42 results on '"Spaczynski, M."'
Search Results
2. Persistence of immune responses to the HPV-16/18 AS04-adjuvanted vaccine in women aged 15–55 years and first-time modelling of antibody responses in mature women: results from an open-label 6–year follow-up study
- Author
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Schwarz, T, Spaczynski, M, Kaufmann, A, Wysocki, J, Gałaj, A, Schulze, K, Suryakiran, P, Thomas, F, and Descamps, D
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- 2015
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3. TLR4 signaling induced by lipopolysaccharide or paclitaxel regulates tumor survival and chemoresistance in ovarian cancer
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Szajnik, M, Szczepanski, M J, Czystowska, M, Elishaev, E, Mandapathil, M, Nowak-Markwitz, E, Spaczynski, M, and Whiteside, T L
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- 2009
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4. Expression of CYP 1A1, CYP1B1 and CYP3A4 genes in normal endometrium and endometrial cancer cells
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Ociepa-Zawal, M., Rubis, B., Malkowska-Walczak, B., Przybylski, M., Spaczynski, M., and Trzeciak, W. H.
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- 2004
5. The association between common vitamin D receptor gene variations and osteoporosis
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Uitterlinden, A. G., Ralston, S. H., Brandi, M. L., Carey, A. H., Grinberg, D., Langdahl, B. L., Lips, P., Lorenc, R., Obermayer-Pietsxch, B., Reeve, J., Reid, D. M., Amedei, A., Bassiti, A., Bustamante, M., Husted, L. B., Diez-Perez, A., Dobnig, H., Dunning, A. M., Enjuanes, A., Fahrleitner-Pammer, A., Fang, Y., Karczmarewicz, E., Kruk, M., Johannes van Leeuwen, Mavilia, C., Meurs, J. B. J., Mangion, J., Mcguigan, F. E. A., Pols, H. A. P., Renner, W., Rivadeneira, F., Schoor, N. M., Scollen, S., Sherlock, R. E., Ioannidis, J. P. A., Parsons, C., Bear, S., Farmer, R., Lukaszkiewicz, J., Bilinski, P., Czerwinski, E., Lewinski, A., Marcinowska-Suchowierska, E., Milewicz, A., Spaczynski, M., Jaworski, M., Nuti, R., Grazio, S., Miazgowski, T., Boonen, R., Masaryk, P., Stepan, J. J., Lopes Vaz, A., Cannata, J., Weber, K., Benevolenskaya, L. I., Todd, C., Khaw, K. -T, Da Silva, J., Bhalla, A., Poor, G., Bruges Armas, J., Lyritis, G., O Neill, T. W., Lunt, M., Compston, J., Cooper, C., Duncan, E., Keen, R., Mclellan, A., Wass, J., Dekema, E., Essen, H., Pluijm, S., Bravenboer, N., Hofman, A., Duijn, C. M., Jong, P. J., Breteler, M. M., Stricker, B. H., Witteman, J. C., Internal medicine, VU University medical center, and Internal Medicine
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Male ,Bone density ,Osteoporosis ,Osteoporosis/*genetics ,Fractures, Bone/genetics ,Calcitriol receptor ,Fractures, Bone ,chemistry.chemical_compound ,Bone Density ,Receptors, Calcitriol/*genetics ,CDX2 Transcription Factor ,Prospective Studies ,Deoxyribonucleases, Type II Site-Specific ,Promoter Regions, Genetic ,education.field_of_study ,biology ,General Medicine ,Middle Aged ,FokI ,Vitamin D3 Receptor ,Female ,musculoskeletal diseases ,Adult ,Bone Density/*genetics ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,TaqI ,Genotype ,Population ,Polymorphism, Genetic ,Homeodomain Proteins/*genetics ,Internal medicine ,Internal Medicine ,medicine ,Vitamin D and neurology ,Humans ,education ,Aged ,Homeodomain Proteins ,business.industry ,medicine.disease ,Endocrinology ,chemistry ,Haplotypes ,biology.protein ,Receptors, Calcitriol ,business - Abstract
Background: Polymorphisms of the vitamin D receptor (VDR) gene have been implicated in the genetic regulation of bone mineral density (BMD). However, the clinical impact of these variants remains unclear. Objective: To evaluate the relation between VDR polymorphisms, BMD, and fractures. Design: Prospective multicenter large-scale association study. Setting: The Genetic Markers for Osteoporosis consortium, involving 9 European research teams. Participants: 26 242 participants (18 405 women). Measurements: Cdx2 promoter, FokI, BsmI, ApaI, and TaqI polymorphisms; BMD at the femoral neck and the lumbar spine by dual x-ray absorptiometry; and fractures. Results: Comparisons of BMD at the lumbar spine and femoral neck showed nonsignificant differences less than 0.011 g/cm2 for any genotype with or without adjustments. A total of 6067 participants reported a history of fracture, and 2088 had vertebral fractures. For all VDR alleles, odds ratios for fractures were very close to 1.00 (range, 0.98 to 1.02) and collectively the 95% CIs ranged from 0.94 (lowest) to 1.07 (highest). For vertebral fractures, we observed a 9% (95% CI, 0% to 18%; P = 0.039) risk reduction for the Cdx2 A-allele (13% risk reduction in a dominant model). Limitations: The authors analyzed only selected VDR polymorphisms. Heterogeneity was detected in some analyses and may reflect some differences in collection of fracture data across cohorts. Not all fractures were related to osteoporosis. Conclusions: The FokI, BsmI, ApaI, and TaqI VDR polymorphisms are not associated with BMD or with fractures, but the Cdx2 polymorphism may be associated with risk for vertebral fractures.
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- 2006
6. Decreased expression of p16 in ovarian cancers represents an unfavourable prognostic factor
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Pawel Surowiak, Materna, V., Maciejczyk, A., Pudelko, M., Suchocki, S., Kedzia, W., Nowak-Markwitz, E., Dumanska, M., Spaczynski, M., Zabel, M., Dietel, M., and Lage, H.
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616 - Patología. Medicina clínica. Oncología ,Ovarian cancer ,Immunohistochemistry - Abstract
Decreased expression of p16 may result from hypermethylation of the promoter or from deletion of the gene. It can lead to intensified proliferation of neoplastic cells and to cytostatic drug resistance. The study was aimed at the examination of prognostic value of p16 expression in relation to Ki67 and caspase-3 in ovarian cancers using immunohistochemistry. The immunohistochemical studies were performed on 73 paraffinembedded samples of ovarian cancers from 43 patients and samples from 6 healthy ovaries. We have used monoclonal antibodies against p16. ABC method and DAB were used for antigens visualisation. The intensity of the immunohistochemical reactions was appraised using the semi-quantitative IRS scale. In healthy ovaries we have shown strong reaction in the nuclei of surface epithelium. In the case of studied ovarian cancers, the reaction of a nuclear and cytoplasmic localization was obtained. The mean overall immunoreactivity score of nuclear p16 expression amounted to 5.30±3.44 SD in primary laparotomy material and 6.61±4.34 SD in secondary cytoreduction material. Statistical analysis demonstrated that lower p16 expression was typical of the younger patients and the patients who died. Kaplan- Meier’s analysis proved that lower expression of p16 was characteristic of cases with shorter overall survival. In the present study we have demonstrated that lowered p16 expression represented an unfavourable prognostic index in ovarian cancer. Lowered p16 expression was also typical for chemotherapy-resistant ceases (cases of lower caspase-3 and higher Ki67 at secondary cytoreduction expression).
