Biomedical subjects

Zsuzsa Schaff

Publications and source records attributed to Zsuzsa Schaff.

At least 37 records · Page 2Linked to original sources

PubMed2005

Expression of ets-1 transcription factor in human head and neck squamous cell carcinoma and effect of histamine on metastatic potential of invasive tumor through the regulation of expression of ets-1 and matrix metalloproteinase-3.

BACKGROUND: Ets-1 controls the expression of critical genes involved in matrix remodeling. The matrix metalloproteinase-3 (MMP-3) and urokinase type plasminogen activator (uPA) are typical ets-1 responsive genes. Recent studies have shown an increase in histamine synthesis and content in various human neoplasias. We hypothesized that the increased local histamine overproduction contributed to activation of matrix remodeling through the activation of MMP-3 expression of peritumoral fibroblasts by means of ets-1 regulation in head and neck squamous cell carcinomas (HNSCCs). METHODS: Paraffin-embedded sections of 30 HNSCCs were immunostained for ets-1. The presence of ets-1 and MMP-3 mRNA in tumor samples was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR). To simulate stromal reaction in vitro, cultured human mucosal fibroblast was used. The level of ets-1 and MMP-3 mRNA was compared by use of RT-PCR, as was their protein with flow-cytometry, in the presence or absence of basic fibroblast growth factor (bFGF) (10 ng/mL) and histamine (1 microM). RESULTS: Correlation between ets-1 expression and clinicopathologic background was not significant. In all cases, expression of ets-1 was seen in the stroma. In in vitro study, histamine upregulates production of ets-1 and MMP-3 in cultured fibroblast, and bFGF can stimulate histamine expression in fibroblast. Immunofluorescence staining supported the results of RT-PCR and flow cytometry. CONCLUSIONS: Ets-1 expression in HNSCCs has no prognostic value; however, ets-1 plays an important role in tumor-host interaction. Histamine may accelerate the spread of HNSCC through an ets-1-related mechanism.

Biomarkers, Tumor↗

PubMed2005

Increased expression of claudins in cervical squamous intraepithelial neoplasia and invasive carcinoma.

Claudins (CLDNs), of which 24 types have been identified, are integral transmembrane proteins of the tight junctions that are critical for maintaining cell adhesion and polarity. They also act as selective barriers. Cells and tissues are characterized by individual CLDN patterns; the composition and levels of expression change during differentiation and tumor formation. Alterations in the expression of individual CLDNs have been detected in several carcinomas and shown to be related to progression and invasion; however, their role in carcinogenesis is controversial. Using a panel of polyclonal (CLDNs 1, 3, and 7) and monoclonal (CLDNs 2 and 4) antibodies, CLDN pattern and expression were studied by immunohistochemistry in 105 cervical tissue specimens, including normal epithelia (n = 20), cervical intraepithelial neoplasias (CINs; CIN 1/2, n = 27; CIN 3, n = 10), carcinoma in situ (CIS, n = 15), and 33 squamous keratinizing and nonkeratinizing invasive carcinomas. No CLDN 3 was observed in normal or intraepithelial neoplastic cells, but significantly increased expression of CLDNs 1, 2, 4, and 7 was detected in the CIN/CIS lesions and invasive carcinomas compared with the normal tissues (P < .001) and reduced reactivity of CLDNs 1 and 2 was observed in invasive cervical cancers compared with CIN 3/CIS (P = .0001) and of CLDNs 2, 4, and 7 compared with CIN 1/2. These results indicate increased expression of CLDNs in the early phase of carcinogenesis in intraepithelial lesions, which decreases during progression to invasive disease. Expression of CLDN 1 was strongest in premalignant stages; thus, it may serve as a good diagnostic marker for the detection of CIN.

Biomarkers, Tumor↗

PubMed2005

The expression of five different claudins in invasive breast carcinomas: comparison of pT1pN1 and pT1pN0 tumors.

