Many members of the human kallikrein gene family were found to be differentially expressed in various malignancies and some are useful cancer diagnostic/prognostic markers. KLK9 is a newly discovered ...human kallikrein gene that is expressed in several tissues including thymus, testis, spinal cord, salivary gland, ovary, and skin. Like other kallikreins, the KLK9 gene was found to be regulated by steroid hormones in cancer cell lines. Our purpose is to examine whether quantitative analysis of KLK9 expression has prognostic value in ovarian cancer. We studied the expression of KLK9 by quantitative reverse transcription-PCR in 168 consecutive ovarian tumors of different stages, grades, and histological types, and correlated the expression with clinicopathological parameters, response to chemotherapy, and patients' survival. We found that KLK9 expression was significantly higher in patients with early disease stages (I or II; P = 0.044) and in patients with optimal debulking (P = 0.019). Kaplan-Meier survival curves demonstrated that patients with KLK9-positive tumors have substantially longer progression-free and overall survival (P < 0.001 and P = 0.016, respectively). When the Cox proportional hazard regression analysis was applied to subgroups of patients, KLK9 expression was found to be a significant predictor of progression-free survival in the subgroup of patients with low-grade tumors hazard ratio (HR), 0.13; P = 0.0015, early stage (HR, 0.099; P = 0.031); and those with optimal debulking (HR, 0.26; P = 0.012). After adjusting for other known prognostic variables, KLK9 retained its independent prognostic value in all of these subgroups of patients. A negative correlation was found between the expression levels of CA125 and KLK9 (rs, 0.350; P = 0.002). Our results indicate that KLK9 is under steroid hormone regulation in ovarian and breast cancer cell lines. Immmunohistochemically, human kallikrein protein (hK9) was localized in the cytoplasm, but not in the nuclei, of the epithelial cells of ovarian cancer tissues. We conclude that KLK9 is a potential new independent favorable prognostic marker for early stage, low-grade, optimally debulked ovarian cancer patients.
Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is closely related to the metabolic syndrome as well as to arterial hypertension and overall cardiovascular (CV) disease. We aimed to ...investigate if those first diagnosed and never treated patients with essential hypertension at high risk for NAFLD, measured by the Hepatic Steatosis Index (HSI), already have an impaired CV risk profile estimated by increased blood pressure burden and accompanied by the presence of hypertension-mediated organ damage (HMOD).
Methods
We studied 300 non-diabetic, first diagnosed and never-treated young hypertensive patients mean age=51+11 years, 60% males, 32% smokers. Ambulatory blood pressure monitoring (24h ABPM), CV risk factors smoking, obesity (BMI), hyperlipidemia and HMOD aortic stiffness (PWV), left ventricular diastolic dysfunction (EEa), cardiac hypertrophy (LVMI), coronary arteries microcirculation (CFR), carotid intima-media thickness (cIMT) and endothelial dysfunction (PBR5-25) were estimated in each patient before treatment initiation. HIS was calculated as 8 times (ALT/AST ratio) +BMI (+2, if female; +2, if diabetes mellitus). Increased HIS levels predispose for augmented risk for NAFLD.
Results
The whole hypertensive population was divided regarding HSI median value=39.5 in two groups, Group A (higher risk for NAFLD group, n=150, age=50+10, 59% males, 33% smokers) and Group B (lower risk for NAFLD group, n=150, age=51+11, 60% males, 31% smokers). Group A patients had increased BMI (32+5 vs. 27+3, p<0.001), systolic night-time ABPM (127+15 vs. 124+11, p=0.05), office systolic (152+19 vs. 145+17 mmHg, p=0.004) and diastolic BP (94+11 vs. 90+11 mmHg, p=0.002), central systolic BP (146+20 vs. 137+15, p=0.006), Chol (216+39 vs. 206+35, p=0.02), LDL (138+35 vs.130=33 mg/dl, p=0.04) and Trigl (139+75 vs. 112+63, p=0.001), E/Ea (7+2 vs. 6+2, p=0.01) and LVMI (83+18 vs. 79+17, p=0.03) compared to Group B. All other studied demographic, laboratory, ABPM and HMOD parameters (PWV, MAU, CFR and cIMT) were similar between groups. HSI was related to BMI (p<0.001) and office BP, both systolic (p=0.001) and diastolic (p=0.008) in total population as well as to LVMI (r=0.17, p=0.02) in males. Finally, in multiple regression analysis, we found that HSI was independently associated with LVMI (beta=0.14, p=0.05) only in male hypertensives.