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- 2008
7. Persistence of immune responses to the HPV ‐16/18 AS 04‐adjuvanted vaccine in women aged 15–55 years and first‐time modelling of antibody responses in mature women: results from an open‐label 6–year follow‐up study
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Schwarz, T, primary, Spaczynski, M, additional, Kaufmann, A, additional, Wysocki, J, additional, Gałaj, A, additional, Schulze, K, additional, Suryakiran, P, additional, Thomas, F, additional, and Descamps, D, additional
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- 2014
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8. Expression and signaling of Toll-like receptor 4 (TLR4) and MyD88 in ovarian carcinoma cells
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Szajnik, M. E., primary, Szczepanski, M. J., additional, Czystowska, M., additional, Elishaev, E., additional, Mandapathil, M., additional, Nowak-Markwitz, E., additional, Spaczynski, M., additional, and Whiteside, T. L., additional
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- 2009
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9. OP05.03: Doppler ultrasound in management of gestational trophoblastic disease
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Pietryga, M., primary, Nowak-Markwitz, E., additional, Spaczynski, M., additional, and Brazert, J., additional
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- 2007
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10. Unfavorable prognostic value of CD24 expression in sections from primary and relapsed ovarian cancer tissue
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SUROWIAK, P., primary, MATERNA, V., additional, KAPLENKO, I., additional, SPACZYNSKI, M., additional, DIETEL, M., additional, KRISTIANSEN, G., additional, LAGE, H., additional, and ZABEL, M., additional
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- 2006
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11. Response and early progression according to CA 125 to assess activity of topotecan vs paclitaxel in relapsed ovarian carcinoma
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Rustin, G.J.S, primary, Nelstrop, A.E., additional, Bolis, G., additional, Gore, M., additional, tenBokkel-Huinink, W., additional, and Spaczynski, M., additional
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- 1997
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12. P1108 Photodynamic diagnosis in detection of cervical intraepithelial lesions
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Szafinska-Dolata, A., Kedzia, W., and Spaczyński, M.
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- 2009
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13. P1083 The assessment of a real-time optoelectronic method for the detection of cervical intraepithelial neoplasia (‘CIN’)
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Pruski, D., Kędzia, W., Przybylski, M., Kędzia, H., Józefiak, A., and Spaczyński, M.
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- 2009
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14. P594 LLETZ/LEEP procedure assisted by the computerized planimetry of uterine cervix in treatment of cervical intraepithelial neoplasia (CIN)
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Rokita, W., Stanislawska, M., Nowak-Markwitz, E., Kedzia, W., Spaczyński, M., Karowicz-Bilinska, A., and Bednarek, W.
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- 2009
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15. O806 Diagnostic hysteroscopy in women with endometrial hyperplasia and endometrial cancer – 9 years of experience, analysis of 142 cases
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Rokita, W., Stanislawska, M., Nowak-Markwitz, E., Kedzia, W., Spaczyński, M., Karowicz-Bilinska, A., and Bednarek, W.
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- 2009
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16. Organization of population-based cancer control programs: Europe and the World
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Otter, R., Qiao, Y. -L, Burton, R., Samiei, M., Parkin, M., Trapido, E., Weller, D., Magrath, I., Sutcliffe, S., Durstine, A. D., Parsons Perez, C., Kitchen Clarke, L., Hill, J., Attiga, F. A., Diab, R., Khatib, S., Nusairat, T., Obeidat, N. A., Aghi, M. B., Pedersen, A. E., Thomas Hack, Maksimowicz, K. M., Poole, B., Bentley, C., Browman, G., Knudsen, J. L., Passman, L. J., Maltoni, L. A., Spaczynski, M., Nowak-Markwitz, E., Karowicz-Bilinska, A., Schopper, D., Fucina, N., Rangel, D. C., Da Prat, C., Kassam, M., Limache-García, A., Amaro-Llanos, K., Preszly, M., Thomsen, C., Segalla, J. G. M., Capra, R. M. M., Veneziano, C. L. A., Veneziano, D. B., Coradazzi, A. L., Machado, P. E. A., Rogers, P. C., Ramphal, R., Penney, A., Depauw, S., Barr, R., Sarwal, K., Torrance, H., Sutcliffe, C. G., Baili, P., Amati, C., Di Salvo, F., Frazzingaro, C., Sanz, N., and Micheli, A.
17. An ultrasonographic morphological index for prediction of ovarian tumor malignancy
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Szpurek, D., Rafal Moszynski, Ziȩtkowiak, W., Spaczynski, M., and Sajdak, S.
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Adult ,Aged, 80 and over ,Ovarian Neoplasms ,Adolescent ,Biopsy ,Middle Aged ,Sensitivity and Specificity ,ROC Curve ,Predictive Value of Tests ,Humans ,Female ,Poland ,Child ,Aged ,Ultrasonography - Abstract
A newly created ultrasonographic scale called the Poznan index as well as scales already well known (introduced by Sassone, De Priest and Lerner) were compared in our group of patients.A morphological index was based on seven sonographic ovarian tumor features. Examinations on 686 patients were evaluated. Comparison of prognostic values of the Poznan index with other applied morphological indices in our group of patients was based on the area under receiver operating characteristic (ROC) curves.The cut-off level of the new index is 8 points. The new morphological index has a specificity of 77.0%, and negative and positive predictive values of 90.7% and 69.1%, respectively. It has a sensitivity of 86.7% and accuracy of 80.6%. The Poznan index proved its usefulness and superiority (AU ROC = 0.89).Using this morphological index it is possible to make a precise prognosis of ovarian tumor malignancy. It also makes it possible to make the right decision concerning the manner of surgical treatment.
18. Correlation of Pyruvate Kinase M2 Expression with Clinicopathological Data in Ovarian Cancer.
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Kobierzycki C, Piotrowska A, Latkowski K, Zabel M, Nowak-Markwitz E, Spaczynski M, Kedzia W, Pula B, Podhorska-Okolow M, and Dziegiel P
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- Cytoplasm metabolism, Female, Fibroblasts metabolism, Humans, Middle Aged, Thyroid Hormone-Binding Proteins, Carrier Proteins metabolism, Membrane Proteins metabolism, Ovarian Neoplasms metabolism, Thyroid Hormones metabolism
- Abstract
Background/aim: It has been shown in many studies that expression of pyruvate kinase (PK) enzyme plays a key role during cellular metabolism. There is evidence that cancer cells manifesting very dynamic proliferation may control their division in various mechanisms, i.a. by expression of PKM2 isoform. The exact role of PKM2 in ovarian cancer (OC) cells and cancer associated fibroblasts (CAFs) have not been elucidated., Materials and Methods: The present study was focused on analysis of PKM2 expression in cancer cells and CAFs in 97 OC cases, mostly of serous histological type. Moreover, relationships between expression of PKM2 and proliferation (Ki-67; MCM-2, -3, -7; cyclin D1), vascular (CD31, D2-40) and mesenchymal (Vim and αSMA) markers as well as receptors (ER, PR, HER2, EGFR) were examined. All observations were evaluated in regard to available clinicopathological data., Results: The expression of PKM2 was disclosed only in cytoplasm of OC cells. No statistically significant correlation between PKM2 and tested markers was found. In regard to available clinicopathological data only an increasing trend of PKM2 expression with increasing grade of histological malignancy G was found (p=0.07)., Conclusion: Due to achieved results concerning expression of PKM2 there is a lack of evidence for its diagnostic and prognostic usage in OC., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
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- 2018
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19. Ten-year immune persistence and safety of the HPV-16/18 AS04-adjuvanted vaccine in females vaccinated at 15-55 years of age.
