CCC.

A clinical and pathologic comparison between stage-matched endometrial intraepithelial carcinoma and uterine serous carcinoma: is there a difference?

PubMed

Hou, June Y; McAndrew, Thomas C; Goldberg, Gary L; Whitney, Kathleen; Shahabi, Shohreh

2014-04-01

Endometrial intraepithelial carcinoma (EIC) is a rare pathologic variant of uterine serous carcinoma (USC). Our aim is to distinguish patterns of clinic-pathologic outcomes in patients with EIC and USC for disease limited to the endometrium (stage 1A) as well as with distant metastasis (stage 4B). Surgically staged patients were retrospectively identified and relevant variables were extracted and compared. Kaplan-Meier was used to generate the survival data. More USC (n = 29) exhibited lymphovascular invasion (stage 4, P = .01) and expressed higher levels of estrogen receptor-α than EIC (P = .0009 and .063 for stages 1 and 4, respectively). The survival is comparable, with 1 recurrence in each group for stage 1A disease. For stage 4 EIC and USC, the progression-free survival (14 vs10 months) and overall survival (19 vs 20 months) are similar to what is previously published. In conclusion, EIC, whether limited to the endometrium, or widely metastatic, imparts similar outcomes and should be treated comparably with stage-matched USC.

Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Hui; Liu, Tao; Zhang, Zhen

Ovarian cancer remains the most lethal gynecological malignancy in the developed world, despite recent advances in genomic information and treatment. To better understand this disease, define an integrated proteogenomic landscape, and identify factors associated with homologous repair deficiency (HRD) and overall survival, we performed a comprehensive proteomic characterization of ovarian high-grade serous carcinomas (HGSC) previously characterized by The Cancer Genome Atlas (TCGA). We observed that messenger RNA transcript abundance did not reliably predict abundance for 10,030 proteins across 174 tumors. Clustering of tumors based on protein abundance identified five subtypes, two of which correlated robustly with mesenchymal and proliferative subtypes,more » while tumors characterized as immunoreactive or differentiated at the transcript level were intermixed at the protein level. At the genome level, HGSC is characterized by a complex landscape of somatic copy number alterations (CNA), which individually do not correlate significantly with survival. Correlation of CNAs with protein abundances identified loci with significant trans regulatory effects mapping to pathways associated with proliferation, cell motility/invasion, and immune regulation, three known hallmarks of cancer. Using the trans regulated proteins we also created models significantly correlated with patient survival by multivariate analysis. Integrating protein abundance with specific post-translational modification data identified subnetworks correlated with HRD status; specifically, acetylation of Lys12 and Lys16 on histone H4 was associated with HRD status. Using quantitative phosphoproteomics data covering 4,420 proteins as reflective of pathway activity, we identified the PDGFR and VEGFR signaling pathways as significantly up-regulated in patients with short overall survival, independent of PDGFR and VEGFR protein levels, potentially informing the use of anti-angiogenic therapies

Underestimation of Risk of a BRCA1 or BRCA2 Mutation in Women With High-Grade Serous Ovarian Cancer by BRCAPRO: A Multi-Institution Study

PubMed Central

Daniels, Molly S.; Babb, Sheri A.; King, Robin H.; Urbauer, Diana L.; Batte, Brittany A.L.; Brandt, Amanda C.; Amos, Christopher I.; Buchanan, Adam H.; Mutch, David G.; Lu, Karen H.

2014-01-01

Purpose Identification of the 10% to 15% of patients with ovarian cancer who have germline BRCA1 or BRCA2 mutations is important for management of both patients and relatives. The BRCAPRO model, which estimates mutation likelihood based on personal and family cancer history, can inform genetic testing decisions. This study's purpose was to assess the accuracy of BRCAPRO in women with ovarian cancer. Methods BRCAPRO scores were calculated for 589 patients with ovarian cancer referred for genetic counseling at three institutions. Observed mutations were compared with those predicted by BRCAPRO. Analysis of variance was used to assess factors impacting BRCAPRO accuracy. Results One hundred eighty (31%) of 589 patients with ovarian cancer tested positive. At BRCAPRO scores less than 40%, more mutations were observed than expected (93 mutations observed v 34.1 mutations expected; P < .001). If patients with BRCAPRO scores less than 10% had not been tested, 51 (28%) of 180 mutations would have been missed. BRCAPRO underestimated the risk for high-grade serous ovarian cancers but overestimated the risk for other histologies (P < .001), underestimation increased as age at diagnosis decreased (P = .02), and model performance varied by institution (P = .02). Conclusion Patients with ovarian cancer classified as low risk by BRCAPRO are more likely to test positive than predicted. The risk of a mutation in patients with low BRCAPRO scores is high enough to warrant genetic testing. This study demonstrates that assessment of family history by a validated model cannot effectively target testing to a high-risk ovarian cancer patient population, which strongly supports the recommendation to offer BRCA1/BRCA2 genetic testing to all patients with high-grade serous ovarian cancer regardless of family history. PMID:24638001

Progesterone Prevents High-Grade Serous Ovarian Cancer by Inducing Necroptosis of p53-Defective Fallopian Tube Epithelial Cells.

PubMed

Wu, Na-Yiyuan; Huang, Hsuan-Shun; Chao, Tung Hui; Chou, Hsien Ming; Fang, Chao; Qin, Chong-Zhen; Lin, Chueh-Yu; Chu, Tang-Yuan; Zhou, Hong Hao

2017-03-14

High-grade serous ovarian carcinoma (HGSOC) originates mainly from the fallopian tube (FT) epithelium and always carries early TP53 mutations. We previously reported that tumors initiate in the FT fimbria epithelium because of apoptotic failure and the expansion of cells with DNA double-strand breaks (DSB) caused by bathing of the FT epithelial cells in reactive oxygen species (ROSs) and hemoglobin-rich follicular fluid (FF) after ovulation. Because ovulation is frequent and HGSOC is rare, we hypothesized that luteal-phase progesterone (P4) could eliminate p53-defective FT cells. Here we show that P4, via P4 receptors (PRs), induces necroptosis in Trp53 -/- mouse oviduct epithelium and in immortalized human p53-defective fimbrial epithelium through the TNF-α/RIPK1/RIPK3/MLKL pathway. Necroptosis occurs specifically at diestrus, recovers at the proestrus phase of the estrus cycle, and can be augmented with P4 supplementation. These results reveal the mechanism of the well-known ability of progesterone to prevent ovarian cancer. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Personal Visual Aids for Aircrew.

DTIC Science & Technology

1981-06-01

oedema or areas of pigmentation or depigmentation, such as central serous retinopathy or focal choroiditis of differing aetiology. Heat induced lenticular ...Fig 11). a. Normal grid pattern b. Pincushion distortion c. Astigmatic distortion d. Para central scotoma Fig 11. Amsler grids illustrating visual...ML). Ophtalmologie. Maladie yeux. Astigmatisme . Corne. Prothbse. Pilotes. Vision. Lunettes. 46. A propos du vol et de la correction des presbytes

Prognostic factors for patients with early-stage uterine serous carcinoma without adjuvant therapy.

PubMed

Tate, Keisei; Yoshida, Hiroshi; Ishikawa, Mitsuya; Uehara, Takashi; Ikeda, Shun Ichi; Hiraoka, Nobuyoshi; Kato, Tomoyasu

2018-05-01

Uterine serous carcinoma (USC) is an aggressive type 2 endometrial cancer. Data on prognostic factors for patients with early-stage USC without adjuvant therapy are limited. This study aims to assess the baseline recurrence risk of early-stage USC patients without adjuvant treatment and to identify prognostic factors and patients who need adjuvant therapy. Sixty-eight patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II USC between 1997 and 2016 were included. All the cases did not undergo adjuvant treatment as institutional practice. Clinicopathological features, recurrence patterns, and survival outcomes were analyzed to determine prognostic factors. FIGO stages IA, IB, and II were observed in 42, 7, and 19 cases, respectively. Median follow-up time was 60 months. Five-year disease-free survival (DFS) and overall survival (OS) rates for all cases were 73.9% and 78.0%, respectively. On multivariate analysis, cervical stromal involvement and positive pelvic cytology were significant predictors of DFS and OS, and ≥1/2 myometrial invasion was also a significant predictor of OS. Of 68 patients, 38 patients had no cervical stromal invasion or positive pelvic cytology and showed 88.8% 5-year DFS and 93.6% 5-year OS. Cervical stromal invasion and positive pelvic cytology are prognostic factors for stage I-II USC. Patients with stage IA or IB USC showing negative pelvic cytology may have an extremely favorable prognosis and need not receive any adjuvant therapies. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer.

PubMed

Lawrenson, Kate; Li, Qiyuan; Kar, Siddhartha; Seo, Ji-Heui; Tyrer, Jonathan; Spindler, Tassja J; Lee, Janet; Chen, Yibu; Karst, Alison; Drapkin, Ronny; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia; Baker, Helen; Bandera, Elisa V; Bean, Yukie; Beckmann, Matthias W; Berchuck, Andrew; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A; Brooks-Wilson, Angela; Bruinsma, Fiona; Butzow, Ralf; Campbell, Ian G; Carty, Karen; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Chen, Anne; Chen, Zhihua; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas T; Edwards, Robert P; Eilber, Ursula; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goode, Ellen L; Goodman, Marc T; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis Nazihah; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus; Hosono, Satoyo; Iversen, Edwin S; Jakubowska, Anna; James, Paul; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kruger Kjaer, Susanne; Kelemen, Linda E; Kellar, Melissa; Kelley, Joseph L; Kiemeney, Lambertus A; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F A G; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; Nevanlinna, Heli; McNeish, Ian; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B; Narod, Steven A; Nedergaard, Lotte; Ness, Roberta B; Azmi, Mat Adenan Noor; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Pearce, Celeste L; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jennifer; Phelan, Catherine M; Pike, Malcolm C; Poole, Elizabeth M; Ramus, Susan J; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schildkraut, Joellen M; Schwaab, Ira; Sellers, Thomas A; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C; Sucheston, Lara; Tangen, Ingvild L; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Timorek, Agnieszka; Tsai, Ya-Yu; Tworoger, Shelley S; van Altena, Anne M; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna H; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Monteiro, Alvaro; Pharoah, Paul D; Gayther, Simon A; Freedman, Matthew L

2015-09-22

Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10(-5)). For three cis-eQTL associations (P<1.4 × 10(-3), FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6 × 10(-10) for risk variants (P<10(-4)) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC.

Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer

PubMed Central

Lawrenson, Kate; Li, Qiyuan; Kar, Siddhartha; Seo, Ji-Heui; Tyrer, Jonathan; Spindler, Tassja J.; Lee, Janet; Chen, Yibu; Karst, Alison; Drapkin, Ronny; Aben, Katja K. H.; Anton-Culver, Hoda; Antonenkova, Natalia; Bowtell, David; Webb, Penelope M.; deFazio, Anna; Baker, Helen; Bandera, Elisa V.; Bean, Yukie; Beckmann, Matthias W.; Berchuck, Andrew; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bruinsma, Fiona; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Chen, Anne; Chen, Zhihua; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas T.; Edwards, Robert P.; Eilber, Ursula; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goode, Ellen L.; Goodman, Marc T.; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis Nazihah; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A. T.; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; James, Paul; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y.; Kruger Kjaer, Susanne; Kelemen, Linda E.; Kellar, Melissa; Kelley, Joseph L.; Kiemeney, Lambertus A.; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F. A. G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; Nevanlinna, Heli; McNeish, Ian; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B.; Narod, Steven A.; Nedergaard, Lotte; Ness, Roberta B.; Azmi, Mat Adenan Noor; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Pearce, Celeste L.; Pejovic, Tanja; Pelttari, Liisa M.; Permuth-Wey, Jennifer; Phelan, Catherine M.; Pike, Malcolm C.; Poole, Elizabeth M.; Ramus, Susan J.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schildkraut, Joellen M.; Schwaab, Ira; Sellers, Thomas A.; Shu, Xiao-Ou; Shvetsov, Yurii B.; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Sucheston, Lara; Tangen, Ingvild L.; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J.; Timorek, Agnieszka; Tsai, Ya-Yu; Tworoger, Shelley S.; van Altena, Anne M.; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A.; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna H.; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Monteiro, Alvaro; Pharoah, Paul D.; Gayther, Simon A.; Freedman, Matthew L.

2015-01-01

Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10−5). For three cis-eQTL associations (P<1.4 × 10−3, FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6 × 10−10 for risk variants (P<10−4) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC. PMID:26391404

Metronomic cyclophosphamide-induced long-term remission after recurrent high-grade serous ovarian cancer: A case study

PubMed Central

de Boo, Leonora Wijnandina; Vulink, Annelie Johanna Elisabeth; Bos, Monique Elisabeth Martina Maria

2017-01-01

Metronomic oral cyclophosphamide has gained increasing interest in recent years as a promising maintenance therapy in advanced, platinum-sensitive, high-grade serous ovarian cancer (HGSOC). Metronomic treatment with cyclophosphamide refers to the frequent, usually daily, administration of a low (oral) dose of cyclophosphamide with no prolonged drug-free breaks. Main advantages of this treatment are the effective reduction of tumour activity, oral administration in an outpatient setting, low cost and the low toxicity profile. Metronomic oral cyclophosphamide can benefit patients suffering from types of cancer known to be sensitive to alkylating agents, such as platinum-sensitive HGSOC. In recent years, several publications have underlined the advantage of this regimen and possible explanations were explored. We here present a patient with multiple recurrences of metastasized HGSOC, platinum-sensitive, with an on-going complete response to monotherapy with oral cyclophosphamide. This observation supports that patients with relapsing HGSOC who responded to platinum-based chemotherapy and cannot continue platinum-based chemotherapy because of toxicity, can be offered a course of metronomic cyclophosphamide. This case may serve as a reminder that old drugs can be used successfully even in the age of new upcoming therapy such as anti-angiogenic agents (VEGF inhibitors) and poly-ADP-ribose polymerase (PARP) inhibitors. PMID:29285388

Metronomic cyclophosphamide-induced long-term remission after recurrent high-grade serous ovarian cancer: A case study.

PubMed

de Boo, Leonora Wijnandina; Vulink, Annelie Johanna Elisabeth; Bos, Monique Elisabeth Martina Maria

2017-12-01

Metronomic oral cyclophosphamide has gained increasing interest in recent years as a promising maintenance therapy in advanced, platinum-sensitive, high-grade serous ovarian cancer (HGSOC). Metronomic treatment with cyclophosphamide refers to the frequent, usually daily, administration of a low (oral) dose of cyclophosphamide with no prolonged drug-free breaks. Main advantages of this treatment are the effective reduction of tumour activity, oral administration in an outpatient setting, low cost and the low toxicity profile. Metronomic oral cyclophosphamide can benefit patients suffering from types of cancer known to be sensitive to alkylating agents, such as platinum-sensitive HGSOC. In recent years, several publications have underlined the advantage of this regimen and possible explanations were explored. We here present a patient with multiple recurrences of metastasized HGSOC, platinum-sensitive, with an on-going complete response to monotherapy with oral cyclophosphamide. This observation supports that patients with relapsing HGSOC who responded to platinum-based chemotherapy and cannot continue platinum-based chemotherapy because of toxicity, can be offered a course of metronomic cyclophosphamide. This case may serve as a reminder that old drugs can be used successfully even in the age of new upcoming therapy such as anti-angiogenic agents (VEGF inhibitors) and poly-ADP-ribose polymerase (PARP) inhibitors.

Genetic heterogeneity after first-line chemotherapy in high-grade serous ovarian cancer.

PubMed

Lambrechts, Sandrina; Smeets, Dominiek; Moisse, Matthieu; Braicu, Elena Ioana; Vanderstichele, Adriaan; Zhao, Hui; Van Nieuwenhuysen, Els; Berns, Els; Sehouli, Jalid; Zeillinger, Robert; Darb-Esfahani, Silvia; Cacsire Castillo-Tong, Dan; Lambrechts, Diether; Vergote, Ignace

2016-01-01

Most high-grade serous ovarian carcinoma (HGSOC) patients benefit from first-line platinum-based chemotherapy, but progressively develop resistance during subsequent lines. Re-activating BRCA1 or MDR1 mutations can underlie platinum resistance in end-stage patients. However, little is known about resistance mechanisms occurring after a single line of platinum, when patients still qualify for other treatments. In 31 patients with primary platinum-sensitive HGSOC, we profiled tumours collected during debulking surgery before and after first-line chemotherapy using whole-exome sequencing and single nucleotide polymorphism profiling. Besides germline BRCA1/2 mutations, we observed frequent loss-of-heterozygosity in homologous recombination (HR) genes and mutation spectra characteristic of HR-deficiency in all tumours. At relapse, tumours differed considerably from their primary counterparts. There was, however, no evidence of events reactivating the HR pathway, also not in tumours resistant to second-line platinum. Instead, a platinum score of 13 copy number regions, among other genes including MECOM, CCNE1 and ERBB2, correlated with platinum-free interval (PFI) after first-line therapy, whereas an increase of this score in recurrent tumours predicted the change in PFI during subsequent therapy. Already after a single line of platinum, there is huge variability between primary and recurrent tumours, advocating that in HGSOC biopsies need to be collected at relapse to tailor treatment options to the underlying genetic profile. Nevertheless, all primary platinum-sensitive HGSOCs remained HR-deficient, irrespective of whether they became resistant to second-line platinum, further suggesting these tumours qualify for second-line Poly APD ribose polymerase (PARP) inhibitor treatment. Finally, chromosomal instability contributes to acquired resistance after a single line of platinum therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

BRCA germline mutations in women with uterine serous carcinoma--still a debate.

PubMed

Lavie, Ofer; Ben-Arie, Alon; Segev, Yakir; Faro, Jonathan; Barak, Frida; Haya, Nir; Auslender, Ron; Gemer, Ofer

2010-12-01

To determine the incidence of BRCA1 and BRCA2 mutations in an enlarged series of uterine serous carcinoma (USC) patients and to determine whether patients with USC are associated with a personal or familial history of breast or ovarian carcinoma. A cohort of all consecutive patients with diagnosed USC was identified for 9 years. Family pedigrees were drawn as far back and laterally as possible. In all patients, genomic DNA was extracted from peripheral blood samples and analyzed for the 3 mutations common in Ashkenazi Jewish patients. All patients went through total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. Tubal, ovarian, and peritoneal carcinoma were ruled out clinically and pathologically in all patients. Of 51 consecutive patients with USC in Ashkenazi Jews studied, we identified 13 patients (25.5%) who were previously found to have breast carcinoma, 17 patients (33.3%) who had a first-degree relative with breast or ovarian carcinoma, and 8 patients (15.7%) who were found to be carriers of 1 of the 3 BRCA germline mutations. This series of USC patients, the largest consecutive series to date, suggests a higher incidence of BRCA carriers among Ashkenazi Jews as compared with the general population. This high rate of BRCA germline mutations in USC patients coupled with a high rate of personal and familial cancer histories may suggest that USC is associated with the hereditary breast-ovarian syndrome. This potential association of USC to the BRCA-associated cancer spectrum may have implications for the clinical management and intervention of unaffected BRCA1-2 germline mutation carriers. However, at the current time, there are insufficient data to provide evidence-based guidelines regarding the optimal timing or specific intervention to prevent cancers in these high-risk women.

Col4a1 mutations cause progressive retinal neovascular defects and retinopathy

PubMed Central

Alavi, Marcel V.; Mao, Mao; Pawlikowski, Bradley T.; Kvezereli, Manana; Duncan, Jacque L.; Libby, Richard T.; John, Simon W. M.; Gould, Douglas B.

2016-01-01

Mutations in collagen, type IV, alpha 1 (COL4A1), a major component of basement membranes, cause multisystem disorders in humans and mice. In the eye, these include anterior segment dysgenesis, optic nerve hypoplasia and retinal vascular tortuosity. Here we investigate the retinal pathology in mice carrying dominant-negative Col4a1 mutations. To this end, we examined retinas longitudinally in vivo using fluorescein angiography, funduscopy and optical coherence tomography. We assessed retinal function by electroretinography and studied the retinal ultrastructural pathology. Retinal examinations revealed serous chorioretinopathy, retinal hemorrhages, fibrosis or signs of pathogenic angiogenesis with chorioretinal anastomosis in up to approximately 90% of Col4a1 mutant eyes depending on age and the specific mutation. To identify the cell-type responsible for pathogenesis we generated a conditional Col4a1 mutation and determined that primary vascular defects underlie Col4a1-associated retinopathy. We also found focal activation of Müller cells and increased expression of pro-angiogenic factors in retinas from Col4a1+/Δex41mice. Together, our findings suggest that patients with COL4A1 and COL4A2 mutations may be at elevated risk of retinal hemorrhages and that retinal examinations may be useful for identifying patients with COL4A1 and COL4A2 mutations who are also at elevated risk of hemorrhagic strokes. PMID:26813606

A Brief Guide to Color Vision Testing for Ophthalmology Residents.

DTIC Science & Technology

1988-02-01

degeneration (ARMD), diabetic retinopathy, central serous retinopathy, cystoid macular edema (CME), and chloroquine toxicity. Uptic nerve problems may be due to...blue caps if the macula is normal. Pseudo-Isochromtic Plates Test If the visual acuity is 20/200 or better, the patient should have no trouble

Serosurvey for the Prevalence of Brucella Canis Antibodies in Dogs in Central Ohio

DTIC Science & Technology

1983-01-01

negative urease production ...................... positive indol production ....................... negative1 0 ,58 ,6 2 citrate utilization...retained its spermatogenic ability. The epididymides had ac- cumulations of lymphocytes in the interstitial cell layers ranging from a few cells to large...There was diffuse in- filtration of plasma cells between the inner plexiform layer and the nerve fiber layer of the retina. Some serous exudate and a few

Surgical approach and optic coherence tomographic evaluation of optic disc anomaly in association with serous macular detachment.

PubMed

Güven, Dilek; Balcıoğlu, Nihal; Türker, Cağrı; Baydar, Yasemin; Sendül, Yekta

2013-12-01

Serous macular detachment (SMD) may accompany optic disc pit (ODP) and cause visual loss if untreated. We want to present different therapeutic approaches and interesting optical coherence tomography (OCT) findings in three consecutive cases. In this case series, two patients with SMD and one patient with partial macular detachment and inferior retinal detachment accompanying ODP were evaluated before and after surgical intervention clinically and by spectral-domain OCT. The patients were 44 (case 1), 22 (case 2) and 24 (case 3) years old. Pars plana vitrectomy (PPV) + silicone oil + laser, PPV + sulfur hexafluoride gas (SF6) + laser and pneumatic retinopexy were applied, respectively. The patients were followed for 18, 15 and 14 months. Preoperative best-corrected visual acuities (BCVAs) were 5/100, 7/10 and counting fingers at 1 m. Vision improved in all cases with resolution of subretinal fluid. Final BCVAs were 3/10, 10/10 and 1/10, respectively. OCT images revealed optic disc anomaly details and changes after surgical intervention, photoreceptor outer segment alterations at the detached area and macular surface changes. Surgical intervention should be tailored individually in cases with SMD. OCT is efficient for in vivo evaluation of this pathological condition and anatomical outcomes of surgery.

Body fluid analysis: clinical utility and applicability of published studies to guide interpretation of today's laboratory testing in serous fluids.

PubMed

Block, Darci R; Algeciras-Schimnich, Alicia

2013-01-01

Requests for testing various analytes in serous fluids (e.g., pleural, peritoneal, pericardial effusions) are submitted daily to clinical laboratories. Testing of these fluids deviates from assay manufacturers' specifications, as most laboratory assays are optimized for testing blood or urine specimens. These requests add a burden to clinical laboratories, which need to validate assay performance characteristics in these fluids to exclude matrix interferences (given the different composition of body fluids) while maintaining regulatory compliance. Body fluid testing for a number of analytes has been reported in the literature; however, understanding the clinical utility of these analytes is critical because laboratories must address the analytic and clinical validation requirements, while educating clinicians on proper test utilization. In this article, we review the published data to evaluate the clinical utility of testing for numerous analytes in body fluid specimens. We also highlight the pre-analytic and analytic variables that need to be considered when reviewing published studies in body fluid testing. Finally, we provide guidance on how published studies might (or might not) guide interpretation of test results in today's clinical laboratories.

Gene expression signatures differentiate ovarian/peritoneal serous carcinoma from breast carcinoma in effusions

PubMed Central

Davidson, Ben; Stavnes, Helene Tuft; Holth, Arild; Chen, Xu; Yang, Yanqin; Shih, Ie-Ming; Wang, Tian-Li

2011-01-01

Abstract Ovarian/primary peritoneal carcinoma and breast carcinoma are the gynaecological cancers that most frequently involve the serosal cavities. With the objective of improving on the limited diagnostic panel currently available for the differential diagnosis of these two malignancies, as well as to define tumour-specific biological targets, we compared their global gene expression patterns. Gene expression profiles of 10 serous ovarian/peritoneal and eight ductal breast carcinoma effusions were analysed using the HumanRef-8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry. Unsupervised hierarchical clustering using all 54,675 genes in the array separated ovarian from breast carcinoma samples. We identified 288 unique probes that were significantly differentially expressed in the two cancers by greater than 3.5-fold, of which 81 and 207 were overexpressed in breast and ovarian/peritoneal carcinoma, respectively. SAM analysis identified 1078 differentially expressed probes with false discovery rate less than 0.05. Genes overexpressed in breast carcinoma included TFF1, TFF3, FOXA1, CA12, GATA3, SDC1, PITX1, TH, EHFD1, EFEMP1, TOB1 and KLF2. Genes overexpressed in ovarian/peritoneal carcinoma included SPON1, RBP1, MFGE8, TM4SF12, MMP7, KLK5/6/7, FOLR1/3, PAX8, APOL2 and NRCAM. The differential expression of 14 genes was validated by quantitative real-time PCR, and differences in 5 gene products were confirmed by immunohistochemistry. Expression profiling distinguishes ovarian/peritoneal carcinoma from breast carcinoma and identifies genes that are differentially expressed in these two tumour types. The molecular signatures unique to these cancers may facilitate their differential diagnosis and may provide a molecular basis for therapeutic target discovery. PMID:20132413

Metastatic ovarian papillary cystadenocarcinoma to the small intestine serous surface: report of a case of high-grade histopathologic malignancy

PubMed Central

2014-01-01

Ovarian cystadenocarcinoma is characterized by marked heterogeneity and may be composed of an admixture of histologic growth patterns, including acinar, papillary and solid. In the present study, a case of isolated small intestine metastasis of ovarian papillary cystadenocarcinoma was reported. A 7-year-old female mixed-breed dog presented with a mass in the left upper quadrant with progressive enlargement of the abdomen, periodic bloody discharge from the vulva and incontinence. The tumor was histologically characterized by the presence of cysts and proliferation of papillae, both lined by single- or multi-layered pleomorphic epithelial cells. Furthermore, the mass was composed by intense cellular and nuclear pleomorphism and numerous mitotic figures. These findings indicate a tumor of high-grade malignancy with infiterative tumor cells resembling the papillary ovarian tumor in the serosal surface of the small intestine along with an intact serosa. Immunohistochemically, tumor was positive for CK7 and negative immunoreactivity for CK20. The histopathologic features coupled with the CK7 immunoreactivity led to a diagnosis of high grade ovarian papillary cystadenocarcinoma. To the best of our knowledge, this is the first case of small intestine serousal surface metastasis from ovarian papillary cystadenocarcinoma. PMID:24636424

Comparison of outcomes in early stage uterine carcinosarcoma and uterine serous carcinoma.

PubMed

Desai, Neil B; Kollmeier, Marisa A; Makker, Vicky; Levine, Douglas A; Abu-Rustum, Nadeem R; Alektiar, Kaled M

2014-10-01

To assess whether contemporary adjuvant management of early stage uterine carcinosarcoma (CS) produces equal outcomes as in uterine serous carcinoma (USC). We reviewed 172 women treated from 2000 to 2011 for stage I-II USC (n=112, 65%) or CS (n=60, 35%). Adjuvant therapy was initiated in 154 (90%) patients, with 111 patients receiving intravaginal radiotherapy (IVRT)/chemotherapy. Median follow up was 4.6 years for surviving patients. Characteristics for USC vs. CS did not differ significantly by age ≥60, pelvic or para-aortic node sampling, stage, lymphovascular invasion, chemotherapy use, RT use or omission of adjuvant therapy. Outcomes were better for USC vs. CS in 5-year actuarial rates of recurrence [17% (C.I. 10-25%) vs. 45% (C.I. 31-59%), p<0.001],disease-related mortality (DRM) [11% (5-17%) vs. 30% (16-44%), p=0.016], and all-cause mortality [12% (C.I. 6-18%) vs. 34% (C.I. 20-48%), p=0.007]. In multivariable analysis, CS histology remained a significant predictor of risk for recurrence [HR 3.1 (C.I. 1.7-5.7), p<0.001], DRM [HR 2.4 (C.I. 1.1-5.1), p=0.024], and all-cause mortality [HR 2.4 (C.I. 1.2-4.8), p=0.012]. On sub-group analysis of 111 patients (77 USC, 34 CS) able to receive IVRT/chemotherapy, CS no longer was associated significantly with increased recurrence (29% vs. 15%, p=0.18), DRM (22% vs. 10%, p=0.39), or all-cause mortality (22% vs. 10%, p=0.45). CS was associated with worse outcomes than USC. However, that difference was not maintained in patients able to receive IVRT and chemotherapy. While intriguing, this result may be due in part to selection against rapid early relapsing CS patients in this group. Copyright © 2014 Elsevier Inc. All rights reserved.

Trametinib in Treating Patients With Recurrent or Progressive Low-Grade Ovarian Cancer or Peritoneal Cavity Cancer

ClinicalTrials.gov

2018-06-11

Low Grade Ovarian Serous Adenocarcinoma; Micropapillary Serous Carcinoma; Ovarian Serous Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

Inhibition of the Receptor Tyrosine Kinase AXL Restores Paclitaxel Chemosensitivity in Uterine Serous Cancer.

PubMed

Palisoul, Marguerite L; Quinn, Jeanne M; Schepers, Emily; Hagemann, Ian S; Guo, Lei; Reger, Kelsey; Hagemann, Andrea R; McCourt, Carolyn K; Thaker, Premal H; Powell, Matthew A; Mutch, David G; Fuh, Katherine C

2017-12-01

Uterine serous cancer (USC) is aggressive, and the majority of recurrent cases are chemoresistant. Because the receptor tyrosine kinase AXL promotes invasion and metastasis of USC and is implicated in chemoresistance in other cancers, we assessed the role of AXL in paclitaxel resistance in USC, determined the mechanism of action, and sought to restore chemosensitivity by inhibiting AXL in vitro and in vivo We used short hairpin RNAs and BGB324 to knock down and inhibit AXL. We assessed sensitivity of USC cell lines to paclitaxel and measured paclitaxel intracellular accumulation in vitro in the presence or absence of AXL. We also examined the role of the epithelial-mesenchymal transition (EMT) in AXL-mediated paclitaxel resistance. Finally, we treated USC xenografts with paclitaxel, BGB324, or paclitaxel plus BGB324 and monitored tumor burden. AXL expression was higher in chemoresistant USC patient tumors and cell lines than in chemosensitive tumors and cell lines. Knockdown or inhibition of AXL increased sensitivity of USC cell lines to paclitaxel in vitro and increased cellular accumulation of paclitaxel. AXL promoted chemoresistance even in cells that underwent the EMT in vitro Finally, in vivo studies of combination treatment with BGB324 and paclitaxel showed a greater than 51% decrease in tumor volume after 2 weeks of treatment when compared with no treatment or single-agent treatments ( P < 0.001). Our results show that AXL expression mediates chemoresistance independent of EMT and prevents accumulation of paclitaxel. This study supports the continued investigation of AXL as a clinical target, particularly in chemoresistant USC. Mol Cancer Ther; 16(12); 2881-91. ©2017 AACR . ©2017 American Association for Cancer Research.

EV-Associated MMP9 in High-Grade Serous Ovarian Cancer Is Preferentially Localized to Annexin V-Binding EVs.

PubMed

Reiner, Agnes T; Tan, Sisareuth; Agreiter, Christiane; Auer, Katharina; Bachmayr-Heyda, Anna; Aust, Stefanie; Pecha, Nina; Mandorfer, Mattias; Pils, Dietmar; Brisson, Alain R; Zeillinger, Robert; Lim, Sai Kiang

2017-01-01

High-grade serous ovarian cancer (HGSOC) is the most aggressive type of ovarian cancer and is responsible for most deaths caused by gynecological cancers. Numerous candidate biomarkers were identified for this disease in the last decades, but most were not sensitive or specific enough for clinical applications. Hence, new biomarkers for HGSOC are urgently required. This study aimed to identify new markers by isolating different extracellular vesicle (EV) types from the ascites of ovarian cancer patients according to their affinities for lipid-binding proteins and analyzing their protein cargo. This approach circumvents the low signal-to-noise ratio when using biological fluids for biomarker discovery and the issue of contamination by large non-EV complexes. We isolated and analyzed three distinct EV populations from the ascites of patients with ovarian cancer or cirrhosis and observed that Annexin V-binding EVs have higher levels of matrix metalloproteinase 9 in malignant compared to portal-hypertensive ascites. As this protein was not detected in other EV populations, this study validates our approach of using different EV types for optimal biomarker discovery. Furthermore, MMP9 in Annexin V-binding EVs could be a HGSOC biomarker with enhanced specificity, because its identification requires detection of two distinct components, that is, lipid and protein.

Treatment of early-stage uterine papillary serous carcinoma at Roswell Park Cancer Institute, 1992-2006.

PubMed

Tchabo, Nana E; McCloskey, Susan; Mashtare, Terry L; Andrews, Christopher; Singh, Anurag K; Mhawech-Fauceglia, Paulette; Odunsi, Kunle; Lele, Shashikant; Jaggernauth, Wainwright

2009-11-01

Optimal management of early-stage uterine papillary serous carcinoma (UPSC) remains controversial. We reviewed our outcomes in this patient population. The Roswell Park Cancer Institute (RPCI) tumor registry identified all patients with Stages I and IIA UPSC treated between January 1992 and June 2006. The Fisher's exact test was used to compare recurrence rates by adjuvant therapy received. Overall survival (OS) estimates were made using the Kaplan-Meier method. Fifty-eight patients with Stage I or IIA UPSC underwent surgery. Thirty-four patients (59%) were surgically staged. Among 21 patients with Stage IA disease, 15 received adjuvant therapy. With a median follow-up of 44.7 months, only one recurrence was observed in a patient who received adjuvant brachytherapy. The 5-year OS was 66%. Among 37 patients with Stages IB-IIA, 30 patients received adjuvant therapy. With a median follow-up of 29 months, there were 7 recurrences. The 5-year OS was 60%. Although there were no significant differences in recurrence by adjuvant therapy received, a significant OS benefit was found in those who received radiation. There was no significant difference in OS distributions of those patients who received Carboplatin/Paclitaxel chemotherapy. Despite the limitations of our retrospective study, we have shown that even comprehensively staged early-stage UPSC patients are still at risk for recurrence despite adjuvant therapy received. Hence, all patients with this histologic diagnosis should be considered at high risk for recurrence and counseled appropriately regarding the risks and benefits of adjuvant therapy.

Papillary serous carcinoma of the uterus: increased risk of subsequent or concurrent development of breast carcinoma.

PubMed

Geisler, J P; Sorosky, J I; Duong, H L; Buekers, T E; Geisler, M J; Sood, A K; Anderson, B; Buller, R E

2001-12-01

Some women with endometrial cancer may be at increased risk for developing breast cancer. The histologic type of endometrial cancer associated with synchronous or subsequent breast cancer has not been clearly established. Our purpose was to determine if a certain histologic type of endometrial cancer was associated with an increased risk of synchronous or subsequent breast cancer. The University of Iowa Hospitals and Clinics tumor registry was queried to ascertain all patients with the diagnosis of uterine cancer from January 1, 1983, to December 31, 1994. Statistics were performed utilizing SPSS for Windows version 9.0 (SPSS Inc., Chicago, IL), including Student's t tests and chi(2) tests. Five hundred ninety-two patients had endometrial adenocarcinoma during the study period. Five hundred thirty-six women had endometrioid adenocarcinoma, 23 women had papillary serous carcinoma (UPSC), 21 women had adenosquamous carcinoma, 10 women had clear-cell carcinoma, and 1 woman each had mucinous or squamous carcinoma. Twelve patients had previously been diagnosed with breast carcinomas. Twenty-five patients were diagnosed with breast cancer either concurrently or subsequent to their diagnosis of endometrial cancer. Synchronous or subsequent breast cancers developed in 3.2% of patients with endometrioid carcinoma and in 25% of patients with UPSC (P < 0.001). Patients with UPSC have an increased risk of development of breast cancer as compared to patients with endometrioid adenocarcinoma of the uterus. (c)2001 Elsevier Science.

Enrichment of putative PAX8 target genes at serous epithelial ovarian cancer susceptibility loci.

PubMed

Kar, Siddhartha P; Adler, Emily; Tyrer, Jonathan; Hazelett, Dennis; Anton-Culver, Hoda; Bandera, Elisa V; Beckmann, Matthias W; Berchuck, Andrew; Bogdanova, Natalia; Brinton, Louise; Butzow, Ralf; Campbell, Ian; Carty, Karen; Chang-Claude, Jenny; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Dansonka-Mieszkowska, Agnieszka; Doherty, Jennifer Anne; Dörk, Thilo; Dürst, Matthias; Eccles, Diana; Fasching, Peter A; Flanagan, James; Gentry-Maharaj, Aleksandra; Glasspool, Rosalind; Goode, Ellen L; Goodman, Marc T; Gronwald, Jacek; Heitz, Florian; Hildebrandt, Michelle A T; Høgdall, Estrid; Høgdall, Claus K; Huntsman, David G; Jensen, Allan; Karlan, Beth Y; Kelemen, Linda E; Kiemeney, Lambertus A; Kjaer, Susanne K; Kupryjanczyk, Jolanta; Lambrechts, Diether; Levine, Douglas A; Li, Qiyuan; Lissowska, Jolanta; Lu, Karen H; Lubiński, Jan; Massuger, Leon F A G; McGuire, Valerie; McNeish, Iain; Menon, Usha; Modugno, Francesmary; Monteiro, Alvaro N; Moysich, Kirsten B; Ness, Roberta B; Nevanlinna, Heli; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Permuth, Jennifer B; Phelan, Catherine; Pike, Malcolm C; Poole, Elizabeth M; Ramus, Susan J; Risch, Harvey A; Rossing, Mary Anne; Salvesen, Helga B; Schildkraut, Joellen M; Sellers, Thomas A; Sherman, Mark; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa; Terry, Kathryn L; Tworoger, Shelley S; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S; Wu, Anna H; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Freedman, Matthew L; Gayther, Simon A; Pharoah, Paul D P; Lawrenson, Kate

2017-02-14

Genome-wide association studies (GWAS) have identified 18 loci associated with serous ovarian cancer (SOC) susceptibility but the biological mechanisms driving these findings remain poorly characterised. Germline cancer risk loci may be enriched for target genes of transcription factors (TFs) critical to somatic tumorigenesis. All 615 TF-target sets from the Molecular Signatures Database were evaluated using gene set enrichment analysis (GSEA) and three GWAS for SOC risk: discovery (2196 cases/4396 controls), replication (7035 cases/21 693 controls; independent from discovery), and combined (9627 cases/30 845 controls; including additional individuals). The PAX8-target gene set was ranked 1/615 in the discovery (P GSEA <0.001; FDR=0.21), 7/615 in the replication (P GSEA =0.004; FDR=0.37), and 1/615 in the combined (P GSEA <0.001; FDR=0.21) studies. Adding other genes reported to interact with PAX8 in the literature to the PAX8-target set and applying an alternative to GSEA, interval enrichment, further confirmed this association (P=0.006). Fifteen of the 157 genes from this expanded PAX8 pathway were near eight loci associated with SOC risk at P<10 -5 (including six with P<5 × 10 -8 ). The pathway was also associated with differential gene expression after shRNA-mediated silencing of PAX8 in HeyA8 (P GSEA =0.025) and IGROV1 (P GSEA =0.004) SOC cells and several PAX8 targets near SOC risk loci demonstrated in vitro transcriptomic perturbation. Putative PAX8 target genes are enriched for common SOC risk variants. This finding from our agnostic evaluation is of particular interest given that PAX8 is well-established as a specific marker for the cell of origin of SOC.

