114 results on '"Marek Spaczyński"'
Search Results
102. Nuclear metallothionein expression correlates with cisplatin resistance of ovarian cancer cells and poor clinical outcome.
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Verena Materna, Adam Maciejczyk, Marek Pudełko, Ewa Markwitz, Marek Spaczyński, Manfred Dietel, and Hermann Lage
- Abstract
Abstract??Elevated metallothionein (MT) expression in ovarian cancers treated with cisplatin-based schemes represents an unfavorable prognostic index. MT expression is significantly higher in tumor samples obtained after chemotherapy. The present study aimed at examining MT expression in ovarian carcinoma cells sensitive (A2780) or resistant (A2780RCIS) against platinum drug treatment as well as examining effects of exposure to cisplatin on MT expression. Subcellular expression of MT was evaluated also in samples originating from 73 ovarian tumors. Cisplatin-resistant A2780RCIS cells were exposed to increasing cisplatin concentrations, and the subcellular expression of MT was determined by immunocytochemistry. The studies demonstrated that cisplatin-resistant A2780RCIS cells exposed to cisplatin typically manifested a nuclear MT expression. The study demonstrated also that exposure to cisplatin was paralleled by growing MT expression in cell nuclei. The nuclear expression of MT was also found to be specific for ovarian cancers of poor clinical outcome. No relationship could be demonstrated between cytoplasmic expression of MT and clinical variables. Nuclear MT expression is induced by cisplatin and seems to protect DNA in the cells from toxic effects of the drug. [ABSTRACT FROM AUTHOR]
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- 2007
103. Taxol-resistance-associated gene-3 (TRAG-3/CSAG2) expression is predictive for clinical outcome in ovarian carcinoma patients.
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Verena Materna, Irina Kaplenko, Marek Spaczyński, Zhenfeng Duan, Manfred Dietel, and Hermann Lage
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Abstract??An obstacle in chemotherapy of ovarian cancer is the development of drug resistance. Taxol (paclitaxel)-resistance-associated gene-3 (TRAG-3/CSAG2) was found to be overexpressed in a paclitaxel-resistant ovarian carcinoma cell line. However, clinical impact of TRAG-3 in ovarian carcinoma has not been demonstrated previously. For demonstration of potential clinical impact of TRAG-3, immunohistochemistry was applied to determine TRAG-3 protein expression in specimens obtained from ovarian carcinoma patients (n?=?37) who received a paclitaxel-based chemotherapy at two different time points, initial laparotomy before chemotherapy, and secondary cytoreduction after chemotherapy. The TRAG-3-specific immunohistochemical staining was correlated with clinical outcome. In ovarian carcinoma specimens obtained at the initial laparotomy, an advantage in overall (P<0.001) and progression-free (P?=?0.003) survival for patients with weak TRAG-3 expression could be demonstrated. Tumor specimens excised at secondary cytoreduction procedure were not predictive for clinical outcome. In summary, TRAG-3 was found to be a prognostic factor for the prediction of clinical outcome after the application of paclitaxel-based chemotherapy. [ABSTRACT FROM AUTHOR]
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- 2007
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104. Augmented expression of metallothionein and glutathione S-transferase pi as unfavourable prognostic factors in cisplatin-treated ovarian cancer patients.
