IN VIVO PERFORMANCE OF THE EXPERIMENTAL CHITOSAN BASED BONE SUBSTITUTE--ADVANCED THERAPY MEDICINAL PRODUCT. A STUDY IN SHEEP.

When evaluating a novel bone substitute material, advanced in vivo testing is an important step in development and safety affirmation. Sheep seems to be a valuable model for human bone turnover and remodeling activity. The experimental material composed with the stem cells is an advanced therapy medicinal product (acc. to EC Regulation 1394/2007). Our research focuses on histological differences in bone formation (guided bone regeneration--GBR) in sheep maxillas after implantation of the new chitosan/tricalcium phosphate/alginate (CH/TCP/Alg) biomaterial in comparison to the commercially available xenogenic bone graft and a/m enhanced with the stem cells isolated from the adipose tissue. Twelve adult female sheep of BCP synthetic line, weighing 60-70 kg were used for the study. The 11 mm diameter defects in maxilla bone were prepared with a trephine bur under general anesthesia and then filled with the bone substitute materials: CH/TCP/Alg, BioOss Collagen, Geistlich AG (BO), CH/TCP/Alg composed with the stem cells (CH/S) or left just with the blood clot (BC). Inbreeding cycle of the animals terminated at 4 months after surgery. Dissected specimens of the maxilla were evaluated histologically and preliminary under microtomography. Histological evaluation showed early new bone formation observed around the experimental biomaterial and commercially available BO. There were no features of purulent inflammation and necrosis, or granulomatous inflammation. Microscopic examination after 4 months following the surgery revealed trabecular bone formation around chitosan based bone graft and xenogenic material with no significant inflammatory response. Different results--no bone recreation were observed for the negative control (BC). In conclusion, the tested materials (CH/TCP/Alg and BO) showed a high degree of biocompatibility and some osteoconductivity in comparison with the control group. Although the handiness, granules size and setting time of CHffCP/Alg may be refined for future clinical tests. The relevant beneficial influence of using the adipose derived stem cells in GBR was not confirmed in this model.

The influence of a thyroxine supplemented diet on selected hepatic redox equilibrium markers, liver morphology and the serum lipid profile in rats treated with doxorubicin.

INTRODUCTION: Cytotoxicity of doxorubicin (DOX) - an anticancer drug, mostly results from reactive oxygen species (ROS) generation. Some enzymes catalyzing this process and enzymes of antioxidant defense are regulated by iodothyronine hormones. Thus, disorders in iodothyronine hormone status may affect doxorubicin-induced redox imbalance and anabolic/catabolic disorders. The aim of this study was to evaluate the influence of doxorubicin and thyroxine (T4) associated treatment on liver morphology, markers of oxidative stress and plasma lipid parameters. MATERIALS AND METHODS: Rats were intraperitoneally treated with doxorubicin (1.5 mg/kg) once a week for ten weeks. Thyroxine was simultaneously given in drinking water (0.2 or 2.0 mg/l) for 14 weeks. RESULTS: There were higher hepatic level of malonyldialdehyde (MDA) of all tested groups and at the same time in rats treated with DOX plus T4 lower concentrations of total glutathione compared to controls were observed. Morphology of liver did not show any features of necrosis or steatosis but a decrease of glycogen content in T4+DOX groups compared to DOX treatment was observed. The concomitant administration of a lower dose of thyroxine and doxorubicin decreased triglycerides (TG) and increased LDL level compared to the DOX group. DISCUSSION: Thyroxin supplementation caused redox equilibrium disorders and oxidative stress in liver of rats receiving DOX. The study revealed the normalizing influence of thyroxin on glycogen deposits that were observed after doxorubicin treatment. Apart from an adverse impact of thyroxine administration on LDL in rats treated with doxorubicin, a beneficial effect of lower dose of thyroxine on serum TG level was revealed.

Different effects of resveratrol on dose-related Doxorubicin-induced heart and liver toxicity.