Enrichment of putative PAX8 target genes at serous epithelial ovarian cancer susceptibility loci

PubMed Central

Kar, Siddhartha P; Adler, Emily; Tyrer, Jonathan; Hazelett, Dennis; Anton-Culver, Hoda; Bandera, Elisa V; Beckmann, Matthias W; Berchuck, Andrew; Bogdanova, Natalia; Brinton, Louise; Butzow, Ralf; Campbell, Ian; Carty, Karen; Chang-Claude, Jenny; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Dansonka-Mieszkowska, Agnieszka; Doherty, Jennifer Anne; Dörk, Thilo; Dürst, Matthias; Eccles, Diana; Fasching, Peter A; Flanagan, James; Gentry-Maharaj, Aleksandra; Glasspool, Rosalind; Goode, Ellen L; Goodman, Marc T; Gronwald, Jacek; Heitz, Florian; Hildebrandt, Michelle A T; Høgdall, Estrid; Høgdall, Claus K; Huntsman, David G; Jensen, Allan; Karlan, Beth Y; Kelemen, Linda E; Kiemeney, Lambertus A; Kjaer, Susanne K; Kupryjanczyk, Jolanta; Lambrechts, Diether; Levine, Douglas A; Li, Qiyuan; Lissowska, Jolanta; Lu, Karen H; Lubiński, Jan; Massuger, Leon F A G; McGuire, Valerie; McNeish, Iain; Menon, Usha; Modugno, Francesmary; Monteiro, Alvaro N; Moysich, Kirsten B; Ness, Roberta B; Nevanlinna, Heli; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Permuth, Jennifer B; Phelan, Catherine; Pike, Malcolm C; Poole, Elizabeth M; Ramus, Susan J; Risch, Harvey A; Rossing, Mary Anne; Salvesen, Helga B; Schildkraut, Joellen M; Sellers, Thomas A; Sherman, Mark; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa; Terry, Kathryn L; Tworoger, Shelley S; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S; Wu, Anna H; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Freedman, Matthew L; Gayther, Simon A; Pharoah, Paul D P; Lawrenson, Kate

2017-01-01

Background: Genome-wide association studies (GWAS) have identified 18 loci associated with serous ovarian cancer (SOC) susceptibility but the biological mechanisms driving these findings remain poorly characterised. Germline cancer risk loci may be enriched for target genes of transcription factors (TFs) critical to somatic tumorigenesis. Methods: All 615 TF-target sets from the Molecular Signatures Database were evaluated using gene set enrichment analysis (GSEA) and three GWAS for SOC risk: discovery (2196 cases/4396 controls), replication (7035 cases/21 693 controls; independent from discovery), and combined (9627 cases/30 845 controls; including additional individuals). Results: The PAX8-target gene set was ranked 1/615 in the discovery (PGSEA<0.001; FDR=0.21), 7/615 in the replication (PGSEA=0.004; FDR=0.37), and 1/615 in the combined (PGSEA<0.001; FDR=0.21) studies. Adding other genes reported to interact with PAX8 in the literature to the PAX8-target set and applying an alternative to GSEA, interval enrichment, further confirmed this association (P=0.006). Fifteen of the 157 genes from this expanded PAX8 pathway were near eight loci associated with SOC risk at P<10−5 (including six with P<5 × 10−8). The pathway was also associated with differential gene expression after shRNA-mediated silencing of PAX8 in HeyA8 (PGSEA=0.025) and IGROV1 (PGSEA=0.004) SOC cells and several PAX8 targets near SOC risk loci demonstrated in vitro transcriptomic perturbation. Conclusions: Putative PAX8 target genes are enriched for common SOC risk variants. This finding from our agnostic evaluation is of particular interest given that PAX8 is well-established as a specific marker for the cell of origin of SOC. PMID:28103614

MAP3K8/TPL-2/COT is a potential predictive marker for MEK inhibitor treatment in high-grade serous ovarian carcinomas.

PubMed

Gruosso, Tina; Garnier, Camille; Abelanet, Sophie; Kieffer, Yann; Lemesre, Vincent; Bellanger, Dorine; Bieche, Ivan; Marangoni, Elisabetta; Sastre-Garau, Xavier; Mieulet, Virginie; Mechta-Grigoriou, Fatima

2015-10-12

Ovarian cancer is a silent disease with a poor prognosis that urgently requires new therapeutic strategies. In low-grade ovarian tumours, mutations in the MAP3K BRAF gene constitutively activate the downstream kinase MEK. Here we demonstrate that an additional MAP3K, MAP3K8 (TPL-2/COT), accumulates in high-grade serous ovarian carcinomas (HGSCs) and is a potential prognostic marker for these tumours. By combining analyses on HGSC patient cohorts, ovarian cancer cells and patient-derived xenografts, we demonstrate that MAP3K8 controls cancer cell proliferation and migration by regulating key players in G1/S transition and adhesion dynamics. In addition, we show that the MEK pathway is the main pathway involved in mediating MAP3K8 function, and that MAP3K8 exhibits a reliable predictive value for the effectiveness of MEK inhibitor treatment. Our data highlight key roles for MAP3K8 in HGSC and indicate that MEK inhibitors could be a useful treatment strategy, in combination with conventional chemotherapy, for this disease.

Cediranib, a pan-VEGFR inhibitor, and olaparib, a PARP inhibitor, in combination therapy for high grade serous ovarian cancer.

PubMed

Ivy, S Percy; Liu, Joyce F; Lee, Jung-Min; Matulonis, Ursula A; Kohn, Elise C

2016-01-01

An estimated 22,000 women are diagnosed annually with ovarian cancer in the United States. Initially chemo-sensitive, recurrent disease ultimately becomes chemoresistant and may kill ~14,000 women annually. Molecularly targeted therapy with cediranib (AZD2171), a vascular endothelial growth factor receptor (VEGFR)-1, 2, and 3 signaling blocker, and olaparib (AZD2281), a poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, administered orally in combination has shown anti-tumor activity in the treatment of high grade serous ovarian cancer (HGSOC). This combination has the potential to change the treatment of HGSOC. Preclinical and clinical studies of single agent cediranib and olaparib or their combination are reviewed. Data are presented from peer-reviewed published manuscripts, completed and ongoing early phase clinical trials registered in ClinicalTrials.gov, National Cancer Institute-sponsored clinical trials, and related recent abstracts. Advances in the treatment of HGSOC that improve progression-free and overall survival have proven elusive despite examination of molecularly targeted therapy. HGSOC patients with deleterious germline or somatic mutations in BRCA1 or BRCA2 (BRCAm) are most responsive to PARP inhibitors (PARPi). PARPi combined with angiogenesis inhibition improved anti-cancer response and duration in both BRCAm and BRCA wild type HGSOC patients, compared to olaparib single agent treatment, demonstrating therapeutic chemical and contextual synthetic lethality.

Three-dimensional power doppler ultrasound is useful to monitor the response to treatment in a patient with primary papillary serous carcinoma of the peritoneum.

PubMed

Su, Jen-Min; Huang, Yu-Fang; Chen, Helen H W; Cheng, Ya-Min; Chou, Cheng-Yang

2006-05-01

To date, this is the first report to monitor changes of intratumor vascularization and the response to radiation and Cyberknife therapy in a patient with recurrent primary papillary serous carcinoma of the peritoneum by three dimensional (3D) power Doppler ultrasonography (PDUS). Transvaginal 3D PDUS detected a recurrent presacral tumor with abundant intratumor vascularity. Serial examinations of the tumor volume and serum CA-125 level were studied before, during, and 6 mo after therapy. Meanwhile, the intratumor blood flow was measured and expressed as vascularity indices. All of the tumor volume, intratumor vascularity indices and serum CA-125 level decreased progressively following therapy. A remaining lesion with nearly absent intratumor power Doppler signals suggested a scarring lesion posttreatment. Indeed, CT-guided tissue biopsy confirmed fibrotic change. 3D PDUS is useful to monitor the response to treatments and to differentiate residual tumors from lesions of scarring change posttreatment. It provides more accurate posttreatment information than pelvic computed tomography.

The role of tandem duplicator phenotype in tumour evolution in high-grade serous ovarian cancer.

PubMed

Ng, Charlotte K Y; Cooke, Susanna L; Howe, Kevin; Newman, Scott; Xian, Jian; Temple, Jillian; Batty, Elizabeth M; Pole, Jessica C M; Langdon, Simon P; Edwards, Paul A W; Brenton, James D

2012-04-01

High-grade serous ovarian carcinoma (HGSOC) is characterized by genomic instability, ubiquitous TP53 loss, and frequent development of platinum resistance. Loss of homologous recombination (HR) is a mutator phenotype present in 50% of HGSOCs and confers hypersensitivity to platinum treatment. We asked which other mutator phenotypes are present in HGSOC and how they drive the emergence of platinum resistance. We performed whole-genome paired-end sequencing on a model of two HGSOC cases, each consisting of a pair of cell lines established before and after clinical resistance emerged, to describe their structural variants (SVs) and to infer their ancestral genomes as the SVs present within each pair. The first case (PEO1/PEO4), with HR deficiency, acquired translocations and small deletions through its early evolution, but a revertant BRCA2 mutation restoring HR function in the resistant lineage re-stabilized its genome and reduced platinum sensitivity. The second case (PEO14/PEO23) had 216 tandem duplications and did not show evidence of HR or mismatch repair deficiency. By comparing the cell lines to the tissues from which they originated, we showed that the tandem duplicator mutator phenotype arose early in progression in vivo and persisted throughout evolution in vivo and in vitro, which may have enabled continual evolution. From the analysis of SNP array data from 454 HGSOC cases in The Cancer Genome Atlas series, we estimate that 12.8% of cases show patterns of aberrations similar to the tandem duplicator, and this phenotype is mutually exclusive with BRCA1/2 carrier mutations. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Inhibition of gamma-secretase activity impedes uterine serous carcinoma growth in a human xenograft model.

PubMed

Groeneweg, Jolijn W; Hall, Tracilyn R; Zhang, Ling; Kim, Minji; Byron, Virginia F; Tambouret, Rosemary; Sathayanrayanan, Sriram; Foster, Rosemary; Rueda, Bo R; Growdon, Whitfield B

2014-06-01

Uterine serous carcinoma (USC) represents an aggressive subtype of endometrial cancer. We sought to understand Notch pathway activity in USC and determine if pathway inhibition has anti-tumor activity. Patient USC tissue blocks were obtained and used to correlate clinical outcomes with Notch1 expression. Three established USC cell lines were treated with gamma-secretase inhibitor (GSI) in vitro. Mice harboring cell line derived or patient derived USC xenografts (PDXs) were treated with vehicle, GSI, paclitaxel and carboplatin (P/C), or combination GSI and P/C. Levels of cleaved Notch1 protein and Hes1 mRNA were determined in GSI treated samples. Statistical analysis was performed using the Wilcoxon rank sum and Kaplan-Meier methods. High nuclear Notch1 protein expression was observed in 58% of USC samples with no correlation with overall survival. GSI induced dose-dependent reductions in cell number and decreased levels of cleaved Notch1 protein and Hes1 mRNA in vitro. Treatment of mice with GSI led to decreased Hes1 mRNA expression in USC xenografts. In addition, GSI impeded tumor growth of cell line xenografts as well as UT1 USC PDXs. When GSI and P/C were combined, synergistic anti-tumor activity was observed in UT1 xenografts. Notch1 is expressed in a large subset of USC. GSI-mediated Notch pathway inhibition led to both reduced cell numbers in vitro and decreased tumor growth of USC some xenograft models. When combined with conventional chemotherapy, GSI augmented anti-tumor activity in one USC PDX line suggesting that targeting of the Notch signaling pathway is a potential therapeutic strategy for future investigation. Copyright © 2014 Elsevier Inc. All rights reserved.

Dual HER2 targeting impedes growth of HER2 gene-amplified uterine serous carcinoma xenografts.

PubMed

Groeneweg, Jolijn W; Hernandez, Silvia F; Byron, Virginia F; DiGloria, Celeste M; Lopez, Hector; Scialabba, Vanessa; Kim, Minji; Zhang, Ling; Borger, Darrell R; Tambouret, Rosemary; Foster, Rosemary; Rueda, Bo R; Growdon, Whitfield B

2014-12-15

Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer that commonly harbors HER2 gene amplification. We investigated the effectiveness of HER2 inhibition using lapatinib and trastuzumab in vitro and in xenografts derived from USC cell lines and USC patient-derived xenografts. Immunohistochemistry and FISH were performed to assess HER2 expression in 42 primary USC specimens. ARK1, ARK2, and SPEC2 cell lines were treated with trastuzumab or lapatinib. Cohorts of mice harboring xenografts derived from ARK2 and SPEC2 cell lines and EnCa1 and EnCa2 primary human USC samples were treated with either vehicle, trastuzumab, lapatinib, or the combination of trastuzumab and lapatinib. Acute and chronic posttreatment tumor samples were assessed for downstream signaling alterations and examined for apoptosis and proliferation. HER2 gene amplification (24%) correlated significantly with HER2 protein overexpression (55%). All models were impervious to single-agent trastuzumab treatment. Lapatinib decreased in vitro proliferation of all cell lines and in vivo growth of HER2-amplified xenografts (ARK2, EnCa1). In addition, dual therapy with trastuzumab and lapatinib resulted in significant antitumor activity only in ARK2 and EnCa1 tumors. Dual HER2 therapy induced on target alteration of downstream MAPK and PI3K pathway mediators only in HER2-amplified models, and was associated with increased apoptosis and decreased proliferation. Although trastuzumab alone did not impact USC growth, dual anti-HER2 therapy with lapatinib led to improved inhibition of tumor growth in HER2-amplified USC and may be a promising avenue for future investigation. ©2014 American Association for Cancer Research.

Optical coherence tomography of the eye

NASA Astrophysics Data System (ADS)

Hee, Michael Richard

1997-10-01

Optical Coherence Tomography (OCT) is a new technique for high-resolution, cross-sectional imaging of tissue in which the time-of-flight delay of light reflected from internal tissue structures is resolved with high precision using interferometry. Tomographic images are obtained which are analogous to those provided by ultrasound except that image contrast relies on differences in optical rather than acoustic properties of tissue. The use of light rather than sound enables higher resolution (10 μm) and non-contact imaging. A clinically viable high-sensitivity, fiber-optic based OCT instrument has been constructed based on engineering principles derived from optical communication theory. Computer algorithms have also been developed for quantitative image analysis and restoration. OCT has been used to image patients with a variety of ocular diseases. In patients with macular pathology, OCT images have been correlated with conventional clinical examination and fluorescein angiography. Optical coherence tomograms are effective in staging macular holes, evaluating the vitreoretinal interface in eyes at risk for a macular hole, and providing a structural assessment of macular hole surgery. In eyes with central serous chorioretinopathy, OCT can evaluate sensory retinal separations undetected at the slit-lamp. Serial OCT images of macular edema are able to track both the progression of macular thickening and the resolution of macular edema following laser photocoagulation. In patients with diabetic retinopathy, measurements of macular thickness correlate with visual acuity and OCT is more sensitive to small changes in retinal thickness than slit-lamp biomicroscopy. OCT may provide a novel method of defining occult choroidal neovascular membranes in patients with age-related macular degeneration. OCT can also profile the thickness of the retinal nerve fiber layer with high resolution which is potentially important for the objective assessment of early glaucoma progression

Clinical research on intravitreal injection of bevacizumab in the treatment of macula lutea and retinal edema of ocular fundus disease.

PubMed

Yan, Ying; Wang, Tao; Cao, Jing; Wang, Meng; Li, Fenghua

2015-07-01

This paper aimed to explore clinically curative effect of intravitreal injection of bevacizumab in the treatment of macula lutea and retinal edema of ocular fundus disease. The number of 300 patients (390 eyes) with ocular fundus diseases including retinal vein occlusion (RVO), diabetic retinopathy (DR), age-related macular degeneration (ARMD), central serous chorioretinopathy (CSC), choridal new vessel (CNV) received and cured in the hospital from February 2010 to February 2014 were given intravitreal injection of bevacizumab (1.5mg) with once per month and a total of 2-3 times. Results of patients' vision and fluorescence fundus angiography (FFA), optical coherence tomography (OCT) before and after treatment were compared and curative effects were evaluated. Vision of 349 eyes (89.49%) improved obviously with the average of more than 2 lines, patient's intraocular pressure (IOP) was normal and all indexes were clearly better; vision of 26 eyes (6.67%) was stable before the treatment and without any changes after the treatment, the situation of fundus got better without increased IOP; vision of 15 eyes (3.85%) decreased to some extent, and the symptoms eased slightly after symptomatic treatment. In the 1st day after intravitreal injection, best-corrected visual acuity increased to 0.239±0.175, best-corrected visual acuity in 1 m was 0.315±0.182, in 3m continuously climbed to 0.350±0.270, and in 6 m was 0.362±0.282. Compared with vision before injection, t value was t=3.184, t=7.213, t=9.274 and t=9.970 (P=0.002, P=0.000, P=0.000 and P=0.000) respectively, and all P were less than 0.01. Furthermore, the difference was significant if a=0.01, which could confirm that 1m best corrected visual acuity of patients after intravitreal injection improved clearly in combination with before injection and 3m and 6 m visions enhanced constantly after injection. To sum up, intravitreal injection of bevacizumab in treating ocular fundus disease improves patient's vision

Spatial and temporal heterogeneity in high-grade serous ovarian cancer: a phylogenetic analysis.

PubMed

Schwarz, Roland F; Ng, Charlotte K Y; Cooke, Susanna L; Newman, Scott; Temple, Jillian; Piskorz, Anna M; Gale, Davina; Sayal, Karen; Murtaza, Muhammed; Baldwin, Peter J; Rosenfeld, Nitzan; Earl, Helena M; Sala, Evis; Jimenez-Linan, Mercedes; Parkinson, Christine A; Markowetz, Florian; Brenton, James D

2015-02-01

The major clinical challenge in the treatment of high-grade serous ovarian cancer (HGSOC) is the development of progressive resistance to platinum-based chemotherapy. The objective of this study was to determine whether intra-tumour genetic heterogeneity resulting from clonal evolution and the emergence of subclonal tumour populations in HGSOC was associated with the development of resistant disease. Evolutionary inference and phylogenetic quantification of heterogeneity was performed using the MEDICC algorithm on high-resolution whole genome copy number profiles and selected genome-wide sequencing of 135 spatially and temporally separated samples from 14 patients with HGSOC who received platinum-based chemotherapy. Samples were obtained from the clinical CTCR-OV03/04 studies, and patients were enrolled between 20 July 2007 and 22 October 2009. Median follow-up of the cohort was 31 mo (interquartile range 22-46 mo), censored after 26 October 2013. Outcome measures were overall survival (OS) and progression-free survival (PFS). There were marked differences in the degree of clonal expansion (CE) between patients (median 0.74, interquartile range 0.66-1.15), and dichotimization by median CE showed worse survival in CE-high cases (PFS 12.7 versus 10.1 mo, p = 0.009; OS 42.6 versus 23.5 mo, p = 0.003). Bootstrap analysis with resampling showed that the 95% confidence intervals for the hazard ratios for PFS and OS in the CE-high group were greater than 1.0. These data support a relationship between heterogeneity and survival but do not precisely determine its effect size. Relapsed tissue was available for two patients in the CE-high group, and phylogenetic analysis showed that the prevalent clonal population at clinical recurrence arose from early divergence events. A subclonal population marked by a NF1 deletion showed a progressive increase in tumour allele fraction during chemotherapy. This study demonstrates that quantitative measures of intra-tumour heterogeneity

Proteomic Analysis of Matched Formalin-Fixed, Paraffin-Embedded Specimens in Patients with Advanced Serous Ovarian Carcinoma

PubMed Central

Smith, Ashlee L.; Sun, Mai; Bhargava, Rohit; Stewart, Nicolas A.; Flint, Melanie S.; Bigbee, William L.; Krivak, Thomas C.; Strange, Mary A.; Cooper, Kristine L.; Zorn, Kristin K.

2013-01-01

Objective: The biology of high grade serous ovarian carcinoma (HGSOC) is poorly understood. Little has been reported on intratumoral homogeneity or heterogeneity of primary HGSOC tumors and their metastases. We evaluated the global protein expression profiles of paired primary and metastatic HGSOC from formalin-fixed, paraffin-embedded (FFPE) tissue samples. Methods: After IRB approval, six patients with advanced HGSOC were identified with tumor in both ovaries at initial surgery. Laser capture microdissection (LCM) was used to extract tumor for protein digestion. Peptides were extracted and analyzed by reversed-phase liquid chromatography coupled to a linear ion trap mass spectrometer. Tandem mass spectra were searched against the UniProt human protein database. Differences in protein abundance between samples were assessed and analyzed by Ingenuity Pathway Analysis software. Immunohistochemistry (IHC) for select proteins from the original and an additional validation set of five patients was performed. Results: Unsupervised clustering of the abundance profiles placed the paired specimens adjacent to each other. IHC H-score analysis of the validation set revealed a strong correlation between paired samples for all proteins. For the similarly expressed proteins, the estimated correlation coefficients in two of three experimental samples and all validation samples were statistically significant (p < 0.05). The estimated correlation coefficients in the experimental sample proteins classified as differentially expressed were not statistically significant. Conclusion: A global proteomic screen of primary HGSOC tumors and their metastatic lesions identifies tumoral homogeneity and heterogeneity and provides preliminary insight into these protein profiles and the cellular pathways they constitute. PMID:28250404

Risk of high-grade serous ovarian cancer associated with pelvic inflammatory disease, parity and breast cancer.

PubMed

Stewart, Louise M; Spilsbury, Katrina; Jordan, Susan; Stewart, Colin; Holman, C D'Arcy J; Powell, Aime; Reekie, Joanne; Cohen, Paul

2018-06-20

Ovarian carcinoma is not a single disease, but rather a collection of subtypes with differing molecular properties and risk profiles. The most common of these, and the subject of this work, is high-grade serous ovarian carcinoma (HGSC). In this population-based study we identified a cohort of 441,382 women resident in Western Australia who had ever been admitted to hospital in the State. Of these, 454 were diagnosed with HGSC. We used Cox regression to derive hazard ratios (HRs) comparing the risk of disease in women who had each of a range of medical diagnoses and surgical procedures with women who did not. We found an increased risk of HGSC associated with a diagnosis of pelvic inflammatory disease (PID) (HR 1.47, 95% CI 1.04-2.07) but not with a diagnosis of infertility or endometriosis with HRs of 1.12 (95% CI 0.73-1.71) and 0.82 (95% CI 0.55-1.22) respectively. A personal history of breast cancer was associated with a three-fold increase in the rate of HGSC. Increased parity was associated with a reduced risk of HGSC in women without a personal history of breast cancer (HR 0.57; 95% CI 0.44-0.73), but not in women with a personal history of breast cancer (HR 1.48; 95% CI 0.74-2.95). Our finding of an increased risk of HGSC associated with PID lends support to the hypothesis that inflammatory processes may be involved in the etiology of HGSC. Copyright © 2018 Elsevier Ltd. All rights reserved.

Talazoparib and HSP90 Inhibitor AT13387 in Treating Patients With Metastatic Advanced Solid Tumor or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple Negative Breast Cancer

ClinicalTrials.gov

2016-07-22

Adult Solid Neoplasm; Estrogen Receptor Negative; Fallopian Tube Serous Neoplasm; HER2/Neu Negative; Ovarian Serous Adenocarcinoma; Ovarian Serous Tumor; Primary Peritoneal Serous Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Triple-Negative Breast Carcinoma

Rationale for Developing a Specimen Bank to Study the Pathogenesis of High-Grade Serous Carcinoma: A Review of the Evidence.

PubMed

Sherman, Mark E; Drapkin, Ronny I; Horowitz, Neil S; Crum, Christopher P; Friedman, Sue; Kwon, Janice S; Levine, Douglas A; Shih, Ie-Ming; Shoupe, Donna; Swisher, Elizabeth M; Walker, Joan; Trabert, Britton; Greene, Mark H; Samimi, Goli; Temkin, Sarah M; Minasian, Lori M

2016-09-01

Women with clinically detected high-grade serous carcinomas (HGSC) generally present with advanced-stage disease, which portends a poor prognosis, despite extensive surgery and intensive chemotherapy. Historically, HGSCs were presumed to arise from the ovarian surface epithelium (OSE), but the inability to identify early-stage HGSCs and their putative precursors in the ovary dimmed prospects for advancing our knowledge of the pathogenesis of these tumors and translating these findings into effective prevention strategies. Over the last decade, increased BRCA1/2 mutation testing coupled with performance of risk-reducing surgeries has enabled studies that have provided strong evidence that many, but probably not all, HGSCs among BRCA1/2 mutation carriers appear to arise from the fallopian tubes, rather than from the ovaries. This shift in our understanding of the pathogenesis of HGSCs provides an important opportunity to achieve practice changing advances; however, the scarcity of clinically annotated tissues containing early lesions, particularly among women at average risk, poses challenges to progress. Accordingly, we review studies that have kindled our evolving understanding of the pathogenesis of HGSC and present the rationale for developing an epidemiologically annotated national specimen resource to support this research. Cancer Prev Res; 9(9); 713-20. ©2016 AACR. ©2016 American Association for Cancer Research.

Her2/neu extracellular domain shedding in uterine serous carcinoma: implications for immunotherapy with trastuzumab.

PubMed

Todeschini, P; Cocco, E; Bellone, S; Varughese, J; Lin, K; Carrara, L; Guzzo, F; Buza, N; Hui, P; Silasi, D-A; Ratner, E; Azodi, M; Schwartz, P E; Rutherford, T J; Pecorelli, S; Santin, A D

2011-10-11

We evaluated shedding of epidermal growth factor type II receptor (Her2/neu) extracellular domain (ECD) in primary uterine serous carcinoma (USC) cell lines and in the serum of USC patients and its biological effects in experiments of trastuzumab-induced cytotoxicity in vitro. Her2/neu expression was evaluated by immunohistochemistry (IHC), real-time PCR and flow cytometry, while c-erbB2 gene amplification was assessed using fluorescent in situ hybridisation (FISH). Her2/neu ECD levels in the supernatants of USC cell lines and in the serum of 38 USC patients and 19 controls were tested using ELISA. The biologic effect of Her2/neu ECD on trastuzumab-induced antibody-dependent cell-mediated cytotoxicity (ADCC) was evaluated in 5-h chromium-release assays. Five out of ten USC cell lines overexpressed Her2/neu by IHC and showed amplification of the c-erbB2 gene. High levels of Her2/neu ECD were found in supernatants of all FISH-positive tumours. In contrast, FISH-negative USC was negative for Her2/neu ECD shedding. Serum Her2/neu ECD levels in patients harbouring 3+Her2/neu tumours were higher than those found in healthy women (P=0.02) or USC patients with 2+ or 1+/negative Her2/neu expression (P=0.02). In cytotoxicity experiments, trastuzumab-mediated ADCC was significantly decreased by the addition of Her2/neu ECD-containing supernatants (P=0.01). FISH-positive c-erbB2 USC cell lines shed high levels of Her2/neu ECD. High levels of Her2/neu ECD in USC patients may reduce trastuzumab-mediated ADCC in vitro and potentially neutralise its therapeutic effect in vivo.

Expression pattern of RAGE and IGF-1 in the human fetal ovary and ovarian serous carcinoma.

PubMed

Poljicanin, Ana; Filipovic, Natalija; Vukusic Pusic, Tanja; Soljic, Violeta; Caric, Ana; Saraga-Babic, Mirna; Vukojevic, Katarina

2015-01-01

The expression pattern of RAGE and IGF-1 proteins in different ovarian cell lineages was histologically analyzed in six fetal, nine adult human ovaries, and nine serous ovarian carcinomas (OSC) using immunohistochemical methods. Mild expression of IGF-1 in ovarian surface epithelium (Ose) and oocytes in the 15-week human ovaries increased to moderate or strong in the stromal cells, oocytes and follicular cells in week 22. Occasional mild RAGE expression was observed in Ose during week 15, while strong expression characterized primordial follicles in week 22. In the reproductive human ovary, IGF-1 was mildly to moderately expressed in all ovarian cell lineages except in theca cells of the tertiary follicle where IGF-1 was negative. RAGE was strongly positive in the granulosa cells and some theca cells of the tertiary follicle, while negative to mildly positive in all cells of the secondary follicle. In the postmenopausal human ovary IGF-1 and RAGE were mildly expressed in Ose and stroma. In OSC, cells were strongly positive to IGF-1 and RAGE, except for some negative stromal cells. Different levels of IGF-1 and RAGE co-expression characterized fetal ovarian cells during development. In reproductive ovaries, IGF-1 and RAGE were co-localized in the granulosa and theca interna cells of tertiary follicles, while in postmenopausal ovaries and OSC, IGF-1 and RAGE were co-localized in Ose and OSC cells respectively. Our results indicate that intracellular levels of IGF-1 and RAGE protein might regulate the final destiny of the ovarian cell populations prior and during folliculogenesis, possibly controlling the metastatic potential of OSC as well. Copyright © 2015. Published by Elsevier GmbH.

The Analysis of Cell Cycle-related Proteins in Ovarian Clear Cell Carcinoma Versus High-grade Serous Carcinoma.

PubMed

Hazama, Yukiko; Moriya, Takuya; Sugihara, Mika; Sano, Rikiya; Shiota, Mitsuru; Nakamura, Takafumi; Shimoya, Koichiro

2017-10-10

In Japan, the frequency of ovarian clear cell carcinoma (CCC) is twice as high as that in the United States and Europe. Often, patient prognosis of CCC is poor because of chemoresistance. Here, we focus on the cell cycle, which is one of the mechanisms of chemoresistance. To detect the informative markers and improve the strategy of chemotherapy for CCC, we performed immunochemical staining of cell cycle-related proteins in ovarian malignant tumors. We detected that each of the 29 samples of CCC and high-grade serous carcinoma (HGSC) were necessary to reveal the significant differences in immunostaining and prognosis. We performed the immunostaining analysis using the antibodies of cell cycle-related proteins such as Ki-67, Cdt1, MCM7, and geminin. The positive rate of Cdt1 in the CCC group was significantly higher than that in the HGSC group (P<0.0001). However, the positive rate of geminin in the HGSC group was significantly higher than that in the CCC group (P<0.0001). The overall survival of CCC patients with high labeling index of Cdt1 was significantly worse than that of CCC patients with low labeling index of Cdt1 (P=0.004). The study results suggested that the cancer cells of CCC and HGSC exist in the G1 phase and S, G2, and M phases, respectively. The differences in cell cycle of CCC might be one of the reasons for chemotherapy resistance. Further investigations are necessary to reveal the usefulness of Cdt1 as a biomarker in CCC.

Birinapant and Carboplatin in Treating Patients With Recurrent High Grade Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2018-04-26

High Grade Fallopian Tube Serous Adenocarcinoma; High Grade Ovarian Serous Adenocarcinoma; Primary Peritoneal High Grade Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

Spatial and Temporal Heterogeneity in High-Grade Serous Ovarian Cancer: A Phylogenetic Analysis

PubMed Central

Schwarz, Roland F.; Ng, Charlotte K. Y.; Cooke, Susanna L.; Newman, Scott; Temple, Jillian; Piskorz, Anna M.; Gale, Davina; Sayal, Karen; Murtaza, Muhammed; Baldwin, Peter J.; Rosenfeld, Nitzan; Earl, Helena M.; Sala, Evis; Jimenez-Linan, Mercedes; Parkinson, Christine A.; Markowetz, Florian; Brenton, James D.

2015-01-01

Background The major clinical challenge in the treatment of high-grade serous ovarian cancer (HGSOC) is the development of progressive resistance to platinum-based chemotherapy. The objective of this study was to determine whether intra-tumour genetic heterogeneity resulting from clonal evolution and the emergence of subclonal tumour populations in HGSOC was associated with the development of resistant disease. Methods and Findings Evolutionary inference and phylogenetic quantification of heterogeneity was performed using the MEDICC algorithm on high-resolution whole genome copy number profiles and selected genome-wide sequencing of 135 spatially and temporally separated samples from 14 patients with HGSOC who received platinum-based chemotherapy. Samples were obtained from the clinical CTCR-OV03/04 studies, and patients were enrolled between 20 July 2007 and 22 October 2009. Median follow-up of the cohort was 31 mo (interquartile range 22–46 mo), censored after 26 October 2013. Outcome measures were overall survival (OS) and progression-free survival (PFS). There were marked differences in the degree of clonal expansion (CE) between patients (median 0.74, interquartile range 0.66–1.15), and dichotimization by median CE showed worse survival in CE-high cases (PFS 12.7 versus 10.1 mo, p = 0.009; OS 42.6 versus 23.5 mo, p = 0.003). Bootstrap analysis with resampling showed that the 95% confidence intervals for the hazard ratios for PFS and OS in the CE-high group were greater than 1.0. These data support a relationship between heterogeneity and survival but do not precisely determine its effect size. Relapsed tissue was available for two patients in the CE-high group, and phylogenetic analysis showed that the prevalent clonal population at clinical recurrence arose from early divergence events. A subclonal population marked by a NF1 deletion showed a progressive increase in tumour allele fraction during chemotherapy. Conclusions This study demonstrates that

DNA Cytometry and Nuclear Morphometry in Ovarian Benign, Borderline and Malignant Tumors.

PubMed

El Din, Amina A Gamal; Badawi, Manal A; Aal, Shereen E Abdel; Ibrahim, Nihad A; Morsy, Fatma A; Shaffie, Nermeen M

2015-12-15

Ovarian carcinoma is a leading cause of death in gynecological malignancy. Ovarian surface epithelial serous and mucinous tumours are classified as benign, borderline, and malignant. The identification of borderline tumours most likely to act aggressively remains an important clinical issue. This work aimed to study DNA ploidy and nuclear area in ovarian serous and mucinous; benign, borderline and malignant tumours. This study included forty ovarian (23 serous and 17 mucinous) tumours. Paraffin blocks were sectioned; stained with haematoxylin and eosin for histopathologic and morphometric studies and with blue feulgen for DNA analysis. All four serous and six out of nine mucinous benign tumours were diploid. All eight serous and five mucinous malignant tumours were aneuploid. Nine of eleven (81.8%) serous and all three mucinous borderline tumours were aneuploid. There were highly significant differences in mean aneuploid cells percentage between serous benign (1.5%), borderline (45.6%) and malignant (74.5%) (p = 0.0001) and between mucinous benign (13.2%) and both borderline (63.7%) and malignant (68.4%) groups (p = 0.0001). There were significant differences in nuclear area between serous benign (26.191%), borderline (45.619%) and malignant (67.634 %) and a significant positive correlation between mean percentage aneuploid value and mean nuclear area in all serous and mucinous groups. We suggest that DNA ploidy and nuclear area combined, may be adjuncts to histopathology; in ovarian serous and mucinous benign, borderline and malignant neoplasms; identifying the aggressive borderline tumours.

Management of end-stage central venous access in children referred for possible small bowel transplantation.

PubMed

Rodrigues, A F; van Mourik, I D M; Sharif, K; Barron, D J; de Giovanni, J V; Bennett, J; Bromley, P; Protheroe, S; John, P; de Ville de Goyet, J; Beath, S V

2006-04-01

The 3-year survival after small bowel transplantation (SBTx) has improved to between 73% and 88%. Impaired venous access for parenteral nutrition can be an indication for SBTx in children with chronic intestinal failure. To report our experience in management of children with extreme end-stage venous access. The study consisted of 6 children (all boys), median age of assessment 27 months (range, 13-52 months), diagnosed with total intestinal aganglionosis (1), protracted diarrhea (1), and short bowel syndrome (4), of which gastroschisis (2) and malrotation with midgut volvulus (2) were the causes. All had a documented history of more than 10 central venous catheter insertions previously. All had venograms, and 1 child additionally had a magnetic resonance angiogram to evaluate venous access. Five of 6 presented with thrombosis of the superior vena cava (SVC) and/or inferior vena cava. Venous access was reestablished as follows: transhepatic venous catheters (5), direct intra-atrial catheter via midline sternotomy (4), azygous venous catheters (2), dilatation of left subclavian vein after passage of a guide wire and then placing a catheter to reach the right atrium (1), radiological recanalization of the SVC and placement of a central venous catheter in situ (1), and direct puncture of SVC stump(1). Complications included serous pleural effusion after direct intra-atrial line insertion, which resolved after chest drain insertion (1), displacement of transhepatic catheter needing repositioning (2), and SVC stent narrowing requiring repeated balloon dilatation. Four children with permanent intestinal failure on assessment were offered SBTx, 3 of which were transplanted and were established on full enteral nutrition; the family of 1 child declined the procedure. In the remaining 2 children in whom bowel adaptation was still a possibility, attempts were made to provide adequate central venous access as feeds and drug manipulations were undertaken. One of them received

KCNN4 and S100A14 act as predictors of recurrence in optimally debulked patients with serous ovarian cancer

PubMed Central

Hu, Ting; Sun, Qian; Wu, Jianli; Lin, Xingguang; Luo, Danfeng; Sun, Chaoyang; Wang, Changyu; Zhou, Bo; Li, Na; Xia, Meng; Lu, Hao; Meng, Li; Xu, Xiaoyan; Hu, Junbo; Ma, Ding; Chen, Gang; Zhu, Tao

2016-01-01

Approximately 50-75% of patients with serous ovarian carcinoma (SOC) experience recurrence within 18 months after first-line treatment. Current clinical indicators are inadequate for predicting the risk of recurrence. In this study, we used 7 publicly available microarray datasets to identify gene signatures related to recurrence in optimally debulked SOC patients, and validated their expressions in an independent clinic cohort of 127 patients using immunohistochemistry (IHC). We identified a two-gene signature including KCNN4 and S100A14 which was related to recurrence in optimally debulked SOC patients. Their mRNA expression levels were positively correlated and regulated by DNA copy number alterations (CNA) (KCNN4: p=1.918e-05) and DNA promotermethylation (KCNN4: p=0.0179; S100A14: p=2.787e-13). Recurrence prediction models built in the TCGA dataset based on KCNN4 and S100A14 individually and in combination showed good prediction performance in the other 6 datasets (AUC:0.5442-0.9524). The independent cohort supported the expression difference between SOC recurrences. Also, a KCNN4 and S100A14-centered protein interaction subnetwork was built from the STRING database, and the shortest regulation path between them, called the KCNN4-UBA52-KLF4-S100A14 axis, was identified. This discovery might facilitate individualized treatment of SOC. PMID:27270322

Poor prognosis of uterine serous carcinoma compared with grade 3 endometrioid carcinoma in early stage patients.

PubMed

Park, Ji Young; Nam, Joo-Hyun; Kim, Young-Tak; Kim, Yong-Man; Kim, Jong-Hyeok; Kim, Dae-Yeon; Sohn, Insuk; Lee, Shin-Wha; Sung, Chang Ohk; Kim, Kyu-Rae

2013-03-01

Difference in prognosis between grade 3 endometrioid carcinoma (G3EC) of the endometrium and uterine serous carcinoma (USC) is controversial. In this study, we further evaluated the difference in prognosis, if any, between G3EC (n = 61) and USC (n = 47) on a total of 565 patients with endometrial cancer. In addition, meta-analysis was performed using data from seven previous publications (n = 8,637) and from the Asan Medical Center (n = 108). Regarding the cases from our institution, USC tended to occur in older patients (≥65 years) than G3EC (P = 0.011). Deep myometrial invasion (more than or equal to half) was more frequently identified in G3EC (36/61, 59.0 %) than in USC (17/47, 36.2 %) (P = 0.021). Between patients with early stage G3EC and USC (stages I and II), there were no significant differences in any clinicopathological parameter, but there was a significant difference in overall survival (P = 0.017) that was not found in advanced stage (P = 0.588). USC was an independent prognostic factor for poor overall survival (hazard ratio, 6.125; P = 0.030) in early stage patients. In the meta-analysis on 5-year survival in patients with early stage cancers, which also included our study results, a higher relative risk (1.92, 95 % CI 1.62-2.27) was demonstrated in USC than in G3EC (P < 0.001). In conclusion, our study reveals that USC is associated with a poorer prognosis compared with G3EC, only in patients with early stage carcinoma, suggesting that different treatment strategies should be considered according to the histologic type in order to improve treatment outcome.

Downregulation of membrane complement inhibitors CD55 and CD59 by siRNA sensitises uterine serous carcinoma overexpressing Her2/neu to complement and antibody-dependent cell cytotoxicity in vitro: implications for trastuzumab-based immunotherapy.

PubMed

Bellone, S; Roque, D; Cocco, E; Gasparrini, S; Bortolomai, I; Buza, N; Abu-Khalaf, M; Silasi, D-A; Ratner, E; Azodi, M; Schwartz, P E; Rutherford, T J; Pecorelli, S; Santin, A D

2012-04-24

We evaluated the expression of CD46, CD55 and CD59 membrane-bound complement-regulatory proteins (mCRPs) in primary uterine serous carcinoma (USC) and the ability of small interfering RNA (siRNA) against these mCRPs to sensitise USC to complement-dependent cytotoxicity (CDC) and antibody (trastuzumab)-dependent cellular cytotoxicity (ADCC) in vitro. Membrane-bound complement-regulatory proteins expression was evaluated using real-time PCR (RT-PCR) and flow cytometry, whereas Her2/neu expression and c-erbB2 gene amplification were assessed using immunohistochemistry, flow cytometry and fluorescent in-situ hybridisation. The biological effect of siRNA-mediated knockdown of mCRPs on HER2/neu-overexpressing USC cell lines was evaluated in CDC and ADCC 4-h chromium-release assays. High expression of mCRPs was found in USC cell lines when compared with normal endometrial cells (P<0.05). RT-PCR and FACS analyses demonstrated that anti-mCRP siRNAs were effective in reducing CD46, CD55 and CD59 expression on USC (P<0.05). Baseline complement-dependent cytotoxicity (CDC) against USC cell lines was low (mean ± s.e.m.=6.8 ± 0.9%) but significantly increased upon CD55 and CD59 knockdown (11.6 ± 0.8% and 10.7 ± 0.9%, respectively, P<0.05). Importantly, in the absence of complement, both CD55 and CD59, but not CD46, knockdowns significantly augmented ADCC against USC overexpressing Her2/neu. Uterine serous carcinoma express high levels of the mCRPs CD46, CD55 and CD59. Small interfering RNA inhibition of CD55 and CD59, but not CD46, sensitises USC to both CDC and ADCC in vitro, and if specifically targeted to tumour cells, may significantly increase trastuzumab-mediated therapeutic effect in vivo.

DNA Cytometry and Nuclear Morphometry in Ovarian Benign, Borderline and Malignant Tumors

PubMed Central

el Din, Amina A. Gamal; Badawi, Manal A.; Aal, Shereen E. Abdel; Ibrahim, Nihad A.; Morsy, Fatma A.; Shaffie, Nermeen M.