The evaluation of the role of claudins (CLDNs) in breast carcinogenesis has recently begun. We investigated the expression of CLDNs 1, 2, 3, 4, and 7 in pT1pN0 and pT1pN1 invasive ductal breast carcinomas. Tissue arrays of 30-30 pT1pN0 and pT1pN1 invasive ductal breast carcinomas of different grades were constructed, and the expression of CLDN 1, 2, 3, 4, and 7 proteins was analyzed using standard and immunofluorescent immunohistochemistry. The results were evaluated by light and confocal microscopy. Regarding CLDN 1, 4, and 7 expressions, differences were noted between normal and tumor cells and also between tumors of different grades, while no remarkable differences were noted between pT1pN0 and pT1pN1 tumors. CLDNs 1 and 7 were found to be downregulated in tumor cells compared to the normal epithelium, while CLDN 4 expression was decreased in grade 1 tumors. CLDN 7 protein was abundant in normal epithelia, and the staining decreased in grade 3 tumors. There were no differences between normal and neoplastic cells regarding CLDN 2 and 3 expressions. As a preliminary result, our observations suggest that the analyzed CLDNs do not promote tumor metastasis. On the basis of our findings, it seems that CLDN 1, CLDN 4, and CLDN 7 may rather have an important role in tumorigenesis or in cell-to-cell adhesion.

Axilla↗

PubMed2005

Scurvy leads to endoplasmic reticulum stress and apoptosis in the liver of Guinea pigs.

Insufficient ascorbate intake causes scurvy in certain species. Beyond its known functions, it has been suggested that ascorbate participates in oxidative protein folding in the endoplasmic reticulum (ER). Because redox imbalance in this organelle might cause ER stress and apoptosis, we hypothesized that this might contribute to the pathology of scurvy. Guinea pigs were divided into 7 groups: the control group was fed a commercial guinea pig food containing 0.1 g/100 g ascorbate for 4 wk, 5 groups consumed an ascorbate-free food for 0, 1, 2, 3, or 4 wk and 1 group was fed this scorbutic diet for 2 wk and then the commercial food plus 1 g/L ascorbate in drinking water for 2 wk. TBARS generation and the expression of some ER chaperones and foldases were determined in hepatic microsomes. The apoptotic index was assessed in histological sections. Although ascorbate, measured by HPLC, was undetectable in the livers of the guinea pigs after they had consumed the scorbutic diet for 2 wk, the microsomal TBARS level was elevated relative to the initial value only at wk 4. Western blot revealed the induction of GRP78, GRP94, and protein disulfide isomerase at wk 3 and 4. Apoptosis was greater than in the control, beginning at wk 3. None of the alterations occurred in the groups fed the commercial guinea pig food or ascorbate-free food followed by ascorbate supplementation. Therefore, persistent ascorbate deficiency leads to ER stress, unfolded protein response, and apoptosis in the liver, suggesting that insufficient protein processing participates in the pathology of scurvy.

Animals↗

PubMed2004

[Hepatitis C virus RNA in the skin eruption from patients with prurigo and chronic hepatitis C].

UNLABELLED: Hepatitis C virus RNA in the skin eruption from patients with prurigo and chronic hepatitis C. Since the discovery of hepatitis C virus (HCV) in 1989, many cutaneous disorders have been observed in patients suffering from chronic HCV infection. The relationship between HCV infection and cryoglobulinemia and porphyria cutanea tarda is clearly established, however, the link between HCV and other skin diseases is still controversial. AIM: Two patients with intense pruritus and secondary prurigo in chronic C hepatitis have been presented. METHODS: The chronic hepatitis C of the patients were proved by elevated ALT and AST level, anti HCV (ELISA), HCV-PCR serological examination and liver biopsy. The skin lesions were accompanied by severe itching. According to clinical symptoms the patients suffered from prurigo simplex. RESULTS: HCV RNA in the skin specimen from the biopsy of the skin lesion was detected by RT PCR method, but the non affected skin specimen from the patients was HCV RNA negative. CONCLUSIONS: This report is a case of prurigo simplex with chronic C hepatitis proving a direct relation between the HCV infection and prurigo.