The aim of the study was to evaluate the effect of resveratrol in doxorubicin-induced cardiac and hepatic toxicity. Doxorubicin was administered once a week throughout the period of 7 weeks with 1.0 or 2.0 mg/kg body weight or concomitantly with resveratrol (20 mg/kg of feed). Heart and liver toxicity was histologically and biochemically evaluated. Resveratrol protected from the heart lipid peroxidation caused by 1 mg doxorubicin and it sharply diminished superoxide dismutase activity. An insignificant effect of resveratrol on the lipid peroxidation level and the superoxide dismutase activity was observed in the hearts of rats administered a higher dose of doxorubicin. However, resveratrol attenuate necrosis and other cardiac histopathological changes were induced by a high dose of doxorubicin. Interestingly, it slightly intensified adverse cardiac histological changes in rats receiving a lower dose of doxorubicin. Resveratrol did not have any protective effect on the hepatic oxidative stress, while exerting a mild beneficial effect on the morphological changes caused by doxorubicin. All in all, this study has shown different effects of resveratrol on dose-related doxorubicin-induced heart and liver toxicity. Resveratrol may modulate the hepatic and cardiac effect of doxorubicin, depending on the drug dose.

Predictive and prognostic value of preoperative symptoms in the surgical treatment of pulmonary aspergilloma.

BACKGROUND: Surgical resection is widely accepted as the treatment of choice for pulmonary aspergilloma (PA). However, the technique involved ranks among the most challenging in thoracic surgery and remains associated with considerable morbidity and mortality. To improve the outcomes, it is essential to establish clear recommendations for optimal timing of surgery and selection of patients. To facilitate this, we analyzed the impact of preoperative clinical factors on the results of treatment. METHODS: Medical records of patients treated surgically for PA between 1979 and 2007 were retrospectively reviewed for clinical variables of potential impact on the surgical outcome with emphasis on preoperative symptoms. RESULTS: Sixty-four patients, including 22 cases of simple aspergilloma and 42 cases of complex aspergilloma were enrolled in the study. Univariable analysis followed by multivariable logistic regression identified weight loss and massive hemoptysis as risk factors for postoperative morbidity [odds ratio (OR) = 8.856, P = 0.006 and OR = 6.9, P = 0.021, respectively]. Ten-year cumulative survival in simple aspergilloma and complex aspergilloma was 88.3% and 70.6%, respectively (P = 0.042). Multivariable analysis by Cox proportional hazard model showed that younger age and lack of massive hemoptysis were independent favorable prognostic factors [hazard ratio (HR) = 1.13, P = 0.0004 and HR = 4.71, P = 0.0319, respectively). CONCLUSION: Massive hemoptysis is an independent unfavorable predictive and prognostic factor in the surgical treatment of PA. We believe that in operable cases, early surgical resection may be recommended even in asymptomatic patients. This strategy may prevent development of life-threatening symptoms and offers a realistic chance of permanent cure with acceptable mortality and morbidity.

99mTc-EDDA/HYNIC-TOC somatostatin receptor scintigraphy in daily clinical practice.

BACKGROUND: This study aimed to assess the impact of 99mTc-EDDA/HYNIC-TOC (99mTc-TOC) somatostatin receptor scintigraphy (SRS) in clinical practice. MATERIAL/METHODS: One hundred seventeen patients were divided into 6 groups: 1, initial detection and localization of suspected neuroendocrine tumor (NET); 2, tumor staging before therapy; 3, staging of NET of unknown origin, 4, restaging after surgery of primary tumor; 5, diagnosis of solitary pulmonary nodules (SPNs), and 6, follow-up after "cold" somatostatin analogues treatment. RESULTS: In group 1, clinical suspicions were not confirmed in any of the patients; in group 2, most of the primary lesions showed overexpression of somatostatin receptors (SSRT); in group 3, the primary tumor was not identified in any of the patients; in group 4, recurrences were depicted in 7 out of 47 patients; in group 5, only 1 malignant SPN was detected, and in group 6, regression of primary mass and metastases were seen on follow-up SRS in 1 patient. CONCLUSIONS: 99mTc-TOC SRS is useful in staging of SSRT-overexpressing tumors of known and unknown primary origin, as well as in restaging after primary tumor surgery. This method is less effective in detecting suspected NET and assessing SPNs. Further investigation is necessary to evaluate the usefulness of SRS in monitoring patients after biological treatment.

Interaction of lymphocytes and thyrocytes in Graves' disease and nonautoimmune thyroid diseases in immunohistochemical and ultrastructural investigations.