2015-01-01

BACKDROUND: Ovarian carcinoma is a leading cause of death in gynecological malignancy. Ovarian surface epithelial serous and mucinous tumours are classified as benign, borderline, and malignant. The identification of borderline tumours most likely to act aggressively remains an important clinical issue. AIM: This work aimed to study DNA ploidy and nuclear area in ovarian serous and mucinous; benign, borderline and malignant tumours. MATERIAL AND METHODS: This study included forty ovarian (23 serous and 17 mucinous) tumours. Paraffin blocks were sectioned; stained with haematoxylin and eosin for histopathologic and morphometric studies and with blue feulgen for DNA analysis. RESULTS: All four serous and six out of nine mucinous benign tumours were diploid. All eight serous and five mucinous malignant tumours were aneuploid. Nine of eleven (81.8%) serous and all three mucinous borderline tumours were aneuploid. There were highly significant differences in mean aneuploid cells percentage between serous benign (1.5%), borderline (45.6%) and malignant (74.5%) (p = 0.0001) and between mucinous benign (13.2%) and both borderline (63.7%) and malignant (68.4%) groups (p = 0.0001). There were significant differences in nuclear area between serous benign (26.191%), borderline (45.619%) and malignant (67.634 %) and a significant positive correlation between mean percentage aneuploid value and mean nuclear area in all serous and mucinous groups. CONCLUSION: We suggest that DNA ploidy and nuclear area combined, may be adjuncts to histopathology; in ovarian serous and mucinous benign, borderline and malignant neoplasms; identifying the aggressive borderline tumours. PMID:27275284

A Mouse Model to Investigate Postmenopausal Biology as an Etiology of Ovarian Cancer Risk

DTIC Science & Technology

2007-11-01

1 mucinous adenocarcinomas 3 clear-cell carcinomas 1 malignant mixed mesodermal tumor 3 metastatic ovarian carcinomas 5 undifferentiated carcinomas 2...serous LMP tumors 2 mucinous LMP tumors 1 benign serous cystadenoma Ovarian tumor blocks 38 18 serous adenocarcinomas 5 mucinous adenocarcinomas 2...endometrioid adenocarcinomas 3 clear cell carcinomas 6 serous LMP 3 mucinous LMP 1 benign fibrous cystadenoma MMPs IN EARLY OVARIAN CANCER DEVELOPMENT

Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients.

PubMed

Mignogna, Chiara; Staropoli, Nicoletta; Botta, Cirino; De Marco, Carmela; Rizzuto, Antonia; Morelli, Michele; Di Cello, Annalisa; Franco, Renato; Camastra, Caterina; Presta, Ivan; Malara, Natalia; Salvino, Angela; Tassone, Pierfrancesco; Tagliaferri, Pierosandro; Barni, Tullio; Donato, Giuseppe; Di Vito, Anna

2016-05-21

High-Grade Serous Ovarian Carcinoma (HGSOC) is the predominant histotype of epithelial ovarian cancer (EOC), characterized by advanced stage at diagnosis, frequent TP53 mutation, rapid progression, and high responsiveness to platinum-based-chemotherapy. To date, standard first-line-chemotherapy in advanced EOC includes platinum salts and paclitaxel with or without bevacizumab. The major prognostic factor is the response duration from the end of the platinum-based treatment (platinum-free interval) and about 10-0 % of EOC patients bear a platinum-refractory disease or develop early resistance (platinum-free interval shorter than 6 months). On these bases, a careful selection of patients who could benefit from chemotherapy is recommended to avoid unnecessary side effects and for a better disease outcome. In this retrospective study, an immunohistochemical evaluation of Aurora Kinase A (AURKA) was performed on 41 cases of HGSOC according to platinum-status. Taking into account the number and intensity of AURKA positive cells we built a predictive score able to discriminate with high accuracy platinum-sensitive patients from platinum-resistant patients (p < 0.001). Furthermore, we observed that AURKA overexpression correlates to worse overall survival (p = 0.001; HR 0.14). We here suggest AURKA as new effective tool to predict the biological behavior of HGSOC. Particularly, our results indicate that AURKA has a role both as predictor of platinum-resistance and as prognostic factor, that deserves further investigation in prospective clinical trials. Indeed, in the era of personalized medicine, AURKA could assist the clinicians in selecting the best treatment and represent, at the same time, a promising new therapeutic target in EOC treatment.

Afatinib demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro and in vivo.

PubMed

Schwab, C L; Bellone, S; English, D P; Roque, D M; Lopez, S; Cocco, E; Nicoletti, R; Bortolomai, I; Bonazzoli, E; Ratner, E; Silasi, D-A; Azodi, M; Schwartz, P E; Rutherford, T J; Santin, A D

2014-10-28

Uterine serous carcinomas (USCs) are an aggressive form of uterine cancer that may rely on HER2/neu amplification as a driver of proliferation. The objective of this paper is to assess the sensitivity of USC cell lines with and without HER2/neu gene amplification to afatinib, an irreversible ErbB tyrosine kinase inhibitor, and to test the efficacy of afatinib in the treatment of HER2-amplified USC xenografts. Eight of fifteen primary USC cell lines (four with HER2 amplification and four without) demonstrating similar in vitro growth rates were treated with scalar concentrations of afatinib. Effects on cell growth, signalling and cell cycle distribution were determined by flow cytometry assays. Mice harbouring xenografts of HER2/neu-amplified USC were treated with afatinib by gavage to determine the effect on tumour growth and overall survival. Primary chemotherapy-resistant USC cell lines harbouring HER2/neu gene amplification were exquisitely sensitive to afatinib exposure (mean ± s.e.m. IC50=0.0056 ± 0.0006 μM) and significantly more sensitive than HER2/neu-non-amplified USC cell lines (mean ± s.e.m. IC50=0.563 ± 0.092 μM, P<0.0001). Afatinib exposure resulted in abrogation of cell survival, inhibition of HER2/neu autophosphorylation and S6 transcription factor phosphorylation in HER2/neu overexpressing USC and inhibited the growth of HER2-amplified tumour xenografts improving overall survival (P=0.0017). Afatinib may be highly effective against HER2/neu-amplified chemotherapy-resistant USC. The investigation of afatinib in patients harbouring HER2/neu-amplified USC is warranted.

Genetics Consultation Rates Following a Diagnosis of High-Grade Serous Ovarian Carcinoma in the Canadian Province of Ontario.

PubMed

McGee, Jacob; Panabaker, Karen; Leonard, Sean; Ainsworth, Peter; Elit, Laurie; Shariff, Salimah Z

2017-03-01

In 2001, the province of Ontario expanded cancer genetic testing eligibility to include all women with high-grade serous ovarian carcinoma (HGSC) of the ovary, fallopian tube, and peritoneum. The aim of this study was to determine the proportion of women who attended genetics counseling for consideration of BRCA1/2 gene analysis. We also sought to examine if regional differences in consultation rate exist across administrative health regions in the province of Ontario. We identified all women with a pathological diagnosis of HGSC in the province of Ontario between 1997 until 2011. Our primary outcome was the 2-year rate of genetics consultation following a diagnosis of HGSC. We compared consultation rates over time and geographical regions and applied multiple logistic regression to identify predictors of genetics consultation. Of the 5412 women with a diagnosis of HGSC over the study period, 6.6% were seen for genetics consultation within 2 years of diagnosis. Factors predictive of genetics consultation included history of breast cancer (odds ratio [OR], 3.56; 95% confidence interval [CI], 1.87-6.78), era of diagnosis (2009-2011 vs 1997-2000; OR, 10.59; 95% CI, 5.02-22.33), and younger age at diagnosis (OR, 0.95; 95% CI, 0.94-0.97 for each additional year). No regional differences in consultation rate were seen. Despite an increasing rate across eras, a small proportion of women with HGSC undergo genetics consultation. Efforts are required to increase cancer genetics consultation in patients with HGSC in the province of Ontario.

Olaparib and Cediranib Maleate in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

ClinicalTrials.gov

2018-06-18

Deleterious BRCA1 Gene Mutation; Deleterious BRCA2 Gene Mutation; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; High Grade Ovarian Serous Adenocarcinoma; Ovarian Endometrioid Tumor; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

Profile of differentially expressed miRNAs in high-grade serous carcinoma and clear cell ovarian carcinoma, and the expression of miR-510 in ovarian carcinoma.

PubMed

Zhang, Xinchen; Guo, Gordon; Wang, Guang; Zhao, Jinyao; Wang, Bo; Yu, Xiaotang; Ding, Yanfang

2015-12-01

Improved insight into the molecular and genetic profile of different types of epithelial ovarian cancer (EOC) is required for understanding the carcinogenesis of EOC and may potentially be exploited by future targeted therapies. The aim of the present study was to identify a unique microRNA (miRNA) patterns and key miRNAs, which may assist in predicting progression and prognosis in high‑grade serous carcinoma (HGSC) and clear cell carcinoma (CCC). To identify unique miRNA patterns associated with HGSC and CCC, a miRNA microarray was performed using Chinese tumor bank specimens of patients with HGSC or CCC in a retrospective analysis. The expression levels of four deregulated miRNAs were further validated using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) in an external cohort of 42 cases of HGSC and 36 cases of CCC. Kaplan‑Meier analysis was performed to analyze the correlation between the expression levels of the four miRNAs and patient prognosis. Among these validated miRNAs, miR‑510 was further examined in another cohort of normal ovarian tissues, as well as the HGSC, low‑grade serous carcinoma (LGSC) and CCC specimens using RT‑qPCR and in situ hybridization. The results revealed that, of the 768 miRNAs analyzed in the microarray, 33 and 50 miRNAs were significantly upregulated and downregulated, respectively, with at least a 2‑fold difference in HGSC, compared with CCC. The quantitative analysis demonstrated that miR‑510 and miR‑129‑3p were significantly downregulated, and that miR‑483‑5p and miR‑miR‑449a were significantly upregulated in CCC, compared with HGSC (P<0.05), which was consistent with the microarray results. Kaplan‑Meier analysis revealed low expression levels of miR‑510 and low expression levels of miR‑129‑3p, advanced International Federation of Gynecology and Obstetrics (FIGO) stage, lymphatic metastasis and that HGSC was significantly associated with the poorer overall

Profile of differentially expressed miRNAs in high-grade serous carcinoma and clear cell ovarian carcinoma, and the expression of miR-510 in ovarian carcinoma

PubMed Central

ZHANG, XINCHEN; GUO, GORDON; WANG, GUANG; ZHAO, JINYAO; WANG, BO; YU, XIAOTANG; DING, YANFANG

2015-01-01

Improved insight into the molecular and genetic profile of different types of epithelial ovarian cancer (EOC) is required for understanding the carcinogenesis of EOC and may potentially be exploited by future targeted therapies. The aim of the present study was to identify a unique microRNA (miRNA) patterns and key miRNAs, which may assist in predicting progression and prognosis in high-grade serous carcinoma (HGSC) and clear cell carcinoma (CCC). To identify unique miRNA patterns associated with HGSC and CCC, a miRNA microarray was performed using Chinese tumor bank specimens of patients with HGSC or CCC in a retrospective analysis. The expression levels of four deregulated miRNAs were further validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in an external cohort of 42 cases of HGSC and 36 cases of CCC. Kaplan-Meier analysis was performed to analyze the correlation between the expression levels of the four miRNAs and patient prognosis. Among these validated miRNAs, miR-510 was further examined in another cohort of normal ovarian tissues, as well as the HGSC, low-grade serous carcinoma (LGSC) and CCC specimens using RT-qPCR and in situ hybridization. The results revealed that, of the 768 miRNAs analyzed in the microarray, 33 and 50 miRNAs were significantly upregulated and downregulated, respectively, with at least a 2-fold difference in HGSC, compared with CCC. The quantitative analysis demonstrated that miR-510 and miR-129-3p were significantly downregulated, and that miR-483-5p and miR-miR-449a were significantly upregulated in CCC, compared with HGSC (P<0.05), which was consistent with the microarray results. Kaplan-Meier analysis revealed low expression levels of miR-510 and low expression levels of miR-129-3p, advanced International Federation of Gynecology and Obstetrics (FIGO) stage, lymphatic metastasis and that HGSC was significantly associated with the poorer overall survival rates (P<0.05). The expression of miR-510

Combined image and genomic analysis of high-grade serous ovarian cancer reveals PTEN loss as a common driver event and prognostic classifier.

PubMed

Martins, Filipe C; Santiago, Ines de; Trinh, Anne; Xian, Jian; Guo, Anne; Sayal, Karen; Jimenez-Linan, Mercedes; Deen, Suha; Driver, Kristy; Mack, Marie; Aslop, Jennifer; Pharoah, Paul D; Markowetz, Florian; Brenton, James D

2014-12-17

TP53 and BRCA1/2 mutations are the main drivers in high-grade serous ovarian carcinoma (HGSOC). We hypothesise that combining tissue phenotypes from image analysis of tumour sections with genomic profiles could reveal other significant driver events. Automatic estimates of stromal content combined with genomic analysis of TCGA HGSOC tumours show that stroma strongly biases estimates of PTEN expression. Tumour-specific PTEN expression was tested in two independent cohorts using tissue microarrays containing 521 cases of HGSOC. PTEN loss or downregulation occurred in 77% of the first cohort by immunofluorescence and 52% of the validation group by immunohistochemistry, and is associated with worse survival in a multivariate Cox-regression model adjusted for study site, age, stage and grade. Reanalysis of TCGA data shows that hemizygous loss of PTEN is common (36%) and expression of PTEN and expression of androgen receptor are positively associated. Low androgen receptor expression was associated with reduced survival in data from TCGA and immunohistochemical analysis of the first cohort. PTEN loss is a common event in HGSOC and defines a subgroup with significantly worse prognosis, suggesting the rational use of drugs to target PI3K and androgen receptor pathways for HGSOC. This work shows that integrative approaches combining tissue phenotypes from images with genomic analysis can resolve confounding effects of tissue heterogeneity and should be used to identify new drivers in other cancers.

Efficacy and Safety of Ranibizumab 0.5 mg for the Treatment of Macular Edema Resulting from Uncommon Causes: Twelve-Month Findings from PROMETHEUS.

PubMed

Staurenghi, Giovanni; Lai, Timothy Y Y; Mitchell, Paul; Wolf, Sebastian; Wenzel, Andreas; Li, Jun; Bhaumik, Amitabha; Hykin, Philip G

2018-06-01

To evaluate the efficacy and safety of ranibizumab 0.5 mg in adult patients with macular edema (ME) resulting from any cause other than diabetes, retinal vein occlusion, or neovascular age-related macular degeneration. A phase 3, 12-month, double-masked, randomized, sham-controlled, multicenter study. One hundred seventy-eight eligible patients aged ≥18 years. Patients were randomized 2:1 to receive either ranibizumab 0.5 mg (n = 118) or sham (n = 60) at baseline and month 1. From month 2, patients in both arms received open-label individualized ranibizumab treatment based on disease activity. A preplanned subgroup analysis was conducted on the primary end point on 5 predefined baseline ME etiologies (inflammatory/post-uveitis, pseudophakic or aphakic, central serous chorioretinopathy, idiopathic, and miscellaneous). Changes in best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study letters) from baseline to month 2 (primary end point) and month 12 and safety over 12 months. Overall, 156 patients (87.6%) completed the study. The baseline characteristics were well balanced between the treatment arms. Overall, ranibizumab showed superior efficacy versus sham from baseline to month 2 (least squares mean BCVA, +5.7 letters vs. +2.9 letters; 1-sided P = 0.0111), that is, a treatment effect (TE) of +2.8 letters. The mean BCVA gain from baseline to month 12 was 9.6 letters with ranibizumab. The TE at month 2 was variable in the 5 predefined etiology subgroups, ranging from >5-letter gain to 0.5-letter loss. The safety findings were consistent with the well-established safety profile of ranibizumab. The primary end point was met and ranibizumab showed superiority in BCVA gain over sham in treating ME due to uncommon causes, with a TE of +2.8 letters versus sham at month 2. At month 12, the mean BCVA gain was high (9.6 letters) in the ranibizumab arm; however, the TE was observed to be variable across the different etiology subgroups

The role of the otorhinolaryngologist in the management of central skull base osteomyelitis.

PubMed

Cavel, Oren; Fliss, Dan M; Segev, Yoram; Zik, Daniel; Khafif, Avi; Landsberg, Roee

2007-01-01

Skull base osteomyelitis (SBO) typically evolves as a complication of external otitis in diabetic patients and involves the temporal bone. Central SBO (CSBO) mainly involves the sphenoid or occipital bones without coexisting external otitis. We characterized a group of patients with CSBO. The endoscopic nasopharyngeal and clival biopsy technique is described. Medical records of patients diagnosed as having SBO were retrospectively analyzed (from 2001 to 2006). Patients' symptoms and signs, laboratory findings, imaging characteristics, endoscopic clival and periclival histopathology results, treatment, and outcome were retrieved. Of 20 patients with SBO, 6 patients without external otitis were studied (age range, 54-76 years; 5 men; mean follow-up, 21 months). All patients suffered from unilateral headache, three of six patients had serous otitis media (SOM), three of six patients had cranial nerve (CN) palsies, and five of six patients had elevated acute-phase reactants. Computed tomography (CT) findings were clival cortical bone erosion and adjacent soft tissue swelling. Magnetic resonance (MR) findings were texture changes and enhancement of the involved bones and soft tissues. Biopsy specimens revealed chronic inflammation. All six patients were treated with antibiotics for 3-6 months. Headache disappeared in five of six patients, SOM resolved in two of three patients, and CN palsies partially recovered in two of three patients. Imaging findings improved in five of six patients. CSBO may mimic malignancy and represents a diagnostic challenge. Typical clinical picture and imaging findings together with a positive response to ciprofloxacin may suffice to establish the diagnosis and obviate the need for biopsies. When in doubt, nasopharyngeal and clival biopsies are performed to rule out malignancy.

TP53 Mutation Status of Tubo-ovarian and Peritoneal High-grade Serous Carcinoma with a Wild-type p53 Immunostaining Pattern.

PubMed

Na, Kiyong; Sung, Ji-Youn; Kim, Hyun-Soo

2017-12-01

Diffuse and strong nuclear p53 immunoreactivity and a complete lack of p53 expression are regarded as indicative of missense and nonsense mutations, respectively, of the TP53 gene. Tubo-ovarian and peritoneal high-grade serous carcinoma (HGSC) is characterized by aberrant p53 expression induced by a TP53 mutation. However, our experience with some HGSC cases with a wild-type p53 immunostaining pattern led us to comprehensively review previous cases and investigate the TP53 mutational status of the exceptional cases. We analyzed the immunophenotype of 153 cases of HGSC and performed TP53 gene sequencing analysis in those with a wild-type p53 immunostaining pattern. Immunostaining revealed that 109 (71.3%) cases displayed diffuse and strong p53 expression (missense mutation pattern), while 39 (25.5%) had no p53 expression (nonsense mutation pattern). The remaining five cases of HGSC showed a wild-type p53 immunostaining pattern. Direct sequencing analysis revealed that three of these cases harbored nonsense TP53 mutations and two had novel splice site deletions. TP53 mutation is almost invariably present in HGSC, and p53 immunostaining can be used as a surrogate marker of TP53 mutation. In cases with a wild-type p53 immunostaining pattern, direct sequencing for TP53 mutational status can be helpful to confirm the presence of a TP53 mutation. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

[Endometrial carcinomas and precursor lesions--new aspects].

PubMed

Schmidt, D

2009-07-01

Endometrial carcinomas can be separated into two groups which are designated as type I and type II carcinomas today. Both groups of tumors are clearly different with regard to conventional light microscopy, immunohistochemistry, molecular pathology and clinical features. Only type I carcinomas are associated with hyperestrogenism. The group of type I carcinomas consists of endometrioid carcinoma and its variants, and mucinous carcinoma. The prototypes of type II carcinomas are serous and clear cell carcinoma. Not all carcinomas, however, can be assigned to one of the two groups, because there are hybrid tumors and mixed carcinomas, e.g. endometrioid carcinoma with a serous component. The precursor lesions of the endometrioid carcinoma and the serous carcinoma are well characterized morphologically and by molecular pathology. Atypical hyperplasia is the precursor lesion of endometrioid carcinoma, whereas endometrial intraepithelial carcinoma (EIC) is the precursor lesion of serous carcinoma. No precursor lesion has as yet been identified for clear cell carcinoma. Immunohistochemical markers for endometrial carcinoma are CK7 and vimentin, for serous carcinoma markers are p53 and p16. Correct typing is of essential prognostic necessity in endometrial carcinoma. Of utmost importance is the detection of a serous component, because serous carcinoma leads to early tumor spread with the necessity of radical surgery, chemotherapy and radiotherapy.

Pembrolizumab, Bevacizumab, and Cyclophosphamide in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2018-05-03

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Olaparib and Onalespib in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple-Negative Breast Cancer

ClinicalTrials.gov

2018-05-18

Estrogen Receptor Negative; HER2/Neu Negative; High Grade Fallopian Tube Serous Adenocarcinoma; High Grade Ovarian Serous Adenocarcinoma; Metastatic Malignant Solid Neoplasm; Primary Peritoneal High Grade Serous Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Triple-Negative Breast Carcinoma; Unresectable Solid Neoplasm

High-grade endometrial carcinoma: serous and grade 3 endometrioid carcinomas have different immunophenotypes and outcomes.

PubMed

Alkushi, Abdulmohsen; Köbel, Martin; Kalloger, Steve E; Gilks, C Blake

2010-07-01

High-grade endometrial carcinomas are a heterogeneous group of tumors and include grade 3 endometrioid (EC-3), serous (SC), and clear cell carcinomas (CCC). There are conflicting data about the prognosis of these subtypes of high-grade endometrial carcinoma; this may be a result of lack of reproducibility in classifying tumor cell type. The purpose of this study was to examine differences in immunophenotype and outcome in a series of high-grade endometrial carcinomas, focusing on the comparison of EC-3 versus SC. We selected 180 endometrial carcinomas of SC, EC, or CCC type. No mixed carcinomas were included in the study. We chose the following immunohistochemical markers, estrogen receptor (ER), insulin-like growth factor 2 mRNA-binding protein 3 (IMP3), p16, p53, progesterone receptor (PR), and phosphatase and tensin homolog (PTEN) as being significantly differentially expressed in endometrial carcinoma subtypes. The tumors were stratified into 4 groups on the basis of their cell type and grade: EC grade 1 or 2, EC-3, SC, and CCC. Univariate survival analysis revealed significant differences in outcome between the 4 groups (P<0.0001), with significantly longer disease-specific survival for grade 1 or 2 EC versus EC-3 (P=0.0001), and EC-3 versus SC (P=0.0003). p16, PTEN, and IMP3 expression was observed more frequently in SC compared with EC-3 (P<0.0001, P=0.021, and P=0.031, respectively). These 3 markers showed the highest sensitivity and specificity in distinguishing between EC-3 and SC, with receiver operating characteristics area under the curve of 0.85, 0.69, and 0.71, respectively. ER and p53 approached but did not reach significance for differential expression in EC-3 versus SC (P=0.055 and P=0.068, respectively). A combination of p16 and PTEN predicts EC-3 versus SC with a sensitivity of 90.0% and specificity of 96.8%. p16 and PTEN can aid in distinguishing between EC-3 and SC of the endometrium, and are superior to ER, PR, and p53 for this purpose. EC-3

Integrated Analyses of microRNAs Demonstrate Their Widespread Influence on Gene Expression in High-Grade Serous Ovarian Carcinoma

PubMed Central

Levine, Douglas A.; Mankoo, Parminder; Schultz, Nikolaus; Du, Ying; Zhang, Yiqun; Larsson, Erik; Sheridan, Robert; Xiao, Weimin; Spellman, Paul T.; Getz, Gad; Wheeler, David A.; Perou, Charles M.; Gibbs, Richard A.; Sander, Chris; Hayes, D. Neil; Gunaratne, Preethi H.

2012-01-01

Background The Cancer Genome Atlas (TCGA) Network recently comprehensively catalogued the molecular aberrations in 487 high-grade serous ovarian cancers, with much remaining to be elucidated regarding the microRNAs (miRNAs). Here, using TCGA ovarian data, we surveyed the miRNAs, in the context of their predicted gene targets. Methods and Results Integration of miRNA and gene patterns yielded evidence that proximal pairs of miRNAs are processed from polycistronic primary transcripts, and that intronic miRNAs and their host gene mRNAs derive from common transcripts. Patterns of miRNA expression revealed multiple tumor subtypes and a set of 34 miRNAs predictive of overall patient survival. In a global analysis, miRNA:mRNA pairs anti-correlated in expression across tumors showed a higher frequency of in silico predicted target sites in the mRNA 3′-untranslated region (with less frequency observed for coding sequence and 5′-untranslated regions). The miR-29 family and predicted target genes were among the most strongly anti-correlated miRNA:mRNA pairs; over-expression of miR-29a in vitro repressed several anti-correlated genes (including DNMT3A and DNMT3B) and substantially decreased ovarian cancer cell viability. Conclusions This study establishes miRNAs as having a widespread impact on gene expression programs in ovarian cancer, further strengthening our understanding of miRNA biology as it applies to human cancer. As with gene transcripts, miRNAs exhibit high diversity reflecting the genomic heterogeneity within a clinically homogeneous disease population. Putative miRNA:mRNA interactions, as identified using integrative analysis, can be validated. TCGA data are a valuable resource for the identification of novel tumor suppressive miRNAs in ovarian as well as other cancers. PMID:22479643

Integrated analyses of microRNAs demonstrate their widespread influence on gene expression in high-grade serous ovarian carcinoma.

PubMed

Creighton, Chad J; Hernandez-Herrera, Anadulce; Jacobsen, Anders; Levine, Douglas A; Mankoo, Parminder; Schultz, Nikolaus; Du, Ying; Zhang, Yiqun; Larsson, Erik; Sheridan, Robert; Xiao, Weimin; Spellman, Paul T; Getz, Gad; Wheeler, David A; Perou, Charles M; Gibbs, Richard A; Sander, Chris; Hayes, D Neil; Gunaratne, Preethi H

2012-01-01

The Cancer Genome Atlas (TCGA) Network recently comprehensively catalogued the molecular aberrations in 487 high-grade serous ovarian cancers, with much remaining to be elucidated regarding the microRNAs (miRNAs). Here, using TCGA ovarian data, we surveyed the miRNAs, in the context of their predicted gene targets. Integration of miRNA and gene patterns yielded evidence that proximal pairs of miRNAs are processed from polycistronic primary transcripts, and that intronic miRNAs and their host gene mRNAs derive from common transcripts. Patterns of miRNA expression revealed multiple tumor subtypes and a set of 34 miRNAs predictive of overall patient survival. In a global analysis, miRNA:mRNA pairs anti-correlated in expression across tumors showed a higher frequency of in silico predicted target sites in the mRNA 3'-untranslated region (with less frequency observed for coding sequence and 5'-untranslated regions). The miR-29 family and predicted target genes were among the most strongly anti-correlated miRNA:mRNA pairs; over-expression of miR-29a in vitro repressed several anti-correlated genes (including DNMT3A and DNMT3B) and substantially decreased ovarian cancer cell viability. This study establishes miRNAs as having a widespread impact on gene expression programs in ovarian cancer, further strengthening our understanding of miRNA biology as it applies to human cancer. As with gene transcripts, miRNAs exhibit high diversity reflecting the genomic heterogeneity within a clinically homogeneous disease population. Putative miRNA:mRNA interactions, as identified using integrative analysis, can be validated. TCGA data are a valuable resource for the identification of novel tumor suppressive miRNAs in ovarian as well as other cancers.

Modeling the Dynamics of High-Grade Serous Ovarian Cancer Progression for Transvaginal Ultrasound-Based Screening and Early Detection

PubMed Central

Lee, Jung-Min; Levy, Doron

2016-01-01

High-grade serous ovarian cancer (HGSOC) represents the majority of ovarian cancers and accounts for the largest proportion of deaths from the disease. A timely detection of low volume HGSOC should be the goal of any screening studies. However, numerous transvaginal ultrasound (TVU) detection-based population studies aimed at detecting low-volume disease have not yielded reduced mortality rates. A quantitative invalidation of TVU as an effective HGSOC screening strategy is a necessary next step. Herein, we propose a mathematical model for a quantitative explanation on the reported failure of TVU-based screening to improve HGSOC low-volume detectability and overall survival.We develop a novel in silico mathematical assessment of the efficacy of a unimodal TVU monitoring regimen as a strategy aimed at detecting low-volume HGSOC in cancer-positive cases, defined as cases for which the inception of the first malignant cell has already occurred. Our findings show that the median window of opportunity interval length for TVU monitoring and HGSOC detection is approximately 1.76 years. This does not translate into reduced mortality levels or improved detection accuracy in an in silico cohort across multiple TVU monitoring frequencies or detection sensitivities. We demonstrate that even a semiannual, unimodal TVU monitoring protocol is expected to miss detectable HGSOC. Lastly, we find that circa 50% of the simulated HGSOC growth curves never reach the baseline detectability threshold, and that on average, 5–7 infrequent, rate-limiting stochastic changes in the growth parameters are associated with reaching HGSOC detectability and mortality thresholds respectively. Focusing on a malignancy poorly studied in the mathematical oncology community, our model captures the dynamic, temporal evolution of HGSOC progression. Our mathematical model is consistent with recent case reports and prospective TVU screening population studies, and provides support to the empirical

Polymorphisms in Stromal Genes and Susceptibility to Serous Epithelial Ovarian Cancer: A Report from the Ovarian Cancer Association Consortium

PubMed Central

Amankwah, Ernest K.; Wang, Qinggang; Schildkraut, Joellen M.; Tsai, Ya-Yu; Ramus, Susan J.; Fridley, Brooke L.; Beesley, Jonathan; Johnatty, Sharon E.; Webb, Penelope M.; Chenevix-Trench, Georgia; Dale, Laura C.; Lambrechts, Diether; Amant, Frederic; Despierre, Evelyn; Vergote, Ignace; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Menon, Usha; Chang-Claude, Jenny; Wang-Gohrke, Shan; Anton-Culver, Hoda; Ziogas, Argyrios; Dörk, Thilo; Dürst, Matthias; Antonenkova, Natalia; Bogdanova, Natalia; Brown, Robert; Flanagan, James M.; Kaye, Stanley B.; Paul, James; Bützow, Ralf; Nevanlinna, Heli; Campbell, Ian; Eccles, Diana M.; Karlan, Beth Y.; Gross, Jenny; Walsh, Christine; Pharoah, Paul D. P.; Song, Honglin; Krüger Kjær, Susanne; Høgdall, Estrid; Høgdall, Claus; Lundvall, Lene; Nedergaard, Lotte; Kiemeney, Lambertus A. L. M.; Massuger, Leon F. A. G.; van Altena, Anne M.; Vermeulen, Sita H. H. M.; Le, Nhu D.; Brooks-Wilson, Angela; Cook, Linda S.; Phelan, Catherine M.; Cunningham, Julie M.; Vachon, Celine M.; Vierkant, Robert A.; Iversen, Edwin S.; Berchuck, Andrew; Goode, Ellen L.; Sellers, Thomas A.; Kelemen, Linda E.

2011-01-01

Alterations in stromal tissue components can inhibit or promote epithelial tumorigenesis. Decorin (DCN) and lumican (LUM) show reduced stromal expression in serous epithelial ovarian cancer (sEOC). We hypothesized that common variants in these genes associate with risk. Associations with sEOC among Caucasians were estimated with odds ratios (OR) among 397 cases and 920 controls in two U.S.-based studies (discovery set), 436 cases and 1,098 controls in Australia (replication set 1) and a consortium of 15 studies comprising 1,668 cases and 4,249 controls (replication set 2). The discovery set and replication set 1 (833 cases and 2,013 controls) showed statistically homogeneous (Pheterogeneity≥0.48) decreased risks of sEOC at four variants: DCN rs3138165, rs13312816 and rs516115, and LUM rs17018765 (OR = 0.6 to 0.9; Ptrend = 0.001 to 0.03). Results from replication set 2 were statistically homogeneous (Pheterogeneity≥0.13) and associated with increased risks at DCN rs3138165 and rs13312816, and LUM rs17018765: all ORs = 1.2; Ptrend≤0.02. The ORs at the four variants were statistically heterogeneous across all 18 studies (Pheterogeneity≤0.03), which precluded combining. In post-hoc analyses, interactions were observed between each variant and recruitment period (Pinteraction≤0.003), age at diagnosis (Pinteraction = 0.04), and year of diagnosis (Pinteraction = 0.05) in the five studies with available information (1,044 cases, 2,469 controls). We conclude that variants in DCN and LUM are not directly associated with sEOC, and that confirmation of possible effect modification of the variants by non-genetic factors is required. PMID:21637745

The Role of Vaginal Brachytherapy in the Treatment of Surgical Stage I Papillary Serous or Clear Cell Endometrial Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barney, Brandon M., E-mail: barney.brandon@mayo.edu; Petersen, Ivy A.; Mariani, Andrea

2013-01-01

Objectives: The optimal adjuvant therapy for International Federation of Gynecology and Obstetrics (FIGO) stage I papillary serous (UPSC) or clear cell (CC) endometrial cancer is unknown. We report on the largest single-institution experience using adjuvant high-dose-rate vaginal brachytherapy (VBT) for surgically staged women with FIGO stage I UPSC or CC endometrial cancer. Methods and Materials: From 1998-2011, 103 women with FIGO 2009 stage I UPSC (n=74), CC (n=21), or mixed UPSC/CC (n=8) endometrial cancer underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy followed by adjuvant high-dose-rate VBT. Nearly all patients (n=98, 95%) also underwent extended lymph node dissection of pelvic andmore » paraortic lymph nodes. All VBT was performed with a vaginal cylinder, treating to a dose of 2100 cGy in 3 fractions. Thirty-five patients (34%) also received adjuvant chemotherapy. Results: At a median follow-up time of 36 months (range, 1-146 months), 2 patients had experienced vaginal recurrence, and the 5-year Kaplan Meier estimate of vaginal recurrence was 3%. The rates of isolated pelvic recurrence, locoregional recurrence (vaginal + pelvic), and extrapelvic recurrence (including intraabdominal) were similarly low, with 5-year Kaplan-Meier estimates of 4%, 7%, and 10%, respectively. The estimated 5-year overall survival was 84%. On univariate analysis, delivery of chemotherapy did not affect recurrence or survival. Conclusions: VBT is effective at preventing vaginal relapse in women with surgical stage I UPSC or CC endometrial cancer. In this cohort of patients who underwent comprehensive surgical staging, the risk of isolated pelvic or extrapelvic relapse was low, implying that more extensive adjuvant radiation therapy is likely unnecessary.« less

Pegylated Liposomal Doxorubicin Hydrochloride With Atezolizumab and/or Bevacizumab in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2018-06-20

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; High Grade Fallopian Tube Serous Adenocarcinoma; High Grade Ovarian Serous Adenocarcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Primary Peritoneal High Grade Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

The Value of Serum CA125 in the Diagnosis of Borderline Tumors of the Ovary: A Subanalysis of the Prospective Multicenter ROBOT Study.

PubMed

Fotopoulou, Christina; Sehouli, Jalid; Ewald-Riegler, Nina; de Gregorio, Nikolaus; Reuss, Alexander; Richter, Rolf; Mahner, Sven; Kommoss, Friedrich; Schmalfeldt, Barbara; Fehm, Tanja; Hanker, Lars; Wimberger, Pauline; Canzler, Ulrich; Pfisterer, Jacobus; Kommoss, Stefan; Hauptmann, Steffen; du Bois, Andreas

2015-09-01

The value of the serum tumor marker CA125 in borderline tumors of the ovary (BOTs) is not well defined, with unclear benefit in both diagnosis and follow-up. The aim of the present project was to identify the predictive value of CA125 for stage and relapse. CA125 data were extracted from the ROBOT multicenter study of patients with BOT treated between 1998 and 2008 in 24 German centers. While patients' data were retrieved retrospectively from hospital records and clinical tumor registries, follow-up and independent central pathology review were performed prospectively. We identified 127 patients from the ROBOT database fulfilling the eligibility criterion of available CA125 at initial diagnosis. Eighty-three (65.3%) patients had increased CA125 levels (>35 U/L). Of the patients, 85.0% presented with serous and 13.4% with mucinous BOT histology, whereas 29.9% had stage I disease. Fifteen (11.8%) patients experienced a relapse. Multivariate analysis identified raised CA125, young age, and serous histology as independent predictors of peritoneal implants of any type at initial presentation. Raised CA125 at initial diagnosis was, however, not an independent predictor of future relapse. Elevated CA125 seems to be associated with the presence of peritoneal implants of any type at initial diagnosis of serous BOT, but failed to have any independent predictive value on future relapse. Prospective multicenter studies are warranted to evaluate CA125 measurements in the follow-up management of BOT.

Carboplatin, Paclitaxel and Gemcitabine Hydrochloride With or Without Bevacizumab After Surgery in Treating Patients With Recurrent Ovarian, Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

ClinicalTrials.gov

2018-06-06

Clear Cell Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Mucinous Adenocarcinoma; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinofibroma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Significantly greater expression of ER, PR, and ECAD in advanced-stage low-grade ovarian serous carcinoma as revealed by immunohistochemical analysis.

PubMed

Wong, Kwong-Kwok; Lu, Karen H; Malpica, Anais; Bodurka, Diane C; Shvartsman, Hyun S; Schmandt, Rosemarie E; Thornton, Angela D; Deavers, Michael T; Silva, Elvio G; Gershenson, David M

2007-10-01

A 2-tier system that classifies ovarian serous carcinoma (OSC) as low grade or high grade is gaining acceptance. Women with low-grade OSC generally have higher 5-year survival rates than do women with high-grade OSC. We examined the expression of various markers to further understand the molecular differences between low-grade and high-grade OSCs: the potential therapeutic targets or prognostic markers Her-2/neu, estrogen receptor, and progesterone receptor (PR); the metastasis-associated markers cyclin D1 (BCL1), E-cadherin, matrix metalloproteinase (MMP) 2, and MMP-9; and the cell proliferation-associated markers BCL1, Ki-67 antigen (Ki-67), and p53. For this immunohistochemical analysis, we used paraffin-embedded specimens from 47 patients with advanced-stage low-grade OSC and from 49 patients with advanced-stage high-grade OSC. Our results showed that low-grade tumors expressed significantly higher levels of estrogen receptor, PR, and E-cadherin than did high-grade tumors, suggesting the involvement of gonadal steroid hormones, especially in the pathogenesis of low-grade OSC; the PR positivity was also observed in the stromal component of these low-grade tumors. On the other hand, high-grade tumors trended toward increased expression of MMP-9, BCL1, p53, and Ki-67, and robust MMP-9 positivity was observed in the stromal component of these high-grade tumors. These differences may lead to the development of different therapeutic strategies for women with either the low-grade or the high-grade form of OSC.

The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer.

PubMed

Suri, Anuj; Sheng, Xiugui; Schuler, Kevin M; Zhong, Yan; Han, Xiaoyun; Jones, Hannah M; Gehrig, Paola A; Zhou, Chunxiao; Bae-Jump, Victoria L

2016-06-28

Our objective was to evaluate the effect of the COX-2 inhibitor, celecoxib, on (1) proliferation and apoptosis in human ovarian cancer cell lines and primary cultures of ovarian cancer cells, and (2) inhibition of tumor growth in a genetically engineered mouse model of serous ovarian cancer under obese and non-obese conditions. Celecoxib inhibited cell proliferation in three ovarian cancer cell lines and five primary cultures of human ovarian cancer after 72 hours of exposure. Treatment with celecoxib resulted in G1 cell cycle arrest, induction of apoptosis, inhibition of cellular adhesion and invasion and reduction of expression of hTERT mRNA and COX-2 protein in all of the ovarian cancer cell lines. In the KpB mice fed a high fat diet (obese) and treated with celecoxib, tumor weight decreased by 66% when compared with control animals. Among KpB mice fed a low fat diet (non-obese), tumor weight decreased by 46% after treatment with celecoxib. In the ovarian tumors from obese and non-obese KpB mice, treatment with celecoxib as compared to control resulted in decreased proliferation, increased apoptosis and reduced COX-2 and MMP9 protein expression, as assessed by immunohistochemistry. Celecoxib strongly decreased the serum level of VEGF and blood vessel density in the tumors from the KpB ovarian cancer mouse model under obese and non-obese conditions. This work suggests that celecoxib may be a novel chemotherapeutic agent for ovarian cancer prevention and treatment and be potentially beneficial in both obese and non-obese women.

The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer

PubMed Central

Suri, Anuj; Sheng, Xiugui; Schuler, Kevin M.; Zhong, Yan; Han, Xiaoyun; Jones, Hannah M.; Gehrig, Paola A.; Zhou, Chunxiao; Bae-Jump, Victoria L.

2016-01-01

Our objective was to evaluate the effect of the COX-2 inhibitor, celecoxib, on (1) proliferation and apoptosis in human ovarian cancer cell lines and primary cultures of ovarian cancer cells, and (2) inhibition of tumor growth in a genetically engineered mouse model of serous ovarian cancer under obese and non-obese conditions. Celecoxib inhibited cell proliferation in three ovarian cancer cell lines and five primary cultures of human ovarian cancer after 72 hours of exposure. Treatment with celecoxib resulted in G1 cell cycle arrest, induction of apoptosis, inhibition of cellular adhesion and invasion and reduction of expression of hTERT mRNA and COX-2 protein in all of the ovarian cancer cell lines. In the KpB mice fed a high fat diet (obese) and treated with celecoxib, tumor weight decreased by 66% when compared with control animals. Among KpB mice fed a low fat diet (non-obese), tumor weight decreased by 46% after treatment with celecoxib. In the ovarian tumors from obese and non-obese KpB mice, treatment with celecoxib as compared to control resulted in decreased proliferation, increased apoptosis and reduced COX-2 and MMP9 protein expression, as assessed by immunohistochemistry. Celecoxib strongly decreased the serum level of VEGF and blood vessel density in the tumors from the KpB ovarian cancer mouse model under obese and non-obese conditions. This work suggests that celecoxib may be a novel chemotherapeutic agent for ovarian cancer prevention and treatment and be potentially beneficial in both obese and non-obese women. PMID:27074576

Pooled clustering of high-grade serous ovarian cancer gene expression leads to novel consensus subtypes associated with survival and surgical outcomes

PubMed Central

Wang, Chen; Armasu, Sebastian M.; Kalli, Kimberly R.; Maurer, Matthew J.; Heinzen, Ethan P.; Keeney, Gary L.; Cliby, William A.; Oberg, Ann L.; Kaufmann, Scott H.; Goode, Ellen L.