Conclusions
Patients first diagnosed arterial hypertension and augmented CV risk (smoking, obesity, hyperlipidemia, BP burden and HMOD) are also at high risk for NAFLD. As successful antihypertensive treatment may lead to HMOD regression, probably there is still time for those patients to be treated for hypertension disease and hyperlipidemia and quit smoking, in order to reduce future CV risk.LVMI and HSI in male hypertensives
Aromatase expression in ovarian epithelial cancers Cunat, S.; Rabenoelina, F.; Daurès, J.-P. ...
The Journal of steroid biochemistry and molecular biology,
2005, 2005-Jan, 2005-1-00, 20050101, Letnik:
93, Številka:
1
Journal Article
Recenzirano
Our study focused on aromatase cytochrome P450 (CYP19) expression in ovarian epithelial normal and cancer cells and tissues. Aromatase mRNA expression was analyzed by real-time PCR in ovarian ...epithelial cancer cell lines, in human ovarian surface epithelial (HOSE) cell primary cultures, and in ovarian tissue specimens (
n
=
94), including normal ovaries, ovarian cysts and cancers. Aromatase mRNA was found to be expressed in HOSE cells, in BG1, PEO4 and PEO14, but not in SKOV3 and NIH:OVCAR-3 ovarian cancer cell lines. Correlation analysis of aromatase expression was performed according to clinical, histological and biological parameters. Aromatase expression in ovarian tissue specimens was higher in normal ovaries and cysts than in cancers (
P
<
0.0001). Using laser capture microdissection in normal postmenopausal ovaries, aromatase was found to be predominantly expressed in epithelial cells as compared to stromal component. Using immunohistochemistry (IHC), aromatase was also detected in the epithelium component. There was an inverse correlation between aromatase and ERα expression in ovarian tissues (
P
<
0.001,
r
=
−0.34). In the cancer group, no significant differences in aromatase expression were observed according to tumor histotype, grade, stage and survival. Aromatase activity was evaluated in ovarian epithelial cancer (OEC) cell lines by the tritiated water assay and the effects of third-generation aromatase inhibitors (AIs) on aromatase activity and growth were studied. Letrozole and exemestane were able to completely inhibit aromatase activity in BG1 and PEO14 cell lines. Interestingly, both AI showed an antiproliferative effect on the estrogen responsive BG1 cell line co-expressing aromatase and ERα.
Aromatase expression was found in ovarian epithelial normal tissues and in some ovarian epithelial cancer cells and tissues. This finding raises the possibility that some tumors may respond to estrogen and provides a basis for ascertaining an antimitogenic effect of AI in a subgroup of ovarian epithelial cancers.
Objective. Methylation of
p16 promoter was evaluated in ovarian cancer to determine the role of
p16 methylation in ovarian cancer prognosis.
Methods. Two hundred and forty-nine patients with primary ...epithelial ovarian cancer were selected for the study; these patients were followed for a median of 31 months. Genomic DNA extracted from fresh frozen tumor tissues were treated with sodium bisulfite and were analyzed for
p16 methylation using methylation-specific PCR (MSP). Cox regression survival analysis was performed to examine the associations of
p16 methylation with progression-free and overall survivals.
Results. Of the 249 patients, 100 (40%) were tested positive for
p16 promoter methylation. The status of
p16 methylation did not change significantly with patient age, disease stage, histological grade, residual tumor size, and debulking results, although
p16 methylation seemed to occur more often in patients with advanced diseases or aggressive tumors. Compared to those without
p16 methylation, patients with
p16 methylation had significantly higher risk for disease progression (
P = 0.01). The relative risk for progression was 1.69 (95% CI: 1.12–2.54), and the association remained statistically significant (RR = 1.54, 95% CI: 1.01–2.34) after adjusting for clinical and pathological variables. The risk for death was also higher in methylation positive patients than in methylation negative patients (RR = 1.33, 95% CI: 0.88–2.00), but the difference was not statistically significant.
Conclusion. The study suggests that promoter methylation in the
p16 gene is associated with ovarian cancer progression, and evaluation of
p16 methylation may have values in predicting ovarian cancer prognosis.