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Paweł Surowiak, Verena Materna, Irina Kaplenko, Marek Spaczyński, Manfred Dietel, Hermann Lage, and Maciej Zabel
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Abstract Resistance to cis- or carboplatin represents the principal cause of therapeutic failures in ovarian carcinoma. The phenomenon of resistance to platinum-based drugs is partly related to expression of metallothionein (MT) and of glutathione S-transferase pi (GST-pi), but opinion on the subject is discordant. Documentation of a negative predictive effect of MT and GST-pi expression for the therapy employing platinum-based drugs would permit to select resistant cases in which other therapeutic approaches could be employed. The present study aimed at examining the relation between intensities of MT and GST-pi expressions in ovarian carcinomas and dynamics of the clinical course in the neoplastic disease in a group of cisplatin-treated patients. The analyses were performed on samples of ovarian carcinoma originating from 43 first-look laparotomies (FLLs) and, in 30 cases, from second-look laparotomies (SLL) from the same patients. Immunohistochemical reactions were performed on paraffin sections of studied tumors, using monoclonal antibodies to MT and GST-pi. The calculations showed that in cases with augmented expression of MT, mortality was higher. On the other hand, augmented expression of GST-pi predisposed to more frequent relapses, deaths and progression of the tumor. Kaplan–Meier analysis showed that a significantly shorter survival time was linked to cases of higher expression of MT at FLL and of higher expression of GST-pi at FLL, whereas a shorter progression-free time was manifested by cases with higher expression of GST-pi at FLL. The performed investigations indicate that augmented expressions of MT at FLL and GST-pi at FLL in ovarian cancer represent an unfavourable predictive factor in cisplatin-treated patients. [ABSTRACT FROM AUTHOR]
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- 2005
105. Paraneoplastic neurological syndromes associated with ovarian tumors
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Marek Spaczyński, Slawomir Michalak, Ewa Nowak-Markwitz, and Mikołaj Piotr Zaborowski
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medicine.medical_specialty ,Pathology ,Cancer Research ,Review – Clinical Oncology ,animal structures ,endocrine system diseases ,Paraneoplastic Syndromes ,Ovarian teratoma ,Pathogenesis ,Ovarian cancer ,Ovarian carcinoma ,Internal medicine ,medicine ,Humans ,Ovarian Teratoma ,Stage (cooking) ,Ovarian Neoplasms ,Hematology ,business.industry ,Incidence ,General Medicine ,Prognosis ,medicine.disease ,Paraneoplastic cerebellar degeneration ,nervous system ,Oncology ,Anti-NMDAR encephalitis ,Female ,Poland ,business ,Encephalitis - 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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106. Expression of the MT1 Melatonin Receptor in Ovarian Cancer Cells
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Karolina Jablonska, Bartosz Pula, Agata Zemla, Christopher Kobierzycki, Witold Kedzia, Ewa Nowak-Markwitz, Marek Spaczynski, Maciej Zabel, Marzenna Podhorska-Okolow, and Piotr Dziegiel
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melatonin ,melatonin receptor ,ovarian cancer ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - 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 (MT1CM) and membrane (MT1M) reactions. A positive correlation between MT1CM and MT1M was found in all the studied cases. There were no significant differences between the expression of MT1CM, MT1M, and histological type, staging, grading, presence of residual disease, or overall survival time. Immunofluorescence showed both MT1M and MT1CM 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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107. SOX18 expression predicts response to platinum-based chemotherapy in ovarian cancer
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Bartosz Puła, Christopher Kobierzycki, Daniel Soliński, Mateusz Olbromski, Ewa Nowak-Markwitz, Marek Spaczyński, Witold Kędzia, Maciej Zabel, and Piotr Dziegiel
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Ovarian Neoplasms ,Cell Line, Tumor ,SOXF Transcription Factors ,Humans ,Female ,Immunohistochemistry ,Platinum - Abstract
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.SOX18 expression was assessed in 85 OC cases using immunohistochemical methods and in ovarian cancer cell lines on the mRNA and protein level.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 (p0.0001) and advanced disease stage (p0.0324) predicted poor patient outcome.SOX18 may be a new predictive marker for OC.
108. Loss of estrogen receptor beta expression correlates with shorter overall survival and lack of clinical response to chemotherapy in ovarian cancer patients
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AGNIESZKA HAŁOŃ, Ewa Nowak-Markwitz, Adam Maciejczyk, Marek Pudełko, Tserenchunt Gansukh, Balazs Gyorffy, Piotr Donizy, Dawid Murawa, Rafal Matkowski, Marek Spaczyński, Hermann Lage, and Pawel Surowiak
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Ovarian Neoplasms ,Survival Rate ,Drug Resistance, Neoplasm ,Cell Line, Tumor ,Estrogen Receptor beta ,Humans ,Female ,Cisplatin ,Drug Screening Assays, Antitumor ,Middle Aged ,Immunohistochemistry ,Neoplasm Staging - Abstract
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).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.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).The loss of ERβ expression in ovarian tumours may be a feature of malignant transformation.