2017-01-01

Purpose Here we assess whether molecular subtyping identifies biological features of tumors that correlate with survival and surgical outcomes of high-grade serous ovarian cancer (HGSOC). Experimental Design Consensus clustering of pooled mRNA expression data from over 2,000 HGSOC cases was used to define molecular subtypes of HGSOCs. This de novo classification scheme was then applied to 381 Mayo Clinic HGSOC patients with detailed survival and surgical outcome information. Results Five molecular subtypes of HGSOC were identified. In the pooled dataset, three subtypes were largely concordant with prior studies describing proliferative, mesenchymal, and immunoreactive tumors (concordance > 70%), and the group of tumors previously described as differentiated type was segregated into two new types, one of which (anti-mesenchymal) had down-regulation of genes that were typically upregulated in the mesenchymal subtype. Molecular subtypes were significantly associated with overall survival (p<0.001) and with rate of optimal surgical debulking (≤1 cm, p=1.9E-4) in the pooled dataset. Among stage III-C or IV Mayo Clinic patients, molecular subtypes were also significantly associated with overall survival (p=0.001), as well as rate of complete surgical debulking (no residual disease; 16% in mesenchymal tumors comparing to >28% in other subtypes; p=0.02). Conclusions HGSOC tumors may be categorized into five molecular subtypes that associate with overall survival and the extent of residual disease following debulking surgery. Because mesenchymal tumors may have features that were associated with less favorable surgical outcome, molecular subtyping may have future utility in guiding neoadjuvant treatment decisions for women with HGSOC. PMID:28280090

Gene Expression Profiles in Stage I Uterine Serous Carcinoma in Comparison to Grade 3 and Grade 1 Stage I Endometrioid Adenocarcinoma

PubMed Central

Mhawech-Fauceglia, Paulette; Wang, Dan; Kesterson, Joshua; Syriac, Susanna; Clark, Kimberly; Frederick, Peter J.; Lele, Shashikant; Liu, Song

2011-01-01

Background Endometrial cancer is the most common gynecologic malignancy in the developed countries. Clinical studies have shown that early stage uterine serous carcinoma (USC) has outcomes similar to early stage high grade endometrioid adenocarcinoma (EAC-G3) than to early stage low grade endometrioid adenocarcinoma (EAC-G1). However, little is known about the origin of these different clinical outcomes. This study applied the whole genome expression profiling to explore the expression difference of stage I USC (n = 11) relative to stage I EAC-G3 (n = 11) and stage I EAC-G1 (n = 11), respectively. Methodology/Principal Finding We found that the expression difference between USC and EAC-G3, as measured by the number of differentially expressed genes (DEGs), is consistently less than that found between USC and EAC-G1. Pathway enrichment analyses suggested that DEGs specific to USC vs. EAC-G3 are enriched for genes involved in signaling transduction, while DEGs specific to USC vs. EAC-G1 are enriched for genes involved in cell cycle. Gene expression differences for selected DEGs are confirmed by quantitative RT-PCR with a high validation rate. Conclusion This data, although preliminary, indicates that stage I USC is genetically similar to stage I EAC-G3 compared to stage I EAC-G1. DEGs identified from this study might provide an insight in to the potential mechanisms that influence the clinical outcome differences between endometrial cancer subtypes. They might also have potential prognostic and therapeutic impacts on patients diagnosed with uterine cancer. PMID:21448288

Gene expression profiles in stage I uterine serous carcinoma in comparison to grade 3 and grade 1 stage I endometrioid adenocarcinoma.

PubMed

Mhawech-Fauceglia, Paulette; Wang, Dan; Kesterson, Joshua; Syriac, Susanna; Clark, Kimberly; Frederick, Peter J; Lele, Shashikant; Liu, Song

2011-03-23

Endometrial cancer is the most common gynecologic malignancy in the developed countries. Clinical studies have shown that early stage uterine serous carcinoma (USC) has outcomes similar to early stage high grade endometrioid adenocarcinoma (EAC-G3) than to early stage low grade endometrioid adenocarcinoma (EAC-G1). However, little is known about the origin of these different clinical outcomes. This study applied the whole genome expression profiling to explore the expression difference of stage I USC (n = 11) relative to stage I EAC-G3 (n = 11) and stage I EAC-G1 (n = 11), respectively. We found that the expression difference between USC and EAC-G3, as measured by the number of differentially expressed genes (DEGs), is consistently less than that found between USC and EAC-G1. Pathway enrichment analyses suggested that DEGs specific to USC vs. EAC-G3 are enriched for genes involved in signaling transduction, while DEGs specific to USC vs. EAC-G1 are enriched for genes involved in cell cycle. Gene expression differences for selected DEGs are confirmed by quantitative RT-PCR with a high validation rate. This data, although preliminary, indicates that stage I USC is genetically similar to stage I EAC-G3 compared to stage I EAC-G1. DEGs identified from this study might provide an insight in to the potential mechanisms that influence the clinical outcome differences between endometrial cancer subtypes. They might also have potential prognostic and therapeutic impacts on patients diagnosed with uterine cancer.

ESR1 methylation in primary tumors and paired circulating tumor DNA of patients with high-grade serous ovarian cancer.

PubMed

Giannopoulou, Lydia; Mastoraki, Sophia; Buderath, Paul; Strati, Areti; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S

2018-05-25

Estrogen receptor, coded by the ESR1 gene, is highly expressed in epithelial ovarian cancer. ESR1 gene is frequently methylated in many types of gynecological malignancies. However, only a few studies attempted to investigate the role of ESR1 methylation and its clinical significance in ovarian cancer so far. The aim of our study was to examine ESR1 methylation status in primary tumors and corresponding circulating tumor DNA of patients with high-grade serous ovarian cancer (HGSC). ESR1 methylation was detected by a highly specific and sensitive real-time methylation-specific PCR assay. Two groups of HGSC samples were analyzed: group A (n = 66 primary tumors) and group B (n = 53 primary tumors and 50 corresponding plasma samples). ESR1 was found methylated in both groups of primary tumors: in 32/66 (48.5%) of group A and in 15/53 (28.3%) of group B. 19/50 (38.0%) corresponding plasma samples of group B were also methylated for ESR1. A significant agreement for ESR1 methylation was observed between primary tumors and paired plasma ctDNA samples (P = 0.004). Interestingly, the presence of ESR1 methylation in primary tumor samples of group B was significantly correlated with a better overall survival (P = 0.027) and progression-free survival (P = 0.041). We report for the first time the presence of ESR1 methylation in plasma ctDNA of patients with HGSC. The agreement between ESR1 methylation in primary tumors and paired ctDNA is statistically significant. Our results indicate a correlation between the presence of ESR1 methylation and a better clinical outcome in HGSC patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Neratinib shows efficacy in the treatment of HER2/neu amplified uterine serous carcinoma in vitro and in vivo.

PubMed

Schwab, Carlton L; English, Diana P; Roque, Dana M; Bellone, Stefania; Lopez, Salvatore; Cocco, Emiliano; Nicoletti, Roberta; Rutherford, Thomas J; Schwartz, Peter E; Santin, Alessandro D

2014-10-01

Uterine serous carcinoma (USC) represents an aggressive variant of endometrial cancer and accounts for a large proportion of deaths annually. HER2/neu amplification is associated with USC in approximately 30-35% of cases. The objective of this study was to determine the sensitivity of a panel of primary USC cell lines to the small tyrosine kinase inhibitor neratinib, an ErbB1 and HER2 inhibitor, both in vitro and in vivo. HER2/neu amplification was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in 24 USC cell lines. Flow cytometry was used to determine the effects of neratinib on cell viability, cell cycle distribution and signaling in vitro. Mice harboring HER2/neu amplified xenografts were treated with neratinib to assess the efficacy of the drug in vivo. HER2/neu amplification was noted in 8/24 primary cell lines. Data regarding the efficacy of neratinib was determined using 4 HER2 amplified cell lines and 4 non-amplified cell lines with similar growth rates. Data revealed that cell lines with HER2/neu amplification were exquisitely more sensitive to neratinib compared to non-amplified cell lines (mean ± SEM IC50: 0.011μM ± 0.0008 vs. 0.312μM ± 0.0456 p<0.0001). Neratinib caused arrest in the G0/G1 phase of the cell cycle and resulted in decreased autophosphorylation of HER2 and activation of S6. Neratinib treated mice harboring xenografts of HER2/neu amplified USC showed delayed tumor growth and improved overall survival compared to vehicle (p=0.0019). Neratinib may be a potential treatment option for patients harboring HER2/neu amplified USC. Clinical trials for this subset of endometrial cancer patients are warranted. Copyright © 2014 Elsevier Inc. All rights reserved.

Monoclonal origin of peritoneal implants and lymph node deposits in serous borderline ovarian tumors (s-BOT) with high intratumoral homogeneity.

PubMed

Horn, Lars-Christian; Höhn, Anne K; Einenkel, Jens; Siebolts, Udo

2014-11-01

Molecular studies have shown that the most prevalent mutations in serous ovarian borderline tumors (s-BOT) are BRAF and/or KRAS alterations. About one third of s-BOT represent peritoneal implants and/or lymph node involvement. These extraovarian deposits may be monoclonal or polyclonal in origin. To test both the hypotheses, mutational analyses using pyrosequencing for BRAF codon 600 and KRAS codon 12/13 and 61 of microdissected tissue was performed in 15 s-BOT and their invasive and noninvasive peritoneal implants. Two to 6 implants from different peritoneal sites were examined in 13 cases. Lymph node deposits were available for the analysis in 3 cases. Six s-BOT showed mutation in exon 2 codon 12 of the KRAS proto-oncogen. Five additional cases showed BRAF p.V600E mutation representing an overall mutation rate of 73.3%. Multiple (2-6) peritoneal implants were analyzed after microdissection in 13 of 15 cases. All showed identical mutational results when compared with the ovarian site of the disease. All lymph node deposits, including those with multiple deposits in different nodes, showed identical results, suggesting high intratumoral mutational homogeneity. The evidence presented in this study and the majority of data reported in the literature support the hypothesis that s-BOT with their peritoneal implants and lymph node deposits show identical mutational status of BRAF and KRAS suggesting a monoclonal rather than a polyclonal disease regarding these both tested genetic loci. In addition, a high intratumoral genetic homogeneity can be suggested. In conclusion, the results of the present study support the monoclonal origin of s-BOT and their peritoneal implants and lymph node deposits.

Quantitative detection of RASSF1A DNA promoter methylation in tumors and serum of patients with serous epithelial ovarian cancer.

PubMed

Bondurant, Amy E; Huang, Zhiqing; Whitaker, Regina S; Simel, Lauren R; Berchuck, Andrew; Murphy, Susan K

2011-12-01

Detection of cell free tumor-specific DNA methylation has been proposed as a potentially useful noninvasive mechanism to detect malignancies, including ovarian cancer, and to monitor response to treatment. However, there are few easily implemented quantitative approaches available for DNA methylation analysis. Our objectives were to develop an absolute quantitative method for detection of DNA methylation using RASSF1A, a known target of promoter methylation in ovarian cancer, and test the ability to detect RASSF1A methylation in tumors and serum specimens of women with ovarian cancer. Bisulfite modified DNAs were subjected to real time PCR using nondiscriminatory PCR primers and a probe with sequence containing a single CpG site, theoretically able to capture the methylation status of that CpG for every allele within a given specimen. Input DNA was normalized to ACTB levels detected simultaneously by assay multiplexing. Methylation levels were established by comparison to results obtained from universally methylated DNA. The assay was able to detect one methylated RASSF1A allele in 100,000 unmethylated alleles. RASSF1A was methylated in 54 of 106 (51%) invasive serous ovarian cancers analyzed and methylation status was concordant in 20/20 matched preoperative serum-tumor pairs. Serial serum specimens taken over the course of treatment for 8 of 9 patients showed fluctuations in RASSF1A methylation concomitant with disease status. This novel assay provides a real-time PCR-based method for absolute quantitation of DNA methylation. Our results support feasibility of monitoring RASSF1A methylation from serum samples taken over the course of treatment from women with ovarian cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

Clear cell carcinomas of the ovary have poorer outcomes compared with serous carcinomas: Results from a single-center Taiwanese study.

PubMed

Ku, Fei-Chun; Wu, Ren-Chin; Yang, Lan-Yan; Tang, Yun-Hsin; Chang, Wei-Yang; Yang, Jung-Erh; Wang, Chun-Chieh; Jung, Shih-Ming; Lin, Cheng-Tao; Chang, Ting-Chang; Chao, Angel; Lai, Chyong-Huey

2018-02-01

To compare the clinical outcomes of Taiwanese patients with ovarian clear cell carcinomas (CCCs) and serous carcinomas (SCs). We retrieved the clinical records of women with epithelial ovarian cancer (Stage I-IV) who received primary surgeries between 2000 and 2013. Cancer-specific survival (CSS), progression-free survival, and survival after recurrence (SAR) of CCC and SC patients were retrospectively compared. Multivariate analysis was used to identify the independent predictors of survival. Of 891 women diagnosed with epithelial ovarian cancer, 169 CCCs and 351 high-grade SCs were analyzed. The 5-year CSS rates of CCC patients were significantly lower than those of SC for both Stage III (22.3% vs. 47.3%, p = 0.001) and Stage IV (0% vs. 24.4%, p = 0.001) disease. In the absence of gross residual malignancies, the 5-year CSS rate was better for CCC (82.3%) than SC (75.2%, p = 0.010). The 5-year SAR rate was significantly lower for CCC than SC (14.3% vs. 24.4%, p = 0.002). Old age and residual malignancies were independent prognostic factors for CSS in the entire cohort of CCC patients. In the subgroup of Stage I CCC, positive cytology was identified as the only adverse prognostic factor for CSS. The clinical outcomes of CCC are generally poorer than SC. Complete cytoreduction to no gross residual disease should be ideally achieved in CCC patients. A greater understanding of the molecular pathogenesis of CCC may lead to tailored therapies, ultimately optimizing outcomes. Copyright © 2017. Published by Elsevier B.V.

Cediranib Maleate and Olaparib or Standard Chemotherapy in Treating Patients With Recurrent Platinum-Resistant or -Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2018-06-15

Deleterious BRCA1 Gene Mutation; Deleterious BRCA2 Gene Mutation; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Elesclomol Sodium and Paclitaxel in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

ClinicalTrials.gov

2017-05-02

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Tumor; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Studying platinum sensitivity and resistance in high-grade serous ovarian cancer: Different models for different questions.

PubMed

Alkema, Nicolette G; Wisman, G Bea A; van der Zee, Ate G J; van Vugt, Marcel A T M; de Jong, Steven

2016-01-01

High-grade serous ovarian cancer (HGSOC) has the highest mortality rate among all gynecological cancers. Patients are generally diagnosed in an advanced stage with the majority of cases displaying platinum resistant relapses. Recent genomic interrogation of large numbers of HGSOC patient samples indicated high complexity in terms of genetic aberrations, intra- and intertumor heterogeneity and underscored their lack of targetable oncogenic mutations. Sub-classifications of HGSOC based on expression profiles, termed 'differentiated', 'immunoreactive', 'mesenchymal' and 'proliferative', were shown to have prognostic value. In addition, in almost half of all HGSOC patients, a deficiency in homologous recombination (HR) was found that potentially can be targeted using PARP inhibitors. Developing precision medicine requires advanced experimental models. In the current review, we discuss experimental HGSOC models in which resistance to platinum therapy and the use of novel therapeutics can be carefully studied. Panels of better-defined primary cell lines need to be established to capture the full spectrum of HGSOC subtypes. Further refinement of cell lines is obtained with a 3-dimensional culture model mimicking the tumor microenvironment. Alternatively, ex vivo ovarian tumor tissue slices are used. For in vivo studies, larger panels of ovarian cancer patient-derived xenografts (PDXs) are being established, encompassing all expression subtypes. Ovarian cancer PDXs grossly retain tumor heterogeneity and clinical response to platinum therapy is preserved. PDXs are currently used in drug screens and as avatars for patient response. The role of the immune system in tumor responses can be assessed using humanized PDXs and immunocompetent genetically engineered mouse models. Dynamic tracking of genetic alterations in PDXs as well as patients during treatment and after relapse is feasible by sequencing circulating cell-free tumor DNA and analyzing circulating tumor cells. We

[Clinical significance and distribution of BRCA genes mutation in sporadic high grade serous ovarian cancer].

PubMed

Liu, W L; Wang, Z Z; Zhao, J Z; Hou, Y Y; Wu, X X; Li, W; Dong, B; Tong, T T; Guo, Y J

2017-01-25

Objective: To investigate the mutations of BRCA genes in sporadic high grade serous ovarian cancer (HGSOC) and study its clinical significance. Methods: Sixty-eight patients between January 2015 and January 2016 from the Affiliated Cancer Hospital of Zhengzhou University were collected who were based on pathological diagnosis of ovarian cancer and had no reported family history, and all patients firstly hospitalized were untreated in other hospitals before. (1) The BRCA genes were detected by next-generation sequencing (NGS) method. (2) The serum tumor markers included carcinoembryonic antigen (CEA), CA(125), CA(199), and human epididymis protein 4 (HE4) were detected by the chemiluminescence methods, and their correlation was analyzed by Pearson linear correlation. Descriptive statistics and comparisons were performed using two-tailed t -tests, Pearson's chi square test, Fisher's exact tests or logistic regression analysis as appropriate to research the clinicopathologic features associated with BRCA mutations, including age, International Federation of Gynecology and Obstetrics (FIGO) stage, platinum-based chemotherapy sensitivity, distant metastases, serum tumor markers (STM) . Results: (1) Fifteen cases (22%, 15/68) BRCA mutations were identified (BRCA1: 11 cases; BRCA2: 4 cases), and four novel mutations were observed. (2) The levels of CEA, CA(199), and HE4 were lower in BRCA mutations compared to that in control group, while no significant differences were found ( P >0.05), but the level of CA(125) was much higher in BRCA mutation group than that in controls ( t =-3.536, P =0.003). Further linear regression analysis found that there was a significant linear correlation between CA(125) and HE4 group ( r =0.494, P <0.01), and the same correlation as CEA and CA(199) group ( r =0.897, P <0.01). (3) Single factor analysis showed that no significant differences were observed in onset age, FIGO stage, distant metastasis, and STM between BRCA(+) and BRCA(-) group

Selumetinib Sulfate in Treating Woman With Recurrent Low-Grade Ovarian Cancer or Peritoneum Cancer

ClinicalTrials.gov

2018-03-30

Borderline Ovarian Epithelial Tumor; Low Grade Ovarian Serous Adenocarcinoma; Primary Peritoneal Carcinoma; Primary Peritoneal Low Grade Serous Adenocarcinoma; Recurrent Borderline Ovarian Surface Epithelial-Stromal Tumor

Metformin Hydrochloride, Carboplatin, and Paclitaxel in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2017-01-24

Ovarian Papillary Serous Carcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer

The long non-coding RNA HOTAIR promotes the proliferation of serous ovarian cancer cells through the regulation of cell cycle arrest and apoptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu, Jun-jun; Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032; Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, 413 Zhaozhou Road, Shanghai 200011

HOX transcript antisense RNA (HOTAIR) is a well-known long non-coding RNA (lncRNA) whose dysregulation correlates with poor prognosis and malignant progression in many forms of cancer. Here, we investigate the expression pattern, clinical significance, and biological function of HOTAIR in serous ovarian cancer (SOC). Clinically, we found that HOTAIR levels were overexpressed in SOC tissues compared with normal controls and that HOTAIR overexpression was correlated with an advanced FIGO stage and a high histological grade. Multivariate analysis revealed that HOTAIR is an independent prognostic factor for predicting overall survival in SOC patients. We demonstrated that HOTAIR silencing inhibited A2780 andmore » OVCA429 SOC cell proliferation in vitro and that the anti-proliferative effects of HOTAIR silencing also occurred in vivo. Further investigation into the mechanisms responsible for the growth inhibitory effects by HOTAIR silencing revealed that its knockdown resulted in the induction of cell cycle arrest and apoptosis through certain cell cycle-related and apoptosis-related proteins. Together, these results highlight a critical role of HOTAIR in SOC cell proliferation and contribute to a better understanding of the importance of dysregulated lncRNAs in SOC progression. - Highlights: • HOTAIR overexpression correlates with an aggressive tumour phenotype and a poor prognosis in SOC. • HOTAIR promotes SOC cell proliferation both in vitro and in vivo. • The proliferative role of HOTAIR is associated with regulation of the cell cycle and apoptosis.« less

Epigenetic Reprogramming Strategies to Reverse Global Loss of 5-Hydroxymethylcytosine, a Prognostic Factor for Poor Survival in High-grade Serous Ovarian Cancer

PubMed Central

Tucker, Douglass W.; Getchell, Christopher R.; McCarthy, Eric T.; Ohman, Anders W.; Sasamoto, Naoko; Xu, Shuyun; Ko, Joo Yeon; Gupta, Mamta; Shafrir, Amy; Medina, Jamie E.; Lee, Jonathan J.; MacDonald, Lauren A.; Malik, Ammara; Hasselblatt, Kathleen T; Li, Wenjing; Zhang, Hong; Kaplan, Samuel J.; Murphy, George F.; Hirsch, Michelle S.; Liu, Joyce F.; Matulonis, Ursula A.; Terry, Kathryn L.; Lian, Christine G.; Dinulescu, Daniela M.

2018-01-01

Purpose A major challenge in platinum-based cancer therapy is the clinical management of chemoresistant tumors, which have a largely unknown pathogenesis at the level of epigenetic regulation. Experimental Design We evaluated the potential of using global loss of 5-hydroxymethylcytosine (5-hmC) levels as a novel diagnostic and prognostic epigenetic marker to better assess platinum-based chemotherapy response and clinical outcome in high-grade serous tumors (HGSOC), the most common and deadliest subtype of ovarian cancer. Furthermore, we identified a targetable pathway to reverse these epigenetic changes, both genetically and pharmacologically. Results This study shows that decreased 5-hmC levels are an epigenetic hallmark for malignancy and tumor progression in HGSOC. In addition, global 5-hmC loss is associated with a decreased response to platinum-based chemotherapy, shorter time to relapse, and poor overall survival in patients newly diagnosed with HGSOC. Interestingly, the rescue of 5-hmC loss restores sensitivity to platinum chemotherapy in vitro and in vivo, decreases the percentage of tumor cells with cancer stem cell markers, and increases overall survival in an aggressive animal model of platinum-resistant disease. Conclusions Consequently, a global analysis of patient 5-hmC levels should be included in future clinical trials, which use pretreatment with epigenetic adjuvants to elevate 5-hmC levels and improve the efficacy of current chemotherapies. Identifying prognostic epigenetic markers and altering chemotherapeutic regimens to incorporate DNMTi pretreatment in tumors with low 5-hmC levels could have important clinical implications for newly diagnosed HGSOC disease. PMID:29263182

Deployable centralizers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grubelich, Mark C.; Su, Jiann-Cherng; Knudsen, Steven D.

2017-02-28

A centralizer assembly is disclosed that allows for the assembly to be deployed in-situ. The centralizer assembly includes flexible members that can be extended into the well bore in situ by the initiation of a gas generating device. The centralizer assembly can support a large load carrying capability compared to a traditional bow spring with little or no installation drag. Additionally, larger displacements can be produced to centralize an extremely deviated casing.

Determination of MEPRS Direct Care Costs for Selected Ambulatory Professional Services and a Comparison to Similar CHAMPUS Care Costs for the United States Army, Health Services Command Hospitals.

DTIC Science & Technology

1991-06-05

103 TOR 5 Costliest Gen SurQerv Diagnoses/ Meade ICD9CM Description CHAMPUS Costs 381.10 Chronic Serous Otitis Media $ 19,655 474.11 Hypertrophy of...Tonsils 6,092 477.9 Allergic Rhinitis, Unspecified 5,739 381.01 Acute Serous Otitis Media 4,729 470. Deviated Nasal Septum 4,550 As previously explained...Description CHAMPUS Costs 381.10 Chronic Serous Otitis Media $ 50,886 474.0 Chronic Tonsillitis 35,158 474.11 Hypertrophy Tonsils 30,741 470

P-MAPA immunotherapy potentiates the effect of cisplatin on serous ovarian carcinoma through targeting TLR4 signaling.

PubMed

de Almeida Chuffa, Luiz Gustavo; de Moura Ferreira, Grazielle; Lupi, Luiz Antonio; da Silva Nunes, Iseu; Fávaro, Wagner José

2018-01-17

Toll-like receptors (TLRs) are transmembrane proteins expressed on the surface of ovarian cancer (OC) and immune cells. Identifying the specific roles of the TLR-mediated signaling pathways in OC cells is important to guide new treatments. Because immunotherapies have emerged as the adjuvant treatment for patients with OC, we investigated the effect of a promising immunotherapeutic strategy based on protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride (P-MAPA) combined with cisplatin (CIS) on the TLR2 and TLR4 signaling pathways via myeloid differentiation factor 88 (MyD88) and TLR-associated activator of interferon (TRIF) in an in vivo model of OC. Tumors were chemically induced by a single injection of 100 μg of 7,12-dimethylbenz(a)anthracene (DMBA) directly under the left ovarian bursa in Fischer 344 rats. After the rats developed serous papillary OC, they were given P-MAPA, CIS or the combination P-MAPA+CIS as therapies. To understand the effects of the treatments, we assessed the tumor size, histopathology, and the TLR2- and TLR4-mediated inflammatory responses. Although CIS therapy was more effective than P-MAPA in reducing the tumor size, P-MAPA immunotherapy significantly increased the expressions of TLR2 and TLR4. More importantly, the combination of P-MAPA with CIS showed a greater survival rate compared to CIS alone, and exhibited a significant reduction in tumor volume compared to P-MAPA alone. The combination therapy also promoted the increase in the levels of the following OC-related proteins: TLR4, MyD88, TRIF, inhibitor of phosphorylated NF-kB alpha (p-IkBα), and nuclear factor kappa B (NF-kB p65) in both cytoplasmic and nuclear sites. While P-MAPA had no apparent effect on tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6, it seems to increase interferon-γ (IFN-γ), which may induce the Thelper (Th1)-mediated immune response. Collectively, our results suggest that P-MAPA immunotherapy combined with cisplatin

Focal Choroidal Excavation in Best Vitelliform Macular Dystrophy: Case Report

PubMed Central

Esfahani, Mohammad Riazi; Esfahani, Hamid Riazi; Mahmoudi, Alireza; Johari, Mohammad Karim

2015-01-01

Focal choroidal excavation (FCE) was first reported as a choroidal posteriorly excavated zone without any scleral change. Choroidal excavation also divided into conforming and nonconforming type. Numerous reports demonstrated association between FCE and other disease such as choroidal neovascularization and central serous choroidoretinopathy. Here, we report a rare case of FCE in a patient with Best disease. The patient was diagnosed by spectoral domain optical coherence tomography (SD-OCT). To the best of our knowledge, our patient is the second report of choroidal excavation in Best vitelliform macular dystrophy. PMID:26155505

Central sleep apnea

MedlinePlus

Sleep apnea - central; Obesity - central sleep apnea; Cheyne-Stokes - central sleep apnea; Heart failure - central sleep apnea ... or conditions of the cervical spine (neck) Severe obesity Certain medicines, such as narcotic painkillers If the ...

Everolimus and Letrozole in Treating Patients With Recurrent Hormone Receptor Positive Ovarian, Fallopian Tube, or Primary Peritoneal Cavity Cancer

ClinicalTrials.gov

2018-03-05

Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

B7-H4 overexpression in ovarian tumors.

PubMed

Tringler, Barbara; Liu, Wenhui; Corral, Laura; Torkko, Kathleen C; Enomoto, Takayuki; Davidson, Susan; Lucia, M Scott; Heinz, David E; Papkoff, Jackie; Shroyer, Kenneth R

2006-01-01

Despite great advances in therapeutic management, the mortality rate for ovarian cancer has remained relatively stable over the past 50 years. This study was designed to evaluate the expression of B7-H4 protein, recently identified as a potential molecular marker of breast and ovarian cancer by quantitative PCR analysis, in benign tumors, tumors of low malignant potential and malignant tumors of the ovary. Archival formalin-fixed tissue blocks from serous, mucinous, endometrioid and clear cell ovarian tumors were evaluated by immunohistochemistry for the distribution of B7-H4 expression, and staining intensity was measured by automated image analysis. Univariate analyses were used to test for statistically significant relationships. B7-H4 cytoplasmic and membranous expression was detected in all primary serous (n = 32), endometrioid (n = 12), and clear cell carcinomas (n = 15), and in all metastatic serous (n = 23) and endometrioid (n = 7) ovarian carcinomas. By contrast, focal B7-H4 expression was detected in only 1/11 mucinous carcinomas. The proportion of positive cells and median staining intensity was greater in serous carcinomas than in serous cystadenomas or serous tumors of low malignant potential, and the differences were statistically significant (P < 0.0001 and P = 0.034, respectively). The median staining intensity was also significantly greater in endometrioid carcinomas than in endometriosis (P = 0.005). The consistent overexpression of B7-H4 in serous, endometrioid and clear cell ovarian carcinomas and the relative absence of expression in most normal somatic tissues indicates that B7-H4 should be further investigated as a potential diagnostic marker or therapeutic target for ovarian cancer.

Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilks, C. Blake; Press, Joshua Z.; De Luca, Alessandro

2008-05-02

Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteenmore » (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumors were high-grade serous or undifferentiated type. None of the endometrioid (n=5), clear cell (n=4), or low grade serous (n=2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumors with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.« less

Ovarian carcinomas with genetic and epigenetic BRCA1 loss havedistinct molecular abnormalities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Press, Joshua Z.; De Luca, Alessandro; Boyd, Niki

2007-07-23

Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteenmore » (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumors were high-grade serous or undifferentiated type. None of the endometrioid (n = 5), clear cell (n = 4), or low grade serous (n = 2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumors with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.« less

Identification of multiple novel protein biomarkers shed by human serous ovarian tumors into the blood of immunocompromised mice and verified in patient sera.

PubMed

Beer, Lynn A; Wang, Huan; Tang, Hsin-Yao; Cao, Zhijun; Chang-Wong, Tony; Tanyi, Janos L; Zhang, Rugang; Liu, Qin; Speicher, David W

2013-01-01

The most cancer-specific biomarkers in blood are likely to be proteins shed directly by the tumor rather than less specific inflammatory or other host responses. The use of xenograft mouse models together with in-depth proteome analysis for identification of human proteins in the mouse blood is an under-utilized strategy that can clearly identify proteins shed by the tumor. In the current study, 268 human proteins shed into mouse blood from human OVCAR-3 serous tumors were identified based upon human vs. mouse species differences using a four-dimensional plasma proteome fractionation strategy. A multi-step prioritization and verification strategy was subsequently developed to efficiently select some of the most promising biomarkers from this large number of candidates. A key step was parallel analysis of human proteins detected in the tumor supernatant, because substantially greater sequence coverage for many of the human proteins initially detected in the xenograft mouse plasma confirmed assignments as tumor-derived human proteins. Verification of candidate biomarkers in patient sera was facilitated by in-depth, label-free quantitative comparisons of serum pools from patients with ovarian cancer and benign ovarian tumors. The only proteins that advanced to multiple reaction monitoring (MRM) assay development were those that exhibited increases in ovarian cancer patients compared with benign tumor controls. MRM assays were facilely developed for all 11 novel biomarker candidates selected by this process and analysis of larger pools of patient sera suggested that all 11 proteins are promising candidate biomarkers that should be further evaluated on individual patient blood samples.

Identification of Multiple Novel Protein Biomarkers Shed by Human Serous Ovarian Tumors into the Blood of Immunocompromised Mice and Verified in Patient Sera

PubMed Central

Beer, Lynn A.; Wang, Huan; Tang, Hsin-Yao; Cao, Zhijun; Chang-Wong, Tony; Tanyi, Janos L.; Zhang, Rugang; Liu, Qin; Speicher, David W.

2013-01-01

The most cancer-specific biomarkers in blood are likely to be proteins shed directly by the tumor rather than less specific inflammatory or other host responses. The use of xenograft mouse models together with in-depth proteome analysis for identification of human proteins in the mouse blood is an under-utilized strategy that can clearly identify proteins shed by the tumor. In the current study, 268 human proteins shed into mouse blood from human OVCAR-3 serous tumors were identified based upon human vs. mouse species differences using a four-dimensional plasma proteome fractionation strategy. A multi-step prioritization and verification strategy was subsequently developed to efficiently select some of the most promising biomarkers from this large number of candidates. A key step was parallel analysis of human proteins detected in the tumor supernatant, because substantially greater sequence coverage for many of the human proteins initially detected in the xenograft mouse plasma confirmed assignments as tumor-derived human proteins. Verification of candidate biomarkers in patient sera was facilitated by in-depth, label-free quantitative comparisons of serum pools from patients with ovarian cancer and benign ovarian tumors. The only proteins that advanced to multiple reaction monitoring (MRM) assay development were those that exhibited increases in ovarian cancer patients compared with benign tumor controls. MRM assays were facilely developed for all 11 novel biomarker candidates selected by this process and analysis of larger pools of patient sera suggested that all 11 proteins are promising candidate biomarkers that should be further evaluated on individual patient blood samples. PMID:23544127

An unusual abdominal cystic mass in the round ligament of the uterus: a case report.

PubMed

Açmaz, Gökhan; Aksoy, Hüseyin; Aksoy, Ülkü; Özyurt, Sezin; Esin, Erkan; Gökahmetoğlu, Günhan

2014-10-01

Cystic tumor of the round ligament is extremely rare. To our knowledge, this is the first case reported in the literature of a round ligament giant serous cystadenoma. A 17-year-old adolescent who presented with massive abdominal swelling and was later identified as a serous cystadenomas of the round ligament with a size of approximately 50 cm. A multidisciplinary team including gynecologist, surgeon, and urologist performed the surgical cyst excision and she has recovered well without any complications. Round ligament serous cystadenomas could grow to any size when there is a diagnosis. In addition, even in unusual locations, round ligament serous cysts should be kept in the differential diagnosis of abdominal masses. Copyright © 2014 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Combining serum microRNA and CA-125 as prognostic indicators of preoperative surgical outcome in women with high-grade serous ovarian cancer.

PubMed

Shah, Jaynish S; Gard, Gregory B; Yang, Jean; Maidens, Jayne; Valmadre, Susan; Soon, Patsy S; Marsh, Deborah J

2018-01-01

The most widely used approach for the clinical management of women with high-grade serous ovarian cancer (HGSOC) is surgery, followed by platinum and taxane based chemotherapy. The degree of macroscopic disease remaining at the conclusion of surgery is a key prognostic factor determining progression free and overall survival. We sought to develop a non-invasive test to assist surgeons to determine the likelihood of achieving complete surgical resection. This knowledge could be used to plan surgical approaches for optimal clinical management. We profiled 170 serum microRNAs (miRNAs) using the Serum/Plasma Focus miRNA PCR panel containing locked nucleic acid (LNA) primers (Exiqon) in women with HGSOC (N=56) and age-matched healthy volunteers (N=30). Additionally, we measured serum CA-125 levels in the same samples. The HGSOC cohort was further classified based on the degree of macroscopic disease at the conclusion of surgery. Stepwise logistic regression was used to identify predictive markers. We identified a combination of miR-375 and CA-125 as the strongest discriminator of healthy versus HGSOC serum, with an area under the curve (AUC) of 0.956. The inclusion of miR-210 increased the AUC to 0.984; however, miR-210 was affected by hemolysis. The combination of miR-34a-5p and CA-125 was the strongest predictor of completeness of surgical resection with an AUC of 0.818. A molecular test incorporating circulating miRNA to predict completeness of surgical resection for women with HGSOC has the potential to contribute to planning for optimal patient management, ultimately improving patient outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of lymph node ratio on survival in stage III ovarian high-grade serous cancer: a Turkish Gynecologic Oncology Group study.

PubMed

Ayhan, Ali; Ozkan, Nazlı Topfedaisi; Sarı, Mustafa Erkan; Celik, Husnu; Dede, Murat; Akbayır, Özgür; Güngördük, Kemal; Şahin, Hanifi; Haberal, Ali; Güngör, Tayfun; Arvas, Macit; Meydanlı, Mehmet Mutlu

2018-01-01

The purpose of this study was to investigate the prognostic value of lymph node ratio (LNR) in patients with stage III ovarian high-grade serous carcinoma (HGSC). A multicenter, retrospective department database review was performed to identify patients with ovarian HGSC at 6 gynecologic oncology centers in Turkey. A total of 229 node-positive women with stage III ovarian HGSC who had undergone maximal or optimal cytoreductive surgery plus systematic lymphadenectomy followed by paclitaxel plus carboplatin combination chemotherapy were included. LNR, defined as the percentage of positive lymph nodes (LNs) to total nodes recovered, was stratified into 3 groups: LNR1 (<10%), LNR2 (10%≤LNR<50%), and LNR3 (≥50%). Kaplan-Meier method was used to generate survival data. Factors predictive of outcome were analyzed using Cox proportional hazards models. Thirty-one women (13.6%) were classified as stage IIIA1, 15 (6.6%) as stage IIIB, and 183 (79.9%) as stage IIIC. The median age at diagnosis was 56 (range, 18-87), and the median duration of follow-up was 36 months (range, 1-120 months). For the entire cohort, the 5-year overall survival (OS) was 52.8%. An increased LNR was associated with a decrease in 5-year OS from 65.1% for LNR1, 42.5% for LNR2, and 25.6% for LNR3, respectively (p<0.001). In multivariate analysis, women with LNR≥0.50 were 2.7 times more likely to die of their tumors (hazard ratio [HR]=2.7; 95% confidence interval [CI]=1.42-5.18; p<0.001). LNR seems to be an independent prognostic factor for decreased OS in stage III ovarian HGSC patients. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

Impact of lymph node ratio on survival in stage III ovarian high-grade serous cancer: a Turkish Gynecologic Oncology Group study

PubMed Central

2018-01-01

Objective The purpose of this study was to investigate the prognostic value of lymph node ratio (LNR) in patients with stage III ovarian high-grade serous carcinoma (HGSC). Methods A multicenter, retrospective department database review was performed to identify patients with ovarian HGSC at 6 gynecologic oncology centers in Turkey. A total of 229 node-positive women with stage III ovarian HGSC who had undergone maximal or optimal cytoreductive surgery plus systematic lymphadenectomy followed by paclitaxel plus carboplatin combination chemotherapy were included. LNR, defined as the percentage of positive lymph nodes (LNs) to total nodes recovered, was stratified into 3 groups: LNR1 (<10%), LNR2 (10%≤LNR<50%), and LNR3 (≥50%). Kaplan-Meier method was used to generate survival data. Factors predictive of outcome were analyzed using Cox proportional hazards models. Results Thirty-one women (13.6%) were classified as stage IIIA1, 15 (6.6%) as stage IIIB, and 183 (79.9%) as stage IIIC. The median age at diagnosis was 56 (range, 18–87), and the median duration of follow-up was 36 months (range, 1–120 months). For the entire cohort, the 5-year overall survival (OS) was 52.8%. An increased LNR was associated with a decrease in 5-year OS from 65.1% for LNR1, 42.5% for LNR2, and 25.6% for LNR3, respectively (p<0.001). In multivariate analysis, women with LNR≥0.50 were 2.7 times more likely to die of their tumors (hazard ratio [HR]=2.7; 95% confidence interval [CI]=1.42–5.18; p<0.001). Conclusion LNR seems to be an independent prognostic factor for decreased OS in stage III ovarian HGSC patients. PMID:29185270

PIK3CA oncogenic mutations represent a major mechanism of resistance to trastuzumab in HER2/neu overexpressing uterine serous carcinomas.

PubMed

Black, Jonathan D; Lopez, Salvatore; Cocco, Emiliano; Bellone, Stefania; Altwerger, Gary; Schwab, Carlton L; English, Diana P; Bonazzoli, Elena; Predolini, Federica; Ferrari, Francesca; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Santin, Alessandro D

2015-09-29

We evaluated the role of PIK3CA-mutations as mechanism of resistance to trastuzumab in primary HER2/neu-amplified uterine-serous-carcinoma (USC) cell lines. Fifteen whole-exome-sequenced USC cell lines were tested for HER2/neu-amplification and PIK3CA-mutations. Four HER2/neu-amplified USC (2-harbouring wild-type-PIK3CA-genes and 2-harbouring oncogenic-PIK3CA-mutations) were evaluated in in vitro dose-titration-proliferation-assays, cell-viability and HER2 and S6-protein-phosphorylation after exposure to trastuzumab. USC harbouring wild-type-PIK3CA were transfected with plasmids encoding oncogenic PIK3CA-mutations (i.e., H1047R/R93Q) and exposed to trastuzumab. Finally, trastuzumab efficacy was tested by using two USC xenograft mouse models. Seven out of fifteen (46%) of the USC cell lines were HER2/neu-amplified by fluorescence in situ hybridisation. Within these tumours four out of seven (57%) were found to harbour oncogenic PIK3CA-mutations vs two out of eight (25%) of the HER2/neu not amplified cell lines (P=0.01). HER2/neu-amplified/PIK3CA-mutated USC were highly resistant to trastuzumab when compared with HER2/neu-amplified/wild-type-PIK3CA cell lines (P=0.02). HER2/neu-amplified/PIK3CA wild-type cell lines transfected with oncogenic PIK3CA-mutations increased their resistance to trastuzumab (P<0.0001). Trastuzumab was effective in reducing tumour growth (P=0.001) and improved survival (P=0.0001) in mouse xenografts harbouring HER2-amplified/PIK3CA wild-type USC but not in HER2-amplified/PIK3CA-mutated tumours. Oncogenic PIK3CA mutations are common in HER2/neu-amplified USC and may constitute a major mechanism of resistance to trastuzumab treatment.

Central line infections - hospitals

MedlinePlus

... infection; CVC - infection; Central venous device - infection; Infection control - central line infection; Nosocomial infection - central line infection; Hospital acquired infection - central line infection; Patient safety - central ...

Frequency of papillary tubal hyperplasia (PTH), salpingoliths and transition from adenoma to borderline ovarian tumors (BOT): A systematic analysis of 74 BOT with different histologic types.