Female↗

PubMed2004

[Proteoglycans in the liver].

Proteoglycans are macromolecules formed by a protein core to which sugar chains are covalently attached. They are present on the cell surface and in the ECM of living things. In normal liver syndecan-1 is the dominant transmembrane proteoglycan, trace amounts of ECM proteoglycans are in the stromal components. The amounts of proteoglycans we studied increase in liver cirrhosis. In liver cancer abnormal localization of syndecan-1 and stroma rich in agrin was characteristic. The core proteins as well as the sugar chains of proteoglycans interact with and modulate the effect of regulatory factors. This implies that structural alterations of proteoglycans contribute to the development of malignant phenotype. Heparan sulfate chains of liver cancer are undersulfated with decreased or altered biological activity. Their binding capacity for transcription factor decreases, and they do not inhibit topoisomerase I enzyme. Truncated form of syndecan-1 lacking the extracellular domain of the molecule induces differentiation of hepatoma cell line and inhibits the shedding of syndecan-1. This phenomenon calls attention to the importance of syndecan-1 shedding in the regulation of cell behavior.

Animals↗

PubMed2004

[Novel factors playing a role in the pathomechanism of diffuse liver diseases: apoptosis and hepatic stem cells].

Liver diseases can basically be categorised into the forms diffuse and focal. In case of diffuse liver diseases the damages in general affect the whole of the liver, but the alterations are usually present in varying degrees and severity. Relatively stereotypical reactions develop in the liver tissues on the effect of various damaging factors. Some of these reactions and their pathogenic backgrounds are well known, while others have only recently come into focus, like apoptosis and the regeneration-proliferation related hepatic stem cells. The number of damaging effects are naturally much higher than the number of possible response reactions and as a consequence, in many cases the etiological factors can not unambiguously be identified from the tissue alterations. The basic reaction types of the liver can be divided into well defined categories; thus adaptive changes, degeneration and intracellular storage, cell death (necrosis/apoptosis), inflammation, fibrosis and structural reorganisation, as well as regeneration/proliferation. The picture of "classic necrosis" is well known; with the detection of cellular swelling, membrane damage. Apoptosis is characterised by cell shrinkage, nuclear and cytoplasmic disruption, while the cell membrane remains intact. Apoptosis occurs in several liver diseases, with a striking form of appearance being the Councilman-like body seen in viral hepatitis. Apoptosis may have role in the pathogenesis of cholestasis, biliary atresia, the "vanishing bile duct syndrome", and alcoholic liver injury. The regenerative ability of the liver is excellent. The process is influenced by several growth factors and cytokines. In the case of chronic liver damage, however, the regeneration equilibrium becomes upset and irregular. Studies on liver regeneration have led to the recognition of hepatic stem cells. These cells of "oval" morphologic appearance are built up of a primitive structure, making them suitable for this task. Ductular proliferation originating from hepatic stem cells can mostly be recognised in three disease groups: liver regeneration following massive or submassive liver necrosis, ductular proliferation without liver insufficiency, and tumorous liver diseases. At present it is still unclear whether the hepatocyte formation originating from haematopoetic stem cells is a rarely occurring accidental transformation, or rather, under appropriate circumstances, a greatly effective "third" protective system. If the latter is true, this can fundamentally change our view on the pathomechanism of liver diseases, making possible numerous novel therapeutic treatments.

Animals↗

PubMed2004

[Malignant rhabdoid tumour in the liver].

The authors describe the case of a 6-months-old child with liver tumour. The newborn was healthy until 6 months of age. Prior to hospitalization meteorism and remarkably enlarged liver were observed. A tumour occupying the right lobe of the liver was found with ultrasound and computer tomography, which proved to be inoperable. Intraoperative liver biopsy and few days later the autopsy histology showed a malignant rhabdoid tumour. Authors describe the clinical and morphological features of a rare case of primary hepatic rhabdoid tumour.