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Schwarz TF, Galaj A, Spaczynski M, Wysocki J, Kaufmann AM, Poncelet S, Suryakiran PV, Folschweiller N, Thomas F, Lin L, and Struyf F
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- Adolescent, Adult, Antibodies, Viral analysis, Bodily Secretions immunology, Cervix Uteri immunology, Female, Follow-Up Studies, Humans, Middle Aged, Papillomavirus Vaccines adverse effects, Vagina immunology, Young Adult, Antibodies, Viral blood, Human papillomavirus 16 immunology, Human papillomavirus 18 immunology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines immunology, Uterine Cervical Neoplasms prevention & control, Vaccination adverse effects
- Abstract
Women remain at risk of human papillomavirus (HPV) infection for most of their lives. The duration of protection against HPV-16/18 from prophylactic vaccination remains unknown. We investigated the 10-year immune response and long-term safety profile of the HPV-16/18 AS04-adjuvanted vaccine (AS04-HPV-16/18 vaccine) in females aged between 15 and 55 years at first vaccination. Females who received primary vaccination with three doses of AS04-HPV-16/18 vaccine in the primary phase-III study (NCT00196937) were invited to attend annual evaluations for long-term immunogenicity and safety. Anti-HPV-16/18 antibodies in serum and cervico-vaginal secretions (CVS) were measured using enzyme-linked immunosorbent assay (ELISA). Serious adverse events (SAEs) were recorded throughout the follow-up period. Seropositivity rates for anti-HPV-16 remained high (≥96.3%) in all age groups 10 years after first vaccination. It was found that 99.2% of 15-25-year olds remained seropositive for anti-HPV-18 compared to 93.7% and 83.8% of 26-45-year olds and 45-55-year olds, respectively. Geometric mean titers (GMT) remained above natural infection levels in all age groups. Anti-HPV-16 and anti-HPV-18 titers were at least 5.3-fold and 3.1-fold higher than titers observed after natural infection, respectively, and were predicted to persist above natural infection levels for ≥30 years in all age groups. At Year 10, anti-HPV-16/18 antibody titers in subjects aged 15-25 years remained above plateau levels observed in previous studies. Correlation coefficients for antibody titers in serum and CVS were 0.64 (anti-HPV-16) and 0.38 (anti-HPV-18). This study concluded that vaccinated females aged 15-55 years elicited sustained immunogenicity with an acceptable safety profile up to 10 years after primary vaccination, suggesting long-term protection against HPV., (© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2017
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20. Paraneoplastic neurological syndromes associated with ovarian tumors.
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Zaborowski MP, Spaczynski M, Nowak-Markwitz E, and Michalak S
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- Female, Humans, Incidence, Ovarian Neoplasms therapy, Paraneoplastic Syndromes therapy, Poland epidemiology, Prognosis, Ovarian Neoplasms diagnosis, Ovarian Neoplasms epidemiology, Paraneoplastic Syndromes diagnosis, Paraneoplastic Syndromes epidemiology
- Abstract
Introduction: Paraneoplastic neurological syndromes (PNS) are neurologic deficits triggered by an underlying remote tumor. PNS can antedate clinical manifestation of ovarian malignancy and enable its diagnosis at an early stage. Interestingly, neoplasms associated with PNS are less advanced and metastasize less commonly than those without PNS. This suggests that PNS may be associated with a naturally occurring antitumor response., Methods: We review the literature on the diagnosis, pathogenesis and management of PNS associated with ovarian tumors: paraneoplastic cerebellar degeneration (PCD) and anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. An approach to the diagnostic workup of underlying tumors is discussed., Results: PCD can precede the manifestation of ovarian carcinoma. Anti-NMDAR encephalitis in young women appears often as a result of ovarian teratoma. Since ovarian tumors and nervous tissue share common antigens (e.g., cdr2, NMDAR), autoimmune etiology is a probable mechanism of these neurologic disorders. The concept of cross-presentation, however, seems insufficient to explain entirely the emergence of PNS. Early resection of ovarian tumors is a significant part of PNS management and improves the outcome., Conclusions: The diagnosis of PNS potentially associated with ovarian tumor indicates a need for a thorough diagnostic procedure in search of the neoplasm. In some patients, explorative laparoscopy/laparotomy can be considered.
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- 2015
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21. Persistence of immune responses to the HPV-16/18 AS04-adjuvanted vaccine in women aged 15-55 years and first-time modelling of antibody responses in mature women: results from an open-label 6-year follow-up study.
- Author
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Schwarz T, Spaczynski M, Kaufmann A, Wysocki J, Gałaj A, Schulze K, Suryakiran P, Thomas F, and Descamps D
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- Adolescent, Adult, Age Factors, Antibodies, Viral blood, Enzyme-Linked Immunosorbent Assay, Female, Follow-Up Studies, Humans, Middle Aged, Papillomavirus Vaccines therapeutic use, Young Adult, Antibodies, Viral immunology, Human papillomavirus 16 immunology, Human papillomavirus 18 immunology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines immunology, Uterine Cervical Neoplasms prevention & control
- Abstract
Objective: Evaluation of the long-term HPV-16/18 AS04-adjuvanted vaccine immunogenicity persistence in women., Design: Multicentre, open-label, long-term follow-up (NCT00947115) of a primary phase-III study (NCT00196937)., Setting: Six centres in Germany and Poland., Population: 488 healthy women (aged 15-55 years, age-stratified into groups: 15-25, 26-45, and 46-55 years) who received three vaccine doses in the primary study., Methods: Immune responses were evaluated in serum and cervicovaginal secretion (CVS) samples 6 years after dose 1. Anti-HPV-16/18 geometric mean titres (GMTs) were measured by enzyme-linked immunosorbent assay (ELISA), and were used to fit the modified power-law and piecewise models, predicting long-term immunogenicity. Serious adverse events (SAEs) were recorded., Main Outcome Measures: Anti-HPV-16/18 seropositivity rates and GMTs 6 years after dose 1., Results: At 6 years after dose 1, all women were seropositive for anti-HPV-16 and ≥97% were seropositive for anti-HPV-18 antibodies. GMTs ranged from 277.7 to 1344.6 EU/ml, and from 97.6 to 438.2 EU/ml, for anti-HPV-16 and anti-HPV-18, respectively. In all age groups, GMTs were higher (anti-HPV-16, 9.3-45.1-fold; anti-HPV-18, 4.3-19.4-fold) than levels associated with natural infection (29.8 EU/ml). A strong correlation between serum and CVS anti-HPV-16/18 levels was observed, with correlation coefficients of 0.81-0.96 (anti-HPV-16) and 0.69-0.84 (anti-HPV-18). Exploratory modelling based on the 6-year data predicted vaccine-induced anti-HPV-16/18 levels above natural infection levels for at least 20 years, except for anti-HPV-18 in the older age group (piecewise model). One vaccine-related and two fatal SAEs were reported., Conclusions: At 6 years after vaccination, immune responses induced by the HPV-16/18 AS04-adjuvanted vaccine were sustained in all age groups., (© 2014 Royal College of Obstetricians and Gynaecologists.)
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- 2015
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22. Expression of the MT1 melatonin receptor in ovarian cancer cells.
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Jablonska K, Pula B, Zemla A, Kobierzycki C, Kedzia W, Nowak-Markwitz E, Spaczynski M, Zabel M, Podhorska-Okolow M, and Dziegiel P
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- Adult, Biomarkers, Tumor genetics, Cell Line, Tumor, Female, Humans, Middle Aged, Ovarian Neoplasms diagnosis, Ovarian Neoplasms pathology, Receptor, Melatonin, MT1 genetics, Biomarkers, Tumor metabolism, Ovarian Neoplasms metabolism, Receptor, Melatonin, MT1 metabolism
- Abstract
Ovarian cancer (OC) is the leading cause of death among women with genital tract disorders. Melatonin exhibits oncostatic properties which it may effect through binding to its membrane receptor, MT1. The aim of this study was to determine the expression of MT1 in OC cells and to correlate this with clinical and pathological data. Immunohistochemistry was performed on 84 cases of OC. Normal ovarian epithelial (IOSE 364) and OC (SK-OV-3, OVCAR-3) cell lines were used to examine the MT1 expression at protein level using the western blot and immunofluorescence technique. The expression of MT1 was observed as cytoplasmic-membrane (MT1(CM)) and membrane (MT1(M)) reactions. A positive correlation between MT1(CM) and MT1(M) was found in all the studied cases. There were no significant differences between the expression of MT1(CM), MT1(M), and histological type, staging, grading, presence of residual disease, or overall survival time. Immunofluorescence showed both MT1(M) and MT1(CM) expression in all the tested cell lines. Western blot illustrated the highest protein level of MT1 in IOSE 364 and the lowest in the OVCAR-3. The results indicate the limited prognostic significance of MT1 in OC cells.