PubMed

Horn, Lars-Christian; Angermann, Karolin; Hentschel, Bettina; Einenkel, Jens; Höhn, Anne Kathrin

2017-04-01

Borderline ovarian tumors (BOT) arise from cystadenomas and represent a transition step within the development of low-grade ovarian carcinomas (Type I tumors). That pathway mirrors the adenoma-to-carcinoma sequence known for colorectal cancer. It has been suggested that papillary tubal hyperplasia (PTH) and salpingoliths may be associated with the development of BOT. To evaluate the frequency of the presence of benign cystadenoma and its transition to BOT in a given patient as well as the presence of PTH and salpingoliths we re-valuated in 74 consecutive cases of BOT with different histologic types. The majority of cases represented serous-BOT (60.8%), followed by mucinous BOT (25.7%), other histologic types were rare. 86.5% showed an adenoma-BOT sequence, which was seen in all mucinous BOT but was missed in 15.6% of serous BOT. Two cases had salpingoliths without associated PTH. PTH was seen in four out of the 74 (5.4%) BOT and occurred only in cases with serous histology. The vast majority of BOT represent a transition from benign cystadenoma to BOT in cases with mucinous and serous histology. Salpingoliths are rarely seen in association with BOT and occurred exclusively in BOT with serous histology. PTH may represent a distinct lesion but is rarely seen in association with BOT, especially in those with non-serous histology. Further studies are needed to evaluate the frequency and pathogenetic association of PTH with BOT. Copyright © 2017 Elsevier GmbH. All rights reserved.

The Emerging Genomic Landscape of Endometrial Cancer

PubMed Central

Le Gallo, Matthieu; Bell, Daphne W.

2014-01-01

BACKGROUND Endometrial cancer is responsible for ~74,000 deaths amongst women worldwide each year. It is a heterogeneous disease that consists of multiple different histological subtypes. In the United States, the majority of deaths from endometrial carcinoma are attributed to the serous and endometrioid subtypes. An understanding of the fundamental genomic alterations that drive serous and endometrioid endometrial carcinomas lays the foundation for the identification of molecular markers that could improve the clinical management of patients presenting with these tumors. CONTENT Herein we review the current state of knowledge of the somatic genomic alterations that are present in serous and endometrioid endometrial tumors. We present this knowledge in a historical context – reviewing the genomic alterations that have been identified over the past two decades or more, from studies of individual genes and proteins, followed by a review of very recent studies that have conducted comprehensive, systematic surveys of genomic, exomic, transcriptomic, epigenomic, and proteomic alterations in serous and endometrioid endometrial carcinomas. SUMMARY The recent mapping of the genomic landscape of serous and endometrioid endometrial carcinomas has resulted in the first comprehensive molecular classification of these tumors and has distinguished four molecular subgroups: a POLE ultramutated subgroup, a hypermutated/microsatellite unstable subgroup, a copy number low/microsatellite stable subgroup, and a copy number high subgroup. This molecular classification may ultimately serve to refine the diagnosis and treatment of women with endometrioid and serous endometrial tumors. PMID:24170611

Expression and Mutational Analysis of c-kit in Ovarian Surface Epithelial Tumors

PubMed Central

Lee, Myung-Hoon; Park, Tae-In; Bae, Han-Ik

2006-01-01

Coexpression of Kit ligand and c-kit has been reported in some gynecologic tumors. To determine whether imatinib mesylate is useful in ovarian epithelial tumors, we performed immunohistochemical and mutational analysis. The cases consisted of 33 cases, which included 13 serous cystadenocarcinomas, 1 borderline serous tumor, 8 mucinous cystadenocarcinomas, 6 borderline mucinous tumors and 5 clear cell carcinomas. Five cases of serous cystadenoma and 5 cases of mucinous cystadenoma were also included. In the immunohistochemical study, 3 cases (3/6, 50%) of borderline mucinous cystic tumor and two cases (2/8, 25%) of mucinous cystadenocarcinoma show positive staining for KIT protein. Only one case (1/13, 7.7%) of serous cystadenocarcinoma had positive staining. On mutational analysis, no mutation was identified at exon 11. However, two cases of borderline mucinous tumors and one case of mucinous cystadenocarcinoma had mutations at exon 17. In these cases, the immunohistochemistry also shows focal positive staining at epithelial component. Although, KIT protein expression showed higher incidence in mucinous tumors than serous tumors, they lack KIT-activating mutations in exon 11. Thus, ovarian surface epithelial tumors are unlikely to respond to imatinib mesylate. PMID:16479070

Adenovirus‑mediated overexpression of cystic fibrosis transmembrane conductance regulator enhances invasiveness and motility of serous ovarian cancer cells.

PubMed

Xu, Jiao; Lin, Liangbo; Yong, Min; Dong, Xiaojing; Yu, Tinghe; Hu, Lina

2016-01-01

The cystic fibrosis transmembrane conductance regulator (CFTR) belongs to the adenosine triphosphate‑binding cassette transporter family, members of which are involved in several types of cancer. Previous studies by our group reported that CFTR was highly expressed in serous ovarian cancer (SOC) tissues, and that knockdown of CFTR suppressed the proliferation of ovarian cancer in vitro and in vivo. Thus, the aim of the present study was to construct a recombinant adenoviral vector for the expression of the human CFTR gene in order to study the role of CFTR overexpression in the malignant invasion and migration of SOC cells in vitro. The present study then focused on the mechanisms of the role of CFTR in the migratory and invasive malignant properties of SOC cells. The CFTR gene was inserted into an adenoviral vector by using the AdEasy system in order to obtain the Ad‑CFTR overexpression vector, which was used to transfect the A2780 SOC cell line. Reverse-transcription polymerase chain reaction, western blot analysis and immunofluorescence were performed to detect the expression and localization of CFTR. Cell invasion and motility of the transfected cells compared with those of control cells were observed using Transwell and wound healing assays. A ~4,700 bp fragment of the CFTR gene was confirmed to be correctly cloned in the adenoviral vector and amplification of Ad‑CFTR was observed in HEK293 cells during package. After 48 h of transfection with Ad‑CFTR, ~90% of A2780 cells were red fluorescence protein‑positive. Immunofluorescence showed that following transfection, CFTR expression was increased and CFTR was located in the cell membrane and cytoplasm. CFTR overexpression was shown to enhance the invasion and motility of A2780 cells in vitro. Furthermore, the effects of CFTR overexpression on the activation c‑Src signaling were observed by western blot analysis. CFTR overexpressing cells showed the lowest activity of phospho‑Src (Tyr530

Dose-Response Relationship of CD8+ Tumor Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer

PubMed Central

Goode, Ellen L; Block, Matthew S; Kalli, Kimberly R; Vierkant, Robert A; Chen, Wenqian; Fogarty, Zachary C; Gentry-Maharaj, Aleksandra; Tołoczko, Aleksandra; Hein, Alexander; Bouligny, Aliecia L; Jensen, Allan; Osorio, Ana; Hartkopf, Andreas D; Ryan, Andy; Chudecka-Głaz, Anita; Magliocco, Anthony M; Hartmann, Arndt; Jung, Audrey Y; Gao, Bo; Hernandez, Brenda Y; Fridley, Brooke L; McCauley, Bryan M; Kennedy, Catherine J; Wang, Chen; Karpinskyj, Chloe; de Sousa, Christiani B; Tiezzi, Daniel G; Wachter, David L; Herpel, Esther; Taran, Florin Andrei; Modugno, Francesmary; Nelson, Gregg; Lubiński, Jan; Menkiszak, Janusz; Alsop, Jennifer; Lester, Jenny; García-Donas, Jesús; Nation, Jill; Hung, Jillian; Palacios, José; Rothstein, Joseph H; Kelley, Joseph L; de Andrade, Jurandyr M; Robles-Díaz, Luis; Intermaggio, Maria P; Widschwendter, Martin; Beckmann, Matthias W; Ruebner, Matthias; Jimenez-Linan, Mercedes; Singh, Naveena; Oszurek, Oleg; Harnett, Paul R; Rambau, Peter F; Sinn, Peter; Wagner, Philipp; Ghatage, Prafull; Sharma, Raghwa; Edwards, Robert P; Ness, Roberta B; Orsulic, Sandra; Brucker, Sara Y; Johnatty, Sharon E; Longacre, Teri A; Eilber, Ursula; McGuire, Valerie; Sieh, Weiva; Natanzon, Yanina; Li, Zheng; Whittemore, Alice S; deFazio, Anna; Staebler, Annette; Karlan, Beth Y; Gilks, Blake; Bowtell, David D; Høgdall, Estrid; Candido dos Reis, Francisco J; Steed, Helen; Campbell, Ian G; Gronwald, Jacek; Benítez, Javier; Koziak, Jennifer M; Chang-Claude, Jenny; Moysich, Kirsten B; Kelemen, Linda E; Cook, Linda S; Goodman, Marc T; García, María José; Fasching, Peter A; Kommoss, Stefan; Deen, Suha; Kjaer, Susanne K; Menon, Usha; Brenton, James D; Pharoah, Paul DP; Chenevix-Trench, Georgia; Huntsman, David G; Winham, Stacey J; Köbel, Martin; Ramus, Susan J

2017-01-01

Importance Cytotoxic CD8+ T lymphocytes (TILs) participate in immune control of ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors. Objective To define the prognostic role of CD8+ TILs in epithelial ovarian cancer. Design Prospective survival cohort. Setting Multi-center observational. Participants Over 5,500 patients, including 3,196 high-grade serous ovarian carcinomas (HGSOCs), followed prospectively for over 24,650 person-years. Exposure(s) Following immunohistochemistry, CD8+ TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+ TILs per high-powered field: negative (none), low (1–2), moderate (3–19), and high (≥20). CD8+ TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines. Main Outcome Measure(s) Overall survival time. Results Among the five major invasive histotypes, HGSOCs showed the most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+ TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+ TILs, respectively (p-trend=4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not the other histotypes. Among HGSOCs, CD8+ TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation, but were not prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+ TIL counts showed a near linear functional form. Conclusions and Relevance This study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship

Vaccine Therapy in Treating Patients With Stage IIIC-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer Following Surgery and Chemotherapy

ClinicalTrials.gov

2017-10-12

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Tumor; Fallopian Tube Mucinous Neoplasm; Fallopian Tube Serous Neoplasm; Fallopian Tube Transitional Cell Carcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

CD103+ intraepithelial T cells in high-grade serous ovarian cancer are phenotypically diverse TCRαβ+ CD8αβ+ T cells that can be targeted for cancer immunotherapy

PubMed Central

Workel, Hagma H.; Tijans, Aline M.; Terwindt, Anouk L.J.; Brunekreeft, Kim L.; Plat, Annechien; Klip, Harry G.; Eggink, Florine A.; Leffers, Ninke; Helfrich, Wijnand; Samplonius, Douwe F.; Bremer, Edwin; Wisman, G. Bea A.; Daemen, Toos; Duiker, Evelien W.; Hollema, Harry; Nijman, Hans W.; de Bruyn, Marco

2016-01-01

CD103+ tumor-infiltrating lymphocytes (TIL) have been linked to specific epithelial infiltration and a prolonged survival in high-grade serous epithelial ovarian cancer (HGSC). However, whether these cells are induced as part of an ongoing anti-HGSC immune response or represent non-specifically expanded resident or mucosal lymphocytes remains largely unknown. In this study, we first confirmed that CD103+ TIL from HGSC were predominantly localized in the cancer epithelium and were strongly correlated with an improved prognosis. We further demonstrate that CD103+ TIL were almost exclusively CD3+ TCRαβ+ CD8αβ+ CD4- T cells, but heterogeneously expressed T cell memory and differentiation markers. Activation of peripheral T cells in the presence of HGSC was sufficient to trigger induction of CD103 in over 90% of all CD8+ cells in a T cell receptor (TCR)- and TGFβR1-dependent manner. Finally, CD103+ TIL isolated from primary HGSC showed signs of recent activation and dominantly co-expressed key immunotherapeutic targets PD-1 and CD27. Taken together, our data indicate CD103+ TIL in HGSC are formed as the result of an adaptive anti-tumor immune response that might be reactivated by (dual) checkpoint inhibition. PMID:27650547

Gemcitabine Hydrochloride With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

ClinicalTrials.gov

2018-06-04

Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

Clinicopathologic analysis of matched primary and recurrent endometrial carcinoma.

PubMed

Soslow, Robert A; Wethington, Stephanie L; Cesari, Matthew; Chiappetta, Daniel; Olvera, Narciso; Shia, Jinru; Levine, Douglas A

2012-12-01

It is unknown whether the type and grade of a primary endometrial carcinoma is reliably maintained in recurrence. All matched primary and recurrent endometrial carcinomas diagnosed from 2000 to 2010 at our institution were identified; 34 cases had available slides. Histologic classification was performed using modifications to the World Health Organization criteria. Immunohistochemical analysis for p53, p16, progesterone receptor (PR), and DNA mismatch-repair proteins (MMR) (MLH1, MSH2, MSH6, and PMS2) was performed. Endometrioid carcinoma recurrences were mostly local, whereas serous carcinoma recurrences were mostly peritoneal. Compared with endometrioid carcinoma patients, serous carcinoma patients were older, presented at high stage, and had shorter survival. Serous carcinomas were the most common recurrent endometrial carcinoma (18/34 cases). Overall, 21 cases (62%) displayed similar morphology when comparing primary and recurrent carcinomas, whereas 13 displayed discordant morphology. Seven of 13 endometrioid carcinomas (54%) had a morphologically discordant recurrence, compared with 3 of 14 serous carcinomas (21%), 1 of 4 morphologically ambiguous carcinomas (25%), and both mixed epithelial carcinomas. Serous and morphologically ambiguous carcinomas therefore demonstrated relative morphologic fidelity compared with endometrioid carcinomas. Four morphologically discordant cases demonstrated either pure clear cell carcinoma or clear cell features at recurrence. Seven of 23 matched pairs displayed discordant PR results, with 5 cases, including both endometrioid and serous carcinomas, showing diminished PR expression at recurrence. p53, p16, and DNA MMR staining results were generally concordant when evaluating matched pairs, with only occasional exceptions. Sixty-four percent of all pure endometrioid carcinomas and mixed epithelial carcinomas with an endometrioid component showed loss of expression of MLH1 and/or PMS2; no serous carcinoma demonstrated this

The number of cycles of neoadjuvant chemotherapy is associated with prognosis of stage IIIc-IV high-grade serous ovarian cancer.

PubMed

Xu, Xia; Deng, Fei; Lv, Mengmeng; Chen, Xiaoxiang

2017-02-01

No consensus exists on the number of chemotherapy cycles to be administered before and after interval debulking surgery (IDS) in patients with advanced stage epithelial ovarian cancer. The present study aims to explore the optimal number of cycles of neoadjuvant chemotherapy (NAC) and post-operation chemotherapy to treat the International Federation of Gynecology and Obstetrics stage IIIc-IV high-grade serous ovarian cancer (HG-SOC). A total of 129 IIIc-IV stage HG-SOC cases were retrospectively analyzed. Cases were comprised of patients who underwent NAC followed by IDS and who achieved clinical complete response (CCR) at the end of primary therapy. Patients were recruited from the Jiangsu Institute of Cancer Research between 1993 and 2013. Optimal IDS-associated factors were explored with logistic regression. The association between progression-free survival (PFS), overall survival (OS) duration, and covariates was assessed by Cox proportional hazards model and log-rank test. The median number of NAC cycle was 3 (range 1-8). CA-125 decreasing kinetics (p = 0.01) was independently associated with optimal IDS. CA-125 decreasing kinetics, optimal IDS, and NAC cycles was independently associated with OS (p < 0.01, p < 0.01, p = 0.03, respectively) and PFS (p < 0.01, p < 0.01, p = 0.04, respectively). The PFS of patients who underwent ≥5 NAC cycles was shorter than those of patients who underwent <5 NAC cycles (12.3 versus 17.2 months). The PFS and OS of patients who underwent <5 cycles of adjuvant chemotherapy post-IDS were shorter than those of patients who underwent ≥5 cycles (14.2 and 20.3 versus 21.2 and 28.8 months). NAC cycles, CA-125 decreasing kinetics, and optimal debulking are independently associated with the prognosis of patients with advanced stage HG-SOC who underwent NAC/IDS and achieved CCR. The number of administered NAC cycles should not exceed 4.

The modularity and dynamicity of miRNA-mRNA interactions in high-grade serous ovarian carcinomas and the prognostic implication.

PubMed

Zhang, Wensheng; Edwards, Andrea; Fan, Wei; Flemington, Erik K; Zhang, Kun

2016-08-01

Ovarian carcinoma is the fifth-leading cause of cancer death among women in the United States. Major reasons for this persistent mortality include the poor understanding of the underlying biology and a lack of reliable biomarkers. Previous studies have shown that aberrantly expressed MicroRNAs (miRNAs) are involved in carcinogenesis and tumor progression by post-transcriptionally regulating gene expression. However, the interference of miRNAs in tumorigenesis is quite complicated and far from being fully understood. In this work, by an integrative analysis of mRNA expression, miRNA expression and clinical data published by The Cancer Genome Atlas (TCGA), we studied the modularity and dynamicity of miRNA-mRNA interactions and the prognostic implications in high-grade serous ovarian carcinomas. With the top transcriptional correlations (Bonferroni-adjusted p-value<0.01) as inputs, we identified five miRNA-mRNA module pairs (MPs), each of which included one positive-connection (correlation) module and one negative-connection (correlation) module. The number of miRNAs or mRNAs in each module varied from 3 to 7 or from 2 to 873. Among the four major negative-connection modules, three fit well with the widely accepted miRNA-mediated post-transcriptional regulation theory. These modules were enriched with the genes relevant to cell cycle and immune response. Moreover, we proposed two novel algorithms to reveal the group or sample specific dynamic regulations between these two RNA classes. The obtained miRNA-mRNA dynamic network contains 3350 interactions captured across different cancer progression stages or tumor grades. We found that those dynamic interactions tended to concentrate on a few miRNAs (e.g. miRNA-936), and were more likely present on the miRNA-mRNA pairs outside the discovered modules. In addition, we also pinpointed a robust prognostic signature consisting of 56 modular protein-coding genes, whose co-expression patterns were predictive for the survival

VSV-hIFNbeta-NIS in Treating Patients With Stage IV or Recurrent Endometrial Cancer

ClinicalTrials.gov

2018-05-09

Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Metastatic Endometrioid Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Recurrent Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IV Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

Comparison of Clinical Characteristic and Prognosis between Ovarian Clear Cell Carcinoma and Serous Carcinoma: A 10-Year Cohort Study of Chinese Patients.

PubMed

Ye, Shuang; Yang, Jiaxin; You, Yan; Cao, Dongyan; Huang, Huifang; Wu, Ming; Chen, Jie; Lang, Jinghe; Shen, Keng

2015-01-01

To compare the clinicopathologic features and prognosis of Chinese patients with ovarian clear cell carcinoma (CCC) and serous carcinoma (SC). A retrospective cohort study was designed to investigate the clinicopathologic characteristic and prognosis of patients with CCC and SC who were diagnosed and treated in in a tertiary referral center (Peking Union Medical College Hospital) between 1999 and 2009. The Kaplan-Meier method and Cox regression were employed in the survival analysis. A total of 504 cases were included in the study, comprising 197 cases of CCC and 307 cases of SC. The mean age of the patients with SC was greater than of CCC patients (3.6±0.94, P<0.001). Patients with CCC were more likely to be early-stage and optimally debulked (P<0.001). Regarding cancer-antigen 125, 22% of the patients with CCC had normal values, and the level was significantly lower than in patients with SC (P<0.001). More CCC patients had platinum-resistant tumors compared with platinum-sensitive disease (45.7% in CCC vs. 61.0% in SC [P=0.008]). The 5-year survival rate was 51.2% in the CCC group vs. 49.8% in the SC group (P=0.428). Patients with advanced CCC had a statistically significant poorer overall survival (OS) compared with their SC counterparts (38.0 vs. 52.0 months; hazard ratio 1.584, 95% confidence interval [CI] 1.167-2.150, P=0.003). However, the advantage of improved progression-free survival (PFS) existed across all stages. Women with ovarian CCC presented at a younger age and early stage. Patients with ovarian CCC also had improved PFS, but they had similar OS compared to patients with SC. However, patients with advanced CCC had decreased survival.

The expression and correlation of Hsp 70 and Hsp 27 in serous middle ear effusion fluids of pediatric patients-a preliminary study.

PubMed

Min, Hyun Jin; Choe, Ji Won; Chang, Moon Young; Kim, Kyung Soo; Lee, Sei Young; Mun, Seog-Kyun

2017-10-01

Several cytokines and innate immune-associated molecules are present in middle ear effusions, but damage-associated molecular patterns (DAMPs) in middle ear effusion have not been studied. Therefore, we evaluated the role of heat shock proteins (Hsps) in the development of otitis media with effusion (OME). Serous middle ear effusions from 22 pediatric patients who were diagnosed with OME and underwent ventilation tube insertion from June 2015 to March 2017 were evaluated in our study. The levels of Hsp 90, 70, 27, IL-8, and TNF-α in effusion fluids were evaluated by enzyme-linked immunosorbent assays. The associations between the levels of these molecules and the degree of tympanic membrane inflammation were statistically evaluated. Finally, the relationships among these molecules were also evaluated. Hsp 70 and Hsp 27 were detected in all middle ear effusions, but Hsp 90 was detected in only five effusion fluid samples. IL-8 was also detected in all middle ear effusions, but TNF-α was detected in only four effusion fluid samples. When we compared the degree of tympanic membrane inflammation with the levels of Hsp 70, Hsp 27, and IL-8, which were detected in all effusion fluids, we could not find statistical significance. However, Hsp 70, Hsp 27, and IL-8 were significantly associated with each other (p < 0.05). Hsp 70 and Hsp 27 were expressed in middle ear effusions. Furthermore, the levels of Hsp 70 and Hsp 27 were positively correlated with each other, and were also positively associated with the neutrophil chemoattractant, IL-8. Our findings suggested that Hsp 70 and Hsp 27 might be involved in the pathophysiology of pediatric OME. Copyright © 2017 Elsevier B.V. All rights reserved.

Utility of α-methylacyl-coenzyme-A racemase (p504s) immunohistochemistry in distinguishing endometrial clear cell carcinomas from serous and endometrioid carcinomas.

PubMed

Fadare, Oluwole; Parkash, Vinita; Gwin, Katja; Hanley, Krisztina Z; Jarboe, Elke A; Liang, Sharon X; Quick, Charles M; Zheng, Wenxin; Rawish, Kojo R; Hecht, Jonathan L; Desouki, Mohamed M

2013-12-01

The expression of α-methylacyl-coenzyme-A racemase (AMACR) has previously been reported in 75% to 100% of urethral/bladder clear cell carcinomas, tumors that are known to display broad phenotypic overlap with their identically named müllerian counterparts. Herein, we assess the utility of AMACR in distinguishing endometrial clear cell carcinomas (CCCs) from endometrial serous carcinomas (ESCs) and endometrial endometrioid carcinomas (EECs). A total of 111 endometrial carcinomas in a tissue microarray, including 49 CCCs, 13 ESCs, and 49 EECs, were assessed for AMACR immunoreactivity, with results scored semiquantitatively (scores 0, 1+, 2+, 3+ for 0%, 1%-5%, 6%-50%, >50% immunoreactive cells, respectively). Fifty (45%) of the 111 carcinomas were AMACR positive, with the following score distribution: CCC: 0 (n = 12), 1+ (n = 12), 2+ (n = 3), 3+ (n = 22); EEC: 0 (n = 38), 1+ (n = 4), 2+ (n = 4), 3+ (n = 3); ESC: 0 (n = 11), 1+ (n = 1), 2+ (n = 0), 3+ (n = 1). AMACR expression was significantly more frequent in CCC (75%) than in ESC (15%) or EEC (22%); P < .0001. The sensitivity and specificity of AMACR expression in classifying a carcinoma as CCC were 0.75 (95% confidence interval [CI], 0.61-0.86) and 0.79 (95% CI, 0.66-0.88), respectively, with an odds ratio of 11.62 (95% CI, 5-28; P < .001) and an area under the curve of 0.79 (95% CI, 0.68-0.88). These findings indicate that AMACR expression is strongly associated with CCC and displays a relatively robust diagnostic test performance. However, its practical utility may be limited by the focal nature of its expression in 32% of the AMACR-positive CCC cases as well as its expression in 15% to 22% of the non-CCC histotypes. © 2013.

Metformin downregulates the insulin/IGF-I signaling pathway and inhibits different uterine serous carcinoma (USC) cells proliferation and migration in p53-dependent or -independent manners.

PubMed

Sarfstein, Rive; Friedman, Yael; Attias-Geva, Zohar; Fishman, Ami; Bruchim, Ilan; Werner, Haim

2013-01-01

Accumulating epidemiological evidence shows that obesity is associated with an increased risk of several types of adult cancers, including endometrial cancer. Chronic hyperinsulinemia, a typical hallmark of diabetes, is one of the leading factors responsible for the obesity-cancer connection. Numerous cellular and circulating factors are involved in the biochemical chain of events leading from hyperinsulinemia and insulin resistance to increased cancer risk and, eventually, tumor development. Metformin is an oral anti-diabetic drug of the biguanide family used for treatment of type 2 diabetes. Recently, metformin was shown to exhibit anti-proliferative effects in ovarian and Type I endometrial cancer, although the mechanisms responsible for this non-classical metformin action remain unclear. The insulin-like growth factors (IGFs) play a prominent role in cancer biology and their mechanisms of action are tightly interconnected with the insulin signaling pathways. Given the cross-talk between the insulin and IGF signaling pathways, the aim of this study was to examine the hypothesis that the anti-proliferative actions of metformin in uterine serous carcinoma (USC) are potentially mediated via suppression of the IGF-I receptor (IGF-IR) pathway. Our results show that metformin interacts with the IGF pathway, and induces apoptosis and inhibition of proliferation and migration of USC cell lines with both wild type and mutant p53. Taken together, our results suggest that metformin therapy could be a novel and attractive therapeutic approach for human USC, a highly aggressive variant of endometrial cancer.

Martian Central Pit Craters

NASA Technical Reports Server (NTRS)

Hillman, E.; Barlow, N. G.

2005-01-01

Impact craters containing central pits are rare on the terrestrial planets but common on icy bodies. Mars is the exception among the terrestrial planets, where central pits are seen on crater floors ( floor pits ) as well as on top of central peaks ( summit pits ). Wood et al. [1] proposed that degassing of subsurface volatiles during crater formation produced central pits. Croft [2] argued instead that central pits might form during the impact of volatile-rich comets. Although central pits are seen in impact craters on icy moons such as Ganymede, they do show some significant differences from their martian counterparts: (a) only floor pits are seen on Ganymede, and (b) central pits begin to occur at crater diameters where the peak ring interior morphology begins to appear in terrestrial planet craters [3]. A study of craters containing central pits was conducted by Barlow and Bradley [4] using Viking imagery. They found that 28% of craters displaying an interior morphology on Mars contain central pits. Diameters of craters containing central pits ranged from 16 to 64 km. Barlow and Bradley noted that summit pit craters tended to be smaller than craters containing floor pits. They also noted a correlation of central pit craters with the proposed rings of large impact basins. They argued that basin ring formation fractured the martian crust and allowed subsurface volatiles to concentrate in these locations. They favored the model that degassing of the substrate during crater formation was responsible for central pit formation due to the preferential location of central pit craters along these basin rings.

MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

PubMed Central

Block, Matthew S.; Vierkant, Robert A.; Rambau, Peter F.; Winham, Stacey J.; Wagner, Philipp; Traficante, Nadia; Tołoczko, Aleksandra; Tiezzi, Daniel G.; Taran, Florin Andrei; Sinn, Peter; Sieh, Weiva; Sharma, Raghwa; Rothstein, Joseph H.; Cajal, Teresa Ramón y; Paz-Ares, Luis; Oszurek, Oleg; Orsulic, Sandra; Ness, Roberta B.; Nelson, Gregg; Modugno, Francesmary; Menkiszak, Janusz; McGuire, Valerie; McCauley, Bryan M.; Mack, Marie; Lubiński, Jan; Longacre, Teri A.; Li, Zheng; Lester, Jenny; Kennedy, Catherine J.; Kalli, Kimberly R.; Jung, Audrey Y.; Johnatty, Sharon E.; Jimenez-Linan, Mercedes; Jensen, Allan; Intermaggio, Maria P.; Hung, Jillian; Herpel, Esther; Hernandez, Brenda Y.; Hartkopf, Andreas D.; Harnett, Paul R.; Ghatage, Prafull; García-Bueno, José M.; Gao, Bo; Fereday, Sian; Eilber, Ursula; Edwards, Robert P.; de Sousa, Christiani B.; de Andrade, Jurandyr M.; Chudecka-Głaz, Anita; Chenevix-Trench, Georgia; Cazorla, Alicia; Brucker, Sara Y.; Alsop, Jennifer; Whittemore, Alice S.; Steed, Helen; Staebler, Annette; Moysich, Kirsten B.; Menon, Usha; Koziak, Jennifer M.; Kommoss, Stefan; Kjaer, Susanne K.; Kelemen, Linda E.; Karlan, Beth Y.; Huntsman, David G.; Høgdall, Estrid; Gronwald, Jacek; Goodman, Marc T.; Gilks, Blake; García, María José; Fasching, Peter A.; de Fazio, Anna; Deen, Suha; Chang-Claude, Jenny; Candido dos Reis, Francisco J.; Campbell, Ian G.; Brenton, James D.; Bowtell, David D.; Benítez, Javier; Pharoah, Paul D.P.; Köbel, Martin; Ramus, Susan J.; Goode, Ellen L.

2018-01-01

Objective To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival. Patients and Methods We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong). Results Expression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P<.001 for both). In HGSOC, strong MyD88 expression was modestly associated with shortened overall survival (hazard ratio [HR], 1.13; 95% CI, 1.01–1.26; P=.04) but was also associated with advanced stage (P<.001). The expression of TLR4 was not associated with survival. In low-grade serous ovarian cancer (LGSOC), strong expression of both MyD88 and TLR4 was associated with favorable survival (HR [95% CI], 0.49 [0.29–0.84] and 0.44 [0.21–0.89], respectively; P=.009 and P=.02, respectively). Conclusion Results are consistent with an association between strong MyD88 staining and advanced stage and poorer survival in HGSOC and demonstrate correlation between strong MyD88 and TLR4 staining and improved survival in LGSOC, highlighting the biological differences between the 2 serous histotypes. PMID:29502561

MyD88 and TLR4 Expression in Epithelial Ovarian Cancer.

PubMed

Block, Matthew S; Vierkant, Robert A; Rambau, Peter F; Winham, Stacey J; Wagner, Philipp; Traficante, Nadia; Tołoczko, Aleksandra; Tiezzi, Daniel G; Taran, Florin Andrei; Sinn, Peter; Sieh, Weiva; Sharma, Raghwa; Rothstein, Joseph H; Ramón Y Cajal, Teresa; Paz-Ares, Luis; Oszurek, Oleg; Orsulic, Sandra; Ness, Roberta B; Nelson, Gregg; Modugno, Francesmary; Menkiszak, Janusz; McGuire, Valerie; McCauley, Bryan M; Mack, Marie; Lubiński, Jan; Longacre, Teri A; Li, Zheng; Lester, Jenny; Kennedy, Catherine J; Kalli, Kimberly R; Jung, Audrey Y; Johnatty, Sharon E; Jimenez-Linan, Mercedes; Jensen, Allan; Intermaggio, Maria P; Hung, Jillian; Herpel, Esther; Hernandez, Brenda Y; Hartkopf, Andreas D; Harnett, Paul R; Ghatage, Prafull; García-Bueno, José M; Gao, Bo; Fereday, Sian; Eilber, Ursula; Edwards, Robert P; de Sousa, Christiani B; de Andrade, Jurandyr M; Chudecka-Głaz, Anita; Chenevix-Trench, Georgia; Cazorla, Alicia; Brucker, Sara Y; Alsop, Jennifer; Whittemore, Alice S; Steed, Helen; Staebler, Annette; Moysich, Kirsten B; Menon, Usha; Koziak, Jennifer M; Kommoss, Stefan; Kjaer, Susanne K; Kelemen, Linda E; Karlan, Beth Y; Huntsman, David G; Høgdall, Estrid; Gronwald, Jacek; Goodman, Marc T; Gilks, Blake; García, María José; Fasching, Peter A; de Fazio, Anna; Deen, Suha; Chang-Claude, Jenny; Candido Dos Reis, Francisco J; Campbell, Ian G; Brenton, James D; Bowtell, David D; Benítez, Javier; Pharoah, Paul D P; Köbel, Martin; Ramus, Susan J; Goode, Ellen L

2018-03-01

To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival. We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong). Expression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P<.001 for both). In HGSOC, strong MyD88 expression was modestly associated with shortened overall survival (hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P=.04) but was also associated with advanced stage (P<.001). The expression of TLR4 was not associated with survival. In low-grade serous ovarian cancer (LGSOC), strong expression of both MyD88 and TLR4 was associated with favorable survival (HR [95% CI], 0.49 [0.29-0.84] and 0.44 [0.21-0.89], respectively; P=.009 and P=.02, respectively). Results are consistent with an association between strong MyD88 staining and advanced stage and poorer survival in HGSOC and demonstrate correlation between strong MyD88 and TLR4 staining and improved survival in LGSOC, highlighting the biological differences between the 2 serous histotypes. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

MV-NIS or Investigator's Choice Chemotherapy in Treating Patients With Ovarian, Fallopian, or Peritoneal Cancer

ClinicalTrials.gov

2018-04-27

Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Endometrioid Tumor; Malignant Ovarian Serous Tumor; Ovarian Seromucinous Carcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Peptide secretion in the cutaneous glands of South American tree frog Phyllomedusa bicolor: an ultrastructural study.

PubMed

Lacombe, C; Cifuentes-Diaz, C; Dunia, I; Auber-Thomay, M; Nicolas, P; Amiche, M

2000-09-01

The development of the dermal glands of the arboreal frog Phyllomedusa bicolor was investigated by immunocytochemistry and electron microscopy. The 3 types of glands (mucous, lipid and serous) differed in size and secretory activity. The mucous and serous glands were apparent in the tadpole skin, whereas the lipid glands developed later in ontogenesis. The peptide antibiotics dermaseptins and the D-amino acid-containing peptide opioids dermorphins and deltorphins are abundant in the skin secretions of P. bicolor. Although these peptides differ in their structure and activity they are derived from precursors that have very similar preproregions. We used an antibody to the common preproregion of preprodermaseptins and preprodeltorphins and immunofluorescence analysis to show that only the serous glands are specifically involved in the biosynthesis and secretion of dermaseptins and deltorphins. Scanning and transmission electron microscopy revealed that the serous glands of P bicolor have morphological features, especially the secretory granules, which differ from those of the glands in Xenopus laevis skin.

Marrow changes in anorexia nervosa masking the presence of stress fractures on MR imaging.

PubMed

Tins, Bernhard; Cassar-Pullicino, Victor

2006-11-01

Patients with anorexia nervosa (AN) usually have abnormal bone and bone marrow metabolism resulting in osteopenia and serous bone marrow change. There is an increased risk of stress/insufficiency fractures and these can be the first presentation of AN. This case report describes a patient with previously undiagnosed AN who presented with foot pain. The serous bone marrow changes of AN were found to mask the MR imaging features of stress fractures, as both had low T1w and high T2w and STIR signal intensities. Contrast enhancement was not helpful but actually masked fractures. Scintigraphy was helpful. The radiologist might be the first clinician to raise the possibility of AN and should be aware of the difficulties in diagnosing stress fractures in bones with underlying serous bone marrow change. In this severe case of AN even the heel fat pad and the fat pad in Kager's triangle had undergone serous change.

Retinal detachment in hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome: Color vision abnormality as the first and predominant manifestation.

PubMed

Morisawa, Hiroyuki; Makino, Shinji; Takahashi, Hironori; Sorita, Mari; Matsubara, Shigeki

2015-11-01

Serous retinal detachment is sometimes caused by hypertensive disorders in pregnancy and its associated conditions, in which the predominant eye symptoms are blurred vision, distorted vision, and reduced visual acuity. To our best knowledge, this is the first report of a puerperal woman with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome in whom color vision abnormality was the first and predominant manifestation of serous retinal detachment. At 32 weeks of gestation, the 34-year-old Japanese woman underwent cesarean section due to HELLP syndrome. She complained of color vision abnormality on day 1 post-partum and ophthalmological examination revealed serous retinal detachment of both eyes. The visual acuity was preserved. With supportive therapy, her color vision abnormality gradually ameliorated and retinal detachment completely resolved on day 34 post-partum without any sequelae. Obstetricians should be aware that color vision abnormality can be the first and predominant symptom of HELLP-related serous retinal detachment. © 2015 Japan Society of Obstetrics and Gynecology.

Morphologic, Immunophenotypic, and Molecular Features of Epithelial Ovarian Cancer.

PubMed

Ramalingam, Preetha

2016-02-01

Epithelial ovarian cancer comprises a heterogeneous group of tumors. The four most common subtypes are serous, endometrioid, clear cell, and mucinous carcinoma. Less common are transitional cell tumors, including transitional cell carcinoma and malignant Brenner tumor. While in the past these subtypes were grouped together and designated as epithelial ovarian tumors, these tumor types are now known to be separate entities with distinct clinical and biologic behaviors. From a therapeutic standpoint, current regimens employ standard chemotherapy based on stage and grade rather than histotype. However, this landscape may change in the era of personalized therapy, given that most subtypes (with the exception of high-grade serous carcinoma) are relatively resistant to chemotherapy. It is now well-accepted that high-grade and low-grade serous carcinomas represent distinct entities rather than a spectrum of the same tumor type. While they are similar in that patients present with advanced-stage disease, their histologic and molecular features are entirely different. High-grade serous carcinoma is associated with TP53 mutations, whereas low-grade serous carcinomas are associated with BRAF and KRAS mutations. Endometrioid and clear cell carcinomas typically present as early-stage disease and are frequently associated with endometriosis. Mucinous carcinomas typically present as large unilateral masses and often show areas of mucinous cystadenoma and mucinous borderline tumor. It must be emphasized that primary mucinous carcinomas are uncommon tumors, and metastasis from other sites such as the appendix, colon, stomach, and pancreaticobiliary tract must always be considered in the differential diagnosis. Lastly, transitional cell tumors of the ovary, specifically malignant Brenner tumors, are quite uncommon. High-grade serous carcinoma often has a transitional cell pattern, and adequate sampling in most cases shows more typical areas of serous carcinoma. Immunohistochemical

Serum and peritoneal fluid concentrations of soluble human leukocyte antigen, tumor necrosis factor alpha and interleukin 10 in patients with selected ovarian pathologies.

PubMed

Sipak-Szmigiel, Olimpia; Włodarski, Piotr; Ronin-Walknowska, Elżbieta; Niedzielski, Andrzej; Karakiewicz, Beata; Słuczanowska-Głąbowska, Sylwia; Laszczyńska, Maria; Malinowski, Witold

2017-04-04

Although immune system plays a key role in the pathogenesis of both endometriosis and ovarian cancer, its function is different. Therefore, we hypothesized, that selected immune parameters can serve as diagnostic markers of these two conditions. The aim of this study was to compare serum and peritoneal fluid concentrations of sHLA-G, IL-10 and TNF-alpha in women with selected ovarian pathologies: benign serous cysts, endometrioma and malignant tumors. Clinical significance of using them for diagnostic purposes in women with serous ovarian cysts, endometriosis, and ovarian cancer, which in the future may improve the early diagnosis of ovarian diseases. The study included women treated surgically for benign serous ovarian cysts, ovarian endometrioma and serous ovarian adenocarcinomas. Peripheral blood and peritoneal fluid samples were obtained intraoperatively. Patients with benign serous cysts, endometrioma and ovarian malignancies did not differ significantly in terms of their serum and peritoneal fluid concentrations of sHLA-G. Ovarian cancer patients presented with significantly higher median serum concentrations of IL-10 and TNF-alpha than other study subjects. Median concentrations of IL-10 and TNF-alpha in peritoneal fluid turned out to be the highest in ovarian cancer patients, followed by women with endometrioma and subjects with benign serous cysts. All these intergroup differences were statistically significant. Irrespective of the group, median concentrations of sHLA-G, IL-10 and TNF-alpha in peritoneal fluid were higher than serum levels of these markers. Elevated serum and peritoneal fluid concentrations of IL-10 and TNF-alpha distinguish ovarian malignancies and endometriomas from benign serous ovarian cysts. In contrast to endometriosis, ovarian malignancies are characterized by elevated peritoneal fluid concentrations of IL-10 and TNF-alpha, elevated serum concentrations of IL-10 and low serum levels of TNF-alpha. Serum and peritoneal fluid

SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody-Drug Conjugate, Shows Antitumor Activity in Uterine Serous Carcinoma with HER2/Neu Expression.

PubMed

Black, Jonathan; Menderes, Gulden; Bellone, Stefania; Schwab, Carlton L; Bonazzoli, Elena; Ferrari, Francesca; Predolini, Federica; De Haydu, Christopher; Cocco, Emiliano; Buza, Natalia; Hui, Pei; Wong, Serena; Lopez, Salvatore; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Litkouhi, Babak; Schwartz, Peter E; Goedings, Peter; Beusker, Patrick H; van der Lee, Miranda M C; Timmers, C Marco; Dokter, Wim H A; Santin, Alessandro D

2016-08-01

Uterine serous carcinoma (USC) is an aggressive form of endometrial cancer. Up to 35% of USC may overexpress the HER2/neu oncogene at strong (i.e., 3+) levels by IHC while an additional 40% to 50% express HER2/neu at moderate (2+) or low (1+) levels. We investigated the efficacy of SYD985, (Synthon Biopharmaceuticals), a novel HER2-targeting antibody-drug conjugate (ADC) composed of the mAb trastuzumab linked to a highly potent DNA-alkylating agent (i.e., duocarmycin) in USC. We also compared the antitumor activity of SYD985 in head-to-head experiments to trastuzumab emtansine (T-DM1), a FDA-approved ADC, against multiple primary USC cell lines expressing different levels of HER2/neu in in vitro and in vivo experiments. Using antibody-dependent cellular cytotoxicity (ADCC), proliferation, viability, and bystander killing assays as well as propidium iodide-based flow cytometry assays and multiple in vivo USC mouse xenograft models, we demonstrate for the first time that SYD985 is a novel ADC with activity against USC with strong (3+) as well as low to moderate (i.e., 1+/2+) HER2/neu expression. SYD985 is 10- to 70-fold more potent than T-DM1 in comparative experiments and, unlike T-DM1, it is active against USC demonstrating moderate/low or heterogeneous HER2/neu expression. Clinical studies with SYD985 in patients harboring chemotherapy-resistant USC with low, moderate, and high HER2 expression are warranted. Mol Cancer Ther; 15(8); 1900-9. ©2016 AACR. ©2016 American Association for Cancer Research.

