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Search Results: 1 - 10 of 14111 matches for " Jan Lubinski "
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Prospective clinical trials on correlations between macro-/ microelements and vitamins and cancer risk
Lubinski Jan
Hereditary Cancer in Clinical Practice , 2012, DOI: 10.1186/1897-4287-10-s3-a15
Analysis of Germline Variants in CDH1, IGFBP3, MMP1, MMP3, STK15 and VEGF in Familial and Sporadic Renal Cell Carcinoma
Christopher Ricketts, Maurice P. Zeegers, Jan Lubinski, Eamonn R. Maher
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006037
Abstract: Background The investigation of rare familial forms of kidney cancer has provided important insights into the biology of sporadic renal cell carcinoma (RCC). In particular, the identification of the von Hippel Lindau (VHL) familial cancer syndrome gene (VHL) provided the basis for the discovery that VHL is somatically inactivated in most sporadic clear cell RCC. Many cases of familial RCC do not have mutations in known RCC susceptibility genes and there is evidence that genetic modifiers may influence the risk of RCC in VHL disease patients. Hence we hypothesised that low-penetrance functional genetic variants in pathways related to the VHL protein (pVHL) function might (a) modify the phenotypic expression of VHL disease and/or (b) predispose to sporadic RCC. Methodology/Principal Findings We tested this hypothesis for functional polymorphisms in CDH1 (rs16260), IGFBP3 (rs2854744), MMP1 (rs1799750), MMP3 (rs679620), STK15 (rs2273535) and VEGF (rs1570360). We observed that variants of MMP1 and MMP3 were significant modifiers of RCC risk (and risks of retinal angioma and cerebellar haemangioblastoma) in VHL disease patients. In addition, higher frequencies of the MMP1 rs1799750 2G allele (p = 0.017, OR 1.49, 95%CI 1.06–2.08) and the MMP1/MMP3 rs1799750/rs679620 2G/G haplotype (OR 1.45, 95%CI 1.01–2.10) were detected in sporadic RCC patients than in controls (n = 295). Conclusions/Significance These findings (a) represent the first example of genetic modifiers of RCC risk in VHL disease, (b) replicate a previous report of an association between MMP1/MMP3 variants and sporadic RCC and (c) further implicate MMP1/MMP3-related pathways in the pathogenesis of familial and sporadic RCC.
Cisplatin in breast cancer treatment in BRCA1 carriers
Gronwald Jacek,Byrski Tomasz,Lubinski Jan,Narod Steven A
Hereditary Cancer in Clinical Practice , 2012, DOI: 10.1186/1897-4287-10-s4-a17
Nonalcoholic fatty liver disease and HFE gene mutations: A Polish study
Joanna Raszeja-Wyszomirska, Grzegorz Kurzawski, Malgorzata Lawniczak, Joanna Miezynska-Kurtycz, Jan Lubinski
World Journal of Gastroenterology , 2010,
Abstract: AIM: To describe a Polish population with nonalcoholic fatty liver disease (NAFLD) with regard to HFE gene mutations, as well as analyzing demographic and clinical data.METHODS: Sixty-two consecutive patients with biopsy-proven NAFLD were included in the study. Demographic, clinical, and laboratory data were summarized in a database. C282Y and H63D mutations of the HFE gene were analyzed using polymerase chain reaction-restriction fragment lenght polymorphism.RESULTS: The analyzed cohort consisted of 62 homogeneic Caucasian participants, 66.1% men and 33.9% women, with a median age of 48 years. The median body mass index was 29.05 kg/m2. Hypercholesterolemia was observed in 74.2% of patients and hypertriglyceridemia in 32.2%; 16.1% had type 2 diabetes mellitus (DMt2). On liver biopsy, 22.6% of NAFLD patients were found to have severe fibrosis. There were no differences between frequencies of HFE gene mutations in subgroups of NAFLD patients with less and more severe liver fibrosis. Obesity, older age, female gender and DMt2 were associated with more advanced fibrosis in this Polish cohort, as well as higher glucose level, serum iron and transaminase aspartate aminotransferase/alanine aminotransferase ratio.CONCLUSION: HFE mutations conferred no additional hepatic fibrosis risk in NAFLD, but higher serum iron was a risk factor for severe liver damage in NAFLD, regardless of HFE mutations.
Necessary Tension in Marine Risers (Continued) Tension des colonnes montantes en mer (suite)
Lubinski A.