Autopsy↗

PubMed2004

The role of TTF-1 in differentiating primary and metastatic lung adenocarcinomas.

Thyroid transcription factor-1 (TTF-1) is a sensitive marker for pulmonary and thyroid adenocarcinomas. The aim of this work was to determine its usefulness in distinction between primary and metastatic lung adenocarcinomas. We have examined the expression of TTF-1 in 100 solitary pulmonary nodules. They included 50 stage I peripheral primary bronchial adenocarcinomas (30 men, 20 women, mean age: 60 years) and 50 metastatic pulmonary adenocarcinomas (21 men, 29 women, mean age: 57 years) of different origins, such as breast (13), colon (13), rectum (13), kidney (7), stomach (2), and thyroid gland (2). TTF-1 immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissues. In primary bronchial adenocarcinomas we found immunopositivity in 46/50 cases, among them 30 cases showed strong nuclear immunostaining. In four primary adenocarcinoma cases the observed immunopositivity was localized to the cytoplasm. Out of the metastatic adenocarcinomas all but the 2 thyroid cancers were negative. Both thyroid tumors showed strong immunopositivity. Our results confirm that TTF-1 immunohistochemistry is a very sensitive and highly specific method in the differential diagnosis of primary and metastatic lung adenocarcinomas and should be used in the everyday clinical practice.

Adenocarcinoma↗

PubMed2004

Detection of Chlamydia pneumoniae in liver transplant patients with chronic allograft rejection.

BACKGROUND: Chlamydia pneumoniae is one of the possible pathogenetic factors of atherosclerotic processes. Foam cell arteriopathy is a generally accepted pathologic feature of chronic liver allograft rejection and has several similarities to the early lesions of atherosclerosis. The aim of the authors' study was to show any existing correlation between the occurrence of Chlamydia pneumoniae and the presence of foam cell arteriopathy in transplanted livers with chronic rejection. METHODS: Ten liver samples from patients with chronic liver rejection including foam cell arteriopathy and 10 liver samples from healthy individuals were analyzed for the presence of Chlamydia pneumoniae by specific immunohistochemistry and polymerase chain reaction (PCR). Liver samples from two transplant patients with chronic liver rejection without any evidence of foam cell arteriopathy and nine patients with acute liver allograft rejection were also investigated by PCR. RESULTS: In all 10 rejected liver samples, Chlamydia pneumoniae was detected by PCR, whereas only one of the healthy control samples and one of the samples with acute rejection were found to be positive. Immunohistochemistry showed similar results. The positive signals of Chlamydia pneumoniae were localized mainly in the hepatocytes, sinusoidal and perisinusoidal cells, and the cells of portal tracts, whereas most of the altered hepatic arteries showed no or very weak positivity. CONCLUSIONS: The results strongly suggest an association between the occurrence of Chlamydia pneumoniae and the presence of foam cell arteriopathy in transplanted livers.

Adult↗

PubMed2004

[Hindgut cyst in the presacral region].

Authors review a case of a 53 years old female patient with a cystic alteration 9 cm in diameter, located in the presacral region, in the medial line. Histological examination proved the mass to be a quite rare hindgut cyst which during surgery, however, did not show any connection with the rectum. The case is reported due to its relative rareness and the differential diagnostic questions emerging.

Colonic Diseases↗

PubMed2004

[Unilateral Sertoli-cell androblastoma in the ovary of a young woman].

The authors present a case of a Sertoli-cell type androblastoma of the ovary. The tumor is mainly seen in young women and is mostly discovered through hormonal dysfunctions linked to it. Histopathological evaluation is indispensable for an exact diagnosis. Because of its rarity, there is little experience with the tumor and the histological identification is also sometimes very challenging. The tumor is occasionally associated with Peutz-Jeghers syndrome, tumor of the thyroid, or goiter. Biologically it follows a low-malignant course with a fair prognosis, long-term complex patient follow up is necessary after unilateral oophorectomy of the diseased organ.

Adolescent↗

PubMed2004

Similarities and differences in hepatitis B and C virus induced hepatocarcinogenesis.