Central Pit Crater

NASA Image and Video Library

2015-11-13

Crater floors can have a range of features, from flat to a central peak or a central pit. This image from NASA 2001 Mars Odyssey spacecraft shows an unnamed crater in Terra Sabaea has a central pit. This unnamed crater in Terra Sabaea has a central pit. The different floor features develop do due several factors, including the size of the impactor, the geology of the surface material and the geology of the materials at depth. Orbit Number: 60737 Latitude: 22.3358 Longitude: 61.2019 Instrument: VIS Captured: 2015-08-23 20:13 http://photojournal.jpl.nasa.gov/catalog/PIA20092

PIK3CA oncogenic mutations represent a major mechanism of resistance to trastuzumab in HER2/neu overexpressing uterine serous carcinomas

PubMed Central

Black, Jonathan D; Lopez, Salvatore; Cocco, Emiliano; Bellone, Stefania; Altwerger, Gary; Schwab, Carlton L; English, Diana P; Bonazzoli, Elena; Predolini, Federica; Ferrari, Francesca; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Santin, Alessandro D

2015-01-01

Objectives: We evaluated the role of PIK3CA-mutations as mechanism of resistance to trastuzumab in primary HER2/neu-amplified uterine-serous-carcinoma (USC) cell lines. Methods: Fifteen whole-exome-sequenced USC cell lines were tested for HER2/neu-amplification and PIK3CA-mutations. Four HER2/neu-amplified USC (2-harbouring wild-type-PIK3CA-genes and 2-harbouring oncogenic-PIK3CA-mutations) were evaluated in in vitro dose-titration-proliferation-assays, cell-viability and HER2 and S6-protein-phosphorylation after exposure to trastuzumab. USC harbouring wild-type-PIK3CA were transfected with plasmids encoding oncogenic PIK3CA-mutations (i.e., H1047R/R93Q) and exposed to trastuzumab. Finally, trastuzumab efficacy was tested by using two USC xenograft mouse models. Results: Seven out of fifteen (46%) of the USC cell lines were HER2/neu-amplified by fluorescence in situ hybridisation. Within these tumours four out of seven (57%) were found to harbour oncogenic PIK3CA-mutations vs two out of eight (25%) of the HER2/neu not amplified cell lines (P=0.01). HER2/neu-amplified/PIK3CA-mutated USC were highly resistant to trastuzumab when compared with HER2/neu-amplified/wild-type-PIK3CA cell lines (P=0.02). HER2/neu-amplified/PIK3CA wild-type cell lines transfected with oncogenic PIK3CA-mutations increased their resistance to trastuzumab (P<0.0001). Trastuzumab was effective in reducing tumour growth (P=0.001) and improved survival (P=0.0001) in mouse xenografts harbouring HER2-amplified/PIK3CA wild-type USC but not in HER2-amplified/PIK3CA-mutated tumours. Conclusions: Oncogenic PIK3CA mutations are common in HER2/neu-amplified USC and may constitute a major mechanism of resistance to trastuzumab treatment. PMID:26325104

RASSF1A promoter methylation in high-grade serous ovarian cancer: A direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA.

PubMed

Giannopoulou, Lydia; Chebouti, Issam; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S

2017-03-28

The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B. Using both assays, RASSF1A promoter was found highly methylated in primary tumors of both groups, and at lower percentages in the adjacent morphologically tumor cell-free tissues. Interestingly, RASSF1A promoter methylation was also observed in ctDNA by real-time MSP. Overall survival (OS) was significantly associated with RASSF1A promoter methylation in primary tumor samples using MS-HRMA (P=0.023). Our results clearly indicate that RASSF1A promoter is methylated in adjacent tissue surrounding the tumor in HGSC patients. We report for the first time that RASSF1A promoter methylation provides significant prognostic information in HGSC patients.

RASSF1A promoter methylation in high-grade serous ovarian cancer: A direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA

PubMed Central

Giannopoulou, Lydia; Chebouti, Issam; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S.

2017-01-01

The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B. Using both assays, RASSF1A promoter was found highly methylated in primary tumors of both groups, and at lower percentages in the adjacent morphologically tumor cell-free tissues. Interestingly, RASSF1A promoter methylation was also observed in ctDNA by real-time MSP. Overall survival (OS) was significantly associated with RASSF1A promoter methylation in primary tumor samples using MS-HRMA (P=0.023). Our results clearly indicate that RASSF1A promoter is methylated in adjacent tissue surrounding the tumor in HGSC patients. We report for the first time that RASSF1A promoter methylation provides significant prognostic information in HGSC patients. PMID:28206954

North Central IPM Center

Science.gov Websites

) solutions, based in the North Central region. North Central IPM Center Invasive Plants in Trade Working webpage to learn about the North Central IPM Center's grants program and other IPM-related funding Tribal IPM Urban Ag IPM Partners In IPM Working Groups Critical Issues Projects North Central IPM

Dose-Response Association of CD8+ Tumor-Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer.

PubMed

Goode, Ellen L; Block, Matthew S; Kalli, Kimberly R; Vierkant, Robert A; Chen, Wenqian; Fogarty, Zachary C; Gentry-Maharaj, Aleksandra; Tołoczko, Aleksandra; Hein, Alexander; Bouligny, Aliecia L; Jensen, Allan; Osorio, Ana; Hartkopf, Andreas; Ryan, Andy; Chudecka-Głaz, Anita; Magliocco, Anthony M; Hartmann, Arndt; Jung, Audrey Y; Gao, Bo; Hernandez, Brenda Y; Fridley, Brooke L; McCauley, Bryan M; Kennedy, Catherine J; Wang, Chen; Karpinskyj, Chloe; de Sousa, Christiani B; Tiezzi, Daniel G; Wachter, David L; Herpel, Esther; Taran, Florin Andrei; Modugno, Francesmary; Nelson, Gregg; Lubiński, Jan; Menkiszak, Janusz; Alsop, Jennifer; Lester, Jenny; García-Donas, Jesús; Nation, Jill; Hung, Jillian; Palacios, José; Rothstein, Joseph H; Kelley, Joseph L; de Andrade, Jurandyr M; Robles-Díaz, Luis; Intermaggio, Maria P; Widschwendter, Martin; Beckmann, Matthias W; Ruebner, Matthias; Jimenez-Linan, Mercedes; Singh, Naveena; Oszurek, Oleg; Harnett, Paul R; Rambau, Peter F; Sinn, Peter; Wagner, Philipp; Ghatage, Prafull; Sharma, Raghwa; Edwards, Robert P; Ness, Roberta B; Orsulic, Sandra; Brucker, Sara Y; Johnatty, Sharon E; Longacre, Teri A; Ursula, Eilber; McGuire, Valerie; Sieh, Weiva; Natanzon, Yanina; Li, Zheng; Whittemore, Alice S; Anna, deFazio; Staebler, Annette; Karlan, Beth Y; Gilks, Blake; Bowtell, David D; Høgdall, Estrid; Candido dos Reis, Francisco J; Steed, Helen; Campbell, Ian G; Gronwald, Jacek; Benítez, Javier; Koziak, Jennifer M; Chang-Claude, Jenny; Moysich, Kirsten B; Kelemen, Linda E; Cook, Linda S; Goodman, Marc T; García, María José; Fasching, Peter A; Kommoss, Stefan; Deen, Suha; Kjaer, Susanne K; Menon, Usha; Brenton, James D; Pharoah, Paul DP; Chenevix-Trench, Georgia; Huntsman, David G; Winham, Stacey J; Köbel, Martin; Ramus, Susan J

2017-12-01

Cytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors. To define the prognostic role of CD8+ TILs in epithelial ovarian cancer. This was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium. More than 5500 patients, including 3196 with high-grade serous ovarian carcinomas (HGSOCs), were followed prospectively for over 24 650 person-years. Following immunohistochemical analysis, CD8+ TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+ TILs per high-powered field: negative (none), low (1-2), moderate (3-19), and high (≥20). CD8+ TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines. Overall survival time. The final sample included 5577 women; mean age at diagnosis was 58.4 years (median, 58.2 years). Among the 5 major invasive histotypes, HGSOCs showed the most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+ TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+ TILs, respectively (P value for trend = 4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not for those with the other histotypes. Among HGSOCs, CD8+ TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation, but were not prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+ TIL counts showed a near-log-linear functional form. This study

Timing of drainage tube removal after thyroid surgery: a retrospective study.

PubMed

Minami, Shigeki; Sakimura, Chika; Hayashida, Naomi; Yamanouchi, Kosho; Kuroki, Tamotsu; Eguchi, Susumu

2014-01-01

The aim of this study was to evaluate the chronological changes in the amount of drainage fluid after thyroidectomy, and to establish standard indications for the drain to be removed. We examined a cohort of 249 patients undergoing thyroid surgery. The patients were divided into four groups: a Graves' group, a non-dissection group, a central-dissection group and a lateral-dissection group. The amount of drainage was measured every 6 h, and the drain was removed postoperatively when the drainage decreased in amount and contained serous fluid after a meal. In all four groups, the most drainage occurred in the first 6 h after surgery. The total amount of drainage from the operation to the time of drain removal was significantly higher in Graves' group and in the lateral-dissection group than in the other two groups. The median wound drainage significantly decreased from 12 to 18 h after surgery in all four groups. In the lateral-dissection group, the wound drainage significantly decreased again in the first 24-30 h. The findings of this study suggest that drains can be removed postoperatively if the drainage was less than 15 mL during a 6-h period and contain serous fluid.

[Language delay in children with chronic suppurative otitis media].

PubMed

Biurrún Unzué, Oscar; Biurrún Unzué, Ana; Villacorta Labairu, Begoña; Andrade Arriaga, Marcela

2003-01-01

The chronic serous otitis media is a well known cause of fluctuant moderated conduction deafness in childhood but not well studied in Castillian speaking areas, as a cause of alterations in the acquisition of language. In the present study we evaluate the chronic serous otitis media as a cause of alterations in the development of the language in childhood. We studied the semantic development level in a group of 18 four years old children affected of chronic serous otitis media of more than one year evolution. The incidence of alterations was of 27.7%. We discuss the results obtained and we propose a management for this pathology.

12 CFR 234.4 - Standards for central securities depositories and central counterparties.

Code of Federal Regulations, 2013 CFR

2013-01-01

... it meets or exceeds the following risk-management standards with respect to the payment, clearing... central counterparty's risk-management procedures. (9) The central securities depository or central... plausible market conditions. (b) The Board, by order, may apply heightened risk-management standards to a...

12 CFR 234.4 - Standards for central securities depositories and central counterparties.

Code of Federal Regulations, 2014 CFR

2014-01-01

... it meets or exceeds the following risk-management standards with respect to the payment, clearing... central counterparty's risk-management procedures. (9) The central securities depository or central... plausible market conditions. (b) The Board, by order, may apply heightened risk-management standards to a...

Central Venous Catheter (Central Line)

MedlinePlus

... the skin entry site. With care, central venous catheters can remain in the body for several months without becoming infected. ■ ■ Blocking or kinking— Blood clots may begin to form in the catheter but ...

Central Nervous System Vasculitis

MedlinePlus

... of Vasculitis / Central Nervous System (CNS) Vasculitis Central Nervous System (CNS) Vasculitis Swap out your current Facebook Profile ... Facebook personal page. Replace with this image. Central nervous system (CNS) vasculitis is inflammation of blood vessel walls ...

Retinal flavoprotein autofluorescence as a measure of retinal health.

PubMed

Elner, Susan G; Elner, Victor M; Field, Matthew G; Park, Seung; Heckenlively, John R; Petty, Howard R

2008-01-01

To establish that increased autofluorescence of mitochondrial flavoproteins, an indicator of mitochondrial oxidative stress, correlates with retinal cell dysfunction. Retinal flavoprotein autofluorescence (FA) was imaged in humans with a fundus camera modified with 467DF8-nm excitation and 535-nm emission filters and a back-illuminated, electron-multiplying, charge-coupled device camera interfaced with a computer equipped with customized image capture software. Multiple digital images, centered on the fovea, were obtained from each eye. Histograms of pixel intensities in grayscale units were analyzed for average intensity and average curve width. Adults with diabetes mellitus, age-related macular degeneration (ARMD), central serous retinopathy, and retinal dystrophies, as well as healthy control volunteers, were imaged. Monolayers of cultured human retinal pigment epithelial (HRPE) cells, HRPE cells exposed to sublethal doses of H2O2, and HRPE cells exposed to H2O2 in the presence of antioxidants were imaged for FA using fluorescent photomicroscopy. Control patients demonstrated low levels of retinal FA, which increased progressively with age. Diabetics without visible retinopathy demonstrated increased FA levels compared to control volunteers (P < .001). Diabetics with retinopathy demonstrated significantly higher FA values than those without retinopathy (P < .04). Patients with ARMD, central serous retinopathy, or retinal dystrophies also demonstrated significantly increased FA. Compared to control RPE cells, cells oxidatively stressed with H2O2 had significantly elevated FA (P < .05), which was prevented by antioxidants (P < .05). Retinal FA is significantly increased with age and diseases known to be mediated by oxidative stress. Retinal FA imaging may provide a novel, noninvasive method of assessing retinal health and retinal dysfunction prior to retinal cell death.

Dual CCNE1/PIK3CA targeting is synergistic in CCNE1-amplified/PIK3CA-mutated uterine serous carcinomas in vitro and in vivo

PubMed Central

Cocco, Emiliano; Lopez, Salvatore; Black, Jonathan; Bellone, Stefania; Bonazzoli, Elena; Predolini, Federica; Ferrari, Francesca; Schwab, Carlton L; Menderes, Gulden; Zammataro, Luca; Buza, Natalia; Hui, Pei; Wong, Serena; Zhao, Siming; Bai, Yalai; Rimm, David L; Ratner, Elena; Litkouhi, Babak; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Santin, Alessandro D

2016-01-01

Background: Clinical options for patients harbouring advanced/recurrent uterine serous carcinoma (USC), an aggressive variant of endometrial tumour, are very limited. Next-generation sequencing (NGS) data recently demonstrated that cyclin E1 (CCNE1) gene amplification and pik3ca driver mutations are common in USC and may therefore represent ideal therapeutic targets. Methods: Cyclin E1 expression was evaluated by immunohistochemistry (IHC) on 95 USCs. The efficacy of the cyclin-dependent kinase 2/9 inhibitor CYC065 was assessed on multiple primary USC cell lines with or without CCNE1 amplification. Cell-cycle analyses and knockdown experiments were performed to assess CYC065 targeting specificity. Finally, the in vitro and in vivo activity of CYC065, Taselisib (a PIK3CA inhibitor) and their combinations was tested on USC xenografts derived from CCNE1-amplified/pik3ca-mutated USCs. Results: We found that 89.5% of the USCs expressed CCNE1. CYC065 blocked cells in the G1 phase of the cell cycle and inhibited cell growth specifically in CCNE1-overexpressing USCs. Cyclin E1 knockdown conferred increased resistance to CYC065, whereas CYC065 treatment of xenografts derived from CCNE1-amplified USCs significantly reduced tumour growth. The combination of CYC065 and Taselisib demonstrated synergistic effect in vitro and was significantly more effective than single-agent treatment in decreasing tumour growth in xenografts of CCNE1-amplified/pik3ca-mutated USCs. Conclusions: Dual CCNE1/PIK3CA blockade may represent a novel therapeutic option for USC patients harbouring recurrent CCNE1-amplified/pi3kca-mutated tumours. PMID:27351214

Assessing the risk of pelvic and para-aortic nodal involvement in apparent early-stage ovarian cancer: A predictors- and nomogram-based analyses.

PubMed

Bogani, Giorgio; Tagliabue, Elena; Ditto, Antonino; Signorelli, Mauro; Martinelli, Fabio; Casarin, Jvan; Chiappa, Valentina; Dondi, Giulia; Leone Roberti Maggiore, Umberto; Scaffa, Cono; Borghi, Chiara; Montanelli, Luca; Lorusso, Domenica; Raspagliesi, Francesco

2017-10-01

To estimate the prevalence of lymph node involvement in early-stage epithelial ovarian cancer in order to assess the prognostic value of lymph node dissection. Data of consecutive patients undergoing staging for early-stage epithelial ovarian cancer were retrospectively evaluated. Logistic regression and a nomogram-based analysis were used to assess the risk of lymph node involvement. Overall, 290 patients were included. All patients had lymph node dissection including pelvic and para-aortic lymphadenectomy. Forty-two (14.5%) patients were upstaged due to lymph node metastatic disease. Pelvic and para-aortic nodal metastases were observed in 22 (7.6%) and 42 (14.5%) patients. Lymph node involvement was observed in 18/95 (18.9%), 1/37 (2.7%), 4/29 (13.8%), 11/63 (17.4%), 3/41 (7.3%) and 5/24 (20.8%) patients with high-grade serous, low-grade-serous, endometrioid G1, endometrioid G2&3, clear cell and undifferentiated, histology, respectively (p=0.12, Chi-square test). We observed that high-grade serous histology was associated with an increased risk of pelvic node involvement; while, histology rather than low-grade serous and bilateral tumors were independently associated with para-aortic lymph node involvement (p<0.05). Nomograms displaying the risk of nodal involvement in the pelvic and para-aortic areas were built. High-grade serous histology and bilateral tumors are the main characteristics suggesting lymph node positivity. Our data suggested that high-grade serous and bilateral early-stage epithelial ovarian cancer are at high risk of having disease harboring in the lymphatic tissues of both pelvic and para-aortic area. After receiving external validation, our data will help to identify patients deserving comprehensive retroperitoneal staging. Copyright © 2017 Elsevier Inc. All rights reserved.

Prognostic predictive value of preoperative intratumoral 2-deoxy-2-(18F)fluoro-D-glucose uptake heterogeneity in patients with high-grade serous ovarian cancer.

PubMed

Liu, Shuai; Feng, Zheng; Jiang, Zhaoxia; Wen, Hao; Xu, Junyan; Pan, Herong; Deng, Yu; Zhang, Lei; Ju, Xingzhu; Chen, Xiaojun; Wu, Xiaohua

2018-05-16

This study aimed to explore the clinical and prognostic significance of pretreatment positron-emission tomography/computed tomography (PET/CT) parameters, especially 2-deoxy-2-(F)fluoro-D-glucose-based heterogeneity, in high-grade serous ovarian cancer (HGSC). We retrospectively investigated 56 patients with HGSC who underwent PET/CT before primary surgery at our hospital between January 2010 and June 2015. None of these patients received neoadjuvant chemotherapy. PET/CT parameters, including maximum and mean standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and intratumoral heterogeneity index (HI), were measured for all patients. Differences of each PET/CT parameter between primary tumors (-P) and omental metastatic lesions (-M) were compared by paired t tests. Progression-free survival (PFS) and overall survival were analyzed by the Kaplan-Meier method and log-rank tests in univariate analyses. Cox regression analyses were used for multivariate analysis. SUVmean-P was higher than SUVmean-M (P=0.001). However, there were no statistical differences of SUVmax, MTV, TLG, or HI between primary and omental lesions. Chemosensitive patients tended to have higher levels of SUVmax-P (P=0.011), MTV-P (P=0.014), TLG-P (P=0.035), and HI-P (P=0.002), respectively. In univariate analyses, higher HI-P was associated with better PFS (P=0.007). However, in multivariate analysis, HI-P was not an independent predictor of PFS (P=0.581). Neither HI-P nor HI-M was the prognostic predictor for overall survival (P=0.078 and 0.063, respectively). 2-Deoxy-2-(F)fluoro-D-glucose-based heterogeneity appears to be a predictive and prognostic factor for patients with HGSC. Parameters of primary tumors have predominant value compared with omental metastatic lesions.

T-DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo

PubMed Central

English, Diana P; Bellone, Stefania; Schwab, Carlton L; Bortolomai, Ileana; Bonazzoli, Elena; Cocco, Emiliano; Buza, Natalia; Hui, Pei; Lopez, Salvatore; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

2014-01-01

Amplification of c-erbB2 has been reported in over 30% of uterine serous carcinoma (USC) and found to confer poor survival because of high proliferation and increased resistance to therapy. In this study, we evaluated for the first time Trastuzumab emtansine (T-DM1), a novel antibody–drug conjugate, against multiple epidermal growth factor receptor-2 (HER2)-positive USC cells in vitro followed by developing a supportive in vivo model. Fifteen primary USC cell lines were assessed by immunohistochemistry (IHC) and flow cytometry for HER2 protein expression. C-erbB2 gene amplification was evaluated using fluorescent in situ hybridization. Sensitivity to T-DM1 and trastuzumab (T)-induced antibody-dependent cell-mediated cytotoxicity was evaluated in 5-h chromium release assays. T-DM1 and T cytostatic and apoptotic activities were evaluated using flow-cytometry-based proliferation assays. In vivo activity of T-DM1 versus T in USC xenografts in SCID mice was also evaluated. High levels of HER2 protein overexpression and HER2 gene amplification were detected in 33% of USC cell lines. T-DM1 was considerably more effective than trastuzumab in inhibiting cell proliferation and in causing apoptosis (P = 0.004) of USC showing HER2 overexpression. Importantly, T-DM1 was highly active at reducing tumor formation in vivo in USC xenografts overexpressing HER2 (P = 0.04) and mice treated with TDM-1 had significantly longer survival when compared to T-treated mice and control mice (P ≤ 0.0001). T-DM1 shows promising antitumor effect in HER2-positive USC cell lines and USC xenografts and its activity is significantly higher when compared to T. T-DM1 may represent a novel treatment option for HER2-positive USC patients with disease refractory to trastuzumab and traditional chemotherapy. PMID:24890382

Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Bevacizumab in Treating Patients With Stage IV Melanoma That Cannot Be Removed by Surgery or Gynecological Cancers

ClinicalTrials.gov

2018-02-05

Cervical Adenosarcoma; Cervical Adenosquamous Carcinoma; Cervical Carcinosarcoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Fallopian Tube Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Epithelial Tumor; Malignant Peritoneal Neoplasm; Ovarian Carcinosarcoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Skin Melanoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma; Uterine Corpus Carcinosarcoma

Carboplatin and Paclitaxel With or Without Bevacizumab in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

ClinicalTrials.gov

2017-10-23

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Paclitaxel, Polyglutamate Paclitaxel, or Observation in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Peritoneal Cancer, or Fallopian Tube Cancer

ClinicalTrials.gov

2017-05-03

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

CENTRAL PLATEAU REMEDIATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

ROMINE, L.D.

2006-02-01

A systematic approach to closure planning is being implemented at the Hanford Site's Central Plateau to help achieve the goal of closure by the year 2035. The overall objective of Central Plateau remediation is to protect human health and the environment from the significant quantity of contaminated material that resulted from decades of plutonium production in support of the nation's defense. This goal will be achieved either by removing contaminants or placing the residual contaminated materials in a secure configuration that minimizes further migration to the groundwater and reduces the potential for inadvertent intrusion into contaminated sites. The approach tomore » Central Plateau cleanup used three key concepts--closure zones, closure elements, and closure process steps--to create an organized picture of actions required to complete remediation. These actions were merged with logic ties, constraints, and required resources to produce an integrated time-phased schedule and cost profile for Central Plateau closure. Programmatic risks associated with implementation of Central Plateau closure were identified and analyzed. Actions to mitigate the most significant risks are underway while high priority remediation projects continue to make progress.« less

BRCA1 is expressed in uterine serous carcinoma (USC) and controls insulin-like growth factor I receptor (IGF-IR) gene expression in USC cell lines.

PubMed

Amichay, Keren; Kidron, Debora; Attias-Geva, Zohar; Schayek, Hagit; Sarfstein, Rive; Fishman, Ami; Werner, Haim; Bruchim, Ilan

2012-06-01

The insulin-like growth factor I receptor (IGF-IR) and BRCA1 affect cell growth and apoptosis. Little information is available about BRCA1 activity on the IGF signaling pathway. This study evaluated the effect of BRCA1 on IGF-IR expression. BRCA1 and IGF-IR immunohistochemistry on archival tissues (35 uterine serous carcinomas [USCs] and 17 metastases) were performed. USPC1 and USPC2 cell lines were transiently cotransfected with an IGF-IR promoter construct driving a luciferase reporter gene and a BRCA1 expression plasmid. Endogenous IGF-IR levels were evaluated by Western immunoblotting. We found high BRCA1 and IGF-IR protein expression in primary and metastatic USC tumors. All samples were immunostained for BRCA1-71% strongly stained; and 33/35 (94%) were stained positive for IGF-IR-2 (6%) strongly stained. No difference in BRCA1 and IGF-IR staining intensity was noted between BRCA1/2 mutation carriers and noncarriers. Metastatic tumors stained more intensely for BRCA1 than did the primary tumor site (P = 0.041) and with borderline significance for IGF-IR (P = 0.069). BRCA1 and IGF-IR staining did not correlate to survival. BRCA1 expression led to 35% and 54% reduction in IGF-IR promoter activity in the USPC1 and USCP2 cell lines, respectively. Western immunoblotting showed a decline in phosphorylated IGF-IR and phosphorylated AKT in both transiently and stably transfected cells. BRCA1 and IGF-IR are highly expressed in USC tumors. BRCA1 suppresses IGF-IR gene expression and activity. These findings suggest a possible biological link between the BRCA1 and the IGF-I signaling pathways in USC. The clinical implications of this association need to be explored.

HER2/neu gene amplification determines the sensitivity of uterine serous carcinoma cell lines to AZD8055, a novel dual mTORC1/2 inhibitor.

PubMed

English, Diana P; Roque, Dana M; Carrara, Luisa; Lopez, Salvatore; Bellone, Stefania; Cocco, Emiliano; Bortolomai, Ileana; Schwartz, Peter E; Rutherford, Thomas; Santin, Alessandro D

2013-12-01

To evaluate c-erbB2 gene amplification in a series of primary uterine serous carcinoma (USC) cell lines. To assess the efficacy of AZD8055, a novel dual mTORC1/2 inhibitor against primary HER2/neu amplified vs HER2/neu not amplified USC cell lines. Twenty-two primary USC cell lines were evaluated for c-erbB2 oncogene amplification by FISH assays. In vitro sensitivity to AZD8055 was evaluated by flow-cytometry-based viability and proliferation assays. Cell cycle profile and downstream cellular responses to AZD8055 were assessed by measuring the DNA content of cells and by phosphorylation of the S6 protein by flow-cytometry. Nine of 22 (40.9%) USC cell lines demonstrated c-erbB2 gene amplification by FISH. AZD8055 caused a strong differential growth inhibition in USC cell lines, with high HER-2/neu-expressors demonstrating significantly higher sensitivity when compared to low HER-2/neu-expressors (AZD-8055 IC50 mean±SEM=0.27±0.05μM in c-erbB2 amplified versus 1.67±0.68μM in c-erbB2 not amplified tumors, P=0.03). AZD8055 growth-inhibition was associated with a significant and dose-dependent increase in the percentage of cells blocked in the G0/G1 cell cycle phase and a dose-dependent decline in pS6 levels in both c-erbB2 amplified vs c-erbB2 not amplified USC cell lines. AZD8055 may represent a novel targeted therapeutic agent in patients harboring advanced/recurrent/refractory USC. c-erbB2 gene amplification may represent a biomarker to identify USC patients who may benefit most from the use of AZD8055. © 2013.

Central and non-central networks, cognition, clinical symptoms, and polygenic risk scores in schizophrenia.

PubMed

Alloza, Clara; Bastin, Mark E; Cox, Simon R; Gibson, Jude; Duff, Barbara; Semple, Scott I; Whalley, Heather C; Lawrie, Stephen M

2017-12-01

Schizophrenia is a complex disorder that may be the result of aberrant connections between specific brain regions rather than focal brain abnormalities. Here, we investigate the relationships between brain structural connectivity as described by network analysis, intelligence, symptoms, and polygenic risk scores (PGRS) for schizophrenia in a group of patients with schizophrenia and a group of healthy controls. Recently, researchers have shown an interest in the role of high centrality networks in the disorder. However, the importance of non-central networks still remains unclear. Thus, we specifically examined network-averaged fractional anisotropy (mean edge weight) in central and non-central subnetworks. Connections with the highest betweenness centrality within the average network (>75% of centrality values) were selected to represent the central subnetwork. The remaining connections were assigned to the non-central subnetwork. Additionally, we calculated graph theory measures from the average network (connections that occur in at least 2/3 of participants). Density, strength, global efficiency, and clustering coefficient were significantly lower in patients compared with healthy controls for the average network (p FDR  < 0.05). All metrics across networks were significantly associated with intelligence (p FDR  < 0.05). There was a tendency towards significance for a correlation between intelligence and PGRS for schizophrenia (r = -0.508, p = 0.052) that was significantly mediated by central and non-central mean edge weight and every graph metric from the average network. These results are consistent with the hypothesis that intelligence deficits are associated with a genetic risk for schizophrenia, which is mediated via the disruption of distributed brain networks. Hum Brain Mapp 38:5919-5930, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Use of peripherally inserted central catheters as an alternative to central catheters in neurocritical care units.

PubMed

DeLemos, Christi; Abi-Nader, Judy; Akins, Paul T

2011-04-01

Patients in neurological critical care units often have lengthy stays that require extended vascular access and invasive hemodynamic monitoring. The traditional approach for these patients has relied heavily on central venous and pulmonary artery catheters. The aim of this study was to evaluate peripherally inserted central catheters as an alternative to central venous catheters in neurocritical care settings. Data on 35 patients who had peripherally inserted central catheters rather than central venous or pulmonary artery catheters for intravascular access and monitoring were collected from a prospective registry of neurological critical care admissions. These data were cross-referenced with information from hospital-based data registries for peripherally inserted central catheters and subarachnoid hemorrhage. Complete data were available on 33 patients with Hunt-Hess grade IV-V aneurysmal subarachnoid hemorrhage. Catheters remained in place a total of 649 days (mean, 19 days; range, 4-64 days). One patient (3%) had deep vein thrombosis in an upper extremity. In 2 patients, central venous pressure measured with a peripherally inserted catheter was higher than pressure measured concurrently with a central venous catheter. None of the 33 patients had a central catheter bloodstream infection or persistent insertion-related complications. CONCLUSIONS Use of peripherally inserted central catheters rather than central venous catheters or pulmonary artery catheters in the neurocritical care unit reduced procedural and infection risk without compromising patient management.

Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer

PubMed Central

Shen, Hui; Fridley, Brooke L.; Song, Honglin; Lawrenson, Kate; Cunningham, Julie M.; Ramus, Susan J.; Cicek, Mine S.; Tyrer, Jonathan; Stram, Douglas; Larson, Melissa C.; Köbel, Martin; Ziogas, Argyrios; Zheng, Wei; Yang, Hannah P.; Wu, Anna H.; Wozniak, Eva L.; Woo, Yin Ling; Winterhoff, Boris; Wik, Elisabeth; Whittemore, Alice S.; Wentzensen, Nicolas; Weber, Rachel Palmieri; Vitonis, Allison F.; Vincent, Daniel; Vierkant, Robert A.; Vergote, Ignace; Van Den Berg, David; Van Altena, Anne M.; Tworoger, Shelley S.; Thompson, Pamela J.; Tessier, Daniel C.; Terry, Kathryn L.; Teo, Soo-Hwang; Templeman, Claire; Stram, Daniel O.; Southey, Melissa C.; Sieh, Weiva; Siddiqui, Nadeem; Shvetsov, Yurii B.; Shu, Xiao-Ou; Shridhar, Viji; Wang-Gohrke, Shan; Severi, Gianluca; Schwaab, Ira; Salvesen, Helga B.; Rzepecka, Iwona K.; Runnebaum, Ingo B.; Rossing, Mary Anne; Rodriguez-Rodriguez, Lorna; Risch, Harvey A.; Renner, Stefan P.; Poole, Elizabeth M.; Pike, Malcolm C.; Phelan, Catherine M.; Pelttari, Liisa M.; Pejovic, Tanja; Paul, James; Orlow, Irene; Omar, Siti Zawiah; Olson, Sara H.; Odunsi, Kunle; Nickels, Stefan; Nevanlinna, Heli; Ness, Roberta B.; Narod, Steven A.; Nakanishi, Toru; Moysich, Kirsten B.; Monteiro, Alvaro N.A.; Moes-Sosnowska, Joanna; Modugno, Francesmary; Menon, Usha; McLaughlin, John R.; McGuire, Valerie; Matsuo, Keitaro; Adenan, Noor Azmi Mat; Massuger, Leon F.A. G.; Lurie, Galina; Lundvall, Lene; Lubiński, Jan; Lissowska, Jolanta; Levine, Douglas A.; Leminen, Arto; Lee, Alice W.; Le, Nhu D.; Lambrechts, Sandrina; Lambrechts, Diether; Kupryjanczyk, Jolanta; Krakstad, Camilla; Konecny, Gottfried E.; Kjaer, Susanne Krüger; Kiemeney, Lambertus A.; Kelemen, Linda E.; Keeney, Gary L.; Karlan, Beth Y.; Karevan, Rod; Kalli, Kimberly R.; Kajiyama, Hiroaki; Ji, Bu-Tian; Jensen, Allan; Jakubowska, Anna; Iversen, Edwin; Hosono, Satoyo; Høgdall, Claus K.; Høgdall, Estrid; Hoatlin, Maureen; Hillemanns, Peter; Heitz, Florian; Hein, Rebecca; Harter, Philipp; Halle, Mari K.; Hall, Per; Gronwald, Jacek; Gore, Martin; Goodman, Marc T.; Giles, Graham G.; Gentry-Maharaj, Aleksandra; Garcia-Closas, Montserrat; Flanagan, James M.; Fasching, Peter A.; Ekici, Arif B.; Edwards, Robert; Eccles, Diana; Easton, Douglas F.; Dürst, Matthias; du Bois, Andreas; Dörk, Thilo; Doherty, Jennifer A.; Despierre, Evelyn; Dansonka-Mieszkowska, Agnieszka; Cybulski, Cezary; Cramer, Daniel W.; Cook, Linda S.; Chen, Xiaoqing; Charbonneau, Bridget; Chang-Claude, Jenny; Campbell, Ian; Butzow, Ralf; Bunker, Clareann H.; Brueggmann, Doerthe; Brown, Robert; Brooks-Wilson, Angela; Brinton, Louise A.; Bogdanova, Natalia; Block, Matthew S.; Benjamin, Elizabeth; Beesley, Jonathan; Beckmann, Matthias W.; Bandera, Elisa V.; Baglietto, Laura; Bacot, François; Armasu, Sebastian M.; Antonenkova, Natalia; Anton-Culver, Hoda; Aben, Katja K.; Liang, Dong; Wu, Xifeng; Lu, Karen; Hildebrandt, Michelle A.T.; Schildkraut, Joellen M.; Sellers, Thomas A.; Huntsman, David; Berchuck, Andrew; Chenevix-Trench, Georgia; Gayther, Simon A.; Pharoah, Paul D.P.; Laird, Peter W.; Goode, Ellen L.; Pearce, Celeste Leigh

2013-01-01

HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds ratio (OR) = 1.13, P = 3.1 × 10−10) and clear cell (rs11651755 OR = 0.77, P = 1.6 × 10−8) epithelial ovarian cancer. Risk alleles for the serous subtype associate with higher HNF1B-promoter methylation in these tumours. Unmethylated, expressed HNF1B, primarily present in clear cell tumours, coincides with a CpG island methylator phenotype affecting numerous other promoters throughout the genome. Different variants in HNF1B associate with risk of serous and clear cell epithelial ovarian cancer; DNA methylation and expression patterns are also notably distinct between these subtypes. These findings underscore distinct mechanisms driving different epithelial ovarian cancer histological subtypes. PMID:23535649

76 FR 22746 - Wiregrass Central Railway, LLC-Acquisition and Operation Exemption-Wiregrass Central Railroad...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-22

... Railway, LLC--Acquisition and Operation Exemption--Wiregrass Central Railroad Company, Inc. Wiregrass Central Railway, LLC (WCR), a noncarrier, has filed a verified notice of exemption under 49 CFR 1150.31 to acquire from Wiregrass Central Railroad Company, Inc. (WGCR), and to operate approximately 21.2 miles of...

Prevalence of macular complications associated with high myopia by multimodal imaging.

PubMed

Lichtwitz, O; Boissonnot, M; Mercié, M; Ingrand, P; Leveziel, N

2016-04-01

To describe the prevalence of macular complications in patients with visual acuity decrease related to high myopia (HM). To establish correlations between these complications and demographic or anatomical characteristics. Cross-sectional observational study including HM patients undergoing best-corrected visual acuity (BCVA), fundus examination, macular SD-OCT, and fluorescein angiography in the case of suspicion of choroidal neovascularization (CNV). The presence of anatomical criteria (staphyloma, subfoveal choroidal thickness [CT]) and macular complications (CNV, lacquer cracks, central chorioretinal atrophy, dome-shaped macula with serous retinal detachment [SRD], retinal foveoschisis, macular hole and epiretinal membrane) was investigated. A total of 87 eyes of 47 patients were included (39 eyes without macular complication and 48 eyes with macular complications). In the case of macular complications, decrease in BCVA was related to CNV in 33%, macular hole in 25%, chorioretinal atrophy in 19%, foveoschisis in 11%, lacquer crack in 6%, to a dome-shape macula with serous retinal detachment in 4% and epiretinal membrane in 2%. After adjusting for interocular correlation and degree of myopia, staphyloma (P=0.0023), choroidal thinning (P=0.0036), and extrafoveal chorioretinal atrophy (P=0.042) were significantly associated with macular complications. High myopic patients with staphyloma or choroidal thinning should undergo regular comprehensive retinal screening for retinal complications. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Balanced Centrality of Networks.

PubMed

Debono, Mark; Lauri, Josef; Sciriha, Irene

2014-01-01

There is an age-old question in all branches of network analysis. What makes an actor in a network important, courted, or sought? Both Crossley and Bonacich contend that rather than its intrinsic wealth or value, an actor's status lies in the structures of its interactions with other actors. Since pairwise relation data in a network can be stored in a two-dimensional array or matrix, graph theory and linear algebra lend themselves as great tools to gauge the centrality (interpreted as importance, power, or popularity, depending on the purpose of the network) of each actor. We express known and new centralities in terms of only two matrices associated with the network. We show that derivations of these expressions can be handled exclusively through the main eigenvectors (not orthogonal to the all-one vector) associated with the adjacency matrix. We also propose a centrality vector (SWIPD) which is a linear combination of the square, walk, power, and degree centrality vectors with weightings of the various centralities depending on the purpose of the network. By comparing actors' scores for various weightings, a clear understanding of which actors are most central is obtained. Moreover, for threshold networks, the (SWIPD) measure turns out to be independent of the weightings.

Dacomitinib (PF-00299804), a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor, demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro.

PubMed

Zhu, Liancheng; Lopez, Salvatore; Bellone, Stefania; Black, Jonathan; Cocco, Emiliano; Zigras, Tiffany; Predolini, Federica; Bonazzoli, Elena; Bussi, Beatrice; Stuhmer, Zachary; Schwab, Carlton L; English, Diana P; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

2015-07-01

Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer that carries an extremely poor prognosis. Up to 35 % of USC may overexpress the epidermal growth factor receptor-2 (HER2/neu) at strong (i.e., 3+) level by immunohistochemistry (IHC) or harbor HER2/neu gene amplification by fluorescence in situ hybridization (FISH). In this study, we assessed the sensitivity of a panel of USC cell lines with and without HER2/neu gene amplification to dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor tyrosine kinase inhibitor. Eight primary cell lines (i.e., four harboring HER2/neu gene amplification by FISH and four FISH- cell lines), all demonstrating similar in vitro growth rates, were evaluated in viability/proliferation assays. The effect of dacomitinib on cell growth, cell cycle distribution, and signaling was determined using flow cytometry-based assays. Dacomitinib caused a significantly stronger growth inhibition in HER2/neu FISH+ USC cell lines when compared to FISH- USC (dacomitinib half maximal inhibitory concentration (IC50) mean ± SEM = 0.02803 ± 0.003355 μM in FISH+ versus 1.498 ± 0.2209 μM in FISH- tumors, P < 0.0001). Dacomitinib growth inhibition was associated with a significant and dose-dependent decline in phosphorylated HER2/neu and S6 transcription factor and a dose-dependent and time-dependent cell cycle arrest in G0/G1 in FISH+ USC. Dacomitinib is remarkably effective against chemotherapy-resistant HER2/neu gene-amplified USC. Clinical studies with dacomitinib in HER2/neu FISH+ USC patients resistant to standard salvage chemotherapy are warranted.

Mixed and Ambiguous Endometrial Carcinomas: A Heterogenous Group of Tumors With Different Clinicopathologic and Molecular Genetic Features.

PubMed

Espinosa, Iñigo; D'Angelo, Emanuela; Palacios, José; Prat, Jaime

2016-07-01

Besides endometrioid, serous, and clear cell carcinomas, there are endometrial carcinomas exhibiting mixed and ambiguous morphologic features. We have analyzed the immunophenotype (p53, p16, β-catenin, ER, HNF-1B, MLH1, and Ki-67) and mutational status (PTEN, KRAS, PIK3CA, and POLE) of 7 mixed carcinomas and 13 ambiguous carcinomas, all of them classified initially as mixed carcinomas. Only 2 of the 7 (28%) mixed carcinomas showed different immunophenotypes in different components. All but 2 tumors (5/7, 71%) overexpressed p53 and p16 and were negative for ER. Both carcinomas (2/7, 28%) showed a prominent micropapillary component that resembled an ovarian low-grade serous carcinoma and merged with villoglandular endometrioid carcinoma. The ambiguous carcinomas exhibited glandular architecture, high nuclear grade, and overlapping features of endometrioid and serous carcinomas. All tumors overexpressed p53 and p16, and the majority of cases (12/13, 92%) were negative for ER. KRAS mutations were identified in 3 of 7 (42%) mixed carcinomas, including the 2 cases with a "low-grade" serous-like component. PIK3CA mutations occurred in 2 (2/13, 15%) ambiguous carcinomas and PTEN mutations in 1 (1/7, 14%) mixed and 1 (1/13, 8%) ambiguous carcinoma. POLE exonuclease domain mutations were encountered in a case of mixed undifferentiated and well-differentiated (dedifferentiated) carcinoma. Two of the 7 (29%) mixed endometrial carcinomas and 5 of the 13 (38%) ambiguous carcinomas had extended beyond the pelvis (stages III and IV). Two of the 7 (29%) patients with mixed endometrial carcinoma and 6 of 12 (50%) patients with ambiguous endometrial carcinoma were alive with disease or had died of tumor. Our results show that, biologically, many so-called mixed carcinomas represent serous carcinomas with ambiguous morphology. Our series include 2 true mixed endometrial carcinomas with a "low-grade serous"-like component, microcystic, elongated, or fragmented features, KRAS mutations

Event centrality prospectively predicts PTSD symptoms.