Oil & Gas Science and Technology , 2006, DOI: 10.2516/ogst:1977043
Abstract: A simple, first approximation method for calculating the necessary tension in a marine riser, is presented. This article is a practical supplement ta the one published under the same title in the March-April 1977 issue of Revue de l'Institut Fran ais du Pétrole. On présente dans cet article une méthode simple permettant de calculer en première approximation la tension d'une colonne montante en mer. Cet article est le complément pratique de celui publié sous le même titre dans le numéro mars-avril 1977 de la Revue de l'Institut Fran ais du Pétrole.
Fatigue of Range 3 Drill Pipe Fatigue des tiges de forage de gamme 3
Lubinski A.
Oil & Gas Science and Technology , 2006, DOI: 10.2516/ogst:1977012
Abstract: Past work on permissible hole curvature ta avoid drill pipe fatigue was bosed upon the assumption that drill pipe does not contact the wall of the hale between tool joints. In the present paper this assumption is removed, and the pipe may either be in contact or in no contact with the hale, whichever is actually the case. Both mothemotics and results in form of grophs are presented and, discussed. The findings of this palper apply mainly to Range 3 drill pipe, but in the case of 3 I/2 in (88.9 mm) drill pipe, application is useful even for Range 2. Usage and field results with Range 3 drill pipe are reported. Les travaux déjà effectués sur la courbure admissible dans les trous de forage ( dag legs ) pour éviter la fatigue des tiges de forage sont basés sur l'hypothèse que celles-ci ne rentrent pas en contact avec la paroi entre deux raccords de tige. Dans cet article on écarte une telle hypothèse : la tige peut être ou non en contact avec la paroi. Les équations mathématiques et les résultats sous forme graphique sont présentés et discutés. Ils s'appliquent principalement aux tiges de gamme 3 mais sont aussi utiles à celles de gamme 2 et de diamètre égal à 3 I/2 pouces (88,9 mm). On indique l'utilisation et les résultats sur chantier pour les tiges de gamme 3.
Necessary Tension in Marine Risers Tension des colonnes montantes en mer
Lubinski A.
Oil & Gas Science and Technology , 2006, DOI: 10.2516/ogst:1977013
Abstract: The tension governing transverse static and dynamic deflections in a riser is not the actual tension but the so-called effective tension The concept of effective tension and effective compression is thoroughly explained, and means for calculating effective forces are given. Numerical examples are worked out for risers whose length is between 152 m (520 ft) and 920 m (3020 ft). The reciprocal of maximum bending moment of the vicinity of the hall joint is plotted versus the effective tension of the ball joint. Bending moments used were obtained through use of static and dynamic computer programs applied ta a variety of conditions of wave loading, use or non-use of buoyant moterial sleeves, etc. The most important parameters affecting riser performance are the effective La tension régissant les déflections transversales statiques et dynamiques d'une colonne montante n'est pas la tension réelle mais ce qu'on appelle la tension effective . Le concept de tension ou de compression effective est expliqué en détail et la fa on de calculer les forces effectives est indiquée dans cet article. Des exemples numériques sont développés pour des colonnes montantes de longueur comprise entre 152 m (520 ft) et 920 m (3 020 ft). On a tracé la courbe de l'inverse du moment fléchissant en fonction de la tension effective à l'articulation. Les moments fléchissants utilisés ont été calculés par ordinateur en utilisant des programmes dynamiques et statiques pour des conditions variées d'action des vagues, la colonne montante étant ou non munie de manchettes de flottabilité, etc. Les deux paramètres les plus importants qui affectent le bon comportement d'une colonne montante sont la tension effective et la charge latérale.