Hepatocellular carcinoma (HCC), the major manifestation of primary liver cancer, is one of the most frequent and malignant diseases worldwide. Among other environmental factors, hepatitis viruses, as the hepatitis B (HBV) and hepatitis C (HCV) viruses, are to be listed in the etiology of HCC. Both of these viruses cause a wide spectrum of clinical manifestations, ranging from healthy carrier state to acute and chronic hepatitis, cirrhosis and HCC. HBV and HCV are different viruses in structure: HBV contains a DNA genome which replicates through an RNA intermediate and requires an active viral reverse transcriptase (RT) polymerase enzyme, while HCV is an RNA virus which has no RT activity and replicates on the cellular membrane by RNA replication. In this review we discuss how these two biologically diverse viruses use common pathways to induce hepatocarcinogenesis despite their significant structural and viral cycle differences. A summary is also given of several observable common and different features. Direct integration of HBV viral sequences into the host genome increases the genomic instability, which does not occur in HCV infection. However, viral proteins may directly play a significant role in the induction of carcinogenesis by both viruses.

Animals↗

PubMed2004

[Pathology of liver tumors].

There is a worldwide increase in the number of focal liver lesions, including liver tumors. Focal liver lesions can either be tumorous or non-tumorous. Cysts and cystic tumors comprise an important group, their latest classification is reported in this paper. The basic classification of tumors has not changed, benign and malignant; epithelial and mesenchymal, as well as those of other origin can be distinguished. The malignant tumors observed in the liver are forty times more frequently metastatic than primary. It is essential to emphasize that not all multiple liver tumors are malignant and that tumors of different origin and dignity can simultaneously be present in the liver. The cytological examination of samples taken by fine needle aspiration technique is becoming more and more significant in the differentiation of focal liver lesions.

Adenoma↗

PubMed2004

Effect of formalin, acetone, and RNAlater fixatives on tissue preservation and different size amplicons by real-time PCR from paraffin-embedded tissue.

RNA recovered from paraffin-embedded tissue has been reported to be a suitable substrate for polymerase chain reaction. During tissue fixation and paraffin embedding, RNA undergoes degradation, but with certain restrictions, it can be used for gene expression studies. At the same time, formalin-fixed, paraffin embedded histopathology archives contain an unestimable collection, which could be analyzed to investigate changes in mRNA expression in pathologic processes. To decide for future tissue conservation of pathology samples, it would be reasonable to satisfy both histologic and molecular biologic needs. The effect of three different fixation methods, RNAlater (SIGMA R 0901, St Louis, MO), acetone, and formalin, were compared by histology, immunohistochemistry, and real-time PCR. To assess tissue structure preservation and antigenicity, hematoxylin-eosin staining and immunohistochemistry were performed; to assess RNA quality, RNA was extracted and the transcription of different amplicon sizes (121, 225, 406 bp for GAPDH; 166, 310, 536 bp for beta globin) were examined on human endometrium samples. The most adequate tissue preservation was found in case of formalin fixation, while there were no significant differences in the three fixatives' yields for various size real-time PCR amplicons. Longer amplicons (above approximately 225 bp) have limited use for gene expression studies, while shorter amplicons could give more reliable results.

Adult↗

PubMed2004

Rising plasma nociceptin level during development of HCC: a case report.

AIM: Although liver cirrhosis is a predisposing factor for hepatocellular carcinoma (HCC), relatively few reports are available on HCC in primary biliary cirrhosis. High plasma nociceptin (N/OFQ) level has been shown in Wilson disease and in patients with acute and chronic pain. METHODS: We report a follow-up case of HCC, which developed in a patient with primary biliary cirrhosis. The tumor appeared 18 years after the diagnosis of PBC and led to death within two years. Alfa fetoprotein and serum nociceptin levels were monitored before and during the development of HCC. Nociceptin content was also measured in the tumor tissue. RESULTS: The importance and the curiosity of the presented case was the novel finding of the progressive elevation of plasma nociceptin level up to 17-fold (172 pg/mL) above the baseline (9.2+/-1.8 pg/mL), parallel with the elevation of alpha fetoprotein (from 13 ng/mL up to 3 480 ng/mL) during tumor development. Nociceptin content was more than 15-fold higher in the neoplastic tissue (0.16 pg/mg) than that in the tumor-free liver tissue samples (0.01 pg/mg) taken during the autopsy. CONCLUSION: Results are in concordance with our previous observation that a very high plasma nociceptin level may be considered as an indicator for hepatocellular carcinoma.