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- 2014
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23. SOX18 expression predicts response to platinum-based chemotherapy in ovarian cancer.
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Pula B, Kobierzycki C, Solinski D, Olbromski M, Nowak-Markwitz E, Spaczynski M, Kedzia W, Zabel M, and Dziegiel P
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- Cell Line, Tumor, Female, Humans, Immunohistochemistry, Ovarian Neoplasms mortality, Ovarian Neoplasms pathology, Platinum therapeutic use, SOXF Transcription Factors analysis, SOXF Transcription Factors genetics, Ovarian Neoplasms drug therapy, SOXF Transcription Factors physiology
- Abstract
Background: SOX18 is a transcription factor known to be involved in blood and lymphatic vessel, hair follicle development, and wound healing processes. In addition, it has been reported that SOX18 may influence cancer growth. The role of SOX18 expression in ovarian cancer (OC) has not been determined., Materials and Methods: SOX18 expression was assessed in 85 OC cases using immunohistochemical methods and in ovarian cancer cell lines on the mRNA and protein level., Results: SOX18 was expressed in cancer cell nuclei as well as the cytoplasm. Higher nuclear SOX18 expression was associated with presence of residual disease following surgical treatment (p=0.0158) and advanced disease stage (p=0.0056). Univariate survival analysis revealed that high SOX18 (p=0.0125) expression, presence of residual disease (p<0.0001) and advanced disease stage (p<0.0324) predicted poor patient outcome., Conclusion: SOX18 may be a new predictive marker for OC., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)
- Published
- 2014
24. Comparison of minichromosome maintenance proteins (MCM-3, MCM-7) and metallothioneins (MT-I/II, MT-III) expression in relation to clinicopathological data in ovarian cancer.
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Kobierzycki C, Pula B, Skiba M, Jablonska K, Latkowski K, Zabel M, Nowak-Markwitz E, Spaczynski M, Kedzia W, Podhorska-Okolow M, and Dziegiel P
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- Adult, Aged, Biomarkers, Tumor metabolism, Female, Humans, Middle Aged, Ovarian Neoplasms pathology, Metallothionein metabolism, Minichromosome Maintenance Proteins metabolism, Ovarian Neoplasms metabolism
- Abstract
Background: Despite great progress in the understanding of ovarian cancer biology, clinicopathological data (i.e. grade, stage, histological type and residual disease after surgery) seem to be the most important prognostic factors., Materials and Methods: The present study aimed to investigate the relationship between expression of minichromosome maintenance proteins (MCM-3, MCM-7), metallothioneins (MT-I/II, MT-III), and Ki-67 in 103 ovarian cancer cases, mostly of the serous histological type., Results: Statistical analysis revealed strong positive correlations in the expression of MCM-3 vs. Ki-67 (r=0.492), MCM-7 vs. Ki-67 (r=0.651), and MCM-3 vs. MCM-7 (r=0.515) (all p<0.0001). The Kruskal-Wallis test showed an association of increased expression of MCM-3 and Ki-67 with increasing grade of histological malignancy (p=0.0011, p=0.029, respectively). Regarding clinical progression, cytoplasmic MT-I/II expression was significantly higher in more advanced disease stages (III+IV vs. I+II; p=0.0247)., Conclusion: Due to the correlations shown here, the determination of MCM proteins as proliferation markers of ovarian cancer, should be strongly considered.
- Published
- 2013
25. Exosomes in Plasma of Patients with Ovarian Carcinoma: Potential Biomarkers of Tumor Progression and Response to Therapy.
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Szajnik M, Derbis M, Lach M, Patalas P, Michalak M, Drzewiecka H, Szpurek D, Nowakowski A, Spaczynski M, Baranowski W, and Whiteside TL
- Abstract
Background: In patients with Ovarian Cancer (OvCa) exosomes released by tumor cells are present in the plasma and could be involved in tumor progression. This study examines the association between the exosome presence/protein content in plasma of OvCa patients and disease outcome, response to standard therapy and/or tumorresistance to therapies in patients studied at diagnosis and also serially during and after therapy., Design and Methods: Exosomes were purified from OvCa patients' plasma (n=22), patients with benign tumors (n=10) or (n=10) healthy controls (NC) using ultracentrifugation. Exosomes were visualized by scanning electron microscopy. Their protein content was measured. The presence of MAGE 3/6 and TGF-β1 in exosomes was evaluated in Western blots., Results: The OvCa patients' plasma contained higher levels of exosomal proteins (p<0.05) compared to those isolated from plasma of patients with benign tumors or NC. Exosomes isolated from OvCa patients's plasma carried TGF-β1 and MAGE3/6, which distinguished OvCa patients from those with benign tumors and NC. High protein levels of exosomes were seen in newly diagnosed patients; however in advanced stages of OvCa patients the protein content of isolated exosomes was significantly higher than that of early stages. The exosome levels variably changed during/after chemotherapy, and correlations between the changes in exosomal protein levels and clinical data suggested that the protein content of exosomes might be useful in predicting responses to therapy and prognosis in OvCa patients., Conclusion: Analysis of plasma exosomes levels offers a novel approach to diagnosis and monitoring response to therapies in OvCa patients.
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- 2013
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26. Effectiveness of the National Population-Based Cervical Cancer Screening Programme in Poland--outcomes, problems and possible solutions 7 years after implementation.
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Januszek-Michalecka L, Nowak-Markwitz E, Banach P, and Spaczynski M
- Subjects
- Female, Humans, Patient Compliance, Poland epidemiology, Women's Health, Mass Screening, National Health Programs, Uterine Cervical Neoplasms epidemiology, Uterine Cervical Neoplasms prevention & control
- Abstract
Cervical cancer is a substantial issue for public health in Poland. In 2006, in order to improve epidemiological data, the National Population-Based Cervical Cancer Screening Programme was developed and implemented. The Programme concerned 9.7 million women aged 25-59 to be screened during a 3-year interval. In 2010, a decline in cervical cancer incidence by 5.7% and 3.4% in mortality rate was observed. However, 5-year survival rates do not exceed 51%. Attendance rate reached 27%, then fell and presently remains on the level of 24%. Currently, the main concern for the screening organizers is searching for areas malfunctioning in local conditions, to improve them, and to provide further progress in cervical cancer prevention. The objective of the presented study was to critically review available data concerning the outcomes of the Screening Program and to suggest possible solutions. Two main factors were taken into account in the study: cost-effectiveness and attendance rate. To encourage attendance, women in Poland are sent personal invitations. This procedure consumes from a quarter up to a half of the budget of the Programme each year, but its effectiveness seems unsatisfactory. In addition to mailing, intensive training of doctors and midwives is conducted. Other activities to increase coverage include developing a social educational campaign. According to the Polish experience, the most effective way to increase coverage is training screening providers and involving them actively in encouraging screening participation. Thus, redistribution of funds from mailing to education and to a social campaign should be considered. Further development of cervical cancer prevention may depend on organizational changes including enhancing reporting, monitoring and quality control in opportunistic screening.