PubMed

Boals, Adriel; Ruggero, Camilo

2016-09-01

Recent evidence suggests that event centrality has a prominent association with post-traumatic stress disorder (PTSD) symptoms. However, evidence for this notion thus far has been mostly correlational. We report two studies that prospectively examined the relationship between event centrality and PTSD symptoms. Study 1 METHODS: Participants (N = 1438) reported their most stressful event ("prior event"), along with event centrality, PTSD symptoms, and neuroticism. At Time 2 participants reported their most stressful event since Time 1 ("critical event"), along with measures of event centrality and PTSD symptoms. Study 1 RESULTS: Event centrality for the critical event predicted PTSD symptoms, after controlling for event centrality and PTSD symptoms of the prior event and neuroticism. Study In the second study (N = 161) we examined changes in event centrality and PTSD symptoms over a month. Study 2 RESULTS: Using a cross-lagged panel design, results revealed event centrality at Time 1 significantly predicted PTSD symptoms at Time 2, but the reverse was not significant. In two studies, a prospective association between event centrality and PTSD symptoms, but not the reverse, emerged. This evidence implicates event centrality in the pathogenesis and/or maintenance of PTSD symptoms.

Central Chemoreceptors: Locations and Functions

PubMed Central

Nattie, Eugene; Li, Aihua

2016-01-01

Central chemoreception traditionally refers to a change in ventilation attributable to changes in CO2/H+ detected within the brain. Interest in central chemoreception has grown substantially since the previous Handbook of Physiology published in 1986. Initially, central chemoreception was localized to areas on the ventral medullary surface, a hypothesis complemented by the recent identification of neurons with specific phenotypes near one of these areas as putative chemoreceptor cells. However, there is substantial evidence that many sites participate in central chemoreception some located at a distance from the ventral medulla. Functionally, central chemoreception, via the sensing of brain interstitial fluid H+, serves to detect and integrate information on 1) alveolar ventilation (arterial PCO2), 2) brain blood flow and metabolism and 3) acid-base balance, and, in response, can affect breathing, airway resistance, blood pressure (sympathetic tone) and arousal. In addition, central chemoreception provides a tonic ‘drive’ (source of excitation) at the normal, baseline PCO2 level that maintains a degree of functional connectivity among brainstem respiratory neurons necessary to produce eupneic breathing. Central chemoreception responds to small variations in PCO2 to regulate normal gas exchange and to large changes in PCO2 to minimize acid-base changes. Central chemoreceptor sites vary in function with sex and with development. From an evolutionary perspective, central chemoreception grew out of the demands posed by air vs. water breathing, homeothermy, sleep, optimization of the work of breathing with the ‘ideal’ arterial PCO2, and the maintenance of the appropriate pH at 37°C for optimal protein structure and function. PMID:23728974

YKL-40 in Serum Samples From Patients With Newly Diagnosed Stage III-IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer Receiving Chemotherapy

ClinicalTrials.gov

2018-05-21

Fallopian Tube Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Brenner Tumor; Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Endometrioid Tumor; Malignant Ovarian Mixed Epithelial Tumor; Malignant Ovarian Mucinous Tumor; Malignant Ovarian Neoplasm; Malignant Ovarian Serous Tumor; Malignant Ovarian Transitional Cell Tumor; Ovarian Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Dual HER2\\PIK3CA targeting overcomes single-agent acquired resistance in HER2 amplified uterine serous carcinoma cell lines in vitro and in vivo

PubMed Central

Lopez, Salvatore; Cocco, Emiliano; Black, Jonathan; Bellone, Stefania; Bonazzoli, Elena; Predolini, Federica; Ferrari, Francesca; Schwab, Carlton L.; English, Diana P.; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E.; Terranova, Corrado; Angioli, Roberto; Santin, Alessandro D.

2015-01-01

HER2/neu gene amplification and PIK3CA driver mutations are common in uterine serous carcinoma (USC), and may represent ideal therapeutic targets against this aggressive variant of endometrial cancer. We examined the sensitivity to neratinib, taselisib and the combination of the two compounds in in vitro and in vivo experiments using PIK3CA mutated and PIK3CA-wild type HER2/neu amplified USC cell lines. Cell viability and cell cycle distribution were assessed using flow-cytometry assays. Downstream signaling was assessed by immunoblotting. Preclinical efficacy of single versus dual inhibition was evaluated in vivo using two USC-xenografts. We found both single agent neratinib and taselisib to be active but only transiently effective in controlling the in vivo growth of USC xenografts harboring HER2/neu gene amplification with or without oncogenic PIK3CA mutations. In contrast, the combination of the two inhibitors caused a stronger and long lasting growth inhibition in both USC xenografts when compared to single agent therapy. Combined targeting of HER2 and PIK3CA was associated with a significant and dose-dependent increase in the percentage of cells in the G0/G1 phase of the cell cycle and a dose-dependent decline in the phosphorylation of S6. Importantly, dual inhibition therapy initiated after tumor progression in single agent-treated mice was still remarkably effective at inducing tumor regression in both large PIK3CA or pan-ErbB inhibitor-resistant USC xenografts. Dual HER2/PIK3CA blockade may represent a novel therapeutic option for USC patients harboring tumors with HER2/neu gene amplification and mutated or wild type PIK3CA resistant to chemotherapy. PMID:26333383

Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo.

PubMed

Lopez, Salvatore; Cocco, Emiliano; Black, Jonathan; Bellone, Stefania; Bonazzoli, Elena; Predolini, Federica; Ferrari, Francesca; Schwab, Carlton L; English, Diana P; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Terranova, Corrado; Angioli, Roberto; Santin, Alessandro D

2015-11-01

HER2/neu gene amplification and PIK3CA driver mutations are common in uterine serous carcinoma (USC) and may represent ideal therapeutic targets against this aggressive variant of endometrial cancer. We examined the sensitivity to neratinib, taselisib, and the combination of the two compounds in in vitro and in vivo experiments using PIK3CA-mutated and PIK3CA wild-type HER2/neu-amplified USC cell lines. Cell viability and cell-cycle distribution were assessed using flow-cytometry assays. Downstream signaling was assessed by immunoblotting. Preclinical efficacy of single versus dual inhibition was evaluated in vivo using two USC xenografts. We found both single-agent neratinib and taselisib to be active but only transiently effective in controlling the in vivo growth of USC xenografts harboring HER2/neu gene amplification with or without oncogenic PIK3CA mutations. In contrast, the combination of the two inhibitors caused a stronger and long-lasting growth inhibition in both USC xenografts when compared with single-agent therapy. Combined targeting of HER2 and PIK3CA was associated with a significant and dose-dependent increase in the percentage of cells in the G0-G1 phase of the cell cycle and a dose-dependent decline in the phosphorylation of S6. Importantly, dual inhibition therapy initiated after tumor progression in single-agent-treated mice was still remarkably effective at inducing tumor regression in both large PIK3CA and pan-ErbB inhibitor-resistant USC xenografts. Dual HER2/PIK3CA blockade may represent a novel therapeutic option for USC patients harboring tumors with HER2/neu gene amplification and mutated or wild-type PIK3CA resistant to chemotherapy. ©2015 American Association for Cancer Research.

[Central diabetes insipidus: diagnostic difficulties].

PubMed

Matoussi, N; Aissa, K; Fitouri, Z; Hajji, M; Makni, S; Bellagha, I; Ben Becher, S

2008-06-01

Central diabetes insipidus is rare in children. Characteristic features include polyuria and polydipsia due to arginine vasopressin deficiency. The differential diagnosis of polyuric states may be difficult. Etiologic diagnosis of central diabetes insipidus may be an equally difficult task. To specify the difficulties encountered in the diagnosis of central diabetes insipidus and to point out features of the etiologic work-up and of long-term follow-up of children with idiopathic central diabetes insipidus. A retrospective study of 12 children admitted with a polyuria/polydipsia syndrome to the pediatric - consultation and emergency unit of the children's hospital of Tunis between 1988 and 2005. Children with acquired nephrogenic central diabetes insipidus were excluded. Fourteen-hour fluid restriction test and/or desmopressin test were used without plasma vasopressin measurement. Eight patients were classified as having central diabetes insipidus, which was severe in seven children and partial in one girl. One patient was classified as having primary polydipsia. The diagnosis remains unclear in three patients. The etiological work-up in eight patients with central diabetes insipidus enabled the identification of Langerhan's-cell histiocytosis in two patients and neurosurgical trauma in one. The cause was considered idiopathic in five patients. The median follow-up of the five patients with idiopathic central diabetes insipidus was five years two months plus or minus six years seven months (range five months, 14.5 years). During this follow-up, neither brain magnetic resonance imaging scans findings nor anterior pituitary function have changed. Fluid restriction and desmopressin tests did not enable an accurate distinction between partial diabetes insipidus and primary polydipsia. Regular surveillance is warranted in patients with idiopathic central diabetes insipidus to identify potential etiologies.

Compression of Video-Otoscope Images for Tele-Otology: A Pilot Study

DTIC Science & Technology

2001-10-25

such as otitis media and glue ear can be diagnosed utilising images of the ear, and telemedicine is a prime candidate for playing a role in...eardrum, T: tympanosclersis, A: atrophic segment/retraction, SOM: serous otitis media , N: normal eardrum. A ‘Y’ indicates the presence of these...typmanosclerosis, R: retraction, S: serous otitis media , N: normal. IV. DISCUSSION There is no definitive answer as to what RMS Error value is

T-DM1, a novel antibody-drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo.

PubMed

English, Diana P; Bellone, Stefania; Schwab, Carlton L; Bortolomai, Ileana; Bonazzoli, Elena; Cocco, Emiliano; Buza, Natalia; Hui, Pei; Lopez, Salvatore; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

2014-10-01

Amplification of c-erbB2 has been reported in over 30% of uterine serous carcinoma (USC) and found to confer poor survival because of high proliferation and increased resistance to therapy. In this study, we evaluated for the first time Trastuzumab emtansine (T-DM1), a novel antibody-drug conjugate, against multiple epidermal growth factor receptor-2 (HER2)-positive USC cells in vitro followed by developing a supportive in vivo model. Fifteen primary USC cell lines were assessed by immunohistochemistry (IHC) and flow cytometry for HER2 protein expression. C-erbB2 gene amplification was evaluated using fluorescent in situ hybridization. Sensitivity to T-DM1 and trastuzumab (T)-induced antibody-dependent cell-mediated cytotoxicity was evaluated in 5-h chromium release assays. T-DM1 and T cytostatic and apoptotic activities were evaluated using flow-cytometry-based proliferation assays. In vivo activity of T-DM1 versus T in USC xenografts in SCID mice was also evaluated. High levels of HER2 protein overexpression and HER2 gene amplification were detected in 33% of USC cell lines. T-DM1 was considerably more effective than trastuzumab in inhibiting cell proliferation and in causing apoptosis (P = 0.004) of USC showing HER2 overexpression. Importantly, T-DM1 was highly active at reducing tumor formation in vivo in USC xenografts overexpressing HER2 (P = 0.04) and mice treated with TDM-1 had significantly longer survival when compared to T-treated mice and control mice (P ≤ 0.0001). T-DM1 shows promising antitumor effect in HER2-positive USC cell lines and USC xenografts and its activity is significantly higher when compared to T. T-DM1 may represent a novel treatment option for HER2-positive USC patients with disease refractory to trastuzumab and traditional chemotherapy. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Study design and data analysis considerations for the discovery of prognostic molecular biomarkers: a case study of progression free survival in advanced serous ovarian cancer.

PubMed

Qin, Li-Xuan; Levine, Douglas A

2016-06-10

Accurate discovery of molecular biomarkers that are prognostic of a clinical outcome is an important yet challenging task, partly due to the combination of the typically weak genomic signal for a clinical outcome and the frequently strong noise due to microarray handling effects. Effective strategies to resolve this challenge are in dire need. We set out to assess the use of careful study design and data normalization for the discovery of prognostic molecular biomarkers. Taking progression free survival in advanced serous ovarian cancer as an example, we conducted empirical analysis on two sets of microRNA arrays for the same set of tumor samples: arrays in one set were collected using careful study design (that is, uniform handling and randomized array-to-sample assignment) and arrays in the other set were not. We found that (1) handling effects can confound the clinical outcome under study as a result of chance even with randomization, (2) the level of confounding handling effects can be reduced by data normalization, and (3) good study design cannot be replaced by post-hoc normalization. In addition, we provided a practical approach to define positive and negative control markers for detecting handling effects and assessing the performance of a normalization method. Our work showcased the difficulty of finding prognostic biomarkers for a clinical outcome of weak genomic signals, illustrated the benefits of careful study design and data normalization, and provided a practical approach to identify handling effects and select a beneficial normalization method. Our work calls for careful study design and data analysis for the discovery of robust and translatable molecular biomarkers.

MAL2 and tumor protein D52 (TPD52) are frequently overexpressed in ovarian carcinoma, but differentially associated with histological subtype and patient outcome.

PubMed

Byrne, Jennifer A; Maleki, Sanaz; Hardy, Jayne R; Gloss, Brian S; Murali, Rajmohan; Scurry, James P; Fanayan, Susan; Emmanuel, Catherine; Hacker, Neville F; Sutherland, Robert L; Defazio, Anna; O'Brien, Philippa M

2010-09-17

The four-transmembrane MAL2 protein is frequently overexpressed in breast carcinoma, and MAL2 overexpression is associated with gain of the corresponding locus at chromosome 8q24.12. Independent expression microarray studies predict MAL2 overexpression in ovarian carcinoma, but these had remained unconfirmed. MAL2 binds tumor protein D52 (TPD52), which is frequently overexpressed in ovarian carcinoma, but the clinical significance of MAL2 and TPD52 overexpression was unknown. Immunohistochemical analyses of MAL2 and TPD52 expression were performed using tissue microarray sections including benign, borderline and malignant epithelial ovarian tumours. Inmmunohistochemical staining intensity and distribution was assessed both visually and digitally. MAL2 and TPD52 were significantly overexpressed in high-grade serous carcinomas compared with serous borderline tumours. MAL2 expression was highest in serous carcinomas relative to other histological subtypes, whereas TPD52 expression was highest in clear cell carcinomas. MAL2 expression was not related to patient survival, however high-level TPD52 staining was significantly associated with improved overall survival in patients with stage III serous ovarian carcinoma (log-rank test, p < 0.001; n = 124) and was an independent predictor of survival in the overall carcinoma cohort (hazard ratio (HR), 0.498; 95% confidence interval (CI), 0.34-0.728; p < 0.001; n = 221), and in serous carcinomas (HR, 0.440; 95% CI, 0.294-0.658; p < 0.001; n = 182). MAL2 is frequently overexpressed in ovarian carcinoma, and TPD52 overexpression is a favourable independent prognostic marker of potential value in the management of ovarian carcinoma patients.

Central control of body temperature.

PubMed

Morrison, Shaun F

2016-01-01

Central neural circuits orchestrate the behavioral and autonomic repertoire that maintains body temperature during environmental temperature challenges and alters body temperature during the inflammatory response and behavioral states and in response to declining energy homeostasis. This review summarizes the central nervous system circuit mechanisms controlling the principal thermoeffectors for body temperature regulation: cutaneous vasoconstriction regulating heat loss and shivering and brown adipose tissue for thermogenesis. The activation of these thermoeffectors is regulated by parallel but distinct efferent pathways within the central nervous system that share a common peripheral thermal sensory input. The model for the neural circuit mechanism underlying central thermoregulatory control provides a useful platform for further understanding of the functional organization of central thermoregulation, for elucidating the hypothalamic circuitry and neurotransmitters involved in body temperature regulation, and for the discovery of novel therapeutic approaches to modulating body temperature and energy homeostasis.

Feature Centrality and Property Induction

ERIC Educational Resources Information Center

Hadjichristidis, Constantinos; Sloman, Steven; Stevenson, Rosemary; Over, David

2004-01-01

A feature is central to a concept to the extent that other features depend on it. Four studies tested the hypothesis that people will project a feature from a base concept to a target concept to the extent that they believe the feature is central to the two concepts. This centrality hypothesis implies that feature projection is guided by a…

Central control of body temperature

PubMed Central

Morrison, Shaun F.

2016-01-01

Central neural circuits orchestrate the behavioral and autonomic repertoire that maintains body temperature during environmental temperature challenges and alters body temperature during the inflammatory response and behavioral states and in response to declining energy homeostasis. This review summarizes the central nervous system circuit mechanisms controlling the principal thermoeffectors for body temperature regulation: cutaneous vasoconstriction regulating heat loss and shivering and brown adipose tissue for thermogenesis. The activation of these thermoeffectors is regulated by parallel but distinct efferent pathways within the central nervous system that share a common peripheral thermal sensory input. The model for the neural circuit mechanism underlying central thermoregulatory control provides a useful platform for further understanding of the functional organization of central thermoregulation, for elucidating the hypothalamic circuitry and neurotransmitters involved in body temperature regulation, and for the discovery of novel therapeutic approaches to modulating body temperature and energy homeostasis. PMID:27239289

Genetics Home Reference: central core disease

MedlinePlus

... Twitter Home Health Conditions Central core disease Central core disease Printable PDF Open All Close All Enable ... to view the expand/collapse boxes. Description Central core disease is a disorder that affects muscles used ...

Normal Central Zone of the Prostate and Central Zone Involvement by Prostate Cancer: Clinical and MR Imaging Implications

PubMed Central

Akin, Oguz; Franiel, Tobias; Goldman, Debra A.; Udo, Kazuma; Touijer, Karim A.; Reuter, Victor E.; Hricak, Hedvig

2012-01-01

Purpose: To describe the anatomic features of the central zone of the prostate on T2-weighted and diffusion-weighted (DW) magnetic resonance (MR) images and evaluate the diagnostic performance of MR imaging in detection of central zone involvement by prostate cancer. Materials and Methods: The institutional review board waived informed consent and approved this retrospective, HIPAA-compliant study of 211 patients who underwent T2-weighted and DW MR imaging of the prostate before radical prostatectomy. Whole-mount step-section pathologic findings were the reference standard. Two radiologists independently recorded the visibility, MR signal intensity, size, and symmetry of the central zone and scored the likelihood of central zone involvement by cancer on T2-weighted MR images and on T2-weighted MR images plus apparent diffusion coefficient (ADC) maps generated from the DW MR images. Descriptive summary statistics were calculated for central zone imaging features. Sensitivity, specificity, and area under the curve were used to evaluate reader performance in detecting central zone involvement. Results: For readers 1 and 2, the central zone was visible, at least partially, in 177 (84%) and 170 (81%) of 211 patients, respectively. The most common imaging appearance of the central zone was symmetric, homogeneous low signal intensity. Cancers involving the central zone had higher prostate-specific antigen values, Gleason scores, and rates of extracapsular extension and seminal vesicle invasion compared with cancers not involving the central zone (P < .05). Area under the curve, sensitivity, and specificity in detecting central zone involvement were 0.70, 0.30, and 0.96 for reader 1 and 0.65, 0.35, and 0.93 for reader 2, and these values did not differ significantly between T2-weighted imaging and T2-weighted imaging plus ADC maps. Conclusion: The central zone was visualized in most patients. Cancers involving the central zone were associated with more aggressive disease

EIGENVECTOR-BASED CENTRALITY MEASURES FOR TEMPORAL NETWORKS*

PubMed Central

TAYLOR, DANE; MYERS, SEAN A.; CLAUSET, AARON; PORTER, MASON A.; MUCHA, PETER J.

2017-01-01

Numerous centrality measures have been developed to quantify the importances of nodes in time-independent networks, and many of them can be expressed as the leading eigenvector of some matrix. With the increasing availability of network data that changes in time, it is important to extend such eigenvector-based centrality measures to time-dependent networks. In this paper, we introduce a principled generalization of network centrality measures that is valid for any eigenvector-based centrality. We consider a temporal network with N nodes as a sequence of T layers that describe the network during different time windows, and we couple centrality matrices for the layers into a supra-centrality matrix of size NT × NT whose dominant eigenvector gives the centrality of each node i at each time t. We refer to this eigenvector and its components as a joint centrality, as it reflects the importances of both the node i and the time layer t. We also introduce the concepts of marginal and conditional centralities, which facilitate the study of centrality trajectories over time. We find that the strength of coupling between layers is important for determining multiscale properties of centrality, such as localization phenomena and the time scale of centrality changes. In the strong-coupling regime, we derive expressions for time-averaged centralities, which are given by the zeroth-order terms of a singular perturbation expansion. We also study first-order terms to obtain first-order-mover scores, which concisely describe the magnitude of nodes’ centrality changes over time. As examples, we apply our method to three empirical temporal networks: the United States Ph.D. exchange in mathematics, costarring relationships among top-billed actors during the Golden Age of Hollywood, and citations of decisions from the United States Supreme Court. PMID:29046619

Determination of BRAF V600E (VE1) protein expression and BRAF gene mutation status in codon 600 in borderline and low-grade ovarian cancers.

PubMed

Sadlecki, Pawel; Walentowicz, Pawel; Bodnar, Magdalena; Marszalek, Andrzej; Grabiec, Marek; Walentowicz-Sadlecka, Malgorzata

2017-05-01

Epithelial ovarian tumors are a group of morphologically and genetically heterogeneous neoplasms. Based on differences in clinical phenotype and genetic background, ovarian neoplasms are classified as low-grade and high-grade tumor. Borderline ovarian tumors represent approximately 10%-20% of all epithelial ovarian masses. Various histological subtypes of ovarian malignancies differ in terms of their risk factor profiles, precursor lesions, clinical course, patterns of spread, molecular genetics, response to conventional chemotherapy, and prognosis. The most frequent genetic aberrations found in low-grade serous ovarian carcinomas and serous borderline tumors, as well as in mucinous cancers, are mutations in BRAF and KRAS genes. The most commonly observed BRAF mutation is substitution of glutamic acid for valine in codon 600 (V600E) in exon 15. The primary aim of this study was to determine whether fully integrated, real-time polymerase chain reaction-based Idylla™ system may be useful in determination of BRAF gene mutation status in codon 600 in patients with borderline ovarian tumors and low-grade ovarian carcinomas. The study included tissue specimens from 42 patients with histopathologically verified ovarian masses, who were operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz (Poland). Based on histopathological examination of surgical specimens, 35 lesions were classified as low-grade ovarian carcinomas, and 7 as borderline ovarian tumors. Specimens with expression of BRAF V600E (VE1) protein were tested for mutations in codon 600 of the BRAF gene, using an automated molecular diagnostics platform Idylla™. Cytoplasmic immunoexpression of BRAF V600E (VE1) protein was found in three specimens: serous superficial papilloma, serous papillary cystadenoma of borderline malignancy, and partially proliferative serous cystadenoma. All specimens with the expression of BRAF V600E (VE1) protein were

Idiopathic central diabetes Insipidus.

PubMed

Grace, Mary; Balachandran, Venu; Menon, Sooraj

2011-10-01

Idiopathic central diabetes insipidus (CDI) is a rare disorder characterized clinically by polyuria and polydipsia, and an abnormal urinary concentration without any identified etiology. We report a case of central diabetes insipidus in a 60-year-old lady in the absence of secondary causes like trauma, infection, and infiltrative disorders of brain.

Evaluating the progenitor cells of ovarian cancer: analysis of current animal models.

PubMed

King, Shelby M; Burdette, Joanna E

2011-07-01

Serous ovarian cancer is one of the most lethal gynecological malignancies. Progress on effective diagnostics and therapeutics for this disease are hampered by ambiguity as to the cellular origins of this histotype of ovarian cancer, as well as limited suitable animal models to analyze early stages of disease. In this report, we will review current animal models with respect to the two proposed progenitor cells for serous ovarian cancer, the ovarian surface epithelium and the fallopian tube epithelium.

Integration of spectral domain optical coherence tomography with microperimetry generates unique datasets for the simultaneous identification of visual function and retinal structure in ophthalmological applications

NASA Astrophysics Data System (ADS)

Koulen, Peter; Gallimore, Gary; Vincent, Ryan D.; Sabates, Nelson R.; Sabates, Felix N.

2011-06-01

Conventional perimeters are used routinely in various eye disease states to evaluate the central visual field and to quantitatively map sensitivity. However, standard automated perimetry proves difficult for retina and specifically macular disease due to the need for central and steady fixation. Advances in instrumentation have led to microperimetry, which incorporates eye tracking for placement of macular sensitivity values onto an image of the macular fundus thus enabling a precise functional and anatomical mapping of the central visual field. Functional sensitivity of the retina can be compared with the observed structural parameters that are acquired with high-resolution spectral domain optical coherence tomography and by integration of scanning laser ophthalmoscope-driven imaging. Findings of the present study generate a basis for age-matched comparison of sensitivity values in patients with macular pathology. Microperimetry registered with detailed structural data performed before and after intervention treatments provides valuable information about macular function, disease progression and treatment success. This approach also allows for the detection of disease or treatment related changes in retinal sensitivity when visual acuity is not affected and can drive the decision making process in choosing different treatment regimens and guiding visual rehabilitation. This has immediate relevance for applications in central retinal vein occlusion, central serous choroidopathy, age-related macular degeneration, familial macular dystrophy and several other forms of retina related visual disability.

Cystic pancreatic neoplasms evaluation by CT and magnetic resonance cholangiopancreatography.

PubMed

Sahani, Dushyant; Prasad, Srinivasa; Saini, Sanjay; Mueller, Peter

2002-10-01

CT provides limited assistance in the differentiation between serous and mucinous neoplasms. Because of the variability in the radiographic appearance of serous cystadenomas and overlap in CT characteristics with mucinous neoplasms, most serous neoplasms still require ancillary testing such as biopsy to reach a definitive diagnosis. MRCP is useful in differentiating benign and malignant mucinous tumors including IPMT of the pancreas. The presence of mural nodules is suggestive of malignancy; however, the absence of mural nodules does not indicate that the tumor is benign. A maximum main pancreatic duct diameter of greater than 15 mm and diffuse dilatation of the main pancreatic duct are suggestive of malignancy in main duct-type tumors. Among branch duct-type tumors, malignant tumors tend to be larger than benign tumors; however, this finding is variable. The presence of main pancreatic duct dilatation may be helpful in determining malignancy of branch duct-type tumors.

Associations between residual disease and survival in epithelial ovarian cancer by histologic type.

PubMed

Melamed, Alexander; Manning-Geist, Beryl; Bregar, Amy J; Diver, Elisabeth J; Goodman, Annekathryn; Del Carmen, Marcela G; Schorge, John O; Rauh-Hain, J Alejandro

2017-11-01

Surgical cytoreduction has been postulated to affect survival by increasing the efficacy of chemotherapy in ovarian cancer. We hypothesized that women with high-grade serous ovarian cancer, which usually responds to chemotherapy, would derive greater benefit from complete cytoreduction than those with histologic subtypes that are less responsive to chemotherapy, such as mucinous and clear cell carcinoma. We conducted a retrospective cohort study of patients who underwent primary cytoreductive surgery and adjuvant chemotherapy for stage IIIC or IV epithelial ovarian cancer from 2011 to 2013 using data from the National Cancer Database. We constructed multivariable models to quantify the magnitude of associations between residual disease status (no residual disease, ≤1cm, or >1cm) and all-cause mortality by histologic type among women with clear cell, mucinous, and high-grade serous ovarian cancer. Because 26% of the sample had unknown residual disease status, we used multiple imputations in the primary analysis. We identified 6,013 women with stage IIIC and IV high-grade serous, 307 with clear cell, and 140 with mucinous histology. The association between residual disease status and mortality hazard did not differ significantly among histologic subtypes of ovarian cancer (p for interaction=0.32). In covariate adjusted models, compared to suboptimal cytoreduction, cytoreduction to no gross disease was associated with a hazard reduction of 42% in high-grade serous carcinoma (hazard ratio [HR]=0.58, 95% confidence interval [CI]=0.49-0.68), 61% in clear cell carcinoma (HR=0.39, 95% CI=0.22-0.69), and 54% in mucinous carcinoma (HR=0.46, 95% CI=0.22-0.99). We found no evidence that surgical cytoreduction was of greater prognostic importance in high-grade serous carcinomas than in histologies that are less responsive to chemotherapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Circulating estrogens and postmenopausal ovarian cancer risk in the Women’s Health Initiative Observational Study

PubMed Central

Trabert, Britton; Brinton, Louise A.; Anderson, Garnet L.; Pfeiffer, Ruth M.; Falk, Roni T.; Strickler, Howard D.; Sliesoraitis, Sarunas; Kuller, Lewis H.; Gass, Margery L.; Fuhrman, Barbara J.; Xu, Xia; Wentzensen, Nicolas

2016-01-01

Background Hormonal and reproductive factors contribute to the development of ovarian cancer, but few studies have examined associations between circulating estrogens and estrogen metabolites and ovarian cancer risk. We evaluated whether serum estrogens and estrogen metabolite levels are associated with ovarian cancer risk among postmenopausal women in a nested case-control study in the Women’s Health Initiative (WHI) Observational Study (OS). Methods We selected all 169 eligible epithelial ovarian cancer cases and 412 matched controls from women enrolled in WHI-OS who were not using menopausal hormones at baseline. Baseline levels of 15 estrogens and estrogen metabolites were measured via LC-MS/MS. Associations with ovarian cancer risk overall and stratified by histologic subtype (serous/non-serous) were analyzed using logistic regression. The mean time from serum collection to cancer diagnosis was 6.9 years. Results Overall we observed modest ovarian cancer risk associations among women with higher levels of estrone [Odds Ratio (95% Confidence Interval) quintile (Q)5 vs. Q1: 1.54 (0.82–2.90), p-trend=0.05], as well as 2- and 4-methoxyestrone metabolites [2.03 (1.06–3.88), p-trend=0.02; 1.86 (0.98–3.56), p-trend=0.01, respectively]. Associations of estrogens and estrogen metabolites varied substantially by histologic subtype. Associations with serous tumors were universally null, while estrone (2.65 (1.09–6.45), p-trend=0.01, p-heterogeneity=0.04), unconjugated estradiol (2.72 (1.04–7.14), p-trend=0.03, p-heterogeneity=0.02) and many of the 2-, 4-, and 16-pathway metabolites were positively associated with non-serous tumors. Conclusions Our study provides novel molecular data showing an association of the parent estrogens and several estrogen metabolites with non-serous ovarian cancers. Impact These findings further support the heterogeneous etiology of ovarian cancer. PMID:26908437

78 FR 15349 - Trade Mission to Central America in Conjunction With the Trade Americas-Opportunities in Central...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-11

... DEPARTMENT OF COMMERCE International Trade Administration Trade Mission to Central America in Conjunction With the Trade Americas--Opportunities in Central America Conference; July 15-19, 2013 AGENCY... (USFCS) is organizing a trade mission to Central America, in conjunction with the Trade Americas...

20 CFR 346.1 - Central register.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Central register. 346.1 Section 346.1 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT RAILROAD HIRING § 346.1 Central register. (a) The Board shall maintain a central register of railroad...

20 CFR 346.1 - Central register.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Central register. 346.1 Section 346.1 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT RAILROAD HIRING § 346.1 Central register. (a) The Board shall maintain a central register of railroad...

20 CFR 346.1 - Central register.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Central register. 346.1 Section 346.1 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT RAILROAD HIRING § 346.1 Central register. (a) The Board shall maintain a central register of railroad...

20 CFR 346.1 - Central register.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Central register. 346.1 Section 346.1 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT RAILROAD HIRING § 346.1 Central register. (a) The Board shall maintain a central register of railroad...

Mammaglobin expression in gynecologic adenocarcinomas.

PubMed

Hagemann, Ian S; Pfeifer, John D; Cao, Dengfeng

2013-04-01

Mammaglobin (MGB) has been proposed as a sensitive and specific immunohistochemical marker for adenocarcinoma of the breast. The differential diagnosis of breast adenocarcinoma versus a gynecologic primary frequently arises. We performed a semiquantitative survey of MGB immunoreactivity in 26 benign gynecologic tissues (6 ectocervices, 9 endocervices, 11 endometria), 86 ovarian adenocarcinomas, 70 endometrial adenocarcinomas, and 10 endocervical adenocarcinomas. Among ovarian tumors, MGB was present in 40% of endometrioid carcinomas; 36%, serous carcinomas; 21%, clear cell carcinomas; and 6%, mucinous carcinomas. Among endometrial cancers, MGB reactivity was present in 57% of endometrioid carcinomas, but only 30% of serous carcinomas and 6% of clear cell carcinomas. MGB was absent in endocervical adenocarcinomas. Across all tumor types with positive staining, MGB was focal or patchy (ie, less than diffuse) in 50 of 57 cases. Using a scale of 0 to 3+, the only 3 tumors with 3+ MGB reactivity were all serous carcinomas (1 ovarian and 2 endometrial). There were no cases with diffuse 3+ MGB expression. On the other hand, diffuse 2+ MGB was seen in 4 cases: 1 endometrioid carcinoma of ovary, 1 serous carcinoma of ovary, and 2 clear cell carcinomas of ovary. In conclusion, a diagnostically significant proportion of gynecologic carcinomas are immunoreactive for MGB. Gynecologic primaries should be considered in the differential diagnosis of MGB-positive malignancies of unknown origin. Copyright © 2013 Elsevier Inc. All rights reserved.

Targeted mutation analysis of endometrial clear cell carcinoma.

PubMed

Hoang, Lien N; McConechy, Melissa K; Meng, Bo; McIntyre, John B; Ewanowich, Carol; Gilks, Cyril Blake; Huntsman, David G; Köbel, Martin; Lee, Cheng-Han

2015-04-01

Endometrial clear cell carcinomas (CCC) constitute fewer than 5% of all carcinomas of the endometrium. Currently, little is known regarding the genetic basis of endometrial CCC. We performed genomic and immunohistochemical analyses on 14 rigorously reviewed pure endometrial CCC. The genomic analysis consisted of sequencing the coding regions of 26 genes implicated previously in endometrial carcinoma. Twelve of 14 tumours displayed a prototypical CCC immunophenotype [napsin A+, hepatocyte nuclear factor-1β (HNF1β(+) ) and oestrogen receptor(-) ] and all showed intact mismatch repair protein expression. We detected mutations in 11 of 14 tumours, and there was a predominance of mutations involving genes that are mutated more frequently in endometrial serous carcinomas than in endometrioid carcinomas. Two tumours displayed a prototypical serous carcinoma mutation profile (concurrent TP53 and PPP2R1A mutations, without PTEN, CTNNB1 or ARID1A mutation). No mutations in PTEN, CTNNB1 or POLE were identified. The overall mutation profile of this cohort of endometrial CCC appears to be more serous-like than endometrioid-like, with a minor subset in the TP53-mutated CCC showing serous carcinoma profile. These findings provide new insights into the molecular features of morphologically prototypical endometrial CCC, and underscore the need for further investigations into the oncogenesis of endometrial CCC. © 2014 John Wiley & Sons Ltd.

Central diabetes insipidus, central hypothyroidism, renal tubular acidosis and dandy-walker syndrome: new associations.

PubMed

Alafif, M M; Aljaid, S S; Al-Agha, A E

2015-01-01

Dandy-Walker syndrome (DWS) is a rare brain malformation involving the cerebellum, and the fluid filled spaces around it, usually detected during the antenatal period or the early infancy. Clinically, it is characterized by mental retardation, developmental delay as well as cerebellar ataxia. It has been frequently associated with other conditions such as congenital heart diseases, primary hypothyroidism, and other disorders of the central nervous, gastrointestinal, genitourinary, and orthopedic systems. In this report, we describe a 3-month-old Saudi boy with the rare association of DWS with central diabetes insipidus, congenital central hypothyroidism, and type-2 renal tubular acidosis.

Central Diabetes Insipidus, Central Hypothyroidism, Renal Tubular Acidosis and Dandy-Walker Syndrome: New Associations

PubMed Central

Alafif, MM; Aljaid, SS; Al-Agha, AE

2015-01-01

Dandy-Walker syndrome (DWS) is a rare brain malformation involving the cerebellum, and the fluid filled spaces around it, usually detected during the antenatal period or the early infancy. Clinically, it is characterized by mental retardation, developmental delay as well as cerebellar ataxia. It has been frequently associated with other conditions such as congenital heart diseases, primary hypothyroidism, and other disorders of the central nervous, gastrointestinal, genitourinary, and orthopedic systems. In this report, we describe a 3-month-old Saudi boy with the rare association of DWS with central diabetes insipidus, congenital central hypothyroidism, and type-2 renal tubular acidosis. PMID:25861538

Does a More Centrally Located School Promote Walking to School? Spatial Centrality in School-Neighborhood Settings.

PubMed

Kim, Hyung Jin; Lee, Chanam

2016-05-01

A public elementary school has traditionally functioned as an important center of a neighborhood, but this role has diminished with sprawling urban developments. Despite the large number of studies of children's walking to/from school (WTS), the school's location in relation to the larger neighborhood context has not been fully explored. This study is to examine the relationship between school's spatial centrality and children's WTS in urban, suburban and rural settings. this study used school travel tally (11,721 students), environment audit, GIS and census data from 71 elementary school/neighborhoods in Texas, and employed the closeness centrality index to estimate a school's spatial centrality. Data were collected from 2009-2012. After controlling for neighborhood characteristics, it was found that more centrally located schools are likely to have higher proportions of WTS in the neighborhoods. And, among urban, suburban and rural settings, urban schools were the most and rural schools were the least likely to be centrally-located in the neighborhoods. The findings offer implications on school and community planning policies that can help promote WTS. Spatial centrality measures can be effective tools to identify environmental factors in complex urban networks related to human behaviors and community-based activities.

Central State University: Phase III Report

ERIC Educational Resources Information Center

Ohio Board of Regents, 2013

2013-01-01

This document is the final report on Central State University's implementation of Section 371 of Ohio Amended Substitute House Bill 153. Implementation of Phase I action items required that deliverables and timelines be shifted to give Central State the best opportunity for early success. In Phase II, Central State responded aggressively to a…

49 CFR 71.6 - Central zone.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Office of the Secretary of Transportation STANDARD TIME ZONE BOUNDARIES § 71.6 Central zone. The third zone, the central standard time zone, includes that part of the United States that is west of the boundary line between the eastern and central standard time zones described in § 71.5 and east of the...

Central blood pressure and chronic kidney disease

PubMed Central

Ohno, Yoichi; Kanno, Yoshihiko; Takenaka, Tsuneo

2016-01-01

In this review, we focused on the relationship between central blood pressure and chronic kidney diseases (CKD). Wave reflection is a major mechanism that determines central blood pressure in patients with CKD. Recent medical technology advances have enabled non-invasive central blood pressure measurements. Clinical trials have demonstrated that compared with brachial blood pressure, central blood pressure is a stronger risk factor for cardiovascular (CV) and renal diseases. CKD is characterized by a diminished renal autoregulatory ability, an augmented direct transmission of systemic blood pressure to glomeruli, and an increase in proteinuria. Any elevation in central blood pressure accelerates CKD progression. In the kidney, interstitial inflammation induces oxidative stress to handle proteinuria. Oxidative stress facilitates atherogenesis, increases arterial stiffness and central blood pressure, and worsens the CV prognosis in patients with CKD. A vicious cycle exists between CKD and central blood pressure. To stop this cycle, vasodilator antihypertensive drugs and statins can reduce central blood pressure and oxidative stress. Even in early-stage CKD, mineral and bone disorders (MBD) may develop. MBD promotes oxidative stress, arteriosclerosis, and elevated central blood pressure in patients with CKD. Early intervention or prevention seems necessary to maintain vascular health in patients with CKD. PMID:26788468

Transferrin facilitates the formation of DNA double-strand breaks via transferrin receptor 1: the possible involvement of transferrin in carcinogenesis of high-grade serous ovarian cancer.

PubMed

Shigeta, S; Toyoshima, M; Kitatani, K; Ishibashi, M; Usui, T; Yaegashi, N

2016-07-07

Fallopian tubal epithelium is a candidate for the origin of high-grade serous ovarian cancer. Transferrin-containing follicular fluid and/or retrograde menstrual blood are possible risk factors for carcinogenesis. Accumulation of DNA double-strand breaks (DNA-DSBs) in the fallopian tubal epithelium is considered to play an important role in the development of cancer. However, the mechanisms by which DNA-DSBs accumulate have not yet been fully elucidated. The hydroxyl radical, which is produced in a Fenton reaction catalyzed by an iron ion, serves as a potent DNA-DSB-inducing molecule, raising the potential of an iron ion transporter of transferrin in the formation of DNA-DSBs. We studied the potential involvement of transferrin in DNA damage and the development of ovarian cancer. Treatment with transferrin facilitated the formation of histone 2AX phosphorylated at Serine 139 (γH2AX), which is known as a DNA-DSB marker, in human fallopian tube secretory epithelial cells and A2780 ovarian cancer cells. Knockdown of transferrin receptor 1 (TfR1), but not transferrin receptor 2, suppressed the transferrin uptake and consequent formation of γH2AX. As hydroxyl radicals in reactive oxygen species (ROS) are involved in DNA-DSBs, the formation of ROS was determined. Treatment with TfR1-specific small interference RNAs significantly diminished transferrin-induced formation of ROS. Moreover, TfR1-dependent uptake of transferrin was revealed to augment the formation of DNA-DSBs in the presence of hydrogen peroxide, which served as a substrate for the Fenton reaction. An ex vivo study with murine fallopian tubes further demonstrated that transferrin treatment introduced DNA-DSBs in the fallopian tubal epithelium. Collectively, these data suggested that the transferrin-TfR1 axis accounts for the induction of DNA-DSBs that potentially lead to DNA damage/genome instability. These findings also suggested that exposure to transferrin initiates and promotes the development of

Central vein sign differentiates Multiple Sclerosis from central nervous system inflammatory vasculopathies.