Biomarkers, Tumor↗

PubMed2003

Viral hepatitis: new data on hepatitis C infection.

Viral hepatitis (VH) is almost as old as human beings, at least as old as known human history. However, the natural history and the epidemiology of the disease has undergone changes during the centuries and even recently we have been facing several new aspects. The estimated global prevalence is around 3-5%, which means that approximately 400 million patients are infected with hepatitis B virus and that there are 170 million infections with hepatitis C virus. The mortality figures are projected to show a 2- to 3-fold increase over the next two decades as hepatitis C virus-infected patients develop cirrhosis, which makes this the leading indication for liver transplantation. These data point to the importance of VH being a significant public health problem worldwide. The list of hepatotropic viruses is well known, including hepatitis A (HAV), B (HBV), C (HCV), D (HDV), E (HEV), G (HGV) and F (HFV). HGV and HFV are excluded from the present review, mainly because they are questionable in relation to the causation of liver disease. Our knowledge of HAV, HBV, HDV and HEV has accumulated over the last decade, so the present discussion is focused on HCV, which is currently generating considerable concern and controversy, and is the leading cause of chronic liver disease worldwide. The main questions to be discussed, are: the characterization of the agents' viral genotypes/subtypes, the viral-cell interaction, the pathogenesis of VH, the extrahepatic manifestations of viral infection and hepatocarcinogenesis.

Hepacivirus↗

PubMed2003

[Clinicopathologic observations on chronic hepatitis C therapy with interferon-alpha].

INTRODUCTION: Chronic hepatitis C is a progressive liver disease. It may lead to cirrhosis within 15-20 years, on the grounds of which hepatocellular carcinoma may develop in around 4% of the cases. The entity can thus be regarded a premalignant condition. Based on the above, early diagnosis is of great importance, as is prompt treatment. AIMS: 1. to find correlations between the activity grade, stage of the disease and the various histologic characteristics, which are befitting representations of the clinical course for chronic hepatitis C, 2. to collect data on changes of nuclear proteins as markers of cell proliferations, 3. to analyse the changes in the expression of the components of the extracellular matrix, which play role in the pathogenesis of the fibrosis. RESULTS: Analysing the 106 biopsy specimens most frequently mild degree of inflammation was found. The majority of cases were in stage 1 (41.5%), however 8.69% were already in stage 4. Lymphoid aggregates/follicles and bile duct lesion were in correlation with the activity of the disease. A considerable decrease in the ALT level and in the histologic activity was induced by the 12 months interferon-alpha treatment. A positive correlation was found for the expression of the nuclear proteins used as proliferation markers in minimal and mild activity cases, while in moderate chronic hepatitis C a remarkable decrease was manifest in respect to cyclin-A activity. After 12 months IFN-alpha treatment the proliferating cell nuclear antigen activity increased, with a decrease in cyclin-A positivity. CONCLUSIONS: Chronic hepatitis C cases with mild activity may also belong to stage 4, the need for liver biopsies should therefore be considered even besides the presence of near normal biochemical parameters in certain cases. The positive correlations between lymphoid follicles/aggregates, bile duct lesions and chronic hepatitis C activity refers to the fact that the above noted histologic differences may be evaluated as prognostic factors. The 12 months interferon-alfa treatment has a moderating effect on cell proliferation, as shown by the lowered cyclin-A expression and does have an effect on particular components playing role in the early phase of fibrogenesis.

Antiviral Agents↗