BACKGROUND: Graves' disease is the archetype for organ-specific autoimmune disorders. It is very important for our understanding of the mechanisms responsible for progression of autoimmunity. The aim of this study was to present interactions of lymphocytes and thyrocytes in the thyroid tissue in Graves' disease and nonautoimmune thyroid diseases. METHODS: The study involved 30 children with Graves' disease, 30 children with nodular goiter, 30 with simple goiter and 30 healthy children. After thyroidectomy, T cells were detected in the thyroid specimens by CD3, CD4, CD8 antibodies, B cells by CD79alpha antibodies and the antigen-presenting dendritic cells with CD1a antibodies (DakoCytomation) and were examined in the EM 900 Zeiss Germany Electron Microscope. RESULTS: The most enhanced immune reaction was observed in the thyroid from children with Graves' disease. The cells of the immune system infiltrated the thyroid follicles and interfollicular compartments; they also formed lymph follicles. CONCLUSION: The immune reaction in Graves' disease and migration of lymphocytes T and B between thyrocytes results in the thickening of the basal membrane of the thyroid follicle. No cytotoxic effect of T cytotoxic/suppressor CD8+ cells on thyrocytes was observed in Graves' disease, while a mild cytotoxic effect was observed in non-autoimmune thyroid disease.

Rosiglitazone, a peroxisome proliferator-activated receptor gamma (PPARgamma)-specific agonist, as a modulator in experimental acute pancreatitis.

BACKGROUND: The purpose of this experiment was to investigate the role of PPAR ligands in the course of inflammation and of rosiglitazone, a PPAR-gamma-specific agonist, on the course of experimental acute pancreatitis (EAP). MATERIAL/METHODS: EAP was induced by administration of 5% sodium taurocholate injected into the pancreatic duct. The inflammatory activity was evaluated by biochemical scores (alpha-amylase, lipase, aminotransferases, and bilirubin), morphological changes (determined by light microscopy, H+E stained), and immunohistochemical reactions (ICAM, nitrotyrosine). RESULTS: Rosilgitazone administered in the course of EAP at a dose 50 mg/kg p.o. decreased the intensity of morphological changes (edema, inflammatory infiltrates, necrosis, and erythrocyte extravasations). In the rosiglitazone-treated animals all the biochemical parameters of EAP were statistically significantly decreased. Immunohistochemical reactions against ICAM-1 and nitrotyrosine showed that rosiglitazone decreased the intensity of inflammatory reactions in the groups of treated animals. CONCLUSIONS: PPAR-gamma agonists modulate the course of the inflammatory reaction. The administration of rosiglitazone decreased the intensity of the inflammatory process in the course of sodium taurocholate-induced EAP.

Liposarcoma of the esophagus: case report and literature review.

BACKGROUND: Liposarcoma is one of the most common soft tissue sarcomas in adults, but it is exceedingly rare in the gastrointestinal tract. To the authors' knowledge, only 17 cases of esophageal liposarcomas have been described in the literature. CASE REPORT: The case of a 56-year-old woman is reported who complained of dyspnea and airway obstruction and was referred for multi-slice computed tomography (MSCT) with the suspicion of mediastinal tumor. MSCT revealed a heterogeneous mass within the esophagus. The density measurements from pre- and post-contrast scanning suggested a fatty tissue component of the lesion and a possible malignant nature. The patient underwent esophagotomy. The diagnosis of liposarcoma was established. Five months after the surgery, follow-up chest MSCT was performed which revealed an inhomogeneous mass behind the left atrium. Additional CT was performed with a perfusion protocol which suggested a malignant nature of the lesion. After thoracotomy with removal of the tumor, the patient underwent adjuvant radiotherapy. The patient is still being followed up and two years after the esophagotomy has been well, with no metastases in subsequent endoscopic and CT examinations. CONCLUSIONS: To the authors' knowledge this is the first case of liposarcoma of the esophagus detected and postoperatively monitored using MSCT. MSCT, even as the first examination, may enable a proper diagnosis of liposarcoma in patients with atypical clinical features.

[Impact of pegylated interferon alpha and ribavirin therapy of chronic hepatitis C on peripheral blood and intrahepatic lymphocytes]. / Wplyw leczenia skojarzonego interferonem pegylowanym alpha i rybawiryna przewleklego zapalenia watroby typu C na zmiany subpopulacji limfocytów krwi obwodowej i wewnatrzwatrobowych.