PubMed

Maggi, Pietro; Absinta, Martina; Grammatico, Matteo; Vuolo, Luisa; Emmi, Giacomo; Carlucci, Giovanna; Spagni, Gregorio; Barilaro, Alessandro; Repice, Anna Maria; Emmi, Lorenzo; Prisco, Domenico; Martinelli, Vittorio; Scotti, Roberta; Sadeghi, Niloufar; Perrotta, Gaetano; Sati, Pascal; Dachy, Bernard; Reich, Daniel S; Filippi, Massimo; Massacesi, Luca

2018-02-01

In multiple sclerosis (MS), magnetic resonance imaging (MRI) is a sensitive tool for detecting white matter lesions, but its diagnostic specificity is still suboptimal; ambiguous cases are frequent in clinical practice. Detection of perivenular lesions in the brain (the "central vein sign") improves the pathological specificity of MS diagnosis, but comprehensive evaluation of this MRI biomarker in MS-mimicking inflammatory and/or autoimmune diseases, such as central nervous system (CNS) inflammatory vasculopathies, is lacking. In a multicenter study, we assessed the frequency of perivenular lesions in MS versus systemic autoimmune diseases with CNS involvement and primary angiitis of the CNS (PACNS). In 31 patients with inflammatory CNS vasculopathies and 52 with relapsing-remitting MS, 3-dimensional T2*-weighted and T2-fluid-attenuated inversion recovery images were obtained during a single MRI acquisition after gadolinium injection. For each lesion, the central vein sign was evaluated according to consensus guidelines. For each patient, lesion count, volume, and brain location, as well as fulfillment of dissemination in space MRI criteria, were assessed. MS showed higher frequency of perivenular lesions (median = 88%) than did inflammatory CNS vasculopathies (14%), without overlap between groups or differences between 3T and 1.5T MRI. Among inflammatory vasculopathies, Behçet disease showed the highest median frequency of perivenular lesions (34%), followed by PACNS (14%), antiphospholipid syndromes (12%), Sjögren syndrome (11%), and systemic lupus erythematosus (0%). When a threshold of 50% perivenular lesions was applied, central vein sign discriminated MS from inflammatory vasculopathies with a diagnostic accuracy of 100%. The central vein sign differentiates inflammatory CNS vasculopathies from MS at standard clinical magnetic field strengths. Ann Neurol 2018;83:283-294. © 2018 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on

CHARACTER AND REGIONAL SIGNIFICANCE OF GREAT FALLS TECTONIC ZONE, EAST-CENTRAL IDAHO AND WEST-CENTRAL MONTANA.

USGS Publications Warehouse

O'Neill, J. Michael; Lopez, David A.

1985-01-01

The Great Falls tectonic zone, here named, is a belt of diverse northeast-trending geologic features that can be traced from the Idaho batholith in the Cordilleran miogeocline, across thrust-belt structures and basement rocks of west-central and southwestern Montana, through cratonic rocks of central Montana, and into southwestern-most Saskatchewan, Canada. Geologic mapping in east-central Idaho and west-central Montana has outlined a continuous zone of high-angle faults and shear zones. Recurrent fault movement in this zone and strong structural control over igneous intrusion suggest a fundamental tectonic feature that has influenced the tectonic development of the Idaho-Montana area from a least middle Proterozoic time to the present. Refs.

Ruxolitinib Phosphate, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2018-02-14

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Serous Neoplasm; High Grade Ovarian Serous Adenocarcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage III Fallopian Tube Cancer AJCC v7; Stage III Ovarian Cancer AJCC v6 and v7; Stage III Primary Peritoneal Cancer AJCC v7; Stage IIIA Fallopian Tube Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIA Primary Peritoneal Cancer AJCC v7; Stage IIIB Fallopian Tube Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIB Primary Peritoneal Cancer AJCC v7; Stage IIIC Fallopian Tube Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IIIC Primary Peritoneal Cancer AJCC v7; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7

Paradigm Shift in the Management Strategy for Epithelial Ovarian Cancer.

PubMed

Fujiwara, Keiichi; McAlpine, Jessica N; Lheureux, Stephanie; Matsumura, Noriomi; Oza, Amit M

2016-01-01

The hypothesis on the pathogenesis of epithelial ovarian cancer continues to evolve. Although epithelial ovarian cancer had been assumed to arise from the coelomic epithelium of the ovarian surface, it is now becoming clearer that the majority of serous carcinomas arise from epithelium of the distal fallopian tube, whereas clear cell and endometrioid cancers arise from endometriosis. Molecular and genomic characteristics of epithelial ovarian cancer have been extensively investigated. Our understanding of pathogenesis of the various histologic types of ovarian cancer have begun to inform changes to the strategies for management of epithelial ovarian cancer, which represent a paradigm shift not only for treatment but also for prevention, which previously had not been considered achievable. In this article, we will discuss novel attempts at the prevention of high-grade serous ovarian cancer and treatment strategies for two distinct entities in epithelial ovarian cancer: low-grade serous and clear cell ovarian carcinomas, which are relatively rare and resistant to conventional chemotherapy.

Measures of node centrality in mobile social networks

NASA Astrophysics Data System (ADS)

Gao, Zhenxiang; Shi, Yan; Chen, Shanzhi

2015-02-01

Mobile social networks exploit human mobility and consequent device-to-device contact to opportunistically create data paths over time. While links in mobile social networks are time-varied and strongly impacted by human mobility, discovering influential nodes is one of the important issues for efficient information propagation in mobile social networks. Although traditional centrality definitions give metrics to identify the nodes with central positions in static binary networks, they cannot effectively identify the influential nodes for information propagation in mobile social networks. In this paper, we address the problems of discovering the influential nodes in mobile social networks. We first use the temporal evolution graph model which can more accurately capture the topology dynamics of the mobile social network over time. Based on the model, we explore human social relations and mobility patterns to redefine three common centrality metrics: degree centrality, closeness centrality and betweenness centrality. We then employ empirical traces to evaluate the benefits of the proposed centrality metrics, and discuss the predictability of nodes' global centrality ranking by nodes' local centrality ranking. Results demonstrate the efficiency of the proposed centrality metrics.

p53 Regulates insulin-like growth factor-I receptor gene expression in uterine serous carcinoma and predicts responsiveness to an insulin-like growth factor-I receptor-directed targeted therapy.

PubMed

Attias-Geva, Zohar; Bentov, Itay; Kidron, Dvora; Amichay, Keren; Sarfstein, Rive; Fishman, Ami; Bruchim, Ilan; Werner, Haim

2012-07-01

The role of the insulin-like growth factors (IGF) in endometrial cancer has been well established. The IGF-I receptor (IGF-IR), which mediates the biological actions of IGF-I, is usually overexpressed in endometrial tumours. Uterine serous carcinoma (USC) constitutes a defined histological category among endometrial cancers. Mutation of the p53 gene appears early in the course of the disease and is considered a key event in the initiation of USC. The aim of the present study was to evaluate the potential interactions between p53 and the IGF-IR in USC. In addition, we investigated the role of p53 as a biomarker in IGF-IR targeted therapies. Immunohistochemical analysis in a collection of 35 USC specimens revealed that IGF-IR is highly expressed in primary and metastatic USC. Likewise, p53 was expressed in 85.7% of primary tumours and 100% of metastases. A significant negative correlation between p53 expression and survival was noticed. In addition, using USC-derived cell lines we provide evidence that p53 regulates IGF-IR gene expression via a mechanism that involves repression of the IGF-IR promoter. We show that the mechanism of action of p53 involves interaction with zinc finger protein Sp1, a potent transactivator of the IGF-IR gene. Finally, we demonstrate that USC tumours overexpressing p53 are more likely to benefit from anti-IGF-IR therapies. In summary, we provide evidence that p53 regulates IGF-IR gene expression in USC cells via a mechanism that involves repression of the IGF-IR promoter. The interplay between the p53 and IGF-I signalling pathways is of major basic and translational relevance. Copyright © 2011 Elsevier Ltd. All rights reserved.

Kinematics of the anthropoid os centrale and the functional consequences of scaphoid-centrale fusion in African apes and hominins.

PubMed

Orr, Caley M

2018-01-01

In most primates, the os centrale is interposed between the scaphoid, trapezoid, trapezium, and head of the capitate, thus constituting a component of the wrist's midcarpal complex. Scaphoid-centrale fusion is among the clearest morphological synapomorphies of African apes and hominins. Although it might facilitate knuckle-walking by increasing the rigidity and stability of the radial side of the wrist, the exact functional significance of scaphoid-centrale fusion is unclear. If fusion acts to produce a more rigid radial wrist that stabilizes the hand and limits shearing stresses, then in taxa with a free centrale, it should anchor ligaments that check extension and radial deviation, but exhibit motion independent of the scaphoid. Moreover, because the centrale sits between the scaphoid and capitate (a major stabilizing articulation), scaphoid-centrale mobility should correlate with scaphocapitate mobility in extension and radial deviation. To test these hypotheses, the centrale's ligamentous binding was investigated via dissection in Pongo and Papio, and the kinematics of the centrale were quantified in a cadaveric sample of anthropoids (Pongo sp., Ateles geoffroyi, Colobus guereza, Macaca mulatta, and Papio anubis) using a computed-tomography-based method to track wrist-bone motion. Results indicate that the centrale rotates freely relative to the scaphoid in all taxa. However, centrale mobility is only correlated with scaphocapitate mobility during extension in Pongo-possibly due to differences in overall wrist configuration between apes and monkeys. If an extant ape-like wrist characterized early ancestors of African apes and hominins, then scaphoid-centrale fusion would have increased midcarpal rigidity in extension relative to the primitive condition. Although biomechanically consistent with a knuckle-walking hominin ancestor, this assumes that the trait evolved specifically for that biological role, which must be squared with contradictory interpretations of

Centralized mouse repositories.

PubMed

Donahue, Leah Rae; Hrabe de Angelis, Martin; Hagn, Michael; Franklin, Craig; Lloyd, K C Kent; Magnuson, Terry; McKerlie, Colin; Nakagata, Naomi; Obata, Yuichi; Read, Stuart; Wurst, Wolfgang; Hörlein, Andreas; Davisson, Muriel T

2012-10-01

Because the mouse is used so widely for biomedical research and the number of mouse models being generated is increasing rapidly, centralized repositories are essential if the valuable mouse strains and models that have been developed are to be securely preserved and fully exploited. Ensuring the ongoing availability of these mouse strains preserves the investment made in creating and characterizing them and creates a global resource of enormous value. The establishment of centralized mouse repositories around the world for distributing and archiving these resources has provided critical access to and preservation of these strains. This article describes the common and specialized activities provided by major mouse repositories around the world.

Digital data sets that describe aquifer characteristics of the Central Oklahoma Aquifer in central Oklahoma

USGS Publications Warehouse

Runkle, D.L.; Christenson, S.C.; Rea, Alan

1997-01-01

ARC/INFO export files The data sets in this report include digitized aquifer boundaries and maps of hydraulic conductivity, recharge, and ground-water level elevation contours for the Central Oklahoma aquifer in central Oklahoma. This area encompasses all or part of Cleveland, Lincoln, Logan, Oklahoma, Payne, and Pottawatomie Counties. The Central Oklahoma aquifer includes the alluvial and terrace deposits along major streams, the Garber Sandstone and Wellington Formations, and the Chase, Council Grove, and Admire Groups. The Quaternary-age alluvial and terrace deposits consist of unconsolidated clay, silt, sand, and gravel. The Permian-age Garber Sandstone and Wellington Formations consist of sandstone with interbedded siltstone and mudstone. The Permian-age Chase, Council Grove, and Admire Groups consist of sandstone, shale, and thin limestone. The Central Oklahoma aquifer underlies about 3,000 square miles of central Oklahoma where the aquifer is used extensively for municipal, industrial, commercial, and domestic water supplies. Most of the usable ground water within the aquifer is from the Garber Sandstone and Wellington Formations. Substantial quantities of usable ground water also are present in the Chase, Council Grove, and Admire Groups, and in alluvial and terrace deposits associated with the major streams. The aquifer boundaries, hydraulic conductivity and recharge values, and ground-water level elevation contours are from previously published reports.

A New Measure of Centrality for Brain Networks

PubMed Central

Joyce, Karen E.; Laurienti, Paul J.; Burdette, Jonathan H.; Hayasaka, Satoru

2010-01-01

Recent developments in network theory have allowed for the study of the structure and function of the human brain in terms of a network of interconnected components. Among the many nodes that form a network, some play a crucial role and are said to be central within the network structure. Central nodes may be identified via centrality metrics, with degree, betweenness, and eigenvector centrality being three of the most popular measures. Degree identifies the most connected nodes, whereas betweenness centrality identifies those located on the most traveled paths. Eigenvector centrality considers nodes connected to other high degree nodes as highly central. In the work presented here, we propose a new centrality metric called leverage centrality that considers the extent of connectivity of a node relative to the connectivity of its neighbors. The leverage centrality of a node in a network is determined by the extent to which its immediate neighbors rely on that node for information. Although similar in concept, there are essential differences between eigenvector and leverage centrality that are discussed in this manuscript. Degree, betweenness, eigenvector, and leverage centrality were compared using functional brain networks generated from healthy volunteers. Functional cartography was also used to identify neighborhood hubs (nodes with high degree within a network neighborhood). Provincial hubs provide structure within the local community, and connector hubs mediate connections between multiple communities. Leverage proved to yield information that was not captured by degree, betweenness, or eigenvector centrality and was more accurate at identifying neighborhood hubs. We propose that this metric may be able to identify critical nodes that are highly influential within the network. PMID:20808943

Central Hypothyroidism in Miniature Schnauzers.

PubMed

Voorbij, Annemarie M W Y; Leegwater, Peter A J; Buijtels, Jenny J C W M; Daminet, Sylvie; Kooistra, Hans S

2016-01-01

Primary hypothyroidism is a common endocrinopathy in dogs. In contrast, central hypothyroidism is rare in this species. The objective of this article is to describe the occurrence and clinical presentation of central hypothyroidism in Miniature Schnauzers. Additionally, the possible role of the thyroid-stimulating hormone (TSH)-releasing hormone receptor (TRHR) gene and the TSHβ (TSHB) gene was investigated. Miniature Schnauzers with proven central hypothyroidism, based on scintigraphy, and the results of a 3-day-TSH-stimulation test, or a TSH-releasing hormone (TRH)-stimulation test or both, presented to the Department of Clinical Sciences of Companion Animals at Utrecht University or the Department of Medicine and Clinical Biology of Small Animals at Ghent University from 2008 to 2012. Retrospective study. Pituitary function tests, thyroid scintigraphy, and computed tomography (CT) of the pituitary area were performed. Gene fragments of affected dogs and controls were amplified by polymerase chain reaction (PCR). Subsequently, the deoxyribonucleic acid (DNA) sequences of the products were analyzed. Central hypothyroidism was diagnosed in 7 Miniature Schnauzers. Three dogs had disproportionate dwarfism and at least one of them had a combined deficiency of TSH and prolactin. No disease-causing mutations were found in the TSHB gene and the exons of the TRHR gene of these Schnauzers. Central hypothyroidism could be underdiagnosed in Miniature Schnauzers with hypothyroidism, especially in those of normal stature. The fact that this rare disorder occurred in 7 dogs from the same breed suggests that central hypothyroidism could have a genetic background in Miniature Schnauzers. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Community centrality and social science research.

PubMed

Allman, Dan

2015-12-01

Community centrality is a growing requirement of social science. The field's research practices are increasingly expected to conform to prescribed relationships with the people studied. Expectations about community centrality influence scholarly activities. These expectations can pressure social scientists to adhere to models of community involvement that are immediate and that include community-based co-investigators, advisory boards, and liaisons. In this context, disregarding community centrality can be interpreted as failure. This paper considers evolving norms about the centrality of community in social science. It problematises community inclusion and discusses concerns about the impact of community centrality on incremental theory development, academic integrity, freedom of speech, and the value of liberal versus communitarian knowledge. Through the application of a constructivist approach, this paper argues that social science in which community is omitted or on the periphery is not failed science, because not all social science requires a community base to make a genuine and valuable contribution. The utility of community centrality is not necessarily universal across all social science pursuits. The practices of knowing within social science disciplines may be difficult to transfer to a community. These practices of knowing require degrees of specialisation and interest that not all communities may want or have.

Community centrality and social science research

PubMed Central

Allman, Dan

2015-01-01

Community centrality is a growing requirement of social science. The field's research practices are increasingly expected to conform to prescribed relationships with the people studied. Expectations about community centrality influence scholarly activities. These expectations can pressure social scientists to adhere to models of community involvement that are immediate and that include community-based co-investigators, advisory boards, and liaisons. In this context, disregarding community centrality can be interpreted as failure. This paper considers evolving norms about the centrality of community in social science. It problematises community inclusion and discusses concerns about the impact of community centrality on incremental theory development, academic integrity, freedom of speech, and the value of liberal versus communitarian knowledge. Through the application of a constructivist approach, this paper argues that social science in which community is omitted or on the periphery is not failed science, because not all social science requires a community base to make a genuine and valuable contribution. The utility of community centrality is not necessarily universal across all social science pursuits. The practices of knowing within social science disciplines may be difficult to transfer to a community. These practices of knowing require degrees of specialisation and interest that not all communities may want or have. PMID:26440071

48 CFR 52.204-7 - Central Contractor Registration.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Central Contractor....204-7 Central Contractor Registration. As prescribed in 4.1105, use the following clause: Central Contractor Registration (APR 2008) (a) Definitions. As used in this clause— Central Contractor Registration...

Prostate cancer susceptibility polymorphism rs2660753 is not associated with invasive ovarian cancer

PubMed Central

Amankwah, Ernest K; Kelemen, Linda E; Wang, Qinggang; Song, Honglin; Chenevix-Trench, Georgia; Beesley, Jonathan; Webb, Penelope M; Pearce, Celeste L; Wu, Anna H; Pike, Malcolm C; Stram, Daniel O; Chang-Claude, Jenny; Wang-Gohrke, Shan; Ness, Roberta B; Goode, Ellen L; Cunningham, Julie M; Fridley, Brooke L; Vierkant, Robert A; Tworoger, Shelley S; Whittemore, Alice S; McGuire, Valerie; Sieh, Weiva; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J; Rossing, Mary Anne; Doherty, Jennifer A; Goodman, Marc T; Carney, Michael E; Lurie, Galina; Wilkens, Lynne R; Kjær, Susanne Krüger; Høgdall, Estrid; Cramer, Daniel W; Terry, Kathryn L; Garcia-Closas, Montserrat; Yang, Hannah; Lissowska, Jolanta; Anton-Culver, Hoda; Ziogas, Argyrios; Schildkraut, Joellen M; Berchuck, Andrew; Pharoah, Paul DP

2011-01-01

Background We previously reported an association between rs2660753, a prostate cancer susceptibility polymorphism, and invasive epithelial ovarian cancer (EOC) [odds ratio (OR)=1.2, 95% confidence interval (CI)=1.0-1.4, Ptrend=0.01] that showed a stronger association with the serous histological subtype (OR=1.3, 95% CI=1.1-1.5, Ptrend=0.003). Methods We sought to replicate this association in 12 other studies comprising 4,482 cases and 6,894 controls of white non-Hispanic ancestry in the Ovarian Cancer Association Consortium. Results No evidence for an association with all cancers or serous cancers was observed in a combined analysis of data from the replication studies (all: OR=1.0, 95% CI=0.9-1.1, Ptrend=0.61; serous: OR=1.0, 95% CI=0.9-1.1, Ptrend=0.85) or from the combined analysis of discovery and replication studies (all: OR=1.0, 95% CI=1.0-1.1, Ptrend= 0.28; serous: OR=1.1, 95% CI=1.0-1.2, Ptrend=0.11). There was no evidence for statistical heterogeneity in ORs across the studies. Conclusions Although rs2660753 is a strong a prostate cancer susceptibility polymorphism, the association with another hormonally related cancer, invasive EOC, is not supported by this replication study. Impact Our findings, based on a larger sample size, emphasize the importance of replicating potentially promising genetic risk associations. PMID:21415361

Ovarian Epithelial Inclusions With Mucinous Differentiation: A Clinicopathologic Study of 42 Cases.

PubMed

Seidman, Jeffrey D; Krishnan, Jayashree

2017-07-01

Ovarian epithelial inclusions lined by mucinous epithelium are rare and of uncertain origin. Ovaries containing such inclusions were studied in 42 women. The inclusions were divided into 3 groups: serous epithelial lined with typical ciliated morphology but with distinct basophilic cytoplasmic mucin in some or all of the lining cells, those lined by typical mucinous epithelium, and those lined by a combination of typical mucinous epithelium and serous epithelium. The mean patient age was 61.5 years. Pure mucinous inclusions were found in 27 patients, serous-type inclusions with cytoplasmic mucin in 20, and mixed type in 10. All 3 types of inclusions were found in 1 patient. Two types of inclusions were found in 13. Four patients had associated mucinous neoplasms (1 mucinous cystadenoma, 1 atypical proliferative seromucinous tumor, and 2 seromucinous cystadenomas), and 11 patients (26%) had endometriosis. The fallopian tubes in 4 patients (9.5%) also displayed mucinous metaplasia; this was not significantly different from the 3.1% we found in our previously reported series of unselected tubes from the same population. These findings suggest that mucinous inclusions may arise as a direct metaplastic change in serous-type inclusions. Other possible origins of mucinous inclusions in the ovarian cortex include endometriosis and Brenner (transitional cell) nests. Whether such inclusions can be a source of mucinous ovarian neoplasms as are Brenner tumors and mature cystic teratomas is unknown and may warrant further investigation.

A novel serum microRNA panel to discriminate benign from malignant ovarian disease.

PubMed

Langhe, Ream; Norris, Lucy; Saadeh, Feras Abu; Blackshields, Gordon; Varley, Rachel; Harrison, Ashling; Gleeson, Noreen; Spillane, Cathy; Martin, Cara; O'Donnell, Dearbhaile M; D'Arcy, Tom; O'Leary, John; O'Toole, Sharon

2015-01-28

Ovarian cancer is the seventh most common cancer in women and the most frequent cause of gynaecological malignancy-related mortality in women. Currently, no standardized reliable screening test exists. MicroRNA profiling has allowed the identification of signatures associated with diagnosis, prognosis and response to treatment of human tumours. The aim of this study was to determine if a microRNA signature could distinguish between malignant and benign ovarian disease. A training set of 5 serous ovarian carcinomas and 5 benign serous cystadenomas were selected for the initial experiments. The validation set included 20 serous ovarian carcinomas and 20 benign serous cystadenomas. The serum/plasma focus microRNA Exiqon panel was used for the training set. For the validation set a pick and mix Exiqon panel, which focuses on microRNAs of interest was used. A panel of 4 microRNAs (let-7i-5p, miR-122, miR-152-5p and miR-25-3p) was significantly down regulated in cancer patients. These microRNAs target WNT signalling, AKT/mTOR and TLR-4/MyD88, which have previously been found to play a role in ovarian carcinogenesis and chemoresistance. let-7i-5p, miR-122, miR-152-5p and miR-25-3p could act as diagnostic biomarkers in ovarian cancer. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Pathology of Endometrial Carcinoma.

PubMed

Lax, Sigurd F

2017-01-01

On a clinicopathological and molecular level, two distinctive types of endometrial carcinoma, type I and type II, can be distinguished. Endometrioid carcinoma, the typical type I carcinoma, seems to develop through an estrogen-driven "adenoma carcinoma" pathway from atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (AEH/EIN). It is associated with elevated serum estrogen and high body mass index and expresses estrogen and progesterone receptors. They are mostly low grade and show a favorable prognosis. A subset progresses into high-grade carcinoma which is accompanied by loss of receptor expression and accumulation of TP53 mutations and behaves poorly. Other frequently altered genes in type I carcinomas are K-Ras, PTEN, and ß-catenin. Another frequent feature of type I carcinomas is microsatellite instability mainly caused by methylation of the MLH1 promoter. In contrast, the typical type II carcinoma, serous carcinoma, is not estrogen related since it usually occurs in a small uterus with atrophic endometrium. It is often associated with a flat putative precursor lesion called serous endometrial intraepithelial carcinoma (SEIC). The molecular pathogenesis of serous carcinoma seems to be driven by TP53 mutations, which are present in SEIC. Other molecular changes in serous carcinoma detectable by immunohistochemistry involve cyclin E and p16. Since many of the aforementioned molecular changes can be demonstrated by immunohistochemistry, they are useful ancillary diagnostic tools and may further contribute to a future molecular classification of endometrial carcinoma as recently suggested based on The Cancer Genome Atlas (TCGA) data.

The evolution of endometrial carcinoma classification through application of immunohistochemistry and molecular diagnostics: past, present and future.

PubMed

Goebel, Emily A; Vidal, August; Matias-Guiu, Xavier; Blake Gilks, C

2017-12-12

Uterine cancer was first subclassified based on anatomic site, separating those tumours arising from the endometrium from cervical cancers. There was then further subclassification of endometrial cancers based on cell type, and this correlated with the Type I and Type II categories identified through the epidemiological studies of Bokhman, with endometrioid carcinoma corresponding (approximately) to Type I and serous carcinoma to Type II. These histotypes are not clearly separable in practice, however, with considerable interobserver variability in histotype diagnosis, especially for high-grade tumours. There followed studies of immunomarkers and then mutational studies of single genes, in attempts to improve subclassification. While these have revealed significant differences in protein expression and mutation profiles between endometrioid and serous carcinomas, there is also considerable overlap, so that there remain challenges in subclassification of endometrial carcinoma. Gene panel testing, using next-generation sequencing, was applied to endometrial cancers and highlighted that there are tumours that show genetic alterations intermediate between classic Type I/endometrioid and Type II/serous carcinomas. The Cancer Genome Atlas studies of endometrioid and serous carcinoma offered revolutionary insight into the subclassification of endometrial carcinoma, i.e. that there are four distinct categories of endometrial carcinoma, rather than two, based on genomic architecture. In this review, we provide an overview of immunohistochemical and molecular markers in endometrial carcinoma and comment on the important future directions in endometrial carcinoma subclassification arising from The Cancer Genome Atlas results.

Endometrial cancers in mutation carriers from hereditary breast ovarian cancer syndrome kindreds: report from the Creighton University Hereditary Cancer Registry with review of the implications.

PubMed

Casey, Murray Joseph; Bewtra, Chhanda; Lynch, Henry T; Snyder, Carrie L; Stacey, Mark

2015-05-01

The aim of this study was to categorize and report endometrial cancers in mutation carriers from hereditary breast ovarian cancer families. Our Hereditary Cancer Registry was searched for gynecologic and peritoneal cancers linked to mutations in BRCA1 or BRCA2. Invasive cancers were registered in 101 mutation carriers with complete pathology reports. Efforts were made to secure diagnostic surgical pathology tissues for review. All records and available diagnostic slides were meticulously studied, and primary cancers were classified. Eight malignancies were classified as primary endometrial cancers. Five of these were low- or intermediate-grade endometrioid carcinomas, and 3 were pure serous carcinomas or contained serous carcinoma elements mixed with high-grade endometrioid carcinoma. Breast cancers were diagnosed in 5 patients before and in 1 patient after endometrial carcinoma. Three endometrioid carcinomas were preceded by estrogen treatment, 2 for many years and the other for only 2 months, and 2 of the patients with serous carcinoma had been treated with tamoxifen. The finding that 8 of gynecologic and peritoneal cancers in 101 mutation carriers were endometrial cancers with a smaller proportion of endometrioid carcinomas than reported in general populations is added to the current controversial literature on endometrial cancer, particularly regarding serous carcinomas, in hereditary breast ovarian cancer syndrome. Well-designed prospective programs for standardized surgical and pathologic handling, processing, and reporting are essential for working out the pathogenesis, true risks, and best management of this disease in carriers of deleterious BRCA1 and BRCA2 germline mutations.

Comparison of blood loss between using non central part cutting knee prosthesis and distal central part cutting.

PubMed

Malairungsakul, Anan

2014-12-01

Patients who undergo knee replacement surgery may need to receive a blood transfusion due to blood loss during the operation. Therefore it was important to improve the design of knee implant operative procedures in an attempt to reduce the rate of blood loss. The present study aimed to compare the blood loss between two types of knee replacement surgery. This is a retrospective study in which 78 patients received cemented knee replacements in Phayao Hospital between October 2010 and March 2012. There were two types of surgical procedure: 1) using an implant position covering the end of the femoral bone without cutting into the central part of the distal femoral, 2) using an implant position covering the end of the femoral bone cutting the central part of the distal femoral. Blood loss, blood transfusion, hemoglobin and hematocrit were recorded preoperatively, immediately postsurgery and 48 hours after surgery. Findings revealed that the knee replacement surgery using the implant position covering the end of the femoral bone without cutting the central part of the distal femoral significantly lowered the rate of blood loss when compared to using the implant position covering the end of the femoral bone with central cutting of the distal femor. The average blood loss during the operation without cutting at the central part of distal femoral was 49.50 ± 11.11 mL; whereas the operation cutting the central part of the distal femoral was 58.50 ± 11.69 mL. As regards blood loss, the knee replacement surgery using the implant position covering the end ofthefemoral bone without cutting the central part of distal femor was better than using the implant position covering the end of the femoral bone cutting at the central part of the distal femor.

The economics of central billing offices.

PubMed

Woodcock, E; Nguyen, L

2000-01-01

The anticipation of economies of scale in physician billing has led many medical practices to consolidate their billing operations. This article analyzes these economies of scale, comparing performance indicators from centralized and decentralized operations. While consolidation provides compliance, control and information, diseconomies of scale can exist in the centralized receivables management process. The authors conclude that physician practices should consider a hybrid approach to billing, thus reaping the benefits of both centralization and decentralization.

Central Asia: A New Great Game?

DTIC Science & Technology

1996-06-17

CENTRAL ASIA: A NEW GREAT GAME? Dianne L. Smith June 17, 1996 ******* The views expressed in this report are those of the author and do not...power vacuum in Central Asia seems a remote concern at first blush. Colonel Smith’s review makes clear, however, that the paramount American stake...will always subordinate its relations with Central Asia to those with Russia. Iran still views Iraq as its greatest regional threat. Teheran will do

Public water supplies in central and north-central Texas

USGS Publications Warehouse

Sundstrom, Raymond W.; Broadhurst, W.L.; Dwyer, B.C.

1949-01-01

This report gives a summarized description of the public water supplies in 35 counties of central and north-central Texas, extending from the southern boundaries of Travis, Blanco, Gillespie, and Kerr Counties northward to the TexasOklahoma State line. It gives the available data as follows for each of the 145 communities: Population of the community; name of the official from whom the information was obtained; ownership of water works, whether private or municipal source of supply, whether ground water or surface water; the amount of water consumed; the facilities for storage; the number of customers served; the character of the chemical and sanitary treatment, if any; and chemical analyses of the water. Where ground water is used, the following is also given: Records of wells, including drillers' logs; character of the pumping equipment; yields of the wells, and records of water levels, if available.

Coverage centralities for temporal networks*

NASA Astrophysics Data System (ADS)

Takaguchi, Taro; Yano, Yosuke; Yoshida, Yuichi

2016-02-01

Structure of real networked systems, such as social relationship, can be modeled as temporal networks in which each edge appears only at the prescribed time. Understanding the structure of temporal networks requires quantifying the importance of a temporal vertex, which is a pair of vertex index and time. In this paper, we define two centrality measures of a temporal vertex based on the fastest temporal paths which use the temporal vertex. The definition is free from parameters and robust against the change in time scale on which we focus. In addition, we can efficiently compute these centrality values for all temporal vertices. Using the two centrality measures, we reveal that distributions of these centrality values of real-world temporal networks are heterogeneous. For various datasets, we also demonstrate that a majority of the highly central temporal vertices are located within a narrow time window around a particular time. In other words, there is a bottleneck time at which most information sent in the temporal network passes through a small number of temporal vertices, which suggests an important role of these temporal vertices in spreading phenomena. Contribution to the Topical Issue "Temporal Network Theory and Applications", edited by Petter Holme.Supplementary material in the form of one pdf file available from the Journal web page at http://dx.doi.org/10.1140/epjb/e2016-60498-7

Genetic identification of the central nucleus and other components of the central extended amygdala in chicken during development

PubMed Central

Vicario, Alba; Abellán, Antonio; Desfilis, Ester; Medina, Loreta

2014-01-01

In mammals, the central extended amygdala shows a highly complex organization, and is essential for animal survival due to its implication in fear responses. However, many aspects of its evolution are still unknown, and this structure is especially poorly understood in birds. The aim of this study was to define the central extended amygdala in chicken, by means of a battery of region-specific transcription factors (Pax6, Islet1, Nkx2.1) and phenotypic markers that characterize these different subdivisions in mammals. Our results allowed the identification of at least six distinct subdivisions in the lateral part of the avian central extended amygdala: (1) capsular central subdivision; (2) a group of intercalated-like cell patches; (3) oval central nucleus; (4) peri-intrapeduncular (peri-INP) island field; (5) perioval zone; and (6) a rostral part of the subpallial extended amygdala. In addition, we identified three subdivisions of the laterodorsal bed nucleus of the stria terminalis (BSTLd) belonging to the medial region of the chicken central extended amygdala complex. Based on their genetic profile, cellular composition and apparent embryonic origin of the cells, we discuss the similarity of these different subdivisions of chicken with different parts of the mouse central amygdala and surrounding cell masses, including the intercalated amygdalar masses and the sublenticular part of the central extended amygdala. Most of the subdivisions include various subpopulations of cells that apparently originate in the dorsal striatal, ventral striatal, pallidal, and preoptic embryonic domains, reaching their final location by either radial or tangential migrations. Similarly to mammals, the central amygdala and BSTLd of chicken project to the hypothalamus, and include different neurons expressing proenkephalin, corticotropin-releasing factor, somatostatin or tyrosine hydroxylase, which may be involved in the control of different aspects of fear/anxiety-related behavior

Central hypothyroidism - a neglected thyroid disorder.

PubMed

Beck-Peccoz, Paolo; Rodari, Giulia; Giavoli, Claudia; Lania, Andrea

2017-10-01

Central hypothyroidism is a rare and heterogeneous disorder that is characterized by a defect in thyroid hormone secretion in an otherwise normal thyroid gland due to insufficient stimulation by TSH. The disease results from the abnormal function of the pituitary gland, the hypothalamus, or both. Moreover, central hypothyroidism can be isolated or combined with other pituitary hormone deficiencies, which are mostly acquired and are rarely congenital. The clinical manifestations of central hypothyroidism are usually milder than those observed in primary hypothyroidism. Obtaining a positive diagnosis for central hypothyroidism can be difficult from both a clinical and a biochemical perspective. The diagnosis of central hypothyroidism is based on low circulating levels of free T 4 in the presence of low to normal TSH concentrations. The correct diagnosis of both acquired (also termed sporadic) and congenital (also termed genetic) central hypothyroidism can be hindered by methodological interference in free T 4 or TSH measurements; routine utilization of total T 4 or T 3 measurements; concurrent systemic illness that is characterized by low levels of free T 4 and normal TSH concentrations; the use of the sole TSH-reflex strategy, which is the measurement of the sole level of TSH, without free T 4 , if levels of TSH are in the normal range; and the diagnosis of congenital hypothyroidism based on TSH analysis without the concomitant measurement of serum levels of T 4 . In this Review, we discuss current knowledge of the causes of central hypothyroidism, emphasizing possible pitfalls in the diagnosis and treatment of this disorder.

Distributed trace using central performance counter memory

DOEpatents

Satterfield, David L; Sexton, James C

2013-10-22

A plurality of processing cores, are central storage unit having at least memory connected in a daisy chain manner, forming a daisy chain ring layout on an integrated chip. At least one of the plurality of processing cores places trace data on the daisy chain connection for transmitting the trace data to the central storage unit, and the central storage unit detects the trace data and stores the trace data in the memory co-located in with the central storage unit.

Distributed trace using central performance counter memory

DOEpatents

Satterfield, David L.; Sexton, James C.

2013-01-22

A plurality of processing cores, are central storage unit having at least memory connected in a daisy chain manner, forming a daisy chain ring layout on an integrated chip. At least one of the plurality of processing cores places trace data on the daisy chain connection for transmitting the trace data to the central storage unit, and the central storage unit detects the trace data and stores the trace data in the memory co-located in with the central storage unit.

Multi-parametric centrality method for graph network models

NASA Astrophysics Data System (ADS)

Ivanov, Sergei Evgenievich; Gorlushkina, Natalia Nikolaevna; Ivanova, Lubov Nikolaevna

2018-04-01

The graph model networks are investigated to determine centrality, weights and the significance of vertices. For centrality analysis appliesa typical method that includesany one of the properties of graph vertices. In graph theory, methods of analyzing centrality are used: in terms by degree, closeness, betweenness, radiality, eccentricity, page-rank, status, Katz and eigenvector. We have proposed a new method of multi-parametric centrality, which includes a number of basic properties of the network member. The mathematical model of multi-parametric centrality method is developed. Comparison of results for the presented method with the centrality methods is carried out. For evaluate the results for the multi-parametric centrality methodthe graph model with hundreds of vertices is analyzed. The comparative analysis showed the accuracy of presented method, includes simultaneously a number of basic properties of vertices.

Centralized Mouse Repositories

PubMed Central

Donahue, Leah Rae; de Angelis, Martin Hrabe; Hagn, Michael; Franklin, Craig; Lloyd, K. C. Kent; Magnuson, Terry; McKerlie, Colin; Nakagata, Naomi; Obata, Yuichi; Read, Stuart; Wurst, Wolfgang; Hörlein, Andreas; Davisson, Muriel T.

2013-01-01

Because the mouse is used so widely for biomedical research and the number of mouse models being generated is increasing rapidly, centralized repositories are essential if the valuable mouse strains and models that have been developed are to be securely preserved and fully exploited. Ensuring the ongoing availability of these mouse strains preserves the investment made in creating and characterizing them and creates a global resource of enormous value. The establishment of centralized mouse repositories around the world for distributing and archiving these resources has provided critical access to and preservation of these strains. This article describes the common and specialized activities provided by major mouse repositories around the world. PMID:22945696

48 CFR 18.102 - Central contractor registration.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Central contractor... Central contractor registration. Contractors are not required to be registered in the Central Contractor.... (See 4.1102). However, contractors are required to register with CCR in order to gain access to the...

Diabetes insipidus - central

MedlinePlus

... Alternative Names Central diabetes insipidus; Neurogenic diabetes insipidus Images Endocrine glands References Brimioulle S. Diabetes insipidus. In: Vincent J-L, Abraham E, Moore FA, Kochanek PM, Fink ...

Effect of Vilon and Epithalon on glucose and glycine absorption in various regions of small intestine in aged rats.

PubMed

Khavinson, V Kh; Egorova, V V; Timofeeva, N M; Malinin, V V; Gordova, L A; Gromova, L V

2002-05-01

Vilon (Lys-Glu) and Epithalon (Ala-Glu-Asp-Gly) administered orally for 1 month improved transport characteristics of the small intestine in aged rats. Vilon enhanced passive glucose accumulation in the serous fluid in inverted sac made from the distal region of the small intestine, while Epithalon enhanced this process in the medial region. Vilon stimulated active glucose accumulation in the serous sac of the medial small intestine, Epithalon - in the proximal and distal small intestinal segments. Glycine absorption increased only in the proximal intestinal segment under the effect of Epithalon.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koch, R.

Attempts were made to determine the action of ionizing radiation on the central nervous system by its altered response to various drugs after irradiation. The influence of the drugs was tested by injecting them in mice 30 min before and 30 min or 6 days after whole-body irradiation with 400 r. Irradiation did not alter the LD 50 of any of the drugs: adrenaline, ephedrine, amphetamine, Pervitin (d-deoxyephedrine), and eventin. Slightly greater toxicity symptoms were noted with amphetamine after irradiation. The convulsive death of rats irradiated with high doses (up to 15000 r) was not altered by injection of themore » central stimulant Metrazole (35 mg/kg). A serous meningoencephalitis was noted in rats irradiated with 15000 r. BETA , BETA '-Iminodipropionitrile, a drug which intensely stimulates the cerebrum and induces a circling activity in mice, was tested for possible radioresistance properties. It significantly increased the LD 50 in female mice to 753 r from a control value of 634 r. Irradiation did not potentiate the action of the drug, and its suppressive effect on radioinduced death was no longer evident 6 months after the drug had been given. The results suggest that the action of central stimulants, unlike narcotics, is not greatly affected by irradiation of the central nervous system.« less

Microsurgical anatomy of the central lobe.

PubMed

Frigeri, Thomas; Paglioli, Eliseu; de Oliveira, Evandro; Rhoton, Albert L

2015-03-01

The central lobe consists of the pre- and postcentral gyri on the lateral surface and the paracentral lobule on the medial surface and corresponds to the sensorimotor cortex. The objective of the present study was to define the neural features, craniometric relationships, arterial supply, and venous drainage of the central lobe. Cadaveric hemispheres dissected using microsurgical techniques provided the material for this study. The coronal suture is closer to the precentral gyrus and central sulcus at its lower rather than at its upper end, but they are closest at a point near where the superior temporal line crosses the coronal suture. The arterial supply of the lower two-thirds of the lateral surface of the central lobe was from the central, precentral, and anterior parietal branches that arose predominantly from the superior trunk of the middle cerebral artery. The medial surface and the superior third of the lateral surface were supplied by the posterior interior frontal, paracentral, and superior parietal branches of the pericallosal and callosomarginal arteries. The venous drainage of the superior two-thirds of the lateral surface and the central lobe on the medial surface was predominantly through the superior sagittal sinus, and the inferior third of the lateral surface was predominantly through the superficial sylvian veins to the sphenoparietal sinus or the vein of Labbé to the transverse sinus. The pre- and postcentral gyri and paracentral lobule have a morphological and functional anatomy that differentiates them from the remainder of their respective lobes and are considered by many as a single lobe. An understanding of the anatomical relationships of the central lobe can be useful in preoperative planning and in establishing reliable intraoperative landmarks.