- Published
- 2013
27. Persistence of immune response to HPV-16/18 AS04-adjuvanted cervical cancer vaccine in women aged 15-55 years.
- Author
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Schwarz TF, Spaczynski M, Schneider A, Wysocki J, Galaj A, Schulze K, Poncelet SM, Catteau G, Thomas F, and Descamps D
- Subjects
- Adjuvants, Immunologic therapeutic use, Adolescent, Adult, Antibodies, Viral blood, Antibodies, Viral immunology, Female, Follow-Up Studies, Humans, Middle Aged, Papillomavirus Infections epidemiology, Papillomavirus Infections immunology, Time Factors, Young Adult, Human papillomavirus 16 immunology, Human papillomavirus 18 immunology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines immunology, Papillomavirus Vaccines therapeutic use
- Abstract
The HPV-16/18 AS04-adjuvanted vaccine (Cervarix®, GlaxoSmithKline Biologicals) has been shown to induce a robust immune response in women aged 15-55 years (103514/NCT00196937). This follow-up study is the first report of persistence of immune response and safety profile through 48 months after vaccination in women aged 15-55 years. In this open-label, age-stratified Phase III study in Germany and Poland (105882/NCT00196937), healthy women aged 15-55 years received 3 doses of HPV-16/18 AS04-adjuvanted vaccine at 0, 1, and 6 months. Anti-HPV-16/18 seropositivity rates and geometric mean antibody titers (GMTs) were assessed by enzyme-linked immunosorbent assay (ELISA) in women aged 15-25 (n=168), 26-45 (n=186) and 46-55 years (n=177) from the time of first vaccination through 48 months. At Month 48, all subjects were seropositive for anti-HPV-16 antibodies and 99.4% were seropositive for anti-HPV-18. Antibody kinetics were as previously reported, with peak response at Month 7 followed by a gradual decline tending towards a plateau in all age groups. Anti-HPV-16/18 GMTs were sustained at Month 48 in all age groups, including women aged 46-55 years in whom GMTs were respectively 11-fold and 5-fold higher than natural infection levels. The vaccine exhibited a clinically acceptable safety profile in all age groups. In summary, the HPV-16/18 AS04-adjuvanted vaccine induces high and sustained immune responses in women aged 15-55 years, with antibody levels remaining several-fold higher than natural infection levels for at least 4 years after the first vaccine dose.
- Published
- 2011
- Full Text
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28. Estrogen receptor alpha expression in ovarian cancer predicts longer overall survival.
- Author
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Halon A, Materna V, Drag-Zalesinska M, Nowak-Markwitz E, Gansukh T, Donizy P, Spaczynski M, Zabel M, Dietel M, Lage H, and Surowiak P
- Subjects
- Cystadenocarcinoma, Serous metabolism, Cystadenocarcinoma, Serous mortality, Cystadenocarcinoma, Serous therapy, Endometrial Neoplasms metabolism, Endometrial Neoplasms mortality, Endometrial Neoplasms therapy, Female, Follow-Up Studies, Humans, Immunoenzyme Techniques, Middle Aged, Ovarian Neoplasms therapy, Prognosis, Retrospective Studies, Tumor Cells, Cultured, Biomarkers, Tumor metabolism, Estrogen Receptor alpha metabolism, Ovarian Neoplasms metabolism, Ovarian Neoplasms mortality
- Abstract
Estrogen as a potential factor of ovarian carcinogenesis, acts via two nuclear receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), but the cellular signal pathways involved are not completely clear so far. In this study we have described the expression of ERα, detected by immunocytochemistry in 11 ovarian carcinoma cell lines and by immunohistochemistry in 43 Federation Internationale des Gyneacologistes et Obstetristes stage III ovarian carcinoma specimens prepared before and after treatment with cisplatin-based schemes. For cisplatin resistance is a major obstacle in the treatment of ovarian carcinoma, analysis of cisplatin sensitivity in 11 ovarian carcinoma cell line was also performed. The strong nuclear ERα expression was only shown in the single A2780P cell line. Expression of ERα in tissue specimens did not reveal any correlations between histopathological parameters (histologic type and grading). We demonstrated a significant association with ERα expression in specimens from primary laparotomies (PL) and cause-specific survival. In the cases terminated by death of the patient, overall immunoreactivity score of ERα expression at PL was significantly lower than in surviving patients. In addition, Kaplan-Meier analysis revealed significantly shorter overall survival time and progression-free time in cases with lower immunoreactivity score of ERα expression at PL. Our findings support the hypothesis that aberrant hormone activity, by way of altered receptor expression, might be an important factor in the malignant transformation of ovarian cancer.
- Published
- 2011
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29. Loss of estrogen receptor beta expression correlates with shorter overall survival and lack of clinical response to chemotherapy in ovarian cancer patients.
- Author
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Halon A, Nowak-Markwitz E, Maciejczyk A, Pudelko M, Gansukh T, Györffy B, Donizy P, Murawa D, Matkowski R, Spaczynski M, Lage H, and Surowiak P
- Subjects
- Cell Line, Tumor, Cisplatin pharmacology, Drug Resistance, Neoplasm, Drug Screening Assays, Antitumor, Estrogen Receptor beta biosynthesis, Female, Humans, Immunohistochemistry, Middle Aged, Neoplasm Staging, Ovarian Neoplasms pathology, Survival Rate, Estrogen Receptor beta deficiency, Ovarian Neoplasms drug therapy, Ovarian Neoplasms metabolism
- Abstract
Background: Estrogen receptor beta (ERβ) belongs to a large family of nuclear receptors. Recent studies have suggested that ERβ in contrast to ERα might act as a tumour suppressor in ovarian cancer (OVCA)., Materials and Methods: Expression of ERβ was detected by immunocytochemistry in 11 OVCA cell lines and by immunohistochemistry in 43 (41 FIGO stage III) OVCA specimens prepared before chemotherapy and 30 specimens from the same group after chemotherapy. Cisplatin sensitivity in the 11 cell lines was also analysed., Results: No significant correlations between cisplatin-sensitivity and expression of ERβ was found in the cell lines. In the cases which responded well to chemotherapy (complete response) ERβ expression at preliminary laparotomy (PL) was significantly higher (p = 0.0004) than in those with progressive disease. Kaplan-Meier analysis revealed that the patients with higher ERβ expression (>30% of cells) at PL had an increased overall survival time and progression-free time (p = 0.00161 and p = 0.03255, respectively) than the patients with lower ERβ expression. Significantly shorter overall survival time characterized the cases with lower immunoreactivity score of ERβ expression at secondary cytoreduction (SCR) (p = 0.00346)., Conclusion: The loss of ERβ expression in ovarian tumours may be a feature of malignant transformation.
- Published
- 2011
30. Correlation between levels of human papillomavirus (HPV)-16 and 18 antibodies in serum and cervicovaginal secretions in girls and women vaccinated with the HPV-16/18 AS04-adjuvanted vaccine.
- Author
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Schwarz TF, Kocken M, Petäjä T, Einstein MH, Spaczynski M, Louwers JA, Pedersen C, Levin M, Zahaf T, Poncelet S, Hardt K, Descamps D, and Dubin G
- Subjects
- Adjuvants, Immunologic administration & dosage, Adolescent, Adult, Aged, Bodily Secretions immunology, Child, Enzyme-Linked Immunosorbent Assay, Female, Human papillomavirus 16 immunology, Human papillomavirus 18 immunology, Humans, Immunoglobulin G analysis, Immunoglobulin G blood, Middle Aged, Papillomavirus Vaccines administration & dosage, Young Adult, Antibodies, Viral analysis, Antibodies, Viral blood, Cervix Uteri immunology, Papillomavirus Vaccines immunology, Serum immunology, Vagina immunology
- Abstract
This pooled analysis of data from four Phase III clinical trials was undertaken to assess the correlation between levels of anti-human papillomavirus (HPV)-16/18 antibodies in serum and cervicovaginal secretions (CVS) in girls and women vaccinated with the HPV-16/18 AS04-adjuvanted vaccine. Serum and CVS samples were collected from a subset of women aged 10-65 years (N=350) at pre-specified time-points from 7 to 36 months post-vaccination. Anti-HPV-16/18 antibody levels in serum and CVS were measured by enzyme-linked immunosorbent assay. Pearson correlation coefficients between serum and CVS antibody levels, standardized for total immunoglobulin G, were calculated at each time-point in women with detectable antibodies in both serum and CVS. All subjects had seroconverted at Month 7 and remained seropositive through Month 36 for both antigens. Geometric mean titers of anti-HPV-16/18 antibodies in serum were substantially higher at all time-points than those in a control group of women who had cleared a natural HPV infection in another trial. In women with detectable antibodies in both serum and CVS, good correlation was seen between HPV-16/18 antibody levels at all time-points (Pearson correlation coefficient: 0.84-0.92 for HPV-16 and 0.90-0.91 for HPV-18). The strong correlation between levels of HPV-16/18 antibodies in serum and CVS up to 36 months post-vaccination in girls and women vaccinated with the HPV-16/18 AS04-adjuvanted vaccine supports transudation of serum antibodies as the mechanism by which antibodies are introduced into CVS. These CVS antibodies may play a role in the protective efficacy of this vaccine.