UNLABELLED: The role of cellular immune response in pathogenesis of liver cell injury and course of chronic hepatitis C have been previously confirmed. The aim of this study was to determine the modification of T-lymphocyte subsets during pegylated interferon alpha (PegIFN) and ribavirin treatment and its correlation with response to the treatment. MATERIAL AND METHODS: The assessment of subsets of intrahepatic lymphocytes and peripheral blood lymphocytes was done in 62 patients with chronic hepatitis C using flow cytometry and immunohistochemical method. RESULTS: Significant increase in peripheral blood CD4+ cells, was observed in week 12 of treatment in patients with both complete and partial response to therapy. There were no significant modifications in nonspecific CD8+ subsets, but after 12 week of treatment in patients with response to therapy, decrease or lack of HCV-specific CD8+ cells were observed. The assessment of subsets of intrahepatic lymphocytes revealed a significantly higher percentage of CD8+ cells in pretreatment liver biopsies from patients with sustained viral response. CONCLUSIONS: The results confirmed the impact of interferon alpha and ribavirin treatment on cellular response. Some immunological host factors should be considered in the early prognosis of successful treatment.

Immunohistochemical analysis of carcinomatous and sarcomatous components in the uterine carcinosarcoma: a case report.

Uterine carcinosarcoma (malignant mixed Mullerian tumor) is an uncommon female genital tract neoplasm characterized by an admixture of epithelial and stromal malignant cells. We report a case of 50-year-old peri-menopausal woman diagnosed to have early-stage (IB due to FIGO) uterine carcinosarcoma of the homologous type with superficial (3mm) myo-invasion. The patient showed no clinical symptoms of the disease and had no family history of female genital tract malignancies. Positive immunostaining for steroid receptors (estrogen-alpha and progesterone receptors), cytokeratin, and EGFR was detected only in the carcinomatous area, whereas beta-catenin, BCL-2, COX-2, p16(INK4a), PTEN, RB-1, and vimentin were immunoreactive in both components. Androgen receptor, CD10, desmin, HER-2/neu, and P53 were found to be negative either in the carcinomatous or in the sarcomatous area. Tumor proliferative activity was higher in the carcinomatous (25%) than in the sarcomatous (2%) component. Based on these findings, immunohistochemical evaluation of multiple receptor status in the carcinomatous and sarcomatous areas of carcinosarcoma may provide a clue to the pathogenesis and hormonal receptor status of this uncommon uterine malignancy.

Immunological system status and the appearance of respiratory system disturbances in thymectomized patients.

INTRODUCTION: Adult-onset thymoma may be responsible for several diseases, such as pure red cell aplasia, myasthenia gravis, and immunodeficiency (Good's syndrome). Thymectomy does not always improve the patient's condition, and may even produce additional symptoms. Its pathogenesis is still not entirely understood, but autoimmunological processes and bone marrow defect are the most frequently suggested. MATERIALS AND METHODS: Eleven patients (mean age: 56.2+/-15.5 years) were analyzed 6 months to 10 years after thymectomy due to thymoma as were 25 healthy persons serving as controls. Enzyme-linked immunosorbent assay (ELISA) and flow cytometry techniques were used to evaluate the immunological status of the subjects. RESULTS: Good's syndrome was diagnosed in one patient, 4 subjects suffered from myasthenia gravis, and recurrent infections of upper and lower respiratory tract appeared in 9 patients. The immunological analyses (ELISA and flow cytometry) revealed a significantly lower IgG level (p<0.05), percentage of peripheral blood B lymphocytes (p<0.0005), and CD4:CD8 ratio (p<0.05) in thymectomized patients compared with the healthy controls. The percentages of CD4+ and CD8+ T lymphocytes expressing CD28 antigen were significantly lower in thymectomized patients than in healthy subjects (p<0.005 and p<0.01, respectively). The percentage of naive T helper lymphocytes was significantly lower in the patients than in the control group (p<0.05). CONCLUSIONS: Immunodeficiency and recurrent infections may be the first symptoms of immunological disturbances after thymectomy in adults. It is suggested that regular medical monitoring of these patients is important in preventing further complications, which may result in irreversible lung tissue destruction.

An immunohistochemical study of cyclin D1 protein expression in laryngeal squamous cell carcinoma.