109. Statement of the Polish Gynecological Society on the application of myo-inozytol in patients with PCOS (Polycystic Ovary Syndrome)
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Ewa Nowak-Markwitz, Agata Karowicz-Bilińska, Tadeusz Issat, Artur Jakimiuk, Jacek Szamatowicz, Przemysław Oszukowski, Marek Spaczyński, and Lechoslaw Putowski
110. 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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Christopher Kobierzycki, Bartosz Puła, Mateusz Skiba, Karolina Jablonska, Krzysztof Łątkowski, Maciej Zabel, Ewa Nowak-Markwitz, Marek Spaczyński, Witold Kędzia, Marzenna Podhorska-Okolow, and Piotr Dziegiel
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Adult ,Ovarian Neoplasms ,Minichromosome Maintenance Proteins ,Biomarkers, Tumor ,Humans ,Female ,Metallothionein ,Middle Aged ,Aged - Abstract
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.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.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 p0.0001). 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).Due to the correlations shown here, the determination of MCM proteins as proliferation markers of ovarian cancer, should be strongly considered.
111. Expression and signaling of Toll-like receptor 4 (TLR4) and MyD88 in ovarian carcinoma cells
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Malgorzata Czystowska, Miroslaw J. Szczepanski, E. Elishaev, Theresa L. Whiteside, Marta Szajnik, M. Mandapathil, Marek Spaczyński, and E. Nowak-Markwitz
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Oncology ,Cancer Research ,Toll-like receptor ,medicine.medical_specialty ,business.industry ,Immune system ,Ovarian carcinoma ,Internal medicine ,Cancer research ,medicine ,TLR4 ,business ,Human cancer - Abstract
e16508 Background: TLR4, expressed by the cells of the immune system play a role in the protection of the host against pathogens. TLRs are also expressed on human cancer cells, but their role in tumor growth is unknown. The aim of this study was to correlate the presence of TLR4 and MyD88 expression with clinicopathologic outcome in patients with ovarian cancer and to analyze the consequences of signaling via the TLR4/MyD88 pathway in ovarian cancer cell lines. Methods: Tumor specimens from 41 patients with ovarian carcinoma were evaluated for TLR4 and MyD88 by immunohistochemistry and correlated with clinical and pathologic disease features. TLR4/MyD88 expression in OVCAR3, SKOV3, and A2780 was determined using RT-PCR, WB, and immunohistochemistry. NF-kB translocation to nucleus was measured by confocal microscopy. Culture supernatants were tested for levels of cytokines in Luminex-based assays. Proliferation of cancer cells was measured in the CFSE assays. Their sensitivity to paclitaxel (PLX) was measured by Annexin V binding. Western Blot analysis was used to measure activation of the PI3K/Akt, IRAK 1, IRAK 4, and TRIF. Results: In ovarian cancer patients TLR4 and MyD88 expression by the tumor was observed in 100% and 83% of tissues, respectively. The expression of MyD88 was associated with shorter progression-free survival (42 vs 31 months, p < 0.05). Ex vivo studies showed that TLR4 was expressed on OVCAR3, SKOV3, and A2780 cell lines, while A2780 did not expressed MyD88. In MyD88+ tumor cells, LPS increased proliferation (PI 17 vs 8, p < 0.05), activated NF-kB pathway and promoted cytokine production (IL-8, IL-6, RANTES, VEGF and MCP-1). LPS and PLX binding to TLR4 on MyD88+ cells induced activation of PI3K/Akt, IRAK4, and IRAK1, but decreased expression of pro-apoptotic TRIF. In contrast, in MyD88(-) cells LPS did not induce proliferation and neither LPS nor PLX induced secretion of pro-inflammatory cytokines. Further, no changes were noted in IRAK1 expression, but strong signal was observed for TRIF. TLR4+/MyD88+ tumor cells showed grater resistance to PLX. Conclusions: Our ex vivo studies elucidate the molecular mechanisms involved in TLR4/MyD88 signaling. Ligation via TLR4 leads to tumor growth, release of proinflammatory cytokines and induction of resistance to PLX-induced apoptosis. No significant financial relationships to disclose.