- Published
- 2010
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31. Continuous, daily levonorgestrel/ethinyl estradiol vs. 21-day, cyclic levonorgestrel/ethinyl estradiol: efficacy, safety and bleeding in a randomized, open-label trial.
- Author
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Teichmann A, Apter D, Emerich J, Greven K, Klasa-Mazurkiewicz D, Melis GB, Spaczynski M, Grubb GS, Constantine GD, and Spielmann D
- Subjects
- Adolescent, Adult, Contraceptives, Oral, Combined administration & dosage, Contraceptives, Oral, Combined adverse effects, Drug Administration Schedule, Female, Humans, Longitudinal Studies, Middle Aged, Patient Selection, Pregnancy, Unplanned, Statistics, Nonparametric, Drug-Related Side Effects and Adverse Reactions, Ethinyl Estradiol administration & dosage, Ethinyl Estradiol adverse effects, Levonorgestrel administration & dosage, Levonorgestrel adverse effects, Metrorrhagia chemically induced
- Abstract
Background: This Phase 3, randomized, open-label, multicenter study conducted at 44 sites in Europe evaluated the safety and efficacy of a continuous, daily regimen of levonorgestrel (LNG) 90 mcg/ethinyl estradiol (EE) 20 mcg compared with a 21-day, cyclic LNG 100 mcg/EE 20 mcg regimen., Study Design: Three hundred twenty-three healthy women were randomized to continuous LNG 90 mcg/EE 20 mcg and 318 subjects to cyclic LNG 100 mcg/EE 20 mcg for 1 year (13 pill packs). Pearl index, adverse event (AE) incidence and bleeding profiles were assessed., Results: No pregnancies occurred with the continuous oral contraceptive (OC) (Pearl index=0.00). As the study progressed, the percentage of women who achieved amenorrhea during each 28-day pill pack increased: 40% at pill pack 7, 53% at pill pack 13. The percentage of women with no bleeding [with or without spotting (defined as not requiring sanitary protection)] was 50%, 69% and 79% at pill packs 3, 7 and 13, respectively. The incidence of AEs was similar to that of the cyclic OC (except for metrorrhagia and vaginal bleeding in the first 6 months)., Conclusions: Continuous LNG 90 mcg/EE 20 mcg was shown to be a safe and effective OC in this direct comparison to a cyclic OC. Suppression of menses and the potential for no bleeding requiring sanitary protection may be provided by this continuous, low-dose OC.
- Published
- 2009
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32. Cutoff value of human chorionic gonadotropin in relation to the number of methotrexate cycles in the successful treatment of ectopic pregnancy.
- Author
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Nowak-Markwitz E, Michalak M, Olejnik M, and Spaczynski M
- Subjects
- Abortifacient Agents, Nonsteroidal administration & dosage, Adult, Chorionic Gonadotropin analysis, Chorionic Gonadotropin standards, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Pregnancy, Pregnancy, Ectopic blood, Pregnancy, Ectopic diagnosis, Prognosis, Reference Values, Retrospective Studies, Sensitivity and Specificity, Treatment Failure, Treatment Outcome, Chorionic Gonadotropin blood, Methotrexate administration & dosage, Pregnancy, Ectopic drug therapy
- Abstract
Objective: To assign cutoff values for human chorionic gonadotropin (beta-hCG) in pretreatment and after one methotrexate (MTX) cycle and determine its correspondence to the number of MTX cycles in successfully treated ectopic pregnancy., Design: Retrospective study., Setting: Polish university hospital., Patient(s): 68 women with ectopic pregnancies who qualified for medical treatment., Intervention(s): A single-dose of MTX (50 mg/m(2)) repeated every 7 days, plus laparoscopy in cases of tubal rupture or increased (>or=50% over 1 week) beta-hCG concentration., Main Outcome Measure(s): Resolution of serum beta-hCG without the necessity of laparoscopy., Result(s): Success rate was 78% (53 of 64 women). The medians of pretreatment beta-hCG levels in the groups treated successfully and unsuccessfully (943 vs. 3085 mIU/mL) and after the first dose of MTX (564 vs. 4049 mIU/mL) were statistically significantly different. The decrease in beta-hCG level after one MTX dose differed statistically significantly only in successfully treated women. The receiver operating characteristic (ROC) curve cutoff value in the success group indicated an initial beta-hCG level of 1790 and 1218 mIU/mL after one MTX cycle. The median of beta-hCG titer was not statistically different in patients requiring one or more treatment cycles., Conclusion(s): When the beta-hCG level is >1790 mIU/mL, the MTX treatment of ectopic pregnancy is at risk of failure. However, the initial beta-hCG titer is not a predictor of the number of MTX cycles that can guarantee a successful outcome.
- Published
- 2009
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33. Immunogenicity and tolerability of an HPV-16/18 AS04-adjuvanted prophylactic cervical cancer vaccine in women aged 15-55 years.
- Author
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Schwarz TF, Spaczynski M, Schneider A, Wysocki J, Galaj A, Perona P, Poncelet S, Zahaf T, Hardt K, Descamps D, and Dubin G
- Subjects
- Adjuvants, Immunologic therapeutic use, Adolescent, Adult, Antibodies, Viral immunology, Female, Human papillomavirus 16 drug effects, Human papillomavirus 16 immunology, Human papillomavirus 18 drug effects, Human papillomavirus 18 immunology, Humans, Safety, Young Adult, Uterine Cervical Dysplasia immunology, Papillomavirus Infections immunology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines administration & dosage, Papillomavirus Vaccines adverse effects, Papillomavirus Vaccines chemistry, Papillomavirus Vaccines immunology, Uterine Cervical Dysplasia prevention & control
- Abstract
The immunogenicity and safety of an HPV-16/18 AS04-adjuvanted vaccine were assessed in women aged 26-55 years and compared with women aged 15-25 years in a Phase III, non-randomised, open-label, age-stratified study. Overall the vaccine was well tolerated and 100% seropositivity was achieved 1 month after the third dose in all age groups. There was a high correlation between HPV-16 and HPV-18 antibody levels (IgG) in cervicovaginal secretions and sera, regardless of age. The HPV-16/18 AS04-adjuvanted vaccine induces a robust and persistent immune response in women >26 years of age and generates antibodies that transudate through the cervix epithelium.