CONCLUSION: Contrary to most reports, our study shows that the expression of cyclin D1 is not an independent prognostic factor in patients with laryngeal cancer (LC). No correlation between cyclin D1 expression and survival rates in LC was found in a multivariate analysis. OBJECTIVES: The aim of this study was to determine the possible relevance of the expression of cyclin D1 protein in LC as prognostic criteria and to analyse correlation of the expression with clinicopathological features and survival rates. MATERIALS AND METHODS: Immunohistochemistry staining was used to detect the expression of cyclin D1 in 130 samples of laryngeal cancer and in 22 specimens of laryngeal nodules. RESULTS: Cyclin D1 expression was found in 52 (40%) LC samples and in 3 (13.6%) samples of laryngeal nodules. There was no significant correlation between cyclin D1 expression and clinicopathological features of LC. A multivariate analysis of survival confirmed that cyclin D1 expression was not an independent prognostic factor in LC.

[Difficulties in using archival paraffin-embedded tissues for RNA expression analysis]. / Trudnosci w wykorzystaniu tkanek z archiwalnych bloczków parafinowych w badaniach ekspresji RNA.

Formalin-fixed and paraffin-embedded tissue sections are used for routine histopathological diagnostics, but they have increasingly become material for molecular studies of genome and gene expression using molecular biological techniques such as PCR and RT-PCR. A major limitation is the significant degree of degradation and chemical modification of the nucleic acids recovered from fixed tissues. The purpose of this review is to provide an overview of studies on the possibility of using routinely prepared paraffin-embedded tissue sections as a source of messenger RNA. Difficulties in recovering high-quality RNA are mainly connected with the influence of formalin on nucleic acids and the effects of other physical and chemical agents on tissue during preservation and fixation. It is necessary to optimize RNA isolation and polymerase chain reaction conditions. Special attention is paid to the rising need to introduce alternative techniques for the fixation of tissue sections that provide for better preservation of both macromolecules and tissue morphology and for conducting histological diagnostics with molecular studies.

Estimation of prognostic value of Bcl-xL gene expression in non-small cell lung cancer.

The aim of our study was to estimate the expression of the Bcl-xL gene, a member of Bcl-2 family, in NSCLC patients. A total of 60 consecutive patients diagnosed with NSCLC that underwent chemotherapy prior to surgery were reviewed. Bcl-xL expression was assessed on paraffin sections by in situ hybridization (ISH) and immunohistochemistry (IMH). We observed the presence of mRNA of Bcl-xL gene and its protein product overexpression in most patients (60 and 81.7%, respectively). In material examined no significant correlation was observed between the pattern of Bcl-xL or protein expression and any clinicopathological factors evaluated. The expression of Bcl-xL protein was low (less than 10% positive cells) in 11 patients (median survival time 29 months) as compared to 49 patients with overexpression (median survival time 21.0 months). The difference was not of statistic significance (p=0.27). In examined group the Bcl-xL mRNA was found in 36 patients, while it was absent in 24 cases. Median survival time was 14.5 and 86.5 months, respectively (p=0.001). In addition, 19.4% of 5-year survivals were achieved in patients with overexpression and 54.2% in patients with no mRNA present (p=0.002). The percentage of 5-year survival in patients with protein expression assessed by IMH was 30.6% (p=0.31). The estimation of Bcl-xL expression on mRNA and protein level was compared by the means of sign test and the significant difference was found (p=0.009). The inconsistency was related to 35% of cases. In comparison with IMH, ISH technique appeared to be more specific and accurate in assessment of 5-year survival (25 and 65%; 65 and 70%, respectively). The results of our study indicate that Bcl-xL mRNA overexpression may suggest poor prognosis in NSCLC.

Primary non-Hodgkin's lymphoma of the uterine cervix mimicking leiomyoma: case report and review of the literature.

Primary malignant lymphoma occurring in the uterine cervix is a rare event. We report a case of primary non-Hodgkin's lymphoma of the uterine cervix mimicking leiomyoma. The immunophenotype of the tumor and the differential diagnostic approach to this uncommon malignancy also are presented.

[Role of mitochondrial protein Smac/Diablo in regulation of apoptotic pathways]. / Rola mitochondrialnego bialka Smac/Diablo w regulacji szlaków apoptotycznych.

This is a review of studies on recently identified protein Smac/Diablo, a factor that has been shown to exit mitochondria in response to apoptotic stimuli and potentate caspase activity, possibly by neutralizing members of IAP family. The current knowlege about structure and function of Smac/Diablo during programmed cell death, both in mitochondrial and receptor pathways are presented. Special attention was paid to the defects of transduction of apoptotic signals in chemoresistant tumor cells such as alteration in expression of IAP and Bcl-2-family and role of Smac/Diablo as an agent, which analyzed deeply may contribute to create new forms of anticancer therapies.