Ovarian cancers mostly derive from the monolayer epithelium that covers the ovary. There are currently very few molecular clues to the etiology of this cancer. Bone morphogenetic proteins (BMPs) are ...required for follicular development and female fertility and are expressed in the ovarian surface epithelium (OSE). We previously reported the expression of human chordin (CHRD), a BMP extracellular regulator, in the ovary. Here we show that CHRD is underexpressed in epithelium ovary cancer and epithelial cancer cell lines as compared with normal tissues and OSE, respectively. Besides, we detected BMP expression in all ovarian cell lines analyzed. To determine the functional relevance of the absence of CHRD mRNA in tumors and cancer cell lines, we studied the effects of CHRD on two cancer cell lines, BG1 and PEO14. Migratory and invasive properties were greatly reduced, whereas cell adhesion to the support was enhanced. In addition, we detected chordin (Chrd) expression in OSE of rat ovaries in a pattern similar to that of BMP4. Altogether, these results suggest that CHRD could participate in regulating BMP activity in normal OSE physiology, and that its mis-expression in OSE may facilitate cancer incidence and/or progression.--Moll, F., Millet, C., Noe̊l, D., Orsetti, B., Bardin, A., Katsaros, D., Jorgensen, C., Garcia, M., Theillet, C., Pujol, P., and François V.
Mobility prediction is one of the most essential issues that need to be explored for mobility management in mobile computing systems. In this paper, we propose a new algorithm for predicting the next ...inter-cell movement of a mobile user in a Personal Communication Systems network. In the first phase of our three-phase algorithm, user mobility patterns are mined from the history of mobile user trajectories. In the second phase, mobility rules are extracted from these patterns, and in the last phase, mobility predictions are accomplished by using these rules. The performance of the proposed algorithm is evaluated through simulation as compared to two other prediction methods. The performance results obtained in terms of
Precision and
Recall indicate that our method can make more accurate predictions than the other methods.
Gazing at the skyline for star scientists Sidiropoulos, A.; Gogoglou, A.; Katsaros, D. ...
Journal of informetrics,
August 2016, 2016-08-00, Letnik:
10, Številka:
3
Journal Article
Recenzirano
•The introduction of the use of skyline operator for scientometric purposes.•Establishment of a methodology based on Principal Component Analysis for selecting the dimensions of the skyline ...operator.•Evaluation of the proposed technique for computer scientists.•Contrast of the skyline members against those being awarded E.F. Codd award, SIGCOMM Lifetime Achievement award, and Turing award.
Admittedly, despite the plethora of scientometric indices proposed to rank scientists, none of them can fully capture the performance and impact of a scientist, since each index quantifies only one or a few aspects of his/her multifarious performance. Therefore, the task of scientometric ranking can be seen as a multi-dimensional ranking problem, where the different indices comprise the dimensions. The application of the skyline operator comes then as a natural solution to the problem. In this article we apply the skyline operator to scientist ranking to identify those scientists whose performance cannot be surpassed by others’ with respect to all attributes. This technique can be used as a tool for short-listing distinguished researchers in case of award nomination.
Human kallikrein 6 protein is a newly discovered human kallikrein. We determined the amount of human kallikrein 6 in extracts of 182 ovarian tumours and correlated specific activity (ng hK6 mg(-1) ...total protein) with clinicopathological variables documented at the time of surgical excision and with outcome (progression free survival, overall survival) monitored over a median interval of 62 months. Thirty per cent of the tumours were positive for human kallikrein 6 (>35 ng hK6 mg(-1) total protein). Human kallikrein 6-specific immunohistochemical staining of four ovarian tissues that included benign, borderline and malignant lesions indicated a cytoplasmic location of human kallikrein 6 in tumour cells of epithelial origin, although the intensity of staining was variable. Tumour human kallikrein 6 (ng hK6 mg(-1) total protein) was higher in late stage disease, serous histotype, residual tumour >1 cm and suboptimal debulking (>1 cm) (P<0.05). Univariate analysis revealed that patients with tumour human kallikrein 6 positive specific activity were more likely to suffer progressive disease and to die (hazard ratio 1.71 (P=0.015) and 1.88 (P=0.022), respectively). Survival curves demonstrated the same (P=0.013 and 0.019, respectively). Multivariate analysis revealed that human kallikrein 6 positivity was retained as an independent prognostic variable in several subgroups of patients, namely those with (low) grade I and II tumours (hazard ratio progression free survival 4.3 (P=0.027) and overall survival 4.1 (P=0.023)) and those with optimal debulking (hazard ratio progression free survival 3.8 (P=0.019) and overall survival 5.6 (P=0.011)). We conclude that tumour kallikrein 6 protein levels have utility as an independent adverse prognostic marker in a subgroup of ovarian cancer patients with otherwise apparently good prognosis.
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