- Published
- 2009
- Full Text
- View/download PDF
34. Decreased expression of p16 in ovarian cancers represents an unfavourable prognostic factor.
- Author
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Surowiak P, Materna V, Maciejczyk A, Pudelko M, Suchocki S, Kedzia W, Nowak-Markwitz E, Dumanska M, Spaczynski M, Zabel M, Dietel M, and Lage H
- Subjects
- Adenocarcinoma mortality, Adenocarcinoma secondary, Adenocarcinoma therapy, Biomarkers, Tumor metabolism, Caspase 9 metabolism, Cell Nucleus metabolism, Cell Nucleus pathology, Combined Modality Therapy, Cytoplasm metabolism, Cytoplasm pathology, Female, Fluorescent Antibody Technique, Indirect, Humans, Immunoenzyme Techniques, Ki-67 Antigen metabolism, Middle Aged, Neoplasm Recurrence, Local, Neoplasm Staging, Ovarian Neoplasms mortality, Ovarian Neoplasms pathology, Ovarian Neoplasms therapy, Ovary pathology, Retrospective Studies, Survival Rate, Adenocarcinoma metabolism, Cyclin-Dependent Kinase Inhibitor p16 metabolism, Ovarian Neoplasms metabolism, Ovary metabolism
- Abstract
Decreased expression of p16 may result from hypermethylation of the promoter or from deletion of the gene. It can lead to intensified proliferation of neoplastic cells and to cytostatic drug resistance. The study was aimed at the examination of prognostic value of p16 expression in relation to Ki67 and caspase-3 in ovarian cancers using immunohistochemistry. The immunohistochemical studies were performed on 73 paraffin-embedded samples of ovarian cancers from 43 patients and samples from 6 healthy ovaries. We have used monoclonal antibodies against p16. ABC method and DAB were used for antigens visualisation. The intensity of the immunohistochemical reactions was appraised using the semi-quantitative IRS scale. In healthy ovaries we have shown strong reaction in the nuclei of surface epithelium. In the case of studied ovarian cancers, the reaction of a nuclear and cytoplasmic localization was obtained. The mean overall immunoreactivity score of nuclear p16 expression amounted to 5.30+/-3.44 SD in primary laparotomy material and 6.61+/-4.34 SD in secondary cytoreduction material. Statistical analysis demonstrated that lower p16 expression was typical of the younger patients and the patients who died. Kaplan-Meier's analysis proved that lower expression of p16 was characteristic of cases with shorter overall survival. In the present study we have demonstrated that lowered p16 expression represented an unfavourable prognostic index in ovarian cancer. Lowered p16 expression was also typical for chemotherapy-resistant ceases (cases of lower caspase-3 and higher Ki67 at secondary cytoreduction expression).
- Published
- 2008
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35. Expression of factors involved in regulation of DNA mismatch repair- and apoptosis pathways in ovarian cancer patients.
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Materna V, Surowiak P, Markwitz E, Spaczynski M, Drag-Zalesinska M, Zabel M, and Lage H
- Subjects
- Adaptor Proteins, Signal Transducing, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carrier Proteins biosynthesis, Caspase 3 biosynthesis, Cyclin-Dependent Kinase Inhibitor p21 biosynthesis, Drug Resistance, Neoplasm physiology, Female, Humans, Immunohistochemistry, Membrane Proteins biosynthesis, Middle Aged, MutL Protein Homolog 1, MutS Homolog 2 Protein biosynthesis, Nuclear Proteins biosynthesis, Ovarian Neoplasms drug therapy, Ovarian Neoplasms mortality, Platinum Compounds therapeutic use, Prognosis, Survival Analysis, Tumor Suppressor Protein p53 biosynthesis, bcl-X Protein biosynthesis, Apoptosis physiology, Biomarkers, Tumor analysis, DNA Mismatch Repair, Ovarian Neoplasms metabolism
- Abstract
A major obstacle in treatment of ovarian cancer is intrinsic or acquired drug resistance causing failure of chemotherapy followed by a poor clinical outcome. Drug resistance of ovarian carcinoma can be caused by dysregulation of cellular factors involved in regulation of apoptosis and DNA repair pathways. In this study, 73 ovarian carcinoma specimens obtained before and after chemotherapy were analysed by immunohistochemistry for expression of seven proteins playing an important role in regulation of DNA mismatch repair and apoptosis. The prognostic significance of these proteins in the meaning of overall and progression-free survival was evaluated in univariate and multivariate analysis. Bcl-xL, hMSH2, caspase-3, p21 and p53 displayed prognostic importance in univariate analysis. Furthermore, it was demonstrated that caspase-3 and p21 were also independent prognostic markers for both, overall and progression-free survival. In conclusion, these data indicate that analysis of proteins involved in DNA mismatch repair and apoptosis can be useful for prediction of clinical outcome in ovarian carcinoma patients.
- Published
- 2007
36. ABCC2 (MRP2, cMOAT) can be localized in the nuclear membrane of ovarian carcinomas and correlates with resistance to cisplatin and clinical outcome.
- Author
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Surowiak P, Materna V, Kaplenko I, Spaczynski M, Dolinska-Krajewska B, Gebarowska E, Dietel M, Zabel M, and Lage H
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cell Line, Tumor, Disease-Free Survival, Drug Resistance, Neoplasm, Female, Follow-Up Studies, Gene Expression Profiling, Humans, Immunohistochemistry, Kaplan-Meier Estimate, Membrane Transport Proteins drug effects, Membrane Transport Proteins genetics, Middle Aged, Multidrug Resistance-Associated Protein 2, Multidrug Resistance-Associated Proteins drug effects, Multidrug Resistance-Associated Proteins genetics, Neoplasm Staging, Ovarian Neoplasms diagnosis, Ovarian Neoplasms metabolism, RNA, Messenger biosynthesis, RNA, Messenger genetics, RNA, Messenger metabolism, Recurrence, Reverse Transcriptase Polymerase Chain Reaction, Structure-Activity Relationship, Survival Rate, Treatment Outcome, Antineoplastic Agents therapeutic use, Cell Membrane metabolism, Cell Nucleus metabolism, Cisplatin therapeutic use, Membrane Transport Proteins metabolism, Multidrug Resistance-Associated Proteins metabolism, Ovarian Neoplasms drug therapy
- Abstract
Purpose: Cisplatin resistance is a major obstacle in the treatment of ovarian carcinoma. ABCC2 is commonly localized in apical cell membranes and could confer cisplatin resistance. Here, we show that ABCC2 can be localized in the cytoplasmic membrane as well as in the nuclear membrane of various human tissues including ovarian carcinoma cells., Experimental Design: For the subcellular detection of ABCC2, immunohistochemistry was done using 41 Federation Internationale des Gynaecologistes et Obstetristes stage III ovarian carcinoma specimens prepared before treatment with cisplatin-based schemes and 35 specimens from the same group after chemotherapy. Furthermore, 11 ovarian carcinoma cell lines as well as tissue microarrays consisting of various human tissues were analyzed., Results: Nuclear membranous localization of ABCC2 was associated with response to first-line chemotherapy at primary (P = 0.0013) and secondary surgery (P = 0.0060). Cases with relapse showed higher nuclear membrane expression at primary (P = 0.0003) and secondary surgery (P = 0.0024). Kaplan-Meier analyses showed that weak nuclear membrane ABCC2 expression before treatment was associated with significantly longer overall (P = 0.04) and progression-free survival (P = 0.001); following chemotherapy, it correlated with significantly longer progression-free survival (P = 0.038). Tissue microarrays confirmed nuclear membranous localization of ABCC2, in particular, in poorly differentiated cells. In ovarian carcinoma cells, it correlated with resistance against cisplatin, whereas localization in the cytoplasmic membrane did not., Conclusions: ABCC2 confers resistance to cisplatin of ovarian carcinoma in cell culture systems and in clinics when expressed in the nuclear membrane. Thus, ABCC2 localization can predict platinum therapy outcome. Furthermore, expression of ABCC2 in nuclear membranes in human tissues is specific for poorly differentiated cells including stem cells.
- Published
- 2006
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37. CD46 expression is indicative of shorter revival-free survival for ovarian cancer patients.
- Author
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Surowiak P, Materna V, Maciejczyk A, Kaplenko I, Spaczynski M, Dietel M, Lage H, and Zabel M
- Subjects
- Female, Humans, Immunohistochemistry, Middle Aged, Paraffin Embedding, Prognosis, Retrospective Studies, Membrane Cofactor Protein biosynthesis, Ovarian Neoplasms immunology
- Abstract
Background: The membrane cofactor protein CD46 represents a complement inhibitor, which protects autologous cells from complement - mediated cytotoxicity. CD46 may exhibit the potential to protect tumor cells from the immune responses of the host. The present study aimed to evaluate the prognostic significance of CD46 expression in ovarian cancers., Materials and Methods: The analyses were performed on 73 ovarian cancer samples. Immunohistochemical reactions were performed on paraffin sections of tumors using monoclonal antibodies directed against CD46. The immunohistochemical reactions and the clinical observations results were subjected to statistical analysis., Results: Expression of CD46 was demonstrated in 60% of primary laparotomy cases and in 70% secondary cytoreduction cases. Kaplan-Meier analysis showed that a significantly shorter revival-free time was linked to cases with CD46 expression at PL (p= 0.01)., Conclusion: Ovarian cancers manifest CD46 expression that is linked to a less favourable prognosis.