Adenomyoepithelioma of the breast with late pulmonary metastases - case report and review of the literature.

BACKGROUND: Adenomyoepithelioma (AME) of the breast is a rare tumour of unpredictable clinical behaviour. Most of the tumours are benign with some giving local recurrences or distant metastases. CASE PRESENTATION: We report a case of late lung metastases in a woman with a history of breast adenomyoepithelioma. Partial lobectomy was performed for lung lesions and initial diagnosis was epithelial-myoepithelial carcinoma. CONCLUSION: Careful slide's revision of both breast and pulmonary lesions showed identical microscopic appearance with lung tumour performing more malignant features. Tumour cells in both: breast and pulmonary lesions were positive for cytokeratin and EMA (epithelial cells) and also for SMA, S100 and vimentin (myoepithelial cells). Two years and 7 months follow-up showed no recurrent neoplastic disease in our patient.

Immunohistochemical detection of hMLH1 and hMSH2 proteins in vulvar carcinoma.

The immunohistochemical (IHC) detection of MMR proteins is an accurate and rapid method to predict the presence of defective DNA MMR genes. MMR protein expression could also serve as a prognostic indicator of human cancers. The results of many studies demonstrate the usefulness of IHC tests with monoclonal antibodies MSH2 and MLH1 in screening the microsatellite sequence instability within both spontaneous and hereditary malignant neoplasms. The aim of our study was to perform an IHC estimation of the hMLH1 and hMSH2 expression in a subset of vulvar carcinomas according to HPV 16/18 status. The level of MMR proteins was further analyzed in relation to histoclinical features of the disease in either HPV-positive or -negative cancers. We identified archival diagnostic phase tissue specimens from 46 cases of vulvar cancer. From the same paraffin blocks containing material from the margin of surgical section during vulvectomy, normal epithelial tissue fragments were collected and designated as the control group. The characteristic of the lesion was examined in comparison with the presence of HPV DNA. Identification of the HPV 16/18 types was performed using PCR. IgG1 monoclonal antibodies detecting those epitopes characteristic for hMLH1 and hMSH2 were used in the study. In the analyzed cases of vulvar cancer, we have observed increased expression of proteins of both hMSH2 and hMLH1 genes compared to the control group. A comparison of the hMLH1 and hMSH2 protein expression levels showed that hMSH2 expression was higher than that of hMLH1 in the case of vulvar carcinomas. The performed analysis of correlation between individual parameters did not reveal statistically significant relationship with both the gradient and status of HPV 16/18. hMSH2 and hMLH1 were definitely interrelated.

Activity of NADPH-cytochrome P-450 reductase of the human heart, liver and lungs in the presence of (-)-epigallocatechin gallate, quercetin and resveratrol: an in vitro study.

NADPH-cytochrome P-450 reductase (P-450 reductase) plays a crucial role in the metabolism of many endogenic compounds and xenobiotics detoxication. The enzyme is also involved in the toxicity of some clinically important antitumour drugs (doxorubicin) and pesticides (paraquat). P-450 reductase activates them to their more toxic metabolites via one electron reduction which triggers free radical cascade. In some cases however, such transformation is essential to produce therapeutic effect in anticancer drugs. The main purpose of the paper was to evaluate the effect of three natural compounds found in human diet: (-)-epigallocatechin gallate (EGCG), quercetin and resveratrol on P-450 reductase activity. The activity of the enzyme was determined spectrophotometrically by measurement of the rate of cytochrome c reduction at 550 nm, in vitro, using human heart, liver and lung microsomes. It was found that quercetin increased the P-450 reductase activity in human organs at all tested doses. The activity of microcosms in all organs was enhanced according to the concentrations of quercetin, which increased the activity in the order lung>heart>liver. Addition of EGCG to the reaction mixture enhanced the P-450 reductase activity in the following order: liver>heart>lung. However, no significant effect of resveratrol on P-450 reductase activity was observed. It seems that the presence of quercetin and EGCG in the diet may increase P-450 reductase activity during doxorubicin therapy with subsequent increased risk of toxicity. A beneficial effect may be obtained in anticancer therapy with bioreductive agents like tirapazamine.

Sarcomatoid carcinoma of the esophagus.

The authors present two rare cases of sarcomatoid carcinoma of the lower thoracic esophagus in a 73-year-old woman and a 42-year-old man. The histogenesis, clinicopathological features and differential diagnosis of this unusual tumor are also discussed.