16 results on '"Spaczynski, M."'
Search Results
2. TLR4 signaling induced by lipopolysaccharide or paclitaxel regulates tumor survival and chemoresistance in ovarian cancer
- Author
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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
- Full Text
- View/download PDF
3. 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
- Subjects
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.
- Published
- 2006
4. Decreased expression of p16 in ovarian cancers represents an unfavourable prognostic factor
- Author
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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.
- Subjects
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).
- Published
- 2008
5. OP05.03: Doppler ultrasound in management of gestational trophoblastic disease
- Author
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Pietryga, M., primary, Nowak-Markwitz, E., additional, Spaczynski, M., additional, and Brazert, J., additional
- Published
- 2007
- Full Text
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6. Correlation of Pyruvate Kinase M2 Expression with Clinicopathological Data in Ovarian Cancer.
- Author
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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
- Subjects
- 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.)
- Published
- 2018
- Full Text
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7. Ten-year immune persistence and safety of the HPV-16/18 AS04-adjuvanted vaccine in females vaccinated at 15-55 years of age.
- Author
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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
- Subjects
- 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.)
- Published
- 2017
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8. Expression of the MT1 melatonin receptor in ovarian cancer cells.
- Author
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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
- Subjects
- 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.
- Published
- 2014
- Full Text
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9. SOX18 expression predicts response to platinum-based chemotherapy in ovarian cancer.
- Author
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Pula B, Kobierzycki C, Solinski D, Olbromski M, Nowak-Markwitz E, Spaczynski M, Kedzia W, Zabel M, and Dziegiel P
- Subjects
- 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
10. 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.
- Author
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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
- Subjects
- 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
11. Effectiveness of the National Population-Based Cervical Cancer Screening Programme in Poland--outcomes, problems and possible solutions 7 years after implementation.
- Author
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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
12. 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.
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- 2011
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13. 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
14. 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
- Full Text
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15. 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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16. 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
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