The Association of the COMT V158M Polymorphism with Endometrial/Ovarian Cancer in HNPCC Families Adhering to the Amsterdam Criteria
Katie A Ashton, Cliff J Meldrum, Mary L McPhillips, Janina Suchy, Grzegorz Kurzawski, Jan Lubinski, Rodney J Scott
Hereditary Cancer in Clinical Practice , 2006, DOI: 10.1186/1897-4287-4-2-94
Abstract: Using Real Time PCR, the COMT V158M polymorphism was examined and its association with disease expression, age of diagnosis of cancer, mutation status and mutation type was assessed in the HNPCC MMR mutation positive and negative groups. This study showed that the V158M polymorphism had no association with disease risk in the HNPCC MMR mutation positive population. However, the polymorphism was significantly associated with endometrial/ovarian cancer risk in HNPCC MMR mutation negative patients (p = 0.002). The heterozygous (Val/Met) genotype was associated with an increased risk of developing endometrial/ovarian cancer whereas the homozygous mutant (Met/Met) showed a decreased risk. The results suggest heterosis, where there is an apparent greater effect of the heterozygous state in this dichotomous trait. In conclusion, this study shows that the COMT V158M polymorphism alters the risk of developing endometrial/ovarian cancer in patients that adhere to the Amsterdam HNPCC criteria but do not have a DNA mismatch repair gene mutation.Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant inherited disorder associated with a familial predisposition to colorectal cancer (CRC) and endometrial cancer (EC). It is characterised by early age of disease (CRC) onset, neoplastic lesions, microsatellite instability (MSI) and an increased incidence of extracolonic cancers [1]. Familial colorectal cancer syndromes, HNPCC and familial adenomatous polyposis (FAP), account for around 3% of all colorectal cancer cases; however, approximately 20% show familial inheritance of which there is no known genetic cause [2]. Mutations of the genes involved in the mismatch repair pathway, hMLH1 and hMSH2, account for a large proportion of patients that fit the HNPCC clinical criteria [1,3]. Approximately 80% of men and 40% of women that have germline mutations in MMR genes develop CRC [1,4] and 25-50% and 8-12% of women develop endometrial cancer and ovarian cancer, respec
The strength and width of Fe Kalpha lines in Seyferts and their correlations with the X-ray slope
Piotr Lubinski,Andrzej Zdziarski
Physics , 2000, DOI: 10.1046/j.1365-8711.2001.04481.x
Abstract: We study properties of Fe K lines of a large sample of Seyfert 1s observed by ASCA. Fits with power laws and Gaussian lines yield the average linewidth and equivalent width of 0.22+-0.03 keV and 0.13+-0.01 keV, respectively. Thus, the typical lines are weak and narrow. We then obtain the average line profile of all our spectra, and find it to consist of a narrow core and blue and red wings, with the red wing being much weaker than that of, e.g., MCG-6-30-15. We obtain three average spectra of Seyferts grouped according to the hardness, and find the equivalent width of the core (originating in a remote medium) to be about 50 eV in all three cases. The wings are well fitted by a broad line from a disc with strong relativistic effects. Its equivalent width correlates with the slope, increasing from ~70 eV for the hardest spectrum to ~120 eV for the softest one. The inner disc radius decreases correspondingly from ~40 to ~10 gravitational radii, and the fitted disc inclination is ~45 degrees. The obtained correlation between the slope and the strength of the broad Fe K line is found to be consistent with the previously found correlation of the slope and Compton reflection.
Results of a phase II open-label, non-randomized trial of cisplatin chemotherapy in patients with BRCA1-positive metastatic breast cancer
Tomasz Byrski, Rebecca Dent, Pawel Blecharz, Malgorzata Foszczynska-Kloda, Jacek Gronwald, Tomasz Huzarski, Cezary Cybulski, Elzbieta Marczyk, Robert Chrzan, Andrea Eisen, Jan Lubinski, Steven A Narod
Breast Cancer Research , 2012, DOI: 10.1186/bcr3231
Abstract: In a phase II, open-label study, 20 patients with metastatic breast cancer who carried a mutation in BRCA1 were treated with cisplatin 75 mg/m2 intravenously every 3 weeks as part of a 21-day cycle for 6 cycles. Restaging studies to assess response were performed after cycles 2 and 6, and every three months thereafter.Between July 2007 and January 2009, 20 patients were enrolled. Baseline characteristics were as follows: 65% had prior adjuvant chemotherapy, 55% had prior chemotherapy for metastatic breast cancer; mean age was 48 years (ranges 32 to 70); 30% estrogen receptor (ER) or progesterone receptor (PR)+, 70% ER/PR/Human Epidermal Growth Factor Receptor 2 (HER2)- and 0% HER2+. Overall response rate was 80%; nine patients experienced a complete clinical response (45%) and seven experienced a partial response (35%). Overall survival was 80% at one year, 60% at two years and 25% at three years. Four of the 20 patients are alive four years after initiating treatment. The median time to progression was 12 months. The median survival from the start of cisplatinum treatment was 30 months. Cisplatin-related adverse events, including nausea (50%), anemia (5%) and neutropenia (35%) were mostly mild to moderate in severity.This phase II study demonstrates that cisplatin chemotherapy has high activity in women with a BRCA1 mutation and metastatic breast cancer and is generally well tolerated.This trial is registered retrospectively on the clinical trials website ClinicalTrials.gov. The identifier is NCT01611727.Among women with a BRCA1 mutation and breast cancer, choice of chemotherapy is a critical issue. There are emerging data which suggest that mutation carriers may respond differently than non-carriers to particular agents [1-3]. BRCA1-associated cancers differ from non-hereditary cancers for a range of pathologic and molecular factors, including tumor grade and histologic appearance [4-7]. Several studies have shown that the response to treatment for women with a BR
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