- Published
- 2006
38. Topoisomerase 1A, HER/2neu and Ki67 expression in paired primary and relapse ovarian cancer tissue samples.
- Author
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Surowiak P, Materna V, Kaplenko I, Spaczynski M, Dietel M, Lage H, and Zabel M
- Subjects
- Adenocarcinoma mortality, Adenocarcinoma pathology, Biomarkers, Tumor, Female, Humans, Middle Aged, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local pathology, Ovarian Neoplasms mortality, Ovarian Neoplasms pathology, Survival Rate, Adenocarcinoma metabolism, DNA Topoisomerases, Type I metabolism, Ki-67 Antigen metabolism, Neoplasm Recurrence, Local metabolism, Ovarian Neoplasms metabolism, Receptor, ErbB-2 metabolism
- Abstract
In the present study we examined prognostic value of immunohistochemical estimation of topoisomerase 1A (TOP 1A) and HER-2/neu expression in ovarian cancers treated with platinum-based drugs but not with topotecan and the relation between expression of these proteins on the one hand and intensity of proliferation (Ki67) on the other. The analyses were performed on 73 samples of ovarian carcinoma originating from 43 first-look laparotomies (FLL) and, in 30 cases, from secondary cytoreductions (SCR)(after chemotherapy) from the same patients. In paraffin sections immunohistochemical reactions were performed using antibodies directed to HER-2/neu, TOP 1A and Ki67. Kaplan-Meier's analysis disclosed a shorter overall survival time in cases with augmented expression of TOP 1A at FLL and with higher expression of Ki67 at SCR. A shorter progression-free time was detected in cases with higher proportion of Ki67 positive cells at FLL. No relationship could be disclosed between HER-2/neu expression and the studied clinicopathological parameters. The studies confirmed high value of Ki67 estimation. The augmented expression of TOP 1A was demonstrated to represent an unfavourable prognostic factor. Thus, in cases with elevated expression of TOP 1A application of topotecan-based therapeutic schemes should be considered.
- Published
- 2006
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39. An ultrasonographic morphological index for prediction of ovarian tumor malignancy.
- Author
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Szpurek D, Moszynski R, Zietkowiak W, Spaczynski M, and Sajdak S
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Biopsy methods, Child, Female, Humans, Middle Aged, Ovarian Neoplasms epidemiology, Ovarian Neoplasms pathology, Poland epidemiology, Predictive Value of Tests, ROC Curve, Sensitivity and Specificity, Ultrasonography methods, Ovarian Neoplasms diagnostic imaging
- Abstract
Purpose of Investigation: A newly created ultrasonographic scale called the Poznan index as well as scales already well known (introduced by Sassone, De Priest and Lerner) were compared in our group of patients., Method: A morphological index was based on seven sonographic ovarian tumor features. Examinations on 686 patients were evaluated. Comparison of prognostic values of the Poznan index with other applied morphological indices in our group of patients was based on the area under receiver operating characteristic (ROC) curves., Results: The cut-off level of the new index is 8 points. The new morphological index has a specificity of 77.0%, and negative and positive predictive values of 90.7% and 69.1%, respectively. It has a sensitivity of 86.7% and accuracy of 80.6%. The Poznan index proved its usefulness and superiority (AU ROC = 0.89)., Conclusion: Using this morphological index it is possible to make a precise prognosis of ovarian tumor malignancy. It also makes it possible to make the right decision concerning the manner of surgical treatment.
- Published
- 2005
40. [Recommendations of the Polish Society of Obstetrics and Gynecology about hormonal replacement therapy].
- Author
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Spaczynski M
- Subjects
- Congresses as Topic, Female, Humans, Menopause, Poland, Primary Prevention standards, Randomized Controlled Trials as Topic, Risk Factors, Societies, Medical, Estrogen Replacement Therapy adverse effects, Estrogen Replacement Therapy standards, Women's Health
- Published
- 2004
41. Clinical evidence for topotecan-paclitaxel non--cross-resistance in ovarian cancer.
- Author
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Gore M, ten Bokkel Huinink W, Carmichael J, Gordon A, Davidson N, Coleman R, Spaczynski M, Héron JF, Bolis G, Malmström H, Malfetano J, Scarabelli C, Vennin P, Ross G, and Fields SZ
- Subjects
- Adult, Aged, Aged, 80 and over, Cross-Over Studies, Drug Resistance, Neoplasm, Europe epidemiology, Female, Humans, Middle Aged, Neoplasm Recurrence, Local mortality, Neoplasms, Glandular and Epithelial mortality, Ovarian Neoplasms mortality, Proportional Hazards Models, Survival Rate, United States epidemiology, Antineoplastic Agents pharmacology, Drug Resistance, Multiple, Neoplasm Recurrence, Local drug therapy, Neoplasms, Glandular and Epithelial drug therapy, Ovarian Neoplasms drug therapy, Paclitaxel pharmacology, Topotecan pharmacology
- Abstract
Purpose: A large, randomized study comparing the efficacy and safety of topotecan versus paclitaxel in patients with relapsed epithelial ovarian cancer showed that these two compounds have similar activity. In this study, a number of patients crossed over to the alternative drug as third-line therapy, ie, from paclitaxel to topotecan and vice versa. We therefore were able to assess the degree of non-cross-resistance between these two compounds., Patients and Methods: Patients who had progressed after one platinum-based regimen were randomized to either topotecan (1.5 mg/m(2)/d) x 5 every 21 days (n = 112) or paclitaxel (175 mg/m(2) over 3 hours) every 21 days (n = 114). A total of 110 patients received cross-over therapy with the alternative drug (61 topotecan, 49 paclitaxel) as third-line therapy., Results: Response rates to third-line cross-over therapy were 13.1% (8 of 61 topotecan) and 10.2% (5 of 49 paclitaxel; P =.638). Seven patients who responded to third-line topotecan and four patients who responded to paclitaxel had failed to respond to their second-line treatment. Median time to progression (from the start of third-line therapy) was 9 weeks in both groups, and median survival was 40 and 48 weeks for patients who were receiving topotecan or paclitaxel, respectively. The principal toxicity was myelosuppression; grade 4 neutropenia was more frequent with topotecan (81.4% of patients) than with paclitaxel (22.9% of patients)., Conclusion: Topotecan and paclitaxel have similar activity as second-line therapies with regard to response rates and progression-free and overall survival. We demonstrated that the two drugs have a degree of non-cross-resistance. Thus, there is a good rationale for incorporating these drugs into future first-line regimens.
- Published
- 2001
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42. [Prognostic value of vaginal ultrasound with color Doppler in differentiating the malignancy of ovarian tumors].
- Author
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Szpurek D, Sajdak S, Obrebowska A, Kedzia W, Opala T, and Spaczynski M
- Subjects
- Female, Humans, Prognosis, Pulsatile Flow, Regional Blood Flow, Vascular Resistance physiology, Ovarian Neoplasms blood supply, Ovarian Neoplasms diagnostic imaging, Ultrasonography, Doppler, Color methods
- Abstract
The authors presented results of research on pathological vascularization in ovarian tumors by Doppler's method. 60 records of blood flow were analysed to estimate: pulsation index (PI) and resistance index (RI). Among benign ovarian tumors (26 cases) PI was 1.82 +/- 0.93 and RI 0.93 +/- 0.36. On the contrary, for malignant neoplasms (11 cases) the blood flow was low resistance PI: 0.89 +/- 0.38 and RI: 0.44 +/- 0.19.
- Published
- 1995
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