112. Expression of factors involved in regulation of DNA mismatch repair- and apoptosis pathways in ovarian cancer patients
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Verena Materna, Pawel Surowiak, Malgorzata Drag-Zalesinska, Hermann Lage, Ewa Markwitz, Maciej Zabel, and Marek Spaczyński
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Cyclin-Dependent Kinase Inhibitor p21 ,Cancer Research ,Programmed cell death ,DNA repair ,bcl-X Protein ,Apoptosis ,Platinum Compounds ,Biology ,DNA Mismatch Repair ,Ovarian carcinoma ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,medicine ,Humans ,Adaptor Proteins, Signal Transducing ,Ovarian Neoplasms ,Oncogene ,Caspase 3 ,Membrane Proteins ,Nuclear Proteins ,Cancer ,General Medicine ,Middle Aged ,Cell cycle ,Prognosis ,medicine.disease ,Immunohistochemistry ,Survival Analysis ,MutS Homolog 2 Protein ,Oncology ,Drug Resistance, Neoplasm ,Immunology ,Cancer research ,Female ,DNA mismatch repair ,Tumor Suppressor Protein p53 ,Carrier Proteins ,MutL Protein Homolog 1 ,Ovarian cancer - 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-x L , 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.
113. [Human papilloma virus genotyping in women with CIN 1].
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Kedzia W, Józefiak A, Pruski D, Rokita W, and Marek S
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- Adult, Carcinoma, Squamous Cell pathology, DNA Probes, HPV, DNA, Viral analysis, Female, Genotype, Humans, Middle Aged, Poland epidemiology, Precancerous Conditions pathology, Risk Assessment methods, Uterine Cervical Neoplasms virology, Women's Health, Young Adult, Uterine Cervical Dysplasia pathology, Carcinoma, Squamous Cell virology, Papillomaviridae classification, Papillomaviridae genetics, Papillomavirus Infections virology, Precancerous Conditions virology, Uterine Cervical Dysplasia virology
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Introduction: Cervical cancer remains a considerable diagnostic and therapeutic problem in Poland. Despite progress in creating an active cancer prevention program in our country Poland occupies one of the last places in the EU in terms of cervical cancer- morbidity and mortality Supplement of secondary prevention of primary prophylaxis-HPV 16, 18 vaccination, offers hope for improvement of the situation. Epidemiology of individual HPV types differs, depending on the geographical location of the study population. So far in Poland, we have had no reliable data on the participation of selected oncogenic HPV types in the development of cervical pathology, Objective: Identification of the most frequent, oncogenic HPV types in women diagnosed with CIN 1, from the Central and Western Poland., Material: In the course of the conducted studies, genotyping of 13 types of human papilloma virus has been done in 126 HPV DNA-positive women diagnosed with CIN 1., Method: Each cell material in which the presence of HPVDNA identified 13 types of oncogenic human papillomavirus was subsequently subjected to genotyping using the molecular test--Linear Array HPV Genotyping (Roche Diagnostics)., Results and Conclusion: In women from the Central and Western Poland diagnosed with CIN 1, HPV 16 (53.97%) was the most common, followed by HPV 33 (21.3%), HPV 18 (16.67%), HPV 31 (10.32%), HPV 45 (7.94%), HPV 52 (1.59%). Current HPV vaccines are designed to protect against two of the three most common genotypes, in women diagnosed with CIN 1 in Central and Western Poland.
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- 2010
114. The diagnostic problems in patient with ascites, elevated Ca 125 level and autoantibodies against nuclear antigens and smooth muscle antigens mimicking advanced ovarian carcinoma--case study.
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Marta S, Ewa NM, Mirosław S, Marek S, Krzysztof L, and Jan Z
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- Adult, Ascites immunology, Autoimmunity immunology, Biomarkers blood, Diagnosis, Differential, Female, Humans, Ovarian Neoplasms diagnosis, Ovarian Neoplasms immunology, Ascites diagnosis, Autoantibodies blood, CA-125 Antigen blood, Hepatitis, Autoimmune diagnosis, Hepatitis, Autoimmune immunology, Muscle, Smooth immunology
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The paper describes a case of 26-year-old patient primarily suspected to suffer from the ovarian or peritoneum cancer due to high level of Ca 125 antigen and ascites. During exploratory laparotomy, neoplastic process was excluded, which was confirmed by histopathological examination. Further diagnostic tests were performed. The patient was not infected with hepatitic B or C virus, and there was no biochemical evidence of liver disease. Detailed, wide biochemical and immunological investigations detected antinuclear and anti smooth muscle autoantibodies in the blood serum. Afterwards, the patient was admitted to the Department of Gastroenterology and autoimmune chronic hepatitis was confirmed.
- Published
- 2008
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